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Biomedical subjects

J Stewart

Publications and source records attributed to J Stewart.

At least 379 records · Page 21Linked to original sources
PubMed1990

A case of thrombotic thrombocytopenic purpura following allogeneic bone marrow transplantation.

A case of thrombotic thrombocytopenic purpura (TTP) is reported in a 40-year-old man 6 months after allogeneic bone marrow transplantation for multiple myeloma. The features of TTP included microangiopathic haemolytic anaemia, severe thrombocytopenia, fluctuating neurological abnormalities, and progressive renal impairment. Despite treatment with anti-platelet agents, prostacyclin infusion, intensive immunosuppression and prolonged plasma exchange, the patient developed end-stage renal failure and is now on maintenance haemodialysis 18 months after the onset of TTP. Graft-versus-host disease and cytomegalovirus infection could not be implicated as aetiological factors, and cyclosporin medication had ceased 1 week before the clinical onset of his disease. The unusually intensive pre-transplant chemotherapy and radiotherapy protocol used in this patient appear to be most likely cause of the generalized endothelial damage resulting in TTP in this patient.

Adult↗
PubMed1989

The effect of dopamine receptor blockade on the development of sensitization to the locomotor activating effects of amphetamine and morphine.

The effect of dopamine (DA) receptor blockade on the development of sensitization to the locomotor activating effects of systemic amphetamine and intra-ventral tegmental area (intra-VTA) morphine was investigated. Rats were pretreated with the D-1 DA receptor antagonist, SCH-23390 (0.04 or 0.2 mg/kg, i.p.) or one of two D-2 DA receptor antagonists, pimozide (0.5 mg/kg, i.p.) and Ro 22-2586 (0.2 mg/kg, i.p.), prior to each of 5 exposures to the sensitizing drug. SCH-23390 blocked the development of sensitization to amphetamine but not to intra-VTA morphine. Pimozide had the opposite effect and Ro 22-2586 had no effect on the development of sensitization to either amphetamine or intra-VTA morphine. All 3 antagonists, at the doses tested, completely blocked the acute locomotor activating effects of these two drugs. Pretreatment in separate animals with low autoreceptor doses of sulpiride (25 mg/kg, i.p. with amphetamine and 10 mg/kg, i.p. with intra-VTA morphine) slightly potentiated the acute locomotor effect and produced a slight enhancement of the sensitized response to amphetamine and intra-VTA morphine. Pretreatment with a higher dose of sulpiride (50 mg/kg, i.p.) blocked the acute locomotor effect of intra-VTA morphine but had no effect on the development of sensitization to this drug. These results suggest that the mechanisms underlying the development of sensitization to the locomotor activating effects of amphetamine and intra-VTA morphine are different even though these may ultimately result in similar changes in the activity of mesencephalic DA neurons. Implications of these findings for the differential involvement of D-1 and D-2 DA receptors and for neural hypotheses of behavioral sensitization are discussed.

Amphetamine↗
PubMed1989

Microinjections of Sch-23390 into the ventral tegmental area and substantia nigra pars reticulata attenuate the development of sensitization to the locomotor activating effects of systemic amphetamine.

Pre-exposure of rats to systemic injections of D-amphetamine sulfate in the presence of bilateral injections of Sch-23390 (0.5 or 1.0 micrograms/side) into the ventral tegmental area (VTA) attenuated the acute locomotor effects of amphetamine and blocked the development of sensitization to amphetamine in a test when only amphetamine was administered, in a dose-dependent manner. Similar, but less potent, effects were observed following injections into substantia nigra pars reticulata. These findings suggest that dopamine released from somatodendritic regions brings about changes in local circuitry in the VTA that underlie the development of sensitization to amphetamine, and that Sch-23390 acts at D1 receptors in these regions to block these changes.

Animals↗
PubMed1989

Effects of castration, steroid replacement, and sexual experience on mesolimbic dopamine and sexual behaviors in the male rat.

The concentrations of dopamine (DA) and a DA metabolite in a terminal field of the mesolimbic DA system, the nucleus accumbens, decreased after castration, an effect that was prevented by treatment with testosterone (T) or estradiol. After castration, DA concentrations were increased in the medial preoptic area, and were unchanged in the caudate-putamen, substantia nigra, and ventral tegmental area. Changes in DA and DA metabolite concentrations in the nucleus accumbens coincided with changes in measures of sexual arousal. Sexual experience did not affect DA concentrations, but did increase DA metabolism in the nucleus accumbens, and also increased the frequency of female-directed behavior in castrated males. These results suggest that T, or its aromatized metabolite, influences the mesolimbic DA system, and that this system is involved in mediating sexual arousability.

Animals↗
PubMed1989

Detection, isolation and characterization of staphylococcal enterotoxin B in protein A preparations purified by immunoglobulin G affinity chromatography.

Studies were performed to detect and isolate trace contaminants of staphylococcal enterotoxin B (SEB) in various protein A preparations isolated by affinity chromatography employing human IgG covalently bound to Sepharose 4B. Utilizing an ELISA technique, trace amounts (0.018-0.138%) of SEB could be detected in protein A preparations after separation of the SEB employing a molecular sizing column in a high pressure liquid chromatography (HPLC) system. Trace contamination by SEB could be removed from protein A preparations by an additional DEAE ion exchange chromatography step employing a low ionic strength buffer system (0.005 M NaCl in 0.01 phosphate buffer, pH 7.50). The resulting protein A preparations possessed a purity higher than that observed prior to the final purification step. Polyacrylamide gel electrophoresis (PAGE) analyses of the trace contamination removed from protein A preparations by ion exchange chromatography revealed, in addition to SEB, several additional contaminating polypeptides of an unknown nature. These studies indicate that protein A preparations of high purity can be prepared by employing DEAE ion exchange chromatography in addition to affinity chromatography utilizing immobilized human IgG.

Chromatography, Affinity↗
PubMed1989

Cholesterol and prostaglandin synthesis by cultured human skin fibroblasts in the Alagille syndrome involving paucity of interlobular bile ducts.

Children with Alagille syndrome show high serum cholesterol (15-20 mmol/L). To establish correlation of this unusual level of cholesterol with the regulation of cholesterol metabolism, 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) activity and synthesis of cholesterol, fatty acids and acidic steroids from [14C]acetate were determined in cultured skin fibroblasts from 2-3 year old children. Prostaglandin E2 (PGE2) synthesis and nucleic acid synthesis were determined in cells when they were growing in medium containing normal, Alagille or fetal bovine serum. These values were similar to values of controls. HMGR activity was found to be similar in cells of control and children with the syndrome, whether the cells were incubated in lipoprotein-deficient or normal medium. Incorporation of acetate into cholesterol was inhibited to a greater extent by lipoprotein-containing medium in control than in children with the syndrome. Fatty acid synthesis was similar in all conditions. 1-7% of the recovered lipid radioactivity in cells and medium separated as acidic steroids. Serum from a donor patient, when included in the medium, did not affect PGE2 or nucleic acid synthesis compared with normal human or fetal bovine serum. The data suggest that cells of children with Alagille syndrome may have a membrane defect of transfer of cholesterol (LDL receptor defect) leading to excessive cholesterol synthesis. Also, synthesis of acidic steroids (bile acid-like material) and their secretion into the medium occurs in normal fibroblasts and those from children with the syndrome.

Acetates↗
PubMed1989

Environment-specific cross-sensitization between the locomotor activating effects of morphine and amphetamine.

Groups of eight rats each were preexposed on four occasions to 10 or 20 mg/kg morphine sulfate, IP, either in activity boxes where activity was measured for two hours (COND, conditioning groups) or in their home cages (UNPAIRED groups). On alternate days these groups were administered saline in the other environment. Two groups of eight rats each served as CONTROL groups (one for each preexposure dose) and were administered saline in both environments. On the day following morphine preexposure, all animals were administered 0.5 mg/kg d-amphetamine sulfate, IP, prior to being tested in the activity boxes. On this test, the COND group preexposed to 10 mg/kg morphine showed higher levels of activity than either of its respective UNPAIRED or CONTROL groups. The COND group preexposed to 20 mg/kg morphine was significantly more active than its unpaired group, but not more active than its CONTROL group. The implications of such environment-specific cross-sensitization between the activity effects of opiate and stimulant drugs are discussed.

Amphetamine↗
PubMed1989

Determination of opiates and other basic drugs by high-performance liquid chromatography with electrochemical detection.

A procedure is described for the extraction and determination of morphine (M), hydromorphone (HM), codeine (C) and metoclopramide (MCP) present in human plasma. The drugs are separated by reversed-phase liquid chromatography and detected amperometrically at a glassy carbon electrode. The method provides high sensitivity and selectivity and has been used successfully in bioavailability studies.

Biological Availability↗
PubMed1989

The relationship between connectivity and tolerance as revealed by computer simulation of the immune network: some lessons for an understanding of autoimmunity.

According to a classical, antigen-driven view of the immune system, autoimmunity is due to the presence of self-reactive lymphocyte clones which have not been eliminated. However, computer simulations of the immune network show that the greater the degree of connectivity of a clone, the greater its degree of tolerance to chronic antigenic stimulation. This tolerance does not correspond to an absence of response on the part of the system as a whole. On the contrary, stimulation by a 'tolerogenic antigen' results in widespread modification and overall activation of the whole network. This suggests that on an autopoietic network view of the immune system, autoimmunity arises not because of the presence of self-reactive clones, which is completely normal, but because such clones are inadequately connected to the network. This amounts to a complete reversal in perspective, whose significance for the clinical treatment of autoimmunity and the future of immunology is discussed.

Animals↗
PubMed1989

The diets of pregnant and post-pregnant women in different social groups in London and Edinburgh: calcium, iron, retinol, ascorbic acid and folic acid.

Dietary records were obtained twice in pregnancy and once post-partum, from 265 women in all social classes in London and Edinburgh. Some Edinburgh women, and lactating women, showed the higher levels of calcium intake. For iron, retinol, ascorbic acid and folic acid, there was a consistent and significant regional and social class gradient in intakes. This favoured English women in 'non-manual' social groups, leaving the Scottish 'manual' class, after pregnancy, with the lowest intakes. Mean intakes of Ca and Fe were consistently below the current UK recommended daily amount (RDA). Intakes of retinol were all above it, and ascorbic acid intakes ranged above and below the RDA.

Ascorbic Acid↗
PubMed1989

The response of New Zealand boys to corporate and sponsorship alcohol advertising on television.

A survey of a random sample of 302 New Zealand boys aged 9-14 years investigated responses to two recent television advertisements featuring alcohol companies. Alcohol product advertising is not allowed on New Zealand television but a corporate advertisement which was allowed was perceived by most of the children to be advertising beer and to be encouraging drinking. A corporate sports sponsorship advertisement had lower association with alcohol, which may have been because of children's limited understanding of the concept of sponsorship. Most of the children remembered both advertisements and many expected their peers to take notice of them. There was strong support for both advertisements being broadcast on television. Overall, the survey suggested that this television advertising was creating strong positive associations between the companies' products and significant cultural and emotional elements, thus contributing to a climate that was not supportive of alcohol education.

Adolescent↗
PubMed1989

Blood group, secretor status and susceptibility to bacterial meningitis.

Epidemiological evidence is summarized for associations of ABO blood group and secretor status with susceptibility to invasive disease due to capsulate organisms responsible for the majority of bacterial meningitis. Host-parasite interactions that might underly these findings are proposed and evidence to support or refute them provided.

Bacterial Infections↗
PubMed1989

Exploring the meaning of connectivity in the immune network.

It is suggested that the immune network possesses a distinct internal structure, such that B-lymphocyte clones fall into four categories: 1) A multi-affinity or "sticker" group A, containing all the immunoglobulins with auto-affinity, and generally having affinity for nearly all the other immunoglobulins; 2) and 3) Two "mirror" groups B and C, characterized by the fact that there is virtually no within-group affinity; the affinities between B and C can be arranged co-linearly so that a clone from group B has affinity with its opposite number(s) in group C; 4) A fourth group of low affinity, each clone having affinity only with clones from group A. Computer simulations show that this way of analyzing the connectivity of the network makes sense (a) in relation to the stereochemical origins of affinity; and (b) in relation to the dynamical behavior of the clones in a functioning network.

Animals↗
PubMed1989

Infants with apparent life threatening events. Cardiac rhythm and conduction.

The role of cardiac dysrhythmias in the pathogenesis of Sudden Infant Death Syndrome (SIDS) is uncertain, but there have been several reports of infants with Apparent Life Threatening Events (ALTE) due to significant dysrhythmias. To further characterize the cardiac rhythm and conduction of these "at-risk for SIDS" infants, we performed 24-hour continuous (Holter) electrocardiograms on 100 full term, healthy infants with ALTE. Sixty-two patients (62%) had one or more dysrhythmias on Holter monitor. Twenty-five patients (25%) had premature ventricular depolarizations (PVD), including five with couplets. Thirty (30%) had QTc greater than 2 SD above the mean, and, of these, 40 percent had PVD's. Fifteen (15%) had premature atrial depolarizations and 39 (39%) had evidence of moderate or marked sinus node irregularity. There was no prexcitation, supraventricular tachycardia, ventricular tachycardia, or atrioventricular block. Two patients with marked sinus node dysfunction were treated with propantheline and did well. All patients were monitored at home, with no deaths or clinically significant dysrhythmias on follow-up (1-32 months (mean = 18]. In summary, when Holter monitoring was performed, a high incidence of dysrhythmia was found in infants with ALTE. Most dysrhythmias were clinically insignificant. The incidence of ventricular dysrhythmias and long QTc are consistent with previously advanced theories of cardiac electrical instability in some of these patients, but no patient with ventricular dysrhythmias required therapy. The incidence of sinus node dysfunction requiring therapy was 2 percent. Although Holter monitoring of infants with ALTE only infrequently determines therapy, it may provide data linking theories of cardiac etiology of SIDS with actual clinical events.

Arrhythmia, Sinus↗
PubMed1989

Cytotoxicity of gelonin conjugated to targeting molecules: effects of weak amines, monensin, adenovirus, and adenoviral capsid proteins penton, hexon, and fiber.

It has been reported previously that ammonium chloride, chloroquine, monensin, and adenovirus-2 potentiate the cytotoxicity of several protein toxins conjugated with various targeting molecules. We have tested whether these agents, and protein components of adenovirus-2, would enhance the cytotoxicity of conjugates of gelonin with J5, an antibody directed against common acute lymphoblastic leukemia-associated antigen, with 5E9, an antibody directed against human transferrin receptor, or with ricin B-chain. We found that none of these agents affected the cytotoxicity of gelonin conjugates to any significant extent. For example, monensin moderately (3-fold) enhanced the cytotoxicity of 5E9-gelonin for Namalwa cells but showed no effect when 5E9-gelonin was tested on HeLa cells. The potentiating effects of these agents for the cytotoxicity of free gelonin varied from marked to nonexistent, depending on the type of cells. In particular, adenovirus-2 potentiated the cytotoxicity of gelonin for HeLa cells but not for Namalwa cells. The three major adenoviral capsid proteins, penton, hexon, and fiber, were isolated. It was shown that penton potentiated the cytotoxicity of gelonin for HeLa cells and that hexon and fiber had no measurable effect on the cytotoxicity of gelonin. However, like the whole virus, penton was not able to affect the cytotoxicity of gelonin conjugates.

Adenoviridae↗
PubMed1989

[Recovering from a lag in psychological development after harmful environmental factors have been eliminated].

This paper reports the long term effects of deprived environments and the possibility of recovery from delays in psychological development after removal of perturbing influences. Two groups of children who had suffered from deprivation with either low IQ (76 for G I) or high IQ (112 for G II) towards the age of 7 have been reared in a private permanent foster care (the SOS children's villages) after family rupture. They have been reassessed between 5-10 years during adolescence (IQ, school attainment, behaviour). Results are compared with those of children with identical IQ still leaving in their deprived homes or under care in traditional foster care families. Thanks to the ecological and environmental change recovery is possible particularly from cognitive delays; behaviour problems need much more time to decrease or to disappear. Age at placement exerts differential effects according to the developmental processes in action (intelligence, behaviour).

Age Factors↗