bromochloroacetic-acid and Atrophy

Submucosal glands (SMGs) present throughout human esophagus with clusters at either the upper third or lower third of the organ. SMGs tend to atrophy with age, and neoplasms arising in these glands are rare. In order to bring convenience to diagnosis, we summarize the histopathologic characteristics of all esophageal submucosal gland tumors (SGTs). Due to the morphological similarity, the nomenclature of salivary tumors is adopted for SGTs. However, there is great confusion about the definition and histogenesis of these tumors, especially the malignant subtypes. In the literature, esophageal mucoepidermoid carcinoma and adenoid cystic carcinoma usually adjoin the surface squamous epithelium and coexist with intraepithelial neoplasia or invasive squamous cell carcinoma (SCC). In addition, the typical gene alterations of salivary tumors have not been reported in these SGTs. Therefore, we propose to apply stringent diagnostic criteria to esophageal SGTs so as to exclude mimickers that are SCCs with various degree of SMG differentiation.

Topics: Aged, 80 and over; Atrophy; Carcinoma in Situ; Carcinoma, Adenoid Cystic; Carcinoma, Mucoepidermoid; Carcinoma, Squamous Cell; Esophageal Neoplasms; Esophagus; Humans; Keratins; Male; Mucin-5B; Neoplasms, Glandular and Epithelial; Retrospective Studies

Meibomian gland dysfunction (MGD) is the major cause of evaporative dry eye disease (EDED) and dysfunction is widely thought to mechanistically involve ductal hyperkeratinization, plugging and obstruction. This review re-evaluates the role of hyperkeratinization in MGD based on more recent findings from mouse models. In these studies, eyelids from normal young and old mice or mice exposed to desiccating stress were evaluated by immunofluorescent tomography and 3-dimensional reconstruction to evaluate gland volume, expression of hyperkeratinization markers and cell proliferation or stimulated Raman scattering (SRS) microscopy to assess lipid quality. Results indicate that aging mice show dropout of meibomian glands with loss of gland volume and a forward migration of the mucocutaneous junction anterior to the gland orifice; similar age-related changes that are detected in human subjects. Atrophic glands also showed evidence of epithelial plugging of the orifice without the presence of hyperkeratinization. Mice exposed to desiccating stress showed hyperproliferation of the meibomian gland and ductal dilation suggesting a marked increase in lipid synthesis. Lipid quality was also affected in EDED mice with an increase in the protein content of lipid within the duct of the gland. Overall, age-related changes in the mouse show similar structural and functional correlates with that observed in clinical MGD without evidence of hyperkeratinization suggesting that gland atrophy may be a major cause of EDED. The response of the meibomian gland to desiccating stress also suggest that environmental conditions may accelerate or potentiate age-related changes.

Topics: Animals; Atrophy; Dry Eye Syndromes; Eye Proteins; Eyelid Diseases; Humans; Keratins; Meibomian Glands; Mice

The diagnosis of prostatic adenocarcinoma relies on a constellation of architectural, cytological, and immunohistochemical features. Although the diagnosis of prostatic adenocarcinoma is straightforward in most cases, due to earlier detection of the disease in the modern era, pathologists have become increasingly challenged in diagnosing small foci of cancer when only a few atypical glands are present in needle biopsies. Immunohistochemistry has therefore become an essential tool in the evaluation of such foci to confirm the absence of basal cells. In this context, the 2 most commonly used basal cell markers are anti-keratin 34BE12 and p63. Furthermore, α-methylacyl-CoA racemase, a marker found to be overexpressed in the cytoplasm of prostatic adenocarcinoma glands, is also commonly used in routine practice. Another diagnostic role of immunohistochemistry is to confirm the prostatic origin of the tumor in the primary or metastatic setting of high-grade prostatic adenocarcinoma, which may be confused with nonprostatic carcinomas. We herein review the utility as well as the limitations of immunohistochemistry in the diagnosis of prostatic adenocarcinoma, and we describe the most important pitfalls in the interpretation of various immunostains that pathologists should be aware of to minimize misdiagnoses.

Topics: Adenocarcinoma; Atrophy; Biomarkers, Tumor; Biopsy, Needle; Diagnosis, Differential; Diagnostic Errors; GATA3 Transcription Factor; Humans; Immunohistochemistry; Keratins; Male; Prostate; Prostatic Neoplasms; Racemases and Epimerases; Transcription Factors; Tumor Suppressor Proteins

One of the major diagnostic challenges in prostate needle biopsy interpretation is definitive establishment of a malignant diagnosis based on a minimal or limited amount of carcinoma in needle biopsy tissue. Major and minor diagnostic criteria should be used for interpretation of small foci of carcinoma. The constellation of findings and a combination of the major and minor diagnostic criteria permit a definitive diagnosis of focal adenocarcinoma. The differential diagnosis of minimal prostatic adenocarcinoma in needle biopsy tissue is broad and includes many benign lesions. The benign entities most likelty to be misdiagnosed as minimal prostatic adenocarcinoma are atypical adenomatous hyperplasia (adenosis) and atrophy. High-grade prostatic intraepithelial neoplasia and a descriptive diagnosis of focal glandular atypia or atypical small acinar proliferation also should be considered before diagnosing minimal adenocarcinoma. The most valuable adjunctive study for the diagnosis of minimal adenocarcinoma is immunohistochemistry using antibody 34 beta E12, reactive against basal cell-specific high-molecular-weight cytokeratins. Most cases can be diagnosed based on H&E-stained sections without this immunostain. Most minimal carcinomas in prostate needle biopsy tissue are of intermediate histologic grade, and most are indicative of pathologically significant carcinoma in the whole prostate gland.

Topics: Adenocarcinoma; Atrophy; Biopsy, Needle; Diagnosis, Differential; Humans; Hyperplasia; Immunohistochemistry; Keratins; Male; Prostatic Neoplasms

A variety of small acinar lesions of the prostate can mimic prostate cancer in punch biopsies and in transurethral resection material. The first part of this review deals with differential diagnostic problems of the central and transition zone, including atypical adenomatous hyperplasia of the prostate, atrophic processes, sclerosing adenosis, basal cell hyperplasia, and low-grade adenocarcinoma. The second part deals with differential diagnostic problems in the peripheral zone: prostatic intraepithelial neoplasia, postatrophic hyperplasia, Cowper's glands, seminal vesicles, and ductal and intraductal carcinoma. Finally, atypical and small acinar proliferations are described. Diagnostic perspectives are discussed. proliferations (ASAP) that cannot be integrated into any of the well-established diagnostic entities [1, 16, 22, 41]. The relevant glandular proliferations of the central, transitional and peripheral zones of the prostate are discussed here with reference to the related carcinomas.

Topics: Adenocarcinoma; Atrophy; Diagnosis, Differential; Humans; Keratins; Male; Precancerous Conditions; Prostate; Prostate-Specific Antigen; Prostatic Diseases; Prostatic Hyperplasia; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms

Prostate carcinoma (PC) is the second most diagnosed cancer in men worldwide. Prostate tissue in needle biopsy expresses a wide variety of architectural patterns some of which are difficult to interpret. Immunohistochemical markers, such as AMACR, p63 and 34βE12 that are currently used in diagnosing prostate cancer, are of great value, but often their interpretation is ambiguous. In 2005 Tomlins et al. identified an emerging marker, erythroblastosis E26 rearrangement gene (ERG), which is a member of the family of genes encoding erythroblast-transformation specific transcription factors (ETS) with frequent expression in PC.. The aim of this study was to investigate the expression of ERG in benign mimickers of PC in needle biopsies and its diagnostic value alone and in combination with AMACK and 34βE12.. Of the selected 46 biopsies, two were eventually diagnosed as PC Gleason score 6 as they were simultaneously ERG and AMACR-positive and 34βE12-negative. One case was considered atypical. The remaining 43 biopsies were diagnosed as benign cases: simple atrophy in 13 cases, partial atrophy in 11, adenosis in 9, basal cell hyperplasia in 3, post-atrophic hyperplasia in 3, clear cell hyperplasia in 2 and sclerotic adenosis in 2 cases. None of the 43 benign cores showed evidence of ERG expression.. ERG could be preferably used in diagnosing prostate needle biopsies, lesions that are hard to interpret and controversial expression of AMACR/34βE12.

Topics: Aged; Aged, 80 and over; Atrophy; Biopsy, Large-Core Needle; Carcinoma; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms; Racemases and Epimerases; ROC Curve; Transcriptional Regulator ERG

We report 3 cases of primary renal cell tumor simulating atrophic kidney with distinct gross, morphologic, immunohistochemical, and molecular genetic features. The tumors were retrieved out of more than 17 000 renal tumors from the Plzen Tumor Registry. Tissues for light microscopy had been fixed, embedded, and stained with hematoxylin and eosin using routine procedures. The tumors were further analyzed using immunohistochemistry, array comparative genomic hybridization, and human androgen receptor. Analyses of VHL gene and loss of heterozygosity (LOH) 3p were also performed. The patients were 2 women and 1 man, with ages ranging from 29 to 35 years (mean, 31.3 years). Grossly, the neoplasms were encapsulated and round with largest diameter of 3.5 cm (mean, 3.2 cm). Follow-up available for all patients ranged from 2 to 14 years (mean, 8 years). No aggressive behavior was noted. Histologically, akin to atrophic (postpyelonephritic) kidney parenchyma, the tumors were composed of follicles of varying sizes that were filled by eosinophilic secretion. Rare areas contained collapsed follicles. Each follicle was endowed with a small capillary. The stroma was loose, inconspicuous, and focally fibrotic. Two types of calcifications were noted: typical psammoma bodies and amorphous dark-blue stained calcified deposits. Immunohistochemically, tumors were strongly positive for cytokeratins (OSCAR), CD10, and vimentin, with weak immunopositivity for CAM5.2 and AE1-AE3. WT1 and cathepsin K were weakly to moderately focally to diffusely positive. Tumors were negative for cytokeratin 20, carbonic anhydrase IX, parvalbumin, HMB45, TTF1, TFE3, chromogranin A, thyroglobulin, PAX8, and ALK. Only 1 case was suitable for molecular genetic analyses. No mutations were found in the VHL gene; no methylation of VHL promoter was noted. No numerical aberrations were found by array comparative genomic hybridization analysis. LOH for chromosome 3p was not detected. Analysis of clonality (human androgen receptor) revealed the monoclonal nature of the tumor. We describe an unknown tumor of the kidney that (1) resembles renal atrophic kidney or nodular goiter of thyroidal gland; (2) contains a leiomyomatous capsule and 2 types of calcifications; (3) lacks mitoses, atypias, necroses, and hemorrhages and nearly lack Ki-67 positivity; and (4) so far showed benign biological behavior.

Topics: Adult; Atrophy; Biomarkers, Tumor; Calcinosis; Comparative Genomic Hybridization; Diagnosis, Differential; DNA Methylation; Female; Goiter, Nodular; Humans; Keratins; Kidney; Kidney Neoplasms; Leiomyomatosis; Loss of Heterozygosity; Male; Mutation; Receptors, Androgen; Thyroid Gland; Vimentin; Von Hippel-Lindau Tumor Suppressor Protein

To describe the morphology of focal prostatic atrophy and propose a comprehensive histologic classification for a proper diagnostic recognition.. A broad immunohistochemical study was performed as an adjunct to its recognition as well as a contribution to pathogenesis.. A morphologic continuum was seen on needle biopsies. Chronic inflammation was present only in complete atrophy. Immunohistochemical findings in partial atrophy are similar to normal acini. Luminal compartment in complete atrophy shows aberrant expression of 34betaE12 favoring an intermediate phenotype. ERG negativity in all variants of atrophy may have value in the identification of the lesion.. The morphologic findings favor a continuum probably partially preceding complete atrophy. Chronic inflammation may be a secondary phenomenon seen only in complete atrophy. Overexpression in complete atrophy of glutathione S-transferase pi relates to oxidative stress possibly related to chronic ischemia, of c-Met favors the concept that intermediate cells may be target for carcinogenesis, and of CD44 may be related to the recruitment of inflammatory cells.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Atrophy; Biopsy, Needle; Diagnosis, Differential; Humans; Hyaluronan Receptors; Immunohistochemistry; Kallikreins; Keratins; Male; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatic Diseases; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms; Sclerosis

Heat-shock protein 27 (hsp27) has been implicated in several biological events. In this experimental study, we aimed at analysing, for the first time, the expression of hsp27 in the diverse stages of oral lichen planus (OLP) lesions.. Thirty-six biopsy specimens of patients with OLP and 10 of healthy patients were selected. OLP specimens were divided into three groups: G1 - moderate or mildly active OLP; G2 - active or moderately active atrophic OLP; G3 - mild or inactive atrophic OLP. Hsp27 expression was analysed by immunohistochemistry (staining intensity and percentage of stained cells), and results of staining were compared between the different groups. Gender, age and anatomical location were also studied.. In the basal layer, an increase of hsp27 expression in both G2 and G3 was observed when compared to G1 and control group. In contrast, a decrease of hsp27 expression in the superficial layer was observed in all groups when compared to control group.. The increased expression of Hsp27 in the basal layer observed during the OLP evolution and the less staining in the superficial layers in all cases of OLP suggest that hsp27 may have a role in the OLP pathogenesis.

Topics: Adult; Atrophy; Biopsy; Cell Nucleus; Coloring Agents; Cytoplasm; Epithelium; Female; HSP27 Heat-Shock Proteins; Humans; Immunohistochemistry; Keratins; Lichen Planus, Oral; Male; Middle Aged; Mouth Mucosa; Tongue

Mutation of the adult hepatocyte keratins K8 and K18 predisposes to liver disease. In contrast, exocrine pancreas K8 and K18 are dispensable and are co-expressed with limited levels of membrane-proximal K19 and K20. Overexpression of mutant K18 or genetic ablation of K8 in mouse pancreas is well tolerated whereas overexpression of K8 causes spontaneous chronic pancreatitis. To better understand the effect of exocrine pancreatic keratin overexpression, we compared transgenic mice that overexpress K18, K8, or K8/K18, associated with minimal, modest, or large increases in keratin expression, respectively, with nontransgenic wild-type (WT) mice. Overexpression of the type-II keratin K8 up-regulated type-I keratins K18, K19, and K20 and generated K19/K20-containing neocytoplasmic typical or short filaments; however, overexpression of K18 had no effect on K8 levels. K8- and K18-overexpressing pancreata were histologically similar to WT, whereas K8/K18 pancreata displayed age-enhanced vacuolization and atrophy of the exocrine pancreas and exhibited keratin hyperphosphorylation. Zymogen granules in K8/K18 pancreata were 50% smaller and more dispersed than their normal apical concentration but were twice as numerous as in WT controls. Therefore, modest keratin overexpression has minor effects on the exocrine pancreas whereas significant keratin overexpression alters zymogen granule organization and causes aging-associated exocrine atrophy. Keratin absence or mutation is well tolerated after pancreatic but not liver injury, whereas excessive overexpression is toxic to the pancreas but not the liver when induced under basal conditions.

Topics: Amylases; Animals; Atrophy; Fluorescent Antibody Technique; Gene Expression Regulation; Humans; Intermediate Filaments; Keratin-18; Keratin-19; Keratin-8; Keratins; Liver; Mice; Mice, Transgenic; Mutation; Pancreas, Exocrine; Pancreatic Diseases; Phosphorylation; RNA, Messenger; Secretory Vesicles

There were investigated 22 cases from which the thymic tissue was removed either during surgery for cardiovascular malformations (n = 14), or for myasthenia gravis (n = 8). Histological sections were stained with routine morphologic methods, and immunohistochemistry was performed for cytokeratin, CD20, CD3, and S100 protein. Aspects characteristic for thymus involution were found in 11 cases without myasthenia gravis and in all cases with myasthenia gravis. Morphological changes of the thymus of involution are age-dependent. There were characterized stages of involution, with special reference to cortical - medulla inversion, lymphocyte depletion and sequestration. In advanced-stage of involution, epithelial cells are arranged in cords or compact islands, and could mimic a thymoma or a metastatic carcinoma. The immunohistochemical profile is similar but not identical to the active thymus. We noticed a decreased expression of cytokeratin, and a reduced number of CD3, CD20, and S100 positive cells. Morphologic and immunohistochemical peculiarities of the thymus of involution are discussed in relation with the specific pathology of the organ.

Topics: Adolescent; Adult; Antigens, CD20; Atrophy; Carcinoma; Cardiovascular Abnormalities; CD3 Complex; Child; Child, Preschool; Diagnosis, Differential; Humans; Infant; Infant, Newborn; Keratins; Lymphatic Diseases; Middle Aged; Myasthenia Gravis; Thymus Gland; Thymus Neoplasms

The hallmark of failing renal transplants is tubular atrophy and interstitial fibrosis (TA/IF). Injury to tubular epithelial cells (TEC) could contribute to fibrogenesis via epithelial-mesenchymal transition (EMT). We examined the features of EMT in renal transplants that developed TA/IF. Biopsies from 10 allograft kidneys with impaired function and TA/IF and 10 biopsies from transplants with stable function were compared to their implantation biopsies. Relative to implantation biopsies, TEC in TA/IF kidneys showed loss of epithelial markers (E-cadherin, cytokeratin) with altered distribution. Some TEC also showed new cytoplasmic expression of mesenchymal markers vimentin, S100A4, and alpha smooth muscle actin (alpha-SMA) and collagen synthesis marker heat shock protein (HSP-47), both in deteriorating and atrophic tubules. Double immunostaining showed coexpression of cytokeratin and vimentin, S100A4 and HSP-47, indicating intermediate stages of EMT in TA/IF. These changes were absent or much less in transplants with stable function. EMT features in the TA/IF group correlated with serum creatinine (vimentin, S100A4, HSP-47), history of T-cell-mediated rejection (cytokeratin, S100A4) and proteinuria (cytokeratin). These findings support a model in which the TEC damage induces loss of epithelial features and expression of fibroblast features, as a common pathway of deterioration by either immunologic or nonimmunologic processes.

Topics: Actins; Adult; Atrophy; Biomarkers; Cadherins; Cell Differentiation; Epithelial Cells; Female; Fibroblasts; Fibrosis; Graft Rejection; Heat-Shock Proteins; HSP47 Heat-Shock Proteins; Humans; Keratins; Kidney Transplantation; Kidney Tubules; Male; Serpins; Transplantation, Homologous; Vimentin

We evaluated the sensitivity and specificity of cytokeratin (CK) 5/6 for distinguishing foci of atrophy from prostatic adenocarcinoma with and without previous hormonal adjuvant therapy and observed the intensity and pattern of staining in mimickers of prostatic adenocarcinoma (basal cell hyperplasia, atypical adenomatous hyperplasia, and tangentially cut high-grade prostatic intraepithelial neoplasia [PIN]). We reviewed 146 acinar proliferations in 81 specimens (radical prostatectomy, previously untreated, 41; radical prostatectomy, following androgen-deprivation therapy, 11; transurethral resection, previously untreated, 29). All benign acinar proliferations stained positively for CK5/6, with immunoreactivity restricted to basal cells. Untreated and androgen-deprived prostatic adenocarcinomas were invariably negative. The pattern of staining was continuous in 79% of the atrophy cases (15/19), and all foci stained with CK5/6. Characteristic double-layer staining in basal cell hyperplasia was observed in 93% of cases (13/14), and foci of high-grade PIN had a characteristic "checkerboard" staining with areas of discontinuity. Foci of atypical adenomatous hyperplasia showed continuous staining, including cauterized acini in 53% of cases (8/15), with a fragmented basal cell layer pattern in 47% of cases (7/15). CK5/6 staining of the basal cells in foci of atrophy is sensitive and specific for excluding prostatic adenocarcinoma with and without androgen-deprivation effect.

Topics: Adenocarcinoma; Androgen Antagonists; Atrophy; Diagnosis, Differential; Humans; Keratins; Male; Prostate; Prostatic Hyperplasia; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms

Diagnostically reliable identification of prostatic basal cells has depended on staining for high molecular weight cytokeratin. The diagnosis of malignancy is often based on the absence of basal cells. False-negative staining is occasionally observed. Thus, a second method of identifying basal cells might prove useful. Selective expression of p63, a homologue of p53, has been demonstrated in prostatic basal cells. We investigated the diagnostic utility of p63 staining in 70 consecutive specimens for which the differential diagnosis included prostatic adenocarcinoma: 68 needle biopsies and 2 transurethral resection blocks. High molecular weight cytokeratin staining was the gold standard when material was available. A total of 61 specimens were diagnosed as carcinoma, 4 as atrophy, 2 as high-grade prostatic intraepithelial neoplasia, 2 as unclassified collections of benign glands, and 1 as carcinoma versus high-grade prostatic intraepithelial neoplasia. Sections mounted on charged slides were used for p63 staining for 14 specimens. Sections previously hematoxylin and eosin stained on uncharged slides were used for 56 specimens. In every case in which there was successful p63 staining (55 specimens), basal cells in benign lesions were properly marked and other cell types were not stained. Uninformative staining in the remaining 15 specimens was due to failure of tissue adherence in 14 specimens in which sections were on uncharged slides and, in 1 specimen, to poor positive internal control staining of benign glands. Thus, p63 staining was informative in 55 of 56 specimens (98%) for which there was material for examination. No case with satisfactory p63 and high molecular weight staining showed disagreement between the two stains. An additional group of 21 transurethral resection specimens was stained (p63 and high molecular weight cytokeratin). There was less false-negative staining for p63 compared with the case of high molecular weight cytokeratin. No false-positive staining was seen. We conclude that p63 staining is at least as sensitive and specific for the identification of basal cells in diagnostic prostate specimens as is high molecular weight cytokeratin staining.

Topics: Adenocarcinoma; Atrophy; Biomarkers; Diagnosis, Differential; DNA-Binding Proteins; Genes, Tumor Suppressor; Humans; Immunohistochemistry; Keratins; Male; Membrane Proteins; Phosphoproteins; Prostate; Prostatic Neoplasms; Sensitivity and Specificity; Trans-Activators; Transcription Factors; Tumor Suppressor Proteins

p63, a homologue of the tumor suppressor gene p53, is expressed in embryonic, adult murine, and human basal squamous epithelium and encodes both transactivating and dominant negative transcript isoforms. Mouse embryos functionally deficient in p63 fail to replenish basal squamous epithelial cells, resulting in multiple defects that include absent genital squamous epithelium. This study investigated the expression of p63 in the human cervical transformation zone and early cervical neoplasia.. Tissue localization of p63 was determined by immunohistochemistry in a wide range of epithelia. A correlation was also made between p63 expression and squamous basal cell (keratin 14), endocervical columnar cell (mucicarmine), and cell-cycle specific (Ki-67) markers.. p63 expression by immunostaining delineated basal and parabasal cells of maturing ectocervical squamous mucosa, squamous metaplasia in the cervix, and basal and subcolumnar cells of the cervical transformation zone. In atrophic epithelia immunostaining for p63 was present in all cell strata. In early cervical neoplasia, p63 expression was inversely correlated with both squamous cell maturation and nonsquamous differentiation in CIN. This biomarker also identified basal cells in a subset of preinvasive cervical neoplasms with endocervical cell differentiation that were bcl-2 and keratin 14 negative.. In the lower female genital tract, p63 is preferentially expressed in immature cells of squamous lineage and is not linked to cell proliferation. The broader range of p63 expression relevant to keratin 14 and bcl-2 indicates that p63 may identify additional subsets of benign and neoplastic epithelial basal cells in the cervical transformation zone and may be useful in studying cell differentiation in the early stages of neoplastic change in this region.

Topics: Adenocarcinoma; Atrophy; Biomarkers, Tumor; Carcinoma in Situ; Cell Cycle; Cell Differentiation; Cervix Uteri; DNA-Binding Proteins; Epithelium; Female; Gene Expression; Genes, Tumor Suppressor; Humans; Keratin-14; Keratins; Ki-67 Antigen; Membrane Proteins; Phosphoproteins; Proto-Oncogene Proteins c-bcl-2; RNA, Messenger; Trans-Activators; Transcription Factors; Tumor Suppressor Proteins; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms

The involvement of Sertoli cells in different spermatogenic impairments has been studied by an immunohistomorphometric technique using cytokeratin-18 (CK-18) as a marker for immature Sertoli cells. CK-18 is known to be expressed in Sertoli cells during prenatal and prepubertal differentiation and is normally lost at puberty. Forty-nine azoospermic men were included in the current study. Quantitative measurements on testicular biopsies revealed the highest CK-18 expression in the mixed atrophy biopsies (22 men), a lower expression in the Sertoli cell-only (SCO) biopsies (12 men), and minimal residual staining in the group considered as representing normal spermatogenesis (six obstructive azoospermia patients). The cytokeratin immunopositive-stained tubules were associated either with arrest in spermatogenesis or with SCO. Examination of sections from nine men with microdeletions in the AZF region of the Y chromosome revealed that these men were either negative for CK-18 expression or showed only weak residual staining. This may suggest that the spermatogenic defect in the AZF-deleted men originates in the germ cell and has no impact on Sertoli cell maturation. The cause that determined the spermatogenic defect in the other cases of male infertility with high CK-18 expression may have damaged both the Sertoli and the germ cells.

Topics: Adult; Atrophy; Biological Factors; Biopsy; Cellular Senescence; Gene Deletion; Humans; Keratins; Male; Middle Aged; Oligospermia; Phenotype; Sertoli Cells; Spermatogenesis; Testis; Y Chromosome

We have seen in consultation a variant of atrophy, which is frequently confused with well-differentiated adenocarcinoma of the prostate. We have designated this entity as partial atrophy to distinguish it from its more common counterpart of fully developed atrophy. Partial atrophy is defined as benign prostate glands with relatively scant cytoplasm, yet the glands are not fully atrophic in that they do not appear basophilic at low magnification. Fifty-one cases of partial atrophy were identified (4 from Johns Hopkins Hospital, 47 from consultation). Within the partial atrophy focus, irregular (crinkled) nuclei were frequent in 23.5% and occasionally present in 33.3% of cases. Visible nucleoli were frequent in 25.4% of cases. Basal cells were not identifiable in 27.4% of cases or were hard to identify in 35.3% of cases. No intraluminal crystalloids or blue-tinged mucinous secretion was identified in partial atrophy. Adenocarcinoma or glands suspicious for cancer were present in other cores in 15.6% of cases. More fully developed atrophy was present in simultaneously obtained needle cores in 35.3% of cases. In the cases in which regular atrophy was the only coexisting condition, it was present within one 10x field from the partial atrophy in 22.2%, farther than one 10x field from the partial atrophy in 11.1%, and present in the same gland as the partial atrophy in 66.7%. Partial atrophy may be confused with low-grade adenocarcinoma because of the focus of crowded glands, irregular nuclei, and visible nucleoli. Clues for recognizing partial atrophy include relatively scant cytoplasm, distinct crinkled nuclei, pale cytoplasm similar to adjacent, more recognizably benign glands, and association with more fully developed benign atrophy.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Atrophy; Biopsy, Needle; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Pathology, Surgical; Prostate; Prostatic Neoplasms

The electric organ (EO) of the weakly electric fish Sternopygus macrurus derives from striated myofibers that fuse and suppress many muscle properties. Mature electrocytes are larger than muscle fibers, do not contain sarcomeres, or express myosin heavy chain (MHC) or tropomyosin. Furthermore, electrocytes express keratin, a protein not expressed in muscle. In S. macrurus the EO is driven continuously at frequencies higher than those of the intermittently active skeletal muscle. The extent to which differences in EO and muscle phenotype are accounted for by activity patterns, or innervation per se, was determined by assessing the expression of MHC, tropomyosin, and keratin 2 and 5 weeks after the elimination of (1) activity patterns by spinal transection or (2) all synaptic input by denervation. Immunohistochemical analyses showed no changes in muscle fiber phenotypes after either experimental treatment. In contrast, the keratin-positive electrocytes revealed an upregulation of MHC and tropomyosin. Nearly one-third of all electrocytes expressed MHC (35%) and tropomyosin (25%) 2 weeks after spinal transection, whereas approximately two-thirds (61%) expressed MHC 2 weeks after denervation. After 5 weeks of denervation or spinal transection, all electrocytes contained MHC and tropomyosin. Newly formed sarcomere clusters also were observed in denervated electrocytes. The MHC expressed in electrocytes corresponded to that present in a select population of muscle fibers, i.e., type II fibers. Thus, the elimination of electrical activity or all synaptic input resulted in a partial reversal of the electrocyte phenotype to an earlier developmental stage of its myogenic lineage.

Topics: Animals; Atrophy; Cell Division; Cells, Cultured; Electric Fish; Electric Organ; Female; Gene Expression; Keratins; Male; Muscle Denervation; Muscle Fibers, Skeletal; Muscle, Skeletal; Myosin Heavy Chains; Phenotype; Sarcomeres; Spinal Cord; Tropomyosin

Acinar cell regeneration in the rat parotid gland after atrophy induced by a one week period of duct obstruction was examined using histology, immunohistochemistry and transmission electron microscopy (TEM). For immunohistochemistry, antibodies to 5-bromo-2'-deoxyuridine (BrdU), injected one hour before tissue collection, and cytokeratin were employed. When clips were removed from the duct, only ductal epithelial cells remained; all acinar cells had been deleted. Some duct cells were BrdU positive. After three days, newly-formed acini comprising immature acinar cells had appeared; many of the cells were BrdU positive and mitotic figures were readily identified. Thereafter progressive acinar cell maturation and proliferation occurred, parotid gland weight returning to control levels by 7 days. Peak BrdU labelling indices for duct and acinar cells were on days 0 and 4, respectively. By TEM, cytoplasmic organelles in epithelial cells of transitional duct-acinar structures seen at 2 days were poorly developed. Immature acinar cells seen on day 3 contained zymogen granules and had increased endoplasmic reticulum and mitochondria. By day 5, maturing acinar cells had abundant endoplasmic reticulum and zymogen granules, resembling acinar cells in control glands. These observations indicated origin of acinar cell precursors from duct cells during regeneration of the acinar cell-free atrophic gland. Subsequent expansion of the acinar cell population was dependent on maturation and proliferation of these newly-formed cells.

Topics: Animals; Atrophy; Cell Division; Constriction, Pathologic; Immunoenzyme Techniques; Keratins; Male; Organ Size; Parotid Diseases; Parotid Gland; Rats; Rats, Sprague-Dawley; Regeneration

Recently, there has been an exponential increase in the use of alpha-hydroxy acids in dermatologic practice. Their inclusion in a myriad of cosmetic preparations underscores their popularity. Among the clinical effects of alpha-hydroxy acids are their ability to prevent the atropy resulting from potent topical corticosteroids, improve the appearance of photoaged skin, and correct disorders of keratinization. Despite this range of desirable effects, very little is known about the specific changes produced by various alpha-hydroxy acid preparations in the epidermis and dermal extracellular matrix. Previous work by others has demonstrated the ability of another alpha-hydroxy acid to increase viable epidermal thickness, and dermal glycosaminoglycans.. In this study, we examined the effect of 20% citric acid lotion, as compared with vehicle alone, on skin thickness, viable epidermal thickness, and dermal glycosaminoglycan content. Biopsy samples were harvested after 3 months of treatment.. Image analysis of biopsy sections revealed increases in viable epidermal thickness and dermal glycosaminoglycans in treated skin.. Topical citric acid produces changes similar to those observed in response to glycolic acid, ammonium lactate, and retinoic acid including increases in epidermal and dermal glycosaminoglycans and viable epidermal thickness. Further studies of citric acid and other alpha-hydroxy acids are warranted to clarify their clinical effects and mechanisms of action.

Topics: Administration, Cutaneous; Aged; Aged, 80 and over; Anti-Inflammatory Agents; Atrophy; Biopsy; Chondroitin Sulfates; Citric Acid; Dermatologic Agents; Epidermis; Extracellular Matrix; Female; Follow-Up Studies; Glucocorticoids; Glycolates; Glycosaminoglycans; Humans; Hyaluronic Acid; Hydroxy Acids; Image Processing, Computer-Assisted; Keratins; Keratolytic Agents; Lactates; Pharmaceutical Vehicles; Quaternary Ammonium Compounds; Skin; Skin Aging; Tissue Survival; Tretinoin

From the first day of birth to the fifth day, daily subcutaneous 100 micrograms tamoxifen (Tx) was injected into new-born male rats. The penises that were taken totally were fixated in 10% formaline, and then they were put in paraffin inclusion. The paraffin sections were stained with Hematoxylen-Eosin, Verhoeff and Triple on days 7, 14, 21, 28, 35 and 60. The alterations in the development of glans penis construction were examined. We found that in the glans penis of animals which were given Tx, from the 21st day, the epidermal projections were erased slowly and on the 60th day the epidermal projections and keratinisation completely ceased altogether. As a result, the development of epidermal projections in rats which were given tamoxifen in the neonatal period were hindered.

Topics: Animals; Animals, Newborn; Atrophy; Epidermis; Epithelium; Estrogen Antagonists; Injections, Subcutaneous; Keratins; Male; Penis; Rats; Tamoxifen

Topics: Adolescent; Atrophy; Diagnosis, Differential; Facial Dermatoses; Female; Humans; Keratins; Prognosis; Skin

Keratin 19 is found primarily in simple epithelia. In mammary epithelia, keratin 19 was localized to a subset of luminal cells, suggesting that keratin 19-negative cells may be the proliferative compartment of the secretory cell lineage. The structural and functional similarities of prostate and breast led us to examine keratin 19 expression in the prostate. Immunohistochemical studies revealed that keratin 19 expression was heterogeneous and frequently occurred in basal as well as in luminal cells of normal, dysplastic, and benign hyperplastic tissues. Keratin 19 was observed in cancer, but usually in a minority of cells. This was in dramatic contrast to invasive breast cancers, which are reportedly uniformly positive for keratin 19. Prostatic epithelial cells cultured from tissues of all histologies expressed keratin 19. In summary, keratin 19 does not obviously correlate with any epithelial cell lineage or phenotype in the prostate.

Topics: Adenocarcinoma; Adult; Antibodies, Monoclonal; Atrophy; Cells, Cultured; Culture Techniques; Humans; Immunoblotting; Immunohistochemistry; Keratins; Male; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms

The aim of this study was to show the micromorphologic findings (epithelium, connective tissue, bone) in a region of pronounced gingival invagination after space closure by analyzing a maxilla taken in autopsy from a 19-year-old woman who was orthodontically treated. The dental records were also at our disposal. The second left premolar was congenitally absent. This area displayed before therapeutic horizontal bone atrophy. For space closure, the first upper left molar was moved mesially with a fixed appliance. After space closure, pronounced gingival invagination was diagnosed. The lateral segments of the specimen were prepared histologically in the horizontal plane. The microscopic observations revealed deep epithelial proliferation, hyperkeratinization, and one isolated keratin pearl in the connective tissue. Irrespective of location, the broad connective tissue layer showed disparate characteristics. Cell-rich, loose connective tissue with low fiber density were dominant in the subepithelial layer. The epiperiosteal layer displayed multiple tough fibers, some running parallel, some with reticular meshing, permeated with many blood vessels. Very few inflammatory cells were detected in the soft tissue. The bone had been resorbed in the mesiopalatal area of the molar (tooth movement direction) apart from one small isolated bony islet. These observations suggest that inflammatory influences were unlikely for marginal bone loss mesiopalatal to the tooth.

Topics: Adult; Alveolar Process; Anodontia; Atrophy; Bicuspid; Blood Vessels; Bone Resorption; Connective Tissue; Diastema; Epithelium; Female; Gingiva; Gingival Diseases; Humans; Keratins; Maxilla; Maxillary Diseases; Molar; Periosteum; Tooth Movement Techniques

Whether idiopathic atrophy of the nails (IAN) should be considered a separate entity or a clinical variant of nail lichen planus is still controversial.. We report here the pathological study of 2 patients with IAN.. Our patients had similar clinical features consisting of severe nail atrophy with and without pterygium.. The nail matrix architecture was markedly deformed with complete disappearance of the keratogenous zone that was replaced by a 3- to 10-cell-thick granular layer.. The hypothesis that IAN is an acute and self-limited variety of lichen planus is still the most presumable. Even though this hypothesis can not be definitely proven, it is nevertheless not excluded by the clinical and pathological findings of our cases.

Topics: Adult; Atrophy; Cicatrix; Female; Follow-Up Studies; Humans; Keratins; Male; Middle Aged; Nails; Nails, Malformed

Radiation therapy is becoming a treatment of choice for many patients with prostatic carcinoma. Distinguishing radiation change in prostate glands from carcinoma may be difficult. In this study we objectively assessed, by morphometric methods, the nuclear characteristics of benign and malignant prostates with a history of radiation treatment (125I implant with or without prior external beam radiation). This is part of our continuing efforts to achieve difficult differential diagnoses by analyzing perimeter, diameter and nuclear profile area of cells or interest and applying methods of statistical classification. Biopsies were performed 18-36 months following implant therapy. Eleven cases with residual prostate tumor constituted the malignant group. These were compared to 20 benign cases (benign glands in the 11 carcinoma cases plus 9 other cases with no residual carcinoma). Immunohistochemical staining with keratin 903 was performed on all cases. Differences in the nuclear parameters were most evident in the average nuclear profile areas (32.5 microns 2 for the malignant groups vs. 39.6 for the benign) and in the mean maximal cord length (diameter) (7.4 microns for the malignant group vs. 9.0 for the benign). Classification, however, is based on the size distribution plots of nuclear profile areas, which, in the malignant cases, had a sharper peak at lower value, while the benign cases had higher value and a broader peak with a trailing off into the larger values. This study emphasized the marked nuclear alterations that occur in irradiated prostates.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenocarcinoma; Atrophy; Biopsy, Needle; Brachytherapy; Cell Nucleus; Diagnosis, Differential; Follow-Up Studies; Humans; Image Processing, Computer-Assisted; Iodine Radioisotopes; Keratins; Male; Prostate; Prostatic Neoplasms

A new highly potent analogue (KH-1060) of vitamin D3 has been recently shown to stimulate the growth and differentiation of keratinocytes. This study was intended to determine the effects of this new analogue on epidermis at the ultrastructural level. KH-1060 was applied topically on the backs of hairless mice for 4 weeks; the skin was then studied by routine electron microscopy. The effects were compared with those of betamethasone-17-valerate and with concomitant treatment of KH-1060 following betamethasone. KH-1060 stimulated normal function of keratinocytes and formed a thick epidermis. The ultrastructure of the thick epidermis represents an enhanced normal process of keratinization and proliferation. Moreover, KH-1060 diminished the atrophogenic effects of betamethasone.

Topics: Administration, Cutaneous; Animals; Atrophy; Betamethasone Valerate; Calcitriol; Cell Differentiation; Cell Division; Cytoplasm; Cytoplasmic Granules; Desmosomes; Epidermis; Female; Hyalin; Intermediate Filaments; Keratinocytes; Keratins; Mice; Mice, Hairless; Microscopy, Electron; Mitochondria; Ribosomes

The concept of epidermal architecture that depends on epidermal turnover time is described. The epidermal architecture is determined, not by a simple proliferative condition, but rather by an epidermal turnover time (that depends both on cell number as well as on the proliferative condition). This is in relation to 'keratinization process' that requires a definite time to be completed. Using the concept, hyperproliferative 'psoriasiform' epidermis and hypoproliferative 'atrophic' epidermis are naturally described.

Topics: Atrophy; Cell Count; Cell Division; Epidermal Cells; Epidermis; Hypertrophy; Keratins; Models, Biological; Psoriasis; Time Factors

The keratin pattern in oral epithelia is related to the type of terminal differentiation observed morphologically (keratinization/nonkeratinization) and to the presence or absence of epithelial dysplasia. Furthermore, it has been suggested recently that inflammatory phenomena influence the keratin expression in human gingiva. The aim of the present study was to describe the keratin pattern in oral lichen planus (OLP) lesions, which are well known to be characterized by hyperkeratinization and severe inflammatory changes, in order to elucidate the role of inflammation in keratin expression of oral epithelia. Tissue sections were stained with antikeratin antibodies directed to groups of keratins (AE1 and AE2) and to single keratin proteins (Nos. 5, 8, 13, and 19). The keratin pattern in OLP lesions differed in some respects from that of leukoplakias and frictional keratoses as characterized in previous studies. No consistent patterns for use in a diagnostic context were found. However, the changes in OLP lesions did not mimic those previously described in inflamed gingival specimens and in oral epithelial dysplasias. Thus, the results encourage further studies on the potential diagnostic use of keratin expression in premalignant oral lesions. Furthermore, the study suggests that the inflammatory reaction seen in OLP lesions does not influence keratin expression in a way comparable with the suggested influence of inflammation in gingival specimens.

Topics: Antibodies, Monoclonal; Atrophy; Connective Tissue; Epithelium; Gingivitis; Humans; Keratins; Lichen Planus, Oral; Mouth Mucosa; Staining and Labeling

Elastosis perforans serpiginosa (EPS) is an uncommon skin disease characterized by transepidermal elimination of abnormal elastic fibers. The disease is frequently associated with congenital connective tissue disorders or Down's syndrome. The pathogenesis of EPS is still unclear. There are a few reports in the literature about a familial occurrence of EPS in which different modes of inheritance are suggested. To support the hypothesis of a congenital origin of the disease, we have studied another family with EPS.. In this study, we describe a family in which two sisters and a brother were affected by EPS. The father and three paternal uncles were most probably affected by the same disease. There were no signs of other congenital connective tissue disease in the family members.. An autosomal dominant mode of inheritance with variable expression of EPS is suggested.

Topics: Adult; Aged; Atrophy; Cicatrix; Connective Tissue Diseases; Elastic Tissue; Elastin; Female; Humans; Keratins; Keratosis; Male; Middle Aged; Neck; Skin Diseases

Anti-keratin and PAP immunohistochemical reaction on atrophic thymus collected from 97 autopsies were studied. Among them, 61 cases belonged to the severs type, whose reticulo-epithelial cells were falling into 4 types: the normal type, the centrally focused type, the diffused type and the depletive type. In 37 out of 61 cases, the reticulo-epithelial cells showed proliferation, especially in the medullary zone. All of 7 cases known as physiological involutional thymus turned to depletive type. 11 cases of atrophic thymus studied by scanning electron microscopy had been classified morphologically into 3 patterns, namely: the reticular form, the honey-combed form and the depletive form respectively.

Topics: Atrophy; Epithelium; Humans; Keratins; Microscopy, Electron, Scanning; Thymus Gland

We have previously demonstrated that human olfactory epithelia can be classified into five grades according to the degree of degeneration present in patients with various kinds of olfactory disorders. In practice, however, the occurrence of additional types of cell changes in other kinds of olfactory disorders and findings with immunohistochemical techniques have led us to re-evaluate our previous classification. In the present study, changes in olfactory epithelia from ten patients with various kinds of olfactory disorders are discussed and a revised classification is proposed. Microvillar and differentiating cells were also evaluated in the epithelium studied.

Topics: Adult; Aged; Atrophy; Cell Nucleus; Dendrites; Epithelium; Female; Humans; Immunohistochemistry; Keratins; Male; Metaplasia; Microvilli; Middle Aged; Olfaction Disorders; Olfactory Mucosa; Phosphopyruvate Hydratase; S100 Proteins; Sensory Receptor Cells; Sensory Thresholds; Smell

Duct-ligated submandibular and sublingual glands of rats were evaluated immunohistochemically for changes in keratin (MoAb 1164), actin, S-100 protein and rat-EGF (rEGF). Normal salivary glands were reactive for keratin, S-100 protein and rEGF in the granular convoluted tubule (GCT) and duct cells, and for actin in the myoepithelium. Submandibular glands showed a marked reduction of S-100 protein and rEGF staining following duct ligation, and no increased staining of proliferating epithelial cells of the late stage in duct ligated glands. Sublingual glands revealed no marked changes for actin staining in myoepithelial cells, irrespective of atrophic changes occurring in acinar and duct cells after duct ligation. Immunohistochemical patterns differed for each type of gland; changes associated with the obstructive lesion were more prominent in the submandibular gland.

Topics: Actins; Animals; Atrophy; Cytoplasmic Granules; Epidermal Growth Factor; Epithelium; Keratins; Ligation; Male; Rats; Rats, Wistar; S100 Proteins; Salivary Gland Diseases; Sublingual Gland; Submandibular Gland; Submandibular Gland Diseases; Time Factors

Keratin 19 (K-19) expression has been strongly correlated with dysplasia in oral epithelium. Expression of K-19 was evaluated by immunoperoxidase staining in formalin-fixed normal ectocervical tissue, normal endocervical tissue, cervical dysplasia, squamous metaplasia, atrophic epithelium, cervical condylomas, and invasive carcinoma to determine if a correlation of K-19 expression with dysplasia was present in the cervical epithelium. Uniform expression of K-19 was seen in endocervical epithelium and in the basal layer of normal ectocervical epithelium in all areas where these epithelia were present. Cervical dysplasia without associated condylomatous changes showed increased expression of K-19 in suprabasal epithelium, corresponding to the level of immature cells. Squamous metaplasia was characterized by scattered cells with increased staining (patch-quilt pattern). There was considerable overlap in the patterns of K-19 expression in dysplastic and metaplastic epithelium. Thus K-19 staining pattern could not be used as a distinctive marker for dysplasia in the cervical epithelium. Atrophic epithelium showed a characteristic uniform but low-level expression of K-19 in suprabasal areas. This pattern may be of diagnostic use in differentiating atrophic lesions from dysplasia. Condylomas showed focal loss of K-19 in the basal layer, suggesting induction of premature differentiation in the basal layer by human papillomavirus infection. Invasive carcinomas showed variable patterns. K-19 is a marker of immature cervical squamous epithelium, with generally distinctive but sometimes overlapping patterns of expression in various diagnostic categories.

Topics: Atrophy; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Cervix Uteri; Condylomata Acuminata; Epithelium; Female; Humans; Immunohistochemistry; Keratins; Uterine Cervical Diseases; Uterine Cervical Neoplasms

To examine the dividing cells in the olfactory epithelium, an experiment using a novel immunohistochemical technique with bromodeoxyuridine (BrdU) was performed. Tissue specimens were obtained from the olfactory epithelium of guinea pigs at days 7 and 21 after olfactory nerve axotomy. BrdU uptake was detected in the epithelial cell layer directly above the basal cell layer rather than in the basal cells per se. The BrdU-immunoreactive cells were found more numerously at 7 days than at 21 days after axotomy. The basal cells showed no immunoreaction to the anti-BrdU antibody on either day. The cells reacting with the anti-BrdU antibody also showed no reaction to the anti-cytokeratin antibody used to identify the basal cells. These findings indicate that the cells showing mitotic activity have characteristics different from those of basal cells, which has been considered previously to be the precursors of regenerating olfactory receptor cells.

Topics: Animals; Atrophy; Basement Membrane; Bromodeoxyuridine; Cell Cycle; Cell Division; Cell Nucleus; Epithelial Cells; Guinea Pigs; Immunohistochemistry; Keratins; Male; Olfactory Mucosa; Olfactory Nerve; Regeneration; Time Factors

From a total material of 184 Swedish users of loose packed moist snuff and 68 users of portion-bag packed moist snuff, cases were selected from subgroups based on a four-point clinical grading scale. The selected material for the study comprised 70 cases (ten from each clinical grade group, no Degree 4 lesion was found among portion-bag users). Features recognized in biopsies from these cases together with findings in previous studies correlated well with the use of a four-point scale for the grading of clinical changes, especially in the context of discriminating lesions for which special efforts should be undertaken to make the patient stop or change the snuff dipping habit and for selecting patients in whom regular clinical follow-up including a biopsy should be carried out. In this article is also discussed the labeling of the clinical oral mucosal changes seen at the site where a quid of snuff is regularly placed. The conceptual use of "snuff dippers' lesions" is recommended instead of e.g. snuff-induced leukoplakia.

Topics: Adult; Atrophy; Epithelium; Humans; Hyperplasia; Keratins; Male; Mitosis; Mouth Diseases; Mouth Mucosa; Necrosis; Plants, Toxic; Sweden; Time Factors; Tobacco, Smokeless

Tissues of human testes, either normal (23 specimens of various developmental stages), or affected by pathological conditions (19 specimens of dystopia, atrophia and/or oligospermia) were immunohistochemically examined for the expression of different cytokeratins, using mainly frozen material. Cytokeratins 8 and 18 were found in varying amounts in Sertoli cells of fetal, prepubertal and senile testes and in all cases of pathological alteration. Cytokeratins were completely absent only in normal, mature seminiferous tubules. Therefore, the immunohistochemical detection of cytokeratins in Sertoli cells seems to provide a sensitive marker for immature or damaged testes.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Atrophy; Child; Child, Preschool; Gene Expression; Humans; Immunohistochemistry; Infant; Keratins; Male; Middle Aged; Seminiferous Tubules; Sertoli Cells; Testis; Vimentin

There are a number of benign, small-acinar lesions in the prostate gland that may be difficult to differentiate from small-acinar adenocarcinoma. An important diagnostic criterion in this differentiation is the loss of the basal layer in small-acinar adenocarcinoma and its preservation in benign conditions. A monoclonal antibody to high-molecular-weight cytokeratins (34 beta E12) has been shown to stain these basal cells preferentially. To assess the usefulness of this antibody in distinguishing benign from malignant small-acinar lesions, we examined 21 cases of small-acinar adenocarcinoma and 47 examples of benign lesions, which included atypical adenomatous hyperplasia, atrophy, post-sclerotic hyperplasia, basal cell hyperplasia, and fibroepithelial nodule. Positive staining with 34 beta E12 was seen in 13/13 cases of atypical adenomatous hyperplasia, although in some cases the staining was weak and focal. Positivity with 34 beta E12 was also demonstrated in all other benign lesions studied. All 21 cases of small-acinar adenocarcinoma showed no reactivity with 34 beta E12. The results suggest that 34 beta E12 is of value in distinguishing between well-differentiated, small-acinar prostatic adenocarcinoma and its mimics. However, care is needed in interpretation of staining in formalin-fixed material due to the variable reactivity, particularly in cases of atypical adenomatous hyperplasia.

Topics: Adenocarcinoma; Adenoma; Antibodies, Monoclonal; Atrophy; Diagnosis, Differential; Evaluation Studies as Topic; Humans; Hyperplasia; Immunoenzyme Techniques; Keratins; Male; Molecular Weight; Prostate; Prostatic Diseases; Prostatic Neoplasms; Staining and Labeling

A patient with epidermolysis bullosa simplex with mottled pigmentation is described. Clinical features include blistering of the skin, especially of the extremities; healing without scars; slight atrophy of the skin; and striking mottled pigmentation of the trunk. Histologic examination of a biopsy specimen from freshly frictioned, clinically uninvolved skin indicated a split inside the basal keratinocytes, focal hyperpigmentation of the basal cells, and pigment incontinence without an inflammatory infiltrate. Indirect immunofluorescence demonstrated focal discontinuity of the basement membrane zone. Electron microscopic examination revealed basal keratinocytes with few intact intracellular organelles, aggregated tonofilaments, and subnuclear splitting with the basal parts of the cells adhering to the basement membrane. Both normal basement membrane and zones of irregular and interrupted structures were seen. Hemidesmosomes and anchoring fibrils appeared to be normal.

Topics: Adolescent; Atrophy; Basement Membrane; Biopsy; Epidermis; Epidermolysis Bullosa; Fluorescent Antibody Technique; Humans; Keratins; Male; Microscopy, Electron; Pigmentation Disorders

This study was to identify histologic tissue changes in the oral mucosa and to compare them in specimens from users of loose can-packed and portion-bag-packed moist snuff. The material consisted of biopsies from 252 regular snuff users. 184 using exclusively loose and 68 portion-bag snuff. An array of structural changes appearing in different combinations were identified among the 252 specimens. Two major patterns were recognized based on changes in the surface layer. Type 1 was characterized by an increased epithelial thickness with vacuolated cells and frequent chevron type changes. Type 2 showed a variably thickened surface layer with evidence of keratinization. Based on these findings, 14 carefully matched pairs of loose and portion-bag users were analyzed and compared. Loose snuff users showed predominantly histologic Type 1 changes while portion-bag users showed more histologic Type 2 or only very discrete changes.

Topics: Adult; Aged; Aged, 80 and over; Atrophy; Case-Control Studies; Cell Membrane; Epithelium; Humans; Hyperplasia; Keratins; Male; Middle Aged; Mouth Mucosa; Nicotiana; Plants, Toxic; Regression Analysis; Sweden; Tobacco, Smokeless

A 29-year-old woman had unilateral essential iris atrophy, corneal endothelial changes, and absolute glaucoma. The enucleated eye was examined by routine light microscopy. Separate portions of unfixed fresh frozen cornea were sectioned and reacted with monoclonal antibodies against keratins, vimentin, and inflammatory cell markers. Stains for filamentous actin (f-actin) were performed using the 7-nitro-benz-2-oxa-1,3-diazolylphallacidin (NBD phallacidin) probe. In addition, portions of cornea and iris were examined by scanning and transmission electron microscopy. Immunocytochemical stains with anti-keratin antibodies showed reactivity only in the corneal epithelium of the patient and normal control. Immunoreactivity with anti-vimentin antibodies was observed in corneal endothelium and keratocytes of the patient and control, but was negative in the epithelium. Staining for f-actin appeared more pronounced in the corneal endothelium of the patient. Scanning electron microscopy of the corneal endothelium showed irregularity in cell size and shape and filopodial processes characteristic of migrating cells. Transmission electron microscopy disclosed abnormalities of Descemet's membrane and endothelium with a posterior collagenous layer. The corneal endothelium displayed normal junctional complexes without desmosomal junctions or increased microvillus projections. Increased 10-nm cytoplasmic filaments were noted consistent with the expression of vimentin. Occasional chronic inflammatory cells perturbed the corneal endothelium and were detected within the endothelial layer. Alterations in the endothelium and Descemet's membrane suggest the acquired nature of this disease.

Topics: Actins; Adult; Atrophy; Corneal Diseases; Endothelium, Corneal; Female; Glaucoma; Humans; Immunohistochemistry; Iris; Iris Diseases; Keratins; Microscopy, Electron; Microscopy, Electron, Scanning; Syndrome

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

A major component of the thymic microenvironment is a network of thymic epithelial cells (TEC) which are able to express class II major histocompatibility complex products and to secrete thymic hormones. In the present investigation, we used a panel of anti-cytokeratin (CK) antibodies to establish distinct cytokeratin-defined TEC subsets. Four subpopulations were identified. One, in the cortex, is defined by anti-CK8 and anti-CK18 monoclonal antibodies (MAb). The other three subsets are medullary, two minor ones respectively reactive with anti-CK19 and KL1 monoclonal antibodies (the latter being specific for CK3 and 10), and a major one characterized by negative reaction with the above-mentioned MAb but strongly positive after labeling with a polyclonal (and polyspecific) anti-keratin immunoserum. Ontogenetic studies revealed that the CK8+/18+ TEC subset is the first to be detected in fetal life. Moreover, the numbers of CK3/10+ cells and CK19+ cells decrease in aging normal mice, a phenomenon that seems to occur early in autoimmune mice. We also observed that these two medullary TEC subsets are sensitive to high-dose in vivo treatment with hydrocortisone, which stimulates a dramatic increase in CK3/10+ cells and a certain decrease in CK19+ cells. Our results indicate that a number of mouse TEC subsets can be distinguished by cytokeratin expression. Such a strategy can be applied to analyze TEC sensitivity to drugs and might also be useful to further understanding of differential TEC function regarding intrathymic T-cell differentiation.

Topics: Age Factors; Animals; Antibodies, Monoclonal; Atrophy; Autoimmune Diseases; Diabetes Mellitus, Experimental; Epithelium; Female; Fluorescent Antibody Technique; Hydrocortisone; Keratins; Male; Mice; Mice, Inbred Strains; Thymus Gland

The thymic epithelium, a major component of the thymic microenvironment, is a heterogeneous tissue bearing distinct monoclonal antibody-defined subsets. Among these, KL1+ cells represent a mouse medullary subpopulation characterized by high mol wt cytokeratin expression. Given the fact that thymic epithelial cells (TEC) express glucocorticoid receptors and that glucocorticoid hormones are known to modulate the expression of keratins, we decided to study the in vivo effects of hydrocortisone on KL1+ cells in normal and autoimmune mice. Within 24 h after a single injection of this steroid we observed a significant increase in the number of KL1+ cells. Interestingly, this effect was reversible and was no longer detected 7 days after treatment. Parallel studies analyzing the effects of hydrocortisone on the secretion of thymulin, a chemically defined thymic hormone revealed a transient decrease in serum levels of this hormone, but with different kinetics than the effects on KL1+ cells. Ontogenetic studies showed that the responsiveness of TEC to hydrocortisone, in terms of high mol wt cytokeratin expression, appeared late in fetal life and disappeared in aging animals. Importantly, aging, but also young adult, autoimmune mice were not responsive. In vitro experiments using a mouse TEC line confirmed the data observed in vivo demonstrating that the increase in KL1+ cells is a direct effect of hydrocortisone on TEC. The bulk of the data presently reported demonstrates that glucocorticoid hormone can act on TEC modulating the expression of both secretory and cytoskeletal protein families.

Topics: Aging; Animals; Atrophy; Autoimmune Diseases; Cell Count; Dose-Response Relationship, Drug; Epithelium; Hydrocortisone; Immunoblotting; Keratins; Kinetics; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred NZB; Molecular Weight; Thymic Factor, Circulating; Thymus Gland

The morphology and numbers of Langerhans' cells vary in epithelia with different patterns of hyperplasia and keratinization. Langerhans' cells stained for ATPase were compared at five phases of the estrous cycle in murine vaginal epithelium. The cells were more dendritic and sparsely distributed with hyperplasia and were less dendritic and more densely distributed with atrophy. Greater numbers of the cells did not accompany keratinization at estrus. Ultrastructurally, three types of Langerhans' cells were discriminated. The first type, active in protein synthesis and phagocytosis, was commonest in sloughing and atrophic epithelium. The second type, containing accumulated and dispersed, electron-dense bodies presumed to be lysosomes, predominated in hyperplastic epithelium. The third, a mature resting cell, was found only after keratinization was complete. This study shows that Langerhans' cells in murine vaginal epithelium vary in morphology and numbers with the epithelial changes of the estrous cycle which may relate to their immunological role, but does not support the contention that their distribution is important for keratinization.

Topics: Adenosine Triphosphatases; Animals; Atrophy; Basement Membrane; Epithelial Cells; Estrus; Female; Hyperplasia; Keratins; Langerhans Cells; Mice; Phagocytosis; Vagina

Topics: Atrophy; Denture, Complete; Epithelium; Humans; Jaw, Edentulous; Keratins; Mouth Mucosa

The use of the synchronous induction method enables both assessment of the sequence and reliability of the appearance of morphologic signs of vitamin A deficiency, and their accurate correlation with biochemical and physiologic abnormalities. In the trachea, hyperplasia of basal epithelial cells was observed by Day 4 (T4) following the withdrawal of retinoic acid from retinoate-cycled, stringently deficient rats. Keratinization was observed by Day 6, the upper part of the trachea showing the highest incidence of keratinization. All such metaplastic changes originated in the narrow strip of tissue directly cojoining the esophagus. In the submaxillary glands, atrophy of the acini, an increase in interlobular spaces, and fibrosis and dilatation of the ducts was observed by Day 10. In more advanced stages of deficiency (T14-T18), cyst formation associated with suppuration and extensive cell atrophy was observed. Morphologic changes were less marked in the sublingual glands, although mucin levels were noticeably depressed by Day 12 of deficiency. Following the oral dosing of deficient animals (T12) with 350 micrograms retinyl palmitate, all such changes were reversed within 6 days in the trachea and within 10 days in the submaxillary and sublingual glands. Similar patterns were observed whether animals were force-fed or were fed ad libitum. Apart, therefore, from cause-effect considerations per se, morphologic changes are also potentially valuable reference indicators of deficiency, particularly in time course studies, or where force-feeding attenuates other signs of deficiency.

Topics: Animals; Atrophy; Keratins; Male; Metaplasia; Rats; Salivary Glands; Sublingual Gland; Submandibular Gland; Trachea; Vitamin A Deficiency

Effects of cyproterone acetate, a synthetic steroidal compound, on the reproductive organs of female rats have been investigated. This agent caused reduction of ovarian weights indicative of suppression of pituitary gonadotrophins. Oestrogenic nature of cyproterone acetate was investigated in intact and ovariectomized rats taking uterine weight and vaginal keratinization as an index of oestrogenicity. Cyproterone acetate in ovariectomized animals induced vaginal keratinization and increased the uterine weights. These effects were parallel to the effect of oestradiol dipropionate in ovariectomized animals, thus indicating oestrogenic activity of cyproterone acetate. We may conclude that the above compound caused antifertility effects due to its oestrogenic nature at the dose level of 2 mg/alternate day in rats when the compound was administered subcutaneously.

Topics: Animals; Atrophy; Body Weight; Castration; Cyproterone; Estradiol; Female; Fertility; Genitalia, Female; Hyperplasia; Hypertrophy; Keratins; Organ Size; Ovary; Rats; Reproduction; Uterus; Vagina

The smoking habits of 345 Danish and 184 Hungarian leukoplakia patients were analysed against the histopathology of the leukoplakias, i.e. type of keratinization, epithelial thickness, epithelial dysplasia and inflammation. In spite of the reasonable size of the numbers forming the basis for the analysis, no statistically significant differences were found between smokers and non-smokers. However, it was found that the frequency of epithelial dysplasia is not higher among smokers than among non-smokers.

Topics: Atrophy; Denmark; Epithelium; Female; Humans; Hungary; Hyperplasia; Inflammation; Keratins; Keratosis; Leukoplakia, Oral; Male; Smoking

In biopsies from the oral mucosa of 235 cases in which the diagnosis was lichen planus, keratosis or leukoplakia, mitotic values were calculated for the stratum basale (M.V. basal) and the stratum spinosum (M.V. spinous). The mean M.V. basal was significantly different from the mean M.V. spinous in the keratosis and leukoplakia groups, but not in the lichen planus group. Within the keratosis and leukoplakia groups, M.V. basal and M.V. spinous were significantly correlated. When each of the mean M.V.s was compared with the M.V.s for the other diagnostic groups, various significant differences were found. The M.V.s were examined in relation to the type of keratinization, the presence of acanthosis or atrophy, and the patient's age, but the M.V.s were not significantly related to these features.

Topics: Acantholysis; Age Factors; Atrophy; Epithelium; Humans; Keratins; Keratosis; Leukoplakia, Oral; Lichen Planus; Mitosis; Mouth Diseases; Mouth Mucosa

Topics: Animals; Atrophy; Epithelium; Inflammation; Keratins; Male; Mitosis; Parotid Gland; Rats; Salivary Glands; Sublingual Gland; Submandibular Gland; Tongue; Vitamin A Deficiency

Topics: Adolescent; Adult; Aged; Aging; Atrophy; Child; Collagen; Glycogen; Humans; Keratins; Keratosis; Middle Aged; Mouth Mucosa; Polysaccharides