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M Kiessling

Publications and source records attributed to M Kiessling.

85 records · Page 5Linked to original sources

Regional impairment of protein synthesis in the rat brain during bicuculline-induced seizures.

Protein synthesis was investigated in rats subjected to 30 min of bicuculline-induced seizures using biochemical and autoradiographic techniques. Incorporation studies were performed on freely convulsive animals following systemic administration of either a tracer dose of L-[1-14C]tyrosine or a flooding dose (7.5 mmol/kg) of L-[1-14C]valine. Using a tracer dose, amino acid incorporation was only moderately reduced (forebrain) or slightly enhanced (cerebellum/brainstem and spinal cord) but the specific radioactivity of [14C]tyrosine in the acid-soluble pool was increased 3- to 5-fold in experimental animals. After a flooding dose of [14C]valine the specific activity of the precursor amino acid was similar in control and convulsed animals. Under these conditions incorporation rates in forebrain and cerebellum/brainstem were reduced to 54 and 75%, respectively. Reduction of amino acid incorporation was even more pronounced in extraneural tissues, e.g. liver (6%), intestine (14%) and kidney (15%). Inhibition of protein synthesis in forebrain and cerebellum/brainstem was paralleled by a similar extent of polyribosome disaggregation in these regions (53 adn 78% of controls). In anaesthetized, mechanically ventilated rats, 30 min of seizure activity reduced forebrain polyribosomes to a similar extent (57%). Extraneural (hepatic) protein synthesis was also affected in physiologically controlled rats, but cerebellar polysomes were completely preserved. Autoradiographic studies using 3H-labelled amino acids were carried out to identify nerve cell populations most heavily affected. In freely convulsive rats both tracer dose and pool overloading revealed a similar regional pattern with preferential inhibition of amino acid incorporation in forebrain cortex, thalamus and the pyramidal cell layer of the hippocampus. These sites were also affected in the physiologically controlled animal, but the focal distribution of hippocampal and thalamic neurones with reduced protein synthesis differed from that in freely convulsive rats.

Animals↗

Morphologic evaluation of stereotactic brain tumour biopsies.

The validity of morphologic diagnosis of stereotactic brain tumour biopsies was evaluated in a series of 600 patients treated since 1977 at the University Hospital, Freiburg. Combined cytological (smear preparations) and histological examination of paraffin-embedded samples revealed the tumour type and approximate grading in 492 (82%) of cases. In 66 patients a clinically suspected neoplasm could be ruled out. In the remaining 42 cases (7%), the presence of a tumour was confirmed but the available samples did not allow an unequivocal classification of the neoplasm. Inaccurate diagnoses were most frequently due to sampling errors in non-homogeneous tumours, i.e. biopsies taken from sites not representative for the entire neoplasm (tumour necroses, infiltration zone). In the future, the use of immunohistochemical methods for the identification of tumour markers and cytoskeleton proteins may partially compensate for the limited size of stereotactic biopsy samples.

Brain↗

Regionally selective inhibition of cerebral protein synthesis in the rat during hypoglycemia and recovery.

Regional cerebral protein synthesis was investigated in anesthetized, mechanically ventilated rats during progressive insulin-induced hypoglycemia and the recovery period following glucose infusion. Polysome profiles from precomatose animals with slow wave/polyspike EEG revealed a slight reduction of polyribosomes and a concurrent increase in monoribosomes, but autoradiographs showed a pattern of L-[3-3H]tyrosine incorporation indistinguishable from that of control rats. During the initial 30 min of insulin-induced isoelectric EEG ("coma"), autoradiographs showed a selective inhibition of protein synthesis in neurons and glial cells of the hippocampus and cerebral cortex, i.e., regions with high susceptibility for the development of hypoglycemic brain damage. Basal ganglia were less affected and areas with low vulnerability (hypothalamus, brainstem, and cerebellum) exhibited a normal pattern of amino acid incorporation. Using a flooding dose of L-[1-14C]valine (7.5 mmol/kg; 15 microCi/mmol), the rate of incorporation in cerebral cortex and cerebellum was found to be reduced to 2% and 80% of control values, respectively. Inhibition of protein synthesis was paralleled by a breakdown of polyribosomes and a concomitant increase in ribosomal subunits, indicating a block in peptide chain initiation. After 90 min of isoelectric EEG all brain structures with the exception of hypothalamus and area postrema showed an almost complete lack of amino acid incorporation. Glucose infusion after a 30-min period of hypoglycemic coma led to a partial restoration of cortical and hippocampal protein synthesis. Within 70-90 min of recovery, L-[1-14C]valine incorporation into neocortical and cerebellar proteins amounted to 47% and 125% of fasted controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗

Regional heterogeneity of L-[3-(3)H]tyrosine incorporation into rat brain proteins during severe hypoglycemia.

Regional protein synthesis was investigated during severe, insulin-induced hypoglycemia in anesthetized, artificially ventilated rats. Three minutes after the cessation of spontaneous EEG activity, animals received a single injection of L-[3H]tyrosine and were killed 30 min later. Autoradiographs revealed an almost complete inhibition of amino acid incorporation in the cerebral cortex, hippocampus, and caudate-putamen of hypoglycemic rats. Thalamus and spinal cord were less affected, and in hypothalamus, cerebellum, and brainstem the pattern of [3H]tyrosine incorporation was identical in control and experimental animals. The areas showing severely reduced protein biosynthesis during hypoglycemia coincide with those exhibiting extensive breakdown of energy metabolism, reduced cerebral metabolic rate for glucose, and high susceptibility to persistent cell damage. High-resolution autoradiography employing tritiated amino acids permits the assessment of regionally impaired protein biosynthesis and may thus be useful for the identification of neuronal populations at risk during hypoglycemia of varying degrees and of those cells most likely to recover after glucose infusion.

Animals↗

Regional protein synthesis in the rat brain during bicuculline-induced epileptic seizures.

The incorporation of L-[3,5-3H]tyrosine into cerebral proteins was investigated during the initial phase (30 min) of bicuculline-induced status epilepticus. Autoradiographs of different parts of the cerebral hemispheres, brain stem, and cerebellum were prepared. Marked local reduction of amino acid incorporation was evident in bilaterally symmetrical areas of the cerebral cortex, hippocampus, thalamic nuclei, and the region of the medial geniculate body. No apparent difference of local [3H]tyrosine incorporation was observed in the lower brain stem nuclei and in the cerebellum of control and convulsed animals. The territories showing a decrease of protein synthesis during epileptic seizures coincide largely with the regions of maximal local glucose metabolism and cerebral blood flow. The present investigation demonstrates that autoradiography of regional protein biosynthesis is a suitable method for the visualization of neuronal populations at risk in the very early stages of seizure activity.

Animals↗

Effect of pretreatment with pregnenolone-16 alpha-carbonitrile and protein-free diet on the metabolism and carcinogenicity of dimethylnitrosamine.

Pretreatment with protein-free diet (PFD) or pregnenolone-16 alpha-carbonitrile (PCN) markedly reduces th toxicity of dimethylnitrosamine (DMN) in rats. PFD causes a shift in DMN metabolism form liver to kidney with a consequent increase in the incidence of kidney tumours. The present study was designed to evaluate the effect of PCN on the carcinogenicity and metabolism of DMN. After pretreatment with PFD, PCN or a combination of both, adult female Wistar rats received a single i.p. dose (60 mg/kg) of DMN. Animals pretreated with PFD and PFD + PCN developed a similar incidence of kidney tumours (83-85%) after a mean survival time of 357 and 396 days, respectively, Animals pretreated with PCN alone had a 50% incidence of renal tumours after a mean survival time of 672 days. This correlates with the initial extent of DMN-induced methylation of kidney DNA. Concentrations of 7-methylguanine and O6-methylguanine were highest and very similar in PFD- and PFD + PCN-pretreated rats, whereas in PCN-conditioned animals the extent of base methylation was 38% lower. Extrarenal tumours, in particular large cystic cholangiomas of the liver, were most frequent in PCN-pretreated rats, probably due to their longer survival time. In contrast to animals pretreated with either PCN or PFD, hepatic DNA methylation was markedly reduced (54-60%) in animals pretreated with both PFD and PCN.

Animals↗

Stereotactic biopsy of brain tumors.

Stereotactic biopsies from deep-seated brain tumors were carried out in 302 patients. There were more men (58 percent) than women. Peak of prevalence was in the second to fourth decade; the youngest patient was 18 months old. The tumors were deep-seated hemispheric in 36 percent, in the basal ganglia in 30 percent, in the diencephalic region, i.e., hypothalamus and suprachiasmatic region, in 21 percent, and in the midbrain and pineal region in 13 percent. The majority of lesions were gliomas (71 percent), the remaining being epithelial and various nonglial tumors. Operative mortality was 2.3 percent; transient deterioration was observed in 3 percent. Diagnosis was made instantly by cytological examination (smear preparations) and confirmed by conventional histological examination. In only 5 percent of the gliomas was a discrepancy found between the diagnosis from the smear preparation and the subsequent histological diagnosis. Integrating computerized tomography (CT) imaging techniques into the stereotactic technique makes it possible to take biopsies at exact and reproducible sites and with low risk. The findings suggest that exploratory craniotomies, risky free-hand punctures, and aspirations deep in the brain can no longer be advocated. No radiation treatment should be considered without histological confirmation.

Adenoma↗

[Effects of levodopa and piribedil on cyclic AMP levels in cerebrospinal fluid in rats (author's transl)].

30 min after injection of levodopa (200 mg/kg) into rats the cAMP levels in the cisternal fluid were significantly elevated by 60% over controls. When dopamine-beta-hydroxylase was inhibited by bis-(4-methyl-1-homopiperazinyl-thiocarbonyl)-disulfide (Fla 63) the levodopa induced increase of cAMP levels was less marked, it was suppressed by propranolol (10 mg/kg), a beta-adrenergic blocking agent. Piribedil (10 mg/kg) failed to influence cisternal cAMP concentrations. The findings do not support the concept of a dopamine-sensitive adenylate cyclase in vivo, and suggest a beta-adrenergic stimulation of cerebral adenylate cyclase by metabolites of levodopa.

Animals↗

Cyclic adenosinemonophosphate in cerebrospinal fluid. Effects of theophylline, L-dopa and a dopamine receptor stimulant in rats.

The effects of L-Dopa and the dopamine receptor stimulant ET-495 on cisternal cAMP levels were studied in rats. L-dopa (100-200 mg/kg) increased cisternal cAMP levels by 60 to 80% of controls. When peripheral Dopa-decarboxylase was inhibited, smaller doses of L-Dopa were effective. Fla-63, an inhibitor of dopamine-beta-hydroxylase lowered the increase induced by L-Dopa which was completely suppressed by propranolol, not by phentolamine, suggesting that the cAMP increase is mediated through a central beta-adrenoceptor stimulation. ET-495 failed to influence cAMP levels which argues against a dopamine-sensitive adenylate cyclase involved in the L-Dopa effect. Moreover, large increases of cisternal cAMP were observed after treatment with theophylline , not papaverine which suggests different effects of these "phosphodiesterase inhibitors" on the cyclic AMP systems in the central nervous system or on transport mechanisms.

Animals↗

Paramedic field instructors: an approach to training the newest paramedics while maintaining the interest of the most successful senior paramedics.

A unique approach to providing orientation and supervised field experience for newly graduated paramedics and for the continuing education and recognition of experienced, skilled, operational paramedics is described. A group of 30 paramedic field instructors (PFI) was selected following application, development of criteria for selection, and interviews. This program had a positive effect in both realms during its first year of operation in the emergency medical services system in which it was implemented.

Clinical Competence↗