bromochloroacetic-acid and Acute-Disease

Topics: Acute Disease; Adrenal Cortex Hormones; Animals; Anti-Bacterial Agents; Cathartics; Cystine; Hoof and Claw; Horse Diseases; Horses; Keratins; Methionine; Microcirculation; Phenylbutazone

The formation of protein inclusions is frequently associated with chronic metabolic diseases. In mice, short-term intoxication with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) leads to hepatocellular damage indicated by elevated serum liver enzyme activities, whereas only minor morphological changes are observed. Conversely, chronic administration of DDC for several weeks results in severe morphological damage, characterized by hepatocellular ballooning, disruption of the intermediate filament cytoskeleton, and formation of Mallory-Denk bodies consisting predominantly of misfolded keratins, Sqstm1/p62, and heat shock proteins. To evaluate the mechanistic underpinnings for this dichotomy we dissected the time-course of DDC intoxication for up to 10 weeks. We determined body weight change, serum liver enzyme activities, morphologic alterations, induction of antioxidant response (heme oxygenase-1, HO-1), oxidative damage and ATP content in livers as well as respiration, oxidative damage and the presence and activity of HO-1 in endoplasmic reticulum and mitochondria (mtHO-1). Elevated serum liver enzyme activity and oxidative liver damage were already present at early intoxication stages without further subsequent increase. After 2 weeks of intoxication, mice had transiently lost 9% of their body weight, liver ATP-content was reduced to 58% of controls, succinate-driven respiration was uncoupled from ATP-production and antioxidant response was associated with the appearance of catalytically active mtHO-1. Oxidative damage was associated with both acute and chronic DDC toxicity whereas the onset of chronic intoxication was specifically associated with mitochondrial dysfunction which was maximal after 2 weeks of intoxication. At this transition stage, adaptive responses involving mtHO-1 were induced, indirectly leading to improved respiration and preventing further drop of ATP levels. Our observations clearly demonstrate principally different mechanisms for acute and chronic toxic damage.

Topics: Acute Disease; Adaptor Proteins, Signal Transducing; Adenosine Triphosphate; Animals; Body Weight; Chemical and Drug Induced Liver Injury; Chemical and Drug Induced Liver Injury, Chronic; Energy Metabolism; Enzyme Induction; Gene Expression; Heat-Shock Proteins; Heme Oxygenase-1; Hepatocytes; Keratins; Liver; Male; Mallory Bodies; Mice; Mitochondria; Oxidative Stress; Protein Folding; Pyridines; Sequestosome-1 Protein; Time Factors

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

Secondary degeneration leads to an expansion of the initial tissue damage sustained during a spinal cord injury (SCI). Dampening the cellular inflammatory response that contributes to this progressive tissue damage is one possible strategy for neuroprotection after acute SCI. We initially examined whether treatment with a PEGylated form of rat interferon-beta (IFN-beta) would modulate the expression of several markers of inflammation and neuroprotection at the site of a unilateral cervical level 5 contusion injury. Adult female Sprague-Dawley rats were injured using the Infinite Horizon Impactor at a force of 200 kdyn (equivalent to a severe injury) and a mean displacement of 1600-1800 mum. A single dose (5x10(6) units) of PEGylated IFN-beta or vehicle was administered 30 min following SCI. Here we demonstrate temporal changes in pro- and anti-inflammatory cytokine levels and the expression of heat shock proteins and iNOS (involved in neuroprotection) at the lesion epicenter and one segment caudally after SCI and PEG IFN-beta treatment. The results suggested a potential therapeutic treatment strategy for modulation of secondary damage after acute SCI. Therefore, we examined whether acute treatment with PEG IFN-beta would improve forelimb function alone or when combined with forced exercise (Ex). Animals began the Ex paradigm 5 days post SCI and continued for 5 days/week over 8 weeks. Locomotion (forelimb locomotor scale [FLS], hindlimb BBB, and TreadScan) and sensorimotor function (grid walking) was tested weekly. Additional outcome measures included lesion size and glial cell reactivity. Significant FLS improvements occurred at 1 week post SCI in the PEGylated IFN-beta-treated group but not at any other time point or with any other treatment approaches. These results suggest that this acute neuroprotective treatment strategy does not translate into long term behavioral recovery even when combined with forced exercise.

Topics: Acute Disease; Animals; Cervical Vertebrae; Combined Modality Therapy; Exercise Therapy; Female; Forelimb; Interferon-beta; Keratins; Locomotion; Myelitis; Neuroprotective Agents; Polyethylene Glycols; Rats; Rats, Sprague-Dawley; Recovery of Function; Spinal Cord Injuries

Clara cell 10 kDa protein (CC10) is the major secretory protein of Clara cells and is thought to play a protective role in the lung owing to its anti-inflammatory properties. There is little information on the anatomical distribution of CC10-positive cells in rat lung following lipopolysaccharide (LPS) challenge. We have determined the expression of CC10 along the tracheobronchial tree in saline-treated and LPS-treated rats. Saline-treated rats showed sporadic CC10 staining in central airways and abundant staining in bronchioles. In transitional airways, most cells were positive except for squamous cells. Following LPS challenge, there was a reduction in staining in the upper airways but little change within bronchioles. Squamous epithelia within the transitional airways now showed positive staining. These cells also co-stained for pancytokeratin and appeared to co-localize with surfactant D- and Ki67-positive cells, indicating the presence of a dedifferentiated cell type with both epithelial and pneumocyte phenotypes. These data show that diffuse inflammatory injury results in generalized loss of CC10 in central airways. Conversely, the transitional airways showed evidence of a dedifferentiated population of squamous cells that now stained for CC10. We hypothesize that this is an attempt by peripheral lung to maintain alveolar sac integrity during an inflammatory episode.

Topics: Acute Disease; Administration, Inhalation; Animals; Biomarkers; Bronchi; Enzyme Inhibitors; Keratins; Ki-67 Antigen; Lipopolysaccharides; Lung Diseases; Male; Pulmonary Surfactant-Associated Protein D; Rats; Respiratory Mucosa; Uteroglobin

The major keratins in the pancreas and liver are keratins 8 and 18 (K8/K18), but their function seemingly differs in that liver K8/K18 are essential cytoprotective proteins, whereas pancreatic K8/K18 are dispensable. This functional dichotomy raises the hypothesis that K8-null pancreata may undergo compensatory cytoprotective gene expression. We tested this hypothesis by comparing the gene expression profile in pancreata of wild-type and K8-null mice. Most prominent among the up-regulated genes in K8-null pancreas was mRNA for regenerating islet-derived (Reg)-II, which was confirmed by quantitative reverse transcription-polymerase chain reaction and by an anti-Reg-II peptide antibody we generated. Both K8-null and wild-type mice express Reg-II predominantly in acinar cells as determined by in situ hybridization and immunostaining. Analysis of Reg-II expression in various keratin-related transgenic mouse models showed that its induction also occurs in response to keratin cytoplasmic filament collapse, absence, or ablation of K18 Ser52 but not Ser33 phosphorylation via Ser-to-Ala mutation, which represent situations associated with predisposition to liver but not pancreatic injury. In wild-type mice, Reg-II is markedly up-regulated in two established pancreatitis models in response to injury and during the recovery phase. Thus, Reg-II is a likely mouse exocrine pancreas cytoprotective candidate protein whose expression is regulated by keratin filament organization and phosphorylation.

Topics: Acute Disease; Amino Acid Sequence; Animals; Cytoplasm; Disease Models, Animal; Keratins; Mice; Molecular Sequence Data; Mutation; Pancreas, Exocrine; Pancreatitis; Pancreatitis-Associated Proteins; Phosphorylation; Proteins; Up-Regulation

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

To determine whether there is a change in the expression of cytokeratins in the epidermal cells of the non-weight-bearing parts of the limb in horses with acute laminitis and thus determine whether the morphologic changes that develop in the periople and chestnut (torus carpeus) of horses early in acute laminitis are caused by inhibition of keratinocyte differentiation.. 8 horses with acute laminitis.. Tissue specimens were obtained from the chestnuts of all 8 horses and from the stratum externum of the hoof wall of 3 horses. Tissue specimens were obtained within 48 hours of the first clinical signs of laminitis. The cytokeratins were characterized by 1- and 2-dimensional gel electrophoresis, and the tissue distribution of the cytokeratins was studied by immunohistochemical staining.. The biochemical findings indicated that the epidermal cells of tissues from horses affected by laminitis contained the same set of cytokeratins as corresponding tissues from clinically normal horses. Immunohistochemistry on sections from specimens of horses with laminitis versus clinically normal horses indicated a difference in the expression of cytokeratin in the basal cells in the matrix of the stratum externum of the hoof wall and in the matrix of the chestnut of horses with laminitis in which the most severe morphologic changes were observed.. Inhibition of keratinocyte differentiation, as observed by immunohistochemical changes, in cells in parts of the chestnut and periople may indirectly indicate that the observed epidermal changes in horses with laminitis are primary and are unaffected by weight-bearing.

Topics: Acute Disease; Animals; Cell Differentiation; Electrophoresis, Polyacrylamide Gel; Epidermis; Female; Foot Diseases; Hoof and Claw; Horse Diseases; Horses; Immunohistochemistry; Keratinocytes; Keratins; Lameness, Animal; Male

A patient with relapsed acute myelomonocytic leukemia (AML, FAB M4) developed skin infiltration by leukemic blasts. On immunochemistry, the blasts showed "bot" positive cytoplasmic staining for cytokeratins AE1/AE3 and CAM 5.2, resembling the pattern seen in Merkel cell carcinoma of skin. However, the blasts were positive for myeloid markers and negative for cytokeratin 19 and chromogranin. Aberrant immunochemical staining can lead to misdiagnosis unless a panel of antibodies of known specificity is used in tumor diagnosis, and the clinical context is taken into account. The possible role of cytokeratin 19 as a more specific marker for epithelia than keratin cocktails is discussed.

Topics: Acute Disease; Adult; Antigens, CD; Biomarkers, Tumor; Female; Humans; Immunoenzyme Techniques; Keratins; Leukemia, Myeloid; Leukemic Infiltration; Skin

STATEMENT OF FINDINGS: An inception cohort of 238 patients having peripheral joint synovitis of less than 12 months duration was evaluated clinically and followed prospectively for 1 year to determine the clinical significance of a number of rheumatoid arthritis (RA) associated autoantibodies. Serum samples collected at the time of the initial evaluation were tested for rheumatoid factor (RF) and antibodies to Sa (anti-Sa), RA-33, (pro)filaggrin [antifilaggrin antibody (AFA)], cyclic citrullinated peptide (anti-CCP), calpastatin, and keratin [antikeratin antibody (AKA)]. RF had a sensitivity of 66% and a specificity of 87% for RA. Anti-Sa, AFA, and anti-CCP all had a specificity of more than 90%, but a sensitivity of less than 50% for this diagnosis. Overall, there was a high degree of correlation between AFA, AKA, anti-Sa or anti-CCP, this being highest between anti-Sa and anti-CCP (odds ratio, 13.3; P < 0.001). Of the 101 patients who were positive for at least one of these four autoantibodies, 57% were positive for only one. Finally, anti-SA identified a subset of predominantly male RA patients with severe, erosive disease. Anti-SA, AFA and anti-CCP are all specific for early RA but, overall, have little additional diagnostic value over RF alone. Although these antibodies may preferentially recognize citrullinated antigens, the modest degree of concordance between them in individual patient sera suggests that it is unlikely a single antigen is involved in generating these responses.

Topics: Acute Disease; Adult; Antibody Specificity; Arthritis, Rheumatoid; Autoantibodies; Calcium-Binding Proteins; Citrulline; Coenzyme A Ligases; Cohort Studies; Epitopes; Female; Filaggrin Proteins; Histocompatibility Testing; Humans; Intermediate Filament Proteins; Keratins; Male; Middle Aged; Peptides, Cyclic; Predictive Value of Tests; Proteins; Rheumatoid Factor; Seroepidemiologic Studies; Synovitis

The cytoskeleton of living keratinocytes consists mainly of cytokeratins that have polymerised into intermediate filaments. The aim of this study was to describe the expression of cytokeratins in the living epidermal cells of the weight-bearing parts of the equine hoof wall during acute spontaneous laminitis. A total of 9 hooves from 3 horses subjected to euthanasia within 48 h of the first clinical signs of laminitis were sectioned and examined. The cytokeratins in the stratum medium and stratum internum of the hoof wall were characterized by 1- and 2-dimensional gel electrophoresis, and the tissue distribution of the cytokeratins was studied by immunohistochemical staining. The biochemical results showed the same set of cytokeratins as was seen in 8 normal horses, reported on previously, used as controls. The immunohistochemical results indicated a difference between normal horses and horses with acute laminitis in the content of cytokeratins in the basal cells of the matrix of the stratum medium of the hoof wall and in the basal and suprabasal cells in the stratum internum at the mid level of the hoof wall. However, no conclusion could be drawn as to whether this change in the cytokeratin distribution in laminitis was primary or was caused by the initiation of the local tissue-repairing process.

Topics: Acute Disease; Animals; Electrophoresis, Gel, Two-Dimensional; Epidermis; Female; Foot Diseases; Hoof and Claw; Horse Diseases; Horses; Immunohistochemistry; Keratins; Laminin

Cytokeratin 19 fragment (CK19) levels in serum have already been documented as a useful tumour marker for lung cancer. In the present study, it was hypothesized that CK19 may be increased in the serum and epithelial lining fluid of the respiratory tract from patients with pulmonary fibrosis. CK19 was measured in the serum and bronchoalveolar lavage fluid (BALF) of patients with pulmonary fibrosis and the correlation between CK19 levels and clinical parameters evaluated. Nineteen patients diagnosed with idiopathic pulmonary fibrosis (IPF), eight with pulmonary fibrosis associated with a collagen vascular disorder (PF-CVD), seven patients with acute interstitial pneumonia (AIP), and 10 normal smokers as a control group were studied. CK19 levels in sera of patients with IPF and patients with PF-CVD were significantly increased compared to those of normal smokers. CK19 levels in sera of patients with AIP were significantly increased compared to those of other groups. CK19 values in the BALF of patients with pulmonary fibrosis were significantly elevated compared to those of normal smokers. CK19 values in sera charged according to the progression or improvement of the acute lung injury. Immunohistochemical study using pulmonary tissues obtained from patients with AIP demonstrated that the hyaline membrane and proliferating type II pneumocytes were stained by anti-human cytokeratin 19 antibody. These data demonstrated that the measurement of cytokeratin 19 fragment is a useful parameter to evaluate the activity of lung epithelial cell damage and repair.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Biomarkers; Bronchoalveolar Lavage; Bronchoalveolar Lavage Fluid; Collagen Diseases; Enzyme-Linked Immunosorbent Assay; Epithelial Cells; Female; Humans; Immunoenzyme Techniques; Keratins; Lung Diseases, Interstitial; Male; Middle Aged; Pulmonary Fibrosis; Vascular Diseases

The development of ductular structures in acute hepatitis with panacinar necrosis was studied in 15 cases of fulminant hepatitis with variable clinical duration, using immunohistochemical markers. The immunophenotype of ductular structures was assessed by the expression of two bile duct epithelium determinants, wide spectrum cytokeratin and epithelial membrane antigen (EMA), and by their glycoconjugate expression using the specific binding lectins Dolichos biflorus agglutinin (DBA) and soybean agglutinin (SBA). Ductular structures showed a predilective, but not a strictly selective location in acinar zone 1 and at the periphery of newly formed parenchymal nodules. All were positive for keratin, while EMA and the lectins were identified less frequently. Cytokeratin expression was additionally observed in hepatic cells with no other phenotypic alteration: this occurred along isolated hepatic cords, within parenchymal remnants, in the spared parenchyma in acinar zone 1 and occasionally at the periphery of parenchymal nodules. The presence of cytokeratin expression in liver cell plates in association with intermediate morphological stages of tubular remodelling speaks in favour of biliary metaplasia of hepatocytes. This process may represent a phenotypic-functional accommodation of hepatocytes to an altered microenvironment, due to loss of parenchymal integrity. During the phenotypic shift, altered cytokeratin expression appears as one of the earliest biliary features, while EMA and the expression of glycoconjugates represent maturation markers.

Topics: Acute Disease; Antigens; Cytoplasm; Glycine max; Hepatitis; Humans; Immunohistochemistry; Keratins; Lectins; Liver; Membrane Glycoproteins; Mucin-1; Mucins; Necrosis; Plant Lectins; Soybean Proteins; Time Factors

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

Merkel cells (MC) were identified immunohistochemically using antibodies specific for cytokeratin (CK) 20 within human epidermis 12 to 72 h after exposure to UVB (4 MED). 12 h after exposure all MC were normally localized within the epidermal basal layer. However, 24 h after exposure 4% of the MC were detected suprabasally, the remaining 96% still being situated in the basal layer. Surprisingly, at 48 h and 72 h more than 50% had lost contact with the basal membrane. The MC of hair follicles did not show any obvious changes. These results argue, in the context of acute epidermal UV damage, for an abnormal turnover in dermatitis.

Topics: Acute Disease; Epidermis; Erythema; Female; Humans; Keratins; Male; Ultraviolet Rays

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

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

A series of 10 cases of biliary obstruction due to primary cholangiocarcinoma has been studied with histological and immunocytochemical means. The total duration of cholestasis (as manifested by jaundice) was between 2 and 11 weeks with variable period of preoperative drainage. Liver biopsy specimens taken during surgery for cholangiocarcinoma were investigated for the presence of ductular proliferation and the development of fibrosis, as demonstrated by Sirius Red F3BA collagen staining. The differentiation of epithelial components was evaluated by AEC-immunostaining with chain-specific monoclonal antibodies specifically directed against human keratins type 7, 18 and 19. Keratin 7, normally occurring only in the ductular system, was expressed in hepatocytes at the periphery of the hepatic lobule (zone I) following about 4 weeks' cholestasis, when an increase of ductular profiles in the enlarged portal areas had become manifest. Such keratin 7 positive cells, however, still retained all morphological aspects of hepatocytes. Keratin 19, normally also restricted to the ductular system in liver, is not expressed by zone I hepatocytes even after longer duration (up to 11 weeks) of cholestasis. It is concluded that the increase in ductular profiles during the first week is mainly due do proliferation of pre-existing ductules, while ductular metaplasia occurs in more chronic cholestasis. Development of fibrosis, not always strictly paralleling the multiplication of ductular profiles in sections through a portal tract, represents an early change, and is clearly apparent after 2 weeks of obstruction.

Topics: Acute Disease; Adenoma, Bile Duct; Aged; Antibodies, Monoclonal; Azo Compounds; Bile Duct Neoplasms; Cholestasis, Extrahepatic; Collagen; Coloring Agents; Female; Hepatic Duct, Common; Humans; Immunohistochemistry; Keratins; Liver; Male; Middle Aged

Antibodies against thymus epithelial cells (anti-TEC) and the basal cell layer (BCLA) of squamous epithelia have been described in association with HDV-related chronic liver disease (CLD). Data are lacking on their presence during nAnB virus infection. Sera from 51 patients with nAnB post-transfusion hepatitis, including acute and chronic cases diagnosed during a prospective study on candidates for cardiac surgery, and 167 with various forms of CLD were tested for the presence of anti-TEC and BCLA using indirect immunofluorescence on human thymus and rat forestomach sections. Both antibodies mainly occurred in nAnB, HDV and cryptogenic CLD (anti-TEC: 51%, 47% and 42%; BCLA: 29%, 38% and 31%, respectively). The prevalence of anti-TEC in nAnB CLD turned out to be higher than that recorded in alcoholic, HBV-related, autoimmune, liver and kidney microsomal antibody positive CLD and primary biliary cirrhosis (p ranging from less than 0.03 to less than 0.0004). Two monoclonal antibodies (Mabs) to cytokeratins gave a pattern superimposable on that of spontaneous anti-TEC (both Mabs) and BCLA (only one). Antibodies against epithelial constituents, presumably targeting cytokeratin-associated antigens, occur not only in HDV CLD, as previously reported, but also in nAnB CLD, where they might represent a diagnostic aid, due to the unavailability of reliable serological markers of nAnB infection. The close similarity of anti-TEC and BCLA status between nAnB and cryptogenic CLD suggests a nAnB etiology of at least a proportion of chronic liver patients at present scored as cryptogenic.

Topics: Acute Disease; Antibodies, Monoclonal; Antibody Specificity; Autoantibodies; Child; Epithelium; Fluorescent Antibody Technique; Hepatitis C; Hepatitis, Chronic; Hepatitis, Viral, Human; Humans; Keratins; Liver Diseases; Prevalence; Prospective Studies; Thymus Gland; Transfusion Reaction

Cutaneous graft-versus-host disease (GVHD) provides a unique model for studying the pathogenesis of several important lymphocyte-mediated skin diseases. Morphologic studies have suggested that Ia antigen (Ia)-bearing epidermal Langerhans cells (LC) may be specific targets for destruction in these conditions. Keratinocytes synthesize and express Ia in GVHD and some other lymphocyte-mediated skin disorders; Ia+ keratinocytes, constitutively able to secrete epidermal cell-derived thymocyte activating factor (ETAF)/interleukin 1, may possess antigen-presenting capacity, thus leading to enhanced cutaneous immune responses and disease chronicity. We therefore investigated the fate of Ia+ LC, and the potential antigen-presenting capacity of Ia+ keratinocytes, in a murine model of GVHD. Lethally irradiated C3H/He (H-2k) mice developed acute cutaneous GVHD, and expressed keratinocyte Iak, 8 days after injection of BALB/c (H-2d) bone marrow and spleen cells. Immunofluorescence studies showed a progressive decrease in the density of Ia+ epidermal LC during the evolution of GVHD. This decrease was paralleled by a progressive reduction in the allostimulatory capacity of GVHD epidermal cells (EC) in the allogeneic EC-lymphocyte reaction (ELR). The fall in the density of Ia+ LC, and in EC allostimulatory capacity in both primary and secondary ELRs, was consistently greater in GVHD mice than in mice treated only with x-irradiation. The allostimulatory capacity of GVHD and x-irradiated EC could not be restored by addition of indomethacin or exogenous ETAF to ELR cultures. The decreased allostimulatory capacity was not the result of inhibition of the ELR, since EC from GVHD and x-irradiated mice did not cause suppression when added to control ELR cultures. The capacity of EC to present ovalbumin, purified protein derivative of tuberculin, 2,4,6-trinitrobenzenesulfonic acid coupled to EC, and native cytochrome c (CYTc) to antigen-specific T-cell lines, clones, or hybridomas was reduced in x-irradiated mice and markedly decreased in GVHD mice. The capacity of EC from x-irradiated and GVHD mice to present CYTc fragment 81-104, which does not require further processing or catabolism by accessory cells, was similarly decreased. Taken together, the results indicate that: the function of LC is markedly and progressively impaired in acute GVHD; LC function is also decreased, but to a lesser extent, following x-irradiation alone; and Ia+ keratinocytes from lethally irradiated mice

Topics: Acute Disease; Animals; Antigen-Presenting Cells; Epidermis; Female; Fluorescent Antibody Technique; Graft vs Host Disease; Histocompatibility Antigens Class II; Isoantigens; Keratins; Langerhans Cells; Lymphocytes; Mice; Mice, Inbred Strains; Skin Diseases

Keratotic and squamous changes characteristic of vitamin A deficiency were minimal even in chicks which were malnourished and growth stunted and had no vitamin A in their diet. However, when these chicks were infected with Newcastle disease virus (NDV), keratotic changes appeared, most markedly in areas regenerating after infection. In chicks raised on full nutrient diets lacking only vitamin A, keratotic changes appeared in several areas of nasal mucosa but were absent from the mucosa of the inner (under) surface of the maxillary turbinate. Following NDV infection, such changes did appear in the inner lining epithelia. It is suggested that depletion of vitamin A causes regenerating epithelial cells to keratinize. Other effects of combined lack of vitamin A plus NDV infection were exhaustion of lymphoid cells from cranial bone marrow and exhaustion of lymphoid cell systems locally from the nose and paranasal glands.

Topics: Acute Disease; Animal Nutritional Physiological Phenomena; Animals; Bone Marrow; Bone Marrow Cells; Chickens; Diet; Harderian Gland; Keratins; Newcastle Disease; Newcastle disease virus; Plasma Cells; Respiratory Tract Infections; Turbinates; Vitamin A Deficiency