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J Goepel

Publications and source records attributed to J Goepel.

8 recordsLinked to original sources
PubMed1999

The human embryonal carcinoma marker antigen TRA-1-60 is a sialylated keratan sulfate proteoglycan.

Human embryonal carcinoma (EC) cells are the stem cells of teratocarcinomas, and they are key components of germ cell tumors (GCTs). They express several high molecular weight glycoprotein antigens that are down-regulated upon differentiation. One of these antigens, defined by monoclonal antibody TRA-1-60, can be detected in the serum of GCT patients and provides a useful complement to the established serum markers human chorionic gonadotropin and alpha-fetoprotein, especially in those patients without elevated serum human chorionic gonadotropin or alpha-fetoprotein. To examine the relationship of the TRA-1-60-defined antigen to similar antigens defined by other monoclonal antibodies, we have carried out comparative Western blot and immunoprecipitation analyses of human GCT-derived cell lines with monoclonal antibodies TRA-1-60, TRA-1-81, GCTM2, and K21. The TRA-1-60 antigen was detected by Western blot analysis in extracts of all human EC cell lines and in clinical specimens of GCT tested as a diffuse band with a molecular weight of >200,000. A similar but noticeably fainter band was detected in GCT composed of seminoma only. The antigen was not expressed by GCT-derived lines without an EC phenotype. Affinity bead-purified TRA-1-60, TRA-1-81, GCTM2 and K21 antigens reacted in Western blot analysis with each of the other antibodies tested, indicating that the epitopes recognized by each antibody are carried by the same molecular species. This molecule could be metabolically labeled with inorganic [35S]sulfate and was degraded by keratanase. Glycopeptides produced from affinity-purified TRA-1-60 antigen by extensive digestion with Pronase exhibited a molecular weight in excess of 10,000 and were degraded by keratanase. The TRA-1-60 epitope was destroyed by digestion with neuraminidase, but the epitopes defined by TRA-1-81, GCTM2, and K21 were not. Our results indicate that human EC cells generally express a cell surface sialylated keratan sulfate proteoglycan that is subject to modification to yield a variety of epitopes, one of which is recognized by the monoclonal antibody TRA-1-60. Sensitivity to milk alkaline digestion suggests that the oligosaccharides of this proteoglycan are O-linked to a core polypeptide.

Antibodies, Monoclonal↗
PubMed1996

Small cell carcinoma of the cervix.

Small cell carcinoma of the cervix represents an uncommon variant of cervical cancer with a particularly poor prognosis. Traditionally, the diagnosis was established from routine histopathological sections, but there has been a trend to refer to this tumour as neuroendocrine carcinoma, with a requirement to demonstrate cytoplasmic granules. Five patients are described, who share the clinical features of young age of onset, early metastasis in the presence of apparently low stage disease, early failure of appropriate local treatment, and extreme chemosensitivity (features that are quite distinct from those seen in squamous cell cancer of the cervix). Light microscopy suggested a diagnosis of small cell cancer in all five tumours, but not all showed evidence of neuroendocrine differentiation. It is proposed that the present criteria for the diagnosis of cervical small cell carcinoma are too strict. The diagnosis should rely on the light microscopy of haemotoxylin and eosin sections and the distinctive clinical behaviour. The absence of neuroendocrine differentiation should not exclude the diagnosis, it does not appear to influence the clinical behaviour. The appropriate management of small cell carcinoma of the cervix is systemic, with chemotherapy as the first line of treatment. Surgery and radiotherapy may improve control of local disease but are unlikely significantly to influence the overall prognosis.

Adult↗
PubMed1985

Gastric lesions in portal hypertension: inflammatory gastritis or congestive gastropathy?

This paper reports the incidence and natural history of macroscopic gastritis in a series of 127 consecutive patients with portal hypertension of various aetiologies. Gastritis was observed endoscopically in 65 patients (51%) and was of two main types. Twenty eight patients had severe or persistent gastritis which caused clinically significant bleeding on 80 occasions and accounted for 25% of the bleeds from all sources. The remainder had mild gastritis. The presence of gastritis seemed to be independent of the severity of liver disease or the degree of rise of wedged hepatic venous pressure and there was no difference in age, sex, or drugs prescribed in patients with or without gastritis. The mean follow up period and the mean number of sclerotherapy treatments was significantly greater (p less than 0.005) in patients with gastritis. Full thickness gastric biopsies in seven surgical patients and 11 autopsy specimens showed dilated and tortuous submucosal veins. Endoscopic biopsies in 14 patients showed vascular ectasia in the mucosal layer which was in excess of the degree of inflammatory infiltrate. Gastritis occurred in patients with portal hypertension of all common aetiologies and the clinical and pathological evidence supports the contention that it reflects a congested gastric mucosa and should be renamed congestive gastropathy. As injection sclerotherapy improves survival from variceal bleeding congestive gastropathy may become more common. The response to conventional ('anti-erosive') therapy is poor and measures aimed at reducing the gastric portal pressure may be the only effective means of treating this condition.

Adult↗
PubMed1979

Immunological cross-reactivity between acid extracts of myelin, liver and neoplastic tissues: studies in immunized guinea-pigs.

Groups of 4 guinea-pigs were immunized with acid extracts prepared from bovine myelin (EF), normal human liver tissue and malignant or benign neoplastic tissues in Freund's complete adjuvant (FCA1. The animals were weighed daily and examined for clinical signs of experimental allergic encephalomyelitis (EAE). All the animals immunized with EF developed clinical symptoms of EAE within 21 days of the initial immunization, whilst some of the animals immunized with certain tumour extracts developed symptoms which closely resembled those of EAE. Control animals immunized with FCA only remained asymptomatic. Cellular immunity to the various extracts in immunized animals was assessed 20 days after immunization by i.d. skin testing, and upon killing at Day 21 with the direct peritoneal-exudate macrophage migration inhibition (MMI) test. Brains and spinal cords were removed at killing, fixed in formalin and processed for histological examination. I.d. skin testing was shown to be most consistent in demonstrating positive delayed hypersensitivity, whilst the MMI test frequently gave negative results in the presence of pronounced skin responses to specific extracts. Thus it was shown that 3/4 animals immunized with basic proteins extracted from an adenocarcinoma of the lung or related hepatic metastases, and 1/2 animals immunized with an extract of a carcinoma of the breast, gave intense erythema and induration responses 5 mm in diameter 24 h after i.d. challenge with EF. No such response was obtained in animals immunized with basic proteins extracted from normal human liver, any of the other neoplastic tissues, or in control animals immunized with FCA only. Examination of brains and spinal cords from animals immunized with EF revealed dense infiltration by mononuclear cells in the ependyma and choroid plexus of levels in the spinal cord. Examination of brains and spinal cords from animals immunized with the lung-tumour extract or related hepatic metastases which showed demonstrable immunological cross-reactivity with EF in immunized animals, revealed a number of inflammatory changes characterized by dense infiltrates of mononuclear cells sub-ependymally, and perivascular cuffing in the cortex. However, no significant lesions were seen in the spinal cords of these animals. Polyacrylamide-gel electrophoresis of the 2 tumour extracts exerting this apparent encephalitogenic effect did not reveal proteins within the mol. wt range of EF. Thus the observed pathological effects and cross-reactivity with EF were probably not due to contamination with nervous-tissue components. It is suggested that these tumour extracts may have contained a component or components other than EF, immunologically cross-reactive with EF, and capable of inducing the observed encephalitis.

Animals↗
PubMed1978

Cellular immunity to encephalitogenic factor as measured by macrophage migration inhibition during tumour induction and growth.

Spleen-cell sensitivity to encephalitogenic factor (EF) was measured with the macrophage migration inhibition (MMI) test over a period of time in hamsters inoculated with SV40-transformed tumour cells and in rats treated with 4-dimethylamino-3'-methylazobenzene.Spleen cells from hamsters receiving 10 or 10(3) SV40 tumour cells gave inhibition of macrophage migration with EF at a significance level of P<0·05 21 days after implantation. Spleen cells from animals receiving 10(5) tumour cells gave inhibition at a significance level of P<0·001 after the same interval.Spleen-cell sensitivity to EF, and the abrogation of this sensitivity by serum, was investigated over a period of time in rats undergoing hepatocarcinogenesis. Sensitivity to EF was seen in 2/10 animals (20%) with minimal lesions of the liver, in 2/16 animals (12%) with proliferative changes and/or cholangiofibrosis, in 7/15 animals (46%) with dysplastic lesions of portal-tract epithelial cells and in all 5 animals with cholangiocarcinoma. None of a control group of 10 animals showed any response to EF. Autologous serum abrogated the spleen-cell response to EF in one sensitized animal with proliferative changes and cholangiofibrosis, in all 7 sensitized animals with dysplastic hepatic lesions and in 4/5 sensitized animals with cholangiocarcinoma. Autologous serum had no effect on macrophage migration in the 10 control animals.These findings indicate that a progressive increase in sensitization to EF occurs during carcinogenesis and is evident at the point of preneoplastic dysplasia. This has an obviously important bearing on the clinical use of such tests.

Animals↗