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Biomedical subjects

M Schwarz

Publications and source records attributed to M Schwarz.

At least 253 records · Page 14Linked to original sources
PubMed1994

1-Hydroxymethylpyrene and its sulfuric acid ester: toxicological effects in vitro and in vivo, and metabolic aspects.

1-Hydroxymethylpyrene (HMP) is activated to a potent mutagen, detectable in Salmonella typhimurium, in the presence of hepatic cytosol, cofactor for sulfotransferases, and chloride anions. The number of induced mutations is linear to the amount of cytosol used over a wide range, allowing for the quantification of this activity. The activity is expressed with high selectivity in certain tissues and cell types. In adult rats, the highest level is found in the liver, the activity in females exceeding that in males about threefold. About half of the activity in the liver of females is provided by hydroxysteroid sulfotransferase a (STa), whereas other enzymes may be more important in males on account of their very low level of STa. The expression of STa is decreased in ATPase-negative, presumably preneoplastic, hepatic foci in female rats. In contrast to its high mutagenicity in bacteria, SMP shows only weak mutagenic activity in mammalian cells (Chinese hamster V79 cells), independently of whether it is externally added, or generated from HMP within the cells by heterologously expressed STa. Sulfation, however, strongly enhances the cytotoxicity of HMP in mammalian cells. The high cytotoxicity and low mutagenicity in mammalian cells in culture have possible correlates in vivo: while HMP is only a weak initiator of ATPase-negative hepatic foci in newborn rats, it shows substantial promoting activity with regard to such foci in female, but not in male rats. We postulate that this promotion results from selective toxification by STa in the normal hepatic parenchyma of female rats, and resistance of ATPase/STa-negative foci.

Adenosine Triphosphatases↗
PubMed1994

Visual and somatosensory evoked potentials are mediated by excitatory amino acid receptors in the thalamus.

In pentobarbital-anaesthetized rats early somatosensory evoked potentials (SEPs) were recorded from the sensory cortex in response to electrical stimulation of the contralateral forepaw and visual evoked potentials (VEPs) from the primary visual cortex in response to single light flashes. Microapplication of the specific non-NMDA antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX) into the ventro-basal thalamus (VB) resulted in a pronounced decrease in amplitude and an increase in latency of SEPs, whereas injection of DNQX into the dorsal lateral geniculate nucleus (DGL) induced a pronounced decrease in amplitude and an increase in latency of VEPs. These changes were: (1) dose-dependent (DNQX 0.01-1.0 nmol), (2) receptor-specific, and (3) site-specific. In contrast, the specific NMDA antagonist 2-amino-7-phosphonoheptanoate (AP7; 0.5-5 nmol) did not affect SEPs after microapplication into the BV and less potently reduced the amplitude and increased the latency of VEPs after microapplication into the DGL. The present findings are consistent with the assumption that an excitatory amino acid serves as transmitter at synapses in the rat thalamus mediating the nervous impulses responsible for the generation of SEPs and of VEPs. In addition the results suggest that this transmitter preferentially interacts with non-NMDA receptors.

2-Amino-5-phosphonovalerate↗
PubMed1994

Effect of time of insemination relative to ovulation on fertility with liquid and frozen boar semen.

Precise data on fertility results following peri- and postovulatory insemination in spontaneously ovulating gilts is lacking. Using transcutaneous sonography every 4 h during estrus as a tool for diagnosis of ovulation, the effects of different time intervals of insemination relative to ovulation were investigated with liquid semen (Experiment 1, n=76 gilts) and frozen semen (Experiment 2, n=80 gilts). In Experiment 3 (n=24 gilts) the number of Day-28 embryos related to the various intervals between insemination and ovulation was determined after the use of liquid semen. Using liquid semen the fertilization rates based on Day-2 to Day-5 embryos and the number of accessory spermatozoa decreased significantly in gilts inseminated with 2 x 10(9) spermatozoa per dosage in intervals of more than 12 h before or more than 4 h after ovulation. In the time interval 4 to 0 h before ovulation, comparable fertilization rates were obtained using frozen semen (88.1%) and liquid semen (92.5%). Fertilization rates and numbers of accessory spermatozoa decreased significantly when gilts were inseminated with frozen semen more than 4 h before or 0 to 4 h after the detection of ovulation. The percentage of Day-28 embryos was significantly higher following preovulatory insemination compared to inseminations 0 to 4 h and 4 to 8 h after ovulation. It is concluded that the optimal time of insemination using liquid semen is 12 to 0 h before ovulation, and 4 to 0 h before ovulation using frozen semen. The results stress the importance of further research on sperm transport and ovulation stimulating mechanisms, as well as studies on the time of ovulation relative to estrus-weaning intervals and estrus duration.

Journal Article↗
PubMed1994

Influence of visual and somatosensory input on leg EMG responses in dynamic posturography in normals.

The contribution of visual and somatosensory input to stabilization after sudden postural disturbances was investigated. Fast transient platform movements (50 degrees/sec, 4 degrees), rotating toe-up around the ankle-joint, evoke EMG responses in the triceps surae (TS) and anterior tibial (TA) muscles. The short and medium latency responses (SL, ML) in the TS destabilize, the long latency responses (LL) in the TA stabilize the upright posture. The influence of vision was tested in normals comparing the conditions eyes open with eyes closed. The influence of additional somatosensory input was tested with the operator's index finger touching the back of the subject with eyes closed. Absent visual input (eyes closed) resulted in a decrease in latency of the stabilizing LL response and an increase in the integrated EMG (iEMG). With eyes closed the latency of the LL response decreased by 4 msec on average (mean eyes open: 111.6 msec (S.D. = 17.3), eyes closed: 107.6 msec (S.D. = 17.5); P < 0.001 (Wilcoxon test)), the iEMG increased by 10% (mean eyes open: 13.9 microV.sec (S.D. = 7.6), eyes closed: 15.5 microV.sec (S.D. = 8.6); P < 0.001). Additional somatosensory input as an external reference for body orientation in space resulted in an increase in latency and decrease in iEMG: the latency increased by 7 msec on average (mean eyes closed: 107.6 msec (S.D. = 17.5), index finger and eyes closed: 114.7 msec (S.D. = 19.9); P < 0.001), the iEMG decreased by 20% (mean eyes closed 15.5 microV.sec (S.D. = 8.6), index finger and eyes closed: 12.3 microV.sec (S.D. = 7.5); P < 0.001). There was no significant change in latency of SL and ML. We conclude that postural EMG responses in leg muscles after fast transient platform movements change according to different functional demands, modulated via visual and somatosensory input.

Adolescent↗
PubMed1994

Mutations and impaired expression in the ACHE and BCHE genes: neurological implications.

The acetylcholine hydrolysing cholinesterases control the termination of cholinergic signalling in multiple tissues and are targets for a variety of drugs, natural and man-made poisons and common insecticides. Molecular cloning and gene mapping studies revealed the primary structure of human acetyl- and butyrylcholinesterase and localized the corresponding ACHE and BCHE genes to the chromosomal positions 3q26-ter and 7q22, respectively. Several different point mutations in the coding region of BCHE were found to be particularly abundant in the Israeli population. Analytical expression studies in microinjected Xenopus oocytes have demonstrated that the biochemical properties of cholinesterases may be modified by rationalized site-directed mutagenesis and in chimeric ACHE/BCHE constructs. These properties are differently altered in the various allelic BCHE variants, conferring resistance to several anti-cholinesterases, which may explain the evolutionary emergence of these multiple alleles. At the clinical level, abnormal expression of both ACHE and BCHE and the in vivo amplification of the ACHE and BCHE genes has been variously associated with abnormal megakaryocytopoiesis, leukemias and brain and ovarian tumors. Moreover, antisense oligonucleotides blocking the expression of these genes were shown to interfere with hemocytopoiesis in culture, implicating these genes in cholinergic influence on cell growth and proliferation.

Acetylcholinesterase↗
PubMed1994

Site-directed mutagenesis of active site residues reveals plasticity of human butyrylcholinesterase in substrate and inhibitor interactions.

In search of the molecular mechanisms underlying the broad substrate and inhibitor specificities of butyrylcholinesterase (BuChE), we employed site-directed mutagenesis to modify the catalytic triad residue Ser198, the acyl pocket Leu286 and adjacent Phe329 residues, and Met437 and Tyr440 located near the choline binding site. Mutant proteins were produced in microinjected Xenopus oocytes, and Km values towards butyrylthiocholine and IC50 values for the organophosphates diisopropylfluorophosphonate (DFP), diethoxyphosphinylthiocholine iodide (echothiophate), and tetraisopropylpyrophosphoramide (iso-OMPA) were determined. Substitution of Ser198 by cysteine and Met437 by aspartate nearly abolished activity, and other mutations of Ser198 completely abolished it. Tyr440 and Leu286 mutants remained active, but with higher Km and IC50 values. Rates of inhibition by DFP were roughly parallel to IC50 values for several Leu286 mutants. Both Km and IC50 values increased for Leu286 mutants in the order Asp < Gln < Lys. In contrast, cysteine, leucine, and glutamine mutants of Phe329 displayed unmodified Km values toward butyrylthiocholine, but up to 10-fold decreased IC50 values for DFP, iso-OMPA, and echothiophate. These findings add Tyr440 and Phe329 to the list of residues interacting with substrate and ligands, demonstrate plasticity in the active site region of BuChE, and foreshadow the design of recombinant BuChEs with tailored scavenging properties.

Animals↗
PubMed1994

Application of an artificial neural network in epiluminescence microscopy pattern analysis of pigmented skin lesions: a pilot study.

In vivo epiluminescence microscopy (ELM) is a non-invasive technique which improves the clinical diagnosis of naevi and malignant melanoma by providing diagnostic criteria that cannot be appreciated by the naked eye. The present study investigated whether ELM criteria pattern analysis can be employed in an objective, observer-trained, computer-aided diagnostic system, and whether artificial neural networks (ANN) can be applied to the diagnosis of pigmented skin lesions (PSL). The ELM criteria patterns of 200 PSL oil immersion images (60 common naevi, 60 dysplastic naevi, and 80 malignant melanomas) were analysed using a standardized questionnaire. One hundred randomly assigned PSL were used as a training set for an ANN, the remaining 100 PSL serving as the test set. The ANN was trained by backward propagation according to the histological diagnosis, and its performance was compared with that of human investigators. Out of the test set the human investigators correctly diagnosed 88% of PSL and the ANN 86%. In a dichotomized model comparing common, compound, and dysplastic naevi vs. malignant melanoma, i.e. benign vs. malignant PSL, the sensitivity and specificity of human diagnosis was 95 and 90%, respectively, whereas the sensitivity and specificity of the ANN diagnosis was 95 and 88%. Our data indicate that artificial neural networks can be trained to diagnose PSL at a human expert level, based on patterns provided by ELM criteria. We suggest that this technique offers a new approach to the diagnosis of PSL.

Diagnosis, Computer-Assisted↗
PubMed1994

Enhancement of endothelium-dependent vasodilation by low-dose nitroglycerin in patients with congestive heart failure.

BACKGROUND: Since organic nitroesters and endothelium-derived nitric oxide mediate vasodilation through a final common pathway, that is, by activation of soluble guanylate cyclase in vascular smooth muscle, nitroglycerin (NTG) could specifically enhance the endothelium-dependent vasodilatory response to acetylcholine (Ach) in patients with congestive heart failure (CHF) and endothelial cell dysfunction. Accordingly, the net effects of an intra-arterial infusion of NTG (10(-9) mol/L) on endothelium-dependent and endothelium-independent vasodilation were assessed in the forearm circulation of patients with CHF. METHODS AND RESULTS: The forearm blood flow responses to intra-arterial administration of graded concentrations of Ach (10(-7) to 10(-5) mol/L) were determined by venous occlusion plethysmography (mL/min per 100 mL) in 18 patients with CHF and 5 age-matched normal subjects before and during intra-arterial infusion of NTG (10(-9) mol/L) for 20 minutes. In eight patients, the duration of the infusion of NTG (n = 5) or vehicle control solution (n = 3) was extended to 12 hours with measurement of the forearm blood flow responses to Ach at 20 minutes, 4 hours, and 12 hours. In five additional patients, forearm blood flow response to intra-arterial administration of two doses of phentolamine (0.05 and 0.5 mg) were determined before and during a 20-minute NTG infusion. Regional administration of NTG 10(-9) mol/L did not change resting forearm blood flow in either normal subjects or patients with CHF. Before administration of NTG 10(-9) mol/L, intra-arterial infusions of Ach 10(-7), 10(-5) and 10(-5) mol/L increased forearm blood flow to 14.7 +/- 6.2, 20.2 +/- 4.7, and 38.4 +/- 7.9 mL/min per 100 mL in normal subjects and to 4.1 +/- 0.8, 5.0 +/- 1.1, and 10.6 +/- 2.3 mL/min per 100 mL in patients with CHF. After administration of NTG 10(-9) mol/L for 20 minutes, the vasodilatory response to Ach significantly increased to 5.6 +/- 1.0, 6.9 +/- 1.6, and 17.7 +/- 3.4 mL/min per 100 mL in patients with CHF but did not change in normal subjects. The enhanced forearm blood flow responses to administration of Ach observed after 20 minutes of NTG administration in patients with CHF were sustained throughout a 12-hour NTG infusion. In contrast, regional administration of NTG did not change the vasodilatory responses to phentolamine. CONCLUSIONS: NTG, when administered intra-arterially for 20 minutes at a dose that does not affect resting forearm blood flow, specifically increased the vasodilatory response to intra-arterial administration of Ach in patients with CHF but not in normal subjects. The vasodilatory response to Ach was consistently enhanced by low-dose NTG throughout a 12-hour period. The vasodilating effects of organic nitroesters on the peripheral vasculature of patients with CHF may result in part from an interaction with the vascular endothelium.

Acetylcholine↗
PubMed1994

Pathophysiological correlates of increased serum tumor necrosis factor in patients with congestive heart failure. Relation to nitric oxide-dependent vasodilation in the forearm circulation.

BACKGROUND: Tumor necrosis factor-alpha (TNF alpha), which we and others have shown to be elevated in patients with severe congestive heart failure (CHF), is involved in the regulation of nitric oxide metabolism. Whether increased concentrations of TNF alpha affect nitric oxide-mediated vasodilation in patients with CHF has not been studied previously. METHODS AND RESULTS: Serum concentrations of TNF alpha, interleukin-1 (IL-1), interleukin-2 (IL-2), and interleukin-6 (IL-6) were determined in venous blood (pg/mL) from 17 patients with stable New York Heart Association classes II and III CHF (mean age, 58 +/- 11 years; mean left ventricular ejection fraction, 19.5 +/- 7.3) and 17 age-matched normal subjects with enzyme-linked immunosorbent assays (detection limit of assays, 20 pg/mL). Forearm blood flows were determined with plethysmography (mL/min per 100 mL) in 17 patients and 7 normal subjects in response to brachial artery administration of graded concentrations of acetylcholine (10(-6) mol/L and 10(-5) mol/L) and nitroglycerin (10(-7) mol/L and 10(-6) mol/L). Serum concentrations of TNF alpha were above the detection limits of the assay in 10 of 17 patients with CHF (mean serum concentration, 39.4 +/- 3.8 pg/mL). Forearm blood flow responses to acetylcholine and nitroglycerin were significantly greater in these 10 patients than in the 7 patients without detectable serum TNF alpha and were closely correlated with TNF alpha serum concentrations (r > or = .81, P < .01 and r > or = .65, P < .05 respectively). In 1 of 17 normal subjects, the serum concentration of TNF alpha was just above the detection limit of the assay. Serum concentrations of IL-2 were above the detection limit of the assay in 14 of 17 patients with CHF (mean serum concentration, 112 +/- 19 pg/mL). IL-2 was not detected in the serum of normal subjects. Serum concentrations of IL-1 and IL-6 were below the detection limit of the assays in all patients and normal subjects assayed. CONCLUSIONS: Increased TNF alpha concentrations are closely correlated with forearm blood flow responses to regional administration of acetylcholine and nitroglycerin. The significant correlation between serum concentrations of TNF alpha and forearm blood flow responses to acetylcholine and nitroglycerin suggests that both the inducible and the constitutive forms of nitric oxide synthase are involved in the regulation of peripheral vasomotor tone in patients with CHF.

Adult↗
PubMed1994

Regional lymph node morphology in malignant melanomas and their prognostic value.

The occurrence of granulomatous epithelioid cell reaction, hyperplasia of lymphatic paracortex and existence of histiocytosis of the intermediary-medullary sinuses observed on sections of lymph nodes of 582 patients suffering from high-risk melanomas, examined during a ten-year period, have been established as reliable indicators of survival. On the other hand, lymphocytic infiltrative processes of the lymph node capsule, medullar plasmocytosis, and hyperplasia of germinal centres have been seen as indicators of a bad prognosis. Lymphocytic paracortical depletion and a predominance of postcapillary venules within the T zone were found to be less important in patients with a low chance of survival. We were able to establish a connection between lymphonodular parameters and the survival rate of the patients. In a multivariate test we found that there were four factors for statistical ascertainment of the prognosis of melanoma patients with lymphadenectomy: mitotic rate of primary tumour, lymphocytic infiltration of the lymph node capsule, existence of paracortical hyperplasia, and sex of the patient.

Follow-Up Studies↗
PubMed1994

[Cerebral angiitis or central side effects after lumbar myelography (with intracerebral vascular spasm)].

This is a case report of severe neurological complications following lumbar radiculography with the non-ionic x-ray contrast agent Iopamidol. The complication, which consisted of serious mnestic disturbances and various neurological deficits including hemiparesis, was due to intracerebral vascular spasms, demonstrated by cerebral angiography, and TCD followed by multiple cerebral infarctions, demonstrated by MRI. A possible causal relationship between the cerebral vascular spasm and intrathecal administration of Iopamidol is discussed.

Cerebral Angiography↗
PubMed1994

Pancreatic interstitial pH regulation: effects of secretory stimulation.

BACKGROUND: Bicarbonate secretion by pancreatic ducts presumably releases an equivalent amount of acid into the parenchyma. The purpose of this study was to determine the effects of this acid load on pancreatic interstitial pH (pHI). In addition, we examined the relationship of pHI to changes in pancreatic blood flow (PBF), which may be important in acid disposal. METHODS: After validation of a microelectrode method for measurement of pHI in anesthetized cats, the effects of secretin (2 IU/kg intravenously) and cholecystokinin (0.08 microgram/kg intravenously) were examined. PBF was measured simultaneously by the H2 gas clearance technique. RESULTS: Secretory stimulation with secretin produced an increase in pancreatic bicarbonate secretion (146 +/- 23 microEq/15 minutes, p < 0.01). This secretion was associated with a fall in pHI from 7.36 +/- 0.02 to 7.31 +/- 0.02 (p < 0.001), which returned to baseline after 25 minutes. There was an accompanying increase in PBF from 118 +/- 32 to 148 +/- 35 ml/min/100 gm (p < 0.01). In contrast, stimulation with cholecystokinin only slightly increased pancreatic secretion (49 +/- 19 microliters/15 minutes) and had no significant effects on pH or blood flow. CONCLUSIONS: These results suggest that pancreatic secretion of bicarbonate, but not protein, releases H+ into the interstitium, an acid tide comparable to the alkaline tide during acid secretion by the stomach. This interstitial acidosis was accompanied by an increase in PBF. The increase in blood flow may be important in pH homeostasis, contributing to the disposal of this acid.

Animals↗
PubMed1993

Pentamidine, an inhibitor of spinal flexor reflexes in rats, is a potent N-methyl-D-aspartate (NMDA) antagonist in vivo.

The present study examined whether the antimicrobial agent pentamidine exerts an antagonistic action at the N-methyl-D-aspartate (NMDA) receptor as tested on spinal reflexes in rats in vivo. After intrathecal injection both the specific NMDA antagonist (-)-2-amino-7-phosphonoheptanoate and pentamidine dose-dependently reduced the magnitude of the polysynaptic flexor reflex without affecting the monosynaptic H-reflex. In contrast, the non-NMDA antagonist 6,7-dinitroquinoxaline-2,3-dione depressed the H-reflex in a dose-dependent manner without affecting the flexor reflex. The depressant effect of pentamidine on the flexor reflex was prevented by coadministration with NMDA but not with the non-NMDA agonist alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid. These data suggest that pentamidine exerts an antagonistic action at the NMDA receptor in vivo.

2-Amino-5-phosphonovalerate↗
PubMed1993

Visual evoked potentials in the rat quinolinic acid model of Huntington's disease.

Intrastriatal injection of quinolinic acid (QA) in rats induces some of the neuropathological and neurochemical alterations observed in the striatum of patients suffering from Huntington's disease (HD). In addition this animal model mimics the diminution of the amplitude of early cortical somatosensory evoked potentials (SEPs) seen in HD patients. The present study investigated whether the QA model also exhibits abnormalities of early cortical visual evoked potentials (VEPs) observed in HD patients. Two weeks after unilateral intrastriatal injection of QA (240 nmol) early VEPs elicited in response to light flashes were not significantly altered in lightly pentobarbital-anaesthetized rats. It is concluded that (1) the QA animal model of HD does not mimic the VEP abnormalities seen in HD patients, and (2) a striatal lesion does not modulate transmission of visual input to the cortex in rats.

Animals↗