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Biomedical subjects

R Schulz

Publications and source records attributed to R Schulz.

At least 127 records · Page 7Linked to original sources
PubMed2000

Localization of a short-term memory in Drosophila.

Memories are thought to be due to lasting synaptic modifications in the brain. The search for memory traces has relied predominantly on determining regions that are necessary for the process. However, a more informative approach is to define the smallest sufficient set of brain structures. The rutabaga adenylyl cyclase, an enzyme that is ubiquitously expressed in the Drosophila brain and that mediates synaptic plasticity, is needed exclusively in the Kenyon cells of the mushroom bodies for a component of olfactory short-term memory. This demonstrates that synaptic plasticity in a small brain region can be sufficient for memory formation.

Adenylyl Cyclases↗
PubMed2000

Matrix metalloproteinase-2 contributes to ischemia-reperfusion injury in the heart.

BACKGROUND: Matrix metalloproteinases (MMPs) contribute to collagen degradation and remodeling of the extracellular matrix after myocardial infarction; however, their role in myocardial dysfunction immediately after ischemia and reperfusion is unknown. METHODS AND RESULTS: We measured the release of MMPs into the coronary effluent of isolated, perfused rat hearts during aerobic perfusion and reperfusion after ischemia. Aerobically perfused control hearts expressed pro-MMP-2 and MMP-2, as well as an unidentified 75-kDa gelatinase. These enzymes were also detected in the coronary effluent. After 20 minutes of global no-flow ischemia, there was a marked increase in pro-MMP-2 in the coronary effluent that peaked within the first minute of reperfusion. The release of pro-MMP-2 into the coronary effluent during reperfusion was enhanced with increasing duration of ischemia and correlated negatively with the recovery of mechanical function during reperfusion (r(2)=0.99). MMP-2 antibody (1.5 to 15 microg/mL) and the inhibitors of MMPs doxycycline (10 to 100 micromol/L) and o-phenanthroline (3 to 100 micromol/L) improved whereas MMP-2 worsened the recovery of mechanical function during reperfusion. CONCLUSIONS: These results show that acute release of MMP-2 during reperfusion after ischemia contributes to cardiac mechanical dysfunction. The inhibition of MMPs may be a novel pharmacological strategy for the treatment of ischemia-reperfusion injury.

Analysis of Variance↗
PubMed2000

EEG predicts surgical outcome in lesional frontal lobe epilepsy.

BACKGROUND: Because of the relatively poor results of frontal lobe epilepsy (FLE) surgery, identification of prognostic factors for surgical outcome is of great importance. METHODS: To identify predictive factors for FLE surgery, we analyzed the data of 61 patients (mean age at surgery 19.2) who had undergone presurgical evaluation and resective surgery in the frontal lobe. Postoperative follow-up ranged from 0.5 to 5 years (mean 1.78). Fifty-nine patients had MRI-detectable lesions. Histopathologic examination showed dysplasia (57.4%), tumor (16.4%), or other lesions (26.2%). Thirty postoperatively seizure-free patients were compared with 31 non-seizure-free patients with respect to clinical history, seizure semiology, EEG and neuroimaging data, resected area, and postoperative data including histopathology. RESULTS: Three preoperative and two postoperative variables were related to poor outcome: generalized epileptiform discharges, generalized slowing, use of intracranial electrodes, incomplete resection detected by MRI, and postoperative epileptiform discharges. The only preoperative factor associated with seizure-free outcome was the absence of generalized EEG signs. Multivariate analysis showed that only the absence of generalized EEG signs predicts the outcome independently. Moreover, the occurrence of a somatosensory aura, secondarily generalized seizures, and negative MRI was identified as additional independent risk factors for poor surgical results. CONCLUSIONS: The absence of generalized EEG signs is the most predictive variable for a seizure-free outcome in FLE surgery. Furthermore, nonlesional MRI, somatosensory aura, and secondarily generalized seizures are risk factors for poor surgical results.

Adolescent↗
PubMed2000

Transcriptional regulation of the human alpha5 nicotinic receptor subunit gene in neuronal and non-neuronal tissues.

The human alpha5 nicotinic receptor subunit gene appears to be expressed in several structures of the nervous system, but also in a number of non-neuronal tissues, with maximal expressions occurring in the entire gastrointestinal tract, thymus and testis. To understand whether specific transcriptional mechanisms are involved in the tissue-specific expression of the alpha5 subunit in neuronal and non-neuronal cells, we isolated the 5'-regulatory region of the human gene and characterized its functional properties. We demonstrate that specific DNA elements, with positive or negative activities depending on the cell type, are responsible for the diversified expression of the alpha5 subunit in different tissues. We therefore conclude that the expression of the alpha5 subunit relies on a highly complex promoter that uses distinct regulatory elements to comply with the different functional and developmental requirements of the various tissues and organs.

HeLa Cells↗
PubMed2000

No involvement of endogenous nitric oxide in classical ischemic preconditioning in swine.

Endogenous nitric oxide (NO) is involved in the protection by classical ischemic preconditioning (IP) against ischemia-induced arrhythmias in anesthetized dogs. Furthermore, NO triggers and mediates protection against infarction and stunning in delayed IP in conscious rabbits. Up to now it is unclear whether or not endogenous NO is also involved in the protection against infarction by classical IP in vivo. In 45 enflurane-anesthetized swine, severe left anterior descending coronary artery hypoperfusion for 90 min followed by 2 h of reperfusion resulted in an infarct size (IS, triphenyl tetrazolium chloride-staining) of 20.5+/-5.4% (S.E.M.) of the area at risk. Inhibition of NO synthase by l -nitro arginine (l -NA, 30 mg/kg i.v.) increased left ventricular (LV) peak pressure from 93+/-3 to 120+/-1 mmHg (P<0.05), but did not alter IS (22.4+/-5. 6%). With aortic constriction to match the increase in LV peak pressure with l -NA, IS was unchanged (18.1+/-5.1%). IP by 10 min ischemia and 15 min reperfusion preceding the 90 min target ischemia reduced IS to 2.0+/-0.8% (P<0.05 v. non-preconditioned groups). This reduction of IS by IP was not affected by l -NA (1.3+/-0.9%, P<0.05 v. non-preconditioned groups). Area at risk and myocardial blood flow (microspheres) during ischemia were not different among groups. Relationships between IS and subendocardial blood flow with l -NA or aortic constriction, respectively, were not different from that with placebo, but were significantly shifted downwards by IP with and without l -NA. Thus, endogenous NO does not alter infarct size development per se and is not involved in the protection against infarction by classical IP in pigs in vivo.

Animals↗
PubMed2000

Glutathione protects against myocardial ischemia-reperfusion injury by detoxifying peroxynitrite.

Peroxynitrite (ONOO(-)) formation during acute reperfusion of the ischemic heart contributes to the poor recovery of mechanical function. As glutathione (GSH) detoxifies ONOO(-), we studied whether it could protect isolated rat hearts subjected to exogenous ONOO(-)or to ischemia-reperfusion. We showed that GSH (300 microm, n=5) abolished the detrimental effect of ONOO(-)(80 microm, n=5) on mechanical function of aerobically perfused hearts. Hearts were subjected to 25 min aerobic perfusion, 20 min global, no-flow ischemia and 30 min reperfusion. GSH (3-300 microm, n=7-12) or saline vehicle (control, n=22) were infused for 10 min prior to ischemia and throughout reperfusion. During reperfusion, GSH caused a concentration-dependent improvement in the recovery of mechanical function, which was not associated with significant changes in the intracellular concentration of GSH. The concentration of dityrosine (a marker of ONOO(-) formation) in the coronary effluent during reperfusion was significantly reduced in GSH-treated hearts. The concentration of myocardial cGMP was significantly elevated by GSH during ischemia and early reperfusion. GSH improves the recovery of myocardial mechanical function after ischemia-reperfusion, an effect which may be related to the detoxification of ONOO(-)by GSH and the stimulation of soluble guanylate cyclase.

Animals↗
PubMed2000

The stress-responsive MAP kinase p38 is activated by low-flow ischemia in the in situ porcine heart.

Stress-responsive p38 MAP kinase is activated by phosphorylation during global and severe regional myocardial ischemia. However, it is unknown whether or not moderate, low-flow ischemia also activates p38 MAP kinase. Therefore, we investigated p38 MAP kinase activation in an established model of short-term hibernation and stunning. In anesthetized swine, coronary blood flow into the left anterior descending coronary artery was decreased in order to reduce regional contractile function by identical with 50%. Transmural myocardial biopsies were taken before (controls) and during ischemia as well as after reperfusion. Creatine phosphate content, after an early ischemic reduction, recovered to control values at 90 min ischemia. The expression of phospholamban, SERCA2a, calsequestrin, and troponin inhibitor was unchanged under these conditions (Northern and Western blotting). At 8 min of ischemia, however, p38 MAP kinase was activated to 221% of the pre-ischemic value as judged by its elevated phosphorylation state. Then, it returned to control values by 85 min ischemia. We conclude that low-flow ischemia transiently activates the stress-responsive p38 MAP kinase which might act to trigger cardioprotective events.

Animals↗
PubMed2000

Myocardial hibernation--adaptation to ischemia.

The concept of myocardial hibernation implies a downregulation of contractile function as an adaptation to a reduction in myocardial blood flow that serves to maintain myocardial integrity and viability during persistent ischemia. Unequivocal evidence for this concept exists in scenarios of myocardial ischemia that last for several hours; the recovery of energy and substrate metabolism, the potential for recruitment of inotropic reserve at the expense of metabolic recovery, and lack of necrosis are established criteria of short-term hibernation. Furthermore, experimental studies have demonstrated regional myocardial dysfunction at reduced resting blood flow that recovered upon reperfusion, which is consistent with chronic hibernation. In patients, the importance of reduced baseline blood flow vs. that of superimposed repetitive stunning is somewhat controversial; however, in most studies blood flow is reduced, and the myocardium must be ischemic often enough to have persistent dysfunction. Morphologically, hibernating myocardium displays features of dedifferentiation with loss of cardiomyocytes and myofibrils and of degeneration with increased interstitial fibrosis. The mechanisms of short-term hibernation, apart from reduced calcium responsiveness, are not clear at present. With the identification of the underlying mechanism(s) of hibernation, it can potentially be recruited and reinforced pharmacologically to delay impending myocardial infarction.

Acute Disease↗
PubMed2000

[Neuromuscular reinnervation of mimetic muscles. A histomorphologic study of the zygomatic muscle of the rabbit].

To evaluate occurrences of reinnervation and degeneration, the portio auricularis of the zygomatic muscle was reinnervated (either primary or secondary reinnervation) with an interval of 6 weeks, using a neuromuscular transplant of the sternohyoid muscle, which was left at the ansa hypoglossi. Histological examination was performed 6 and 12 weeks later. Enzymatic stains for myofibrillar ATPase were used for differentiation of muscle fibre types. Histomorphological features of denervation and reinnervation were analysed. Six weeks after denervation and primary neuromuscular transplantation, type grouping in regions close to the transplanted muscle were detectable as signs of reinnervation. After a period of 12 weeks, the progressing reinnervation was proved by type grouping in distal areas of the muscle far from the area of transplantation. At the same time, differentiation of fibre typing in the type grouping areas increased. All denervated and reinnervated muscles had pathological variations of fibre diameter. Primary reinnervated muscles showed tendency of normalization in variation of diameter. Compared with primary reinnervated muscles, secondary reinnervated muscles with an interval of 6 weeks showed pronounced polymorphology of fibres and a high pathological increase of the variation of fibre diameters. The interfascicular space was significantly spread. The tendency of reinnervation with incidence of fibre type grouping was comparable to primary reinnervated muscles and also occurred 6 weeks after transplantation.

Animals↗
PubMed2000

X-ray densitometry for the measurement of regional myocardial perfusion.

The evaluation of regional myocardial blood flow (RMBF) during cardiac catheterization is of particular diagnostic interest. The purpose of this investigation was to validate x-ray densitometric parameters for the evaluation of RMBF. In five anesthetized dogs, arterial flow in the circumflex coronary artery was measured continuously with an electromagnetic flowmeter, and RMBF was determined by colored microspheres. Five different perfusion levels were created by mechanical obstruction of the coronary artery or by intravenous infusion of adenosine. At each steady-state perfusion level, digital subtraction coronary angiograms were obtained for densitometric analysis. Results documented a close correlation between the related time parameters 1/Mean Transit Time (1/MTT, r2 = 0.969), and 1/Rise Time (1/RT, r2 = 0.965) and RMBF over a wide range between 0.36 ml/(min x g) and 11.16 ml/(min x g). Maximum myocardial contrast density (Imax) also showed a good, but inverse correlation (r2 = 0.889) with RMBF and, therefore, did not reflect vascular volume. Contrast medium Appearance Time (AT) showed no correlation to RMBF (r2 = 0.017). Repeat densitometric measurements for different perfusion levels revealed a good reproducibility for MTT (accuracy: 0.001 s; precision: 0.447 s or 6.7 %) and RT (accuracy: 0.014 s; precision: 0.202 s or 10.4 %), while AT (accuracy: 0.072 s; precision: 0.420 s or 68.5%) and Imax (accuracy: 0.022 GL; precision: 1.197 GL or 44.5%) showed substantial variation. Myocardial perfusion reserve (MPR) calculated from RT (r2 = 0.90) or MTT (r2 = 0.94) showed better correlations to RMBF reserve than MPR calculated from AT (r2 = 0.04). In conclusion, only 1/MTT and 1/RT showed a good reproducibility and a close correlation to RMBF. Therefore, only these parameters can be recommended for calculations of RMBF and its reserve under clinical conditions.

Absorptiometry, Photon↗
PubMed2000

Toxicity of fenvalerate to caddisfly larvae: chronic effects of 1- vs 10-h pulse-exposure with constant doses.

Episodic pollution events such as runoff or spraydrift can lead to a short-term (few hours) contamination of aquatic ecosystems with pesticides. So far, different short-term exposures with respect to long-term effects have not been studied. In the present study, caddisfly larvae, typical for agricultural streams (Limnephilus lunatus Curtis, 2nd and 3rd instar) were exposed for 1- vs 10-h to three different equivalent doses (microg h) of fenvalerate. After transfer into an artificial stream microcosm with pesticide-free water, chronic effects were observed over 240 days. Comparison of 1- and 10-h exposure revealed that 1-h contamination leads to stronger effects. The differences were significant for the sublethal endpoints emergence pattern and dry weight of adults (ANOVA, Fisher's PLSD; P < 0.05). In terms of exposure dose, the difference between 1- and 10-h exposure equals a factor of 6 as a mean of all endpoints studied. The following significant effect levels for the 1-h exposure were obtained for the different endpoints investigated: reduced emergence success and production at 0.1 microg l(-1), temporal pattern of emergence at 0.001 microg l(-1), dry weight of adults at 0.01 microg l(-1).

Animals↗
PubMed2000

The biology of myocardial hibernation.

Patients with chronic coronary artery disease frequently have contractile dysfunction that recovers upon reperfusion. The concept of myocardial hibernation views the observed reduction in contractile function not as the result of an ongoing energetic deficit, but as an adaptive down-regulation that serves to maintain myocardial integrity and viability. In the experiment, sustained perfusion-contraction matching, recovery of energy and substrate metabolism during ongoing ischemia, the potential for recruitment of inotropic reserve, lack of necrosis, and therefore recovery of function upon reperfusion are established features of hibernation. Apart from reduced calcium responsiveness, the underlying mechanisms are still unclear. In patients, the importance of reduced baseline blood flow vs. that of superimposed repetitive stunning is somewhat controversial; however, in most studies blood flow is reduced, and the myocardium must be ischemic often enough to have persistent dysfunction. Morphologically, hibernating myocardium displays features of dedifferentiation, with loss of cardiomyocytes and myofibrils, and of degeneration, with increased interstitial fibrosis. Patients with hibernating myocardium must be identified and undergo revascularization. With a better understanding of the underlying mechanisms of hibernation, these adaptive responses to ischemia can potentially be recruited and reinforced pharmacologically to delay impending myocardial infarction.

Calcium↗
PubMed2000

Triamcinolone acetonide aqueous nasal spray versus loratadine in seasonal allergic rhinitis: efficacy and quality of life.

BACKGROUND: The new aqueous formulation of triamcinolone acetonide (TAA) was compared with loratadine in patients with seasonal allergic rhinitis. OBJECTIVE: The primary objective of the study was to compare the safety and efficacy of TAA aqueous with loratadine in relieving the symptoms of seasonal allergic rhinitis. METHODS: A total of 351 patients were enrolled into this 4-week, double-blind, double-dummy, randomized, parallel group study. Patients received either TAA aqueous nasal spray (220 microg) or loratadine (10 mg) once daily. Efficacy variables were rhinitis symptom changes from baseline, physician global evaluations, and the patient dropout rate due to insufficient treatment effect. Safety and quality of life also was evaluated. RESULTS: Both TAA aqueous-treated and loratadine-treated patients had improvement in symptoms as early as day 1. Overall, TAA aqueous was significantly (P < .05) more effective than loratadine in reducing total nasal symptoms and individual symptoms of nasal congestion, nasal itch, and sneezing. Ocular symptoms improved from baseline in both groups. There was no statistically significant difference between groups based on physician global evaluation. A similar number of patients in each group discontinued the study due to ineffective treatment. Triamcinolone acetonide aqueous patients maintained a significantly (P < .05) better quality of life in three of the dimensions (activity, nasal symptoms, and practical problems) and for overall quality of life. There were no differences between the two treatment groups in the incidence of adverse events, none of which were clinically significant. CONCLUSIONS: Both TAA aqueous and loratadine were effective and well-tolerated in the treatment of patients with seasonal allergic rhinitis. Triamcinolone acetonide aqueous was significantly (P < .05) more effective than loratadine in controlling nasal symptoms of seasonal allergic rhinitis and maintaining a better quality of life for the patients.

Administration, Intranasal↗
PubMed2000

Group support interventions for women with breast cancer: who benefits from what?

Research on the benefits of social support groups has been inconclusive. One reason is that individual differences in intervention responses have rarely been examined. The authors determined the extent to which individual difference variables moderated the effects of an information-based educational group and an emotion-focused peer discussion group on the mental and physical functioning of women with breast cancer (n = 230). The authors administered the SF-36 (S.E. Ware, K.K. Snow, M. Kosinski, & B. Gandek, 1993), a multidimensional quality of life instrument, pre- and postintervention. Educational groups showed greater benefits on the physical functioning of women who started the study with more difficulties compared with less difficulties (e.g., lacked support or fewer personal resources). Peer discussion groups were helpful for women who lacked support from their partners or physicians but harmful for women who had high levels of support. Implications of these results for clinical interventions are discussed.

Adult↗
PubMed2000

Negative and positive health effects of caring for a disabled spouse: longitudinal findings from the caregiver health effects study.

Data from the first 2 waves of the Caregiver Health Effects Study (n = 680) were analyzed to examine the effects of changes in caregiving involvement on changes in caregiver health-related outcomes in a population-based sample of elders caring for a disabled spouse. Caregiving involvement was indexed by levels of (a) spouse physical impairment, (b) help provided to the spouse, and (c) strain associated with providing help. Health-related outcomes included perceived health, health-risk behaviors, anxiety symptoms, and depression symptoms. Increases in spouse impairment and caregiver strain were generally related to poorer outcomes over time (poorer perceived health, increased health-risk behaviors, and increased anxiety and depression), whereas increased helping was related to better outcomes (decreased anxiety and depression). Results suggest that caring for a disabled spouse is a complex phenomenon that can have both deleterious and beneficial consequences.

Aged↗
PubMed2000

A comparison of primary stressors, secondary stressors, and depressive symptoms between elderly caregiving husbands and wives: the Caregiver Health Effects Study.

The present study examined gender differences in the experience of primary and secondary caregiving stressors, depressive symptoms, and their interrelationships using a sample of 283 elderly spouse caregivers (145 women, 138 men). Two primary stressors, two secondary stressors, and depressive symptoms were assessed. In general, t-tests indicated that caregiving husbands experience fewer stressors and depressive symptoms than their female counterparts. Multiple group analysis revealed that the primary stressors were more useful in explaining variance associated with the secondary stressors for women than men and that the path coefficients linking amount of caregiving assistance to caregivers' activity restriction was significantly different across men and women. Other paths linking primary stressors, secondary stressors, and depressive symptoms, however, were statistically equivalent across men and women. Hence, although caregiving women and men may vary in their reports of caregiving stressors, the complexity of the caregiving experience appears to be quite uniform for both groups.

Aged↗