Role of phospholipase A in multiorgan failure with special reference to ARDS and acute renal failure (ARF).

In 150 patients admitted to an ICU phospholipase A serum activity was measured daily. The correlation between the increase of phospholipase A serum activity and the severity of adult respiratory distress syndrome (ARDS) and the incidence of acute renal failure (ARF), two important target systems in multiple organ failure (MOF) syndrome was studied as well as the efficacy of a treatment with phospholipase A inhibitors (methylprednisolone and dexamethasone). The results of this study show that there exists a statistically significant correlation between the increase of phospholipase A activity and the incidence of multiple organ failure.

Genetic analysis of IDDM: summary of GAW5 IDDM results.

This paper summarizes the analyses by participants in the insulin-dependent diabetes mellitus (IDDM) component of Genetic Analysis Workshop 5 (GAW5). The data were obtained from 94 families with two or more IDDM sibs. Topics treated in the Workshop analysis included the following: methods for detecting associations and linkage, the contribution by HLA-linked and -unlinked loci to IDDM susceptibility, the role of subtypes of the serologically defined HLA specificities, the implications of associated diseases other than IDDM in the families, the significance of antibodies to Coxsackie viruses, and of autoantibodies to pancreatic islet cells and insulin, and the use of genetic models to analyze the inheritance of IDDM.

Linkage analysis in granular corneal dystrophy (Groenouw I), Schnyder's crystalline corneal dystrophy, and Reis-Bücklers' corneal dystrophy.

Tight linkage was excluded for 8 markers in 37 blood relatives from 3 families, 29 of whom had granular corneal dystrophy (Groenouw I). Inconclusive results were obtained for linkage with four marker loci. The highest positive LOD score was 0.

Genetic analysis of IDDM: the GAW5 multiplex family dataset.

In a collaborative effort by 12 centers from Europe and North America, data were assembled from 94 multiplex families with insulin-dependent diabetes mellitus (IDDM) for analysis of genetic and other factors of possible etiological importance. The dataset contains information on the following genetic markers: HLA-DR beta and -DQ beta restriction fragment length polymorphisms (RFLPs), three RFLPs detected with two probes that map 5' to the insulin gene, the serologically defined HLA loci, and the immunoglobulin allotypes. Data also were included for auto-antibodies to insulin and pancreatic islet cells as possible indicators of pathogenesis and for antibodies to certain viruses that have been implicated as "triggering" agents in IDDM.

Association and sibpair analysis for the HLA, Gm, Km, and insulin polymorphisms in multiplex IDDM families.

A log-linear model was used to analyze three-way interactions between IDDM and pairs of genetic markers. To do this, a special sample dataset was selected by taking one affected and one unaffected child from each family. Some three-way interactions were found for associations between insulin-dependent diabetes mellitus (IDDM), HLA-DR, and DQ restriction enzyme fragment length polymorphism (RFLP) patterns.

Gene targeting in plants.

Although the generation of transgenic plants is now routine, the integration of foreign genetic information has so far been at random sites in the genome. We now present evidence for directed integration into a predicted location in the host plant genome. Protoplasts of transgenic tobacco (Nicotiana tabaccum) plants carrying copies of a partial, non-functional drug-resistance gene in the nuclear DNA were used as recipients for DNA molecules containing the missing part of the gene.

Family studies in scleroderma (systemic sclerosis) demonstrating an HLA-linked increased chromosomal breakage rate in cultured lymphocytes.

An increased chromosomal breakage rate (ICBR) was found in 27 of 28 patients with scleroderma (systemic sclerosis, SS) - 5 with the syndrome including calcinosis cutis, Raynaud phenomenon, esophagus hypomotility, sclerodactyly and telangiectasia (CREST), 4 incomplete CREST, 1 overlapping syndrome, 18 progressive systemic sclerosis (PSS). Not only the patients, but also about half of their first-degree relatives showed an increased chromosomal breakage rate (more than 5 breaks per 100 metaphases). This character segregated as a dominant marker in nine families of scleroderma patients.

Genetic heterogeneity, modes of inheritance, and risk estimates for a joint study of Caucasians with insulin-dependent diabetes mellitus.

From 11 studies, a total of 1,792 Caucasian probands with insulin-dependent diabetes mellitus (IDDM) are analyzed. Antigen genotype frequencies in patients, transmission from affected parents to affected children, and the relative frequencies of HLA-DR3 and -DR4 homozygous patients all indicate that DR3 predisposes in a "recessive"-like and DR4 in a "dominant"-like or "intermediate" fashion, after allowing for the DR3/DR4 synergistic effect. Removal of DR3 and DR4 reveals an overall protective effect of DR2, predisposing effects of DR1 and DRw8, and a slight protective effect of DR5 and a predisposing effect of DRw6.

Aberrant MN bloodgroup inheritance in a German family: a 'silent' allele?

By means of extensive serogenetic testing of a family, RFLP analysis and biostatistic evaluation we present evidence for the rare transmittance of a 'silent' information at the MN blood group locus in a Caucasian family.

The clinical course of lung metastases from breast cancer.

The clinical course of 50 breast cancer patients whose first metastases were found in the lungs was investigated. 18 months after the start of primary treatment 50% of the patients had developed pulmonary metastases (range: 0-81 months). In 23% of patients a solitary, and in 68% more than one, lung metastases were detected.

Chromosomal assignment of human cytochrome P-450 (debrisoquine/sparteine type) to chromosome 22.

In order to determine on which chromosome the gene controlling human cytochrome P-450 (debrisoquine/sparteine type) is located a linkage study of polymorphic sparteine oxidation (PSO) to various polymorphic markers was carried out. Positive information for linkage between PSO and the P1 blood group was obtained with a maximal LOD-score of LOD = 3.35 for both male and female recombination fraction estimates of theta m = theta f = 0.

A comprehensive search for segregation distortion in HLA.

Segregation distortion, the non-Mendelian segregation of gametes, has been well documented among diverse groups of organisms. These cases are characterized by extreme segregation ratios found only in males. Previous reports have suggested the existence of segregation distortion operating in the HLA system of humans, a tightly linked complex of genes which regulates the immune system.

No fallacies in the formulation of the paternity index.

In a recent publication, Li and Chakravarti claim to have shown that the paternity index is not a likelihood ratio. They present a method of estimating the prior probability of paternity from a sample of previous court cases on the basis of exclusions and nonexclusions. They propose calculating the posterior probability on the basis of this estimated prior and the test result expressed as exclusion/nonexclusion.

Contrasting evolutionary histories among tightly linked HLA loci.

Genes comprising the major histocompatibility complex (MHC) play a central role in governing the immune response of vertebrates. A great deal of information has been revealed on the molecular biology and physiology of these loci, but three features-the high polymorphism, tight linkage among the loci, and the nonrandom association of alleles-make the system of particular interest from the perspective of population genetics. Information on the dynamic evolutionary forces that have acted on a locus can be inferred from the number and distribution of alleles that it carries.

Extended polymorphism of the human esterase D isozyme system: description of a "new" allele EsD*11.

Using "new" techniques (malic acid thin layer agarose gel electrophoresis and/or isoelectric focusing), the polymorphism of the human red cell isozyme system esterase D (ESD) was shown to be extended. We report the gene frequencies observed among 312 unrelated Caucasian individuals living in the Düsseldorf area. The finding of a "new" allele at the ESD locus is also described.

Human C81 (alpha-gamma) polymorphism: detection in the alpha-gamma subunit on SDS-PAGE, formal genetics and linkage relationship.

The molecular basis of human C81 (alpha-gamma) polymorphism could be elucidated by immunoprecipitation of human C81 allotypes and separation of the alpha-gamma and beta subunits on sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE) under nonreducing conditions. If the C8 molecules were completely reduced, C81 polymorphism was no longer detectable on SDS-PAGE. It is concluded that C81 variation depends on charge rather than molecular weight differences.

Homogeneity of HLA-DQ,DR phenotypes in lymphocyte subsets of normal individuals.

The study was performed to evaluate the association of HLA-DQ and DR antigens with the composition of peripheral blood lymphocytes. B cells, T cells, and T subsets were enumerated in 200 normal individuals by indirect immunofluorescence microscopy using the monoclonal antibodies OKT3, OKT4, OKT8, and OKIa1. Results were related to the HLA-DQ,DR phenotypes of the investigated population.

HLA-DR effects in a large German IDDM dataset.

DR4 and DR3 are in strongest linkage disequilibrium with IDDM susceptibility genes, and DR1 demonstrates a lesser degree of positive disequilibrium. DR3/DR4 heterozygotes have the highest risk. The DR1 increase occurs almost exclusively in DR4/DR1 heterozygotes, suggesting that DR1 may be in disequilibrium with the same susceptibility gene as DR3.

Genetic analysis workshop IV: insulin dependent diabetes mellitus--summary.

The Insulin Dependent Diabetes Mellitus (IDDM) study was one of the topics of Genetic Analysis Workshop IV (GAW IV) discussed October 7 - 8 at a pre-workshop meeting and presented October 9, 1985 at the American Society of Human Genetics meeting in Salt Lake City. The aim of the study was to have different groups analyze an identical body of real data in order to compare their analytical methods and the results based on their different approaches. This summary describes the available datasets and presents the main results of the nine participating groups.

No interaction between HLA and immunoglobulin IgG heavy chain allotypes in early onset type 1 diabetes.

Immunoglobulin heavy and light chain genes are often discussed as susceptibility genes for insulin dependent (type 1) diabetes mellitus (IDDM) in addition to HLA-DR3 and DR4. Accordingly we analysed 175 unrelated patients for an interaction between immunoglobulin allotype antigens (Gm) and HLA. While DR3 and DR4 antigens and DR3/DR4 heterozygotes occur significantly more often among diabetics than among normal controls, their Gm allotype frequencies are very similar.

Millimeter-scale variations of stable isotope abundances in carbonates from banded iron-formations in the Hamersley Group of Western Australia.

Several diamond drill cores from formations within the Hamersley Group of Western Australia have been studied for evidence of short-range variations in the isotopic compositions of the carbonates. For a set of 32 adjacent microbands analyzed in a specimen from the Marra Mamba Iron Formation, carbon isotope compositions of individual microbands ranged from -2.8 to -19.