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Biomedical subjects

M Kessler

Publications and source records attributed to M Kessler.

At least 397 records · Page 22Linked to original sources

Biochemical effects of high-frequency synaptic activity studied with in vitro slices.

Brain slices have a number of features that may be of value in the analysis of how physiological events affect neuronal chemistry. This paper discusses this topic and describes slice experiments concerned with the chemical events responsible for long-term potentiation (LTP) of synaptic responses found in hippocampus after brief episodes of high-frequency stimulation. Work with two variants of the slice procedure indicated that LTP is accompanied by an increase in the sodium-independent binding of [3H]glutamate to partially purified synaptic membranes; this effect very likely results from an increase in the numbers of a particular postsynaptic receptor. Stimulation that produces long-term potentiation also causes a significant change in the endogenous phosphorylation of pyruvate dehydrogenase (PDH), a key mitochondrial enzyme. Inasmuch as the phosphorylated state of PDH is strongly correlated with calcium sequestration by mitochondria, it is possible that LTP is triggered by a transient perturbation of the calcium buffering function provided by mitochondria. Low micromolecular levels of calcium increase glutamate binding to purified membranes apparently via the activation of a calcium-sensitive thiol proteinase. This mechanism could account for the increase in glutamate binding found in slices exhibiting LTP. These experiments suggest a possible explanation for long-term potentiation and indicate that slices can be used to detect at least some of the biochemical consequences of repetitive synaptic activity.

Animals↗

[Use of radiological diagnosis in sport injuries and lesions].

The diagnosis of a sport injury or a sport damage is usually made by the clinical investigation. However, the X-ray examination is indispensable. In addition to standard projections further radiologic techniques such as passive motion, tomography, computed tomography, arthrography or angiography are necessary. The relevant use of these X-ray methods with regard to sport injuries or damages of the particular regions of the locomotor system are described.

Adolescent↗

[Practical interest of the determination of urinary fibrin degradation products in the early monitoring of kidney transplants].

We studied daily urinary excretion of fibrin degradation products (UFDP) during the first month following renal transplantation in 31 patients using the Merskey technique. Passed the 48 first hours a rise of UFDP was observed in 3 circumstances: 1) acute rejection: twenty four acute rejections were observed in twenty two patients. The increase of UFDP was constant. It preceded the clinical diagnosis of rejection in 63 p. 100 of the patients. It has a predictive value in all cases. 2) Severe urinary infection. In 5 patients with urologic complications UFDP rose markedly. 3) Macroscopic hematuria. In 2 patients with gross hematuria very high rates of excretion were observed.

Circadian Rhythm↗

[Comparative CT study of the anterior cruciate ligament in direct projection and using sagittal reconstruction].

The authors present an indirect method for the visualization of the anterior crucial ligament, using the method of sagittal reconstruction. Positioning in the so-called tailor's seat is often impossible in freshly injured persons. The abdominal positioning described in this article, with external rotation of the leg, is tolerated by almost all patients. Sagittal reconstruction yields adequate information in fresh lesions and if there is an obstruction to bending. However, this method is diagnostically not as infallible as the direct visualization. The authors discuss whether additional reconstructions on different planes and with pixels of different thickness (so-called thick pixel reconstruction) may be able to contribute to improved diagnostic results in future. In addition, the authors compare their own examination results with normal and pathological findings published by other authors.

Humans↗

[2-dimensional echoencephalography or cranial CT in premature or newborn infants with suspected intracranial hemorrhages].

65 newborns or low-birthweight infants with suspicion of intracranial hemorrhage were examined with B-mode small part scanners. In 12 cases the diagnosis made by ultrasound could be compared with CT. There was a similar accuracy of both methods in case of intraventricular (IVH) and subependymal (SEH) hemorrhage. SEH seems to be easier detected by US. On the other hand there are problems in diagnosing subdural (SDH) and intracerebral (IHC) hemorrhages by US. These problems are caused by the adjacent skull, but does not exist for CT. B-mode-Echoencephalography is the method of choice for examination of high risk infants and for the follow up, because US is a cribside method and of high diagnostic accuracy. CT-studies should be done in case of hemorrhage adjacent to the skull and if the US-diagnosis seems not to be reliable.

Cerebral Hemorrhage↗

Denervation-induced decrease in mitochondrial calcium transport in rat hippocampus.

Calcium accumulation by mitochondria and the activity and in vitro phosphorylation of pyruvate dehydrogenase were measured in control and partially denervated hippocampus. Calcium uptake was measured with a calcium-sensitive electrode and 45Ca2+ accumulation; both methods indicated that lesions of the entorhinal cortex produced a sizable reduction of calcium transport when mitochondria were fueled with pyruvate while much smaller changes were observed using succinate or ATP as energy sources. The decrease in calcium transport was evident by 24 hr after the lesion and was still present 6 months later. Synaptic and nonsynaptic mitochondria were similarly affected by the lesions. The activity and in vitro phosphorylation of pyruvate dehydrogenase were also significantly reduced following lesions of the entorhinal cortex, suggesting that denervation altered the endogenous state of phosphorylation of the mitochondrial enzyme. Commissural lesions but not septal lesions also resulted in a decrease in mitochondrial calcium transport when mitochondria were fueled with pyruvate. These findings suggest that denervation disturbs mitochondrial regulation of free calcium via an action on enzymes which regulate pyruvate dehydrogenase phosphorylation and activity. The potential relationship of this effect to degenerative changes associated with deafferentation and certain disease states is discussed.

Adenosine Triphosphate↗

The regulation of pyruvate dehydrogenase activity in rat hippocampal slices: effect of dichloroacetate.

The effects of dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase, on the phosphorylation of the alpha-subunit of pyruvate dehydrogenase and on the activity of pyruvate dehydrogenase (pyruvate:lipoamide oxidoreductase (decarboxylating and acceptor-acetylating), EC 1.2.4.1, PDH) were investigated in rat hippocampal slices. Incubating hippocampal slices with increasing concentrations of DCA resulted in an increase in the active portion of PDH, without changes in the total PDH activity, as well as an increase in the in vitro phosphorylation of alpha-PDH. The effect of DCA on PDH activity was very rapid, being almost maximal after 5 min. These results indicate that DCA in the hippocampal slice preparation inhibits PDH kinase and consequently stimulates PDH activity by decreasing its endogenous state of phosphorylation. Moreover the time-course of the effect of DCA suggests that the turnover rate of the phosphate group carried by alpha-PDH is very rapid and can be manipulated by altering PDH kinase activity.

Acetates↗

Phlorizin as a probe of the small-intestinal Na+,D-glucose cotransporter. A model.

(1)'Uptake' of phlorizin by intestinal brush border membrane vesicles is stimulated, much as that of D-glucose, by the simultaneous presence of Naout+ and delta psi much less than 0. However, phlorizin contrary to D-glucose, fulfills all criteria of a non-translocated ligand (i.e., of a fully competitive inhibitor) of the Na+,D-glucose cotransporter. (2) The stoicheiometry of Na+/phlorizin binding is 1, as shown by a Hill coefficient of approx. 1 in the Naout+-dependence of phlorizin binding. (3) The preferred order of binding at delta psi much less than 0 is Na+ first, phlorizin second. (4) The velocity of association of phlorizin to the cotransporter, but not the velocity of its dissociation therefrom, responds to delta psi. These observations, while agreeing with the effect of delta psi much less than 0 on the Kd of phlorizin binding in the steady-state time range, also confirm that the mobile part of the cotransporter bears a negative charge of 1. (5) A model is proposed describing the Na+, delta psi-dependent interaction of phlorizin with the cotransporter and agreeing with a more general model of Na+, D-glucose cotransport. (6) The kon, koff and Kd constants of phlorizin interaction with the Na+,D-glucose cotransporter are smaller in the kidney than in the small-intestinal brush border membrane, which results in a number of quantitative differences in the overall behaviour of the two systems.

Animals↗

Entorhinal cortex lesions induce a decreased calcium transport in hippocampal mitochondria.

Lesions to the entorhinal afferent of the hippocampus in rats caused marked changes in calcium transport into mitochondria. Pyruvate-supported calcium transport into mitochondria from the denervated hippocampus was decreased to a larger extent than succinate-supported transport, and adenosine triphosphate-supported transport was not significantly modified. Although cytochrome oxidase and succinate dehydrogenase activities were not significantly changed by entorhinal lesions, pyruvate flux through pyruvate dehydrogenase was significantly decreased, and this effect was correlated with changes in pyruvate-supported calcium transport. The active portion of pyruvate dehydrogenase decreased, whereas total pyruvate dehydrogenase was not modified. These data suggest that denervation might initiate dendritic atrophy and subsequent growth responses by modifying calcium regulation through a change in the phosphorylation of pyruvate dehydrogenase.

Adenosine Triphosphate↗

Cortical oxygen pressure during acute venous kidney obstruction.

Different degrees of obstruction to the renal venous drainage were produced in rabbits, and the cortical oxygen pressures in the kidney measured with the multiple-wire surface electrode of Kessler and Luebbers. Sudden complete occlusion of the inferior vena cava (IVC) above the renal vein, or above and below the renal vein simultaneously, produced a slight decrease of about 27%. Sudden complete occlusion of the renal vein itself caused a severe decrease of 67% (obstruction near the IVC) or 100% (obstruction near the kidney). One hour later different degrees of incomplete recovery were found. The PO2 curves for the renal cortex revealed different pressure-dependent pathophysiological changes in the microcirculation. The multiple-wire surface electrode may well prove to be of use during renal surgery in which venous obstruction is a critical factor.

Animals↗

Retrograde amnesia for forty years.

We describe a patient who, in the absence of anterograde amnesia, experienced sudden onset of profound retrograde amnesia for the last forty years of his life. The amnesia encompassed all knowledge, including motor skills, acquired during these forty years. There has been no recovery in over eighteen months. His symptoms seem most consistent with a vascular etiology. Current understanding of memory disorders fails to explain these symptoms. It may be that his case represents a previously undescribed disorder.

Activities of Daily Living↗

Cation transport in erythrocytes of patients with renal failure.

Na+, K+-ATPase activity in erythrocytes (RBC) has been assessed indirectly by the 86Rb uptake method in 10 patients with acute renal failure (ARF), 11 patients with chronic renal failure (CRF) on haemodialysis and 13 patients treated by kidney transplantation, and compared to age-matched healthy controls. In each patients, the sensitivity of 86Rb uptake to digoxin (IC50) has been measured. Na+, K+-ATPase activity was decreased in patients with ARF and in patients with CRF but not in transplanted patients. IC50 was lowered in transplanted patients. The implications of these findings are discussed in terms of possible mechanisms of the changes in Na+, K+-ATPase activity in RBC of patients with renal failure.

Acute Kidney Injury↗

Binding of 3H-Sertoli cell factor to rat anterior pituitary in vitro.

The binding characteristics of Sertoli Cell Factor (SCF) to the anterior pituitaries were examined using tissue homogenates and cultured cells. Tritium-labeled SCF (3H-SCF), synthesized by rat Sertoli cells in vitro in the presence of 3H-leucine and partly purified by Sephadex gel chromatography, was used to the ligand. The binding of 3H-SCF to the pituitary homogenates or cultured cells was considerably greater (3-6X) compared to homogenates of brain, kidney, liver, spleen and testis. The pituitary binding at 37 C occurred after approximately 60 time dependent, and directly related to the receptor concentration. Maximum binding at 37 C occurred after approximately 60 min of incubation. Over 90% of the bound 3H-SCF was competitively inhibited by an excess of unlabeled SCF, but not by other substances. There was a good correlation between the binding of 3H-SCF and its biological activity, as evidenced by a selective suppression of basal FSH release in pituitary cell cultures. These data indicate that, in analogy to other protein hormones, specific binding to target cell receptors may represent an initial step of SCF action in the pituitary. The binding should also prove valuable in the development of a rapid radio-receptor assay for SCF and possibly for other inhibin preparations.

Animals↗