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Biomedical subjects

R Schulz

Publications and source records attributed to R Schulz.

At least 397 records · Page 22Linked to original sources

Characterization of "hibernating" and "stunned" myocardium with focus on the use of calcium antagonists in "stunned" myocardium.

In the initial seconds after a sudden reduction in coronary blood flow, a temporary mismatch between myocardial energy demand and supply exists. The mechanisms underlying the rapidly ensuing reduction in contractile function in the ischemic myocardium are still unknown. In the presence of some residual blood flow, a state of "perfusion-contraction matching" develops. The metabolic status of such hypoperfused myocardium improves, since myocardial lactate production is attenuated and creatine phosphate (CP), after an initial reduction, returns toward control values. The hypoperfused myocardium responds to inotropic stimulation by dobutamine. The recruitment of an inotropic reserve implies increased energy utilization. During inotropic stimulation, after partial normalization, lactate production is again increased, and CP is decreased again. Thus, a supply-demand imbalance that had been at least partially corrected by the ischemia-induced decrease in regional contractile function is precipitated again. A situation of chronic contractile failure in viable myocardium that normalizes upon reperfusion has been termed myocardial "hibernation." Myocardial "stunning" is characterized by a reversible postischemic contractile dysfunction despite full restoration of blood flow. The details of the underlying mechanisms are not clear. An inadequate energy supply and impaired sympathetic neurotransmission have been excluded. Potential mechanisms, which are not mutually exclusive, may include (a) damage of membranes by free radicals, (b) an increase in free cytosolic calcium during ischemia and reperfusion, and (c) a decrease in the calcium sensitivity of the myofibrils. The equally pronounced increases in regional contractility in normal and "stunned" myocardium during postextrasystolic potentiation and the infusion of calcium or the calcium-sensitizing agent AR-L-57, however, suggest an unchanged calcium sensitivity of reperfused myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium↗

Neuroanatomical sites mediating the central actions of beta-endorphin as mapped by changes in glucose utilization: involvement of mu opioid receptors.

Local cerebral glucose utilization, which is a correlate of neuronal activity, was measured to obtain information on the neuroanatomical sites mediating the different behaviors elicited by i.c.v. administration of the opioid peptide beta-endorphin (beta-END). The selective mu and delta opioid receptor antagonists d-Phe-Cys-Tyr-d-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) and ICI 174,864 (N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH), respectively, were used to characterize the opioid receptor type involved in the actions of beta-END. beta-END was found to produce profound increases in glucose utilization in limbic regions such as the lateral septal nucleus, the amygdalo-hippocampal transition area, the nucleus accumbens and the hippocampal formation. The ventral hippocampus proved the most sensitive structure, displaying increases in glucose utilization of up to 200%; changes in the dorsal part amounted up to 100%. Only moderate effects were induced by beta-END in motor areas, such as the substantia nigra, pars reticulata and the nucleus ruber. This regional pattern of changes is assumed to underlie the epileptogenic-, motivational-, mood- and possibly memory-modulating actions of beta-END. The effects of beta-END on local cerebral glucose utilization were blocked by pretreatment with the mu antagonist, CTOP, whereas the selective delta opioid antagonist ICI 174,864 was less effective. An involvement of predominantly mu opioid receptors in the central actions of beta-END is, therefore, suggested.

Animals↗

Description of a variably expressed and labile epitope of thyroglobulin and its occurrence in different thyroid diseases using a monoclonal antibody.

A new category of epitopes of human thyroglobulin is being described defined by a monoclonal antibody (TuTg 1). The epitope shows a very variable expression in normal individuals as well as in different thyroid diseases. According to gel filtration data the epitope is located at the intact molecule and is very sensitive to tryptic digestion. The monoclonal antibody was used in an IRMA system for plasma measurements in the follow-up of thyroid cancer patients. In individuals with high epitope expression the sensitivity to detect recurrency during T4 treatment was higher than a sensitive commercial TG IRMA.

Antibodies, Monoclonal↗

Acetylsalicylic acid and blood coagulation in the horse.

Equine blood may contain salicylic acid (SA) taken up as free acid or represents the metabolite of acetylsalicylic acid (ASA). To obtain information of SA in race horses we screened blood samples of trotting-horses routinely drawn to be analyzed for doping substances. The individual values determined followed a Gaussian distribution displaying a geometric mean of 19 ng SA per ml serum. A probit analysis revealed linear relationship (r = 0.995). Additional studies examined the antithrombotic efficacy of ASA in the horse. An oral dose of 300 mg ASA considerably elevated the bleeding time for more than 2 hours with concomitant SA serum levels between 800 and 1000 ng/ml. It is concluded that salicylate levels even below 1 microgram/ml serum bring about considerable pharmacologic effects such as prolongation of bleeding time, decrease in blood viscosity and possibly dilatation of blood vessels. These effects may improve the tissue supply with blood including oxygen.

Animals↗

Social discomfort and depression in a sample of adults with leg amputations.

We examined the relationship between social discomfort and depression in a sample of 89 adults with leg amputations at two outpatient clinics. It was hypothesized that individuals who reported being uncomfortable with social contacts involving acknowledgement of their amputation or prosthesis were more prone to depression than other patients. A set of questions addressing different aspects of social discomfort demonstrated internal consistency and were used as a scale. Social discomfort was significantly correlated with scores on the Center for Epidemiologic Studies-Depression Scale depression scale (r = .41). Multiple regression analysis showed that social discomfort was a significant independent predictor of depression, after holding constant the effects of age, gender, social support, time since amputation, reason for amputation, and perceived health. These data indicate that health care professionals should view the expression of social discomfort by amputee patients as a possible "marker" for depression. Further studies are planned to develop and validate an expanded social discomfort scale.

Adult↗

Use of enzyme immunoassay and reverse-phase high-performance liquid chromatography to detect and confirm identity of dexamethasone in equine blood.

An enzyme immunoassay (EIA) was developed for detection of dexamethasone in equine blood. Dexamethasone 21-hemisuccinate-bovine serum albumin was used for immunization of rabbits, and prednisolone 21-hemisuccinate-horseradish peroxidase was used as enzyme conjugate. The assay had sensitivity in the low-picogram range (detection limit, 0.3 pg/well, 50% inhibition of binding at 4.5 +/- 0.7 pg/well). Apart from cortisol, which was recognized by the antiserum at concentration > 8.5 ng/ml, the dexamethasone antiserum failed to interfere with endogenous steroids, but cross-reacted with triamcinolone, flumethasone, and betamethasone. Thus, the antiserum was used to perform simultaneous screening for these synthetic glucocorticoids and to confirm their identity by combining reverse-phase high-performance liquid chromatography (RP-HPLC) and EIA. The immunoreactivity obtained by direct serum measurements was characterized by means of 2 independent RP-HPLC systems. Serum extracts were submitted to RP-HPLC systems I and II, and the fractions were tested by EIA. Immunoreactive peaks were identified by comparing their retention time with that of the standard glucocorticoids used for calibration. Coinjection of an internal standard (methylprednisolone) in RP-HPLC system II yielded reproducible relative retention times. The effectiveness of the test system was evaluated, using blood from a horse treated with commonly used veterinary preparations of dexamethasone. Administration of the free alcohol of dexamethasone and of dexamethasone 21-trioxaundecanoate, both given IV, was detected, and the identity of each was confirmed for up to 48 hours. Intramuscular administration of dexamethasone 21-isonicotinate was continued for at least 14 days after injection of a therapeutic dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Physician satisfaction in a managed care environment.

BACKGROUND: The professional literature suggests that changes toward the bureaucratization of medical practice have led to increasing job dissatisfaction, especially in primary care. To investigate this claim, we surveyed physicians in Dane County, Wisconsin, who practice in a bureaucratic setting. Dane County has experienced essentially a demise in independent practice, ie, most physicians practice in organizational settings where expenses and total patient income are pooled. About 85% of physicians have joined one of the six competing health maintenance organizations (HMOs). METHODS: In 1986 all 850 physicians in Dane County were surveyed to determine their perceptions of clinical freedom, satisfaction with income, status in their profession, autonomy, resources, and professional relations, and their overall satisfaction. RESULTS: We found that over 69% of primary care physicians were very satisfied or satisfied with their practices overall compared with 68% of physicians in all specialties. Differences between family practice and other primary care specialties were not statistically significant. Our regression analysis showed that only for satisfaction with income were responses from primary care physicians significantly different from those of physicians in surgical specialties. Perceptions of clinical autonomy and specific organizational settings were more important to predicting satisfaction. Also, age and sex contributed to differences in satisfaction with resources and status, respectively. CONCLUSIONS: We conclude that satisfaction can be fairly high for primary care physicians in bureaucratic settings similar to that of Dane County.

Group Practice↗

Development and mechanism of a specific supersensitivity to nitrovasodilators after inhibition of vascular nitric oxide synthesis in vivo.

The mechanism of the increased sensitivity to nitrovasodilators after removal of endothelial nitric oxide (NO) was investigated in vitro and in vivo. The vasoconstrictor potency of phenylephrine and the force of contraction of rat isolated aortic rings were significantly enhanced after endothelium removal or treatment with inhibitors of endothelial NO synthase. Furthermore, these procedures led to a significant decrease in the basal levels of cGMP in the vascular rings. Moreover, the potency of glyceryl trinitrate (n3Gro) and sodium nitroprusside (SNP) as relaxing agents and the ability of SNP to induce increases in cGMP in aortic rings were significantly enhanced in those rings denuded of endothelium or treated with the inhibitors. These procedures did not affect the vasodilator actions of isoprenaline or 8-bromo-cGMP. In the anesthetized rat, treatment with the inhibitors enhanced significantly the hypotensive responses to n3Gro without affecting those to isoprenaline. These data indicate that the removal of the basal NO-mediated vasodilator tone in the cardiovascular system leads, at the level of the soluble guanylate cyclase, to a specific supersensitivity to nitrovasodilators in vivo. The existence of such a phenomenon has important implications for understanding the local physiological control of blood flow, its pathological disturbances, and the mechanism of action of nitrovasodilators.

Acetylcholine↗

Effect of light on the NADPH-protochlorophyllide oxidoreductase of Arabidopsis thaliana.

A cDNA encoding the NADPH-protochlorophyllide oxidoreductase (Pchlide reductase) of Arabidopsis thaliana has been isolated and sequenced. The cDNA contains the complete reading frame for the precursor of the Pchlide reductase. The deduced amino acid sequence of the Arabidopsis enzyme closely resembles the corresponding sequences of barley and oat. The cDNA has been used as a template for the synthesis of the enzyme protein in Escherichia coli. An antiserum was raised against this enzyme protein and both the antiserum and the cDNA were used as experimental tools to study the effects of light on the Pchlide reductase in A. thaliana. When etiolated seedlings of Arabidopsis were exposed to light the enzyme activity and the concentration of the enzyme protein rapidly declined. Similar light effects have been described previously for other angiosperms. In contrast to most of these species, however, in Arabidopsis only minor changes in Pchlide reductase mRNA content could be observed when etiolated seedlings were exposed to light.

Amino Acid Sequence↗

Inactivation of recombinant plasmid DNA from a human erythropoietin-producing mouse cell line grown on a large scale.

Experiments were carried out to assess the survival of recombinant plasmid DNA during large-scale production of recombinant human erythropoietin (rhuEPO) in a fermentation pilot plant. The analyses revealed DNA-degrading activities in the fermentation broth and in the waste-water, leading to rapid destruction of plasmid DNA added to medium or waste-water. The capability of the plasmid-DNA-spiked samples to transform competent bacteria was drastically reduced. The DNA-degrading activity in the waste-waters could be blocked by addition of EDTA or by boiling, indicating the presence of DNA-degrading enzymes (DNases). No plasmid-specific DNA sequences were detected in waste-water samples by in-vitro amplification with Taq-polymerase. Genomic DNA preparations of cell debris collected from waste-water samples only contained degraded plasmid DNA. Furthermore, it was shown that intact plasmid DNA could be degraded to fragments of less than 1000 bp by incubation at 121 degrees C for 20 min, leading to a decrease in the plasmid-specific transforming capacity by a factor of 10(3) per minute. Thus, DNA from the rhuEPO production pilot plant was efficiently inactivated at three different levels: (i) in the fermentation medium (DNase), (ii) in the waste-water container (DNase), and (iii) by heat inactivation for 20 min at 120 degrees C. These results indicate that the probability of delivery of recombinant DNA into the environment is extremely low in such biotechnological production processes.

Animals↗

Pressure-flow characteristics in the right and left ventricular perfusion territories of the right coronary artery in swine.

Regional pressure-flow relationships within the right coronary artery (RCA) circulation of swine were determined. Enflurane-anaesthetized swine (n = 7) were studied during step-wise reductions of RCA perfusion pressure using an extracorporeal circuit. Regional blood flow was measured using microspheres and contractile function of the right ventricle was measured using sonomicrometry. The RCA perfusion territory was divided into its anatomic components: right ventricular free wall (RV), interventricular septum (with further division in transmural thirds; SEP-LV, SEP-MID and SEP-RV) and right atrium (RA). Pressure-flow relations were constructed for each region and autoregulatory capacity assessed through calculation of an autoregulatory index (AI, closed-loop gain). The pressure-flow relationship for the entire RCA exhibited autoregulation down to a pressure of 40 mmHg. The SEP-LV exhibited a similar relationship with loss of autoregulation at approximately 40 mmHg. The pressure-flow relationship of the RV, however, showed autoregulation to a pressure of 30 mmHg with a decrease of blood flow only at a pressure of 20 mmHg. Little autoregulation was observed in the RA. Autoregulatory gain assessed by AI was similar in RV, SEP-LV and SEP-RV as pressure was reduced from 90 to 55 mmHg (RV = 0.54 +/- 0.41; SEP-LV = 0.58 +/- 0.36; SEP-RV = 0.83 +/- 0.36). With further reductions of pressure, AI was highest in the RV, followed by the SEP-RV and then SEP-LV.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Interventricular redistribution of myocardial blood flow during metabolic vasodilation.

To determine the effect of metabolic vasodilation on the blood flow distribution within the hypoperfused left anterior descending coronary artery (LAD) of the pig (a perfusion bed containing both left and right ventricular myocardium), 28 anesthetized (isoflurane) pigs were studied during intracoronary dobutamine infusion (2.5 +/- 1, SD, micrograms/min) at two levels of reduced, constant coronary inflow. In 8 pigs, coronary inflow was reduced from 59 +/- 9 ml/min to 42 +/- 10 ml/min; coronary perfusion pressure fell to 62 +/- 2 mm Hg (8260 +/- 260 Pa) and then fell further to 54 +/- 6 mm Hg (7190 +/- 800 Pa) during dobutamine infusion. Subendocardial blood flow in the anterior wall of the left ventricle perfused by the LAD decreased from 0.64 +/- 0.12 ml min-1 g-1 with hypoperfusion alone, to 0.40 +/- 0.14 ml min-1 g-1 (P less than 0.002) with the addition of dobutamine. Conversely, blood flow to the right ventricular region supplied by the LAD increased significantly from 0.78 +/- 0.40 ml min-1 g-1 (hypoperfusion alone) to 0.92 +/- 0.50 ml min-1 g-1 (P less than 0.008) with dobutamine. In 10 pigs, a more severe reduction of coronary inflow to 26 +/- 12 ml/min and subsequent dobutamine infusion resulted in a similar redistribution of blood flow from the left to the right ventricular portion of the perfusion bed. Infusion of dobutamine during hypoperfusion, but with a pressure-constant perfusion system, was associated with increases in blood flow to both the right and left ventricular portions of the perfusion territory.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Origin and characterization of atrial natriuretic peptide in the rat parotid gland.

The heart atria represent the major site of synthesis for atrial natriuretic peptide (ANP) which exerts potent natriuretic, diuretic and vasoactive functions. Recently, ANP-immunoreactivity has been detected in extracardial organs involved in water and electrolyte homeostasis, such as the intestine and certain exocrine glands. The present study investigates ANP in the parotid gland. It was found by immunohistochemical techniques that the peptide is localized in ductal cells of the gland. An analysis of the immunoreactive material by high-pressure liquid chromatography and radioimmunoassay revealed the prohormone of ANP (ANP 1-126) and the biologically active fragment (ANP 99-126). Furthermore, Northern blot hybridization disclosed the presence of mRNA coding for ANP. It is suggested that ANP is synthesized and released from the parotid gland and functions in the control of saliva production.

Animals↗

Extragonadal 17 beta-hydroxysteroid dehydrogenase activity in rainbow trout.

Blood cells of male and female rainbow trout showed 17 beta-hydroxysteroid dehydrogenase (17 beta HSD) activity in vitro, reducing 11 beta-hydroxyandrostenedione and 11-ketoandrostenedione (OA) to 11 beta-hydroxytestosterone and 11-ketotestosterone (OT), respectively. Enzyme activity did not vary with gonadal development in either sex. The conversion of tritiated precursors was partly inhibited in the presence of steroid-free serum or radioinert steroid, but inhibition was less strong when radioinert androgens were added to steroid-free serum or when the serum contained endogenous steroids. Treatment of male trout with salmon gonadotropin in vivo and/or incubation with a pituitary extract of mature salmon in vitro did not affect OA conversion when blood cells were incubated in the absence of serum, whereas it was slightly but significantly higher when they were incubated in the presence of serum and pituitary extract. In addition to blood cells and steroidogenic tissues, spleen, intestine, brain, liver, excretory kidney, and skin tissue also produced an OA metabolite isopolar to OT in vitro, so that 17 beta HSD appears to be present in a variety of trout issues. With respect to the biological significance of extragonadal steroid metabolism in vivo, the ligand binding characteristics of circulating steroid binding proteins may be of primary relevance in regulating substrate availability.

17-Hydroxysteroid Dehydrogenases↗

Antagonistic blue- and red-light regulation of cab-gene expression during photosynthetic adaptation in Scenedesmus obliquus.

During adaptation of the photosynthetic apparatus of the green alga Scenedesmus obliquus to various light qualities, the accumulation of chlorophylls and pigment-protein complexes (with specific consideration of chlorophyll a/b-binding (Cab) proteins) and cab-gene expression were determined. The fluence rate dependences for chlorophyll accumulation and cab-gene expression were very different. Very low fluence rates of violet (404 nm), blue (461 nm) and red (650 nm) light below the photosynthetic threshold, i.e. between 10(-3) and 10(-1) mumol m-2 s-1, inhibited all of these reactions in cells grown under heterotrophic conditions. At elevated fluence rates (above 1 mumol m-2 s-1), red light retained its negative regulation, whereas blue light stimulated pigment accumulation. Under autotrophic conditions the pattern was more complex, because chlorophyll accumulation was unaffected by light below the photosynthetic threshold. However, the expression of cab-genes was inhibited by red light but stimulated by blue light. Cells adapted to fluence rates, which ensured photosynthetic energy supply (above 1 mumol m-2 s-1), showed an increase in chlorophyll accumulation, blue light being more effective than red light. The results confirm and extend our previous discovery of two antagonistically acting photoreceptors in Scenedesmus which mediate and coordinate the complex functional and structural changes associated with photosynthetic adaptation. One of these receptor pigments is a blue-light receptor with positive action; the other is a violet-red-light receptor which can operate far below the photosynthetic threshold and exerts a negative regulation.

Blotting, Northern↗

A 2-year longitudinal study of depression among Alzheimer's caregivers.

Results from a 2-year (4 waves) longitudinal study show strong evidence for patient decline and high levels of depressive symptomatology among caregivers. Female caregivers reported high, stable rates of depressive symptomatology throughout the study, whereas male caregivers exhibited significant increases in depression over time. Cross-sectional multivariate analyses revealed significant positive relationships between depression and number of patient problem behaviors, negative social support, and concern about financial resources; negative relationships were found between depression and social support, quality of prior relationship, and satisfaction with social contacts. Three significant independent predictors of change in depression were found: Lower depression scores at Time 1 were related to increases in depression over time; men were more likely than women to experience increases; and a decline in social support resulted in increased depression.

Activities of Daily Living↗

Nitric oxide synthase in cultured endocardial cells of the pig.

1. Endocardial cells release factors which regulate myocardial contractility and guanosine 3':5'-cyclic monophosphate (cyclic GMP) levels. One of these factors is indistinguishable from endothelium-derived relaxing factor (EDRF). 2. The effluent from pig heart endocardial cells cultured on microcarrier beads caused the relaxation of a pig coronary artery ring denuded of endothelium. This relaxation was enhanced by a combination of superoxide dismutase and catalase and was attenuated by haemoglobin, which binds nitric oxide (NO), and by inhibitors of NO synthase, NG-monomethyl-L-arginine (L-NMMA) or NG-nitro-L-arginine. 3. A Ca(2+)-, L-arginine- and NADPH-dependent enzyme activity which generated NO was detected by a specific spectrophotometric assay in cytosol prepared from endocardial cells. The formation of NO was inhibited in a concentration-dependent manner by L-NMMA (but not D-NMMA) and this could be partially reversed upon addition of excess L-arginine. 4. Like endothelial cells from the blood vessels, the endocardial cells possess the ability to synthesize NO, which may act to regulate myocardial contractility.

Amino Acid Oxidoreductases↗