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Biomedical subjects

P Andrews

Publications and source records attributed to P Andrews.

At least 91 records · Page 5Linked to original sources
PubMed1989

Inhibition of lymphocyte circulation in mice by pertussis toxin.

Pertussis toxin (PT), a protein toxin of Bordetella pertussis, also called pertussigen, has a wide range of biological activities, including the induction of lymphocytosis. This phenomenon was investigated by studying lymphocyte circulation in mice. Lymph node cell suspensions were exposed to PT in vitro and then injected intravenously. A double radiolabel technique was employed, in which PT-treated and control cells were injected into the same animals. The protocol used in these experiments was chosen to demonstrate a direct effect of PT on the injected cells. After exposure to PT in vitro, cells were profoundly excluded from lymph nodes over the succeeding six days. Entry into both mesenteric and peripheral lymph nodes, but not into the spleen was inhibited by PT, and there was an accumulation of the PT-treated cells in the blood. Cells were excluded from the lymph nodes after treatment with as little as 2 ng/mL of PT. This dose was over two orders of magnitude lower than the threshold dose of the same PT preparation required to induce lymphocyte mitogenesis in vitro. The findings in the present communication are consistent with studies using genetically modified PT in which the ADP-ribosylating capacity of the A-subunit was necessary for the effect of PT on lymphocytosis.

Animals↗
PubMed1988

Genetic and fossil evidence for the origin of modern humans.

The origin of living Homo sapiens has once again been the subject of much debate. Genetic data on present human population relationships and data from the Pleistocene fossil hominid record are used to compare two contrasting models for the origin of modern humans. Both genetics and paleontology support a recent African origin for modern humans rather than a long period of multiregional evolution accompanied by gene flow.

Africa↗
PubMed1988

Morphological alterations of the glomerular (visceral) epithelium in response to pathological and experimental situations.

The glomerular (visceral) layer of Bowman's capsule is comprised of a unique population of cells which have been termed "podocytes." Arising from these cells are large major processes and numerous smaller foot processes which completely surround underlying glomerular capillary loops. Podocyte foot processes interdigitate with each other and are separated by spaces (filtration slits) which are designed to facilitate flow of a large amount of filtrate across the glomerular wall. Podocytes exhibit dramatic morphological changes in response to the nephrotic syndrome and some forms of acute renal failure and may play an important role in the pathophysiology of these conditions. In vitro and in vivo studies have shown that a reduction in the sialic acid component of a thick anionic surface coat plays a major role in the morphological changes that these cells exhibit in the nephrotic syndrome. Also, it has been shown that filamentous actin concentrated mainly within podocyte foot processes are the contractile elements responsible for altering the shapes of these processes. There is evidence to suggest that by altering the shapes of their foot processes, podocytes in the normal kidney are able to alter the number of fully patent filtration slits and thereby actively regulate the rate of solute efflux across the glomerular wall. In vitro and in vivo studies have indicated that cytoplasmic microtubules are probably not involved in alterations of the podocyte foot processes but do appear important in maintaining the morphological integrity of podocyte cell bodies and their major processes. In the present paper, the morphological changes which glomerular podocytes exhibit in response to the nephrotic syndrome, various forms of acute renal failure, and during in vitro incubation are discussed along with studies of the possible roles of cytoplasmic microtubules, microtubules, and the glomerular anionic surface coat in these changes.

Acute Kidney Injury↗
PubMed1988

Influence of praziquantel and Ca2+ on the bilayer-isotropic-hexagonal transition of model membranes.

Praziquantel induces a bilayer to isotropic transition in the absence of Ca2+ in a mixed phospholipid membrane consisting of phosphatidylethanolamine (PE) and phosphatidylserine (PS) at a molar ratio of 2:1 at 25 degrees C or 35 degrees C, irrespective of the lipid/drug molar ratio (10:1; 2:1). Addition of Ca2+ at different PS/Ca2+ molar ratios (4:1, 2:1 or 1:1) leads to a transition to a hexagonal (HII) state. With a phospholipid membrane of different composition (PE/PS molar ratio 4:1) praziquantel exerts quite different effects in the presence of Ca2+ (PS/Ca2+ molar ratio 1:1). An isotropic-signal appears together with a bilayer one at 25 degrees C, while a HII-signal can be detected at 35 degrees C. Thus, two separate phases coexist at this PE/PS molar ratio, while at a PE/PS molar ratio of 2:1, praziquantel and Ca2+ induce only a HII-signal. The results with these model membranes show that praziquantel and Ca2+ exert drastic influences on bilayer-isotropic-hexagonal transitions. The possibility that this drug might act in the schistosomal tegumental membranes in the same way is discussed.

Animals↗
PubMed1987

Praziquantel impairs the ability of exogenous serotonin to stimulate carbohydrate metabolism in intact Schistosoma mansoni.

Praziquantel (PZQ) (Droncit, Biltricide) at 10 microM completely abolishes the stimulatory effect of serotonin on glucose uptake and lactate excretion of Schistosoma mansoni. Fluoxetine (FXT) exerts similar effects on the serotonin-induced stimulation of glucose uptake and lactate excretion, however, at 100-fold higher concentrations. In comparison with PZQ, which is inhibitory at 10 microM, FXT and other amphiphilic cationic drugs (amitriptyline, propranolol, imipramine, chlorpromazine) inhibit glucose uptake or lactate excretion in schistosomes at 1 mM; the strongest inhibitor is FXT. Glycogen breakdown is maximally stimulated by PZQ in the absence or presence of serotonin. There is an additive effect of 50 microM chlorpromazine or FXT and 0.01 to 0.1 microM PZQ on glycogen breakdown. The rate of sodium-sensitive or insensitive serotonin uptake in Schistosoma mansoni is reduced by 10 microM PZQ by about 40%, as is the sodium-sensitive excretion of serotonin. The results show that PZQ interferes with the ability of serotonin to stimulate carbohydrate metabolism. The possibility that PZQ may act through an effect on tegumental integrity is discussed.

Animals↗
PubMed1987

Chlorpromazine, other amphiphilic cationic drugs and praziquantel: effects on carbohydrate metabolism of Schistosoma mansoni.

The effects of the amphiphilic cationic drugs chlorpromazine, imipramine, amitriptyline, propranolol and fluoxetine and praziquantel were investigated on glucose uptake and lactate excretion of Schistosoma mansoni. While praziquantel enhances glucose uptake and lactate excretion at a concentration of 10(-7) M, all the other drugs exert the same effects at concentrations above 10(-5) M. Generally, a constant molar ratio of 1:2 is found between glucose uptake and lactate excretion. Above 10(-5) M, praziquantel inhibits glucose uptake and lactate excretion. Similar effects are caused by amphiphilic cationic drugs at 10(-3) M. Pre-incubation of S. mansoni with 10(-5) M praziquantel completely abolish the stimulation of carbohydrate metabolism by serotonin and by 5 X 10(-5) M chlorpromazine or fluoxetine. The action of praziquantel on S. mansoni resembles that of amphiphilic cationic drugs with respect to their influence on carbohydrate metabolism. This, together with data obtained from electrophysiological and electron microscopic studies, provides evidence for the hypothesis that praziquantel exerts its effect by interacting with membrane structures.

Amitriptyline↗
PubMed1987

Conformation-activity relationships of opiate analgesics.

Extensive conformational calculations were performed on the potent opiate analgesics etorphine, PET, R30490 and etonitazene to determine all of their many low-energy conformations. The results were used to characterize four possible models for binding of a simple pharmacophore, comprising two phenyl rings plus a protonated nitrogen, to opiate analgesic receptors. These four models may define the necessary three-dimensional features leading to particular opiate actions. The model favoured for mu receptor activity can accommodate a protonated nitrogen, an aromatic ring (which may be substituted with an electronegative group) and a second lipophilic group. These structural features must be presented in a precise three-dimensional arrangement. It appears likely that a hydrophilic substituent in a certain region of the analgesic pharmacophore may also interact with the receptor as a secondary binding group.

Analgesics, Opioid↗
PubMed1986

Purification of the fructose 1,6-bisphosphate-dependent lactate dehydrogenase from Streptococcus uberis and an investigation of its existence in different forms.

The fructose 1,6-bisphosphate [Fru(1,6)P2]-dependent lactate dehydrogenase in cells of Streptococcus uberis N.C.D.O. 2039 was purified by a procedure that included chromatography on DEAE-cellulose and Blue Sepharose CL-6B in phosphate buffers. The enzyme appeared to interact with Blue Sepharose through NADH-binding sites. The homogeneous enzyme had catalytic properties that were generally similar to those of other Fru(1,6)P2-dependent lactate dehydrogenases, and it had no catalytic activity in the absence of Fru(1,6)P2. Its existence in different forms, depending on conditions, was investigated by ultracentrifugation, analytical gel filtration and activity measurements. It consisted of subunits with Mr 35,900 +/- 500 and, in the presence of adequate concentrations of Fru(1,6)P2, phosphate or NADH, it existed as a tetramer, whereas when these ligands were in lower concentrations or absent, the subunits were in a concentration-dependent association-dissociation equilibrium. Dissociation occurred slowly and inactivated the enzyme, and although added ligands reversed the dissociation, the lost activity was at best only partly restored. An exception occurred when dissociation was caused by a decrease in temperature, in which case the lost activity was fully restored at the original temperature. The tetramer also lost activity at certain ligand concentrations without dissociating. The results together indicated the presence on the enzyme of two classes of binding site for both Fru(1,6)P2 and NADH, and the likelihood that phosphate bound at the same sites as Fru(1,6)P2. Two different ligands together were much more effective at preventing inactivation and dissociation than was expected from their effectiveness when present separately. It was concluded that tetrameric forms of the enzyme rather than the enzyme in association-dissociation equilibrium were involved in the regulation of its activity in vivo.

Amino Acids↗
PubMed1986

Fine structure of adult Litomosoides carinii (Nematoda: Filarioidea).

The fine structure of the body wall and the intestine of male and female Litomosoides carinii was studied in sections through the middle and posterior regions of the worms. In the sublateral cells of the female hypodermis the organelles are arranged in regular layers. The zone with the basal labyrinth is the most prominent layer. The intestinal epithelium of the female worm varies considerably in thickness. The cytoplasm of these cells contains many large droplets. The lateral hypodermal chords of the male worm are very narrow bands. The muscle cells of the male worm are of the circomyarian type, without an afibrillar portion. The intestinal lumen of the male worm is very narrow, and the epithelial cells contain very large droplets. In both sexes the hypodermis contains bacteria. Larger glycogen deposits were absent in the hypodermal chords and in the muscle cells of the midbody regions.

Animals↗
PubMed1986

Histology of adult Litomosoides carinii (Nematoda: Filarioidea).

The histology of male and female Litomosoides carinii was studied in serial sections. The body wall of the female worm consists of a rather thin cuticle, very extended lateral hypodermal chords and small sectors of shallow coelomyarian muscle cells. In the female worm an intestinal lumen is found, which is filled with material throughout the worm's length. Both ovaries are situated close to the posterior end. In both genital tubes all stages of oogenesis and embryogenesis could be observed in approximately equal stages of development in most of the sections. The lateral chords of the male worm are very small, whereas the somatic muscle cells are large and of the circomyarian type. The intestine is a minute tube beside the much thicker testis and vas deferens. Considerable sexual dimorphism could be observed in almost all organs of adult Litomosoides carinii.

Animals↗
PubMed1986

A new approach for detection and assignment of disulfide bonds in peptides.

A new procedure is described for identification of disulfide bonds in peptides by fast atom bombardment mass spectrometry (FABMS). Prolonged bombardment of a disulfide-containing peptide in solution by a high-energy xenon beam results in gradual reduction of the disulfide bond. The reduction is the result of reaction intermediates initially produced by the xenon beam. The method for characterization of interchain disulfide bonds is based on the increase in the relative intensity of the pseudomolecular ions of the reduced peptides with a simultaneous decrease in the relative intensity of the protonated molecular ion of the oxidized peptide. This information allows one to identify peptide fragments covalently linked via intermolecular disulfide bonds. The intrachain disulfide bonds are identified by the increase in the relative intensity of the protonated molecular ion of the reduced peptide, relative to the intensity of the protonated molecular ion of the oxidized peptide. These results indicate that this method can be used to detect disulfide bonds of peptides and provides unambiguous information regarding disulfide bond assignment in peptides. Approximately 1 nmol of sample is required.

Chemical Phenomena↗
PubMed1986

Effects of praziquantel on human intestinal flukes (Fasciolopsis buski and Heterophyes heterophyes).

Human intestinal flukes (Fasciolopsis buski and Heterophyes heterophyes) were treated with praziquantel in vivo or in vitro and then studied by transmission (TEM) and scanning (SEM) electron microscopy. F. buski worms recovered from patients, which had been cured by oral treatment of 1 X 15, 1 X 25 or 1 X 40 mg praziquantel/kg body weight, showed typical contraction and alterations together with vacuolization and bleb formation of their tegument. H. heterophyes worms recovered from an experimentally infected dog were incubated in media containing 1 microgram praziquantel/ml for 5-60 min. Their tegument showed lesions the extent and duration of which increased with exposure time, finally leading to death. The damage observed in vitro was very similar to that found in F. buski recovered from cured patients. The cure rate was very high when using 1 X 15 mg praziquantel/kg.

Animals↗
PubMed1985

Thymus hormones do not induce proliferative ability or cytolytic function in PNA+ cortical thymocytes.

A variety of thymus hormone preparations, as well as drugs known to perturb cell differentiation, were tested for their ability to induce nonfunctional cortical thymocytes to become functional precursor cells. Murine cortical thymocytes, defined as the high peanut agglutinin (PNA) binding or as the low H-2K, major [86%] thymocyte subpopulation, were isolated by fluorescence-activated cell sorting. Their function was assessed in a high cloning efficiency, growth factor saturated, concanavalin A-stimulated limit-dilution culture system, determining the number of precursors of extended clones (PTL-p), or determining with a lectin-mediated tumor-lysis readout the number of precursors of cytolytic clones (CTL-p). The hormone preparations tested were crude or partially purified culture supernatants from thymus "epithelial" monolayers (TES), soluble extracts of thymic nonlymphoid tissue (STF), semipure thymus humoral factor (THF), and the pure peptides thymopoietin 32-36 (TP5) and "facteur thymique sérique" (FTS). These preparations were either added directly to the limit dilution cultures, or were first preincubated with the cells, which were then subjected to limit-dilution culture. In no case did the hormone preparations cause any increase in the level of PTL-p or CTL-p in the PNA+ or low H-2K thymocyte population, even though a conversion of only a few percent to functional cells could have been detected. Two possible explanations are considered. One is that the main function of these materials is to control post-thymic peripheral T cells, rather than to induce intrathymic differentiation. Another is that the typical cortical thymocyte is beyond the stage at which thymocytes can be induced by hormones, a view that is strengthened by the failure of either 5-azacytidine or the phorbol ester 12-O-tetradecanoyl phorbol 13-acetate to activate these cells. In this latter explanation the true intrathymic target of hormone action may be an earlier, and very minor, thymus subpopulation.

Animals↗