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Biomedical subjects

M Koch

Publications and source records attributed to M Koch.

At least 361 records · Page 20Linked to original sources

Family history of ovarian cancer patients: a case-control study.

In order to obtain a more correct estimate of cancer incidence in relatives of cases with ovarian cancer and relatives of age-matched controls, information was obtained on family size, date of birth and death, and cancer history. The average total number of first degree (parents and siblings) and some second degree (uncles and aunts) relatives for cases (15.03) and controls (15.22) is very similar. Of all the relatives 33% were Alberta residents or decreased in Alberta after 1966 so they could be checked in the population based Alberta Cancer Registry. There was a 14% level of error in the information provided, 9% for first degree relatives and 25% for uncles and aunts. The errors included missed malignancies, benign lesions quoted as malignancies, incorrect cancer site and inaccurate dates of birth, diagnosis or death. Results were compared between the relatives of cases and controls using either all relatives or only Alberta residents. For the Alberta residents, expected numbers of malignancies were calculated by age/sex-specific person/years and age/sex-specific incidence rates. The number of relatives with ovarian cancer is significantly higher in cases than in controls in both data sets, but shows a limited relative risk of 2.61 (95% confidence limits 1.12-1.59). Clustering of cases is exceptional, only one patient out of 197 had two relatives with ovarian cancer and this was a case with a larger than average total number of relatives. In conclusion, although there is a significantly higher incidence of ovarian cancer in the family history of cases than of controls, it is not very common and only nine out of 197 cases (4.6%) presented with such background.

Adolescent↗

Linkage studies of Myotonia congenita and Paramyotonia congenita.

Six German families segregating for Myotonia congenita (MC) and eight families from Germany and Great Britain with Paramyotonia congenita (PC) were tested for linkage relationships using 35 serological and biochemical markers. No linkage of MC to any of the markers was evident, but a positive sum of lod scores for PC vs. the HP locus (z = 1.16, theta = 0.16) was found. The results encourage further investigations involving chromosome 16 markers.

Chromosome Mapping↗

[Total synthesis of oxa-9-anthracyclines].

Racemic 7-hydroxy-9-oxa-anthracyclinone (5a) has been synthetised in seven steps from quinizarin (6) and its resolution achieved after glycosylation with 3,4-di-O-acetyl-2-deoxy-L-fucose. Chiral pool syntheses of (8S)-8-hydroxymethyl-9-oxa-anthracyclinone (5b) and of (8S,10R) and (8S,10S)-8-hydroxymethyl-10-methyl-9-oxa-anthracyclinones (5c and 5d) have been achieved using (R)-2,3-O-isopropylideneglyceraldehyde (12) and leucoquinizarin (13) as starting materials. Glycosylation of aglycones 5b-5d by either 3,4-di-O-acetyl-2-deoxy-L-fucose or various 3-amino-2,3,6-trideoxy-L-hexoses yielded the corresponding anthracyclines. The synthetic glycosides do not show significant cytotoxic activity at a concentration of 1 microgram/ml against L 1210 cells.

Animals↗

[Plants from New Caledonia. Alkaloids from Sarcomelicope dogniensis Hartley stem bark].

Two new pyranofuroquinoline alkaloids, cis-1,2-dihydroxy-1,2 dihydroacronydine 2 and trans-1,2-dihydroxy-1,2-dihydroacronydine 3 have been isolated from Sarcomelicope dogniensis stem bark. Their structures have been elucidated by spectral analysis and chemical correlations. In addition, 11 other alkaloids have been isolated from the stem bark of this species.

Alkaloids↗

Synthesis and cytotoxic effects of hydroxymethyl-3-pyridyl- and 2-chloro-5-pyridyltriazene derivatives.

3-Hydroxymethyl-3-methyl-1-(3-pyridyl)-triazene (III) and 3-hydroxymethyl-3-methyl-1-(2-chloro-5-pyridyl)-triazene (VI) were synthesized and their cytotoxic effects towards S180 cells compared with those of the corresponding dimethyltriazene and monomethyltriazene derivatives. The hydroxy-methyltriazenes were one to two orders of magnitude more inhibitory than the corresponding dimethyl analogs, as assessed by cell growth, colony forming and macromolecular synthesis assays. Comparable effects were observed with the related monomethyl triazenes indicating that the activity of (III) and (VI) could result, at least in part, from release of monomethyl derivatives. The corresponding dimethyltriazenes were much less toxic to S180 cells and exerted only an unspecific cytotoxic activity at the maximal attainable dose (5 X 10(-3) M). The cytotoxic activities of the tested triazenes were correlated with their chemical half-lives under near physiological conditions (pH 7.5).

Animals↗

Survival rates among patients with cancer in Alberta in 1974-78.

We calculated 5-year crude and relative survival rates, by age and sex, for patients in Alberta in whom cancer was diagnosed between 1974 and 1978. Cancers with low overall 5-year relative survival rates (less than 35%) included stomach cancer, cancer of the pancreas, lung cancer, brain cancer, multiple myeloma and myeloid leukemia. Cancers with high overall 5-year relative survival rates (more than 70%) included melanoma, breast cancer, cancer of the uterus, cancer of the bladder and Hodgkin's disease. Five-year relative survival rates were generally lower in the highest age group (75 years or more). A strong inverse relation between age and survival was noted for brain cancer, non-Hodgkin's lymphoma, Hodgkin's disease and myeloid leukemia.

Adult↗

Scintigraphic distribution of 123 I labelled proinsulin, split conversion intermediates and insulin in rats.

Insulin, biosynthetic human proinsulin and 2 human proinsulin conversion intermediates, des (64, 65) human proinsulin and des (31, 32) human proinsulin, were labelled with 123 I and the derivatives monosubstituted on Tyr A14 were purified by reverse phase high performance liquid chromatography. The four tracers were injected into anaesthetized rats via a jugular or a portal vein and time activity curves were generated for the liver and kidneys using a gamma camera and an online computer. Liver extraction coefficients varied in the order insulin (38%), des (64, 65) human proinsulin (11.7%), des (31, 32) human proinsulin (3.2%), human proinsulin (1.6%); whereas half-life of hepatic activity varied in the reverse order, from 6 min for insulin, to 45 min for human proinsulin. As expected for a non-receptor mediated process, kidney extraction varied conversely to liver extraction, being highest for human proinsulin and lowest for insulin. It is concluded that the kinetics of human proinsulin conversion intermediates depends upon the site of cleavage and deletion and is intermediate between those of insulin and intact human proinsulin.

Animals↗

Advantages and pitfalls of radioimmune and enzyme linked immunosorbent assays of insulin antibodies.

Human sera were tested for insulin antibodies by fluid and solid phase assays. Radioimmune titres determined with 125-I Tyr A14 insulin were not correlated with those obtained using insulin coated microplates and enzyme linked immunodetection (n = 60). Several reasons for this lack of correlation were found. Iodine substitution on the A14 residue of insulin may significantly alter the avidity of some insulin antibodies for their ligand; hence, disclosing a heretofore unsuspected pitfall for antibody determination by radioimmunoassay. Specificity for bovine insulin was easily demonstrable in fluid phase by comparing the binding of monoiodinated bovine, porcine and human insulin. By contrast, in solid phase assay, titres obtained with microplates coated with bovine or human insulin were almost equal, regardless of the serum specificity for bovine insulin. This lack of specificity of the solid phase assay is not due to denaturation or unavailability of the bovine specific epitope because: bovine specificity could be demonstrated by competitive assay, after preincubation of the serum with insulin of the different species; and, coating with crosslinked insulin dimers or oligomers instead of monomers did not unmask bovine specificity. It is concluded that radioimmune methods are best suited to study specificity but may be biased by the presence of the radioiodine label whereas solid phase assay detects low avidity antibodies with great efficiency but is less appropriate to study specificity.

Animals↗

Localization of a human Na+,K+-ATPase alpha subunit gene to chromosome 19q12----q13.2 and linkage to the myotonic dystrophy locus.

The gene coding for a Na+,K+-ATPase alpha subunit (ATP1A3) has been localized to the q12----q13.2 region of human chromosome 19, potentially close to the myotonic dystrophy (DM) gene. In view of previous studies implicating a Na+,K+-ATPase in the pathology of DM, we have examined the possibility that ATP1A3 is a candidate for the DM locus. Although linked, several clear instances of recombination between ATP1A3 and DM rule out the possibility that mutations in ATP1A3 cause the disease. Examination of multiply informative pedigrees indicates the gene order DM-APOC2-ATP1A3.

Animals↗

Studies on quantitative morphology. XIII. Heterogeneity in the mammary gland of rats.

In the rat mammary gland, the distribution of tissues forming this organ is not homogeneous. In order to get representative information about the percentual distribution of lumina, epithelial, adipous and connective tissues it is necessary to take serial sections from the whole organ. This is a very strenuous procedure and is defensible at most in small organs. We demonstrated that, in general, 2-4 histological sections are satisfying all demands when they are taken at distances of about 600-1,000 micron. The percentages of glandular constituents are appropriately ascertained by using a net point system with distances of about 600 micron between single points, provided there is sufficient number of hits. For special purposes, e.g. the recording of drug effects, it is advisable to reduce the distances of step sections to 400-500 micron with net point distances of about 200 micron. Here we found a good compromise complying with both accuracy of results and expenditure of measuring time.

Adipose Tissue↗

Effects of intracoronary nitroglycerin on coronary vascular volume in man, assessed by a double-indicator dilution technique.

The effects of 0.2 mg nitroglycerin administered directly into the left coronary artery were studied in 7 patients with coronary artery disease. A multipurpose catheter designed for simultaneous measurement of coronary sinus flow and great cardiac vein flow by thermodilution and for addition recording of dye dilution curves by a fiberoptic method was introduced from a right antecubital vein into the coronary sinus and advanced with its tip to the great cardiac vein/anterior cardiac vein juncture. Coronary sinus flow and great cardiac vein flow were measured using the constant infusion technique. Selective bolus injections of indocyanine green dye were measured using the constant infusion technique. Selective bolus injections of indocyanine green dye were performed into the left coronary system via a 8 French Judkins catheter and dye dilution curves were recorded in the upper great cardiac vein. From these curves, coronary transit time was assessed and coronary vascular volume was calculated as great cardiac vein flow times coronary transit time. Intracoronary nitroglycerin led to a transient drop in regional coronary resistance that was associated with an almost parallel increase in intravascular volume. Since this increase in coronary vascular volume exceeded the well-known dilatory effect on the epicardial arteries, and lasted slightly longer than the drop in regional resistance, these data imply that the vasodilatory action of nitroglycerin is different in magnitude as well as in time course in different parts of the coronary circulation.

Blood Volume↗