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Biomedical subjects

C Barbatis

Publications and source records attributed to C Barbatis.

At least 19 recordsLinked to original sources

Molecular analysis of p53 gene in laryngeal premalignant and malignant lesions. p53 protein immunohistochemical expression is positively related to proliferating cell nuclear antigen labelling index.

This study was undertaken in order to investigate the molecular nature of the p53 gene in 19 laryngeal squamous cell carcinomas and dysplasias. Moreover, we have examined the possible relationship between proliferating cell nuclear antigen (PCNA) expression and p53 protein detection status in 42 laryngeal premalignant and malignant lesions in which 14 of the 19 samples used in the molecular study were included. p53 gene analysis was performed with the single-strand conformation polymorphism technique. PCNA was stained with the peroxidase/antiperoxidase immunohistochemical method using the monoclonal antibody PC-10. Data from previous work concerning p53 expression was used. We found that 9 of 12 of the immunohistochemically p53 positive (+) cases had mutations in exons 5 or 6. In the remaining immunohistochemically p53(+) and p53 negative (-) specimens there was no indication of sequence alterations. Furthermore, we did not observe any deletions in the chromosomal region 17p31.1 which encodes exons 4-8 of the p53 gene. The PCNA labelling index (LI) increased progressively with p53 protein detection status (percentage of cells immunohistochemically positive for p53). The difference between the group with the higher percentage of p53(+) cells and the others was statistically significant. These data show that although there is a discrepancy between immunohistochemical demonstration of p53 and molecular analysis, a large proportion of the former harbours the mutant form of the protein. In addition, p53 overexpression is positively correlated with PCNA LI, a finding which accompanies tumour progression.

Base Sequence

Molecular and immunohistochemical evaluation of epidermal growth factor receptor and c-erb-B-2 gene product in transitional cell carcinomas of the urinary bladder: a study in Greek patients.

In this study, the expression of epidermal growth factor receptor (EGFr) and c-erb-B-2 was evaluated in 35 formalin-fixed, paraffin-embedded cases of transitional cell carcinomas of the urinary bladder (TCCs). EGFr and c-erb-B-2 expression was assessed with immunohistochemistry, and molecular analysis of the respective genes was performed with the differential polymerase chain reaction. The results were statistically analyzed in relationship to histologic grade, stage, and clinical outcome. Strong cytoplasmic expression of the EGFr using the polyclonal antibody Ab-4 was found in three (25%) Grade 2 and eight (67%) Grade 3 TCCs (P < 0.01). Two Grade 2 (17%) and 11 (92%) Grade 3 TCCs strongly expressed the anti-c-erb-B-2 Ab-3 antibody. None of Ta/T1 TCCs cases showed strong expression against EGFr, in contrast to c-erb-B-2 where two cases (18%) were found to express an intense immunosignal. Eleven (85%) T2/T3 cases showed strong positivity either against EGFr or c-erb-B-2 (P < 0.001). Eleven patients died within 12 months after the diagnosis, and all of them showed strong expression of EGFr and c-erb-B-2. Amplification of EGFr and c-erb-B-2 genes was identified in one (3%) and four (11%) TCCs cases, respectively. All patients with amplified genes died within 12 months from the date of diagnosis. Our results indicate that simultaneous expression of EGFr and c-erb-B-2 occurs in TCCs, is related to the histologic grade and the stage of the disease, and denotes aggressive biologic behavior.

Aged

Expression of p53 protein in laryngeal squamous cell carcinoma and dysplasia: possible correlation with human papillomavirus infection and clinicopathological findings.

In order to evaluate the expression of p53 protein in 28 premalignant and 40 malignant squamous cell proliferations of the larynx and its relationship to tobacco consumption, human papillomavirus infection and differentiation grade of the lesions, p53 expression was examined by means of a microwave post-fixation immunohistochemical method using the PAb 240 and PAb 1801 monoclonal antibodies. HPV infection was assessed by non-isotopic in situ hybridization (NISH) and polymerase chain reaction (PCR). A large proportion of carcinomas (77.5%) and dysplasias (61%) expressed p53. No difference was found between differentiation grades of the lesions regarding p53 detection (P > 0.1), but moderate or intense p53 expression was more frequent in the carcinomas (P < 0.05). A statistical correlation was found between cigarette consumption and both p53 detection and p53 staining intensity (P < 0.05 in each case). HPV study revealed HPV 16 and 18 infection only in carcinomas. The frequency was 28% and the physical state of the virus as demonstrated by NISH was integration into the genome. We observed an inverse relationship between HPV infection and p53 expression (P = 0.006). Our findings suggest that p53 overexpression is a common and early event which increases in frequency with progression of laryngeal squamous cell carcinoma. The expression of p53 is influenced by tobacco and high-risk types of HPV.

Base Sequence

Liver involvement in primary Sjögren's syndrome.

Three hundred patients with primary Sjögren's syndrome (pSS) were investigated for liver involvement using clinical, biochemical, immunological and histological data. Seven per cent of patients showed evidence of liver disease either subclinical (2%) or asymptomatic (5%) with elevated liver enzymes. In 6.6% of patients antimitochondrial antibodies (AMA) were detected by immunofluorescence and 27% of pSS patients showed antibodies to pyruvate dehydrogenase (a-PDH) using ELISA. AMA-positive patients were further investigated with transcutaneous liver biopsy. Ninety-two per cent of patients with AMA showed liver involvement with features of chronic cholangitis similar to stage I primary biliary cirrhosis. It is concluded that liver involvement in pSS patients is rare and subclinical with histological features predominantly of stage I primary biliary cirrhosis. AMA is the most sensitive indicator of underlying liver pathology in pSS patients.

Adult

Is beta-human chorionic gonadotrophin production by transitional cell carcinoma of the bladder a marker of aggressive disease and resistance to radiotherapy?

The biopsies from 75 patients with transitional cell carcinoma of the bladder (25 Ta-T1; 45 T2-T4, 5M) were studied immunohistochemically for the expression of beta-human chorionic gonadotrophin (beta-HCG). Only 5 Ta-T1 tumours contained a small number of beta-HCG positive cells but 24 invasive tumours and all patients with metastases showed increased numbers of positive cells. A significant correlation was found between beta-HCG immunoreactivity and tumour category. In 30 patients with muscle-invasive disease (T2-T4,N0,M0) who were treated with radical radiotherapy a significant correlation was observed between response to treatment and beta-HCG expression; beta-HCG positive tumours did not respond to treatment. A difference in survival was found between patients with tumours negative for beta-HCG compared with patients with positive tumours, all treated with radical radiotherapy. The results indicate that beta-HCG expression increases with tumour invasiveness and the use of immunohistochemistry may prove a useful means of identifying radioresistant and aggressive forms of bladder cancer.

Aged

Erdheim-Chester disease with epiphyseal and systemic disease.

A case of Erdheim-Chester disease which affected the epiphysis and showed evidence of systemic disease is presented. Clinical and histopathological similarities with other forms of disseminated Langerhans' cell histiocytosis are noted, particularly reaction of infiltrating histiocytes for S100 and HLA-DR.

Aged

Serial soluble interleukin 2 receptor levels in rheumatoid arthritis: differences in response to glucocorticoid treatment and chrysotherapy.

OBJECTIVE: To analyze the changes in soluble interleukin 2 receptor (sIL-2R) levels following treatment of patients with rheumatoid arthritis (RA). METHODS: Serial measurements of sIL-2R levels were made over 24 weeks in 40 patients with RA, treated with intramuscular (im) gold plus 3 im injections of either 120 mg methylprednisolone acetate or placebo. RESULTS: sIL-2R levels were reduced in the glucocorticoid treated group in contrast to the gold only group, where levels initially increased. At 24 weeks, mean sIL-2R levels did not significantly differ from pretreatment levels in either group, despite improvements in clinical measures. CONCLUSIONS: In our study, sIL-2R levels do not correlate with short term clinical measures of disease activity. Their significance for longer term prognostic use remains to be determined.

Adult

Intra-abdominal desmoplastic small-cell tumours with divergent differentiation. Report of two cases and review of the literature.

Two intraabdominal desmoplastic small cell tumours presenting in young adult males and involving the entire peritoneum, with no evident single primary site, have been studied. The histological pattern was suggestive of a metastatic small cell epithelial neoplasm, but immunohistochemical study revealed strong reactivity for cytokeratins, vimentin and desmin indicating synchronous epithelial and myogenous differentiation. In addition epithelial membrane antigen and neuron specific enolase were also positive. Electron microscopy showed fairly undifferentiated tumour cells with striking desmosome-like junctions, containing prominent paranuclear whorls of intermediate filaments, and a typical myofibroblastic stroma around neoplastic islands. Although the histogenesis of these recently described and rare tumours still remains uncertain, it seems that they constitute a reproducible entity which requires differential diagnosis from other small cell tumours of childhood and young adulthood.

Abdominal Neoplasms

Monoclonal antibody treatment in rheumatoid arthritis: the clinical and immunological effects of a CD7 monoclonal antibody.

Six patients with rheumatoid arthritis were treated with a CD7 mouse monoclonal antibody, RFT2, daily for 15 days. Only two patients had a significant improvement in clinical disease activity which lasted 7-14 days. No serious adverse effects occurred although all patients developed antibodies against mouse immunoglobulin. During treatment T-lymphocyte numbers decreased and T-lymphocyte CD7 expression was absent in all but one patient.

Adult

Gold treatment of rheumatoid arthritis decreases synovial expression of the endothelial leukocyte adhesion receptor ELAM-1.

Leukocyte adhesion receptors on endothelial cells play an important role in the evolution of synovitis. We studied sequential synovial biopsies at Weeks 0, 2 and 12 in 11 patients with rheumatoid arthritis beginning parenteral gold therapy either alone or combined with 120 mg intramuscular methylprednisolone acetate at Weeks 0, 4 and 8 of treatment. Expression of endothelial leukocyte adhesion molecule 1 (ELAM-1) decreased on synovial blood vessels after both 2 and 12 weeks treatment (p less than 0.05), while the overall vascularity of the synovium did not change. Neutrophil numbers within the synovial membrane also decreased although this did not reach statistical significance. In contrast, there was no significant change in numbers or subset distribution of T cells or in Class II MHC expression by synovial lining cells, mononuclear cells or endothelial cells. Our results suggest that one of the early effects of intramuscular gold and glucocorticoid therapy may be a downregulation of the acute inflammatory process associated with the endothelial expression of a neutrophil adhesion receptor and the subsequent recruitment of neutrophils into the joint.

Adolescent

Expression of intestinal mucin antigens in the gastric epithelium and its relationship with malignancy.

The expression of large and small intestinal mucin antigens (LIMA and SIMA) was investigated in 30 gastrectomy specimens of carcinoma and in 11 controls resected for various pathologic conditions. One hundred eighty-five samples of normal mucosa, hyperplasia, intestinal metaplasia (types I, II, and III), dysplasia, and tumor were studied to identify phenotypes indicative of premalignant change. Our results showed LIMA and SIMA were not detected in normal gastric epithelium from either control or carcinoma specimens. SIMA characterized goblet cell mucin in all types of intestinal metaplasia and was not discriminatory between controls and carcinoma groups. On the other hand, LIMA was extensively expressed in columnar and goblet cells in carcinoma-bearing stomachs (97 per cent) but was absent in controls. There was a crescendo intensity and frequency of LIMA staining in an inverse relation to the degree of cell maturation and differentiation from type I intestinal metaplasia (60 per cent) to type II (85 per cent), type III (100 per cent), and dysplasia (100 per cent). In contrast, intestinal metaplasia of any type in controls did not show LIMA. The distribution of LIMA seemed to be intimately related to cell differentiation in the proliferative zone at the base of metaplastic glands. Carcinomas revealed antigenic phenotype heterogenicity. Our data indicate that LIMA sharpens the diagnosis of dysplasia, discriminates between reactive and preneoplastic epithelium (particularly within intestinal metaplasia), and detects abnormal phenotypes that may represent early stages in carcinogenesis.

Antigens, Neoplasm

Histopathology of intestinal inflammation related to reactive arthritis.

This study has identified a group of patients with inflammatory chronic, or relapsing acute arthritis who even in the absence of gastrointestinal symptoms have histological evidence of ileocolitis. At colonoscopy simultaneous biopsies of the terminal ileum and colon were taken from 108 patients with reactive arthritis (n = 55) or ankylosing spondylitis (n = 53), 47 patients with other rheumatic diseases and 19 control patients suffering from colonic polyps, adenocarcinoma, or chronic constipation. All control patients and all but one patient with rheumatoid arthritis, juvenile chronic arthritis, systemic lupus erythematosus, lumbar back ache, and psoriatic arthritis did not have histological evidence of acute or chronic inflammatory bowel disease. In contrast, in 30 of 35 (56.6%) patients with ankylosing spondylitis, and in 37 of 55 (67%) patients with reactive arthritis, regardless of HLA B27 phenotype, there was histological evidence of inflammatory bowel disease with features either of acute enterocolitis, or early Crohn's disease. Only 18 of 67 (27%) of the patients with histological gut inflammation, however, had intestinal symptoms.

Adolescent

Immunocytochemical analysis of HLA class II (DR) antigens in liver disease in man.

The in situ distribution of the major histocompatibility (HLA) class II (DR) antigens was studied in 113 liver biopsy specimens and five livers obtained at necropsy, using monoclonal antibody CR3/43. In 20 normal livers HLA-DR antigens were not detected in bile duct epithelium, hepatocytes, or portal vein endothelium. Normal arteriolar, sinusoidal and central venous endothelium often expressed HLA-DR. Kupffer cells always expressed these antigens. HLA-DR positive spindle cells were identified in the connective tissue of portal tracts, large hepatic veins, and liver capsule: most shared antigens common to all leucocytes and reacted with the histiocytic maker EBM11. Bile duct epithelium expresses HLA-DR in primary biliary cirrhosis, large duct obstruction, and drug induced cholestasis, indicating that HLA-DR positive spindle cells are phenotypically similar to histiocytes.

Antibodies, Monoclonal

Disorganisation of intermediate filament structure in alcoholic and other liver diseases.

The distribution of Mallory body antigens JMB1 and 2 was examined in 82 human fresh diagnostic needle liver biopsies and 28 necropsies by the indirect immunoperoxidase technique using 2 monoclonal antibodies (anti-JMB1 and 2) against Mallory bodies. The JMB1 antigen was detectable in bile duct epithelium and in hepatocytes of histologically normal livers. It was also found in all Mallory bodies in various hepatic disorders. This antigen was markedly increased in the cytoplasm of all liver cells in acute alcoholic hepatitis superimposed on alcoholic cirrhosis, in most cases of acute alcoholic hepatitis, and in severe fatty infiltration of the liver with or without Mallory body formation. Mallory bodies contained this antigen but the cytoplasm of Mallory body containing cells lacked JMB1. In normal liver the JMB2 antigen was localised on the cytoplasmic intermediate filament network of hepatocytes and bile duct epithelium; and almost all Mallory bodies also contained this antigen but the adjacent cytoplasm of these cells lacked JMB2. In severe alcoholic liver disease these antigens could not be detected in large zones of hepatocytes even when these hepatocytes did not contain Mallory bodies. It is evident that there is disorganisation of intermediate filament constituents in severe alcoholic liver disease.

Antibodies, Monoclonal

Localisation of Ca and HMFG2 antigens in breast tissue by immunoperoxidase, immunofluorescence, and immunoelectron microscopy.

The reactivities of Ca1 and HMFG2 monoclonal antibodies were compared on paraffin wax embedded breast tissues using indirect immunoperoxidase. The expression of Ca antigen, like HMFG2, is not exclusive to malignancy: Ca was present in 41/53 (77%) and HMFG2 in 42/53 (79.2%) non-malignant conditions and both were present in 33/35 (94%) carcinomas. Similar results were obtained when cryostat sections were used. Both antigens showed striking similarities in their topographical distributions, although quantitative differences were seen. Their cellular and sub-cellular localisations were investigated by double labelling immunofluorescence and immunogold electron microscopy, which showed that the expression of Ca and HMFG2 antigens was closely associated on cell membranes but that the epitopes were distinct.

Adenofibroma

Histological features of sclerosing cholangitis in patients with chronic ulcerative colitis.

Primary sclerosing cholangitis was diagnosed radiologically in 16 of 681 patients (2.2%) with chronic ulcerative colitis in a follow up study at the gastroenterology unit in Oxford. On the basis of established histological criteria, the liver biopsy was considered diagnostic in only half of the cases. The histological findings in these cases were therefore reassessed to determine whether the accuracy of biopsy diagnosis could be improved. The most common specific histological feature was periductal concentric fibrosis of small interlobular bile ducts, even in the absence of inflammation. Other common features were bile ductular proliferation associated with diminution or absence of interlobular bile ducts. Degeneration of bile duct epithelium and diffuse infiltration of portal tracts by mononuclear cells and polymorphonuclear leucocytes were accompanying features. Piecemeal necrosis without rosette formation was found in about half the biopsies. When all these features were considered together a biopsy diagnosis of primary sclerosing cholangitis was established in 14 of 16 cases.

Adult