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Biomedical subjects

M Webb

Publications and source records attributed to M Webb.

At least 91 records · Page 5Linked to original sources
PubMed1992

Expression of functional bradykinin receptors in Xenopus oocytes.

mRNA prepared from various tissues and cultured cells was injected into Xenopus laevis oocytes. Three to five days after injection, the response of the oocytes to the peptide bradykinin was monitored. The oocytes were voltage clamped and the membrane currents generated on application of agonist were recorded. mRNA from NG108-15, rat uterus, and human fibroblast cell line WI38 gave similar responses to bradykinin (1 microM), with an initial inward current (10-20 nA) followed by a prolonged period of membrane current oscillations. The same pattern of response was given by total RNA from rat dorsal root ganglia. No response to bradykinin (10 microM) was recorded from oocytes injected with rat brain mRNA, although these oocytes gave peak inward currents of about 75 nA in response to serotonin (10 microM). mRNA from both NG108-15 cells and rat uterus was fractionated on sucrose gradients. This resulted in an approximately five-fold increase in the size of the response compared to that given by unfractionated mRNA. The largest responses were given by mRNA fractions with a size of approximately 4.5 kb. Data were obtained consistent with the expression of both B1 and B2 receptors by WI38 human fibroblasts and with the expression of only the B2 type of receptor by NG108-15 cells.

Animals↗
PubMed1992

Effects of extended speaking on resonance of patients with cleft palate.

Groups of listeners and rating scales were used to study the effects of extended speaking on resonance and voice quality in eight adults with cleft palate and mild to moderate hypernasality and a matched group of noncleft adults, with normal resonance and voice quality. Authors interpret their findings as indicating that resonance changes were greater and vocal quality changes less, for the cleft group, but that changes were not extensive nor always in the direction of increased hypernasality or decreased vocal quality.

Adolescent↗
PubMed1991

Potential availability of cadaver organs for transplantation.

OBJECTIVE: To determine the potential number of cadaver kidney donors by applying defined donor criteria to people dying in hospital. DESIGN: Prospective study of all deaths occurring in 21 hospitals from 1 September 1988 to 31 August 1989. Questionnaires were administered to medical and nursing staff and families of potential donors aged 1-69. SETTING: Acute care hospitals in Gwent, South Glamorgan, Mid Glamorgan, West Glamorgan, Pembrokeshire, and East Dyfed health authorities, serving a population of 2.2 million. MAIN OUTCOME MEASURES: Cause of death, age, ventilation at time of death, diagnosis of brain death, and consideration of consent. RESULTS: Adequate data were available for 9840 of 10,095 hospital deaths (97.5% coverage). 188 patients aged 0-69 were identified as potential organ donors (widest definition), and of these 108 died without being ventilated at the time of death. Tests of brain stem death were formally completed in 57 cases, and organ donation was considered by the families of 47 of these potential donors. 26 patients became organ donors. Patients aged 50-69 with stroke were less likely to be ventilated than those aged less than or equal to 49 (21/96 v 24/34). Families of potential donors aged 20-39 were least likely to give permission. CONCLUSIONS: The supply of donor organs (specifically kidneys) could be increased by altering the management of patients aged 50-69 dying of severe cerebrovascular disease in general medical wards, in particular by increasing the proportion ventilated. The ethics of elective ventilation for the purposes of organ donation require discussion.

Adolescent↗
PubMed1991

Eight-year outcome of problem drinking among medical inpatients.

Male medical inpatients rated alcoholic on the Michigan Alcoholism Screening Test in 1982 were compared with non-alcoholic controls admitted to medical wards in the same year. By 1990 the alcoholic subjects had moderated their drinking, although peak consumption at follow-up was twice that of controls. A similar number of health and social disabilities occurred during the follow-up period among alcoholics and controls. Untraced and dead alcoholics had scored highly on MAST and the Severity of Alcohol Dependence Questionnaire in 1982.

Adult↗
PubMed1991

d-fenfluramine/prolactin response throughout the menstrual cycle: evidence for an oestrogen-induced alteration.

The prolactin (PRL) response to fenfluramine (FEN), a serotonin (5-HT) releasing agent, is used as an index of 5-HT sensitivity in studying disorders associated with central 5-HT abnormality. Plasma oestrogen levels are known to augment PRL responses to a variety of stimuli. In order to examine the effect that ovarian steroids have on this response nine, healthy women were tested twice at three time points in the menstrual cycle: early follicular, mid-cycle and late luteal phase with either d-FEN, a more specific 5-HT agent than the racemic mixture, or placebo. Responses to d-FEN were maximal at mid-cycle, lowest during the early follicular phase, with responses premenstrually being intermediate between the two. Responses to placebo did not vary. Plasma oestradiol levels fluctuated in parallel with neuroendocrine responses to d-FEN. The possible mechanisms are discussed, including an effect that oestradiol may exert at central serotonin sites.

Adult↗
PubMed1990

Characterization of bradykinin receptors solubilized from rat uterus and NG108-15 cells.

In this paper we report the solubilization of bradykinin B2 binding sites from membranes prepared from NG 108-15 tumours and rat uterus with retention of binding activity. Digitonin was found to solubilize the receptors from both tissues, and the addition of CHAPS increased the yield of soluble receptor from rat uterus only. The affinity of a range of bradykinin analogues has been shown to have the same rank order for both the soluble and membrane receptors from both tissues, and in corresponding functional assays. In addition, the binding of bradykinin ligands to the soluble and membrane receptors is similarly modulated by the presence of sodium ions. We conclude that the soluble binding sites correspond to the physiological bradykinin B2 receptor present in these tissues.

Animals↗
PubMed1989

A radioimmunoassay for bradykinin based on monoclonal antibodies.

We describe two monoclonal antibodies with recognise the peptides bradykinin and kallidin. These antibodies were used in a study to assess the feasibility of using monoclonal antibodies in place of conventional sera for radioimmunoassay. Antibody SBK1 recognises bradykinin with a Kd of 0.67 +/- 0.17 nM. It fails to recognise bradykinin from which any carboxyl terminal amino acid has been removed. Antibody SBK2 recognises bradykinin with a Kd of 58.11 +/- 7.55 nM; it recognises 1-8 and 1-7 bradykinin about 30% as effectively as the full-length sequence, and shorter carboxyl terminal truncated sequences with a progressively declining efficiency. In this model system, bradykinin concentrations of 0.2 nM could be reliably measured, and carboxyl truncated versions of the peptide could be distinguished from the parent molecule. The feasibility of using monoclonal antibodies to assay bradykinin and other small peptides is discussed in the light of these results.

Animals↗
PubMed1989

A developmentally regulated axonal glycoprotein (7-8D2 antigen) with a restricted distribution in mature rat brain.

7-8D2 is a mouse monoclonal IgGl antibody which recognizes a neuronal cell surface antigen in rat brain. Immunohistochemical techniques reveal the antigen to be present most abundantly in the cerebellum of the adult brain, where it is expressed by the cell bodies and fibres of the granule neurons. Lower levels of staining were found in the neuropil of the hippocampus, in some fibres of the corpus callosum and in the most superficial layer of the cerebral cortex. Immunoelectron microscopy confirmed that the antigen was present on the surface of the parallel fibres in the cerebellum and showed that it was absent from glial, Purkinje or stellate cell membranes. The antigen had a more widespread distribution early in development, and the restricted adult distribution was achieved by the end of the second postnatal week. Immunoblotting of samples of adult rat brain shows that the antigen appears as a close doublet of bands at 211,000 mol. wt. This result was confirmed by immunoprecipitating the antigen from metabolically labelled glycoproteins prepared from cultured cerebellar interneurons. Immunoblotting and immunohistochemical experiments were in agreement that the cerebellum contained high levels of the antigen, and that lower but significant amounts could be found in other brain regions, notably the hippocampus and the cerebral cortex. The localization data and the changes in the distribution of the antigen may suggest some role for this molecule during early brain development.

Animals↗
PubMed1989

Synthesis and structure-activity relationship of substituted tetrahydro- and hexahydro-1,2-benzisothiazol-3-one 1,1-dioxides and thiadiazinones: potential anxiolytic agents.

Several novel substituted tetrahydro- and hexahydro-1,2-benzisothiazol-3-one 1,1-dioxides and thiadiazinones were prepared and examined in a series of in vitro and in vivo tests to determine their pharmacological profile. Most compounds were orally active in blocking the conditioned avoidance response (CAR) but did not antagonize apomorphine-induced stereotyped behavior. Several compounds demonstrated moderate to high affinity for the 5-HT1A receptor binding site, with compounds 37 and 38 containing 2-pyrimidinylpiperazinyl and [3-(trifluoromethyl)phenyl]piperazinyl moieties and compound 47 containing the 2-pyrazinylpiperazinyl moiety displaying the highest affinity (Ki values of 10, 4, and 9 nM, respectively). Compound 37, 3-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butyl]hexahydro-4, 7-etheno-1H-cyclobut [f]-1,2-benzisothiazol-3(2H)-one 1,1-dioxide, buspirone, and ipsapirone showed similarities in their neurochemical and behavioral profiles. They were similar in potency in blocking CAR with AB50 values of 39, 32, and 42 mg/kg, respectively. They also demonstrated high affinity and selectivity for the 5-HT1A receptor site (Ki = 10 nM) and exhibited partial agonist/antagonist activity in the serotonin syndrome test. In addition, compound 37 inhibited apomorphine-induced climbing behavior much more potently (ED50 of 3.4 mg/kg) than stereotyped behavior (ED50 of 32.2 mg/kg) and will be evaluated further. Structure-activity relationships within this series of compounds are discussed.

Animals↗
PubMed1989

Directed forgetting and posthypnotic amnesia: information processing and social contexts.

In three experiments we compared posthypnotic amnesia (PHA) with directed forgetting (DF), evaluating subjects' hypnotic susceptibility, hypnotized or not. Experiment 1 suggested that the memory processes in PHA and DF were not the same. Low and high susceptibility subjects responded differently in the two contexts. Experiment 2 demonstrated a context effect for highly susceptible subjects: They showed the usual DF response outside hypnosis but not during hypnosis. Experiment 3 showed that high and low susceptibility subjects responded similarly to DF instructions outside hypnosis, eliminating the susceptibility as an important variable in the DF response. We concluded: (a) The interaction of context and susceptibility was the important determinant of unusual DF responses for high susceptibles, and (b) information processing concepts are too limited to explain PHA and perhaps DF. Theories that include interactions appear necessary for an accurate understanding of hypnotic phenomena and perhaps some phenomena usually focused on by cognitive psychology.

Amnesia↗
PubMed1989

The distribution of alcohol dependence severity among in-patient problem drinkers.

One hundred and sixty problem drinkers admitted to in-patient care were rated according to the severity of their alcohol dependence by means of two standardized questionnaires (SADQ and SADD). A bimodal distribution of scores previously reported with the SADQ was not reproduced with either questionnaire, but there was a highly significant correlation (r = 0.806) between the SADQ and SADD scores. There was 59% agreement between the two questionnaires in their placing of scores within three categories of dependence severity. The results suggest a degree of caution in equating current estimates of minimal, mild to moderate and severe dependence on the SADQ with low, medium and high dependence, respectively, on the SADD. Some difficulties experienced by subjects in completing the two questionnaires are discussed.

Adult↗
PubMed1989

Construction of a physiologically active photoaffinity probe based on the structure of bradykinin: labelling of angiotensin converting enzyme but not candidate bradykinin receptors on NG108-15 cells.

The peptides bradykinin and kallidin are released in response to noxious stimuli and mediate various physiological effects, including a direct stimulation of nociceptive afferent neurones. The nature of the receptor molecules through which these ligands act is presently unknown. We synthesised an iodinatable photoaffinity probe, N epsilon-4-azidosalicylylkallidin, and used it in an attempt to identify candidate bradykinin receptors on the NG108-15 neuroblastoma X glioma hybrid cell line. The ligand bound in subdued light to a particulate fraction of NG108-15 tumours and could be displaced by bradykinin with an IC50 of 0.33 nM. In a physiological assay, it behaved as an agonist equipotent with bradykinin. Gel analysis of the labelled products after photolysis of the iodinated ligand in the presence of NG108-15 cells or tumour membranes revealed bradykinin-blockable labelling of a glycoprotein with an Mr of 166,000. The probe was also able to label purified commercial angiotensin converting enzyme. The band labelled in NG108-15 cells was immunoprecipitable with a polyclonal antiserum to angiotensin converting enzyme, an enzyme shown to be present in low amounts in these preparations by direct binding using the iodinatable specific ligand MK351A.

Affinity Labels↗
PubMed1989

A monoclonal antibody, Py, distinguishes different classes of hippocampal neurons.

A monoclonal antibody, Py, was produced by immunizing mice with a glycoprotein fraction isolated from 3-week-old rat hippocampus. Py antibodies gave strong immunocytochemical staining of the perikarya and dendrites of large neurons in many areas of the rat brain, including the cerebral cortex, hippocampus, cerebellum, brain stem, and olfactory bulb. Immunoelectron microscopy showed the antigen to be predominantly intracellular, although its presence on the neuronal cell surface was not excluded. The antibody gave differential staining of adult hippocampal neurons, large pyramids of field CA3 being strongly immunoreactive, while CA1 pyramids and the dentate granule cells were unstained. Some interneurons were positive in each of the hippocampal fields. In developing hippocampus, the Py antigen appeared by the middle of the first postnatal week, and the adult pattern of staining was achieved by the end of the second week. Immunoblotting showed the antigen to have a relative mobility of 146 kDa with an additional faint band at 166 kDa. Differential Py staining of neurons was seen in dissociated cultures of embryonic hippocampus and in subdissected hippocampal fragments transplanted into adult host brains. This antibody can therefore be used for identification of hippocampal neurons that have been removed from their normal anatomical context.

Animals↗
PubMed1988

The teratogenicity of cadmium-metallothionein in the rat.

A single dose in the range 0.25-1.0 mg metallothionein-bound cadmium (MT-Cd)/kg body weight, when administered parenterally to the rat between day 8 and day 14 of gestation (gd 8-gd 14), is teratogenic. In vitro, the development of the isolated rat conceptus, explanted at 8.5 days of gestation, is unaffected by the addition of 1.5 microM MT-Cd to the culture medium, whereas the same concentration of ionic Cd (as CdCl2) is lethal. The incorporation of appreciable amounts of Cd into the embryo (860 pg), placenta (970 pg) and yolk sac (65.4 ng) without toxic manifestations under the former conditions suggests that the metalloprotein is incorporated pinocytotically, but without degradation, by the conceptus in vitro. It does not follow, therefore, that MT-Cd is without embryo/foetotoxicity in the pregnant rat since, in-vivo, liberation of some of the protein-bound Cd is known to occur in the blood. At short times after injection of 0.25 mg MT-Cd/kg body weight on gd 12, however, the maximal foetal and placental contents of Cd (less than 25 pg and 2 ng, respectively) are low in comparison with those after a teratogenic dose of CdCl2 and are of the same order as those in the embryo (46 pg) and placenta (100 pg) + yolk sac (3.8 ng) of the rat conceptus, cultured in the presence of the highest no-effect concentration of CdCl2 (0.065 microM). From this evidence, therefore, it is concluded that the uptake by the conceptus in vivo of either CdMT, or of Cd liberated therefrom, is unlikely to contribute to the teratogenic response. In the pregnant, as in the non-pregnant rat, the kidney appears to be the only organ that is affected directly by the metalloprotein. All doses in the range 0.25-1.0 mg MT-Cd/kg body weight are nephrotoxic and, because of this, result in prolonged anorexia in the pregnant animal. While some of the foetal deformities that occur in the CdMT-dosed animal seem to be direct consequences of the renal dysfunction, others apparently are secondary to the maternal anorexia, since they are induced in pregnant, normal rats by appropriate reductions in food intake. In rats that are injected i.p. on gd 12 with 0.25 mg MT-Cd/kg body weight, renal uptake of Cd is slower, but the final concentration is higher than in animals that are given the same dose i.v.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗