Search PubMed⌕ Search

Biomedical subjects

P Collins

Publications and source records attributed to P Collins.

At least 271 records · Page 15Linked to original sources
PubMed1990

Pathophysiology of angina.

The development and pathophysiology of myocardial ischaemia is a dynamic process in which increased myocardial oxygen demand or decreased coronary blood flow are not the sole determinants. Both these factors are inappropriately altered before, during, or after the onset of ischaemia, and a vicious cycle ensues. Drug therapy should be aimed at not only preventing the development of myocardial ischaemia but also at reversing the abnormal hormonal, metabolic, and haemodynamic effects.

Angina Pectoris↗
PubMed1990

Cellular cholesterol regulation--a defect in the type 2 (non-insulin-dependent) diabetic patient in poor metabolic control.

This study investigates the relationship between Type 2 (non-insulin-dependent) diabetes mellitus and hypercholesterolaemia with regard to delivery of cholesterol to cells and regulation of endogenous cholesterol synthesis. The ability of LDL, from hypercholesterolaemic and Type 2 diabetic patients, to suppress cellular cholesterologenesis and to enhance mitogen-stimulated lymphocyte proliferation was compared. Cholesterol synthesis was estimated by measuring [14C]-acetate incorporation into cholesterol and lymphocyte proliferation was assessed by [3H]-thymidine incorporation into mitogen-stimulated normal lymphocytes. The results indicate that LDL from both Type 2 diabetic patients in poor metabolic control and hypercholesterolaemic patients was significantly less effective (p less than 0.001) than LDL from non-diabetic normocholesterolaemic subjects in suppressing cholesterol synthesis in lymphocytes. LDL from all hypercholesterolaemic patients enhanced lymphocyte proliferation to a greater extent than LDL from normocholesterolaemic subjects and this effect was significantly increased using LDL from Type 2 diabetic, hypercholesterolaemic patients. Both suppression of [14C]-acetate incorporation and enhancement of [3H]-thymidine uptake could be related to an increased esterified/free cholesterol ratio in the LDL particle. The fact that cholesterol synthesis and cell proliferation were markedly altered by the above changes in LDL composition suggests a mechanism for cellular cholesterol accumulation in the Type 2 diabetic patient, even in the absence of elevated serum cholesterol levels.

Apolipoproteins B↗
PubMed1990

Repair of the ependyma in hydrocephalic brains.

Hydrocephalus was induced in 12-day-old rats by the cisternal infusion of concentrated kaolin suspension. At 19 days of age, a lesion, 100 or 150 microns in diameter, was made in the ependymal lining of the lateral ventricles. Animals were killed at intervals from 1 h to 20 days after the lesion was made. The damaged area was examined by scanning electron microscopy, light and transmission electron microscopy. Between 1 h and 48 h the hole was still open. Small round cells, identified as free subependymal cells, were associated with the edges of the hole from 1 h after the lesion was made. From 48 h, the lesion was completely covered with cell bodies and their processes and no hole was present. Signs of differentiation were seen in the free subependymal cells from 4 days, the cells becoming more electron lucent. By 15 days, three types of cell arrangement were seen within the damaged area: 1 clusters of small cells, with few processes, resembling subependymal cells; 2 small numbers of cells with flat cytoplasmic processes which formed the lining of the ventricular wall; 3 clusters of cells with long thin processes attached to the surface of the ventricular wall but not forming the ependymal lining. The results of this study suggest that, in the hydrocephalic brain, ependymal damage and the repair of a defect within the ventricular wall is initiated by subependymal cells.

Animals↗
PubMed1990

The antibody repertoire of early human B cells. I. High frequency of autoreactivity and polyreactivity.

Cord blood and fetal liver B cells were immortalized using Epstein-Barr virus, and IgM antibodies from the resulting lines and clones were examined for their binding to a variety of auto-antigens and micro-organisms by ELISA and fluorescence assays. Auto-antigens tested included Fc of IgG, ssDNA and dsDNA, cardiolipin, histones 1-4, collagens type I and II, thyroglobulin, cytoskeletal components, and a tissue section screen. Of 71 cell lines tested, all but 19 showed some autoreactivity. All 32 fetal liver lines reacted to some self-antigens. In cord blood clones, 16 out of 26 bound to auto-antigens. Many of the clones reacted with more than one auto-antigen and were 'polyreactive'. Some of the cord blood clones bound to extracts of micro-organisms, showing specificity for both endogenous and exogenous antigens. The high frequency of CD5+ B cells in the cord blood (greater than 50%) and fetal liver (greater than 70%) argues for many of these clones being derived from this subset. Therefore, our data support the concept that many 'early' B cells produce polyreactive IgM which can bind to a variety of different auto-antigens and micro-organisms. These IgM antibodies are similar to those described by others as 'natural antibodies'.

Antibody Specificity↗
PubMed1990

Investigation of the effects of progesterone on neuropeptide Y-stimulated luteinizing hormone-releasing hormone secretion from the median eminence of ovariectomized and estrogen-treated rats.

We have investigated the hypothesis that administration of progesterone to estrogen-treated ovariectomized (OVX) rats enhances the stimulatory effects of neuropeptide Y (NPY) on the secretion of luteinizing hormone-releasing hormone (LHRH) from median eminence (ME) fragments in vitro. Adult rats were bilaterally OVX and after 2-4 weeks various doses of estrogen were administered subcutaneously in Silastic capsules. Three days later animals were injected subcutaneously with progesterone (1, 2 or 19 mg) or oil vehicle. Three hours later animals were killed, trunk blood collected, and the ME dissected and rinsed in culture medium. Incubation medium was collected after 30 min (control) and synthetic porcine NPY (0.1-10 microM) was applied during the test period. LHRH released into the medium and plasma luteinizing hormone were measured with RIA. NPY significantly stimulated LHRH secretion from MEs obtained from estrogen-treated OVX rats injected with oil vehicle. This stimulation was directly dependent on the degree of estrogen replacement. Administration of physiological doses of progesterone had no effect on NPY-stimulated LHRH release at low physiological levels of estrogen replacement. However, injection of 1 or 2 mg of progesterone into animals receiving the high physiological dose of estrogen slightly, although not significantly, reduced NPY (10 microM)-stimulated LHRH secretion. Treatment with the pharmacological dose of progesterone (19 mg) significantly decreased the ability of NPY to stimulate LHRH release when compared to vehicle-injected controls or to animals receiving 1 mg of progesterone. These results do not support the hypothesis that progesterone enhances NPY-stimulated LHRH secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Leukotriene A4 hydrolase: analysis of some human tissues by radioimmunoassay.

Leukotriene A4 hydrolase was quantitated by radioimmunoassay, in extracts from eight human tissues. The enzyme was detectable in all tissues, with the highest level (2.6 mg per g soluble protein) in leukocytes, followed by lung and liver. The polyclonal antiserum did not cross-react with cytosolic epoxide hydrolase purified from mouse or human liver. When incubated with leukotriene A4, formation of leukotriene B4 was evident in all tissues. Furthermore, enzymatic formation of (5S,6R)-dihydroxy-7,9-trans-11,14-cis-eicosatetraenoic acid from leukotriene A4, was found in extracts from liver, kidney and intestines.

Blotting, Western↗
PubMed1989

Effect of nerve growth factor and thyrotropin releasing hormone on cholinergic neurones in developing rat brain reaggregate cultures lesioned with ethylcholine mustard aziridinium.

Foetal rat whole brain reaggregate cultures were prepared in a serum-supplemented (S+) or serum-free medium (S-). Ethylcholine mustard aziridinium (ECMA) was added to the cultures at 9 days in vitro (DIV) at concentrations of 12.5, 25 or 50 microM. Choline acetyltransferase (ChAT) activity was measured at +2, +48 and +96 hr following treatment. In certain experiments the neurotrophic factors, thyrotropin releasing hormone (TRH: 50 micrograms/ml, daily from 9 DIV) or nerve growth factor (NGF: 7S subunit, 5 ng/ml, 0 and +48 hr following ECMA) were added during ECMA treatment. In both types of reaggregate cultured in S+ and S- media there was a 40-80% loss of ChAT activity following ECMA exposure (final concentration = 12.5 microM), presumed to reflect cholinergic cell loss. In both S+ and S- brain reaggregates NGF produced increased ChAT activity with more marked effects in S+ (45-55% increase, +48-96 hr) than in S- medium (20-25% increase, 2-96 hr). No effect on cholinergic muscarinic receptors (specific 3H-QNB binding) was evident after treatment with NGF. TRH had no effect on ChAT activity in the S+ cultures but produced small increases in the S- culture condition (approx 20%, +2-48 hr). Despite a residual "ECMA-resistant" pool of ChAT in the cultures, neither neurotrophic agent was found to cause a reversal of the lesion. In conclusion, the cholinotoxin ECMA appears to produce a cholinergic deficit in both developing S+ and S- reaggregates. This was not reversible by NGF or TRH at the concentrations and under the conditions tested. NGF had marked effects on ChAT activity without affecting muscarinic receptors in untreated developing brain reaggregates cultured in an S+ medium.

Animals↗
PubMed1989

Access of proteinase K to partially translocated nascent polypeptides in intact and detergent-solubilized membranes.

We have used proteinase K as a probe to detect cytoplasmically and luminally exposed segments of nascent polypeptides undergoing transport across mammalian microsomal membranes. A series of translocation intermediates consisting of discrete-sized nascent chains was prepared by including microsomal membranes in cell-free translations of mRNAs lacking termination codons. The truncated mRNAs were derived from preprolactin and the G protein of vesicular stomatitis virus and encoded nascent chains ranging between 64 and 200 amino acid residues long. Partially translocated nascent chains of 100 amino acid residues or less were insensitive to protease digestion from the external surface of the membrane while longer nascent chains were susceptible to digestion by externally added protease. We conclude that the increased protease sensitivity of larger nascent chains is due to the exposure of a segment of the nascent polypeptide on the cytoplasmic face of the membrane. In contrast, low molecular weight nascent chains were remarkably resistant to protease digestion even after detergent solubilization of the membrane. The protease resistant behaviour of detergent solubilized nascent chains could be abolished by release of the polypeptide from the ribosome or by the addition of protein denaturants. We propose that the protease resistance of partially translocated nascent chains can be ascribed to components of the translocation apparatus that remain bound to the nascent chain after detergent solubilization of the membrane.

Biological Transport↗
PubMed1989

Characterization of a DNA polymerase mutant of herpes simplex virus from a severely immunocompromised patient receiving acyclovir.

A series of herpes simplex virus isolates were recovered from a bone marrow transplant patient who received prolonged acyclovir therapy for indolent herpes simplex mouth and throat ulceration. Of 14 isolates received 10 were resistant to acyclovir and partially resistant to phosphonoacetic acid. Biochemical characterization revealed that resistance was due to an alteration in the virus DNA polymerase. DNA sequence analysis of the polymerase gene of a plaque-purified resistant virus isolate revealed a single nucleotide change when compared with the sequence of the gene of a plaque-purified sensitive isolate. This single base change resulted in a predicted amino acid substitution of Gly to Ser at residue number 841, a putative functional region of the polymerase.

Acyclovir↗
PubMed1989

Biological and biochemical characterization of clinical isolates of herpes simplex virus type 2 resistant to acyclovir.

A series of clinical isolates of herpes simplex virus type 2 were taken from a patient with chronic lymphocytic leukemia. Acyclovir (ACV) susceptibility assays revealed that some isolates were resistant to ACV and cross-resistant to ganciclovir but not to phosphonoacetic acid. The nature of the resistance was examined further. A number of cloned variants were generated, and thymidine kinase and DNA polymerase assays were carried out. Variants that were resistant to ACV were found to be thymidine kinase deficient. Evidence for alteration in the DNA polymerase was not found when ACV triphosphate or phosphonoacetic acid was used as the inhibitor. In vivo studies with the plaque-purified viruses showed that ACV resistance was associated with a reduced neurovirulence. In a zosteriform model, virus resistant to ACV was unable to induce secondary spread in the same dermatome, to invade the peripheral nervous system or the central nervous system, or to establish latent infections.

Acyclovir↗
PubMed1989

Relationships between gastric emptying of solid and caloric liquid meals and alcohol absorption.

The effects of three variations in meal composition (a solid and a liquid meal consumed together, a liquid meal consumed alone, and a liquid meal consumed 90 min after a solid meal) on the rates and patterns of solid and liquid gastric emptying were examined in 13 volunteers. By including alcohol (0.5 g/kg body wt) in the liquid meal, the relationship between alcohol absorption and gastric emptying was also assessed. The lag phase and the initial emptying phase of the solid meal were prolonged (P less than 0.001) when the liquid meal was consumed with the solid meal, compared with when the liquid meal was consumed 90 min after the solid meal. In this latter situation, consumption of the liquid meal caused the cessation of emptying of solid food, and this second lag phase was followed by a slower (P less than 0.001) than initial emptying phase. Gastric emptying of the liquid meal was slower (P less than 0.005) when solid food was present and was slowest (P less than 0.05) when liquid was consumed 90 min after the solid meal. Alcohol absorption was fastest (P less than 0.05) when the liquid meal was consumed alone and slower (P less than 0.01) when alcohol was consumed with or after the solid meal. For all three meals there was a close correlation (r greater than or equal to 0.91; P less than 0.001) between alcohol absorption and liquid emptying. We conclude that gastric emptying of liquid may be influenced by solid food and that the rate and pattern of solid emptying may be modified by the presence of liquid.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Neuropeptide-Y stimulation of luteinizing hormone-releasing hormone secretion from the median eminence in vitro by estrogen-dependent and extracellular Ca2+-independent mechanisms.

The roles of estrogen and extracellular calcium (Ca2+) in neuropeptide-Y (NPY)-stimulated LHRH release from median eminence (ME) fragments in vitro were examined. Ovariectomized (OVX) rats received one or several sc implants of Silastic tubes containing estradiol benzoate (235 micrograms/ml sesame oil) or vehicle. Plasma estrogen concentrations were similar to levels during the estrous cycle. These estrogen treatments were equally effective in reducing the elevated plasma levels of LH in vehicle-treated OVX rats. Animals were killed 3 days after implantation, and ME fragments were incubated in medium for 30 min (control), followed by a second 30-min period (test) in medium containing NPY or potassium chloride (K+). Estrogen treatment increased the basal release of LHRH and the ME concentration of LHRH in a dose-related fashion. NPY (0.1-10 microM) increased LHRH secretion in a dose-related manner from ME fragments obtained from estrogen-treated OVX rats, but had no effect on MEs from hormonally untreated OVX rats. Treatment with higher doses of estrogen enhanced the LHRH secretory response of ME fragments to NPY (1-10 microM). K+-stimulated LHRH release from ME fragments from estrogen-treated rats was completely eliminated in Ca2+-free medium containing EGTA. In contrast, LHRH release elicited by NPY (10 microM) was unchanged in Ca2+-free medium in both the absence and presence of cobalt chloride (Co2+). Decreasing the Ca2+ concentration from 2.5 to 0.25 mM reduced K+-stimulated LHRH release 7-fold, while NPY-stimulated LHRH secretion was not affected. These results indicate that NPY stimulation of LHRH release from the ME in vitro is related to prior circulating levels of estrogen, but does not require extracellular Ca2+ in the incubation medium. NPY may enhance LHRH release in an estrogen-dependent manner during the estrous cycle and before the LH surge on proestrous.

Animals↗
PubMed1989

Gastric and oesophageal emptying in obesity.

Gastric and oesophageal emptying were evaluated in 31 obese patients and 31 control subjects. A double-isotope technique was used to measure gastric emptying of a mixed solid/liquid meal, and oesophageal emptying was measured as the time taken for a bolus of the solid meal to enter the stomach. Gastric emptying of the solid (p less than 0.001) and the liquid (p less than 0.02) meal and oesophageal emptying (p less than 0.001) were delayed in the obese patients compared with the control subjects. There were no significant relationships among gastric emptying, oesophageal emptying, and upper gastrointestinal symptoms in the obese patients alone, but in the total group of 62 subjects there were significant correlations between body mass index and both gastric (r = 0.44, p less than 0.01) and oesophageal (r = 0.45, p less than 0.001) emptying. These results indicate that delayed gastric and oesophageal emptying occurs frequently in obesity and that these abnormalities relate to body weight.

Adolescent↗