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Biomedical subjects

R Schulz

Publications and source records attributed to R Schulz.

At least 343 records · Page 19Linked to original sources
PubMed1994

Role of NO in vascular smooth muscle and cardiac muscle function.

NO is a key transducer of a vasodilator message from the endothelium to vascular smooth muscle. Recently, its actions as a negative inotrope in cardiac muscle have been discovered. In the vasculature, it is synthesized under physiological conditions following activation of a low-output, Ca(2+)-dependent NO synthase (NOS) in endothelial cells. Immune activation triggers the expression of a high-output, Ca(2+)-independent NOS in the vasculature and myocardium, causing the overproduction of NO and significant cardiovascular dysfunction. In this article, Richard Schultz and Chris Triggle briefly review recent findings concerning the role of NO, and other endothelium-derived factors, in vascular smooth muscle function and consider the consequences of its production in the heart.

Animals↗
PubMed1994

The relationship between age and major league baseball performance: implications for development.

Lifetime performance data of 388 baseball players active in 1965 were analyzed to determine the age of peak performance for skills required to play baseball, to derive age-performance curves for athletic productivity, and to assess the magnitude of individual differences among elite and less able players. Cross-sectional and longitudinal analyses show that athletic performance on key indicators rises relatively quickly from age 19 to a peak age of 27 and then declines. The primary difference between elite and less able players is that performance of the elite players remains high for a longer period of time and decays more gradually. The performance of the most elite players is superior to that of less able players even at very early ages. These results parallel findings reported for other achievement domains and can be explained in terms of basic developmental processes involving the interaction of experience, physiological capacity, and motivation.

Adolescent↗
PubMed1994

Retinoic acid-induced differentiation of human neuroblastoma SH-SY5Y cells is associated with changes in the abundance of G proteins.

Western blot analysis, using subtype-specific anti-G protein antibodies, revealed the presence of the following G protein subunits in human neuroblastoma SH-SY5Y cells: Gs alpha, Gi alpha 1, Gi alpha 2, Go alpha, Gz alpha, and G beta. Differentiation of the cells by all-trans-retinoic acid (RA) treatment (10 mumol/L; 6 days) caused substantial alterations in the abundance of distinct G protein subunits. Concomitant with an enhanced expression of mu-opioid binding sites, the levels of the inhibitory G proteins Gi alpha 1 and Gi alpha 2 were found to be significantly increased. This coordinate up-regulation is accompanied by functional changes in mu-opioid receptor-stimulated low-Km GTPase, mu-receptor-mediated adenylate cyclase inhibition, and receptor-independent guanosine 5'-(beta gamma-imido)triphosphate [Gpp(NH)p; 10 nmol/L]-mediated attenuation of adenylate cyclase activity. In contrast, increased levels of inhibitory G proteins had no effect on muscarinic cholinergic receptor-mediated adenylate cyclase inhibition. With respect to stimulatory receptor systems, a reciprocal regulation was observed for prostaglandin E1 (PGE1) receptors and Gs alpha, the G protein subunit activating adenylate cyclase. RA treatment of SH-SY5Y cells increases both the number of PGE1 binding sites and PGE1-stimulated adenylate cyclase activity, but significantly reduced amounts of Gs alpha were found. This down-regulation is paralleled by a decrease in the stimulatory activity of Gs alpha as assessed in S49 cyc- reconstitution assays.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗
PubMed1994

[Prenatal diagnosis of severe stenosis of the ductus arteriosus Botalli in a twin pregnancy].

Premature ductus arteriosus stenosis is a rare cardiovascular disease, which has a poor prognosis. The case presented was detected even in early pregnancy and was progressed rapidly to the stage of severe foetal heart failure. The patient was first seen at 20 weeks of gestation with one of the foetuses of a twin pregnancy, showing signs of cardiac decompensation and advanced hydrops fetalis universalis. Obstruction of the ductus arteriosus may result from maternal tocolysis treatment with prostaglandin synthetase inhibitors, such as indomethacin or maternal salicylate or in conjunction with foetal post maturity.

Adult↗
PubMed1994

Tolerance induction by elimination of subsets of self-reactive thymocytes.

Immature thymocytes expressing TCRs which confer reactivity to self-MHC molecules are subject to efficient elimination as a result of negative selection. Previously, we have identified a lineage of H-2Kb Tg mice, CD2Kb-3, which fails to reject skin grafts from mice expressing H-2Kb even though H-2Kb-specific cytotoxic T cells can be generated in vitro. We now show that bone marrow derived cells are responsible for tolerance induction and that tolerance is acquired, at least in part, by negative selection in CD2Kb-3 mice. Thymocytes expressing two different transgenic TCR (TCR-Tg) clonotypes conferring reactivity to H-2Kb are eliminated prior to the CD8+CD4+ stage of differentiation in double Tg (CD2Kb-3 x TCR-Tg)F1 mice. As in other cases where thymocytes from TCR-Tg mice develop in the presence of deleting ligands, large numbers of TCR+ CD8-CD4- T cells accumulate in double Tg mice. However, these T cells fail to respond to H-2Kb in vitro but can be activated with immobilized anti-clonotypic antibody. Consequently, thymocytes expressing these types of TCR molecules represent a fraction of H-2Kb-reactive thymocytes which are unable to mature into T cells capable of mounting H-2Kb-specific cytotoxic responses. Presumably, precursors of H-2Kb-specific cytotoxic T cells found in the periphery of CD2Kb-3 mice express a distinct repertoire of TCR molecules conferring reactivity to H-2Kb. We consider potential explanations to account for this discrepancy and their wider implications, including the possibility that the repertoire of thymocytes able to recognize self-H-2Kb molecules in CD2Kb-3 mice is divided into distinct subsets; those which are, and those which are not, subject to negative selection.

Animals↗
PubMed1994

Selection bias and nonresponse to health promotion in older adults.

Some epidemiologic studies have compared the characteristics of individuals who participate, refuse, and are unreachable in population studies, but results have been inconsistent. The Rural Health Promotion Project attempted to recruit all Medicare Part B noninstitutionalized individuals age 65-79 years in a rural community for a trial of preventive health services. Of 962 potential subjects, 360 (37.4%) participated, 253 (26.3%) refused, 176 (18.3%) were ineligible, and 152 (15.8%) were never reached by phone or mail. Approximately 3 years later, we reinterviewed the participants, refusals, and as many of the unreachables as possible. The 3-year mortality was similar for both refusals and participants (approximately 9%) but was much higher for ineligibles (29.0%) and unreachables (23.7%). Participants were more likely to have disease history, to have behavioral risk factors for disease, and to use health screening services. Refusals were the healthiest and possibly chose not to participate because they did not have risk factors targeted by the program. The unreachables had the highest prevalence of disability and health care inpatient reimbursement and may have been ineligible for the demonstration had they volunteered. We conclude that failure to reach potential participants for health promotion services may be a warning of "high risk."

Aged↗
PubMed1994

Atrial natriuretic peptide and plasma volume of dogs suffering from heart failure or dehydration.

Studies in humans and experimental animal models suggest that volume overload increases and volume underload decreases release of atrial natriuretic peptide (ANP), a hormone intimately linked to water and electrolyte homeostasis. This relationship was examined in dogs suffering from heart failure or dehydration and the data presented here are in support of this general concept. Plasma ANP concentration in dogs with congestive heart failure (CHF) was elevated with the severity of the disease (NYHA classification, class II: 21.4 +/- 9.2 fmol ANP/ml; class III: 65.5 +/- 72.6; class IV: 119.7 +/- 87.1; healthy dogs: 13.9 +/- 7.5). The increment in plasma ANP concentration in cardiac patients was also positively correlated with the plasma volume. The blood volume of dogs with moderate and severe CHF was significantly (P < 0.05) elevated and a normotonic blood pressure prevailed. In contrast, dehydrated dogs tend to display reduced ANP plasma concentration (7.7 +/- 5.6 fmol/ml) as well as significantly lower plasma volume and reduced blood pressure (P < 0.05). In dogs with severe CHF, ANP precursor material is present in the blood, which is normally undetectable. These data further support the concept of a regulatory function of ANP in volume homeostasis of dogs.

Animals↗
PubMed1994

Self-reported causes of physical disability in older people: the Cardiovascular Health Study. CHS Collaborative Research Group.

OBJECTIVE: To determine the major conditions and symptoms reported to cause difficulty in 17 physical tasks of daily life and the criterion validity of self-report of diseases given as the causes of the difficulty in functioning, in community-dwelling older people. DESIGN: Cross sectional analyses of data obtained in an observational cohort study. SETTING: Research clinics in four US communities: Winston-Salem, NC, Hagerstown, MD, Pittsburgh, PA, and Sacramento, CA. PARTICIPANTS: 5201 community-dwelling people > or = 65 years old. RESULTS: Arthritis and other musculoskeletal diseases were given as the primary causes of difficulty in performing physical tasks by 49.0% of the participants reporting difficulty in any task, followed by heart disease (13.7%), injury (12.0%), old age (11.7%), lung disease (6.0%), and stroke (2.9%). The self-reports of diseases that caused disability varied by task. Whereas arthritis was given as a cause of difficulty in most of the 17 different tasks, heart and lung disease were more likely to be reported as causing difficulty with activities requiring high aerobic work capacity such as walking one-half mile or doing heavy housework. Stroke was more likely to be reported as causing difficulty with use of the upper extremities and in performing basic activities of daily living. There was a high degree of consistency (91%) between the diseases and symptoms reported to cause disabilities. The percentage of people who reported a disease as the cause of their difficulty performing a task and had independent confirmation of the diagnosis was 85% in men and 71% in women, and varied according to type of disease and the individual's cognitive status and health status. CONCLUSION: These data suggest that age-related chronic diseases are important causes of disability in older people but that the type of disability is dependent on the underlying disease that causes the disability. Also, self-report of the cause of disability appears to be generally accurate but is influenced by gender, health status, and type of disease.

Activities of Daily Living↗
PubMed1994

Involvement of activation of ATP-dependent potassium channels in ischemic preconditioning in swine.

This study evaluated the importance of ATP-dependent potassium channels (KATP) for ischemic preconditioning (IP) in swine. Swine were studied because due to the sparsity of their innate collateral circulation infarct size (IS) development closely resembles that observed in humans. Ninety minutes of ischemia at a blood flow reduction sufficient to reduce regional myocardial work by 90% caused 13.2 +/- 8.9% (SD) IS of the area at risk. A single cycle of 10-min preconditioning ischemia followed by 15-min reperfusion reduced IS after 90 min of ischemia to 2.8 +/- 2.7%. The epicardial monophasic action potential duration at 50% repolarization (MAP50) was decreased more markedly during the initial 10 min of the prolonged ischemia than during the first 10 min of the preconditioning ischemic period (84 +/- 4 vs. 89 +/- 2%). Transmural myocardial adenosine (ADO) uptake was reversed to net release during both ischemic periods and during the initial phase of reperfusion. Glibenclamide (0.5 mg/kg, followed by 50 micrograms/min i.v.) abolished the reduction in MAP50 without altering ADO release. Glibenclamide did not alter IS per se (13.0 +/- 7.6%) but abolished the beneficial effect of IP (IS: 13.6 +/- 6.2%). Thus blockade of KATP with glibenclamide abolishes the IS-reducing effect of IP in swine but does not reduce ADO release.

Action Potentials↗
PubMed1994

Gene expression and secretion of atrial natriuretic peptide by murine macrophages.

An increased expression of atrial natriuretic peptide (ANP) has been reported in activated macrophages of the acutely involuted rat thymus. We communicate here that ANP may reflect a common constituent of macrophages, as mRNA coding for ANP is present in peritoneal- as well as in bone marrow-derived macrophages (PM, BMM). Furthermore, both types of macrophages synthesize and release ANP which was found to mainly represent the biologically active fragment ANP99-126. ANP expression in macrophages is regulated by compounds affecting the activity of these immune cells. For example, incubation of PM or BMM in vitro with LPS and zymosan, respectively, increased ANP-mRNA up to sixfold as determined by competitive PCR quantification. Exposure of macrophages to dexamethasone (Dex, 10(-7) M) elicits moderate effects (1.4-fold), while PMA (10(-7) M) failed to affect its abundance. These findings are complemented by data regarding ANP synthesis and secretion. Incubation of macrophages with LPS, Dex or a combination of both results in an up to 3.5-fold increase of intracellular ANP99-126 (basal 10 fmol/mg protein), and an up to 6.6-fold increase of its secretion (basal 40 fmol/mg protein, 24 h). Since macrophages synthesize and release ANP, the peptide may be involved in the complex mechanisms of host defense, a major function of these immune cells.

Animals↗
PubMed1994

Predictors of perceived health status in elderly men and women. The Cardiovascular Health Study.

Baseline data on the perceived health status of participants (N = 5,201) in the Cardiovascular Health Study of the Elderly (CHS) are reported. The authors examined the predictive utility of health-related factors representing eight different domains, assessed gender differences in the prediction of perceived health, and tested a hypothesis regarding the role of known clinical conditions versus subclinical disease in predicting perceived health. Multivariate analyses showed that the majority of the explained variance in self-assessed health is accounted for by variables that fall into four general categories. Although gender differences were small, the analysis showed that the relative importance of several predictor variables did vary by gender.

Aged↗
PubMed1994

Mechanisms of cytokine-induced destruction of rat insulinoma cells: the role of nitric oxide.

Cytokines produced by immune system cells infiltrating pancreatic islets are candidate mediators of islet beta-cell destruction in insulin-dependent diabetes mellitus. In this study, we examined the role of nitric oxide (NO) as a mediator of cytokine-induced islet beta-cell destruction in a rat insulinoma cell line (RINm5F). The cytokine combination of interleukin-1 beta (IL-1 beta; 10 U/ml), tumor necrosis factor-alpha (10(3) U/ml), and interferon-gamma (10(3) U/ml) induced DNA fragmentation (first detected at 6 h), mitochondrial damage (by 12 h), and death (by 24 h) of RIN cells, whereas the individual cytokines did not have these destructive effects. Also, the cytokine combination of IL-1 beta, tumor necrosis factor-alpha, and interferon-gamma induced a 10-fold increase in NO production by RIN cells, and L-NG-monomethyl arginine, an inhibitor of NO synthase, produced a dose-dependent inhibition of cytokine-induced NO production, DNA fragmentation, and cell destruction. However, IL-1 beta, acting alone, induced a 7-fold increase in NO production without causing DNA fragmentation, mitochondrial damage, or cell destruction. In addition, nicotinamide, a known inhibitor of ADP ribosylation and scavenger of oxygen free radicals, inhibited cytokine-induced DNA fragmentation and cell destruction without affecting NO production. We conclude that stimulation of NO production may be a necessary, but not sufficient, condition for cytokine-induced destruction of islet beta-cells.

Animals↗
PubMed1994

Human pancreatic islet beta-cell destruction by cytokines is independent of nitric oxide production.

The inflammatory cytokines, interleukin-1 beta, tumor necrosis factor-alpha, and interferon-gamma are cytotoxic to human islet beta-cells in vitro. To determine the possible role of nitric oxide (NO) as a mediator of cytokine-induced islet beta-cell destruction, we studied the relationships between NO production and destruction of human pancreatic islet cells incubated with cytokines in vitro. The cytokine combination of interleukin-1 beta (50 U/mL), tumor necrosis factor-alpha (10(3) U/mL), and interferon-gamma (10(3) U/mL) induced a significant increase in NO production and significant decreases in DNA and insulin contents of the islet cell cultures after a 48-h incubation. L-NG-Monomethyl arginine, an inhibitor of NO synthase, completely prevented cytokine-induced NO production during incubations of 18, 36, 60, and 84 h. Cytokine-induced decreases in DNA and insulin contents of the islet cell cultures, however, were unaffected by the NO synthase inhibitor. Conversely, nicotinamide prevented cytokine-induced islet beta-cell destruction without inhibiting NO production. We conclude that cytokine-induced NO production in human islet cells may be neither necessary nor sufficient to destroy the islet beta-cells and that cytotoxic mechanisms, independent of NO, exist and can be inhibited by nicotinamide.

Arginine↗
PubMed1994

The value of the physician executive role to organizational effectiveness and performance.

With the growing importance of medical management as a component of health care delivery, it is important to understand the extent to which physician executives assist their organizations in the provision of health care that is efficient and of high quality. To date, research on the role of physician executives in large health care organizations has been limited. This research attempts to address some of the gaps in our understanding of the value of the role of the physician executive and explores the anticipated opportunities for expansion of that role as health care organizations attempt to respond to a rapidly changing health care environment.

Chi-Square Distribution↗
PubMed1994

Characterization of hibernating and stunned myocardium.

Both the hibernating and the stunned myocardium are characterized by reversible contractile dysfunction. In hibernating myocardium ischemia is still ongoing, whereas in stunned myocardium blood flow is fully or almost fully restored. Both the hibernating and the stunned myocardium retain an inotropic reserve. In hibernating myocardium the increase in contractile function is at the expense of metabolic recovery whereas in stunned myocardium no metabolic deterioration occurs during inotropic stimulation. Therefore, inotropic stimulation in combination with metabolic imaging may help not only to identify viable, dysfunction myocardium but also to distinguish hibernating and stunned myocardium. The only causal therapy of hibernating myocardium is to restore blood flow to the hypoperfused tissue. Myocardial stunning per se requires no therapy at all, since by definition blood flow is normal and contractile function will recover spontaneously. If, however, myocardial stunning involves large parts of the left ventricle and thus impairs global left ventricular function, the extent of myocardial stunning can be reduced by inotropic stimulation, without inducing further damage to the myocardium. In the experimental setting, antioxidant agents, calcium antagonists and ACE inhibitors attenuate stunning, most effectively when administered before ischemia.

Adenosine Triphosphate↗
PubMed1994

Physician satisfaction with the development of HMOs in Dane County: 1983-1993.

In September 1993, the 1,196 active physicians in Dane County were surveyed to learn their satisfaction with the development of HMOs and comparisons to similar satisfaction surveys in 1986 and 1983. Among the 675 usable responses, 65% reported that they were satisfied or very satisfied with their current work, which is about the same as the 1986 survey when 68% reported that they were satisfied. Other findings suggest support for HMO development in Dane County. Moreover, 66% reported support for the basic principles of the Clinton health system reform plan announced in September 1993.

Attitude of Health Personnel↗
PubMed1993

Alterations in the expression of G-proteins and regulation of adenylate cyclase in human neuroblastoma SH-SY5Y cells chronically exposed to low-efficacy mu-opioids.

Western-blot analysis of human neuroblastoma SH-SY5Y cells (mu- and delta-receptors) revealed the presence of the following G-protein subunits: Gi alpha 1, Gi alpha 2, Gs alpha, G(o) alpha, Gz alpha, and G beta, a pattern resembling that observed in central nervous tissue. Chronic treatment of differentiated [all-trans-retinoic acid (10 microM; 6 days)] SH-SY5Y cells with D(-)-morphine (10 microM; 3 days) significantly increased the abundance of all G-protein subunits identified. Co-incubation of morphine-exposed cells together with naloxone (10 microM; 3 days) or the mu-selective opioid antagonist CTOP (10 microM; 3 days), but not with the delta-selective antagonist ICI-174,864 (10 microM; 3 days), completely abolished this effect, suggesting that the increase in G-protein abundance is specifically mediated by mu-receptors. Moreover, the biologically inactive enantiomer L(+)-morphine (10 microM; 3 days) failed to produce a similar effect. G-protein up-regulation developed in a time- and dose-dependent manner and is most likely due to enhanced protein synthesis de novo, since concomitant treatment of the cells with cycloheximide (100 micrograms/ml; 3 days) prevented this effect. Chronic treatment with the low-efficacy mu-selective opioid peptide morphiceptin (10 microM; 3 days), but not with the highly potent mu-agonist DAGO (0.1 microM; 3 days) produced a comparable increase in G-protein abundance. Coincident with quantitative effects on G-protein levels in morphine-tolerant/dependent SH-SY5Y cells, we found elevated levels of basal, forskolin (1 microM)- and prostaglandin-E1 (1 microM)-stimulated adenylate cyclase activities. Reconstitution experiments using S49 cyc- lymphoma-cell membranes suggest that this increase is most likely due to elevated levels of functionally intact Gs. Chronic treatment with both morphine and DAGO induces high degrees of tolerance in this cell line. However, the intrinsic activity of G1 was unchanged, as assessed in functional studies with low-nanomolar concentrations of guanosine 5'-[beta gamma- imido]triphosphate. Our data demonstrate that chronic treatment of SH-SY5Y cells with low-efficacy mu-opioids increases G-protein abundance, a phenomenon which might contribute to the biochemical mechanisms underlying opioid tolerance/dependence.

Adenylyl Cyclases↗