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J Thomas

Publications and source records attributed to J Thomas.

At least 307 records · Page 17Linked to original sources
PubMed1996

Impact of social confrontation on rat CD4 T cells bearing different CD45R isoforms.

The impact of social defeat on lymphocyte subpopulations and T helper subsets was investigated in Long Evans rats. CD4 T helper cell subsets with distinct functional properties and different cytokine profiles can be distinguished by using the mAbs OX-22 (anti-CD45RC) and OX-7 (anti-CD90, Thy1.1). Male intruders were exposed for 2, 6, or 48 h to aggressive resident pairs. All intruders were attacked upon introduction and were defeated as indicated by frequent display of full submissive postures. After 2 and 48 h of confrontation, drastic but differential effects on blood leukocyte numbers, CD4 and CD8a cells, and CD4 subsets were evident. However, after 6 h of confrontation most lymphocyte subset numbers corresponded to baseline levels. Focusing on CD4 subsets after 2 h of confrontation, we demonstrated that only the number of the CD45RC-CD90(-) subset declines, whereas neither the number of the CD45RC+CD90(-) subset nor the number of the CD45RC-CD90(+) subset (recent thymic emigrants) was influenced. Con A stimulation of sorted subsets identified the CD45RC-CD90(-) as a poor producer of IFN-gamma. The data clearly demonstrate that social factors might differentially influence not only T cell subsets but also T helper cell subsets with distinct cytokine profiles in a possibly time-dependent manner. Such a stress-induced shift toward a CD45RC+CD90(-)-dominated milieu may have important consequences in interpreting results obtained from mitogenic stimulation of blood lymphocytes and cytokine production profiles measured after such a stimulation. In addition, a shift toward a CD45RC+CD90(-) dominance may modify the type and magnitude of immune response, at least temporarily.

Animals↗
PubMed1996

8-(N,N-diethylamino)octyl 3,4,5-trimethoxybenzoate (TMB-8) acts as a muscarinic receptor antagonist in the epithelial cell line HT29.

8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8) is a widely used pharmacological tool to investigate the involvement of intracellular Ca2+ stores in cellular responses. In this study we investigate the effect of TMB-8 as a putative inhibitor of "Ca2+ signalling" in single fura-2 loaded HT29 colonic epithelial cells stimulated by ATP, carbachol (CCH) and neurotensin (NT). TMB-8 effectively inhibited the CCH-induced (100 mumol/l intracellular Ca2+ ([Ca2+]i) transient with an IC50 of 20 mumol/l. However, [Ca2+]i transients induced by other phospholipase C coupled agonists ATP (10 mumol/l, n = 4) and NT (10 nmol/l, n = 4) remained unaffected by TMB-8 (50 mumol/l). The agonist-induced [Ca2+]i transients remained equally unaffected by 100 mumol/l TMB-8 when the stimulatory concentration was reduced to 0.5 mumol/l for ATP (n = 4) or 1 nmol/l for NT (n = 4). The competitive nature of the TMB-8-induced inhibition of the CCH-induced [Ca2+]i transient was demonstrated by examining the agonist at various concentrations in absence and presence of the antagonist. High TMB-8 concentrations (100 mumol/l) alone induced a small [Ca2+]i increase (delta[Ca2+]i: 40 +/- 5 nmol/l, n = 7). We assume that this increase is a consequence of a TMB-8 induced intracellular alkalinization (delta pH: 0.1 +/- 0.02, n = 7) occurring simultaneously with the increase in [Ca2+]i. From these results we draw the following conclusions: (1) In sharp contrast to a large number of other studies, but in agreement with studies in other types of cells, these results substantially challenge the value of the "tool" TMB-8 as an "intracellular Ca2+ antagonist"; (2) TMB-8 acts a muscarinic receptor antagonist at the M3 receptor; (3) TMB-8 does not influence the release of Ca2+ from intracellular stores when IP3 signal transduction is activated by ATP or NT; (4) TMB-8 as a weak organic base alkalinizes the cytosol at high concentrations; and (5) TMB-8 induces small [Ca2+]i transients at higher concentrations.

Adenosine Triphosphate↗
PubMed1996

The effect of anoxia on cardiomyocyte glucose transport does not involve an adenosine release or a change in energy state.

The action of anoxia on glucose transport was investigated in isolated resting rat cardiomyocytes. Incubation of these cells in the absence of oxygen for 30 min resulted in a 4- to 5-fold increase in glucose transport (with a lag period of 5-10 min). Up to 40 min of anoxia failed to alter the cellular concentrations of ATP, phosphocreatine, and creatine. Adenosine deaminase (1.5 U/ml), the A1-adenosine receptor antagonist 1,3-diethyl-8-phenylxanthine (1 microM), or the A2-selective antagonist 3,7-dimethyl-1-propargylxanthine (20 microM) had no effect on anoxia-dependent glucose transport. Moreover, adenosine (10-300 microM, added under normoxia) did not stimulate glucose transport. Wortmannin (1 microM) did not influence the effect of anoxia, but completely suppressed that of insulin. On the other hand, the effects of anoxia and insulin were not additive. These results indicate (i) that the effect of anoxia on cardiomyocyte glucose transport is not mediated by a change in energy metabolism, nor by an adenosine release; (ii) that it probably does not involve a phosphatidylinositol 3-kinase, in contrast to the effect of insulin, and (iii) that the signal chains triggered by anoxia or insulin may converge downstream of this enzyme, or, alternatively, that anoxic conditions may impair the action of the hormone.

Adenosine↗
PubMed1996

Failure to induce resistance to cytotoxic drugs in normal lymphocytes.

Lymphocytes from patients who had received chemotherapy for lung cancer were examined for evidence of drug resistance using an in vitro assay for sensitivity to the effects of chlorambucil and etoposide. There was no evidence of induced resistance to the effects of chlorambucil or etoposide in the patients' lymphocytes when compared to the sensitivity of the normal control subjects' lymphocytes. In four patients, in whose lymphocytes sensitivity to chlorambucil was measured before and after a course of treatment, there was no significant change in the in vitro drug sensitivity. These findings are in contrast to those made previously using the lymphocytes of patients with chronic lymphocytic leukaemia and indicate that acquired drug resistance is a property of malignant cells and is not inducible in normal lymphocytes.

Antineoplastic Agents↗
PubMed1996

Methicillin-resistant Staphylococcus aureus: investigation of a hospital outbreak using a case-control study.

A retrospective case-control study of 50 MRSA-positive patients was carried out during an outbreak of methicillin-resistant Staphylococcus aureus (MRSA) at an acute general hospital in London. Controls were randomly selected from MRSA-negative patients admitted during the outbreak period. Risk factors investigated included length of admission prior to screening, number of ward changes, main diagnosis, extent of staff contact, pressure sores, surgical and other invasive procedures and antibiotic treatment. Outcome variables examined were rates of infection (versus colonization) with MRSA and mortality. Patients with MRSA were in hospital longer before microbiological specimens were taken and moved wards more often than controls. In a logistic regression analysis, length of stay in hospital, pressure sores, physiotherapy and surgical procedures were associated with a significantly increased risk of acquiring MRSA. Odds ratios (and 95% confidence intervals) for having acquired MRSA were: 8.3 (1.02-71.43) if a patient had pressure sores; 3.7 (1.10-12.5) if they received physiotherapy; and 3.2 (1.82-10.0) if they underwent surgical procedures. The rate of clinical infection amongst patients with this strain of MRSA was 26% and included life-threatening infections such as septicaemia, underlining the potential virulence of MRSA. Surgery and physiotherapy may have been markers of debility. Physiotherapy was probably a marker of increased rates of contact with all hospital staff, and high standards of hand hygiene should be promoted amongst all staff as the most important factor in controlling an outbreak of MRSA. Good bed management is essential for hospital infection control.

Aged↗
PubMed1996

The outlook for pharmacist initiation and modification of drug therapy.

Changing state laws to permit an expanded scope of practice for pharmacists is a key step in positioning pharmacists to provide pharmaceutical care. Sixteen states currently allow pharmacists to initiate and/or modify drug therapy; legislation is proposed in 15 other states. Twenty-eight of the 44 states that completed the survey allow pharmacists neither dependent nor independent authority to prescribe. Physician opposition was often cited as a barrier to passage of legislation. The Indian Health Service and the Department of Veterans Affairs extend pharmacists independent prescribing authority.

Drug Prescriptions↗
PubMed1996

Mapping of a gene for type 2 diabetes associated with an insulin secretion defect by a genome scan in Finnish families.

Non-insulin dependent diabetes mellitus (NIDDM) affects more than 100 million people worldwide and is associated with severe metabolic defects, including peripheral insulin resistance, elevated hepatic glucose production, and inappropriate insulin secretion. Family studies point to a major genetic component, but specific susceptibility genes have not yet been identified-except for rare early-onset forms with monogenic or mitochondrial inheritance. We have screened over 4,000 individuals from a population isolate in western Finland, identified 26 families (comprising 217 individuals) enriched for NIDDM and performed a genome-wide scan using non-parametric linkage analysis. We found no significant evidence for linkage when the families were analysed together, but strong evidence for linkage when families were classified according to mean insulin levels in affecteds (in oral glucose tolerance tests). Specifically, families with the lowest insulin levels showed linkage (P = 2 x 10(-6)) to chromosome 12 near D12S1349. Interestingly, this region contains the gene causing the rare, dominant, early-onset form of diabetes MODY3. Unlike MODY3 families, the Finnish families with low insulin have an age-of-onset typical for NIDDM (mean = 58 years). We infer the existence of a gene NIDDM2 causing NIDDM associated with low insulin secretion, and suggest that NIDDM2 and MODY3 may represent different alleles of the same gene.

Adult↗
PubMed1996

Trisomy 3 in marginal zone B-cell lymphoma: a study based on cytogenetic analysis and fluorescence in situ hybridization.

Trisomy 3 represents the most frequent and consistent chromosomal abnormality characterizing the recently defined entity marginal zone B-cell lymphoma (MZBCL). By cytogenetic analysis and/or fluorescence in situ hybridization (FISH) on interphase nuclei we found in increased copy number of chromosome 3 in 22/36 (61%) successfully analysed cases, including 8/12 cases with extranodal MZBCL, 8/13 cases with nodal MZBCL, and 6/11 patients with splenic MZBCL. Sensitivity of interphase cytogenetics was somewhat higher than that of conventional cytogenetic investigation. Structural chromosomal changes involving at least one chromosome 3 were seen in 11/20 cases with an increased copy number of chromosome 3: +de(3)(p13) was demonstrated in three cases, and was the sole chromosomal abnormality in one of them; +i(3)(q10) was seen in two other patients; and rearrangements involving various breakpoints on the long arm of chromosome 3 were found in the remaining cases. FISH on metaphase spreads confirmed these structural abnormalities and additionally showed two unexpected translocations involving chromosome 3. We conclude that: (1) trisomy 3 occurs in a high proportion of extranodal, nodal and splenic MZBCL; (2) FISH on interphase nuclei is an additional and sensitive tool in detecting an increased copy number of chromosome 3 in MZBCL; (3) additional structural abnormalities involving the long arm of chromosome 3 are frequent but non-recurrent and are perhaps secondary changes; and (4) abnormalities such as +del(3)(pl3) and +i(3)(q10) suggest that genes located on the long arm of chromosome 3 are of particular importance in the pathogenesis of MZBCL.

Adult↗
PubMed1996

Bacteraemia with Leptotrichia buccalis: report of a case and review of the literature.

We report here on a new case of L. buccalis bacteraemia. To our knowledge 16 other cases of L. buccalis bacteraemia have been reported in the literature, most of them in neutropenic patients. However L buccalis endocarditis does occasionally occur in non-neutropenic patients. The identification of L. buccalis is based on well known phenotypic features and confirmed by the detection of a large peak of lactic acid by gas chromatography for non volatile organic acids. L. buccalis is sensitive to a wide range of antibiotics including beta-lactam antibiotics, but it is resistant to aminoglycosides and macrolides.

Aged↗
PubMed1996

Macrozamia toxicosis in a dog.

A case of Macrozamia riedlei seed poisoning is described in a young Dachshund. Vomiting and depression commenced within 6 h of ingestion; other signs that developed included severe hepatopathy, jaundice, abdominal pain that was unresponsive to analgesics, severe gastro-intestinal haemorrhage and thrombocytopenia as well as crystalluria and marrow dyserythropoiesis. The dog was euthanased 6 days after ingestion of the seeds.

Animals↗
PubMed1996

Viral replication is required for induction of ocular immunopathology by herpes simplex virus.

Corneal infection of BALB/c mice with herpes simplex virus type 1 results in a chronic inflammatory response in the stroma termed herpetic stromal keratitis (HSK). This disease is considered to be immunopathological and mediated primarily by CD4+ T cells of the type 1 cytokine profile. However, the nature of the antigens, virus or host derived, which drive the inflammatory response remains in doubt. In this study, the relevance of infection with replicating virus for the subsequent development of HSK was evaluated with immunocompetent mice as well as with SCID mice reconstituted with herpes simplex virus-immune CD4+ T cells. In the corneas of immunocompetent mice, infectious virus, viral antigen, and mRNA expression were detectable for only a brief period of time (< or = 7 days postinfection), and all were undetectable by the time clinical lesions were evident (10 to 15 days). Viral replication, however, was necessary for the development of HSK in both models, since infection with UV-inactivated virus or with mutant viruses which were incapable of multiple rounds of replication in vivo failed to induce HSK. The inactivated and mutant viral preparations did, however, stimulate T-cell immune responses in immunocompetent mice. The results are discussed in terms of possible involvement of host antigens exposed in response to transient progeny virion replication in the immune-privileged cornea.

Animals↗
PubMed1996

Contraction-independent effects of catecholamines on glucose transport in isolated rat cardiomyocytes.

The effects of catecholamines on glucose transport were studied in noncontracting isolated rat cardiomyocytes. alpha-Adrenergic treatment (phenylephrine, or norepinephrine + propranolol) led to an approximately fourfold stimulation of glucose transport in basal cells (no insulin). The effect of phenylephrine was suppressed by the alpha 2-antagonist yohimbine or the beta-antagonist propranolol. The beta-adrenergic agonist isoproterenol partially counteracted the action of phenylephrine (but not that of insulin). Phenylephrine increased glucose transport in two phases with apparent half times of 3.2 and 13.0 min, respectively. Correspondingly, different EC50 values were found after 10 and 45 min on phenylephrine addition (5.0 +/- 1.9 vs. 31.6 +/- 9.6 microM, respectively). Maximal stimulation by phenylephrine was at least partially additive to that of insulin and of other stimulators of glucose transport (e.g., H2O2, vanadate, lithium). Phenylephrine significantly increased the level of cell surface glucose carriers GLUT-1 (1.54-fold) and GLUT-4 (1.78-fold), as assessed by using the specific photolabel 2-N-[4-(1-azi-2,2,2-trifluoroethyl)benzoyl]- 1,3-bis(D-mannos-4-yloxy)propyl-2-amine. In conclusion, catecholamines stimulate cardiomyocyte glucose transport through alpha 1-adrenergic receptors independently or downstream of a contraction-evoked stimulus. This effect is at least partially explained by a recruitment of glucose transporters to the cell surface. The mechanism(s) and/or signals involved differ from those triggered by insulin and insulinomimetic agents.

Adrenergic Agents↗
PubMed1996

Signals mediating stimulation of cardiomyocyte glucose transport by the alpha-adrenergic agonist phenylephrine.

Phenylephrine, a potent stimulator of cardiomyocyte glucose transport (GT), caused a rapid rise in cytosolic Ca2+ by 30%. Agents inducing a similar Ca2+ response did not stimulate (angiotension II, vasopressin) or inhibited GT by 20% (elevated extracellular Ca2+). Stimulation of GT by phorbol myristate acetate was additive to both phases of phenylephrine's effect (4 min, 60 min). Phenylephrine had no influence on the adenosine 3', 5'-cyclic monophosphate (cAMP) and guanosine 3',5'-cyclic monophosphate (cGMP) levels. Agents raising cAMP (isoproterenol) or cGMP (e.g., nitroprusside) did not stimulate GT. Wortmannin (inhibitor of 1-phosphatidylinositol 3-kinase) suppressed the action of insulin on GT but not that of phenylephrine. In contrast, the Na+/H+ exchange inhibitor amiloride (which blocks phenylephrine-induced cytosolic alkalinization or even lowers cellular pH) depressed the effect of phenylephrine by 50%, whereas insulin-stimulated GT was little affected. However, raising extracellular pH up to 8.4 failed to increase GT. Lowering pH to 6.8 decreased phenylephrine's effect by 40% whereas insulin-dependent GT was not significantly altered. Clorgyline, tranylcypromine (monoamine oxidase inhibitors), and added catalase suppressed the slow phase of phenylephrine's action, whereas amiloride also affected the fast phase. We conclude that 1) stimulation of cardiomyocyte GT by phenylephrine does not involve cAMP, cGMP, or 1-phosphatidylinositol 3-kinase; 2) protein kinase C activation cannot explain the full extent of stimulation; 3) Ca2+ release or cytosolic alkalinization may be required but is not sufficient to trigger phenylephrine's action, and 4) the slow phase of stimulation is mediated by the monoamine oxidase-dependent degradation of phenylephrine and by the resulting H2O2 formation.

Adrenergic alpha-Agonists↗
PubMed1996

Community nurses and health promotion: ethical and political perspectives.

This paper brings together ideas from two perspectives on ethics and health promotion. A discussion of the ethical dimension of the health promotion practice of community nurses is set in the wider context of health policy, with particular reference to health gain and individual responsibility. It is widely held that nurses have a key role to play in health promotion and that this is particularly the case for nurses working in primary health care. This assumption is reinforced by policy documents from the World Health Organization, the Department of Health and statutory bodies such as the United Kingdom Central Council for Nursing, Midwifery and Health Visiting. The approach of many nurses to health promotion has tended on the one hand to be somewhat naive and on the other to be authoritarian and didactic; there has been little discussion in the nursing literature of the ethical aspects of health promotion. However, recent developments in nurse education, such as Project 2000 and the consequent changes to preregistration programmes, have resulted in increased attention to both ethics and health promotion within the curriculum.

Community Health Nursing↗
PubMed1996

Development of a scale to measure directive guidance by pharmacists.

OBJECTIVE: To develop and test a questionnaire that can be used to measure directive guidance behaviors by pharmacists. QUESTIONNAIRE DESIGN: The Purdue Pharmacist Directive Guidance (PPDG) scale was developed based on the directive guidance dimension of socially supportive behaviors, as described by Barrera and Ainlay. The final scale consists of 10 items. SUBJECTS: Individuals on the Walker Test Crew database who were 18 years of age or older and self-reported taking medications for asthma, hypertension, and/or diabetes in the past 3 months were eligible for inclusion. All data were collected through telephone interviews. A total of 464 contacts were made, resulting in 300 responses. DATA ANALYSIS: Principal components analysis was performed to determine the construct subscales of the PPDG. Internal consistency of the PPDG and its subscales was assessed using Cronbach's alpha and corrected item-total correlations. Pearson product-moment correlations of the PPDG with measures of family and friend support (FFS) and self-reported medication adherence were used to determine convergent validity. Spearman rank-order correlations of the PPDG with the total number of prescription medications as well as those for asthma, hypertension, and diabetes taken in the past 3 months were obtained. ANOVA and Student's t-tests were used to determine differences in PPDG across demographic characteristics. RESULTS: Principal components analysis yielded two subscales for the PPDG. These were named Instruction and Feedback and Goal Setting, based on their content. The PPDG scale had good internal consistency (Cronbach's alpha = 0.86), and correlated positively and significantly with FFS (r = 0.27), giving some evidence of convergent validity. The PPDG scale and its subscales also had logically intuitive positive and significant correlations with the total number of prescription drugs taken in the past 3 months. CONCLUSIONS: The PPDG is short and easy to administer, and showed validity and reliability. The PPDG scale should be useful in developing a better understanding of the process by which pharmacists influence healthcare outcomes, assessing variations in pharmaceutical care, and as a tool in identifying means of overcoming barriers to higher levels of pharmaceutical care.

Adult↗
PubMed1996

Pressure-relieving supports in an ICU.

Intensive care wards have a high incidence of pressure sores. This trial, in an eight-bed unit, aimed to compare the cost-effectiveness of constant-low-pressure and alternating-pressure support systems for preventing pressure sores. Patients without sores with a Norton risk score of < 13 were allocated to either alternating- or constant-low-pressure supports according to their hospital number. The cheapest supports were used initially, and changed for more sophisticated types if the patient's pressure areas deteriorated. None of the 23 patients using low-cost alternating-pressure supports developed open sores and only one had to be transferred to a more sophisticated mattress because of persistent erythema. Eleven out of 20 patients on constant-low-pressure mattresses or overlays developed either persistent erythema (three) or sores (eight). Ten were transferred to more expensive support systems. The mean cost of supports per patient in the alternating-pressure group was 44.50 pounds and in the constant-low-pressure group 86.20 pounds.

Adult↗