PubMed HealthSearch

Biomedical subjects

J Slack

Publications and source records attributed to J Slack.

At least 37 records · Page 2Linked to original sources

Perceived risk not actual risk predicts uptake of amniocentesis.

A consecutive cohort of 71 women eligible for amniocentesis because they were over 38 years of age completed questionnaires during the first trimester of pregnancy. Sixty-one women underwent amniocentesis, an uptake rate of 86%. Uptake was associated with a less negative attitude towards termination of an affected baby and a higher perceived risk of the fetus being abnormal. It was not associated with actual age-related risks. There was no significant relation between actual risk and perceived risk. The results of this study suggests that it is important for doctors to understand the basis of women's decisions to have amniocentesis, and the difference between actual and perceived risk if they are to communicate effectively with women about the test and their options.

Abortion, Therapeutic

Pain management.

Patients with pain are not a new phenomena. For centuries, the incidence of pain has been well-documented. Responsibility for pain management has not been a universal priority for health care providers; however, pain management must be considered an integral part of the nursing role. The health care system must facilitate the improved management of patient's pain. A better understanding of the factors that underpin the effective management of a patient's pain is necessary. In this article, the theoretical foundation and conceptual model used in the expansion of this knowledge is presented. Further, the physiologic and pharmacologic principles related to this patient care issue are discussed. Appropriate consideration of the nurse's significant part in the management of pain is emphasized.

Analgesia, Epidural

Induction of an interleukin-1 receptor (IL-1R) on monocytic cells. Evidence that the receptor is not encoded by a T cell-type IL-1R mRNA.

Primary human monocytes and the human monocytic cell line THP-1 were induced to express receptors for interleukin-1 alpha (IL-1 alpha) and IL-1 beta. Treatment of primary monocytes with dexamethasone resulted in a 10-fold increase in receptor number over untreated cells, to approximately 2,000 receptors/cell. Treatment of THP-1 cells with phorbol ester followed by prostaglandin E2 and dexamethasone resulted in the expression of approximately 30,000 receptors/cell. Competitive binding assays on THP-1 cells showed that both IL-1 alpha and IL-1 beta bind to the same receptor. The monocyte IL-1R is significantly smaller (63 kDa) than the T cell IL-1R (80 kDa) and is immunologically distinct. However, induction of monocytes and monocytic cell lines leads to the appearance of an abundant mRNA of approximately 5,000 bases which hybridizes to a cDNA probe from the T cell-type IL-1R. Sequence data obtained from a cDNA clone of this mRNA indicate that the message is identical to the T cell IL-1R mRNA throughout the coding region. A smaller mRNA, also homologous to the T cell IL-1R mRNA, accumulated in induced THP-1 cells and has a shorter 3'-untranslated region than the larger. Data are presented which suggest that neither form of this message encodes the 63-kDa IL-1R, but rather that this protein is the product of a separate nonhomologous mRNA.

Cell Line

Cytokine receptors and B cell functions. I. Recombinant soluble receptors specifically inhibit IL-1- and IL-4-induced B cell activities in vitro.

IL-1 and IL-4 are important mediators of B cell growth and differentiation. The cell-surface receptors for these cytokines have recently been cloned and recombinant soluble receptors have been produced that bind their respective ligand. The ability of soluble forms of the murine IL-1R (sIL-1R) and IL-4R (sIL-4R) to inhibit B cell functions in vitro was examined. Proliferation of B cells treated with anti-Ig plus IL-1 or IL-4 was inhibited by the appropriate soluble receptor. sIL-4R also inhibited IL-4-dependent B cell differentiation as measured by: induction of IgG1 and IgE secretion by LPS blasts, down-regulation of IgG3 secretion by LPS blasts, increased Ia expression, and increased Fc epsilon R (CD23) expression. The inhibitory effects of the soluble receptors were found to be highly specific in that sIL-4R had no effect on IL-1-induced B cell activity and sIL-1R had no effect on IL-4 activity, further demonstrating the existence of two independent pathways of B cell activation directed by IL-1 and IL-4.

Animals

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

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

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

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

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

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

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

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

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