bromochloroacetic-acid and Chronic-Disease

Esophagogastric ulcer is an independent disease in swine that is characterized by ulcerous autodigestion of the cutaneous mucosa, which does not exhibit a tendency to recover, but, on the contrary, a tendency toward severe hemorrhaging, with a predominantly lethal outcome. Since it develops in the part of the stomach that is morphologically and functionally different from other glandular mucosa, it was questioned earlier whether it could be a peptic ulcer based on its nature. Spontaneous ulcers, usually of the stomach, commonly occur in many domestic animals. Some of these lesions are chronic and they may occur in either the glandular or squamous-lined regions of the stomach. As with the human disease, the pathogenesis in domestic animals is multifactorial, poorly understood, and variable between and within species. Environmental stress and dietary factors are very important in the ulcer disease in swine. It has been shown that the Helicobacter spp. is strongly associated with naturally occurring ulcer and preulcer lesions of the pars esophagea in swine, which raises the possibility that Helicobacter spp. is an important factor in the pathogenesis of these lesions. The dynamics of the development of esophagogastric ulcers imply hyperplastic lesions (parakeratosis and hyperkeratosis), keratolysis, erosions, peptic necrosis, and the development of ulcers with all the characteristics of peptic ulcerations in other localities. In addition, K6 is expressed in association with the mucosal changes. The pattern of the intermediate filaments of keratin suggests that epithelial proliferation, which leads to visible hyperkeratosis, constitutes the essence of gastric ulcers in swine.

Topics: Animals; Cell Proliferation; Chronic Disease; Diagnosis, Differential; Diet; Esophageal Diseases; Esophagogastric Junction; Helicobacter Infections; Humans; Intermediate Filaments; Keratins; Stomach; Stomach Ulcer; Swine

The keratin intermediate filament (IF) cytoskeleton of hepatocytes has continuously gained medical relevance over the last two decades. Originally it was mainly recognized as a differentiation marker for diagnostic purposes in pathology. However, keratin IFs were soon identified as major cellular structures to be affected in a variety of chronic liver diseases, such as alcoholic and non-alcoholic steatohepatitis (ASH, NASH), copper toxicosis, and cholestasis. Based on observations in keratin gene knock-out mice, the insight into the functional role of keratins was extended from a mere structural role providing mechanical stability to hepatocytes, to an additional role as target and modulator of toxic stress and apoptosis. The functional relevance of keratins in human diseases has recently been underlined by the identification of mutations in keratin genes in patients with liver cirrhosis.

Topics: Biliary Tract; Cholestasis; Chronic Disease; Cytoskeleton; Epithelial Cells; Hepatitis; Humans; Keratins; Liver; Liver Diseases; Liver Neoplasms; Mutation

This review indicates that the patient-to-patient uniqueness commonly seen in chronic laminitis represents the variable presence of the digital pathologies. Although some degree of mechanical failure is always present, the secondary metabolic and growth dysplasias, vascular pathologies, and sepsis may or may not be evident. The presence and severity of these pathologies appear to have a more significant impact on the prognosis of individual cases than does the displacement of the distal phalanx. It should be reiterated that it is often the combined presence of these individual pathologies that gives rise to the patient that is totally refractory to treatment. In the absence of these pathologies, many horses with significant displacement of the distal phalanx are not in pain and are not in need of treatment. It thus follows that a key to the improved rehabilitation of difficult patients is focusing research on the physiopathology and diagnosis of these nonmechanical problems.

Topics: Animals; Chronic Disease; Foot Diseases; Hoof and Claw; Horse Diseases; Horses; Inflammation; Keratins

Topics: Antibodies; Arthritis, Rheumatoid; Chronic Disease; Humans; Intermediate Filament Proteins; Keratins; Lupus Erythematosus, Systemic; Rheumatic Diseases; Scleroderma, Systemic; Sjogren's Syndrome; Spondylitis, Ankylosing; Vimentin

Exacerbation of chronic psoriasis can be associated with streptococcal throat infections, and T cells that respond to peptide sequences common to streptococcal M proteins and skin keratins have been detected in patients' blood. To our knowledge, we have conducted the first blinded, prospective study to assess the impact of tonsillectomy on psoriasis. Twenty-nine patients with chronic psoriasis and history of exacerbation after sore throat were randomly assigned to tonsillectomy (n = 15) or control (n = 14) groups and monitored for 2 y clinically and by enumeration of circulating skin homing T cells that respond to short homologous M protein or keratin peptides. Thirteen patients (86%) showed sustained improvement after tonsillectomy ranging from 30 to 90% reduction in disease severity. Furthermore, there was a close correlation between the degree of clinical improvement in individual patients and reduction in the frequency of peptide-reactive skin-homing T cells in their circulation. No corresponding clinical or immunologic changes were observed among the controls. These findings indicate that tonsillectomy may have a beneficial effect on chronic psoriasis because the palatine tonsils generate effector T cells that recognize keratin determinants in the skin.

Topics: Adolescent; Adult; Antigens, Bacterial; Bacterial Outer Membrane Proteins; Carrier Proteins; Cell Movement; Child; Child, Preschool; Chronic Disease; Epitopes, T-Lymphocyte; Female; Humans; Keratins; Lymphopenia; Male; Middle Aged; Palatine Tonsil; Prospective Studies; Psoriasis; Skin; T-Lymphocyte Subsets; Tonsillectomy; Young Adult

Keratin proteins have been shown to play a key role in wound healing. Controlled keratin gene (KRT) expression promotes cell growth, migration and differentiation, and as an example of the importance of keratin proteins, absence of KRT17 has been shown to delay wound closure. In addition, downregulation of KRT6 and KRT16 in non-healing chronic venous ulcers suggests that deregulation of keratin expression contributes to non-healing phenotype. A sample of 45 chronic wounds of mixed aetiologies presenting in 31 patients were treated with keratin-based novel topical wound healing products. Thirty-seven wounds or 82% of wounds were either healed or reduced in size of >50% during treatment, with 29 (64%) healing completely and an additional 8 wounds experiencing 50% wound size reduction or greater. Of the wounds that responded, 15 required antimicrobial treatment during their course of treatment, suggesting that keratin dressing treatment should be interrupted briefly and then restarted when wound infection occur.

Topics: Adult; Aged; Aged, 80 and over; Bandages; Chronic Disease; Female; Humans; Hydrogels; Keratins; Male; Middle Aged; Prospective Studies; Wound Healing; Wounds and Injuries; Young Adult

Most tympanic membrane (TM) perforations heal spontaneously, but approximately 10-20% remain open as chronic TM perforations. Chronic perforations can lead to an impaired hearing ability and recurrent middle ear infections. Traditionally, these perforations must be surgically closed, which is costly and time consuming. Therefore, there is a need for simpler therapeutic strategies. Previous studies by us have shown that plasminogen (plg) is a potent pro-inflammatory regulator that accelerates cutaneous wound healing in mice. We have also shown that the healing of TM perforations is completely arrested in plg-deficient (plg(-/-)) mice and that these mice develop chronic TM perforations. In the present study, we investigated the therapeutic potential of local plg injection in acute and chronic TM perforation mice models.. Plg(-/-) mice and wild-type mice were subjected to standardized TM perforations followed by local injection of plg into the soft tissue surrounding the TM. TM perforations with chronic characteristics were induced by leaving TM perforations in plg(-/-) mice untreated for 9 days before treatment. The healing process was observed through otomicroscope and finally confirmed by immunostaining. The quality of TM healing was evaluated based on the morphology of the TM.. Daily local injections of plg into the soft tissue surrounding the TM restored the ability to heal TM perforations in plg-/- mice in a dose-dependent manner, and potentiated the healing rate and quality in wild-type mice. A single local injection of plg initiated the healing of the chronic-like TM perforations in these mice, resulting in a closed TM with a continuous but rather thick outer keratinocyte layer. However, three plg injections led to a completely healed TM with a thin keratinizing squamous epithelium covering a connective tissue layer.. Our data suggests that plg is a promising drug candidate for the treatment of chronic TM perforations in humans.

Topics: Animals; Chronic Disease; Dose-Response Relationship, Drug; Immunohistochemistry; Injections, Intraperitoneal; Injections, Subcutaneous; Keratins; Mice; Mice, Inbred C57BL; Plasminogen; Tympanic Membrane Perforation; Wound Healing

Chronic rhinosinusitis (CRS) defines a group of disorders characterized by persistent inflammation of the sinonasal tract. Epithelial changes and structural remodelling are present, but whether epithelial differentiation is altered remains uncertain.. To evaluate the differentiation state of the sinonasal epithelium in CRS, sinonasal biopsies from patients with CRS with nasal polyps (CRSwNP) or CRS without nasal polyps (CRSsNP), or with allergic rhinitis (AR), as compared to controls, were processed by immunohistochemistry and RT-qPCR for terminal differentiation (E-cadherin, high molecular weight cytokeratins (Hmw CK) and CK5, vimentin) and lineage differentiation (ß-tubulin IV+ ciliated cells, MUC5AC+ goblet cells, p63 + basal cells). Findings were correlated with subepithelial fibrosis and clinical CT score.. Expression of E-cadherin was decreased at protein and mRNA levels in CRSwNP and CRSsNP, as compared to controls. Staining for Hmw CKs was also reduced in CRSwNP and CRSsNP, and CK5 mRNA was decreased in CRSwNP. These features were not due to changes in lineage specification, but associated with increases in vimentin-expressing epithelial cells. In addition, vimentin expression correlated with the basement membrane thickening and with CT score, as well as with tissue eosinophils.. Features of epithelial dedifferentiation towards a mesenchymal phenotype are observed in CRSwNP and CRSsNP and correlate with airway fibrosis and inflammation.

Topics: Adolescent; Adult; Aged; Airway Remodeling; Cadherins; Case-Control Studies; Cell Count; Cell Dedifferentiation; Chronic Disease; Epithelial-Mesenchymal Transition; Female; Fibrosis; Gene Expression; Goblet Cells; Humans; Keratins; Male; Middle Aged; Nasal Polyps; Phenotype; Respiratory Mucosa; Rhinitis; Risk Factors; Sinusitis; Tomography, X-Ray Computed; Vimentin; Young Adult

Established middle-ear cleft cholesteatoma is associated with keratinous debris, which is likely to be an ideal medium for saprophytic fungal colonisation. This prospective case study aimed to explore the incidence and nature of fungal elements in cholesteatoma keratin samples obtained during primary mastoid surgery.. All cases of middle-ear cleft cholesteatoma treated with primary mastoid surgery at the El-Sahel Teaching Hospital over a seven-month period were included. Keratinous debris obtained from the mastoid antrum was subjected to mycological analysis at the Department of Medical Microbiology and Immunology, Faculty of Medicine, Cairo University. A literature search was performed to determine the clinical and pathological relevance of fungal colonisation in cholesteatoma.. Eighteen patients underwent primary mastoid surgery for cholesteatoma (nineteen ears in total) in a seven-month period starting 30 March 2013. Patients included 13 males and 5 females, with an age range of 9 to 45 years (mean 23 years). Fungal cultures were obtained from 17 keratin samples (89 per cent). Of these, five fungal isolates belonged to the dermatophyte group (21 per cent).. Fungal colonisation in middle-ear cleft cholesteatoma probably plays a significant role in disease progression. Moreover, saprophytic fungal colonisation in cholesteatoma keratin may be responsible for the fetor commonly associated with the ear discharge.

Topics: Adolescent; Adult; Child; Cholesteatoma, Middle Ear; Chronic Disease; Disease Progression; Female; Fungi; Granulation Tissue; Humans; Keratins; Male; Mastoid; Middle Aged; Otitis Media; Prospective Studies; Young Adult

Cells of the epidermis renew constantly from germinal layer stem cells. Although epithelial cell differentiation has been studied in great detail and the role of Wnt signaling in this process is well described, the contribution of epidermal Wnt secretion in epithelial cell homeostasis remains poorly understood. To analyze the role of Wnt proteins in this process, we created a conditional knockout allele of the Wnt cargo receptor Evi/Gpr177/Wntless and studied mice that lacked Evi expression in the epidermis. We found that K14-Cre, Evi-LOF mice lost their hair during the first hair cycle, showing a reddish skin with impaired skin barrier function. Expression profiling of mutant and wild-type skin revealed up-regulation of inflammation-associated genes. Furthermore, we found that Evi expression in psoriatic skin biopsies is down-regulated, suggesting that Evi-deficient mice developed skin lesions that resemble human psoriasis. Immune cell infiltration was detected in Evi-LOF skin. Interestingly, an age-dependent depletion of dendritic epidermal T cells (DETCs) and an infiltration of γδ(low) T cells in Evi mutant epidermis was observed. Collectively, the described inflammatory skin phenotype in Evi-deficient mice revealed an essential role of Wnt secretion in maintaining normal skin homeostasis by enabling a balanced epidermal-dermal cross talk, which affects immune cell recruitment and DETC survival.

Topics: Animals; CD3 Complex; Cell Proliferation; Chronic Disease; Dendritic Cells; Dermatitis; Epidermis; Gene Deletion; Humans; Inflammation; Intracellular Signaling Peptides and Proteins; Keratinocytes; Keratins; Lymphocyte Activation; Mice; Mice, Transgenic; Neutrophil Infiltration; Phenotype; Psoriasis; Receptors, Antigen, T-Cell, gamma-delta; Receptors, G-Protein-Coupled; STAT3 Transcription Factor; T-Lymphocytes; Wnt Proteins

Current insight into the histopathological course of events during disease progression in hidradenitis suppurativa (HS) is fragmentary.. To identify histological alterations and leucocyte subsets in normal-appearing perilesional skin, and early and chronic HS lesions.. In this observational study we examined eight perilesional skin samples, and six early and 10 chronic prototypic HS lesions, as well as skin samples from four healthy donors using in situ immunostaining.. Perilesional skin showed mild psoriasiform hyperplasia and follicular plugging as well as a low-grade influx of tryptase-positive mast cells, CD3+ T cells, CD138+ plasma cells and factor XIIIa+ dendritic cells. In early HS lesions, neutrophilic abscess formation and influx of mainly macrophages, monocytes and dendritic cells predominated. In chronic disease, the infiltrate expanded with markedly increased frequencies of CD20+ and CD79a+ B cells and CD138+ plasma cells. As in early lesions, free keratin fibres were detected in the dermis and within giant cells. Single detached keratinocytes and strands of follicular epithelium were observed in the dermis, the latter frequently expressing Ki67, indicative of active proliferation.. Psoriasiform hyperplasia, follicular plugging and low-grade leucocytic infiltration are already present in normal-appearing perilesional skin. Keratin fibres in the dermis are associated with clinical disease. Early lesions are characterized by neutrophilic abscess formation and influx of mainly histiocytes, and chronic lesions mainly by expansion of B cells and plasma cells in 'pseudo' follicles. Proliferating strands of follicular epithelium may initiate fistula formation. Mast cells are increased in all stages of HS including perilesional skin.

Topics: Acute Disease; Cell Proliferation; Chronic Disease; Epidermis; Hidradenitis Suppurativa; Humans; Hyperplasia; Immunohistochemistry; Immunophenotyping; Keratins; Leukocytes; Skin

Epiboly represents the process by which keratinocytes migrate to envelop a surface. The authors have been investigating a living bilayered skin construct (BSC) that is used in the treatment of lower extremity wounds due to venous insufficiency and diabetes. The construct demonstrates epiboly after injury and incubation in vitro, and this model may be useful for studying epidermal migration and the process of skin maturation. Punch biopsies of the construct in vitro were cultured and immunostained for specific keratins at baseline and at 24 to 72 hours. For comparison, skin biopsy specimens from human chronic venous ulcers and acute healing wounds were similarly processed. The authors found that K1 and K10 were fully expressed in the epidermis of the fully epibolized surface on BSC. K1 was also present in the migrating edge of specimens, whereas K10 was not detectable. K16 and K6 were evident in normal skin and the epibolized area of the construct; K6 expression was very prominent in the migrating edge. Importantly, K17 was distinctly limited to the epibolized surface and the migrating edge, and its expression was very similar to that observed in healing human wounds. In conclusion, differential expression of keratins in this epiboly model closely reflects in vivo studies and supports keratin specificity in the processes of migration and differentiation of new epidermis. Therefore, these findings provide further and important validity for the study of epithelialization and the hope of developing prognostic markers for venous ulcer healing.

Topics: Bioengineering; Cell Differentiation; Chronic Disease; Epidermis; Humans; In Vitro Techniques; Keratinocytes; Keratins; Models, Theoretical; Skin, Artificial; Varicose Ulcer; Wound Healing

Discovery of the significant impact of filaggrin (FLG) mutations on the genetic predisposition to atopic dermatitis (AD) focused attention on the 1q21 locus, where not only FLG but also other epidermal genes are located. In the present study, we compared 1q21 gene expression in lesional versus nonlesional AD skin.. A real-time quantitative PCR analysis of 10 1q21 genes, selected on the basis of a previous microarray study, was performed in skin biopsies from 33 individuals with AD. Three alternative pathway keratins were also evaluated.. In chronic AD skin lesions, we observed an increase in RNA encoding involucrin, S100 calcium-binding proteins A2 and A7-A9 and small proline-rich region (SPRR) proteins 1A and 2C, with fold changes ranging from 2.0 for S100A2 to 15.4 for S100A8 (p < 0.001, Bonferroni corrected), in parallel to the overexpression of the alternative pathway keratins 6A, 6B and 16. The loricrin (LOR) expression level was significantly decreased in lesional AD skin (fold change 0.5; p < 0.01). The expression of the majority of 1q21 genes and alternative keratins was closely correlated; however, for SPRR1A (and SPRR2C) in lesional skin, the correlation with other genes was lost.. We hypothesize that the deregulated increase in SPRR1A expression in chronic atopic skin lesions reflects an insufficient rise in SPRR transcripts, unable to compensate for the lack of LOR and thus contributing to the persistence of chronic AD skin lesions. Turning off the stress response in the skin may be regarded as a goal in the treatment of AD skin lesions, and SPRR genes might be targets for such an approach.

Topics: Adult; Chronic Disease; Cornified Envelope Proline-Rich Proteins; Dermatitis, Atopic; Female; Filaggrin Proteins; Gene Expression Regulation; Humans; Immunoglobulin E; Intermediate Filament Proteins; Keratins; Male; Membrane Proteins; Middle Aged; Protein Precursors; S100 Proteins; Skin

To clarify the relationship between clinical symptoms and histological status in patients with ocular cicatricial pemphigoid (OCP) and Stevens-Johnson syndrome (SJS).. Clinical symptoms of four OCP and eight SJS patients in the chronic phase were scored with our recently proposed grading system. The histological status of the pannus tissue removed from the corneal surface during surgery was investigated using immunohistological techniques.. All participants showed total loss of the palisades of Vogt and conjunctivalization of the entire corneal surface. All pannus tissues expressed the conjunctival epithelium marker CK4/13. The pannus tissue in clinically keratinized SJS expressed skin epidermal major cytokeratins, but the tissues of nonkeratinized SJS did not.. Clinical observation and the use of our recently proposed grading system agreed with the immunohistological status with respect to keratinization, cell proliferation, and corneal/conjunctival cell typing. These findings facilitate our understanding of the pathogenesis of OCP and SJS, and will hopefully contribute to the development of future treatment strategies and improve predictions of the postoperative prognosis of ocular surface reconstruction in patients with OCP and SJS.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antigens, CD; Biomarkers; Cell Proliferation; Chronic Disease; Conjunctiva; Conjunctival Diseases; Cornea; Corneal Diseases; Epithelial Cells; Female; Fluorescent Antibody Technique, Indirect; Humans; Keratins; Ki-67 Antigen; Male; Middle Aged; Pemphigoid, Benign Mucous Membrane; Preoperative Period; Stem Cells; Stevens-Johnson Syndrome; Visual Acuity; Young Adult

Keratinocytes at wound margins undergo partial epithelial to mesenchymal transition (EMT). Based on previous in vitro and ex vivo findings, Slug (Snai2), a transcriptional regulator of EMT in development, may play an important role in this process.. This study was designed to validate an in vivo role for Slug in wound healing.. Excisional wounds in Slug null and wild type mice were examined histologically at 6, 24, 48, and 72h after wounding; reepithelialization was measured and immunohistochemistry for keratins 8, 10, 14, and 6 and E-cadherin was performed. In 20 Slug null and 20 wild type mice exposed three times weekly to two minimal erythemal doses of UVR, the development of non-healing cutaneous ulcers was documented. Ulcers were examined histologically and by immunohistochemistry.. The reepithelialization component of excisional wound healing was reduced 1.7-fold and expression of the Slug target genes keratin 8 and E-cadherin was increased at wound margins in Slug null compared to wild type mice. In contrast, no differences in expression of keratins 10 or 14 or in markers of proliferation K6 and Ki-67 were observed. Forty per cent of Slug null mice but no wild type mice developed non-healing cutaneous ulcers in response to chronic UVR. Keratinocytes at ulcer margins expressed high levels of keratin 8 and retained E-cadherin expression, thus resembling excisional wounds.. Slug is an important modulator of successful wound repair in adult tissue and may be critical for maintaining epidermal integrity in response to chronic injury.

Topics: Animals; Cadherins; Chronic Disease; Female; Keratinocytes; Keratins; Male; Mice; Mice, Knockout; Radiation Injuries, Experimental; Skin; Skin Ulcer; Snail Family Transcription Factors; Transcription Factors; Wound Healing

In the present study, the immunoprofile of chronic sclerosing sialadenitis, also known as Kuttner tumor, was analyzed. Two cases that occurred in the submandibular gland of male patients were submitted to immunohistochemical reactions to different antibodies. Histological examinations showed a submandibular gland exhibiting various degrees of atrophy with destruction of acini, infiltration by inflammatory cells, and periductal fibrosis. Reactions to cytokeratins (CKs) showed acini and duct remnants positive to CKs 7, 8, 19, and 13. CK14 stained myoepithelial cells around preserved acini and intercalated duct, and also basal cell of excretory ducts, but was negative in proliferating and branching ducts. Smooth muscle actin (SMA) was expressed by myofibroblasts in periductal fibrosis, and an intense expression of extracellular components was also seen. Lymphocyte markers showed, besides mature follicles, a higher presence of CD45RO positive cells. Thus, the immunoprofile of Kuttner is much more in keeping with an inflammatory-induced degenerative disease than with a preneoplastic lesion.

Topics: Adult; Biomarkers; Chronic Disease; Fluorescent Antibody Technique, Indirect; Humans; Immunoenzyme Techniques; Keratins; Male; Sclerosis; Sialadenitis; Submandibular Gland

The pathogenesis of respiratory epithelial adenomatoid hamartoma (REAH) and inverted papilloma (IP) is poorly understood, especially compared with sinonasal adenocarcinoma (SNAC). One feature of malignant glandular lesions is loss of the basal/myoepithelial layer. The immunophenotype of the basal/myoepithelial layer has not been fully examined in benign glandular lesions of the sinonasal tract.. To examine benign and malignant glandular lesions in the sinonasal tract for the immunophenotype of basal/myoepithelial cells, proliferation index, and cytokeratin and intestinal differentiation profiles.. Sinonasal adenocarcinoma (intestinal-type adenocarcinoma [ITAC] and nonintestinal type adenocarcinoma [non-ITAC]), REAH, IP, and chronic sinusitis (CS) were stained for cytokeratin (CK) 7, CK20, 34betaE12, CDX-2, p63, Ki-67, smooth muscle actin (SMA), S100 protein, and calponin.. Basal/myoepithelial cells in CS and REAH were positive for p63 and 34betaE12 but negative for SMA, S100 protein, and calponin. Proliferative activity was localized to the compartment containing p63-positive cells. Inverted papilloma demonstrated broad areas staining for p63 and 34betaE12, with intermediate proliferative activity in these areas. Sinonasal adenocarcinoma had the highest Ki-67 labeling index, and p63-positive SNACs had higher proliferation indices than p63-negative SNACs. REAH, IP, CS, and most SNACs expressed CK7. Only SNAC expressed CK20. Sixty percent of morphologic ITACs expressed CDX-2.. Basal/myoepithelial cells in CS and REAH should be considered basal and not myoepithelial cells. In benign lesions, proliferative activity is limited to the compartments with p63 staining. In SNAC and IP, p63 expression correlates with proliferation index. REAH, IP, and CS share similar immunoprofiles (CK7+, CK20-, and CDX-2-), contrasting with SNAC (CK7+, CK20+/-, CDX-2-/+).

Topics: Actins; Adenocarcinoma; Biomarkers, Tumor; Calcium-Binding Proteins; Calponins; CDX2 Transcription Factor; Cell Proliferation; Chronic Disease; Diagnosis, Differential; Epithelial Cells; Female; Hamartoma; Homeodomain Proteins; Humans; Immunohistochemistry; Immunophenotyping; Keratins; Ki-67 Antigen; Male; Membrane Proteins; Microfilament Proteins; Middle Aged; Papilloma; Paranasal Sinus Neoplasms; S100 Proteins; Sinusitis; Trans-Activators

Anal fistulas are the result of chronic infection of an intersphincteric gland. Despite the passage through mesenchymal tissue, fistulas seldom lead to systemic infection. Antimicrobial peptides are secreted by a variety of epithelia, belonging to the innate immune system and are potential factors contributing to infection control. The aim of this study was to investigate whether epithelium is present in the fistulas and what the origin might be.. Forty-seven chronic anal fistulas from patients, excluding Crohn's disease, were compared with healthy rectal and perianal control tissue. Expression of antimicrobial peptide mRNA was analysed by real-time polymerase chain reaction (RT-PCR) and immunohistochemistry. Tissue was further studied by cytokine and cytokeratin staining.. Chronic anal fistulas express high levels of hBD-2 and hBD-3 and the newly identified antimicrobial peptides RNase7 and psoriasin compared to rectal mucosa from control patients. Perianal skin has almost identical levels of RNase7 and psoriasin expression to those in fistulas. IL-1b and IL-8 were the only cytokines detectable in fistulas. Fistulas are lined with squamous epithelium that expresses identical cytokeratines as skin.. Epithelialization and local production of antimicrobial peptides in anal fistulas serve as defence mechanisms to prevent local and systemic infection by microbes from faeces passing through the fistula tract.

Topics: Adult; beta-Defensins; Calcium-Binding Proteins; Chronic Disease; Epithelium; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Rectal Fistula; Rectum; Reverse Transcriptase Polymerase Chain Reaction; Ribonucleases; S100 Calcium Binding Protein A7; S100 Proteins; Skin

To investigate the expression of different cytokeratins (CKs) in gastric epithelium of adult patients with chronic gastritis infected with Helicobacter pylori (H pylori) cagA+ strains.. The expression of CK 7, 8, 18, 19 and 20 was studied immunohistochemically in antral gastric biopsies of 84 patients. All the CKs were immunostained in cagA+H pylori gastritis (57 cases), non-H pylori gastritis (17 cases) and normal gastric mucosa (10 cases).. In cagA+ H pylori gastritis, CK8 was expressed comparably to the normal antral mucosa from surface epithelium to deep glands. Distribution of CK18 and CK 19 was unchanged, i.e. transmucosal, but intensity of the expression was different in foveolar region in comparison to normal gastric mucosa. Cytokeratin 18 immunoreactivity was significantly higher in the foveolar epithelium of H pylori-positive gastritis compared to both H pylori-negative gastritis and controls. On the contrary, decrease in CK19 immunoreactivity occurred in foveolar epithelium of H pylori-positive gastritis. In both normal and inflamed antral mucosa without H pylori infection, CK20 was expressed strongly/moderately and homogeneously in surface epithelium and upper foveolar region, but in H pylori -induced gastritis significant decrease of expression in foveolar region was noted. Generally, in both normal antral mucosa and H pylori-negative gastritis, expression of CK7 was not observed, while in about half cagA+ H pylori-infected patients, moderate focal CK7 immunoreactivity of the neck and coiled gland areas was registered, especially in areas with more severe inflammatory infiltrate.. Alterations in expression of CK 7, 18, 19 and 20 together with normal expression of CK8 occur in antral mucosa of H pylori-associated chronic gastritis in adult patients infected with cagA+ strains. Alterations in different cytokeratins expression might contribute to weakening of epithelial tight junctions observed in H pylori-infected gastric mucosa.

Topics: Adult; Antigens, Bacterial; Bacterial Proteins; Chronic Disease; Female; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Prospective Studies

Although the causative agent of Lyme disease is definitively known to be the tick-borne spirochete, Borrelia burgdorferi, the etiology of chronic joint inflammation that ensues in a subset of patients remains less well understood. Persistence of arthritis after apparent eradication of the spirochete suggests an autoimmune reaction downstream of the original bacterial infection. We have generated recombinant Ab probes from synovial lesions within affected arthritic joints in an attempt to recapitulate disease-relevant Ag-binding specificities at the site of injury. Using this panel of intra-articular probes, as well as Ab fragments derived from patient peripheral blood, we have identified cytokeratin 10, present in synovial microvascular endothelium, as a target ligand and a putative autoantigen in chronic, antibiotic treatment-resistant Lyme arthritis. Furthermore, there is cross-reactivity between cytokeratin 10 and a prominent B. burgdorferi Ag, outer surface protein A. Release of the self protein in the context of inflammation-induced tissue injury and the resulting in situ response to it could set in motion a feed-forward loop, which amplifies the inflammatory process, thereby rendering it chronic and self-perpetuating, even in the absence of the inciting pathogen.

Topics: Autoantibodies; Autoantigens; Binding Sites, Antibody; Chronic Disease; Drug Resistance, Bacterial; Endothelium, Vascular; Humans; Keratin-10; Keratins; Lyme Disease; Synovial Membrane

Both Helicobacter pylori and gastro-oesophageal reflux disease (GORD) may cause inflammation in cardiac mucosa. Intestinal metaplasia (IM) is found more often in GORD associated inflammation than in inflammation caused by H pylori, especially in young individuals.. To examine morphological differences in chronic inflammation in these two conditions by immunohistochemistry.. Tissue blocks from cardiac mucosa of patients <45 years were available as follows: 10 patients with chronic inflammation of cardiac mucosa (carditis) and H pylori gastritis (group 1); 10 patients with (possibly GORD related) carditis, but normal antrum and corpus (group 2); and 10 patients with non-inflamed cardiac mucosa and normal antrum and corpus (group 3). Haematoxylin and eosin staining and immunohistochemical staining for various inflammatory cells were performed for patients in groups 1 and 2 as follows: CD20 (B cells), CD3 (T cells), CD4 (T helper cells), CD8 (T suppressor cells), CD163 (macrophages), CD138 (plasma cells), and CD117 (mast cells). For all patients, cytokeratin 7/20 (CK7/20) staining was performed.. No clear differences were seen in the morphology of chronic inflammation between groups 1 and 2. In both, plasma cells were most abundant. CK7/20 staining showed no differences between these groups.. Helicobacter pylori negative (possibly GORD associated) and H pylori related carditis cannot be distinguished on a morphological basis. The stronger tendency towards IM in the first entity cannot be explained by differences in the type of inflammation. Barrett-type CK7/20 staining seems typical for cardiac mucosa, irrespective of the type of inflammation or presence of IM.

Topics: Adult; Antigens, CD; Biomarkers; Chronic Disease; Connective Tissue Cells; Female; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Male; Mucous Membrane; Myocarditis; Plasma Cells; T-Lymphocytes

According to recent reports, deformity and size of mesothelial cells reflect mesothelial condition. We applied flow cytometry (FCM) to the analyzation of mesothelial cells in peritoneal dialysis effluent (PDE) and the relationship between the period of peritoneal dialysis (PD) and peritoneal function. Eighteen patients treated for two to 89 months by PD were selected. Their dialysate: plasma creatinine ratio (D/P creatinine)was 0.67 +/- 0.086 (0.53 to 0.87). Overnight PDE was drained and centrifuged. The cell population of peritoneal cells identified by anti-cytokeratin, CD14 and 45 antibodies was studied by FCM. Cytokeratin positive cells were identified as mesothelial cells, distinct from macrophages, granulocytes or lymphocytes. The forward scatter (FSC) of cytokeratin positive cells, fluorescence intensity of cytokeratin and percentage of cytokeratin-positive cells in PDE were 395.6 +/- 55.5 (298.31 to 527.72), 333.9 +/- 272.9 (67.55 to 1,071.95), and 6.75 +/- 6.1% (0.44 to 21.14), respectively. There was a positive correlation between D/P creatinine and FSC, and a negative correlation between D/P creatinine and cytokeratin fluorescence intensity or the percentage of cytokeratin positive cells. However, there was no correlation between the period of PD and FSC, cytokeratin fluorescence intensity or the percentage of cytokeratin-positive cells. It was suggested that the alteration of mesothelial cells is not necessarily influenced by the period of PD, but influences peritoneal function. It was found that the analysis of cell population by FCM reflects the morphological and functional changes in the peritoneum of patients on PD.

Topics: Adult; Aged; Cell Separation; Chronic Disease; Dialysis Solutions; Epithelial Cells; Female; Flow Cytometry; Glomerulonephritis; Humans; Keratins; Male; Middle Aged; Peritoneal Dialysis; Peritoneum

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Chronic Disease; Cytosine; Guanine; Hepatitis, Autoimmune; Hepatitis, Viral, Human; Histidine; Humans; Keratin-8; Keratins; Liver Cirrhosis; Liver Diseases; Middle Aged; Mutation, Missense; Tyrosine

There is evidence that neuropeptides, especially the opiate receptor agonists, are involved in wound healing. We have previously observed that beta-endorphin, the endogenous ligand for the mu-opiate receptor, stimulates the expression of cytokeratin 16 in a dose-dependent manner in human skin organ cultures. Cytokeratin 16 is expressed in hyperproliferative epidermis such as psoriasis and wound healing. Therefore we were interested to study whether epidermal mu-opiate receptor expression is changed at the wound margins in acute and chronic wounds. Using classical and confocal microscopy, we were able to compare the expression level of mu-opiate receptors and the influence of beta-endorphin on transforming growth factor beta type II receptor in organ culture. Our results show indeed a significantly decreased expression of mu-opiate receptors on keratinocytes close to the wound margin of chronic wounds compared to acute wounds. Additionally beta-endorphin upregulates the expression of transforming growth factor beta type II receptor in human skin organ cultures. These results suggest a crucial role of opioid peptides not only in pain control but also in wound healing. Opioid peptides have already been used in animal models in treatment of wounds; they induce fibroblast proliferation and growth of capillaries, and accelerate the maturation of granulation tissue and the epithelization of the defect. Furthermore opioid peptides may fine-tune pain and the inflammatory response while healing takes place. This new knowledge could potentially be used to design new locally applied drugs to improve the healing of painful chronic wounds.

Topics: Acute Disease; beta-Endorphin; Chronic Disease; Dose-Response Relationship, Drug; Gene Expression Regulation; Humans; Keratins; Organ Culture Techniques; Protein Serine-Threonine Kinases; Receptor, Transforming Growth Factor-beta Type II; Receptors, Opioid, mu; Receptors, Transforming Growth Factor beta; Wound Healing; Wounds and Injuries

Damaged mucosal sites seem to be vulnerable to tumor cell implantation. We describe a case of exfoliated tumor cells from a sigmoid colon cancer seeding a long-standing anal fistula. The implications of this finding are reviewed.

Topics: Adenocarcinoma; Aged; Chronic Disease; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Male; Neoplasm Seeding; Sigmoid Neoplasms

Intestinal metaplasia is a histologic hallmark of Barrett's esophagus and chronic gastritis. Intestinal metaplasia may progress to dysplasia or carcinomas without proper treatment. Most cases of intestinal metaplasia are easily recognized on hematoxylin and eosin-stained sections. However, some cases of intestinal metaplasia may be hard to recognize if they lack the characteristic mucin-producing cells and Paneth cells, or if they are small in size. Recently, keratin 7, keratin 20, and MUC2 expression patterns were reported to be useful in confirming the diagnosis of intestinal metaplasia. We studied hepatocyte (Hep) antigen (a hepatocellular antigen mainly expressing in normal and neoplastic hepatic tissues) in 33 cases of Barrett's esophagus (9 cases associated with esophageal adenocarcinoma) and 13 cases of chronic gastritis associated with intestinal metaplasia and gastric adenocarcinoma. Hep monoclonal antibody recognizes intestinal metaplasia in all cases. We also compared expression of Hep with that of keratin 7, keratin 20, and MUC2 in intestinal metaplasia. The specificity and sensitivity of Hep for intestinal metaplasia were higher than that of keratin 7 and keratin 20, or MUC2. We conclude that Hep may be used as a single diagnostic marker for intestinal metaplasia.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Barrett Esophagus; Biomarkers, Tumor; Chronic Disease; Esophageal Neoplasms; Gastritis; Hepatocytes; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Metaplasia; Mucin-2; Mucins; Precancerous Conditions; Sensitivity and Specificity; Stomach Diseases

Topics: Chronic Disease; Humans; Keratin-8; Keratins; Pancreatitis

Keratin 8 (K8) and 18 (K18) are the major components of the intermediate filament cytoskeleton of pancreatic acinar cells and play a relevant role in pancreatic exocrine homeostasis. Transgenic mice for K8 have shown to display progressive exocrine pancreas alterations, including dysplasia, loss of acinar architecture, redifferentiation of acinar to ductal cells, inflammation, fibrosis, and substitution of exocrine tissue by adipose tissue.. To investigate whether mutations in the keratin 8 gene are associated with chronic pancreatitis.. Mutations in the keratin 8 gene were determined by polymerase chain reaction/restriction fragment length polymorphism in 67 chronic pancreatitis patients and 100 normal controls. Sequence analysis was performed when necessary.. Glycine-to-cysteine mutations at position 61 (G61C) of the keratin 8 gene were found in six patients (8.9 vs. 0%, p(c) < 0.003, odds ratio = 21.24, confidence interval = 2.74-164.42); none of the controls presented the mutation. No tyrosine-to-histidine mutations at position 53 (Y53H) were detected in any subject.. G61C mutation of the keratin 8 gene, together with other environmental factors and/or genetic factors, could predispose to chronic pancreatitis, by interfering with the normal organization of keratin filaments.

Topics: Chronic Disease; Female; Humans; Keratin-8; Keratins; Male; Middle Aged; Mutation; Pancreatitis

An 83-year-old patient presented herself with a ten-year history of keratotic papules on her trunk. A biopsy of this process revealed granular parakeratosis confined to the infundibulum of a follicle. Exclusive follicular involvement in granular parakeratosis has not been previously described.

Topics: Aged; Aged, 80 and over; Chronic Disease; Female; Folliculitis; Hair Follicle; Humans; Keratins; Parakeratosis

Cure for ductal adenocarcinoma of the pancreas is restricted to resectable tumors, but survival after surgery is still poor. Despite apparently curative resection, these cancers rapidly recur. Thus, the present pathologic examination should be enriched by sensitive methods to detect minimal residual disease. In a prospective setting we studied the frequency of minimal residual disease after curative resection by routine histopathology, immunohistology, and polymerase chain reaction (PCR) for mutated K-ras. Furthermore, the prognostic implication of detecting of MRD was determined. Prospectively, tumor tissue and corresponding paraaortic lymph nodes were obtained from 78 patients, who underwent surgery for pancreatic head tumors between 1999 and 2001. Sixty-nine of 78 cases were diagnosed for ductal adenocarcinoma (study group), whereas nine cases were diagnosed for benign pancreatic tumors (control group). Paraaortic lymph nodes were examined in step sections by routine histopathology (hematoxylin and eosin) and immunohistology using a pan-cytokeratin antibody. DNA of the primary tumor and corresponding paraaortic lymph nodes were analyzed by PCR-based assays with respect to mutated K-ras in codon 12. The recurrence-free survival and overall survival were correlated with the results of the latter methods. In 3 of 69 patients tumor cells were detected in paraaortic lymph nodes by routine histopathology and in 5 of 69 patients by immunohistology. K-ras mutations were detected in 42 of 69 ductal adenocarcinomas (61%), whereas 12 (17%) were positive in paraaortic lymph nodes. All of the latter patients had recurrence after surgery and a significant poorer survival than those without mutated K-ras. Furthermore, paraaortic lymph nodes diagnosed for K-ras mutation were independent prognostic markers in multivariate analysis. In the control group K-ras mutations were detected in one adenoma of Vater's papilla but not in paraaortic lymph nodes. Tumor cell DNA can be detected more sensitively by the described PCR method than with hematoxylin and eosin or immunohistologic staining, leading to a higher sensitivity for detection of micrometastases. The described PCR method clearly determines subgroups of patients after curative resection with early recurrence and poor survival and could therefore enrich the pathologic examination.

Topics: Adenocarcinoma; Aged; Aorta; Chronic Disease; Cystadenoma; Diagnostic Tests, Routine; DNA, Neoplasm; Female; Genes, ras; Humans; Immunohistochemistry; Keratins; Lymphatic Metastasis; Male; Middle Aged; Multivariate Analysis; Mutation; Neoplasm Staging; Pancreatic Neoplasms; Pancreaticoduodenectomy; Pancreatitis; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Predictive Value of Tests; Prognosis; Sequence Analysis, DNA; Survival Analysis

We report a case of early adenocarcinoma arising in foci of intestinal metaplasia (IM) at a normal-appearing gastroesophageal junction (GEJ). The tumor infiltrated the submucosa without nodal involvement (T1N0). Non-neoplastic mucosa adjacent to neoplasia had foci of incomplete IM with a band-like CK20 positivity of the surface epithelium and a diffuse CK7 staining of both superficial and deep glands. There were histological features of reflux esophagitis as well as chronic non-atrophic, Helicobacter pylori-related pangastritis, without IM, at the extensively assessed gastric mucosa. In this case, the CK7/20 pattern of IM adjacent to neoplasia, the demonstration of reflux esophagitis, and the absence of IM in the stomach favor the theory that the pathogenesis of IM and associated adenocarcinoma of the GEJ is related to gastroesophageal reflux rather than H. pylori infection.

Topics: Adenocarcinoma; Aged; Cardia; Chronic Disease; Esophagogastric Junction; Gastrectomy; Gastric Mucosa; Gastritis; Humans; Immunohistochemistry; Keratins; Male; Metaplasia; Stomach Neoplasms

The pathological lining epithelium of destructive periodontitis was studied by analysis of the expression of intermediate filament proteins in biopsies of untreated advanced periodontitis. The cytokeratin (CK) pair 8/18 characteristic of simple epithelia was expressed consistently in a distribution pattern confined to the reactive pocket epithelium. The pattern of CK8/18 expression was complex with two broad presentations evident. In two-thirds of the advanced disease biopsies, the entire pathological lining epithelium was strongly reactive for both CK8 and CK18. In the remainder, the more superficial lining epithelium was mixed with foci of reactive and unreactive cells, with the deeper epithelium uniformly reactive. Only occasional highly localised reactivity for the simple keratins (CK8/18) was found in the lining epithelia of biopsies from minimally inflamed periodontal tissues. The pathological lining epithelium of advanced periodontitis was further characterised by the co-expression in basal layers of CK14, and of CK13 but not CK4, which are characteristic of suprabasal layers of stratified squamous epithelia. Cytokeratin 17, a marker of high turnover and migrating epithelial cells was extremely variable with no clear association between expression pattern and location of the epithelium ordisease status. There was no reactivity for CK10/11 typical of cornifying cells nor of vimentin, the characteristic intermediate filament of mesenchymal cells. The intermediate filament protein profile of the reactive lining epithelium was indistinguishable from the reactive epithelium present in three of five biopsies of periapical granulomas containing hyperplastic epithelium from activation of the developmental remnants of Hertwig's sheath, known as the cell rests of Malassez. The data reported are compatible with a contribution by remnants of developmental epithelium, including the reduced enamel epithelium and the cell rests of Malassez, to the reactive lining epithelium of the subgingival pocket in the pathogenesis of chronic periodontitis.

Topics: Adult; Aged; Chronic Disease; Enamel Organ; Epithelial Attachment; Epithelial Cells; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Periodontal Ligament; Periodontal Pocket; Periodontitis; Tooth Root

Based on the fact that pancreatic carcinoma is still associated with poor outcome, the aim of the study was to determine frequency of early tumor cell dissemination using immunohistology in lymph nodes classified as tumor-free by conventional histopathology.. Fifteen patients with ductal pancreatic carcinoma and 10 patients with carcinoma of the papilla of Vater underwent radical tumor resection (resection status R0, tumor staging pTxpN0M0). In total, 229 lymph nodes classified as tumor-free by histopathology were investigated for disseminated tumor cells using antibodies against cytokeratin and CA19-9. As control, 81 lymph nodes obtained from patients with chronic pancreatitis were analyzed.. In 55 of 229 lymph nodes (26.3%), cytokeratin-positive, disseminated tumor cells were detected. Cytokeratin-positive cells were found in at least one resected lymph node of each patient with ductal carcinoma of the pancreatic head (100%), whereas in patients with carcinoma of the papilla of Vater, no disseminated tumor cells were detected using the antibody against cytokeratin. Similarly, there was no detection of tumor cells (false-positive) in patients with chronic pancreatitis. In contrast, CA19-9 antigen was detectable in resected lymph nodes of each of the 25 carcinoma patients (pancreatic carcinoma and carcinoma of the papilla of Vater). Interestingly, 52 of 81 lymph nodes (64.2%) from the control group (chronic pancreatitis) were false-positive.. Detection of disseminated tumor cells in lymph nodes using an antibody against cytokeratin is specific and suitable while use of an antibody against CA19-9 is not recommendable because of the high rate of false-positive results. The results may indicate that ductal pancreatic carcinoma generates early dissemination of tumor cells into lymph nodes. This may be one explanation for the poor outcome of this carcinoma compared with that of the carcinoma of the papilla of Vater (14 versus 48 months P < 0.05).

Topics: Adenocarcinoma; Adult; Aged; Ampulla of Vater; Biomarkers, Tumor; CA-19-9 Antigen; Carcinoma; Chronic Disease; Common Bile Duct Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Pancreatic Neoplasms; Pancreatitis; Predictive Value of Tests; Prognosis

To investigate anti-crypt keratin (CK) immunologic histochemical changes in children with chronic tonsillitis.. Removed tonsilla were fixed by 10% formaldehyde. Immunologic histochemical method was used to determine the changes of anti-broad spectrum (KD 68, 56, 56, 50) CKSP.. In 230 cases, obvious keratosis was 90.9%, no keratosis was 9.1%, 3 cases were found with fungus filaments and bacteria in the bottom of crypts. Anti-broad spectrum and hypermolecule CK of tonsil cryptic epithelium were positive reaction, anti-broad spectrum CK of cryptic keratosis in all cases was positive reaction.. During the period of episode, cryptic epitheliums of tonsilla was destroyed repeatly, therefore, immunoglobulin production was reduce. Because the immune function of tonsilla was reduced, bacteria and virus might be invade into organism. This reduplicative malignant circles must be interrupted or blocked only by tonsillectomy.

Topics: Adolescent; Antibodies; Child; Child, Preschool; Chronic Disease; Epithelium; Female; Humans; Immunohistochemistry; Keratins; Keratosis; Male; Palatine Tonsil; Tonsillitis

Differentiating chronic aseptic meningitis from leptomeningeal carcinomatosis or gliomatosis can be difficult, particularly when the differentiation is based solely on routine cytologic examination. The diagnosis of cerebrospinal fluid tumor dissemination in at-risk patients requires cytologic examination of cerebrospinal fluid and radiography of the leptomeninges. Routine cytologic examination alone has proven less than desirable, in most instances providing confirmation in as little as 50% of cases in the first lumbar puncture. This percentage increases to 85% to 90% after multiple lumbar punctures. We retrospectively reviewed 2 cases of leptomeningeal dissemination (one gliomatosis, the other carcinomatosis) with initial false-negative test results. However, after further examination of the cerebrospinal fluid by selected battery of immunocytochemical stains, both cases were identified as positive for malignancy (ie, false negatives). Immunocytochemistry can be useful in distinguishing chronic aseptic meningitis from leptomeningeal carcinomatosis or gliomatosis in patients at risk or when abnormal cells are seen on routine cerebrospinal fluid cytologic examination.

Topics: Adult; Aged; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Brain Edema; Calcinosis; Cerebrospinal Fluid; Cholangiocarcinoma; Chronic Disease; Diagnosis, Differential; Fatal Outcome; Female; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Keratins; Male; Meningeal Neoplasms; Meningitis, Aseptic; Mucin-1; Neoplasms, Neuroepithelial; Retrospective Studies

Myofibroblasts are the primary cells responsible for increased matrix deposition in hepatic fibrosis. Activation of hepatic stellate cells and portal fibroblasts to myofibroblasts during cholestatic liver injury is accompanied by increased expression of the activation marker, alpha-smooth muscle actin (SMA), and collagen genes. In contrast to our understanding of injury, the cellular mechanisms of liver repair are not well defined. This study was designed to examine the morphological relationship between bile duct hyperplasia, matrix deposition and myofibroblast phenotype in a model of chronic cholestatic liver injury and repair.. Reversible extrahepatic obstruction was accomplished in rats using a soft vessel loop suspended from the anterior abdominal wall: duct manipulation alone was performed in sham-operated controls. After 7 days, rats were either sacrificed or decompressed by release of the loop and subsequently sacrificed 2-10 days after reversal. Liver sections were obtained for in situ hybridization for procollagen alpha1(I) mRNA, immunohistochemical staining for SMA and cytokeratin 19, and histochemical staining for reticulin.. Cholestatic livers demonstrated bile duct hyperplasia, which reversed to normal within 10 days after decompression. Fibrosis was also substantially reduced during this period. SMA-positive myofibroblasts were abundant and localized to regions adjacent to proliferating ducts and excess matrix in the obstructed animals. Decompressed livers showed a dramatic time-dependent reduction in the number of SMA-positive cells and in the expression of procollagen I mRNA.. Our results show that the disappearance of bile duct hyperplasia after biliary decompression is accompanied by a similarly rapid loss of SMA-positive myofibroblasts. Both cellular events may abrogate enhanced matrix synthesis and allow repair to occur.

Topics: Actins; Alanine Transaminase; Animals; Bile Ducts; Bilirubin; Cholestasis, Extrahepatic; Chronic Disease; Disease Models, Animal; Extracellular Matrix; Fibroblasts; gamma-Glutamyltransferase; Histocytochemistry; Hyperplasia; Keratins; Liver; Liver Cirrhosis, Experimental; Liver Regeneration; Male; Procollagen; Rats; Rats, Sprague-Dawley; Reticulin; RNA, Messenger

The expression of keratins and filaggrin by keratinocytes is a highly regulated process and depends on their state of differentiation and proliferation. As such, these proteins can be used as markers to determine if keratinocyte differentiation is normal. Mutant cpdm/cpdm mice develop a chronic skin disease characterized by epidermal hyperplasia and inflammation. Immunohistochemical staining for the basal keratins K5 and K14 revealed expression in the basal and suprabasal cell layers. The expression of K1 and K10 was reduced and limited to the outer layers of the stratum spinosum. Keratin 6 was expressed in the suprabasal layers of affected skin, and throughout all layers in severely affected skin. Filaggrin was present in the stratum granulosum which had variable thickness. These results indicate that the differentiation of keratinocytes in cpdm/cpdm mice was normal. The altered distribution and expression of keratins in comparison with the skin of control mice was the result of hyperproliferation.

Topics: Animals; Chronic Disease; Dermatitis; Filaggrin Proteins; Hyperplasia; Immunohistochemistry; Intermediate Filament Proteins; Keratinocytes; Keratins; Mice; Mice, Inbred C57BL; Mutation; Skin

Hepatocytes of normal adult liver express cytokeratins (CKs) 8/18, but bile duct cells additionally contain CK7/19. We have previously demonstrated the frequent occurrence of foci of altered hepatocytes in association with hepatic tumors in humans and provided evidence for a preneoplastic nature of the focal lesions. In this study, we investigated the CK expression in both the preneoplastic lesions and extrafocal parenchyma. Sixty-seven explanted livers with cirrhosis or advanced fibrosis harboring preneoplastic focal lesions, with or without hepatitis B virus (HBV) infection, as well as 9 livers with HBV-associated fulminant hepatitis, were studied for the expression of CK7/8/14/18/19. Five livers from woodchucks infected with the woodchuck hepatitis virus (WHV) were also investigated. Glycogenotic clear hepatocytes were negative or weakly positive for CK8/18, while amphophilic hepatocytes were strongly positive for these CKs, the changes being associated with marked reduction and increase, respectively, of highly organized membranous components in their cytoplasm. This allows the distinct recognition of the clear-cell and clear-cell-dominant preneoplastic lesions in the human and woodchuck livers. In ground-glass hepatocytes expressing viral antigens, an unusual accumulation of CK8/18 was observed, but there was no evidence of preferential necrosis of ground-glass hepatocytes. Many CK7- and CK19-positive ductular (oval) cells were found in extrafocal liver tissue, but only rarely were they present within focal lesions.

Topics: Adult; Animals; Chronic Disease; Glycogen; Hepadnaviridae Infections; Hepatitis B; Humans; Immunohistochemistry; Keratins; Liver; Marmota; Microscopy, Electron; Precancerous Conditions

Chronic infection of woodchucks with woodchuck hepatitis virus (WHV) invariably leads, within 2-4 years, to the appearance of hepatocellular carcinoma (HCC). HCC is preceded by an extended period of chronic liver damage, probably resulting from the immune response to viral antigens. It may be that infection itself also induces changes in the hepatocyte population. To begin to identify some of the changes in the liver prior to the appearance of HCC, monoclonal antibodies (MAbs) were generated from mice immunized with hepatocytes from a woodchuck chronically infected with WHV or with a tumor lysate. Immunofluorescence microscopy was used to select MAbs that reacted with host markers whose patterns of expression would distinguish chronically infected from uninfected liver or from liver tumors. One of these MAbs (2F2) reacted strongly with a subset of hepatocytes in chronically infected liver; a similar staining pattern was not detected in uninfected or transiently infected liver. Evidence is presented that this strong staining reaction reflects the overexpression or accumulation of the hepatocyte-specific intermediate filament protein, cytokeratin K18, a protein previously implicated in cryptogenic cirrhosis of the liver in humans (Ku, N. O. , Wright, T. L., Terrault, N. A., Gish, R., and Omary, M. B. J. Clin. Invest. 99: 19-23, 1997). Double immunofluorescent staining with antibodies to K18 and M-envelope protein of WHV suggested that strong reactivity to K18 was limited to cells expressing high levels of one or both of the large viral-envelope proteins, M and L; however, high expression of these viral proteins was not always associated with a strong K18 staining reaction.

Topics: Animals; Antibodies, Monoclonal; Chronic Disease; Female; Hepatitis B; Hepatitis B Virus, Woodchuck; Immunohistochemistry; Keratins; Liver; Mice; Mice, Inbred BALB C

The presence of keratin in the middle ear cavity is usually associated with the diagnosis of cholesteatoma or epidermoid metaplasia. Analysis of a series of 18 cases suggests that it may correspond to a specific entity developing in the course of severe or long-lasting opened chronic otitis. This condition, we called mallear epidermosis, is characterized by: i) a perforation of the tympanic membrane lining the handle of the malleus and the umbo; ii) a proliferation of keratin surrounding the handle of the malleus and diffusing into the mesotympanum on the internal side of the tympanic membrane, without matrix; and iii) a mild inflammation of the middle ear epithelium. The process is usually limited to the mesotympanum and does not extend towards the attic and the posterior cavities. Epidemiological, clinical, pathophysiological, and histological features allow this entity to be distinguished from cholesteatoma and epidermoid metaplasia. Management is either medical consisting of local treatment and microaspiration, or surgical including resection of the umbo, removal of the tympanic membrane invaded by the adherent hyperkeratotic layers and repair by conventional underlay myringoplasty. This report emphasizes the need for a clear identification of the various types of chronic otitis media presenting with keratin in the middle ear, as they do not share the same course and do not require the same therapeutic management.

Topics: Adolescent; Adult; Aged; Cholesteatoma, Middle Ear; Chronic Disease; Diagnosis, Differential; Ear, Middle; Epithelium; Female; Humans; Keratins; Male; Malleus; Metaplasia; Middle Aged; Myringoplasty; Otitis Media; Suction; Tympanic Membrane; Tympanic Membrane Perforation

Clinical, histological and immunohistochemical data on 71 parotid gland tumors were analyzed. Benign neoplasms accounted for 71.8% of the case material and malignant tumors 22.6%. Chronic parotitis occurred in 5.6% of the total case number. Pleomorphic adenomas and mucoepidermoid carcinomas were the most frequently occurring benign and malignant neoplasms. Pleomorphic adenomas stained positive for S-100 protein, tenascin, smooth muscle actin, synaptophysin and chromogranin A. This immunohistochemical, histological and clinical analysis was believed to be of potential assistance in the diagnosis, treatment and prognosis of parotid gland tumors.

Topics: Actins; Adenoma, Pleomorphic; Antigens, Neoplasm; Carcinoma, Mucoepidermoid; Chromogranin A; Chromogranins; Chronic Disease; Desmin; Glycoproteins; Humans; Immunoglobulin A, Secretory; Immunohistochemistry; Keratins; Parotid Neoplasms; Parotitis; Prognosis; S100 Proteins; Secretory Component; Synaptophysin; Tenascin; Tumor Suppressor Protein p53

Cytokeratin 19 (CK19) is a specific cytoskeletal structure of simple epithelia, including bronchial epithelial cells (BEC). Since CK19 is released from injured bronchial epithelium, we investigated the levels of CK19 fragments in the bronchoalveolar lavage fluid (BALF) of eight patients with chronic airway inflammatory diseases (CAID) using an enzyme-linked immunosorbent assay (ELISA). Included in our test group were four cases of chronic bronchitis, three cases of bronchiectasis, and one case of diffuse panbronchiolitis. There were also 15 control subjects (five asymptomatic smokers and 10 nonsmokers). BALF from the nonsmokers as well as from the asymptomatic smokers contained few CK19 fragments (0.2 +/- 0.2 and 1.9 +/- 0.8 pg/ml, respectively). In contrast, significantly high levels of CK19 were present in the BALF of patients with CAID (21.7 +/- 5.7 pg/ml; p < 0.01 versus nonsmoking controls). In addition, CK19 fragment concentrations in BALF correlated significantly with the number of neutrophils (r = 0.722, p < 0.01) but not with the numbers of macrophages or lymphocytes in BALF. BALF from patients with CAID contained high levels of neutrophil elastase (NE) activity, suggesting that NE might be an important stimulus for the release of CK19 from BEC. To prove this, we incubated BET-1A cells, a human immortalized bronchial epithelial cell line, both in the absence and the presence of inflammatory mediators (including NE, tumor necrosis factor-alpha [TNF-alpha], and hydrogen peroxide). We then measured the concentration of CK19 fragments in the culture supernatants with ELISA. BET-1A cells released CK19 fragments into their culture supernatants after treatment with NE but not after treatment with TNF or hydrogen peroxide. Further, we demonstrated that CK19 cleaved by NE could not be detected by ELISA. Our results suggest that CK19 measurement in BALF is useful for assessing the presence of bronchial epithelial injuries.

Topics: Adult; Aged; Biomarkers; Bronchi; Bronchiectasis; Bronchiolitis; Bronchitis; Bronchoalveolar Lavage Fluid; Case-Control Studies; Cells, Cultured; Chronic Disease; Enzyme-Linked Immunosorbent Assay; Female; Humans; Inflammation Mediators; Keratins; Male; Middle Aged; Smoking

Multinucleated giant cells in the pancreas (five giant cell carcinomas, a mucinous cystadenocarcinoma attended with many osteoclast-like giant cells, 42 invasive ductal carcinomas and 29 chronic pancreatitises) were examined. Three types of multinucleated giant cell were identified: epithelial type, coexpressive type, mesenchymal type. Epithelial type expressed epithelial markers, such as keratin and EMA in 23 ductal carcinomas. Coexpressive type expressed both epithelial markers and mesenchymal marker vimentin was in four ductal carcinomas. Mesenchymal type expressed mesenchymal markers, vimentin and CD68 in four osteoclastoid type giant cell carcinomas, the mucinous cystadenocarcinoma, six ductal carcinomas and ten chronic pancreatitises. Epithelial and coexpressive type were considered to be epithelial neoplastic origin, those had bizarre appearance and transitional area from definite adenocarcinoma area. Vimentin expression is associated with sarcomatous proliferation. Mesenchymal type was considered to be nonneoplastic and a certain type of macrophage polykaryons.

Topics: Adult; Aged; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Biomarkers; Carcinoma, Ductal, Breast; Carcinoma, Giant Cell; Chronic Disease; Cystadenocarcinoma, Mucinous; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Mucin-1; Pancreatic Neoplasms; Pancreatitis; Vimentin

Human neonatal temporal bones frequently show the formation of granulation tissue provoked by amniotic fluid keratin contents, desquamated keratinized epithelial cells and lanugo hair. Similar histopathologic findings have been produced previously in a short-term animal model. To test the hypothesis that those short-term pathologic observations could have theoretical relevance for ear disease in older patients, a longer term animal model study was necessary.. Into the right bulla of 10 chinchilla pups was placed an aliquot of autogenous, nonviable epidermal scrapings and hair. Into the left bulla was placed 1 mm2 viable autogenous epidermal tissue. Animals were killed at intervals up to 11 months and then studied by light microscopy.. Chronic ear histopathologic changes such as granulation tissue, osteoneogenesis, adhesions, and cholesteatoma were present. Over time, these secondary pathologic changes became more obvious than the initial keratin implant.. The authors conclude that chronic pathologic changes resembling human ear disorders persist and that this model further extends the hypothesis that prenatally acquired keratin eventually could account for some cases of human ear disease.

Topics: Animals; Chinchilla; Chronic Disease; Ear Diseases; Ear, Middle; Epidermis; Granulation Tissue; Hair; Keratins; Transplantation, Autologous

Lichen amyloidosus (LA) is generally said to be a pruritic type of amyloidosis of unknown cause. Histopathologically, it is characterized by epidermal changes of lichen simplex chronicus and by deposits of amyloid in the papillary dermis that are derived from keratin peptides of necrotic keratinocytes. Chronic scratching is responsible for the development of lichen simplex chronicus and may lead to necrosis of individual keratinocytes.. Our purpose was to evaluate whether chronic scratching may also be responsible for the formation of amyloid in LA.. We studied patients with LA in regard to histopathologic findings, onset of pruritus, associated diseases, and response to treatment.. In most cases, pruritus had preceded the skin lesions. Eight of nine patients suffered from diseases other than LA that may be associated with pruritus. Histopathologically, amyloid was confined to areas that also showed signs of lichen simplex chronicus. Systemic treatment with sedating antihistamines and intense local treatment with corticosteroids were found to be effective.. LA is considered to be a variant of lichen simplex chronicus in which scratching leads to necrosis of keratinocytes and eventually to the formation of amyloid in the papillary dermis. Because chronic scratching seems to be the cause and not the result of the deposits of amyloid, treatment should be directed at the amelioration of pruritus.

Topics: Administration, Cutaneous; Adrenal Cortex Hormones; Aged; Amyloid; Amyloidosis; Antipruritics; Chronic Disease; Collagen; Disease; Female; Histamine H1 Antagonists; Humans; Keratinocytes; Keratins; Keratosis; Leg Dermatoses; Male; Middle Aged; Necrosis; Neurodermatitis; Pruritus; Remission Induction; Skin; Skin Diseases

The monitoring of serum concentrations of Cyfra 21-1, tumor polypeptide antigen (TPA), and tissue polypeptide specific antigen (TPS) has been demonstrated to be useful in the clinical treatment of patients with lung cancer. This study was planned to evaluate the clinical usefulness of the assay of these tumor markers on bronchial washing (BW) fluid and to compare it with serum assay in patients with neoplastic and nonneoplastic disease.. Serum and BW fluid levels of Cyfra 21-1, TPA, and TPS were measured in 40 subjects (10 control subjects, 11 with chronic bronchitis, 10 with squamous cell lung cancer, and 9 with nonsquamous cell lung cancer) undergoing diagnostic bronchoscopy. BW was performed using 25 mL of pyrogen-free saline solution instilled through the working channel of the bronchoscope, and successively aspirated. The quantity of the fluid recovered was measured and used for the assay of albumin, Cyfra 21-1, TPA, and TPS.. Mean BW concentrations of Cyfra 21-1, TPA, and TPS concentrations were significantly higher than serum concentrations (p < 0.01). Serum Cyfra 21-1, TPA, and TPS concentrations were significantly lower in controls and in those with chronic bronchitis than in patients with epidermoid and nonepidermoid carcinoma (p < 0.01). No difference in serum concentrations of the three markers was observed between controls and patients with chronic bronchitis. On the contrary, BW Cyfra 21-1 and TPA concentrations were significantly higher in those with chronic bronchitis and in cancer patients than in controls (p < 0.01), whereas they did not differ between patients with chronic bronchitis and cancer patients. No significant difference in BW TPS concentration was observed among the four groups. Sensitivity and specificity of the BW markers in diagnosing lung cancer were as follows: 68.4% and 61.9% for Cyfra 21-1; 68.4% and 66.6% for TPA; and 57.9% and 66.6% for TPS.. BW fluid concentrations of Cyfra 21-1 and TPA are increased in patients with chronic bronchitis and in patients with lung cancer. Being unable to distinguish malignant from nonmalignant inflammatory conditions, the measurement of airway concentrations of such markers has a too-low specificity to be considered useful in diagnosing malignant abnormalities of the lung.

Topics: Adult; Aged; Albumins; Antigens; Antigens, Neoplasm; Biomarkers, Tumor; Bronchitis; Bronchoalveolar Lavage Fluid; Bronchoscopy; Carcinoma; Carcinoma, Squamous Cell; Chronic Disease; Female; Humans; Keratins; Lung Neoplasms; Male; Middle Aged; Peptides; Sensitivity and Specificity; Tissue Polypeptide Antigen

The present study was designed to determine, in a cross-sectional study, whether there was any relationship between the keratin-positive material in gingival crevicular fluid and the clinical periodontal status. Keratins were selected as putative indicators of degradation of epithelial cells cytoskeletal proteins. Keratin positive material was determined by enzyme-linked immunosorbent assay in 42 subjects exhibiting clinical sites of health, chronic gingivitis and chronic periodontitis. The concentration of keratin in parotid saliva was also measured for each subject. Keratin concentration in gingival crevicular fluid samples was significantly greater at sites exhibiting signs of gingivitis and periodontitis compared with healthy sites. No differences were detected between sites exhibiting gingivitis and periodontitis. No differences were found between the 3 groups for the saliva keratin-positive material which was significantly less than that detected in gingival crevicular fluid. These results suggest that gingival crevicular fluid keratin concentration may serve as a marker of gingival damage.

Topics: Adult; Biomarkers; Chronic Disease; Cross-Sectional Studies; Enzyme-Linked Immunosorbent Assay; Gingival Crevicular Fluid; Gingivitis; Humans; Keratins; Middle Aged; Peritonitis; Saliva; Statistics, Nonparametric

Exfoliative cheilitis is an uncommon condition affecting the vermilion zone of the upper, lower or both lips. It is characterized by the continuous production and desquamation of unsightly, thick scales of keratin; when removed, these leave a normal appearing lip beneath. The etiology is unknown, although some cases may be factitious. Attempts at treatment by a wide variety of agents and techniques have been unsuccessful. Three patients with this disease are reported and its relationship to factitious cheilitis and candidal cheilitis is discussed.

Topics: Adolescent; Adult; Candidiasis, Oral; Cheilitis; Chronic Disease; Factitious Disorders; Female; Humans; Keratins; Male; Middle Aged

Many theories concerning the development of chronic pilonidal sinus have been proposed. A histologic study of primary pilonidal sinus in 53 patients is presented. Subcutaneous tissue contained sinuses surrounded by chronic inflammation. Hair in sinuses was found in three quarters of the specimens examined. Examination showed that hair entered via one of the sinus openings created. Pits (defined as darker spots of varying width in the midline of the internatal cleft) were found to be indentations of the skin containing keratin plugs and debris. They may be isolated or connected with hair follicles. Pilonidal sinuses are chronic inflammatory processes of the skin caused by keratin plugs and debris clinically observed as pits, having penetrated the dermis.

Topics: Adolescent; Adult; Chronic Disease; Female; Hair; Humans; Inflammation; Keratins; Male; Middle Aged; Pilonidal Sinus

The two major intermediate filament proteins in glandular epithelia are keratin polypeptides 8 and 18 (K8/18). To evaluate the function and potential disease association of K18, we examined the effects of mutating a highly conserved arginine (arg89) of K18. Expression of K18 arg89-->his/cys and its normal K8 partner in cultured cells resulted in punctate staining as compared with the typical filaments obtained after expression of wild-type K8/18. Generation of transgenic mice expressing human K18 arg89-->cys resulted in marked disruption of liver and pancreas keratin filament networks. The most prominent histologic abnormalities were liver inflammation and necrosis that appeared at a young age in association with hepatocyte fragility and serum transaminase elevation. These effects were caused by the mutation since transgenic mice expressing wild-type human K18 showed a normal phenotype. A relative increase in the phosphorylation and glycosylation of detergent solubilized K8/18 was also noted in vitro and in transgenic animals that express mutant K18. Our results indicate that the highly conserved arg plays an important role in glandular keratin organization and tissue fragility as already described for epidermal keratins. Phosphorylation and glycosylation alterations in the arg mutant keratins may account for some of the potential changes in the cellular function of these proteins. Mice expressing mutant K18 provide a novel animal model for human chronic hepatitis, and for studying the tissue specific function(s) of K8/18.

Topics: 3T3 Cells; Animals; Arginine; Cell Line; Chronic Disease; Cysteine; Cytoskeleton; Disease Models, Animal; Glycoproteins; Glycosylation; Hepatitis, Animal; Histidine; HT29 Cells; Humans; Intermediate Filament Proteins; Keratins; Mice; Mice, Transgenic; Mutagenesis, Site-Directed; Phosphorylation; Solubility; Spodoptera

In this study we have investigated epidermal growth and differentiation during wound healing in human skin. The studies were performed in excisional wounds in normal skin and in chronic venous ulcers. Tissues were analyzed by immunohistochemical staining for proliferation-associated nuclear antigens (PCNA and Ki-67 antigen) and cytokeratin 16. Healing of excisional wounds was studied from day 2 to 14. Recruitment of resting (G0) epidermal cells started within 2 days after wounding; the number of cycling cells was maximal at day 4 and continued to be increased (compared to baseline levels in normal skin) after wound closure (7-14 days). Cytokeratin 16, a proliferation-associated keratin, was induced within 48 h and was expressed in the suprabasal keratinocytes of the wound edge. Cytokeratin 16 expression was maximal at day 4 and was still present in the neo-epidermis after restoration of epidermal continuity (7-14 days). Surprisingly, in chronic venous ulcers, cycling cells were present in the wound edges of all stages of the leg ulcers studied. Both the number and localization of cycling cells were similar to those in normal wound healing. Cytokeratin 16 was strongly expressed in all these ulcers. Our in vivo data demonstrate that recruitment of G0-cells into the cell cycle is not impaired in venous ulcers, which suggests that epidermal proliferation is not a limiting factor in the healing process of chronic venous ulcers.

Topics: Adult; Aged; Cell Differentiation; Cell Division; Chronic Disease; Epidermis; Humans; Keratinocytes; Keratins; Middle Aged; Varicose Ulcer; Wound Healing

All interferons display antiviral properties, but gamma-interferon especially has an immunomodulatory effect and may induce autoimmune phenomena. Therefore the formation of autoantibodies was investigated in patients with chronic hepatitis B treated with gamma-interferon. Eleven patients (all HBs-Ag and HBe-Ag positive) were treated for 6 months with recombinant gamma-interferon. The following antibodies were tested: anti-nuclear antibodies, smooth muscle antibodies, anti-actin, anti-mitochondrial antibodies of subgroup anti-M2 and anti-M9 as well as naturally occurring antibodies, antibodies to liver-kidney microsomes, vascular endothelial cell antibodies, sarcolemmal antibodies, parietal cell antibodies, thyroglobulin antibodies and antibodies to laminin and keratin. All patients produced autoantibodies during therapy. The maximum antibody formation and the highest titres were observed in the period between the 3rd and 6th month after therapy began. The cumulative frequencies of the different antibody specificities were as follows: n = 6 anti-nuclear antibodies, n = 7 smooth muscle antibodies, n = 1 anti-actin, n = 12 antibodies to laminin or keratin, n = 6 endothelial cell antibodies/sarcolemmal antibodies, n = 6 anti-mitochondrial antibodies, n = 1 antibodies to liver-kidney microsomes, n = 2 thyroglobulin antibodies, n = 4 parietal cell antibodies. Antibodies persisted in six patients over a period of 3 months (two cases of parietal cell antibodies and one case of antibodies to liver-kidney microsomes) and were still detectable in three patients 6 months after therapy. In three patients new antibody formation occurred 1 month after therapy. So far, clinical signs of an autoimmune disorder have not appeared in any of the patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Actins; Adolescent; Adult; Antibodies; Antibodies, Antinuclear; Antibody Formation; Antibody Specificity; Autoimmunity; Chronic Disease; Endothelium, Vascular; Female; Hepatitis B; Humans; Interferon-gamma; Keratins; Laminin; Male; Microsomes, Liver; Middle Aged; Mitochondria; Muscle, Smooth

To see how useful the application of a bile duct specific cytokeratin antibody (AE1) was in identifying and counting bile ducts in liver allograft biopsy specimens.. Eighteen liver biopsy specimens showing acute rejection and 17 biopsy specimens plus six hepatectomy specimens showing chronic rejection were studied. Serial sections were cut and stained with haematoxylin and eosin and AE1 antibody. Two pathologists (RFH and KP) examined the sections with respect to a range of histological features.. Similar numbers of bile ducts were identified on haematoxylin and eosin sections as on corresponding sections stained by AE1 in cases of acute rejection and end stage chronic rejection. Greater numbers of bile ducts were identified by AE1 during the early stages of chronic rejection, especially when dense portal inflammatory infiltrates were present. These were often incomplete structures or individual cells within portal tracts, and bile ducts subsequently disappeared in all cases. Ductular proliferation was clearly shown by AE1 in acute rejection and the extent seemed to correlate with the severity of rejection present. By contrast, no ductular proliferation was observed in chronic rejection.. Haematoxylin and eosin stained sections are adequate for counting bile ducts in most biopsy specimens from patients with suspected chronic rejection. Immunostaining for biliary cytokeratins using AE1 is of limited use in occasional cases where bile ducts are obscured by inflammatory cells.

Topics: Acute Disease; Antibodies; Bile Ducts, Intrahepatic; Chronic Disease; Graft Rejection; Humans; Immunohistochemistry; Keratins; Liver Transplantation; Portal System; Staining and Labeling

The nature and origin of the epithelial layers in acquired cholesteatoma is still unclear. Although previous morphological studies comparing external meatal and cholesteatoma epithelium have shown no significant difference, bone resorption is generally much more severe with cholesteatoma than with chronic otitis media without cholesteatoma. It is possible that cholesteatoma epithelium has undergone transformation leading to its enhanced bone destroying role. In this study the cytokeratin patterns of aural and cholesteatoma epithelia grown in cell culture were compared using monoclonal antibodies. No significant difference in staining patterns were found suggesting that there has been no change in cell phenotype which maintains that of external auditory meatus epithelium. This study therefore supports the immigration theory of cholesteatoma genesis.

Topics: Antibodies, Monoclonal; Bone Resorption; Cell Movement; Cells, Cultured; Cholesteatoma, Middle Ear; Chronic Disease; Ear Canal; Epithelium; Gene Expression; Humans; Immunohistochemistry; Keratins; Otitis Media; Phenotype; Skin

The patterns of cytokeratin as determined by murine monoclonal antikeratin antibody lu-5 (mAb lu-5) were quantitated in paraffin-embedded liver tissue from normal and diseased subjects. In tissue from healthy medical students, mAb lu-5 was found to decorate 2-4 periportal and 2-3 perivenular cell layers. Alcoholic liver disease was accompanied by a marked increase in intensity of mAb lu-5 antigen expression in zone I and III hepatocytes. Moreover, additional liver cells of both zones were progressively recruited, so that in advanced lesions all three lobular zones became positive. In mechanical as well as in drug-induced cholestasis, a similar increase of mAb lu-5 antigen expression was already observed in earlier stages of disease, including an earlier recruitment of zone II hepatocytes. In both alcoholic and cholestatic biopsies the intensity and extent of mAb lu-5 epitope expression increased with the duration and severity of disease. In primary biliary cirrhosis (PBC) and seemingly also in primary sclerosing cholangitis the increase and extent was more marked in zone I, the zone of assumed cholate accumulation. Changes in zone III, the territory of histologic cholestasis (bilirubinostasis), became evident only in late stages of PBC. Mallory bodies of alcoholic and cholestatic liver disease showed an identical mAB lu-5 antigen expression, thus giving rise to four different staining patterns. Changes of cytokeratin expression are similar in alcoholic and cholestatic liver diseases. In chronic viral hepatitis, however, cytokeratin alterations are discrete and restricted to precirrhotic/cirrhotic stages.

Topics: Antibodies, Monoclonal; Biopsy; Cholestasis; Chronic Disease; Epithelium; Hepatitis, Viral, Human; Humans; Keratins; Liver Diseases, Alcoholic; Paraffin Embedding; Reproducibility of Results; Retrospective Studies

Recent studies of an endemic occurrence of chronic arsenism in a limited area on the southwest coast of Taiwan are focusing on its cytokeratin analysis in hopes of tracing the disease's biochemical expression. Specimens were obtained from uninvolved skin and arsenical cancers including Bowen's disease, basal cell carcinoma, and squamous cell carcinoma. In this study, we used two-dimensional polyacrylamide gel electrophoresis to analyse cytokeratin expression. Progressive alterations in cytokeratin expression were found in various skin lesions. These include an expression of K16 in the uninvolved skin; K16 and K6 in Bowen's disease; and K16, K6 and K17 in squamous cell carcinoma and basal cell carcinoma. In addition, we found that the K1 isoelectric variants shifted to more acidic forms with the complete absence of K1 in basal cell carcinoma. K16 expression in uninvolved skin indicates that it is nevertheless in a hyperproliferative status. K17 was expressed in squamous cell carcinoma and basal cell carcinoma, but not in Bowen's disease. The progressive impairment of phosphorylation of K1 and K2 in the process of chronic arsenism provides us with a suitable model for studying the biological significance of phosphorylation in intermediate filaments during chemical carcinogenesis.

Topics: Arsenic Poisoning; Bowen's Disease; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Chronic Disease; Electrophoresis, Polyacrylamide Gel; Humans; Keratins; Poisoning; Skin; Skin Neoplasms; Taiwan

The proliferative activity and ultrastructural characteristics of proliferating biliary epithelial cells were analysed immunohistocytochemically in 39 biopsied liver specimens from patients with acute viral hepatitis, chronic hepatitis and liver cirrhosis using a monoclonal antibody against DNA polymerase alpha (DNA-PA). In acute viral hepatitis with perivenular confluent necrosis, proliferation of typical bile ducts was found frequently in portal areas. In chronic aggressive hepatitis and cirrhosis, ductular proliferation of both typical and atypical forms was found in enlarged portal and periportal areas and in confluent necrotic areas. The number of proliferating biliary epithelial cells that stained positive for DNA-PA was small. There were very few positively stained cells in atypical bile ducts in confluent necrotic areas of cirrhosis. Atypical bile ducts seen in chronic aggressive hepatitis, cirrhosis and acute hepatitis with confluent necrosis were positively stained for both cytokeratins 8 and 19. In cirrhosis, the number of stained biliary epithelial cells in typical bile ducts was larger than the number of such cells in atypical bile ducts (P < 0.01). By electron microscopy, the cells positively stained for DNA-PA were mostly so-called clear cells with irregular nuclei containing coarse nucleoplasm, and a few small cells with scanty cytoplasm and few organelles.

Topics: Adult; Aged; Antibodies, Monoclonal; Bile Ducts; Biopsy; Cell Division; Chronic Disease; Cytoplasm; DNA Polymerase II; Epithelium; Female; Hepatitis; Hepatitis, Viral, Human; Humans; Immunohistochemistry; Keratins; Liver; Liver Cirrhosis; Liver Diseases; Male; Microscopy, Electron; Middle Aged; Organelles

An ABC immunohistochemical study of the expression of cytokeratin (CK19 and CK18) was carried out in 315 cases of HBV-caused hepatitis, early-cirrhotic and cirrhotic livers. It was shown that hepatocytes in 73% of chronic active hepatitis (CAH) (80/110) and 81% of early-cirrhotic and cirrhotic livers (117/144) expressed CK19 (the abnormal CK expression), which could be of help in differentiating CAH from chronic persistent hepatitis, subtype CAH (mild, moderate to severe type) and in determining the activity of early-cirrhotic and cirrhotic livers. The abnormal CK expression was shown to be closely related to the activity of liver disorders. The CK19 expression in hepatocytes had the closest relations with the piece-meal necrosis of hepatocytes, isolation of hepatocytes into groups by connective tissue, and fibrosis. It is suggested that CK19 expression may be one of the local reactions to the piece-meal necrosis of hepatocytes.

Topics: Chronic Disease; Hepatitis B; Hepatitis, Chronic; Humans; Immunohistochemistry; Keratins; Liver; Liver Cirrhosis

Expression of intermediate filaments (IF) is regulated during development and differentiation. The authors have studied the expression of vimentin and cytokeratins (CK) 4, 7, 8, 13, 18, 19 in normal pancreas, chronic pancreatitis, and pancreas cancer using monoclonal antibodies. Immunohistochemical assays were performed on fresh frozen tissue sections and on cultured pancreas cancer cells using the streptavidin-peroxidase method. In normal pancreas, acinar cells expressed CK 8 and 18, whereas ductal cells expressed CK 7, 8, 18, and 19. CK 4 was expressed by 5-10% of pancreas duct cells in all specimens of normal pancreas. CK 13 was not detected in any epithelial cells of normal pancreas or pancreatitis. CK 7, 8, 18, and 19 were homogeneously expressed in all pancreas cancers, whereas CK 4 was expressed only in 5-50% of cells in 10/16 tumors. Foci of squamous metaplasia expressed CK 13 but showed partial loss of expression of CK 7, 8, 18, and 19. Thirteen pancreas cancer cell lines examined showed homogeneous expression of CK 7, 8, 18, and 19; 2/11 lines expressed CK 4 weakly, and 6/11 expressed vimentin. CK 13 was not detected in any of the lines. These results indicate that pancreas cancer cells consistently express cytokeratin polypeptides characteristic of ductal epithelial cells and that this phenotype is retained in pancreas cancer cell lines. In addition, squamous metaplasia is associated with a coordinate change in the expression of CK polypeptides.

Topics: Biomarkers; Cell Differentiation; Chronic Disease; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratins; Pancreas; Pancreatic Neoplasms; Pancreatitis; Reference Values; Tumor Cells, Cultured

The clinicopathological features of the scarring alopecia of discoid lupus erythematosus (DLE) were studied. Scarring alopecia was present in 34% of 89 patients with DLE and was associated with a prolonged disease course. More than half these patients had scalp involvement at the onset of the disease. There was a significant reduction in size of sebaceous glands in affected scalp. Perifollicular lymphocytic inflammation was maximal around the mid-follicle at the level of the sebaceous gland, which seems to be an important functional level in the follicle. There are changes in the expression of the matrix molecules, the proteoglycans, in the connective tissue sheath and the keratin intermediate filaments in the outer root sheath cells at this level in normal scalp and in diseased scalp. Loss of a population of mid-follicular stem cells may be important in the pathogenesis of scarring alopecia in DLE.

Topics: Adolescent; Adult; Aged; Alopecia; Chronic Disease; Female; Humans; Immunohistochemistry; Keratins; Lupus Erythematosus, Discoid; Male; Middle Aged; Scalp; Sebaceous Glands; Skin Diseases

Although unilateral clamping of the renal artery to induce chronic ischemia of the kidney tissue has been utilized in several animal species, the resultant morphologic, ultrastructural and immunologic changes have never been well characterized. Moreover, the pathogenesis of these changes, as well as their roles in causing or facilitating the development of chronic tubulointerstitial nephritis have not been known. To examine some of these issues, male Sprague-Dawley rats were subjected to unilateral stenosis of the left main renal artery for 28 days. Stenotic and contralateral kidneys of experimental animals and kidneys from sham-operated controls were subjected to: (1) light microscopic, electron microscopic and immunofluorescent studies; (2) morphometric quantitation of the structural changes; (3) staining for actin, epithelial membrane antigen, keratin, and vimentin by immunoperoxidase technique; (4) staining for complex glycoproteins by a panel of 13 lectins; and (5) phenotyping and quantitation of the interstitial inflammatory infiltrates by monoclonal antibodies, using immunoperoxidase technique. The results reveal that: (1) The ischemic kidney tissue displays marked tubulointerstitial damages including abundant interstitial chronic inflammatory infiltrates, with good preservation of glomerular structure, which is consistent with the standard criteria of chronic tubulointerstitial nephritis. (2) The antigenic profile of the ischemic tubular epithelium displayed marked alterations including a neo-expression of vimentin and keratin, as well as a loss of endogenous avidin binding activity, Ia antigen and several complex surface glycoproteins detectable by lectins. (3) Neither electron dense deposits nor immunoglobulins are detectable in the kidneys from experimental or control animals. (4) Tubulitis, defined as infiltration of tubular epithelium by inflammatory cells, was present in up to 42.2% of tubular cross sections of the ischemic kidneys. (5) The interstitial inflammatory infiltrates were composed of B lymphocytes, T helper lymphocytes, and macrophages whereas the T non-helper lymphocytes were scanty, a phenotypic pattern similar to that of several other experimental rat models of chronic tubulointerstitial nephritis. It is concluded that: (1) In the Sprague-Dawley rats, ischemia alone can cause a constellation of changes fulfilling the accepted features of chronic interstitial nephritis; (2) ischemia alters the antigenic profile of the tubular ep

Topics: Animals; Chronic Disease; Histocompatibility Antigens Class II; Immunohistochemistry; Ischemia; Keratins; Kidney; Lymphocytes; Male; Microscopy, Electron; Nephritis, Interstitial; Rats; Rats, Inbred Strains; Renal Artery Obstruction; Vimentin

Obstructive sialoadenitis was examined by immunohistochemical techniques for keratin (MoAb KL1, PKK1 and K8.12) and actin. Electronmicroscopy (EMS) was used to identify ultrastructural changes in myoepithelial cells and ductal basal cells. With immunohistochemistry, actin staining was used as a marker of myoepithelium, MoAbs KL1 and PKK1 for ductal luminal cells, and MoAb K8.12 for ductal basal cells. Histologic features of the lesion usually showed degenerative changes of acinar and duct cells with cell infiltration and fibrous replacement. Immunohistochemical findings indicated that actin staining in the changed myoepithelial cells was irregularly positive or negative, and also keratin staining in luminal and ductal basal cells was reduced or disappeared. Ultra-structural features of the changed myoepithelial cells indicated that these cells appeared less altered than adjacent acinar and ductal cells and showed increased amounts of lipid droplets and lipofuscin granules, and also wrinkled processes filled the prominent myofilament material.

Topics: Actins; Acute Disease; Cell Membrane; Chronic Disease; Cytoplasm; Epithelium; Fibrosis; Humans; Immunohistochemistry; Keratins; Microscopy, Electron; Organelles; Sialadenitis; Submandibular Gland; Submandibular Gland Diseases

The olfactory mucosa was examined by immunohistochemistry in patients with olfactory disturbance: anosmia due to choanal atresia and chronic sinusitis, early-stage common cold, late-stage common cold, and head trauma. The results indicate that the olfactory mucosa of patients with olfactory disturbance shows specific kinds of immunoreactive patterns and that immunohistochemistry is useful for examining the degree of degeneration of pathologic human olfactory mucosa and for clarification of prognosis.

Topics: Choanal Atresia; Chronic Disease; Common Cold; Craniocerebral Trauma; Humans; Immunoenzyme Techniques; Keratins; Olfaction Disorders; Olfactory Mucosa; Phosphopyruvate Hydratase; S100 Proteins; Sinusitis

Autoantibodies reacting with human pancreatic exocrine cells were investigated by immunofluorescent techniques in 107 patients with Type 1 (insulin-dependent) diabetes mellitus, 20 first-degree relatives of the Type 1 diabetic patients, 347 patients with Type 2 (non-insulin-dependent) diabetes, 34 with alcoholic pancreatitis, 26 with rheumatoid arthritis and 107 normal control subjects. Both immunoblotting analysis and double-immunostaining methods were used to characterize the antigens targeted by the pancreatic exocrine cell autoantibodies. Sera positive for human pancreatic exocrine cell cytoplasm, producing a "fine fibrillar" pattern, were found in 21% (23/107) of the Type 1 diabetic patients. The autoantibodies were present in 39% (15/38) of Type 1 diabetic patients diagnosed within 3 months, and the prevalence decreased with duration of diabetes. The antibodies were of the IgM class in 87% (13/15) of recent-onset Type 1 diabetes cases, but IgG-autoantibodies became more prevalent with increasing duration of diabetes. Three out of 347 (0.9%) Type 2 diabetic patients and 4 of 20 (20%) first-degree relatives of Type 1 diabetic patients had autoantibodies targeted against pancreatic exocrine cells. None of the patients with alcoholic pancreatitis or rheumatoid arthritis and none of the control subjects had these antibodies. Immunoblotting analysis and double-immunostaining demonstrated that the autoantibodies reacted with 40 kilodalton cytokeratin in pancreatic exocrine cell cytoplasm. The antibody was absorbed by the Triton X-100-insoluble fraction of pancreatic extract. These results indicate the presence of distinct autoantibodies to pancreatic exocrine cells in Type 1 diabetes. This suggests the provocative concept that the cytoskeletal system of pancreatic exocrine cells is involved in the pathogenetic process of Type 1 diabetes.

Topics: Adolescent; Adult; Alcoholism; Arthritis, Rheumatoid; Autoantibodies; Chronic Disease; Diabetes Mellitus, Type 1; Family; Female; Fluorescent Antibody Technique; Humans; Islets of Langerhans; Keratins; Male; Pancreas; Pancreatitis; Reference Values

Sweat gland abnormalities occur much more frequently than hitherto described in cutaneous graft versus host disease (GVHD). Two patterns of abnormalities were identified in 80 per cent of cases of acute GVHD: a cytopathic pattern consisting of a combination of basal vacuolopathy with or without lymphocytic infiltration and basal cell degeneration, and a proliferative pattern consisting of basal cell hyperplasia. In chronic GVHD, complete sweat gland destruction with fibrosis was commonly observed. Squamous metaplasia and dilation of the sweat glands were less frequently identified. Ki67 immunostaining confirmed proliferative activity in the basal cells of the distal duct. HLA-DR antigens were expressed on the basal cells of the duct and secretory glands in acute GVHD but not in normal skin. Langerhans cells were absent in both normal and abnormal sweat glands. The role of HLA-DR or Langerhans cells in the initiation of GVHD is questioned in the light of the new data and the primary involvement of proliferating cells is confirmed.

Topics: Acute Disease; Adolescent; Adult; Aged; Cell Survival; Child; Child, Preschool; Chronic Disease; Female; Graft vs Host Disease; Humans; Hyperplasia; Keratins; Male; Middle Aged; Skin Diseases; Sweat Glands

The novel extracellular matrix glycoprotein tenascin was studied immunohistochemically in normal and fibrotic human liver. Its localization was compared to that of laminin, fibronectin and collagen type IV. In the normal liver, a weak staining for tenascin was detected along sinusoids, while portal tracts were negative. In both alcoholic and cholestatic liver disease and acute and chronic hepatitis, sinusoidal immunoreactivity for tenascin was variably increased as compared to the normal liver. Most striking, however, was the preferential accumulation of tenascin at connective tissue-parenchymal interfaces between proliferating ductules and in areas of piecemeal necrosis. As compared to laminin, fibronectin and collagen type IV, tenascin has the most restricted distribution. Our findings indicate that tenascin is a component of the extracellular matrix of the human liver. Its preferential expression at connective tissue-parenchymal interfaces in fibrosing areas in contrast to its absence from mature fibrous septa suggest a transient role in early matrix organization.

Topics: Alcoholism; Cell Adhesion Molecules, Neuronal; Cholestasis; Chronic Disease; Collagen; Extracellular Matrix; Fibronectins; Hepatitis; Humans; Immunohistochemistry; Keratins; Laminin; Liver; Liver Cirrhosis; Liver Diseases; Tenascin

We studied the cell infiltrates and antigenic characteristics of keratinocytes in biopsies from purpura pigmentosa chronica (PPC), with eleven monoclonal antibodies against several cell surface markers of effector and/or accessory cells of the immune system and compared the reactivity patterns with those in biopsies from uninvolved skin. Immunohistochemical staining revealed a predominance of activated helper T lymphocytes in the cutaneous inflammatory infiltrate. In contrast to uninvolved skin, lesional keratinocytes were found to express HLA-DR, OKM5, Leu-8 and Leu-11b (CD16) antigens in all biopsies from the involved skin. We demonstrate here for the first time the in vivo expression of several effector and/or accessory cell markers on lesional keratinocytes and infiltrate cells in PPC.

Topics: Adolescent; Adult; Aged; Antibodies, Monoclonal; Antigens, Differentiation, T-Lymphocyte; Antigens, Surface; Chronic Disease; Epidermis; Female; HLA Antigens; Humans; Keratins; Male; Middle Aged; Pigmentation Disorders; Purpura

There are at least six variants of junctional epidermolysis bullosa (JEB). About 20 cases of the generalized atrophic benign variant of JEB (GABEB) have been previously reported. We present an additional case of GABEB, occurring in a 14-year-old girl. Generalized cutaneous blisters occurred since birth and healed without severe scarring or milia, but with slight atrophy. In addition, mucous membrane involvement and hair, nail and tooth abnormalities were found. Electron microscopic examination showed a cleavage within the lamina lucida and the presence of numerically and structurally abnormal hemidesmosomes.

Topics: Adolescent; Atrophy; Basement Membrane; Blister; Chronic Disease; Desmosomes; Epidermolysis Bullosa; Female; Humans; Keratins; Skin

Cultured keratinocytes were used as allografts to treat 51 patients with chronic venous ulceration or rheumatoid ulcers unresponsive to all previous conventional treatments including split skin grafts. Although early epithelialization could be seen in the centre of some ulcers, a major effect appeared to be healing from the previously indolent edge. This treatment appears to provide some clinical benefit in healing of chronic ulceration.

Topics: Aged; Aged, 80 and over; Arthritis, Rheumatoid; Bandages; Biological Dressings; Cells, Cultured; Chronic Disease; Epidermal Cells; Female; Humans; Keratins; Leg Ulcer; Male; Middle Aged; Skin Transplantation; Transplantation, Homologous; Venous Insufficiency

Lectin-binding profiles and keratin distribution in obstructive adenitis of human submandibular glands (SMGs) are reported and compared those of normal SMGs. Histologically, obstructive changes in the SMGs included acinar atrophy, duct-like structure formation in the early stage, and disappearance of acinar cells and dilation of ductal segments in the later, chronic stage. The following lectins were used: Con A (Glc, Man), PNA(Gal, GalNAc), RCA-I(Gal), DBA(GalNAc), SBA(Gal, Gal-NAc), UEA-I(alpha-L-Fuc) and WGA(GlcNAC, NeuNAc). Lectin staining in atrophic acinar cells was usually reduced except for SBA binding and was irregularly distributed in altered acinar and ductal epithelia. Binding of DBA and UEA-I lectins were particularly intense along the luminar borders of ductal segments in the lesions. Immunohistochemically detectable keratins were characterized by intense staining in atrophic acinar cells and in all the ductal segments, whereas normal acinar cells, either serous or mucous, were negative.

Topics: Chronic Disease; Humans; Immunoenzyme Techniques; Keratins; Lectins; Salivary Gland Diseases; Sialadenitis; Staining and Labeling; Submandibular Gland; Submandibular Gland Diseases

The expression of the histocompatibility antigens HLA-DR and HLA-A, B, C within periodontally diseased tissue was investigated using immunohistological and histochemical techniques. Tissue was obtained from 18 patients with periodontal disease and from 2 healthy volunteers. HLA-DR antigen was expressed by the keratinocytes of the oral epithelium in all inflamed samples but was not a feature of normal tissue where HLA-DR reactivity was confined to Langerhans cells. These results are consistent with an underlying cellular immune process. Using a variety of phenotypic markers it was possible to characterize the macrophage population within the connective tissue into 2 distinct types: an antigen-presenting cell type located subjacent to the oral epithelium and a phagocytic cell type situated deep within the connective tissue.

Topics: Chronic Disease; Fluorescent Antibody Technique; Gingiva; Gingivitis; Histocompatibility Antigens Class II; Histocytochemistry; HLA-DR Antigens; Humans; Keratins

The presence of intermediate filament proteins of cytokeratin/prekeratin type and vimentin type was evaluated in non-neoplastic thyroid glands and in different types of thyroid neoplasms. Follicular epithelium of both normal and goitrous thyroids showed a strong reaction with anticytokeratin antibodies that widely cross-react with various simple epithelia. On the other hand, in normal thyroid, there were only occasionally (in one of 12 cases) solitary cells reacting with antibodies to epidermal prekeratin. In nodular goiters, such cells were often seen (eight of 18), especially among the lining cells of cysts, and in chronic thyroiditis in all (12 of 12) cases. Only the stromal cells and intraluminal macrophages reacted with antibodies to vimentin. Neoplastic cells of papillary carcinomas showed a positive staining reaction both with antibodies to cytokeratins and to epidermal prekeratin. Follicular carcinoma cells, although positive for cytokeratins, could generally not be stained with antibodies to epidermal prekeratin. Medullary carcinoma cells also showed cytokeratin positivity and, only occasionally, positivity for epidermal prekeratin. Anaplastic carcinomas were also reactive with antibodies to cytokeratin but, for the most part, were negative for epidermal prekeratin. Interestingly, some neoplastic cells of all types of thyroid carcinomas also appeared to contain vimentin, as shown with both polyclonal and monoclonal antivimentin antibodies. In contrast to carcinomas, the intermediate filaments of thyroid sarcomas and lymphomas were only of vimentin type. Furthermore, it was found that the papillary structures in benign goiters were only reactive with cytokeratin antibodies and lacked, in contrast to papillary carcinomas, epidermal prekeratin-like immunoreactivity. Hence, the analysis of intermediate filament proteins of thyroid tumors can be utilized to differentiate between papillary and follicular carcinomas and between benign and malignant papillary lesions as well as between anaplastic thyroid carcinomas and sarcomas or lymphomas.

Topics: Adenocarcinoma; Carcinoma; Carcinoma, Papillary; Chronic Disease; Epithelium; Fluorescent Antibody Technique; Goiter, Nodular; Humans; Intermediate Filament Proteins; Keratins; Lymphoma; Protein Precursors; Sarcoma; Thyroid Gland; Thyroid Neoplasms; Thyroiditis; Vimentin

Controversy surrounds the importance of keratinized gingiva in maintaining periodontal health. A well-defined animal model system is necessary to evaluate longitudinally the role of keratinized gingiva when plaque control is inadequate or where dental procedures (restorative, prosthetic or orthodontic) alter the periodontal environment. Facial gingiva was excised from eight primary incisors in miniature swine. Contralateral teeth were used as controls. The experimental teeth exhibited mucogingival defects at 3 and 6 month observation periods. The secondary teeth erupting into the experimental regions also exhibited recession and chronic mucogingival defects. The marginal tissue in regions devoid of keratinized gingiva demonstrated clinical signs of inflammation. No progressive gingival recession was present. Excision of keratinized gingiva to produce mucogingival defects in swine provides a convenient model system for evaluating the effect of dental procedures on periodontal health where little or no keratinized gingiva is present.

Topics: Animals; Chronic Disease; Gingiva; Gingival Diseases; Gingivectomy; Keratins; Longitudinal Studies; Male; Swine; Swine, Miniature

The epidermal ultrastructure of 11 allogeneic bone marrow recipients with chronic graft-versus-host disease (GVHD) was compared with that of 4 recipients without chronic GVHD. This electron microscope study revealed three patterns of epidermal injury typical of chronic GVHD. The first type was a nonacantholytic (nondissecting) injury with a prominent cellular infiltrate consisting primarily of lymphocytes accompanied by a few macrophages. The second type was an acantholytic (dissecting) injury with a prominent infiltrate, while the third was a nondissecting injury with a sparse infiltrate. Broad-zone contact was observed between lymphocytes and all epidermal cell types as well as between other lymphocytes and macrophages. Point contact was only observed between lymphocytes and epidermal cells. Lymphocytes appeared to detach desmosomes from adjacent keratinocytes by isolating them with cytoplasmic projections, a phenomenon not previously described. Typical damage to the epidermal cells in the basal and spinous layers consisted of either swelling of the organelles or condensation of the cytoplasm and nucleus. In the keratinocyte, the condensation reaction resulted in the formation of colloid bodies, some of which were phagocytized by macrophages. Besides the cytolytic events, a concurrent stimulatory reaction occurred in the epidermal cells. The number of melanosomes in melanocytes and of Langerhans cell granules and dense bodies in the Langerhans cells all increased. Extensive areas of replication and disruption of the basal lamina were subjacent to areas of necrosis in the basal layer.

Topics: Chronic Disease; Epidermis; Graft vs Host Reaction; Humans; Keratins; Langerhans Cells; Lymphocytes; Macrophages; Melanocytes; Pigments, Biological

In a collection of 1,100 operated ears, 426 of which had cholesteatoma and 674 had not, the various defects of the ossicular chain are described and related to the nature of the disease and the site of perforation. The analysis showed marked differences between the various diseases and in the frequency of the individual ossicular defects or combinations of defects. Defects of the head of the malleus and of the body of the incus were found exclusively in chiolesteatomas, most often those affecting the attic. Isolated defects of the malleus handle were most common in cholesteatoma of the parts tensa and in total perforations. Defects of the long process of the incus occurred in 74--88 per cent of cholesteatomatous diseases, defects of the stapedial arch in 47 per cent of ears with sinus cholesteatoma. In granulating otitis without cholesteatoma and in sequelae to otitis there was less ossicular pathology, and 57 per cent of these ears had an intact ossicular chain. Total or posterior perforations were associated with pathology of the ossicles more often than inferior or anterior perforations. All cases with destruction of the body of the incus and the head of the malleus showed squamous epithelium in close relation to the ossicular defect, indicating a marked--presumably enzymatic--influence by the squamous epithelium upon the bone resorption.

Topics: Bone Resorption; Cholesteatoma; Chronic Disease; Ear Diseases; Ear Ossicles; Ear, Middle; Epithelium; Humans; Keratins

"Keratin pools," previously characterized clinically and histochemically in the superficial epithelium of chronic hyperplastic oral mucosa, were studied by light and electron microscopy. These occured as small beaded and larger coalescent masses which varied in metachromasia. Ultrastructurally, the "keratin pools" consisted of electron-dense, amorphous or finely-granular material developing and coalescing, chiefly as extracellular deposits. The "pools" frequently possessed a layered arrangement alternating with cells having distinct tonofilaments, desmosomes, and definite cell membranes. Occasional bands of filamentous-like material, possibly representing tonofilament bundles, were observed in some "pools."

Topics: Aged; Cell Nucleus; Chronic Disease; Desmosomes; Epithelium; Female; Humans; Hyperplasia; Inclusion Bodies; Keratins; Microscopy, Electron; Mouth Diseases; Mouth Mucosa

Topics: Body Fluids; Cell Membrane Permeability; Chronic Disease; Cytoplasmic Granules; Desmosomes; Epithelium; Glycogen; Hyalin; Keratins; Microscopy, Electron; Periodontitis

Topics: Adult; Aged; Cell Membrane; Chronic Disease; Connective Tissue; Dental Prophylaxis; Epithelium; Female; Gingiva; Glycogen; Humans; Keratins; Male; Microscopy, Electron; Microscopy, Phase-Contrast; Microscopy, Polarization; Middle Aged; Periodontitis

Topics: Adult; Aged; Autopsy; Child; Cholesteatoma; Chronic Disease; Connective Tissue; Ear, Middle; Epithelial Cells; Epithelium; Granulation Tissue; Humans; Hyperplasia; Hypertrophy; Keratins; Male; Metaplasia; Microtomy; Middle Aged; Mucous Membrane; Otitis Media; Staining and Labeling; Temporal Bone; Tympanic Membrane

Topics: Alveolar Process; Animals; Blood Cell Count; Bone Marrow Cells; Chronic Disease; Gingivitis; Keratins; Periodontal Diseases; Periodontium; Phagocytosis; Rabbits

Topics: Bone and Bones; Cholesteatoma; Chronic Disease; Ear Diseases; Ear Ossicles; Epithelium; Granulation Tissue; Humans; Keratins; Mucus; Otitis Media

Morphologic observations on a peculiar type of corneal reaction with a predisposition for the superficial stroma of the interpalpebral portion of the cornea are reviewed. Histochemical evidence is provided which indicates that the corneal concretions, though not homogenous, are proteinaceous in nature and contain amino acids not normally detectable in the cornea. The corneal concretions were associated with conjunctival elastosis (pingueculae) in all 22 instances in which the eyes were sectioned in the horizontal plane. Identical concretions were identified within these associated pingueculae, as well as in a large percentage of other pingueculae and cutaneous lesions with actinic elastosis. The findings suggest that the abnormal material arises in the pericorneal conjunctival connective tissue from whence it diffuses into, and deposits in, the superficial corneal stroma. The data also raise the possibility that the concretions may be derived, at least in part, from altered elastic tissue. Morphologic and epidemiologic observations on the condition taken together strongly suggest that this unique reaction is a sequel to the cumulative effect of chronic actinic irradiation. Further observations on this keratopathy are needed to establish whether this unique response can be provoked by other noxious stimuli.

Topics: Adult; Aged; Biopsy; Chronic Disease; Conjunctiva; Cornea; Corneal Opacity; Disulfides; Elastic Tissue; Eye Diseases; Female; Histocytochemistry; Humans; Keratins; Male; Microscopy, Electron; Middle Aged; Radiation Injuries

Topics: Adolescent; Child; Chronic Disease; Ear Diseases; Female; Humans; Keratins; Male; Middle Aged; Otitis