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Biomedical subjects

C Schulz

Publications and source records attributed to C Schulz.

At least 91 records · Page 5Linked to original sources

Activation of noradrenergic neurons in the locus coeruleus by corticotropin-releasing factor. A microdialysis study.

In the present study the effects of different doses of corticotropin-releasing factor (CRF) and the CRF antagonist alpha-helical CRF on locus coeruleus (LC) neurons were studied in anesthetized male Wistar rats. To monitor the release of noradrenaline (NA) and its metabolite 3-methoxy-4-hydroxyphenylethylene glycol (MHPG), a microdialysis probe was implanted into the parietal cortex, a major projection area of the LC. Saline, 0.17, 0.51 nmol CRF and a combination of 5.1 nmol alpha-helical CRF and 0.51 nmol CRF were applied to the LC via a fused silica capillary. While both doses of CRF augmented NA in parietal cortex dialysates (0.51 nmol CRF: from 0.0206 to 0.0266 pmol/sample; 0.17 nmol CRF: from 0.0147 to 0.0170 pmol/sample), saline did not affect NA concentration. The metabolite MHPG also increased, but in a more prolonged time course. The antagonist alpha-helical CRF attenuated the CRF effects. The increase of extraneuronal NA concentration monitored in the cortical samples indicates an augmented depolarization rate of noradrenergic LC neurons. This clearly demonstrates the activation of these neurons by CRF, suggesting physiological interactions of CRF and noradrenergic neurons.

Animals↗

ENDOR studies of the primary donor cation radical in mutant reaction centers of Rhodobacter sphaeroides with altered hydrogen-bond interactions.

The electronic structure of the cation radical of the primary electron donor was investigated in genetically modified reaction centers of Rhodobacter sphaeroides. The site-directed mutations were designed to add or remove hydrogen bonds between the conjugated carbonyl groups of the primary donor, a bacteriochlorophyll dimer, and histidine residues of the protein and were introduced at the symmetry-related sites L168 His-->Phe, HF(L168), and M197 Phe-->His, FH(M197), near the 2-acetyl groups of the dimer and at sites M160 Leu-->His, LH(M160), and L131 Leu-->His, LH(L131), in the vicinity of the 9-keto carbonyls of the dimer. The single mutants and a complete set of double mutants were studied using EPR, ENDOR, and TRIPLE resonance spectroscopy. The changes in the hydrogen bond situation of the primary donor were accompanied by changes in the dimer oxidation midpoint potential, ranging from 410 to 710 mV in the investigated mutants [Lin, X., Murchison, H. A., Nagarajan, V., Parson, W. W., Williams, J. C. & Allen, J. P. (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 10265-10269]. It was found that the addition or removal of a hydrogen bond causes large shifts of the spin density between the two halves of the dimer. Measurements on double mutants showed that the unpaired electron can be gradually shifted from a localization on the L-half of the dimer to a localization on the M-half, depending on the hydrogen bond situation. As a control, the effects of the different hydrogen bonds on P.+ in the mutant HL(M202), which contains a BChlL-BPheM heterodimer as the primary donor with localized spin on the BChl aL [Bylina, E. J., & Youvan, D. C. (1988) Proc. Natl. Acad. Sci. U.S.A. 85, 7226-7230; Schenck, C. C., Gaul, D., Steffen M., Boxer S. G., McDowell L., Kirmaier C., & Holten D. (1990) in Reaction Centers of Photosynthetic Bacteria (Michel-Beyerle M. E., Ed.) pp 229-238, Springer, Berlin] were studied. In this mutant only small local changes of the spin densities (< or = 10%) in the vicinity of the hydrogen bonds were observed. The effects of the introduced hydrogen bonds on the spin density distribution of the dimer in the mutants are discussed in terms of different orbital energies of the two BChl a moieties which are directly influenced by hydrogen bond formation. The observed changes of the spin density distribution for the double mutants are additive with respect to the single mutations.(ABSTRACT TRUNCATED AT 400 WORDS)

Cations↗

Femorodistal vein grafts: the utility of graft surveillance criteria.

PURPOSE: This retrospective review of femorodistal vein grafts was analyzed to determine the usefulness of various graft surveillance criteria. METHOD: The surveillance schedule involved evaluations at 1 month, every 3 months the first year, and then every 6 months. Salvage intervention or graft occlusion occurring within the next follow-up interval defined surveillance end points. One hundred two grafts (329 surveillance visits) had an ankle/brachial index (ABI). A duplex scanning-determined midgraft peak systolic flow velocity (PSFV) was available for 81 grafts (262 visits). Forty-eight grafts (137 visits) had both a PSFV and entire graft duplex scanning (EGDS) to determine stenosis greater than 50%, whereas 40 grafts (91 visits) had simultaneous ABI and EGDS. RESULTS: When a greater than 15% decrease in ABI denoted an abnormal surveillance study result, a positive predictive value (PPV) of 24.3% and negative predictive value of 94.5% were noted. Similarly, a PSFV cutoff of less than 35 cm/sec demonstrated values of 26.3% and 94.2%, respectively. When an EGDS of greater than 50% stenosis or a PSFV of less than 35 cm/sec were the cutoff criteria, the PPV was 36.7% and negative predictive value 99.1%, whereas characterizing abnormal results further with ABI (> 15% decreases) increased the PPV to 83.3%. CONCLUSION: The combination of an EGDS, midgraft PSFV, and ABI provides optimal follow-up for our patients with a femorodistal vein graft.

Ankle↗

Combined amyloidosis of the upper and lower respiratory tract.

Pulmonary and laryngeal manifestations of localized and organ-limited amyloidosis are sometimes seen, although pulmonary and laryngeotracheal amyloidosis are not always associated. Diagnosis can only be established histologically by the characteristic green birefringence in polarized light after Congo red staining and by immunohistochemical techniques. We describe the case of a 77-year-old woman who presented with hoarseness and an unproductive cough due to extensive amyloid deposits in both the upper and lower respiratory tract, immunohistochemically proven as the A lambda-type.

Aged↗

Nitric oxide and prostaglandin systems inhibition on the isolated perfused human placenta from normal and preeclamptic pregnancies.

Isolated human placental cotyledons from normal (NG) and preeclamptic gestants (PG) were perfused in vitro, and the effect of N omega-nitro-L-arginine (L-NA, 100 microM), methylene blue (MB, 50 microM), and indomethacin (INDO, 10 microM), on resting perfusion pressure and on the 5-hydroxytryptamine (5-HT)-induced vasoconstriction was established. In the HG, L-NA and MB increased resting perfusion pressure (p < 0.001) and INDO had no significant effect on resting pressure. In the PG, these agents did not significantly modify resting perfusion pressure. In the PG, 5-HT (10 microM-1 microM) caused greater maximal increases in perfusion pressure than in NG. In the NG, L-NA greatly enhanced the 5-HT-induced pressure, however INDO attenuated this effect. In the PG, L-NA did not modify significantly the 5-HT-induced response, but INDO reduced this response. These results suggest that basal release of nitric-oxide but not of vasodilator prostanoids may contribute to the low resting vascular tone in the NG and attenuates the strong vasoconstrictor effect induced by 5-HT. Impairment of action of nitric oxide could contribute to the enhanced pressor response to 5-HT observed in the PG.

Anti-Inflammatory Agents, Non-Steroidal↗

Zygotic caudal regulation by hunchback and its role in abdominal segment formation of the Drosophila embryo.

caudal (cad) is a maternally and zygotically expressed gene in Drosophila whereby the two phases of expression can functionally replace each other. The zygotic expression forms an abdominal and a posterior domain, whereby only the posterior domain has so far been studied with respect to its regulation and function. We show here that the abdominal cad domain is regulated by the hunchback (hb) gradient through repression at high concentrations and activation at low concentrations of HB protein. To study the function of the abdominal cad domain in the absence of redundant interactions, we have utilized an experimental system in which the embryo lacks the normal bicoid (bcd) and hb expression. An artificial hb gradient is then introduced into such embryos, which results in an induction of an ectopic zygotic cad domain in the more anterior region. Employing this system, we show that the cad domain functions by activating the expression of the abdominal gap genes knirps (kni) and giant (gt). We conclude that cad is the so far missing region-specific activator of abdominal segmentation genes.

Abdomen↗

The stress-, but not corticotropin-releasing hormone-induced activation of the pituitary-adrenal axis in man is blocked by alprazolam.

A number of experimental studies clearly suggest that benzodiazepines attenuate the corticotropin-releasing hormone (CRH) secretion possibly through inhibitory GABAergic neurons. There is some evidence that benzodiazepines act to inhibit stress-induced activation of the hypothalamic-pituitary-adrenal axis. A comparison of the effects of a benzodiazepine on the stress- and CRH-induced activation in man has not been undertaken so far. We thus investigated the effects of the triazolobenzodiazepine alprazolam on both the stress- and CRH-induced changes in ACTH, cortisol, and prolactin secretion in ten healthy volunteers. In addition, hemodynamic parameters were studied. The subjects received either alprazolam (0.5 mg orally) or placebo 90 min prior to administration of CRH (100 ug i.v.) and to the performance of a mental stress technique. Blood samples, blood pressure and heart rate were taken every 15 min. The administration of alprazolam led to a highly significant attenuation of the ACTH increase following the stress interview. While ACTH increased from 12.4 to 26.7 pg/ml 15 min after the stress procedure in the placebo condition, there was almost no increase following alprazolam intake. An identical effect was found for cortisol secretion. Basal levels of prolactin were slightly enhanced in the alprazolam situation, while the stress-induced increase was not attenuated. Basal and stimulated systolic and diastolic blood pressure levels and heart rate were also significantly attenuated by alprazolam intake. Following administration of CRH, the ACTH augmentation was only slightly affected following alprazolam, while there were no changes in cortisol and prolactin secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Pharmacological actions of the selective and non-selective beta-adrenoceptor antagonists celiprolol, bisoprolol and propranolol on human bronchi.

1. The pharmacological actions of the beta-adrenoceptor antagonists, celiprolol, bisoprolol and propranolol were investigated in human lung tissue by radioligand binding experiments as well as in human isolated bronchi by functional experiments in organ baths. 2. Data from lung tissue were compared to those obtained from myocardial membranes. 3. Lung tissue was obtained from 10 patients having undergone lung resection for bronchial carcinoma and myocardial tissue from a patient who had received a heart transplantation. 4. In radioligand binding experiments, celiprolol exhibited a high affinity binding to beta 1-adrenoceptors in heart and a low affinity binding to beta 2-adrenoceptors in lung tissue. The selectivity obtained for the beta 1-adrenoceptor was calculated to a factor of eleven. 5. Compared to bisoprolol and propranolol, celiprolol elicited the lowest affinity for the beta-adrenoceptor, as judged from the K1-values. 6. In the absence and presence of the guanine nucleotide Gpp(NH)p celiprolol did not affect receptor binding. 7. In functional experiments on intact bronchi, celiprolol, bisoprolol and propranolol failed to produce relaxation (+/- forskolin) or a significant difference in efficacy in antagonizing the relaxant effects of isoprenaline. However, a rank order of potencies was revealed (propranolol:bisoprolol:celiprolol = 46:12:1). 8. Plasma concentrations for celiprolol and bisoprolol usually achieved in vivo were below the IC50 value obtained in vitro. In contrast, for propranolol, plasma concentrations were nearly identical with the IC50 value. 9. It is concluded that celiprolol is a selective beta 1-adrenoceptor antagonist on human heart and has no agonistic properties on intact human bronchi. Compounds such as celiprolol and bisoprolol may in comparison to propranolol, possess reasonable therapeutic advantages in the treatment of patients with obstructive lung disease due to their low affinity for beta 2-adrenoceptors.

Adrenergic beta-1 Receptor Antagonists↗

Effects of thyrotropin- and corticotropin-releasing hormone on blood pressure and plasma catecholamines in the anesthetized rat.

The neuropeptides thyrotropin-releasing hormone (TRH) and corticotropin-releasing hormone (CRH) have been found to be potent stimulators of the autonomic nervous system in both experimental animals and humans. We studied the effects of different doses of CRH and TRH given intracerebroventricularly in the urethane-anesthetized rat and a single dose of CRH in the chloral hydrate-anesthetized rat to elucidate the effects of these peptides in the unconscious state. All TRH doses studied enhanced blood pressure and noradrenaline and adrenaline secretion. Surprisingly, there were no blood pressure increases following administration of 0.4, 1.3 and 1.7 nmol CRH. In general, there was a tendency for blood pressure to decrease with the largest drop observed after 1.7 nmol CRH. Our data suggest that only TRH clearly augments blood pressure and catecholamine secretion in the anesthetized animal, while CRH does not exert major effects under the two anesthetic conditions employed.

Animals↗

Autonomous concentration-dependent activation and repression of Krüppel by hunchback in the Drosophila embryo.

The subdivision of the anterior-posterior axis in Drosophila is achieved by a cascade of spatially regulated transcription factors which form short-range gradients at the syncytial blastoderm stage. These factors are assumed to have concentration-dependent regulatory effects on their target genes. However, there is so far little direct in vivo evidence that a single factor can autonomously activate and repress a given target gene. We have analysed here the regulatory capabilities of the gap gene hunchback by creating an artificial gradient of hunchback in the early embryo. This was achieved by providing the maternally expressed mRNA of hunchback with the anterior localization signal of the bicoid RNA. The effects of this artificial hunchback gradient were then studied in different types of mutant background. We show that under these conditions hb is autonomously capable of activating the target gene Krüppel at low concentrations and repressing it at high concentrations. In addition, we show that the artificially created hunchback gradient can organize a large part of the segment pattern, although it is expressed at a different position and in a different shape than the wild-type gradient of hunchback.

Animals↗

[Penetrating thoracic injuries--a 10 year analysis of 179 patients].

179 patients with penetrating chest wall and thoracic injuries were treated at the University Hospital "Rudolf Virchow" in Berlin between 1982 and 1992. Most patients (72.4%) were successfully treated with closed tube thoracostomy alone. 33 (18.4%) patients required thoracotomy, 14 (7.8%) due to injury of the great vessels and 15 (8.3%) due to cardiac injuries. In 10 (5.5%) patients also abdominal organs were compromised, so that also a laparotomy had to be done. Seven (3.9%) patients died. All but one patients who died, died in the OR or within 24 h of admission. So lethality in the group of cardiac wounds was 44.6% (7 out of 15). This underlines the necessity of most rapid transport to the hospital in case of thoracic injury.

Adolescent↗

[Resection with primary anastomosis in complicated diverticulitis. Risk analysis].

107 patients operated for complicated diverticulitis 1988 until 1993 were analysed retrospectively regarding perioperative risk of resection with primary anastomosis (n = 94). 53 of them had peridiverticulitis with stenosis (mortality 0), 41 had emergency operations (mortality 14.6%). Hartmann procedure (n = 13, mortality 7.6%) has been accepted only for the following situations: 1. ileus with secondary damage of the bowel, 2. extended diffuse peritonitis with secondary organ failure, 3. poor blood supply of the bowel, 4. the patient under immunosuppression after transplantation. Regarding these recommendations mortality rate in emergency operations (12.9%) has been lower as compared to 15 to 20% in literature. So regarding the recommendations named above resection with primary anastomosis seems to be a safe procedure in complicated diverticulitis.

Adult↗

Adrenocortical carcinoma in children: clinical aspects and prognosis.

Although adrenocortical carcinoma is seen infrequently in children in most countries, it is occurs with significant frequency in Southern Brazil. This has enabled a study of the pattern of this disease in the pediatric age group. Of 78 patients with adrenocortical carcinoma seen at two hospitals in Curitiba, Brazil, 55 were adequately documented, with minimum of 2 years' follow-up, and formed the basis of this paper. Ninety-five percent of the patients showed some degree of virilization, notably pubic and/or body hair, clitoris or penis enlargement, and adult voice. Cushing's syndrome was present in 73% of these cases. The prognosis is age related and is dependent on the resectability of the tumor. Whereas 82% of the children under the age of 2 years survived, the figure for those over the age of 2 years was only 29%. When total resection of the tumor was possible, the survival rate was 67%, with no survival when only partial excision was performed.

Adrenal Gland Neoplasms↗

[Cholinergic action of Bay K-8644 on the rat heart sinus node automaticity].

The actions of different concentrations of a dihydropyridine agonist (Bay K-8644) on rat heart sinus node automaticity and their interactions with atropine, were studied. The experiments were performed using a portion of the right atrium that contained the sinus node, perfused with Tyrode's solution at 37 degrees C and registering the action potentials with intracellular microelectrodes (Ag-KCL). The series of Bay K with or without atropine were perfused during 10 min. Atropine, 1 x 10(-5) M, did not change sinus frequency after 30 min of perfusion (237 +/- 6 to 229 +/- 7 action potentials/min; n = 24). Bay K, 2.8 x 10(-8) M (10 ug/L) did not change sinus frequency (240 +/- 9 to 246 +/- 12; n = 8, but in the presence of atropine, caused an increment (225 +/- 7 to 256 +/- 12 p < 0.05). Bay K, 7 x 10(-8) M (25 ug/L) and 1.4 x 10(-7) M (50 ug/L, caused an increase in sinus frequency (237 +/- 5 to 279 +/- 15; n = 9 p < 0.05 and 254 +/- 6 to 291 +/- 6; n = 6 p < 0.05 respectively) that occurred sooner in the presence of atropine. It is concluded that Bay-K has a cholinergic effect that interferes with its positive chronotropic action, specially at low concentrations.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Cardiac inotropic as well as coronary and pulmonary artery actions of epinine in human isolated tissues.

The present study was aimed to characterize the effects of epinine, the metabolite of the p.o. active dopamine derivate ibopamine in human cardiovascular tissues such as myocardium, coronary artery and pulmonary artery. Isometric force of contraction was studied in electrically driven papillary muscle strips from nonfailing (brain death), moderately failing (New York Heart Association class II-III, mitral valve replacement) and terminally failing human myocardium (New York Heart Association class IV, heart transplants) as well as in auricular trabeculae (aortocoronary bypass operation). Epinine increased force development in a concentration-dependent manner. In comparison to isoprenaline, epinine had a significantly lower potency but a similar efficacy to enhance force of contraction. Depending on the degree of myocardial failure, the effectiveness of epinine was reduced, whereas the potency was similar. Only in nonfailing myocardium, epinine increased force of contraction as effectively as Ca++. Prestimulation with forskolin or milrinone enhanced the potency of the epinine-mediated inotropic effect. In contrast, the beta-1-selective antagonist CGP 207.12A [2-hydroxy-5-(2-(hydroxy-3-(4-((1-methyl-4-trifluoromethyl)-1-H-imidazol -2-yl)-phenoxy)-propyl)-aminoethoxyl)-benzamide] and the beta-2-selective antagonist ICI 118.551 [erythro-(+-)-1-(7-methylindan-4-yloxy)-3- isopropylaminobutan-2-ol-hydrochloride] shifted the concentration-response curve of epinine significantly to the right, indicating action at both beta-2 and beta-1 adrenoceptors. Epinine exerted higher affinity at beta-2 compared to beta-1 adrenoceptors in radioligand binding experiments ([125I]iodocyanopinodolol). In human coronary artery rings and pulmonary artery rings epinine alone as well as epinine in the presence of propranolol initiated a concentration-dependent increase in tension development in precontracted (prostaglandin F2 alpha, 0.3 mumol/l) as well as in non-precontracted rings. These results suggest that epinine exerts no direct vasodilatory activity in human coronary and pulmonary arteries at concentrations which are capable to produce positive inotropic activity. The supposed beneficial effects of ibopamine in the treatment of heart failure may not be due to positive inotropic actions as the concentrations producing positive inotropy are much higher than the clinically observed plasma concentrations.

Adenylyl Cyclases↗

Force-frequency relationship and inotropic stimulation in the nonfailing and failing human myocardium: implications for the medical treatment of heart failure.

In isolated papillary muscle strips from nonfailing donor hearts (NF) and from the hearts of patients with dilated cardiomyopathy with severe heart failure (NYHA IV), the force-frequency relationship was studied. Experiments were performed under basal conditions and in the presence of 0.01 microM or 0.1 microM isoprenaline and 0.02 microM ouabain. In NF, there was a positive inotropic effect following an increase of the stimulating frequency, whereas in NYHA IV, the force gradually declined under these conditions. Low concentrations (0.01 microM) of isoprenaline prevented the negative inotropic effect in NYHA IV, whereas at 0.1 microM the mechanical function deteriorated in NF and NYHA IV. Ouabain had no effect on the force-frequency relationship compared to basal conditions. It is concluded that a reduction of high frequencies does improve the contractility in the failing myocardium. It is not unreasonable to speculate that this mechanism might be involved in the beneficial effects of drugs which reduce the heart rate, such as beta-adrenoceptor antagonists and cardiac glycosides, in the condition of congestive heart failure in which the sympathetic tone is high.

Adult↗