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K Lange

Publications and source records attributed to K Lange.

At least 145 records · Page 8Linked to original sources
PubMed1988

Effects of non-steroidal anti-inflammatory drugs on rat gastric mucosal leukotriene C4 and prostanoid release: relation to ethanol-induced injury.

1. The effects of oral and subcutaneous administration of the non-steroidal anti-inflammatory drugs sodium salicylate, aspirin and indomethacin on ex vivo gastric mucosal release of leukotriene C4 (LTC4) prostaglandin E2 (PGE2), 6-oxo-PGF1 alpha and thromboxane B2 (TXB2) were investigated in rats under basal conditions as well as after challenge with ethanol. 2. Basal release of PGE2, 6-oxo-PGF1 alpha and TXB2 was inhibited by oral administration of aspirin (0.6-400 mgkg-1) and indomethacin (4 or 20 mgkg-1), but not by sodium salicylate (up to 400 mgkg-1), in a dose-dependent manner. Oral administration of aspirin in the dose range 3.2-400 mgkg-1 and of indomethacin (20 mgkg-1) additionally inhibited release of LTC4, while sodium salicylate (up to 400 mgkg-1) had no effect. Indomethacin (20 mgkg-1) and aspirin (400 mgkg-1) administered subcutaneously inhibited generation of cyclo-oxygenase products of arachidonate metabolism, but did not significantly affect LTC4 synthesis. 3. Oral instillation of ethanol caused gastric mucosal damage and simultaneously induced a selective increase in the ex vivo release of LTC4 from rat gastric mucosa, while release of cyclo-oxygenase products of arachidonate metabolism was not significantly affected. Oral pretreatment of rats with sodium salicylate protected the gastric mucosa and simultaneously inhibited the ethanol-stimulated gastric mucosal LTC4 release in a dose-dependent manner. Sodium salicylate had no effects on the release of PGE2 and TXB2, while that of 6-oxo-PGF1 alpha was slightly increased. 4. Pretreatment with indomethacin (4 or 20mg kg- p.o.) or aspirin in doses up to 25mg kg-1 p.o. prior to oral instillation of ethanol did not inhibit gastric mucosal damage and had no effect on the stimulatory action of ethanol on LTC4 release. Higher doses of aspirin (100mgkg-1 or 400mgkg-1 p.o.) reduced the mucosal damaging effect of ethanol and simultaneously inhibited LTC4 release. 5. The results suggest that aspirin and indomethacin in concentrations higher than those necessary to inhibit the cyclo-oxygenase pathway of arachidonate metabolism additionally inhibit gastric mucosal LTC4 synthesis under basal conditions, while sodium salicylate has no such effect. On the other hand, sodium salicylate, but not indomethacin or low doses of aspirin (up to 25mg kg 1), by an unknown mechanism inhibits stimulation of LTC4 biosynthesis by ethanol and simultaneously protects the gastric mucosa against ethanol-induced damage. Similar effects of high oral doses (> 100mgkg- 1) of aspirin might be due to significant formation of salicylate. These results suggest that there is a causal relationship between enhanced LTC4 biosynthesis and the development of ethanol-induced gastric injury.

Animals↗
PubMed1988

The affected-pedigree-member method of linkage analysis.

This paper describes a generalization of the affected-sib-pair method of linkage analysis to pedigrees. By substituting identity-by-state relations for identity-by-descent relations, we develop a test statistic for detecting departures from independent segregation of disease and marker phenotypes. The statistic is based on the marker phenotypes of affected pedigree members only. Since it is more striking for distantly affected relatives to share a rare marker allele than a common marker allele, the statistic also includes a weighting factor based on allele frequency. The distributional properties of the statistic are investigated theoretically and by simulation. Part of the theoretical treatment entails generalizing Karigl's multiple-person kinship coefficients. When the test statistic is applied to pedigree data on Huntington disease, the null hypothesis of independent segregation between the marker locus and the disease locus is firmly rejected. In this case, as expected, there is a loss of power when compared with standard lod-score analysis. However, our statistic possesses the advantage of requiring no explicit assumptions about the mode of inheritance of the disease. This point is illustrated by application of the test statistic to data on rheumatoid arthritis.

Female↗
PubMed1987

Preliminary ranking procedures for multilocus ordering.

N linked loci can be arranged in N!/2 possible orders. We describe two criteria for providing a preliminary ranking of the possible orders based on the N(N-1)/2 pairwise lod score curves for the loci. For a given order the first criterion is the sum of the N-1 maximal lod scores corresponding to the adjacent pairs of loci in the order. The second criterion is the minimum of a least-squares problem due to J.M. Lalouel (1977, Heredity 38(1): 61-77). This least-squares problem requires the maximum likelihood recombination fraction estimates and their standard errors. For N small it is feasible to evaluate these measures for every possible order. For N large we use a simulated annealing algorithm. This gives a fairly complete listing of the best-candidate orders without sampling every possible order. These ranking methods are applied to data from linkage groups on chromosomes 1, 6, 11, and 13.

Algorithms↗
PubMed1987

Genetic linkage studies of ataxia-telangiectasia: phenotypic blood markers.

We have tested thirty-two phenotypic blood markers on sixteen families with with ataxia-telangiectasia (AT) in an attempt to identify the chromosomal location of the AT gene(s). Although at least five complementation groups have been defined, it is not known whether the corresponding AT genes are clustered or dispersed in the genome. Both clustered and dispersed genetic models were considered in linkage analyses. No significant linkages were found. The data exclude approximately 7 per cent of the autosomal genome for a 'clustered' model and 2 per cent of the autosomal genome for a 'dispersed' model. Several genomic areas were identified which warrant further study.

Ataxia Telangiectasia↗
PubMed1987

An algorithm for automatic genotype elimination.

Automatic genotype elimination algorithms for a single locus play a central role in making likelihood computations on human pedigree data feasible. We present a simple algorithm that is fully efficient in pedigrees without loops. This algorithm can be easily coded and has been instrumental in greatly reducing computing times for pedigree analysis. A contrived counter-example demonstrates that some superfluous genotypes cannot be excluded for inbred pedigrees.

Algorithms↗
PubMed1986

Univariate and bivariate analyses of cholesterol and triglyceride levels in pedigrees.

A multivariate normal model for pedigree analysis is applied to fasting total serum cholesterol and total serum triglyceride measurements on 771 individuals in 95 pedigrees from Rochester, MN. Univariate and bivariate analyses are carried out to determine to what extent the aggregation and coaggregation in families of these two traits may be attributed to shared genetic and environmental factors. Pedigrees were ascertained through a sample of schoolchildren enriched for those with serum cholesterol levels in the highest and lowest deciles of their age- and sex-specific distributions. Ascertainment is corrected for by conditioning the likelihood on the trait values of the probands. Univariate results confirm the findings of previous studies indicating that familial aggregation of serum cholesterol and triglyceride levels is due both to shared genes and to shared environmental factors. Results of the bivariate analyses suggest that the coaggregation of cholesterol and triglyceride levels in these families is strongly influenced by both shared genes (pleiotropy) and shared environmental factors. These findings are consistent with our understanding of lipid metabolism and of specific environmental factors known to influence both traits.

Adolescent↗
PubMed1986

Cohabitation, convergence, and environmental covariances.

Temporal variation in traits has long been a central theme in epidemiology. However, human geneticists have largely avoided this topic. Recently, several authors have shown how temporal variation in relative-to-relative covariances can be accommodated within the framework of variance components analysis. The present paper attempts to clarify the mathematics implicit in their approach. A stochastic mechanism is discussed that causes covariances to converge or diverge exponentially fast as relatives cohabit or lead separate lives.

Environment↗
PubMed1986

The genetic transmission of schizophrenia: application of Mendelian latent structure analysis to eye tracking dysfunctions in schizophrenia and affective disorder.

The first-degree relatives of probands with schizophrenia tend to have abnormal smooth pursuit eye tracking, even when the proband's smooth pursuit is normal. In order to account for this finding, we propose that schizophrenia and disturbed eye tracking are independent expressions of an underlying "latent" trait which is genetically transmitted. The data on manic-depressive illness, but not schizophrenia, fit a simpler model in which abnormal smooth pursuit is a consequence of the psychiatric illness, rather than an independent expression of an underlying trait.

Bipolar Disorder↗
PubMed1986

Ethanol stimulates formation of leukotriene C4 in rat gastric mucosa.

Ethanol-induced gastric mucosal damage is characterized by microcirculatory changes such as stasis and plasma leakage. Sluggish blood flow and stasis have also been observed after administration of exogenous leukotriene (LT) C4. The effect of ethanol on the release of LTC4 from rat gastric mucosa was therefore investigated. It was found that intragastric instillation of ethanol increases gastric mucosal release of LTC4 in a dose- and time-dependent manner parallel to the production of gastric lesions. The lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) and the anti-ulcer drug carbenoxolone (CX) inhibited mucosal release of LTC4 and simultaneously protected against gastric damage caused by ethanol. It is concluded that increased formation of LTC4 and/or other 5-lipoxygenase-derived products of arachidonate metabolism may be involved in ethanol-induced gastric damage. Furthermore, inhibition of the 5-lipoxygenase pathway may be an important mechanism of action of gastric protective drugs.

Animals↗
PubMed1986

A test statistic for the affected-sib-set method.

This paper discusses generalizations of the affected-sib-pair method. First, the requirement that sib identity-by-descent relations be known unambiguously is relaxed by substituting sib identity-by-state relations. This permits affected sibs to be used even when their parents are unavailable for typing. In the limit of an infinite number of marker alleles each of infinitesimal population frequency, the identity-by-state relations coincide with the usual identity-by-descent relations. Second, a weighted pairs test statistic is proposed that covers affected sib sets of size greater than two. These generalizations make the affected-sib-pair method a more powerful technique for detecting departures from independent segregation of disease and marker phenotypes. A sample calculation suggests such a departure for tuberculoid leprosy and the HLA D locus.

Alleles↗
PubMed1986

Glucose transporter in plasma membranes of cultured neural cells, as characterized by cytochalasin B binding.

Identification of hexose transporter sites by cytochalasin B binding was conducted with a centrifugation assay. The determination of KD and Bmax values by LIGAND computer analysis provided binding data that are similar in primary astrocytes (238 nM and 14 pmol/mg protein) and neuroblastoma cells (179 nM and 13.6 pmol/mg protein). In contrast, only an insignificant number of transporter sites was detectable in C6 glioma cells, irrespective of whether membrane fractions were obtained by a two-phase polymer system or by a latex phagocytosis technique yielding inside-out plasma membranes. The latter membrane preparation was utilized to identify and quantitate the transporter molecules at the inner membrane surface of primary astrocytes, i.e., 160 nM (KD) and 5.8 pmol/mg protein (Bmax), respectively.

Animals↗
PubMed1986

Approximate confidence intervals for risk prediction in genetic counseling.

In current genetic counseling practice, a single risk estimate is often quoted to a family rather than a range of risks. Such point estimates are predicated on knowing basic parameters like recombination fractions exactly when, in fact, there may be considerable uncertainty about them. Using the large sample theory of statistics, it is possible to derive approximate risk intervals that incorporate known statistical imprecision. The necessary theory will be briefly discussed and illustrated by an application to family counseling for Duchenne muscular dystrophy in the presence of two flanking markers. Some of the problems of the theory will be mentioned. These include lack of adequate sample size to justify the conclusions of large sample theory, pronounced nonlinearity in the risk function, and failure to take into proper account genetic interference. Except in trivial cases, sophisticated computer software is needed to carry out the computations of risk intervals.

Female↗