Biomedical subjects

K Winkler

Publications and source records attributed to K Winkler.

334 records · Page 19Linked to original sources

PubMedDate not supplied

A method of determining intrinsic hepatic clearance from the first-pass effect.

1. The relation between systemic hepatic clearance, intrinsic hepatic clearance and hepatic blood fow is considered from the point of view of the sinusoidal perfusion (parallel tube) model of the liver. 2. It is shown how intrinsic hepatic clearance may be calculated, for substrates eliminated in the liver and the kidney only, from data obtained by introducing successively an oral and an intravenous dose (i.e., by using the first-pass effect) with the clinically cumbersome catheterization of the liver vein. 3. The rate of hepatic blood flow is shown to follow from the same data.

Animals↗

PubMedDate not supplied

Mitochondrial tRNA(Cys) mutation A5823G in a patient with motor neuron disease and temporal lobe epilepsy.

We discovered a new homoplasmic mutation in the mitochondrial cysteine tRNA of a 60-year-old Caucasian male suffering from asymmetrical pure lower motor neuron disease (MND) and temporal lobe epilepsy (TLE). Furthermore, titrations with Amytal, an inhibitor of NADH:CoQ oxidoreductase, revealed mild mitochondrial dysfunction in skeletal muscle tissue, which was described in patients with MND in an earlier report. The mutation was undetectable in 155 Caucasian controls of both sexes, in 40 MND patients and in 13 individuals suffering from TLE. It was, however, detected in a heteroplasmic state in the patient's mother, who did not suffer from a neurological disorder. Since this rare mutation affected a nonconserved base position and was not observed in MND or TLE materials, its relation to disease remains unclear.

Blotting, Southern↗

PubMedDate not supplied

Studies of the RB1 gene and the p53 gene in human osteosarcomas.

We analyzed 14 native osteosarcoma tissue samples for alterations of the tumor suppressor genes RB1 and p53 on the DNA level, and as far as possible, the RNA level. Southern blot analyses concerning both tumor suppressor genes were carried out in all osteosarcomas. In two cases we could demonstrate a deletion within the RB1 gene. DNA analysis of a third osteosarcoma patient revealed a rearrangement of the p53 gene. We had the opportunity of performing corresponding northern analyses in eight native osteosarcoma specimens. The RB1 gene expression was significantly decreased or completely absent in six tumor samples. In two of these tissue probes the expression of both tumor suppressor genes was missing. We determined coexistence of decreased expression of both tumor suppressor genes in one additional case. In summary, 7/14 or 6/8 cases of osteosarcomas (including only those cases which allowed both analyses) showed RB1 gene alteration. In 3/14 or 3/8 osteosarcomas we could determine p53 gene abnormalities. This may indicate that either loss of p53 function is etiologically important only for the development of some osteosarcomas, or a major part of p53 gene mutations are subtle ones and their detection requires more sophisticated techniques, which are currently under development.

Bone Neoplasms↗

PubMedDate not supplied