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Biomedical subjects

W Schmidt

Publications and source records attributed to W Schmidt.

At least 559 records · Page 31Linked to original sources

Exocytotic exposure and retrieval of membrane antigens of chromaffin granules: quantitative evaluation of immunofluorescence on the surface of chromaffin cells.

The exocytotic exposure of antigens of chromaffin granule membranes was studied with chromaffin cells isolated from bovine adrenal medulla. Antigens on the cell surface were visualized by indirect membrane immunofluorescence employing antisera against glycoprotein III and dopamine beta-hydroxylase. With unstimulated cells, only weak immunofluorescence on the cell surface was observed, whereas stimulated cells (with carbachol or Ba2+) exhibited much stronger reactions. In all cases the staining appeared as dots and patches. To quantitatively prove these observations, we analyzed the immunostained cells using a fluorescence-activated cell sorter. After stimulation, the average fluorescence intensity of the cell population was enhanced. This increase correlated with the degree of catecholamine secretion. The fluorescence intensity of stimulated cells varied over a broad range indicating that individual cells reacted variably to the secretagogues. When stimulated cells were incubated at 37 degrees C for up to 45 min after stimulation, a decrease of membrane immunofluorescence approaching that of unstimulated control cells was observed. Apparently, the membranes of chromaffin granules, which had been incorporated into the plasma membrane, were retrieved by a specific and relatively fast process. This retrieval of the antigen from the cell surface was blocked by sodium azide, but not influenced by colchicine, cytochalasin B, and trifluoperazine. The quantitative methods established in this paper should prove useful for further study of the kinetics of the exo-endocytotic cycle in secretory tissues.

Adrenal Medulla↗

Isolation and phenotypic characterization of Tetrahymena thermophila size mutants: the relationship between cell size and regulation of DNA content.

Temperature-sensitive size mutants of the ciliate Tetrahymena thermophila were selected following chemical mutagenesis. Phenotypical characteristics are given for seven cell lines, which have a range of average cell volumes from 8000 microns 3 to more than 100 000 microns 3. wild-type Tetrahymena cells have an average cell volume of 15 000 microns 3. Two of the mutagenized cell lines have comparatively small cells at 29 degrees C but normal cells at 37 degrees C; whereas the other five lines are normal at 29 degrees C but large at 37 degrees C. While the small cells are poor growers, the large cells grow excellently at 37 degrees C. Measurements of DNA, RNA and protein contents indicate a significant correlation between all parameters and cell size. However, since the cells tolerate considerably different concentrations of each class of macromolecules, the amount of any of these macromolecules cannot be tightly controlled by cell size.

DNA↗

Maternal perception of fetal movements and real-time ultrasound findings.

Two real-time ultrasound instruments were used simultaneously for comprehensive recording of "total" fetal motor activity in 50 patients in the second half of pregnancy. Synchronously, cardiotocographic findings and maternal perception of fetal movements were stored on magnetic tape. In most cases fetal "gross" movements were perceived by the mothers (mean: 63%). Isolated movements of fetal extremities were reported by the mother in only about 15% of all cases. Mothers registered a total of all movements in 37%. We found a statistically significant difference in the percentage of perceived fetal movements with regard to parity (p less than 0.001) and with regard to gestational age (p less than 0.01). With multiparity or an increasing gestational age the body movements of the fetuses were felt more accurately by the mothers. In 30% of all cases the mothers perceived movements without sonographic confirmation. The findings of this study suggest that maternal perception of major fetal body movements is accurate in the majority of cases. However, the relatively high rate of false positive maternal perception should be taken into consideration if the maternal record of daily fetal movements is to be used for fetal monitoring.

Female↗

Substance P: binding to unilamellar and multilamellar liposomes made from mixtures of phosphatidylcholine and phosphatidic acid.

Binding of the undecapeptide substance P to unilamellar and multilamellar lipid vesicles, made from mixtures of phosphatidylcholine and phosphatidic acid, was investigated, because liposomes may be supposed to become a useful pharmaceutical tool for the delivery of low molecular mass peptide hormones. It is demonstrated that binding is largely electrostatic in nature, and that the amount of bound peptide may be varied within rather broad limits by changing the lipid matrix and/or the aqueous medium conditions. Concerning the distribution of the peptide between inner and outer surfaces of the liposomes, large differences may be realised too, as revealed by enzymatic hydrolysis of the outside bound portions of substance P. But additionally, electrostatic binding is demonstrated also to bring about peculiar, unexpected properties of the system. These imply special relevance to a potential pharmaceutical application of substance P liposomes as well as some general relevance to in vivo application of liposomes as drug carriers.

Drug Stability↗

Histochemical localization of aspartate aminotransferase activity in the hippocampal formation and in peripheral ganglia of the rat with special reference to the glutamate transmitter metabolism.

The regional distribution and cellular localization of aspartate aminotransferase (AspAT), an glutamate/aspartate metabolizing enzyme, was studied in the hippocampal formation, in dorsal root ganglia, and in superior cervical ganglia during the postnatal development of the rat. In the dendritic layers of the hippocampal formation the enzyme activity was found to be very low in newborns, increased markedly from the second week of life and reached adult levels during the postweaning period. These results coincide with parameters of the maturation of glutamatergic structures in this brain region. The staining intensity of AspAT in the peripheral ganglia, in which glutamate/aspartate inputs do not obviously occur, did not display any evident differences during the postnatal development. The increase of AspAT activity parallel to the maturation of glutamatergic/aspartatergic mechanisms suggest that the enzyme studied is involved in glutamate/aspartate neurotransmitter metabolism.

Age Factors↗

Brain gastrin/CCK immunoreactivity in sand rat (Psammomys obesus): decrease of number of positive neurons in diabetic animals.

Gastrin/CCK immunoreactivity appears to be widely distributed throughout the mammalian CNS, being most abundant in the cerebral cortex [Vanderhaeghen et al. 1975; Straus et al. 1977; Beinfeld et al. 1981]. Besides its putative role as a co-transmitter in dopaminergic neurotransmission [Hökfelt et al. 1980], cholecystokinin is apparently involved in the central regulation of appetite and satiety [Gibbs et al. 1973; Antin et al. 1975; Parret and Batt 1980; Smith 1980; Smith and Gibbs 1981] Furthermore, it has been shown that the brain concentration of the peptide is decreased in genetically obese mice as compared to non-obese animals [Strauss and Yalow 1979]. The sand rat (Psammomys obesus) is a desert rodent which tends to become diabetic when it is fed with normocaloric diet and restricted in movement [Haines et al. 1965; Hahn et al. 1971]. However, the usefulness of this animal as a paradigm of diabetes is now being revised, since because in its typical expression this metabolic dysfunction appears to be an obesity syndrome [Rice and Robertson 1980]. Therefore, it seems to be necessary to study the distribution of gastrin/CCK-immunoreactive nerve cells in the brain of normal and diabetic (obese) sand rats to get further information about mechanism underlying the development of this form of diabetes.

Animals↗

[Postoperative tube feeding of maxillary surgery patients with the high molecular drinking and tube feeding solution Fresubin].

41 patients, who underwent maxillo-facial surgery received mostly for 10 days the instant formula diet Fresubin liquid during the postoperative period. The diet was applied via a nasogastric tube. Feeding had to be interrupted in 5 patients (12.5%) due to nausea, vomitus and diarrhoea. The incidence of nausea, diarrhoea and eructuation with short duration was in relation to the days of tube feeding 0.9%. The mean frequency of defacation was 0.7/24 hours. Giving about 25 kcal/kg body weight/day we did not see significant changes of body weight, of the Na, K and Ca serum concentrations or other effects. Caused by operation and anesthesia we found a decrease of the hemoglobin, hematocrit, albumin in the serum, and an increase of SGOT and SGPT.

Adolescent↗

Intracellular electrolytes during antihypertensive treatment with a loop diuretic.

The effect of the loop diuretic, piretanide (12 mg/day on blood pressure and intracellular electrolyte composition in red blood cells during a six-week treatment period was studied in 14 previously untreated essential hypertensive patients. Blood pressure fell continuously during the six weeks, intracellular Na+ activity in red blood cells increased slightly (P less than 0.05), and there was a marked decrease in intracellular Ca2+ activity (P less than 0.01). Intracellular K+ concentration was not altered. It is concluded therefore, that intracellular free Na+ does not correlate with the actual blood pressure, whereas the fall in blood pressure is associated with a decrease in intracellular free Ca2+, suggesting that intracellular free Ca2+ is involved in the regulation of vascular tone.

Adult↗

[The validity of various audiometric testing methods in tumor-induced hearing disorders].

In order to study the diagnostic possibilities for detecting acoustic neuromas respectively tumors of the cerebello pontine angle 60 patients with secured tumor (op. confirmed) were preoperatively examined audiologically . The test results were worked out statistically and checked of their validity in respect of the diagnosis. It could be found, that the results of the conventional audiometry, if taken in its entirety, approved a secure diagnosis in most of the cases; though very discretely marked constellations of test results had to be considered. Routine-audiometric failures were essentially restricted to patients which were deaf or had a high-grade hearing loss ( Lehnhardt 1983). The recordings of auditory brain stem responses of them selves showed in all cases a result in the sense of retrocochlear hearing disorder, not only with regard to prolonged absolute latency times of JV/P6 but also of prolonged interpeak latency times between JI and JV. In cases of monaurale deafness, the ERA supplied a secure criterion for a brain stem disorder because of delayed latency times on the not affected side.

Acoustic Impedance Tests↗

The problem of cell debris in pulse-cytophotometry: a probability theoretic model.

The problem of cell debris in pulse-cytophotometry is considered on the basis of a probability-theoretic model and the results are compared with the model of a pure exponential function for the portions of the DNA fragments in the channels of the flow cyclometer, which is generally used in practice. The model is based on the assumption that the possible decomposition of the DNA content of a single cell into some parts as a consequence of the necessary preparation of the cell material for measurement can be interpreted as a Poisson point process. Therefore the number of divisions of the DNA content of a cell is assumed as a Poisson random variable. It follows a well-defined distribution function of the DNA content in the common population of intact cells and fragments depending on the apriori distribution before pretreatment. This distribution determines a theoretical histogram which can be compared with the measurements. The results corroborate the assumption of a pure exponential course for the portions of DNA fragments only in the area of very small DNA contents. For greater DNA contents there are differences between the pure exponential course and the model described here depending on the a priori distribution and on the intensity of the cell disintegration process. As a byproduct, an estimation of the fraction of disintegrated cells is obtained with respect to the fraction of fragments. A corresponding computer program was applied to a number of experimental histograms. The results have shown that the theory describes the measured histograms satisfactory in most cases.

Cell Cycle↗

Comparative studies of purified and reconstituted monoamine oxidase from bovine liver mitochondria.

Monoamine oxidase, a strictly membrane-bound flavoenzyme, has been purified using a modified procedure recently developed. Probably similarly to other preparations known from the literature, the enzyme solubilizes to a clear suspension, which represents large clusters ranging in size from 5 to 50 nm containing appreciable amounts of residual lipids. The purified and reconstituted enzymes are inhibited differently by deoxycholate. In contrast to deoxycholate, Triton X-100 does not inhibit the purified enzyme, but rather disintegrates the lipid-enzyme clusters to the smallest active units. However, removal of the detergent leads to reconglomeration to larger lipid-enzyme aggregates. Using the irreversible destruction of the enzyme by deoxycholate as assay, reconstitution of the enzyme with exogeneous lipids has been studied. All basic enzyme properties, such as stability, maximal activity (V), Michaelis constant (Km), pH- and temperature-dependence of the purified and reconstituted systems, are significantly different.

Animals↗

Potassium load in spontaneously hypertensive rats. Effects on blood pressure, renin-angiotensin, aldosterone, and intracellular electrolytes.

To study the mechanisms by which K+ influences vascular tone in hypertension, spontaneously hypertensive and normotensive rats were examined during an oral K+ load. There was a marked decrease in blood pressure in spontaneously hypertensive but not in normotensive rats. Intraerythrocytic K+ concentration and activity increased in normotensive but not in spontaneously hypertensive rats. Intraerythrocytic Na+ concentration and activity declined in both strains, the decrease in Na+ activity being more prominent in spontaneously hypertensive rats (P less than 0.05). Intraerythrocytic Ca2+ activity decreased in spontaneously hypertensive rats (P less than 0.01) but not in normotensive rats. In both strains plasma aldosterone concentration increased during K+ load, the plasma renin activity being suppressed. The basal levels of plasma aldosterone in spontaneously hypertensive rats exceeded those in normotensive rats. It is concluded that intraerythrocytic Ca2+, and to a lesser extent Na+, correlate best with the blood pressure changes. These ionic changes may be mediated by hormonal factors. The significance of the elevated plasma aldosterone levels has not yet been entirely clarified.

Aldosterone↗

Postnatal changes in the activity of glutamate dehydrogenase and aspartate aminotransferase in the rat nervous system with special reference to the glutamate transmitter metabolism.

The activities of aspartate aminotransferase (AAT) and glutamate dehydrogenase (GIDH), the major glutamate metabolizing enzymes, were studied in hippocampal formation, cerebellar cortex, dorsal root ganglia, superior cervical ganglia and liver as a function of postnatal development. At birth, in all these nervous tissues the enzyme activities were quite low and showed similar levels (AAT 7-15 U/g wet weight; 0.18-0.23 U/mg protein; GIDH 3.4-13 U/g wet weight; 0.07-0.18 U/mg protein). Based on protein, AAT activity increased during the postnatal period studied 5.8 and 3.8 times in the hippocampal formation and cerebellar cortex, respectively, while the respective GIDH rise was 5.2 and 2.3 times. During postnatal maturation, enzyme activities in dorsal root ganglia showed only minor changes. In superior cervical ganglia, AAT and GIDH were remarkably constant. In liver the enzyme activities changed during postnatal development, but the activity curve profile was quite distinct from those obtained for brain regions. The steep rise of AAT and GIDH activities in brain regions is discussed as being a consequence of the maturation of preferably glutamatergic structures. Glutamatergic transmission processes obviously do not take place in superior cervical ganglia and dorsal root ganglia, and certainly not in liver. The present results suggest a quantitatively significant participation of glutamate transmitter metabolism in proportion to the whole glutamate metabolism of the CNS.

Aging↗

Variation in mortality from ischemic heart disease in relation to alcohol and milk consumption.

A simple correlation analysis of data for 19 Western countries confirmed previously reported findings that the rate of mortality from ischemic heart disease (IHD) varies inversely with total alcohol consumption and positively with the consumption of unfermented milk proteins. However, when milk protein consumption was held constant in a multiple-partial correlation analysis, the association between total alcohol consumption and the IHD mortality rate was reduced to non-significance. In contrast, when alcohol consumption was held constant there was little effect on the high correlation between the mortality rate and the consumption of milk proteins. Multiple regression analysis confirmed the importance of the milk factor over alcoholic beverages as a determinant of variation in IHD mortality rates. It was concluded that the inverse association between alcohol consumption and IHD mortality, observed in international comparisons, is probably largely an artifact of a negative association between alcohol and milk consumption. An hypothesis is offered respecting the component of milk which might be responsible for its apparent atherogenicity.

Alcohol Drinking↗

Zinc and glutamate dehydrogenase in putative glutamatergic brain structures.

A certain topographic parallelism between the distribution of histochemically (TIMM staining) identified zinc and putative glutamatergic structures in the rat brain was demonstrated. Glutamate dehydrogenase as a zinc containing protein is in consideration to be an enzyme synthesizing transmitter glutamate. In a low concentration range externally added zinc ions (10(-9) to 10(-7) M) induced an increase in the activity of glutamate dehydrogenase (GDH) originating from rat hippocampal formation, neocortex, and cerebellum up to 142.4%. With rising molarity of Zn(II) in the incubation medium, the enzyme of hippocampal formation and cerebellum showed a biphasic course of activation. Zinc ions of a concentration higher than 10(-6) M caused a strong inhibition of GDH. The effect of Zn(II) on GDH originating from spinal ganglia and liver led only to a decrease of enzyme activity. These results are discussed in connection with a functional correlation between zinc and putatively glutamatergic system.

Animals↗