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Biomedical subjects

I Forster

Publications and source records attributed to I Forster.

6 recordsLinked to original sources
PubMed1995

Inward rectification of neuronal nicotinic acetylcholine receptors investigated by using the homomeric alpha 7 receptor.

The strong inward rectification observed in neuronal nicotinic ACh receptors was examined by using alpha-bungarotoxin sensitive, homomeric alpha 7 neuronal nicotinic ACh receptors derived from chick brain. Receptors were expressed in Xenopus laevis oocytes and functionally assessed by the two electrode voltage clamp technique. Site directed mutagenesis of residues thought to line the putative ion pore revealed that negatively charged glutamate residues located at the inner mouth of the channel are essential for rectification. This finding was confirmed both for the active open state and for receptors mutated to conduct in one of the desensitized states. No outward tail relaxations were observed with voltage jumps to depolarizing potentials, suggesting that rectification was not due to intrinsic gating. For the wild type receptor, intracellular injection of CDTA, a chelating agent having a high affinity for Mg2+, reduced rectification in a dose dependent manner, suggesting that rectification originates, in part, from open channel block by internal free Mg2+. These findings support the hypothesis that charged residues at the inner mouth of the pore influence the Mg2+ affinity of the blocking site.

Amino Acid Sequence↗
PubMed1994

Transient bifrontal solitary periventricular cysts in term neonates.

We describe three children born at term investigated for neonatal seizures or transient apnoea. Cranial ultrasound and MRI unexpectedly revealed symmetrical periventricular cysts adjacent to the anterior horns. We found no evidence of prenatal viral infection, intraventricular or subependymal haemorrhage or hypoxic-ischaemic lesions. The lesions were not seen on MRI at 3 months of age, but there was no compensatory dilatation of the anterior horns nor secondary loss of white matter. The appearance and location of these transient cysts were different from those of the cystic changes which typically follow germinal matrix haemorrhage or periventricular leukomalacia. Their pathogenesis and clinical significance remain to be determined.

Brain Diseases↗
PubMed1983

Cyclosporine in human bone marrow transplantation. Serum concentration, graft-versus-host disease, and nephrotoxicity.

Serum concentrations of cyclosporine were studied in 42 patients given cyclosporine for the prevention of graft-versus-host-disease (GVHD) following allogeneic bone marrow transplantation (BMT). Serum trough levels for cyclosporine were determined in each patient at least once weekly during the first 3 months and were compared with the occurrence of GVHD and with nephrotoxicity. Cyclosporine was given as 20 mg/kg i.m. or as a 24-hr infusion for the first 5-7 days. This was followed by a single daily oral dose of 12.5 mg/kg for 6 months. Cyclosporine was then gradually reduced and stopped after one year. After a median observation period of 2 years 25 of the 42 patients (59%) are alive. Twenty six patients (62%) developed GVHD, which was stage II or more in 11 (26%) and fatal in 2 patients (5%). Five patients developed GVHD 6-8 weeks after withdrawal of cyclosporine one year after BMT. All patients improved after restarting cyclosporine. No correlation between cyclosporine serum concentration and GVHD was observed, but patients with GVHD had greater fluctuations of their serum trough levels. Serum creatinine increased in all patients soon after BMT and was correlated with cyclosporine serum concentration during the first month. Serum creatinine, however, rose further despite lower cyclosporine concentrations in the second month. These results show that cyclosporine effectively reduces the severity, but not the incidence, of GVHD suggesting that there is a subset of cells resistant to cyclosporine. The therapeutic range, however, between high doses (which are often associated with nephrotoxicity) and the minimal effective dose of cyclosporine, has yet to be defined.

Adolescent↗
PubMed1982

Histoincompatible skin and marrow grafts in rabbits on cyclosporin A.

Cyclosporin A (Cy A; 15 mg/kg s.c.) allows allogeneic histoincompatible skin graft survival in 10 of 10 rabbits as long as the drug is given. The same dose of Cy A does not affect acute graft-versus-host disease (GVHD) and increase survival of rabbits after allogeneic bone marrow transplantation between the same two strains, when two groups of 15 animals are tested. Median survival of 14 engrafted animals without Cy A was 23 days, of 12 engrafted animals with Cy A 22 days (not significant). Cryopreservation of bone marrow delays the onset of GVHD and increases survival of engrafted animals. Median survival of 5 engrafted animals without Cy A was 33 days, of 14 engrafted animals with Cy A 35 days. Our hypothesis is that one part of early GVHD as well as of early graft rejection is mediated by a subclass of cells which is resistant to Cy A. This hypothesis is supported by the finding that most transplanted skins show a self-limited period of infiltration and induration. Skin grafts survive this period of infiltration. If the same potentially self-limited process occurs in the liver or the intestine during acute GVHD, animals die. this hypothesis could explain why Cy A allows skin graft survival but does not affect acute GVHD.

Animals↗