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Biomedical subjects

M Zimmermann

Publications and source records attributed to M Zimmermann.

At least 163 records · Page 9Linked to original sources
PubMed1997

[Hemangioblastoma: description of a disease picture and report of 41 cases].

Hemangioblastomas are benign tumors of the central nervous system (CNS) with a predominance of the cerebellar hemispheres. They are one of the most frequent tumors of the posterior fossa in adults. In this retrospective study the data of 41 operated patients (23 men and 18 women) with a hemangioblastoma of the CNS are demonstrated. The mean age of the patients was 42.2 years (Range 4-70 years). 76% of the hemangioblastomas were located in the cerebellum, 9% in the cerebral hemispheres, 7% in the spinal canal and 5% in the brain stem. Signs of increased intracranial pressure and cerebellar dysfunction were the most frequent symptoms. Complete tumor removal was achieved in 90% of all operated cases. 82% of the hemangioblastomas were cystic and 18% solid. The mean diameter of the tumor cysts was 36 mm (Range 20-60 mm) and 18 mm (Range 2-40 mm) of the solid tumors. In 7% of the cases tumor recurrence was seen with a mean time interval of 5.7 years.

Adolescent↗
PubMed1997

Endothelin in cerebral vasospasm. Clinical and experimental results.

Since their discovery in 1988, endothelins have attracted scientific interest because of their extremely potent and long lasting vasoconstrictive effects. In the clinical part of the study plasma and cerebrospinal fluid (CSF) concentrations of big endothelin-1, endothelin-1 and endothelin-3 in patients with aneurysmal subarachnoid hemorrhage (SAH) were measured serially for 2 weeks after the onset of SAH. Big endothelin-1 was the predominant peptide present in CSF. The CSF concentrations of big ET-1, ET-1 and ET-3 were significantly higher in older than in younger patients. In patients with cerebral vasospasm postoperative concentrations of endothelins in the CSF remained at or were increased above levels measured before surgery. The volume of hematoma in the basal cisterns was predictive of the concentrations of endothelins in CSF. In the experimental study the efficacy of the orally active endothelin-receptor-antagonist RO 47-0203 for the prevention of cerebral vasospasm after experimental SAH, using the canine two-hemorrhage model, was investigated. Twenty-eight beagle dogs were used in this laboratory experiment. Fourteen animals each were assigned to the treatment and to the control group. In the treatment group each dog received two single doses of 30 mg/kg RO 47-0203 orally per day. The diameter of the basilar artery decreased from 1.36 +/- 0.17 mm at day 1 to 1.19 +/- 0.23 mm at day 8 in the treatment group while in the control group the vessel diameter decreased from 1.48 +/- 0.19 mm at day 1 to 1.02 +/- 0.22 mm at day 8. These results corresponded to a decrease of vessel diameter of 13.1% +/- 11.2% in the treatment group and a decrease of vessel diameter of 30.7% +/- 12.4% in the control group (p < 0.001). Concentrations of endothelin-1 in CSF significantly increased with time after SAH. These results underline the important role of endothelin in the development of cerebral vasospasm, and gives for the first time evidence that prevention of cerebral vasospasm can be achieved by the endothelin-receptor-antagonist RO 47-0203.

Adolescent↗
PubMed1997

[Treatment of amiodarone-induced hyperthyroidism: corticosteroids or potassium perchlorate? What value do interleukin-6 levels have?].

We report 11 cases of amiodarone-induced hyperthyroidism. We tried to classify them into 2 groups, according to Bartelena et al. (JCEM 81: 2930, 1996). The serum level of interleukin-6 (IL-6) was measured in 7 patients by an immunoenzymometric assay. In type I (cases 1-3) the thyroid was abnormal (goiter, Graves' disease) but IL-6 levels were normal. These cases were successfully managed by the combined use of thionamide drugs (carbimazol or propylthioruacil = PTU) and potassium perchlorate. In type II (case 4), the thyroid seemed to be normal but the serum level of IL-6 was increased, possibly due to a destructive thyroiditis. Treatment with prednisone (40 mg/day) and PTU resulted in a prompt normalization of T3. Contrary to Bartalena et al., we observed cases with normal thyroid and normal levels of IL-6 (cases 5-8) (type III). In these cases prednisone (40 mg/day for 2 weeks) was ineffective but the combined use of thionamide drugs and perchlorate was associated with a normalization of thyroid hormones. This combined treatment seems to be effective in most patients (type I, III). In case of failure of this treatment, a high dose of prednisone (1 mg/kg) could be tried or a lower dosage (40 mg/day) could be used in cases with high IL-6 levels (type II).

Adult↗
PubMed1996

Expression pattern of candidate cell death effector proteins Bax, Bcl-2, Bcl-X, and c-Jun in sensory and motor neurons following sciatic nerve transection in the rat.

Numerous studies have demonstrated a prolonged expression of c-Jun transcription factor in neurons following axotomy, and it has been hypothesized that c-Jun may be causally involved in neuroregeneration in vivo. By contrast, there is growing evidence from in vitro studies that induction of c-Jun may be necessary for neuronal cell death induced by growth factor starvation. It has been demonstrated that protein levels of cell death repressor Bcl-2 and cell death promotor Bax determine the threshold for neuronal cell death and that their expression is dynamically modulated at the onset of neurodegeneration. In the present study, we investigated by double-immunolabeling methods activation of c-Jun transcription factor and expression of members of the Bcl-2 family of cell death effector proteins in axotomized neurons. Six days after transection of the sciatic nerve in young rats, when axotomized neurons start to degenerate, strong nuclear Jun immunostaining in spinal cord motoneurons was associated with intense cytoplasmic Bax labeling and signs of neuronal atrophy. Bcl-2 and Bcl-X proteins were present only at moderate to low levels. In situ end-labeling by terminal transferase revealed nuclear DNA fragmentation in scattered motoneurons of the ipsilateral ventral horn (1 or 2 labeled nuclei per section). In the L5 dorsal root ganglia (DRG) levels of Bax, Bcl-2, and Bcl-X proteins were highly variable. High levels of Bax immunoreactivity together with intense Jun immunofluorescence were frequently observed in small-diameter sensory neurons. RT-PCR analysis revealed expression of exclusively the anti-apoptotic bcl-xL mRNA isoform in rat DRG which decreased significantly following sciatic nerve transection. These findings indicate that the high susceptibility of central neurons and small-sized DRG neurons to axotomy-induced cell death might be related to their low ratio of cell death repressor Bcl-2 and Bcl-XL to cell death promotor Bax expression. It should be noted, however, that numerous strongly Jun-positive DRG neurons contained low levels of Bax or high levels of Bcl-2 and Bcl-X immunoreactivity. Thus, high levels of c-Jun protein in axotomized neurons do not necessarily suggest a destination to die, and other factors may determine the outcome of axotomy.

Animals↗
PubMed1996

[Not Available].

Explore the source record for details and available documents.

Journal Article↗
PubMed1996

Altered expression of Bcl-2, Bcl-X, Bax, and c-Fos colocalizes with DNA fragmentation and ischemic cell damage following middle cerebral artery occlusion in rats.

Permanent occlusion of the middle cerebral artery in rats was used to assess the effects of focal ischemia on the expression of members of the bcl-2 family which have been implicated in the regulation of programmed cell death. Intraluminal occlusion of one middle cerebral artery for 6 h resulted in histologically detectable brain damage within the ipsilateral caudate putamen, basolateral cortex and parts of the thalamus. In the infarcted basolateral cortex and thalamus fragmentation of DNA was detected in many nuclei using in-situ end-labeling of DNA breaks by terminal transferase, whereas only scattered labeled nuclei were visible in the infarcted caudate putamen. Immunohistochemical analysis revealed activation of c-Fos in the infarcted cortex and thalamus and in the non-infarcted cingulate cortex as has been shown by others. A decrease in immunoreactivity for Bcl-2, and Bcl-X and an increase in immunostaining for Bax was observed exclusively in neurons within the ischemic cortex and thalamus. Within the infarcted caudate putamen, however, protein levels of all bcl-2 family members declined and c-Fos remained absent. By reverse transcription and polymerase chain reaction it was demonstrated that levels of bcl-2 mRNA markedly decreased in the ipsilateral hemisphere, whereas the amount of bax mRNA was elevated. These findings suggest that a shift in the ratio of cell death repressor Bcl-2 to cell death effector Bax and a concomitant activation of c-Fos may contribute to neuronal apoptosis in the infarcted thalamus and cortex.

Animals↗
PubMed1996

[Late ventricular potentials: significance, electrophysiology and clinical importance in coronary disease].

Ventricular late potentials are high-frequency, low-amplitude abnormal electrical signals occurring in the terminal QRS complex or on the ST segment of the electrocardiogram during sinus rhythm. They are thought to represent delayed activation of some areas of a diseased myocardium and are therefore considered as a marker of an arrhythmogenic substrate, especially in patients after myocardial infarction. An association between the presence of ventricular late potentials and the occurrence of malignant re-entrant ventricular arrhythmias has been clearly demonstrated, and the prognostic value of late potentials after myocardial infarction has been confirmed by several large prospective trials. Because it is a simple and noninvasive technique, the detection of ventricular late potentials allows a first risk stratification of postmyocardial infarction patients, together with the Holter recording, the exercise stress test, the echocardiography and the radionuclide ventriculography. Such a risk stratification strategy is essential because the empirical use of antiarrhythmic drugs has been associated with an adverse prognosis and because significant advances have been made in the management of malignant ventricular arrhythmias. The clinical value of ventricular late potentials is mainly related to their negative predictive value (93 to 98%), and their positive predictive value has been shown to be low (6 to 19%). But even if the prognostic value of late potentials after myocardial infarction is now well established, their exact role for the management of individual patients still needs to be defined.

Action Potentials↗
PubMed1996

[Not Available].

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Journal Article↗
PubMed1996

Evidence for apoptotic cell death in the choroid plexus following focal cerebral ischemia.

Focal cerebral ischemia in rats subjected to middle cerebral artery (MCA) occlusion results in apoptotic DNA fragmentation and activation of putative cell death effector genes in neurons and functional impairment of the plexus choroideus. In the present study we investigated whether cerebral ischemia may induce apoptotic cell death in the choroid plexus. Using in situ end-labeling by terminal transferase and fluorescein-dUTP, nuclear DNA breaks were detected in the choroid plexus of the lateral ventricle of the ischemic hemisphere after 6 h but not after 1.5 h of MCA occlusion. Intense cytoplasmic immunostaining for pro-apoptotic Bax protein and moderate immunolabeling for Bcl-X was observed in the epithelium of the choroid plexus of the lateral and third ventricles. However, constitutive expression of Bax and Bcl-X proteins in the plexus choroideus did not change significantly following focal ischemia. Thus, cells of the choroid plexus may die by apoptosis after several hours of cerebral ischemia. Modulation of cell death effector genes of the bcl-2 family however, may not be required for apoptotic cell death to occur.

Animals↗
PubMed1996

Antisense oligodeoxynucleotides to bax mRNA promote survival of rat sympathetic neurons in culture.

Previous in vitro studies have shown that the presence of high levels of Bax protein accelerated the rate of cell death following growth factor deprivation and that the ratio of cell death repressor Bcl-2 to cell death effector Bax may determine the susceptibility to apoptosis. Both Bcl-2 and Bax protein expression has been detected in sympathetic neurons in vivo, and overexpression of bcl-2 in cultured sympathetic neurons prevented apoptosis after deprivation of nerve growth factor (NGF). In the present study, we investigated the expression of bax and bcl-2 in primary cultures of sympathetic neurons from rat superior cervical ganglia. Furthermore, we tested the effects of a partially phosphorothioated bax antisense oligodeoxynucleotide (ODN) on the survival of sympathetic neurons in cultures supplied with suboptimal concentrations of NGF (0.5 ng/ml). A constitutive expression of bax mRNA at high levels was detected by reverse transcription and polymerase chain reaction which did not change significantly following NGF reduction or treatment with bax antisense ODN. A decrease in Bcl-2 immunoreactivity was observed by immunocytochemistry in tyrosine hydroxylase-positive neurons when cultured under suboptimal NGF concentrations, whereas Bcl-2 immunolabeled non-neuronal cells were not affected. Maximal number of neurons was obtained in control cultures containing 50 ng/ml of NGF. Few neurons survived in cultures grown in 0.5 ng/ml of NGF for 2 days (12.0 +/- 1.5% of controls, mean +/- SEM). Addition of two control ODNs at 1 microM had no effect on neuronal survival (10.1 +/- 1.2% and 11.0 +/- 1.3%, respectively), while the number of neurons was significantly increased in NGF-reduced cultures treated with a bax antisense ODNs (1 microM) (31.5 +/- 1.9%). Administration of fluorescein-labeled ODNs demonstrated intracellular uptake into cultured neurons. Treatment with bax antisense ODNs caused a significant reduction of Bax protein levels in SCG neurons by 46 +/- 2.6% as assessed by immuno-cytochemistry and digital image analysis. Taken together, our data demonstrate a constitutive expression of bax mRNA in sympathetic neurons suggesting that activation of bax expression may not be required for neuronal cell death after NGF withdrawal. After changing to suboptimal NGF concentrations, the cell-specific reduction in Bcl-2 immunoreactivity preceded morphological signs of degeneration indicating that growth factor starvation may down-regulate neuronal bcl-2 expression. Treatment with bax antisense ODNs indicated that suppression of Bax protein synthesis may promote neuronal survival in the threshold situation of insufficient trophic support.

Animals↗
PubMed1996

Increase in bax expression in substantia nigra following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment of mice.

Administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to mammals causes damage to the nigrostriatal pathway similar to that observed in Parkinson's disease. In the present study, we have investigated alterations in cell death effector gene expression induced by the neurotoxin MPTP in mouse substantia nigra. Intraperitoneal MPTP injections in mice resulted in a significant increase in bax mRNA by about two- and three-fold after 3 and 6 days, respectively. The up-regulation of bax mRNA was associated with concomitant increase in Bax immunoreactivity observed mainly in large- and medium-sized neurons in the substantia nigra that are destined to die. Our results indicate a pathophysiological significance of bax, which promotes programmed cell death, in MPTP neurotoxicity.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1996

Activation of c-Fos contributes to amyloid beta-peptide-induced neurotoxicity.

Amyloid beta peptide, a major component of Alzheimer's disease plaques, is directly toxic to various neuronal cell lines and primary neurons in culture. The mechanism underlying A beta neurotoxicity may include an increase in intracellular calcium and reactive oxygen species. In the present study, exposure of a mouse hippocampal cell line (HT-22) to the 25-35 peptide fragment of A beta (10 microM) caused a rapid and sustained increase in nuclear c-Fos immunoreactivity. Inhibition of A beta-mediated c-Fos activation by c-fos antisense oligodeoxynucleotides (5 microM) significantly protected against A beta toxicity as assessed by MTT assay. The signal transduction pathway for c-fos induction remains speculative, however, there seems to be a causal relationship between c-Fos transcription factor and A beta toxicity.

Alzheimer Disease↗
PubMed1996

Intracellular retention of cytosine arabinoside triphosphate in blast cells from children with acute myelogenous and lymphoblastic leukemia.

The importance of the cellular pharmacokinetics of cytarabine triphosphate (ara-CTP) with regard to therapeutic efficacy is well established. In vitro and in vivo monitoring of pharmacokinetic parameters of leukemic blast cells were initiated in order to contribute to the pharmacological basis of optimal ara-C treatment strategies. Peripheral or bone marrow blast cells from 66 leukemic patients [51 acute myelogenous leukemia (ALL), 15 acute lymphoblastic leukemia (AML) were separated and incubated with ara-C for 1 hour and in ara-C-free medium for another 3 hours, and the intracellular formation and retention of ara-CTP was measured. In eight children who received continuous ara-C infusion for induction treatment, the ara-CTP concentration in circulating blast cells was monitored in vivo. The in vitro values observed in this assay corresponded to the cellular levels monitored in vivo. The ara-CTP retention differed clearly among the individual groups, as classified by immunophenotype at the time of the initial diagnosis: non-T-ALL 67+/-25% (x+/-SD, n=33), T-ALL 37+/-15% (n=8), and AML 34+/-18% (n=14). The difference in ara-CTP retention between non-T-All and AML (P<0.05) as well as T-ALL (P<0.05) was significant. There was a tendency toward lower ara-CTP retention in relapsed as compared with newly diagnosed ALL, but the difference was not significant. The maximal accumulation of ara-CTP (after 1 hour incubation) was comparable in AML, T-ALL, non-T-ALL, and blast cells from children in relapse. The observed similarity of cellular accumulation in all groups and the significantly more rapid decrease in T-ALL and AML provide the pharmacokinetic rationale supporting the prolonged infusion duration for ara-C in these subgroups as an alternative to the intensification by high-dose ara-C schedules with short-term infusion.

Adolescent↗
PubMed1996

Long-term evaluation of EC-IC bypass patency.

The EC-IC Bypass Study Group could not detect any benefit from surgery compared to medical management in the prevention of stroke in 1985 [15]. During the past years surgical revascularization was re-evaluated and considered as an appropriate treatment for a small subgroup of patients with recurrent focal cerebral ischaemia and impaired haemodynamics. This retrospective study examines the long-term benefit and patency rate of bypass. We present a follow-up of 5.6 years of 47 patients, all of whom underwent bypass surgery after 1985. Forty patients suffered recurring transient ischaemic attacks due to uni- or bilateral internal carotid artery occlusion. Examination included neurologic status, TCD with CO2 or Diamox challenge, angiography, CT and SPECT scans. Neurological improvement was seen in 23% of patients with better results after early surgery, a worsening in 22% suffering further ischaemic events on a postoperative average of 2.8 years. Patency rate for vein graft material was 50%, for the STA-MCA procedure 91%. Occlusion of the vein graft occurred on an average after 1.4 years, other anastomosis after 2.7 years. We conclude that only few patients derived long-term benefit from EC-IC bypasses. Functioning of the bypass worsens over time, suggesting a role for surgery predominantly in the first year of ischaemic events due to insufficient collateral supply. Actual indications for bypass surgery may be patients with failure of maximal medical therapy and progressive ischaemia and haemodynamic compromise.

Adult↗
PubMed1996

Peculiarities of the regulation of fermentation and respiration in the crabtree-negative, xylose-fermenting yeast Pichia stipitis.

The respiration of Pichia stipitis was not repressed by either high concentrations of fermentable sugars or oxygen limitation. Fermentation was not induced by high sugar concentrations, but was inactivated by aerobic conditions. The activity of pyruvate dehydrogenase was constitutive. In contrast, pyruvate decarboxylase, alcohol dehydrogenase, and aldehyde dehydrogenase were induced by a reduction in the oxygen tension. It was demonstrated that in P. stipitis, the pyruvate decarboxylase is not induced by a signal from glycolysis. Contrary to Saccharomyces cerevisiae, the pyruvate decarboxylase was not inhibited by phosphate.

Alcohol Dehydrogenase↗
PubMed1996

Prevention of cerebral vasospasm after experimental subarachnoid hemorrhage by RO 47-0203, a newly developed orally active endothelin receptor antagonist.

Since their discovery in 1988, endothelins have attracted scientific interest because of their extremely potent and long-lasting vasoconstrictive effects, similar to cerebral vasospasm in humans. In this study, the efficacy of the orally active endothelin receptor antagonist RO 47-0203 for prevention of cerebral vasospasm after experimental subarachnoid hemorrhage, using the two-hemorrhage dog model, was investigated. Twenty-eight beagle dogs were used in this laboratory experiment. Fourteen animals each were assigned to the treatment and control groups. In the treatment group, each dog received two single doses of 30 mg/kg RO 47-0203 orally per day. The diameter of the basilar artery decreased from 1.36 +/- 0.17 mm on Day 1 to 1.19 +/- 0.23 mm on Day 8 in the treatment group, whereas in the control group, the vessel diameter decreased from 1.48 +/- 0.19 mm on Day 1 to 1.02 +/- 0.22 mm on Day 8. These results corresponded to a decrease of vessel diameter of 13.1% +/- 11.2% in the treatment group and a decrease of vessel diameter of 30.7% +/- 12.4% in the control group (P < 0.001). Concentrations of endothelin-1 in cerebrospinal fluid significantly increased with time after subarachnoid hemorrhage. These results emphasize the important role of endothelin in the development of cerebral vasospasm and present first-time evidence that prevention of cerebral vasospasm can be achieved by the endothelin receptor antagonist RO 47-0203.

Administration, Oral↗