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Biomedical subjects

T Bennett

Publications and source records attributed to T Bennett.

At least 19 recordsLinked to original sources
PubMed1997

Regulation of CD28 costimulation in human CD8+ T cells.

Optimal stimulation and prevention of anergy in T cells requires signaling through the CD28 molecule. During HIV disease progression, CD28 expression is lost, particularly on CD8+ T cells. Because alterations in cytokine production patterns occur during HIV infection, we determined whether CD8+ T cell phenotype or function was affected by cytokine environment. Treatment of CD8+ T cells with IL-4 decreased levels of both CD28 surface expression and message and increased CD8 expression. Furthermore, CD8+ T cells that had down-regulated CD28 had reduced proliferative capacity. The inhibitory effects of CD28 reduction could be compensated either by increased anti-CD3 or by exogenous IL-2, suggesting that the strength of T cell signaling necessary for the production of IL-2 and subsequent proliferation is negatively regulated by IL-4. CD8+ subpopulations with differential CD28 expression produced different patterns of cytokines, particularly IL-2 and IFN-gamma. Furthermore, CD8+ T cells that had reduced CD28 levels but made their own IL-2 were able to proliferate in response to TCR stimulation. These results suggest that loss of CD28 expression and CD8 T cell function can be regulated by the cytokine environment, which may be altered during HIV disease progression. Whether the dysfunction of CD8+ T cells in HIV infection occurs by such a mechanism is the subject of future investigation.

Antibodies, Monoclonal↗
PubMed1997

Enhanced cardiac preconditioning in the isolated heart of the transgenic ((mREN-2) 27) hypertensive rat.

OBJECTIVE: Cardiac preconditioning represents an important cardioprotective mechanism which limits myocardial ischaemic damage. The aim of this investigation was to assess the impact of preconditioning in hypertension, which is a major risk factor for ischaemic heart disease. METHODS: Hearts isolated from male transgenic ((mREN-2)27) hypertensive (TGH) rats, and their normotensive controls (Hannover Sprague-Dawley; SD rats), were perfused at constant flow using the Langendorff technique, and were subjected to either ischaemic preconditioning (3 x 4 min ischaemia) or continuous perfusion. Global ischaemia was then induced for 30 min, followed by 60 min of reperfusion, during which time mechanical performance was assessed (left ventricular developed pressure (LVDP), heart rate, and end-diastolic pressure). RESULTS: In the absence of preconditioning, mechanical performance was substantially depressed on reperfusion, and there was no difference between TGH hearts and SD hearts (area under the curve (AUC) for the LVDP (LVDP0-60) plot against time for reperfusion = 356 +/- 115 and 296 +/- 206 mmHg.min, respectively). Cardiac preconditioning caused significant protection in both groups, but this was significantly (P < 0.05) greater (3-fold) in the TGH hearts (AUC for LVDP0-60 = 3349 +/- 610 mmHg.min) compared to the SD hearts (AUC for LVDP0-60 = 1153 +/- 527 mmHg.min). In both groups, preconditioning induced significant protection of diastolic function. The enhanced effects of preconditioning on mechanical performance in the TGH hearts were unaffected by the angiotensin AT1-receptor antagonist, losartan (3 microM). However, losartan did partially reverse the beneficial effects of preconditioning on post-ischaemic diastolic function in the TGH hearts. CONCLUSIONS: The results of the present investigation clearly show that cardiac preconditioning is substantially enhanced in hearts from TGH rats. Furthermore, the beneficial effects of preconditioning on diastolic function, but not mechanical performance, in TGH hearts is partially mediated by AT1-receptors.

Animals↗
PubMed1997

Long-term psychological adjustment to witnessing interparental physical conflict during childhood.

A retrospective survey of undergraduate students was used to examine the long-term psychological impact of witnessing interparental physical aggression during childhood. Two hundred and three of 1,452 young adults surveyed (14%) reported witnessing as children at least one incident of physical aggression between their parents. Both men and women who witnessed interparental physical conflict reported higher levels of current psychological distress than a comparison group of young adults who never observed physical aggression between their parents. This group difference remained even after controlling for parental divorce, parental SES, physical abuse of the child, parental alcoholism, and nonphysical discord witnessed between parents. Additional analyses found that the negative effect of witnessing interparental aggression was intensified when the aggression was serious enough to warrant some type of outside assistance for the victim and when the parent of the same-sex was seen being victimized. Although these findings provided support for the theory that witnessing interparental physical aggression is a traumatic experience that may have long-term psychological ramifications, we also found that a substantial proportion of the variance accounted for in adult adjustment by interparental physical conflict was mediated through decreased parental caring and warmth during childhood. Implications for these results, limitations of the present study, and directions for further research are discussed.

Adolescent↗
PubMed1997

Employment status and high blood pressure in women: variations by time and by sociodemographic characteristics.

PURPOSE: The association between employment status and high blood pressure in women was examined at two time periods to determine if associations between employment status and high blood pressure varied by time period or by age, race, education, marital status, or parental status. METHODS: Women participants from the National Health Examination Survey (1960) and the Second National Health and Nutrition Survey (1976-1980) between the ages of 25 and 64 and currently employed or keeping house were included. Logistic regression analysis was used to examine the cross-sectional association between employment status and high blood pressure in each survey, taking into account potential effect modifiers and covariates. RESULTS: In 1960 employment was associated with a slight, but not statistically significant, elevation in odds of high blood pressure. In 1976-1980, it was associated with a modest but significant reduction in odds of high blood pressure. Variations in associations occurred by marital status (protective associations were limited to unmarried women) and race (associations were of stronger magnitude among African-American women). CONCLUSIONS: The employment status-high blood pressure relationship shifted across surveys. Changes in the composition of the employed and nonemployed groups account for at least part of the varying relationships.

Adult↗
PubMed1997

Regulation of the taurine transporter gene in the S3 segment of the proximal tubule.

Traditionally, bulk amino acid reabsorption in the kidney has been thought to be localized to the early portions of the proximal nephron. Adult Sprague-Dawley rats were fed diets with low, normal, and high taurine content for two weeks. Kidneys were hybridized with an 35S-radiolabeled complementary RNA probe to the rB16a subclone encoding the extracellular and transmembrane domains of the rat brain taurine transporter. Identical fragments were generated by RT-PCR from rat brain and kidneys as confirmed by DNA sequencing. Hybridization was localized to the outer zone of the medulla of all the kidneys. In the normal diet animals, taurine transporter mRNA was localized to the S3 segment of the proximal tubule, to the loop of Henle in the medulla, and to the glomerular epithelial cell layer. With taurine restriction, taurine transporter mRNA expression was up-regulated predominantly in the S3 segment and was virtually absent in this segment in animals supplemented with taurine. These experiments have precisely localized the rat kidney taurine transporter gene, demonstrating regulation that is limited to the S3 segment of the proximal tubule.

Animals↗
PubMed1997

Haemodynamic effects of adrenomedullin in human resistance and capacitance vessels.

AIMS: The haemodynamic effects of adrenomedullin and calcitonin gene-related peptide (CGRP) were studied in resistance and capacitance vessels of healthy volunteers. METHODS: Adrenomedullin and CGRP were infused into the brachial artery of eight healthy subjects on two separate occasions at doses between 0.3-30 pmol min(-1). Forearm blood flow was measured using venous occlusion plethysmography. Venodilatation to adrenomedullin and CGRP was assessed in a further eight subjects by infusing the peptides at doses between 0.3-10 pmol min(-1) into a dorsal hand vein preconstricted with noradrenaline. Venodilator responses were measured as percentage reduction in noradrenaline preconstriction. RESULTS: Adrenomedullin and CGRP at a dose of 30 pmol min(-1), produced an increase in forearm blood flow of 288 +/- 42% and 252 +/- 30% respectively (mean +/- s.e. mean, P<0.001). At doses between 3 and 10 pmol min(-1) adrenomedullin was significantly more potent than CGRP. The vasodilatation to both peptides was of similar duration with a biological half-life of approximately 18 min. Adrenomedullin reversed constriction in dorsal hand veins by 84 +/- 2% (P<0.001) at a dose of 10 pmol min(-1). CGRP produced a similar effect reversing constriction by 72 +/- 12% at the same dose (P<0.01). In veins, adrenomedullin was also more potent than CGRP at doses between 0.3 and 3 pmol min(-1). CONCLUSIONS: The lowest dose of adrenomedullin producing significant arteriolar dilatation was calculated to produce plasma levels similar to those found in heart failure. These findings suggest that in pathophysiological conditions such as heart failure circulating levels of adrenomedullin may be within a range capable of influencing vascular resistance directly.

Adrenomedullin↗
PubMed1997

Insulin-like growth factor (IGF) and IGF binding protein gene expression in multicystic renal dysplasia.

Multicystic dysplastic kidney disease is the most common form of renal dysplasia that leads to ESRD in children. This study describes the histopathological changes of multicystic dysplasia that occur from early fetal life to the postnatal period. At 14 wk gestation, early cystic enlargement of various segments of the nephron have been identified, in addition to a displaced metanephric blastema adjacent to zones of normal nephrogenesis. At later stages, the predominant features include cyst enlargement with marked fibromuscular collars, architectural disorganization, and replacement of the interstitium with a disarray of mesenchymal tissue. This study investigated the expression of the mRNA encoding the insulin-like growth factors (IGF) and IGF binding proteins (IGFBP) and have demonstrated IGF-II, IGFBP-2, and IGFBP-3 to be altered. Apart from their expression in the displaced metanephric blastema, both IGF-II and IGFBP-2 were overexpressed in abnormal tissue elements in all kidneys from fetal to postnatal life. IGF-II gene expression was localized to mesenchymal tissue, specifically in the periductal fibromuscular collars. IGFBP-2 mRNA was found to be expressed exclusively in the cyst epithelia of all cysts at all ages studied, whereas IGFBP-3 mRNA was absent from these epithelia. This study details the failure of normal IGF expression in the development of multicystic renal dysplasia and suggests a role for the IGF system in the progressive histopathological changes of this disorder.

Child, Preschool↗
PubMed1996

An endogenous cannabinoid as an endothelium-derived vasorelaxant.

Since the identification of nitric oxide (NO) as an important mediator of endothelium-dependent relaxation, it has become clear that there is an additional endothelial relaxant factor, termed the endothelium-derived hyperpolarizing factor (EDHF). The identity of EDHF has remained elusive, but it is thought to be an arachidonic acid metabolite. We now report that EDHF-mediated relaxations in the rat mesenteric arterial bed are blocked by a highly selective cannabinoid receptor antagonist, SR141716A, consistent with EDHF being a cannabinoid-like substance. Furthermore, in conscious rats,. the NO-independent depressor and regional vasodilator effects of bradykinin were inhibited by SR141716A. The relaxations in the isolated mesentery were accompanied by the accumulation of an arachidonic acid metabolite, which co-eluted on TLC separation with arachidonoylethanolamide (anandamide), an endogenous cannabinoid derived from arachidonate. We further report that anandamide is a potent vasorelaxant in the mesentery, acting via a hyperpolarizing mechanism. These findings suggest that an endogenous cannabinoid is an endothelium-derived vasorelaxant, which may be EDHF.

Animals↗
PubMed1996

Identification of a novel myosin heavy chain gene expressed in the rat larynx.

Based on reactivity to antibodies against known myosin heavy chains, expression of a novel fast myosin heavy chain (MHC) gene was suspected in the thyroarytenoid (TA) muscle of the rat larynx. The 3' ends of MHC transcripts in the TA were amplified by RT-PCR using a primer to a highly conserved MHC sequence and to the poly(A) tail. The resultant products were cloned and fourteen PCR products were screened by dot-blotting with oligonucleotides specific for known skeletal muscle MHC genes. A clone that reacted weakly to the 2B oligo was sequenced and found to encode a novel fast MHC transcript, termed 2L, that appears to represent an eighth vertebrate skeletal muscle MHC gene. By homology analysis, the 2L sequence is most similar to the extraocular MHC, suggesting a possible evolutionary relationship between MHCs associated with the branchial arches.

Amino Acid Sequence↗
PubMed1996

Adverse effects of dextromethorphan on the spatial learning of rats in the Morris water maze.

The effects of the non-competitive NMDA receptor antagonist dextromethorphan on spatial learning were assessed using the Morris water maze. Dextromethorphan was administered to 4 groups of rats in 10, 20, 30, and 40 mg/kg doses. An additional group of rats was administered saline to serve as a vehicle control group. Dextromethorphan impaired learning dose dependently in the initial training phase of the experiment. During the probe trial, dose-dependent performance deficits were noted in the first 15 s of the trial only. Search strategy differences between the lowest and highest dose groups were also observed during the probe trial. During the reversal training phase, when the platform was moved to a new location, the dose-dependent impairment was seen again, but the 40 mg/kg group perseverated to the former location longer than the other groups. A cued control trial indicated that in addition to the learning impairment produced, the highest dose of dextromethorphan may also impair sensory-motor coordination.

Animals↗
PubMed1996

Initial experience with an implantable hemodynamic monitor.

BACKGROUND: Measurement of intracardiac hemodynamic parameters has been limited to brief periods in the acute care setting. We developed and evaluated an implantable hemodynamic monitor that is capable of measuring chronic right ventricular oxygen saturation and pulmonary artery pressure. METHODS AND RESULTS: The device consists of an electronic controller placed subcutaneously and two transvenous leads placed in the right ventricle (reflectance oximeter) and pulmonary artery (variable capacitance pressure sensor). Implantation was performed in 10 patients with severe left ventricular dysfunction. Average implant pulmonary artery pressures were systolic, 52 +/- 16 mm Hg; diastolic, 29 +/- 11 mm Hg; and mean, 40 +/- 12 mm Hg. The mean right ventricular oxygen saturation at implant was 51%. Provocative maneuvers, including postural changes, sublingual nitroglycerin, and bicycle exercise, demonstrated expected changes in measured oxygen saturation and pulmonary artery pressures over time. At follow-up of 0.5 to 15.5 months, there were no significant differences between pulmonary artery pressures or oxygen saturation values transmitted from the device and simultaneous measurement with balloon flotation catheters. Four of the pulmonary artery leads dislodged and three demonstrated sensor drift, whereas two of the oxygen saturation sensors failed. Four patients died and four received transplants. Pathological study did not demonstrate injury to the right ventricular outflow tract or pulmonic valve. CONCLUSIONS: Chronic measurement of hemodynamic parameters in the outpatient setting with implantable sensor technology appears to be feasible. The devices are well tolerated without significant untoward effects, and the sensors generally function well over time, providing reliable information. Clinical usefulness remains to be established.

Adult↗
PubMed1996

Long-term recording of cardiac output via an implantable haemodynamic monitoring device.

Long-term monitoring of central haemodynamics with implanted monitoring systems might be valuable in managing heart failure patients. Such systems offer an opportunity for repeated 'semi-invasive' cardiac output determinations according to the Fick principle. Five patients, four with chronic heart failure and one with chronic pulmonary disease, underwent supine exercise testing during cardiac catheterization at 0, 2, 6 and 11 months after implantation of a right ventricular mixed venous oxygen saturation sensor connected to an implantable haemodynamic monitor. The monitor provided a continuous measure of oxygen saturation via a radio-telemetry link to a metabolic cart capable of measurement of breath-by-breath oxygen consumption. Cardiac output was computed using oxygen consumption, mixed venous oxygen saturation, arterial oxygen saturation by pulse oximetry and haemoglobin oxygen capacity. Biosensor-derived oxygen saturation compared to blood samples from the pulmonary artery showed an excellent correlation over time, r2 = 0.94 (implant), r2 = 0.91 (6-11 months). There was a strong correlation between semi-invasive-determined cardiac output using the biosensor and the invasive technique, which persisted over the entire follow-up period. Repeated semi-invasive cardiac output measurements using an implanted haemodynamic monitoring system in chronic heart failure patients is feasible and the data may be of value for optimizing therapy.

Adult↗