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Biomedical subjects

R Schulz

Publications and source records attributed to R Schulz.

At least 361 records · Page 20Linked to original sources

Analysis of myocardial plasmalogen and diacyl phospholipids and their arachidonic acid content using high-performance liquid chromatography.

A high-performance liquid chromatographic method for the assay of diacyl and plasmalogen (alk-1-enyl) phospholipid content and the determination of their fatty acid content from tissue homogenates is described. Myocardial phospholipids are rich in plasmalogens and have a high content of unsaturated fatty acids, including arachidonic acid, esterified in the sn-2 position. Using a three-stage HPLC assay we have analyzed the phospholipid subclass content and the amount of arachidonic acid esterified to these fractions extracted from isolated perfused rat hearts. After HPLC separation of total myocardial phospholipids, the phosphatidylcholine and phosphatidylethanolamine peak fractions are treated with phospholipase C to remove polar head groups and ultraviolet-absorbing benzoate derivatives are made. Separation and quantification of diacyl and plasmalogen content of the total phospholipids with nanomolar sensitivity is then achieved using isocratic elution with a silicic acid HPLC column. The separated plasmalogen and diacyl glycerobenzoates are then subjected to alkaline hydrolysis to remove fatty acids from the sn-2 position. The 2-(2,3-napthalimino)ethyltrifluoromethanesulfonate esters of the free fatty acids are then prepared and analyzed with subnanomolar sensitivity using reverse-phase chromatography with gradient elution. As plasmalogen-specific phospholipase A2 is activated during myocardial ischemia and comprises the majority of total phospholipase A2 activity in the heart, this methodology allows for a sensitive and complete determination of the changes in the mass of these phospholipids and their arachidonic acid content.

Animals↗

Characterization and purification of a hydrogenase from the eukaryotic green alga Scenedesmus obliquus.

Several catalytic properties of the hydrogenase from Scenedesmus obliquus have been examined to optimize the purification conditions. The Km-value for H2-evolution in the presence of the most effective electron mediator methylviologen is 0.66 mM. The pH-optimum is 6.3, the temperature-optimum is 50 degrees C and the energy of activation is 38.4 +/- 2 kJ.mol-1. The soluble hydrogenase from the green alga, Scenedesmus obliquus, was purified 1290-fold to homogeneity. The enzyme consists of two subunits with molecular masses of 55 kDa and 36 kDa. The molecular weight of the native enzyme, determined by gel filtration, is 150 +/- 5 kDa.

Chlorophyta↗

A probably familial saccular aneurysm of the anterior communicating artery in a neonate.

A 32-day-old boy died of recurring cerebral hemorrhages starting on the 4th day of life. Autopsy disclosed a remittingly ruptured saccular aneurysm of the anterior communicating artery. A 7-day-old brother of his had previously died of recurring subarachnoid hemorrhages as well. The young age of the patient, the site of the aneurysm, and its probably familial occurrence make this case a unique one. Nonaneurysmatic basal cerebral arteries showed remarkable histological changes partly resembling those seen in fibromuscular dysplasia, some of them probably representing preaneurysmatic alterations. A known underlying systemic disease could not be found, and immunohistochemical detection of type III collagen revealed no identifiable deficiency.

Aneurysm, Ruptured↗

CORDAT II: a new program for data acquisition and on-line calculation of hemodynamic and regional myocardial dimension parameters.

The present paper describes a new computer program for data acquisition and on-line evaluation of hemodynamic parameters. The hardware setup is based on a standard i486 personal computer equipped with an analog to digital converter and an additional display controller. During data acquisition the multitasking program automatically detects the beginning and the end of a cardiac cycle. Immediately after the recognition of a cardiac cycle the program calculates and displays user-defined hemodynamic parameters and mean values over a given time or a given number of beats. There is a high correlation between manually determined hemodynamic parameters and the parameters determined automatically by CORDAT II.

Aorta↗

Gender bias in the measurement properties of the Center for Epidemiologic Studies Depression Scale (CES-D).

Confirmatory factor-analytic models are used to examine gender biases of individual items of the Center for Epidemiologic Studies Depression (CES-D) Scale. In samples containing 708 cancer patients and 504 caregivers of the chronically ill elderly, two CES-D items are identified as producing biased responses in comparisons of male and female respondents. Three additional CES-D items are excluded on the basis of other psychometric problems, yielding a subset of 15 CES-D items that capture almost all the information of the original 20-item CES-D scale but are free of any gender bias. Gender differences in mean levels of depressive symptomatology are significantly reduced, but not eliminated, when the 15-item scale is used.

Activities of Daily Living↗

Phototransformation of monovinyl and divinyl protochlorophyllide by NADPH:protochlorophyllide oxidoreductase of barley expressed in Escherichia coli.

The chlorophyll precursors monovinyl protochlorophyllide (MV-PChlide) and divinyl protochlorophyllide (DV-PChlide) were extracted from mutant C-2A' of the unicellular green alga Scenedesmus obliquus which accumulates both protochlorophyllide derivatives in the dark. The two pigments were characterized by absorption and fluorescence spectroscopy and by plasma desorption mass spectrometry. The molecular masses of MV-PChlide and DV-PChlide were determined as 612 and 610 atomic mass units (amu) respectively. Both MV-PChlide and DV-PChlide were accepted as substrates and photoconverted to chlorophyllides in vitro by NADPH:protochlorophyllide oxidoreductase of barley expressed in Escherichia coli.

Chlorophyta↗

Transcutaneous pCO2-monitoring for the evaluation of the anaerobic threshold. Comparison to lactate and ventilatory thresholds.

The monitoring of transcutaneous pCO2 (pCO2(tc) is an alternative to the invasive determination of the anaerobic threshold by analysis of arterial lactate concentration or to the uncomfortable determination of the ventilatory threshold. We compared the threshold determination by pCO2(tc)-monitoring to the 4 mmol/l lactate threshold and to the ventilatory threshold (point where the ventilatory equivalent of oxygen started to increase continuously) in 15 athletes during cycle exercise. The first distinct deflection point in the pCO2(tc) time course after the start of exercise was chosen to indicate the anaerobic threshold. The mean threshold determined by pCO2(tc) occurred at the same workload as the ventilatory threshold but at a lower workload than the lactate threshold. In spite of the good correspondence in the respective means there was a wide range of individual differences between the pCO2(tc) derived thresholds and both reference thresholds. Thus, looking at an individual, the continuous monitoring of the pCO2(tc) does not provide reliable data on the occurrence of the transition from aerobic to anaerobic metabolism.

Adolescent↗

Post-ejection wall thickening as a marker of successful short term hibernation.

OBJECTIVE: Short term hibernating myocardium is characterised by a decrease in contractile function in proportion to the reduced blood flow, the recovery of creatine phosphate despite ongoing ischaemia, a recruitable inotropic reserve, and the absence of necrosis. During acute myocardial ischaemia systolic wall thickening decreases and post-ejection wall thickening develops. The extent of post-ejection thickening during severe ischaemia correlates with the recovery of contractile function during reperfusion. Whether the extent of post-ejection wall thickening can also distinguish short term hibernating myocardium from more severely ischaemic, infarcting myocardium and thus predict the amount of viable tissue was tested in 13 anaesthetised pigs. METHODS: The left anterior descending coronary artery (LAD) was cannulated and perfused at constant flow. After control measurements of regional myocardial blood flow (with radiolabelled microspheres) and wall thickening (sonomicrometry), coronary inflow was reduced to produce a reduction in regional contractile function by 60-100%. After 85 minutes of ischaemia, dobutamine was infused into the LAD for five minutes to determine the extent of inotropic reserve. Transmural biopsies were taken to measure regional myocardial creatine phosphate content and infarct size was determined after two hours of reperfusion by staining with triphenyl tetrazolium chloride. RESULTS: The extent of post-ejection wall thickening after 85-90 minutes of ischaemia correlated with the myocardial creatine phosphate content (r = 0.812, n = 11, p < 0.01) and the extent of the dobutamine recruitable inotropic reserve (r = 0.783, n = 7, p < 0.05). A negative correlation existed between the extent of post-ejection wall thickening and % infarct size (r = -0.699, n = 10, p < 0.05 for the transmural piece of tissue containing the ultrasonic crystals; r = -0.743, n = 10, p < 0.05 for the area of the left ventricle at risk). Finally, post-ejection wall thickening after 85-90 minutes of ischaemia correlated with the recovery of contractile function at 30 minutes reperfusion (r = 0.657, n = 10, p < 0.05). CONCLUSION: The extent of post-ejection wall thickening may indicate the amount of viable tissue after 85-90 minutes of low flow ischaemia. The greater the post-ejection wall thickening, the more myocardium is successfully hibernating.

Animals↗

Psychosocial and behavioral dimensions of physical frailty.

Findings from a decade of research on physical frailty in diverse elderly populations are summarized and integrated. While much of the literature focuses on the physical and functional consequences of chronic and acute illness, we emphasize the psychosocial and behavioral aspects of physical frailty. The underlying assumption of our approach is that the psychological representation of illness and disability, as well as the social contexts in which they occur, are important determinants of their impact on patients and family members. We focus on both patients and their primary support persons and on the comparative analysis of different disabling conditions. A patient and family caregiver impact model is used to summarize major findings of our research program and to make recommendations for intervention research.

Aged↗

The perspective of the patient with Alzheimer's disease: a neglected dimension of dementia research.

The patient perspective has been largely ignored in studies of Alzheimer's disease. The person with dementia is often relegated to the status of object rather than legitimate contributor to the research process and much can be gained from a systematic study of patients' views regarding their illness and care. We examine the status of dementia patients in three research areas and identify research challenges and opportunities that may substantially increase our understanding of dementia.

Alzheimer Disease↗

Coping with specific stressors in Alzheimer's disease caregiving.

Strategies used to cope with specific caregiving stressors were examined in a sample of 170 Alzheimer's disease (AD) caregivers. The most commonly identified stressors were memory deficits, loss of ability to communicate, and gradual decline of a loved one. Wishfulness was related to more depressed affect, regardless of stressor type. Other strategies related to more depressed affect included taking direct action when coping with patient memory deficits and stoicism in response to decline of a loved one. Strategies related to less depressed affect included relaxation in response to memory deficits, acceptance in dealing with communication impairments and decline of a loved one, and seeking social support in coping with decline of a loved one.

Adaptation, Psychological↗

Porcine ventricular endocardial cells in culture express the inducible form of nitric oxide synthase.

1. We have investigated whether porcine endocardial cells in culture express the inducible, Ca(2+)-independent form of nitric oxide (NO) synthase. 2. NO synthase activity in cytosolic extracts of endocardial cells was measured by estimation of the rate of formation of L-[14C]-citrulline from L-[14C]-arginine. 3. Treatment of the cells in culture with lipopolysaccharide or cytokines induced a Ca(2+)-independent NO synthase activity in the cell cytosol. The combination of tumour necrosis factor (TNF alpha, 10 ng ml-1) and interleukin-1 beta (IL-1 beta, 10 ng ml-1) induced the greatest enzyme activity. 4. The increased Ca(2+)-independent NO synthase activity following exposure to cytokines was paralleled by an increase in guanosine 3':5'-cyclic monophosphate (cyclic GMP) levels in the endocardial cell cytosol. 5. Simultaneous addition of dexamethasone (0.01-1 microM) or cycloheximide (0.03-3 microM) inhibited in a concentration-dependent manner TNF alpha- and IL-1 beta-induced expression of Ca(2+)-independent NO synthase activity. Neither dexamethasone (1 microM) nor cycloheximide (3 microM) had any effect on the activity of the constitutive NO synthase. 6. The possible pathophysiological consequences of endocardial expression of the inducible NO synthase are discussed.

Amino Acid Oxidoreductases↗

Age-related trends in cardiovascular morbidity and physical functioning in the elderly: the Cardiovascular Health Study.

OBJECTIVE: To describe relationships between age and sub-clinical cardiovascular disease, manifest chronic disease, and physical functioning and limitations among persons aged 65 years and older, with emphasis on the "oldest old," those 85 years and older. DESIGN: Observational population-based study. SETTING: Four U.S. communities: Forsyth County, North Carolina; Sacramento County, California; Washington County, Maryland; and Pittsburgh, Pennsylvania. PARTICIPANTS: 5,201 men and women aged 65 years and older. MEASUREMENTS: Demographic data; histories of cardiovascular disease (CVD), chronic lung disease, arthritis, diabetes, and hypertension; measures of subclinical disease including arm and ankle blood pressures, internal carotid wall thickness and stenosis, ejection fraction, left ventricular mass, fractional shortening, and diastolic function, electrocardiographic left ventricular hypertrophy and cardiac injury score, forced expiratory flow and volume; functional status including self-reported physical functioning, hearing and sight limitations and health status, and performance-based measures of function. These variables were examined among men and women in three age groups: 65-74 years, 75-84 years, and 85 + years. Subgroups of participants with and without manifest CVD were also examined. MAIN RESULTS: In women, the prevalence of CVD and other chronic conditions increased with age, and the highest rates occurred among those 85 years and older. In men, prevalence rates increased between the two younger groups, but the oldest group had lower than expected rates for coronary heart disease, cerebrovascular disease, hypertension, and chronic lung disease. In contrast, there were strong age-related linear trends in most of the subclinical measures of blood pressure, atherosclerosis and pulmonary function and in virtually all measures of functional status in both gender groups across the age range. There was a particularly marked decline in functional status between the two older age groups. While subclinical disease was greater and functional status was poorer among those with manifest CVD, with few exceptions, age-related trends were not significantly different between the two groups. CONCLUSIONS: Lower than expected prevalence rates of CVD among those aged 85 years and older, particularly among men, in this study of community-dwelling elderly may represent selection bias or a real plateauing in disease prevalence with age. However, subclinical disease appears to increase and functional status to decline across the age range in both men and women regardless of the presence of CVD. The apparent increase in subclinical disease with age indicates potential for CVD prevention after age 65.

Activities of Daily Living↗

Heart rate variability and circulating catecholamine concentrations during steady state exercise in healthy volunteers.

OBJECTIVES: To assess whether exercise induced suppression of heart rate variability in the low frequency domain (0.06-0.15 Hz) is related to the increase in circulating catecholamine concentrations. DESIGN: Randomised crossover trial of three exercise tests characterised by different workloads. Pharmacological simulation of exercise-induced changes in vagal and sympathetic activity. PARTICIPANTS: Six healthy men with a mean age of 31.2 (SD 3.0) years. INTERVENTIONS: Three different workloads of steady state cycling ergometry: control state without cycling, cycling at a target heart rate of 100 beats/min, and cycling at a target heart rate of 150 beats/min. Intravenous infusion of atropine (target heart rate 100 beats/min) followed by the additional infusion of adrenaline and noradrenaline. MAIN OUTCOME MEASURES: Fast Fourier analysis of heart rate variability; blood pressure; and venous plasma concentrations of lactate, adrenaline, and noradrenaline. RESULTS: During the control exercise period there were no changes in the assessed variables compared with the preceding resting period. During exercise at a heart rate of 100 beats/min systolic blood pressure increased and heart rate variability decreased. During exercise at a heart rate of 150 beats/min systolic blood pressure and lactate, adrenaline, and noradrenaline concentrations increased. In addition, low frequency (LF) was lower than during exercise at 100 beats/min, high frequency (HF 0.15-0.80 Hz) resembled that during exercise at 100 beats/min, and diastolic blood pressure was reduced. Infusion of atropine caused no changes in blood pressure or plasma concentrations of lactate, adrenaline, and noradrenaline and decreased heart rate variability. The additional infusion of adrenaline and noradrenaline completely suppressed heart rate variability and increased blood pressure. CONCLUSIONS: The reduction in LF and HF during exercise at a heart rate of 100 beats/min, which is not characterised by increased plasma catecholamine concentrations, and during atropine infusion suggests that heart rate variability in the supine state is largely influenced by vagal activity. The additional reduction in LF during exercise at 150 beats/min and during catecholamine infusion may reflect a negative feedback of circulating catecholamines on the sympathetic control of heart rate.

Adult↗

Production of 15-HETE by cultured smooth muscle cells from cerebral artery.

Hydroperoxyeicosatetraenoic acids (HPETEs) are potent vasoconstrictors which have been implicated in the pathogenesis of the delayed cerebrovascular spasm which follows subarachnoid haemorrhage. We have previously shown that one of their stable breakdown products, 15-hydroxyeicosatetraenoic acid (15-HETE), is the major lipoxygenase product released from isolated cerebral arteries. To investigate the vascular cell type responsible for their production we have established the culture of smooth muscle cells from cerebral arteries and have measured their release of HETEs upon stimulation with arachidonic acid. The cultured cells isolated from bovine cerebral arteries expressed smooth muscle phenotype as they stained positively for smooth muscle alpha-actin and not factor VIII-related antigen. Furthermore, these cells possessed the calcium and potassium conductances characteristic of smooth muscle cells. Upon incubation with arachidonic acid, the major lipoxygenase product was 15-HETE; no leukotrienes were detected. The formation of 15-HETE was concentration-dependent and was attenuated by nordihydroguaiaretic acid, but not by indomethacin. Similar to intact cerebral artery, cultured cerebrovascular smooth muscle cells have lipoxygenase activity, the major product of which is 15-HETE. These results are consistent with a possible role of the HPETEs in the pathogenesis of cerebral vasospasm.

Animals↗

Development of short-term myocardial hibernation. Its limitation by the severity of ischemia and inotropic stimulation.

BACKGROUND: Short-term hibernating myocardium is characterized by a decrease in contractile function in proportion to the reduced myocardial blood flow. Myocardial creatine phosphate content, initially decreased during the first minutes of ischemia, returns to near-control values, the ischemia-induced net lactate production is attenuated, and the myocardium remains viable despite ongoing hypoperfusion and contractile dysfunction. Hibernating myocardium after 85 minutes of ischemia maintains an inotropic reserve and responds to short-term intracoronary dobutamine infusion with increased work; however, this inotropic response is at the expense of metabolic recovery. We therefore hypothesized that the development of myocardial hibernation is a delicate process that is easily disturbed by unfavorable alterations in the oxygen-supply demand balance. METHODS AND RESULTS: To study the impact of prolonged inotropic stimulation on the development of myocardial hibernation, the left anterior descending coronary artery was cannulated and hypoperfused at constant flow in 12 enflurane-anesthetized swine. The reduction of coronary inflow was followed by a reduction of regional myocardial work (sonomicrometry) from 248 +/- 59 mm Hg.mm to 73 +/- 35 mm Hg.mm (P < .05) at 5 minutes of ischemia. Dobutamine (2.5 +/- 1 micrograms/min) was then infused for an additional 85 minutes. Work was increased at 5 minutes of dobutamine to 139 +/- 34 mm Hg.mm (P < .05 versus 5 minutes of ischemia). However, this increase was only transient, and after 85 minutes of dobutamine, work was decreased below the initial ischemic value (42 +/- 34 mm Hg.mm). At 5 minutes of ischemia, creatine phosphate content was reduced from 8.80 +/- 1.97 to 6.21 +/- 3.87 mumol/g wet wt, and myocardial ATP content was decreased slightly from 4.75 +/- 0.92 to 4.12 +/- 1.29 mumol/g wet wt (both, P = NS). After 5 minutes of dobutamine, further reductions in creatine phosphate content to 3.11 +/- 0.76 mumol/g wet wt and in ATP to 3.14 +/- 0.81 mumol/g wet wt were observed (both, P < .05 versus control). During the remainder of the continuous dobutamine infusion, creatine phosphate content remained unchanged, whereas ATP further decreased significantly to 1.68 +/- 0.96 mumol/g wet wt. The beta-adrenoceptor density of the left anterior descending coronary artery-perfused myocardium was 36.5 +/- 5.8 fmol (-)-[125I]iodocyanopindolol/mg protein under control conditions, and this was unchanged during ischemia and the subsequent dobutamine infusion. Following 90 minutes of ischemia with 85 minutes of dobutamine and 2 hours of reperfusion, infarct size (triphenyl tetrazolium chloride staining) was 26.3 +/- 7.5% of the area at risk. With constant hypoperfusion, dobutamine redistributed blood flow away from the subendocardium (0.20 +/- 0.08 versus 0.11 +/- 0.04 mL.min-1.g-1) toward the subepicardium (0.45 +/- 0.13 versus 0.51 +/- 0.21 mL.min-1.g-1) as well as to the right ventricle (0.26 +/- 0.08 versus 0.32 +/- 0.09 mL.min-1.g-1). Therefore, in two other groups of six and five swine, the severity of ischemia was increased to achieve an 80% or a 90% reduction in regional function, respectively, and the importance of the severity of blood flow reduction per se for the development of myocardial infarction was studied. The infarct size in the animals undergoing 85 minutes of dobutamine (26.3 +/- 7.5%) was increased above the level expected from the blood flow reduction alone (6.3 +/- 6.4%, P < .01). CONCLUSIONS: Both the increased severity of ischemia and the enhanced energy expenditure induced by dobutamine impair the development of myocardial short-term hibernation and precipitate myocardial infarction.

Animals↗

Predictors of in-home and out-of-home service use by family caregivers of Alzheimer's disease patients.

Few studies have examined whether the use of different types of services is predicted by different characteristics of elderly care recipients and primary kin caregivers. Most research aggregates services into a single category, thereby assuming that different services have the same predictors. This investigation differs from the aggregation approach by comparing four groups of elderly care recipients: in-home service of users, out-of-home service users, users of both in- and out-of-home services, and those who do not use services. Data come from personal interviews with 171 family caregivers of mild to moderate dementia patients who reside in the community. Using the modified Andersen framework and multiple group discriminant analysis, results show that care recipients who do not use services and those using only in-home services have inadequate informal supports, more emotionally strained caregivers, and more functionally impaired care recipients compared with users of out-of-home or both in- and out-of-home services.

Alzheimer Disease↗

Detection of C-type natriuretic peptide (CNP) transcript in the rat heart and immune organs.

Previous studies suggested the expression of mRNA, coding for CNP, exclusively in the central nervous system. In the present study, using the polymerase chain reaction (PCR) technique instead of the less sensitive Northern blot hybridization, CNP-specific sequences have also been detected in rat atria and ventricles of the heart as well as in organs of the immune system (thymus, spleen and lymph nodes). Parallel PCR-assays documented ANP-mRNA in these tissues. To verify specificity of the PCR-products, Southern blots have been hybridized with a third internal oligonucleotide and amplification products have been sequenced. The relative level of CNP-mRNA in these tissues was estimated to be in the range of 1-9% of total brain CNP transcripts. The results suggest that the peptide may have a peripheral as well as a central site of action. In light of its pronounced effect on cell proliferation, particular interest should focus on a possible role of CNP in the immune system.

Animals↗