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Biomedical subjects

J Slack

Publications and source records attributed to J Slack.

At least 55 records · Page 3Linked to original sources
PubMed1990

Risk of cancer death in first-degree relatives of patients with hereditary non-polyposis cancer syndrome (Lynch type II): a study of 130 kindreds in the United Kingdom.

To estimate the relative risks of cancer in first-degree relatives of index patients, 130 pedigrees of dominantly inherited Lynch type II cancer family syndrome have been analysed. The risk of death from all causes was significantly increased in women over 45 years of age and the overall liability to cancer in women was greater than for men. A sevenfold increase in risk of colon cancer was found in both sexes. In female relatives the risk of breast cancer was increased fivefold and lifetime risk of breast cancer was 1 in 3.7. A screening programme based on estimated risks could be offered to first-degree relatives of index patients with Lynch type II cancer family syndrome.

Adolescent↗
PubMed1990

Prenatal diagnosis of Conradi's syndrome. Case report.

A case is described of the diagnosis by ultrasound scanning during the second trimester of Conradi-Hünermann's syndrome (asymmetrical rhizomelic limb shortening or chondrodysplasia calcificans punctata). The prenatal diagnosis of limb shortening deformities is discussed.

Adult↗
PubMed1990

Molecular heterogeneity of interleukin-1 receptors.

Previous studies have shown that binding of IL-1 to its receptor and intracellular processing of the IL-1/IL-1 receptor complex appear to be different in B- and T-cells. The current report summarizes recent studies from our laboratory that show that the murine and human IL-1 receptors present on T-cells and fibroblasts are identical in primary sequence within each species, and highly similar even when the two species are compared. At present no cDNA clones have been isolated for IL-1 receptors present on B-cells. However, a monoclonal antibody raised to the receptor on murine T-lineage cells did not bind to a pre-B-lymphoma cell line that displays IL-1 binding sites, nor would cDNA probes derived from a T-cell IL-1 receptor clone cross hybridize at high stringency to mRNA prepared from these cells. In addition the two receptors differ substantially in size, as determined by affinity crosslinking with radiolabeled IL-1 alpha. Taken together, these observations show that major structural differences exist between the IL-1 receptors on B and T lymphocytes, while the receptors on T-cells and fibroblasts are identical polypeptides. We propose that the T-cell/fibroblast receptor be called IL-1RI and the B-cell type IL-1RII.

Animals↗
PubMed1989

IL-1 induces rapid phosphorylation of the IL-1 receptor.

The IL-1R on murine T cells is a Mr = 80,000 plasma membrane glycoprotein. cDNA cloning and transfection experiments have shown that this is an integral membrane protein, which binds both IL-1 alpha and IL-1 beta and transduces the IL-1 signal. A mAb, RM-5, which binds an epitope on the receptor which is distinct from the IL-1 binding site has been produced in rats. RM-5 has been used to immunoprecipitate the IL-1R from 32P-orthophosphate labeled CHO cells which express approximately 100,000 functional, murine rIL-1R/cell. Phosphorylation of the receptor was observed as early as 1 min after the addition of IL-1 and continued for periods of up to 30 min. Phosphorylation increases as the concentration of IL-1 increases from 10(-13) to 10(-8) M. Potassium hydroxide hydrolysis of the phosphorylated IL-1R shows that more than 90% of the phosphate is incorporated into serine or threonine. Thus, one of the earliest events after IL-1 binding to the IL-1R is activation of a serine/threonine protein kinase and phosphorylation of the IL-1R itself.

Animals↗
PubMed1989

A phase I study of meta-azidopyrimethamine ethanesulphonate (MZPES)--a new dihydrofolate reductase inhibitor.

A total of 68 patients were treated in a phase I study of meta-azidopyrimethamine ethanesulphonate (MZPES)--a novel lipophilic dihydrofolate reductase (DHFR) antagonist. The dose was increased from 5.4 mg/m2 to 460 mg/m2 given as a 1-h infusion, with 460 mg/m2, 600 mg/m2 and 800 mg/m2 given as a 24-h infusion. The dose-limiting toxicity was nausea and vomiting, which was marked at doses above 360 mg/m2 by 1-h infusion and 600 mg/m2 by 24-h infusion. Above 250 mg/m2 patients also described subjective neurological symptoms, although no objective signs were apparent. Myelosuppression was not consistent at any dose level. No objective responses were seen. In view of the lack of anti-folate activity at toxic levels, no phase II trials are currently proposed; toxicological and in vitro studies will continue.

Antineoplastic Agents↗
PubMed1989

Severity of disease induced by a pancreatropic Coxsackie B4 virus correlates with the H-2Kq locus of the major histocompatibility complex.

Coxsackie B viruses are known etiological agents of pancreatic diseases, including diabetes. The pathogenesis of these infections is influenced by both host and viral factors. In this report, we examined whether the outcome of Coxsackie B4 virus infection is dependent on the genes within the major histocompatibility complex (MHC). We generated a pancreatic variant, CB4-V and established an animal model system of pancreatitis with concurrent hypoglycemia in mice. Infection of various B10 H-2 congenic strains of mice revealed that the development of hypoglycemia with accompanying pancreatitis was independent of the MHC haplotype. However, the severity of the disease as monitored by the extent and duration of hypoglycemia and by mortality rate was found to be associated with the H-2 haplotype, specifically the H-2Kq locus. Pancreatic damage induced by CB4-V appeared to be both immune-mediated and viral-mediated. Histological examination of pancreatic tissue from infected B10 H-2 congenic mice revealed an association between acute destruction of the exocrine pancreas and lymphocytic infiltration. This infiltration may correlate with immune-mediated destruction of the infected pancreatic tissue. Since preferential replication of CB4-V was not observed in the most susceptible B10 mouse strain, direct viral destruction may not be the major mechanism of pancreatic injury.

Animals↗
PubMed1989

Evidence for different interleukin 1 receptors in murine B- and T-cell lines.

Previous studies have shown that binding of interleukin 1 (IL-1) to its receptor and intracellular processing of the IL-1/IL-1 receptor complex appear to be different in B- and T-lymphocyte cell lines. In this study we used a B-lymphoid cell line, 70Z/3, and T-lymphoid cell line, EL-4 6.1 C10, to explore further the differences that exist between IL-1 receptors on cells of B and T lineage. We show that a monoclonal antibody against the IL-1 receptor on EL-4 cells does not bind to the IL-1 receptor on 70Z/3 cells. This finding suggests that there are structural differences in the extracellular domains of the IL-1 receptors on the two cell lines. Furthermore, affinity crosslinking showed that the molecular mass of the IL-1 receptor on EL-4 is 87 kDa, whereas that of 70Z/3 is significantly lower (66 kDa). Activation of phospholipid/Ca2+-dependent protein kinase, protein kinase C, by phorbol 12-myristate 13-acetate (PMA) greatly reduced the number of IL-1 binding sites on 70Z/3. But, in sharp contrast, PMA had no effect on surface IL-1 receptor expression on EL-4 cells despite having an equally potent effect in activating protein kinase C. The different effects of protein kinase C suggest that the cytoplasmic domains of the IL-1 receptors in 70Z/3 and EL-4 may also be different. Lastly, a probe containing the entire coding region of the murine T-cell IL-1 receptor hybridized under high stringency conditions with mRNA from EL-4 cells but not with mRNA from 70Z/3 cells. Taken together, the observations made in this study suggest that major structural differences exist between the IL-1 receptors on B and T lymphocytes.

Animals↗
PubMed1989

Urinary polyamine excretion patterns in patients with epithelial ovarian cancer.

Free and acetylated urinary putrescine, spermine and spermidine levels (UPA) and total polyamine excretion were measured by high-performance liquid chromatography in 57 patients with epithelial ovarian cancer (EOC) and 43 control patients. Mean UPA levels were higher and the number of abnormal UPAs per sample greater for cancer patients but maximum single UPA sensitivity was only 29%. No control subject had more than 2 abnormal UPA values compared with 42% of patients with EOC. Rising UPA levels reflected progressive disease in 83% of patients and fell with tumour response in 66%.

Adult↗
PubMed1989

Inherited disorders associated with colorectal cancer.

There is an increased risk of colorectal cancer among first degree relatives of affected men and women which is greater among relatives of young index patients. The high risk in some families can be explained by Mendelian patterns of inheritance and some syndromes associated with colorectal cancer have been recognized. Syndrome recognition with an accurate knowledge of the natural history of diseases caused by a single gene effect can offer opportunities for exploration of some of the mechanisms of carcinogenesis as well as enable more accurate predictions of diagnosis in susceptible individuals and in pregnancy. Recent progress with familial adenomatous polyposis illustrates some of the opportunities for prevention of colorectal cancer which may arise with syndrome recognition in the future.

Adenoma↗
PubMed1988

Development of a self-administered questionnaire to measure women's knowledge of prenatal screening and diagnostic tests.

A prerequisite to an informed decision to undergo any screening or diagnostic test is knowledge about such a test. This study describes the development of a self-administered questionnaire to measure knowledge of prenatal tests, for use in studies concerning the uptake of these tests. Both the reliability (internal and test-retest) and predictive validity are evaluated. Validity is assessed in two studies: first, comparison is made between three criterion groups (two with experience of pregnancy, one without); and second, scores on the questionnaire are compared before and after women have been provided with information about possible tests. The results show this to be both a reliable and valid measure of knowledge about prenatal tests. The results also highlight aspects of knowledge that are lacking. For example, a sizeable minority of women were uncertain or incorrect in identifying which tests they had undergone in a recent pregnancy.

Amniocentesis↗
PubMed1988

Inheritance and bleeding in factor XI deficiency.

A study of 20 Jewish and four non-Jewish kindreds transmitting factor XI deficiency (164 individuals) confirmed inheritance to be autosomal with severe deficiency in homozygotes (mean factor XI level 3.8 u/dl, SD 2.91) and partial deficiency in heterozygotes (mean factor XI level 57 u/dl, SD 10.42; normal mean factor XI level 96 u/dl, SD 11.6). The probability of an individual being heterozygous can be predicted from the factor XI level using a graph derived from this data. The accuracy is increased by including the prior probability derived from the pedigree. A high frequency of heterozygote to heterozygote mating was observed in the Jewish families consistent with an estimated gene frequency of 13.4% in this racial group. The relationship between factor XI level and bleeding tendency is poor; a third of heterozygotes had bled excessively after surgery, including six with factor XI levels above 50 u/dl, showing this condition to have clear signs of expression in heterozygotes. The lower limit of the normal range (2 SDs from the mean) was found to be 72 u/dl.

Adolescent↗
PubMed1987

An economic appraisal of screening for Down's syndrome in pregnancy using maternal age and serum alpha fetoprotein concentration.

The direct and indirect costs and benefits of expanding the existing screening programme for Down's syndrome by using maternal age and serum alpha fetoprotein concentrations have been calculated using an ascertainment of Down's syndrome pregnancies from the North East Thames Regions in 1982. In addition, a possible approach to evaluating the total costs and benefits to the families concerned is presented. If the uptake of the proposed screening programme is maximal, the replacement rate is zero and a discount rate of 5% is used, the benefit cost ratio is 23.6. If the uptake of the programme is 50%, the replacement rate is 100% and a discount rate of 7% is used, the benefit cost ratio is 12.2. The proposed screening programme, based upon a risk of Down's syndrome of at least 1 in 220 using maternal age and serum alpha fetoprotein is both equitable for families at risk and of economic benefit to both families and society.

Abortion, Induced↗