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Biomedical subjects

C Hall

Publications and source records attributed to C Hall.

At least 289 records · Page 16Linked to original sources

4,4'-Diisothiocyanatostilbene-2,2'-disulfonic acid inhibits CD3-T cell antigen receptor-stimulated Ca2+ influx in human T lymphocytes.

Stimulation of the CD3-T cell antigen receptor complex on T lymphocytes results in a rapid rise in intracellular calcium from both intra- and extracellular sources. The former is thought to be released from the endoplasmic reticulum in response to inositol trisphosphate, while the latter enters the cells through a membrane potential-sensitive transporter (Oettgen, H. C., Terhorst, C., Cantley, L. C., and Rosoff, P. M. (1985) Cell 40, 583-590). In this report we show that the stilbene disulfonate, DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid), inhibited the ability of monoclonal anti-CD3 complex antibodies to stimulate an influx of calcium in the human T lymphocyte cell line, Jurkat. DIDS had no effect on either antibody binding to the receptor or receptor-stimulated phosphatidylinositol turnover. The Ki was approximately 25 microM in the presence of extracellular Cl- and 10 microM when labeling was performed in the absence of Cl-, suggesting that DIDS was competing with Cl- for binding to the cell membrane. The reduced form of DIDS, dihydroDIDS, was only 50% as effective as DIDS itself, and the monoisothiocyanate stilbene, 4-acetamido-4'-isothiocyantostilbene-2,2'-disulfonic acid, was totally ineffective, even to concentrations of 0.750 mM. Removal of extracellular Cl- also inhibited the antibody-stimulated influx of calcium. These data suggest that the function of the CD3-T cell receptor-activated calcium channel/transporter may be dependent on or regulated by extracellular Cl-.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

Fifty six continence advisers, one peripatetic teacher.

The increasing demand for the services of a continence nurse led to a novel plan to combat such demand in Leicestershire. The district nursing service seconded a nurse to be trained as an adviser and then to return to the community to set up continence clinics in each health centre. The adviser selected nurses to run these clinics and taught them the skills required to do so. She also carried her own caseload. One hundred and one patients were seen in the clinics in the first year, of whom 30 were cured. In a further one third continence was greatly improved, and the remainder benefited from advice and consultation. The adviser has worked in only six health centres but has had a greater impact on dealing with incontinence than a series of lectures and seminars for district nurses over many years had had.

Adult↗

Plasma concentrations of atrial natriuretic factor in acute left ventricular failure in the dog.

Acute ischemic left ventricular failure was induced in anesthetized dogs by repeated coronary embolization with 50 microns microspheres. Plasma concentrations of atrial natriuretic factor (ANF) were measured by radioimmunoassay of arterial and venous samples before and after failure induction. Heart failure was accompanied by a doubling of arterial ANF concentration, whereas there were only insignificant changes on the venous side. The increase in arterial ANF correlated significantly to the increase in left ventricular end-diastolic pressure, but not to the increase in right atrial pressure. Measurements of pericardial pressure indicated that a pericardial constraint acted to reduce atrial distension and thereby cardiac ANF release during failure.

Animals↗

Regional cerebral blood flow during acute left ventricular failure in the dog: effect of converting enzyme inhibition.

Regional cerebral blood flow (rCBF) was studied in anesthetized dogs subjected to acute left ventricular failure and its treatment with enalaprilat (MK-422). When failure was induced a reduction in rCBF paralleling the reduction in systemic blood pressure was observed. After treatment rCBF did not change in spite of further blood pressure reduction. The results are explained by changes in vascular resistance of larger cerebral arteries. Vasoconstriction in these vessels during failure was counteracted by enalaprilat through reduction in circulating angiotensin II.

Angiotensin-Converting Enzyme Inhibitors↗

Methotrexate: assessment of in vivo clastogenicity and carcinogenicity.

The genotoxic and oncogenic potentials of methotrexate were studied in Sprague-Dawley rats. The rats received 0.1, 0.2, or 0.4 mg/kg of methotrexate as dietary admixtures on a 5 days on, 9 days off, regimen for 23 months. In the females of the high-dose group, there was a significant increase in mortality starting at 18 months. Significant increases in the number of rats with focal pulmonary interstitial fibrosis were seen in both sexes at the high-dose level. At the mid- and high-dose levels of both sexes, there was a significantly increased number of rats with myeloid and erythroid bone marrow hypoplasia. There was no evidence of either early onset or increased incidence of any tumor type in the treatment groups. Therefore, it is concluded that methotrexate does not have oncogenic potential. Also, at terminal sacrifice, bone marrow cells were harvested from selected animals on the last day of the 5-day dosing cycle and cytogenetic evaluation was performed. No significant increase in chromosomal aberrations was seen in any dose group relative to the control group. This observation further substantiates the absence of oncogenic potential due to methotrexate in rats.

Animals↗

Redistribution of peripheral blood flow during acute left ventricular failure in the dog.

Acute left ventricular failure was induced in anaesthetized dogs by repeated embolization of the left coronary artery with 57 micron microspheres. Tissue blood flow was measured with isotope-labelled microspheres in two stages of heart failure. With increasing doses of embolizing solution there was a progressive decline in systemic blood pressure and cardiac output. Failure was accompanied by a significant decrease in blood flow in all tissues examined except for intestine, adrenal gland, skin and right ventricle. Overall cardiac output distribution was estimated by combining flow data with data on relative tissue weights obtained from a dissection study in a separate group of dogs. A selective redistribution of cardiac output took place in the failure state. The blood flow was redirected away from the skeletal muscles and the spleen in favour of the intestines, kidneys, heart and brain.

Animals↗

Postnatal disappearance of the pregnancy-associated reduced sensitivity of plasma cortisol to feedback inhibition.

We recently observed that the characteristic insensitivity of the pituitary-adrenal system in women to feedback inhibition during pregnancy persists for at least four days postnatally. We therefore examined women during the first five weeks after delivery to assess when the sensitivity of plasma cortisol to glucocorticoid inhibition returns to normal. Dexamethasone (DEXA, 1 mg) was ingested at 11 pm by normal healthy women, once between the 3rd and 27th postnatal days, and again on day 35. Blood plasma was collected at 4 pm on the following day for cortisol assay. Plasma cortisol levels (nmol/L, mean +/- sem [n]) after DEXA in the first two weeks (216 +/- 28, [47]) were higher (p less than 0.001) than in nonmedicated nonpregnant women (47.4 +/- 8.9 [12]) and were normal by the 35th day after delivery (41.7 +/- 4.8 [74]). A negative association was found between post-DEXA cortisol and time after delivery in the first 4 post-partum weeks (r = -0.46, p less than 0.001). The study confirms that insensitivity of plasma cortisol to feedback inhibition persists beyond normal pregnancy in a significant proportion of healthy women for two to three weeks, and is absent by the 5th postnatal week.

Dexamethasone↗

Expression and developmental regulation of two unique mRNAs specific to brain membrane-bound polyribosomes.

Translation in vitro of membrane-bound polyribosomal mRNAs from rat brain has shown several to be developmentally regulated [Hall & Lim (1981) Biochem. J. 196, 327-336]. Here we describe the isolation and characterization of cDNAs corresponding to two such brain mRNAs. One cDNA (M444) hybrid-selected a 0.95 kb mRNA directing the synthesis in vitro of a 21 kDa pI-6.3 polypeptide, which was processed in vitro by microsomal membranes. A second cDNA (M1622) hybridized to a 2.2 kb mRNA directing the synthesis of a 55 kDa pI-5.8 polypeptide. Both mRNAs were specific to membrane-bound polyribosomes. Restriction maps of the corresponding genomic DNA sequences are consistent with both being single copy. The two mRNAs were present in astrocytic and neuronal cultures, but not in liver or spleen or in neuroblastoma or glioma cells. The two mRNAs were differently regulated during brain development. In the developing forebrain there was a gradual and sustained increase in M444 mRNA during the first 3 weeks post partum, whereas M1622 mRNA appeared earlier and showed no further increase after day 10. In the cerebellum the developmental increase in M444 mRNA was biphasic. After a small initial increase there was a decrease in this mRNA at day 10, coincident with high amounts of M1622 mRNA. This was followed by a second, larger, increase in M444 mRNA, when amounts of M1622 mRNA were constant. The contrasting changes in these two mRNAs in the developing cerebellum are of particular interest, since they occur during an intensive period of cell proliferation, migration and altering neural connectivity. As these mRNAs are specific to differentiated neural tissue, they represent useful molecular markers for studying brain differentiation.

Animals↗

Localization of a human heat-shock HSP 70 gene sequence to chromosome 6 and detection of two other loci by somatic-cell hybrid and restriction fragment length polymorphism analysis.

The human 70 kdalton heat-shock protein (HSP 70) is a member of a multigene family which is expressed in response to various physiological stresses including elevated temperatures. Using a cloned genomic HSP 70 DNA sequence we demonstrate by somatic cell hybrid and restriction fragment length polymorphism (RFLP) analyses that there are a minimum of three distinct HSP 70 loci in the human genome, one of which is located on chromosome 6.

Animals↗

Effect of ACE-inhibition on tissue blood flow during acute left ventricular failure in the dog.

Anesthetized dogs in acute left ventricular failure were treated with the ACE-inhibitor enalaprilat (MK-422). ACE-inhibition produced a fall in the mean blood pressure and a redistribution of cardiac output to the brain, right ventricle, upper gastrointestinal tract, and the inner and middle part of the renal cortex. The flow to the spleen, adrenals, skin, muscle, fat, lower gastrointestinal tract, and outer renal cortex did not change significantly. The differential sensitivity of the tissues to ACE-inhibition is most likely due to differences in sensitivity to circulating angiotensin II.

Angiotensin-Converting Enzyme Inhibitors↗

The nonsuppressibility of plasma cortisol persists after pregnancy.

To determine if normal balance is restored to the hypothalamic-pituitary-adrenal axis after pregnancy, we compared the dexamethasone suppressibility of plasma cortisol in women four days after delivery of their infant, with that of nonpregnant women. Plasma concentrations of cortisol before dexamethasone administration were similar in the post-partum women and in women taking oestrogen contraceptives, but both were higher than in normally cycling women. After dexamethasone, plasma cortisol in the post-partum women was significantly higher than in both oestrogen-taking and normally cycling nonpregnant women. The reduced dexamethasone-suppressibility of plasma cortisol, which is characteristic of pregnancy, extends into the post-partum period.

Contraceptives, Oral↗

Trifluoperazine activates and releases latent ATP-generating enzymes associated with the synaptic plasma membrane.

Neurone-specific enolase (NSE) and the brain form of creatine phosphokinase (CPK-BB) were previously found to be present in rat synaptosomal plasma membranes (SPM) using two-dimensional gel (2-D gel) and peptide analysis; enzymatic activities of these and of pyruvate kinase (PK), all involved in ATP generation, were shown to be "cryptic" unless the SPM were treated with Triton X-100. We now show that enzymatic activation also occurs when the SPM are treated with trifluoperazine (TFP). TFP activation occurred even when the enzymes were membrane associated, showing that solubilization was not responsible for "unmasking" the enzyme activities. When TFP treatment was performed at alkaline instead of neutral pH, NSE and CPK-BB were released as well as PK, nonneuronal enolase, and aldolase which were identified by 2-D gel and tryptic peptide analysis. Other proteins released included calmodulin, actin, and the 70-kilodalton heat-shock cognate protein. Tubulin, synapsin I, and a 35-kilodalton basic protein were largely unaffected. The latter was identified as the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase on the basis of 2-D gel and peptide analyses and subsequent partial sequencing of a rat brain cDNA coding for the same protein. TFP treatment is thus useful for activating latent enzymes as well as for distinguishing enzymes that have a different disposition on the membrane.

Adenosine Triphosphate↗

Epiphyseal dysplasia of the femoral head, mild vertebral abnormality, myopia, and sensorineural deafness: report of a pedigree with autosomal dominant inheritance.

A family is presented with short stature, femoral epiphyseal dysplasia, mild vertebral changes, and sensorineural deafness inherited as an autosomal dominant trait. Myopia and retinal detachment presenting in adult life were also present in some affected members. We suggest that this disorder may be a distinct entity within the spondyloepiphyseal dysplasia group of disorders.

Abnormalities, Multiple↗