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Biomedical subjects

T Reich

Publications and source records attributed to T Reich.

At least 145 records · Page 8Linked to original sources
PubMed1983

Genetic analysis of manic-depressive illness.

Two threshold models, a single locus model, and two combined models are fitted to data on familial incidence of bipolar affective disorder in 194 nuclear families ascertained through a bipolar proband. The relative fit of alternative transmission models is tested by a likelihood ratio chi-square with the degrees of freedom defined by the difference in the number of parameters estimated by each model. All parameters are estimated by the method of maximum likelihood. The simplest threshold model, permitting only a single background familial correlation, is found to provide a statistically poorer fit than any of the alternative models, and may be rejected as a model for the etiology of bipolar affective disorder. The four remaining models are statistically indistinguishable. It is suggested, however, that the involvement of a major locus in the etiology of this disorder deserves further scrutiny since any of the models incorporating a major locus, with or without a multifactorial background, are consistently associated with greater likelihoods than the complex threshold model. It is also noted that diagnostic criteria are critical in the analysis. In the present study, relatives of probands are considered affected if a diagnosis of bipolar or unipolar affective disorder is present. When only bipolar relatives are considered affected, none of the transmission models may be rejected. Finally, the results of these analyses are found to be independent of the ascertainment parameter.

Biometry↗
PubMed1983

HLA and disease: haplotype sharing in multiplex families.

Recently it has been argued that the distribution of shared haplotypes in multiplex sibships for HLA-associated diseases may be an indicator of the disorder's underlying mode of transmission. Specifically, it has been suggested that the presence of multiple disease susceptibility genes and/or loci may be inferred when an inverse relationship between the amount of haplotype sharing and the number of affected sibs is observed in families where neither parent is affected. This claim is evaluated using extensive computer simulations. It is shown that a variety of haplotype sharing patterns are possible, even for the simplest models, and that for a large segment of the parameter space the actual distribution of shared haplotypes is opposite to that predicted. Accordingly, the inference that more than one locus is involved in the etiology of an HLA-associated non-Mendelian disease, if based only on the distribution of shared haplotypes in multiplex sibships, is unjustified.

Genetic Diseases, Inborn↗
PubMed1983

A defense of path analysis in genetic epidemiology.

Contemporary models of multifactorial inheritance are described and justified from the perspective of their intended use in genetic epidemiology and their developmental sequence. Substantial empirical data and statistical theory support the practical adequacy of the assumptions of path analysis for most multifactorial traits that show vertical inheritance. The choice of scale for quantitative traits must be considered on an individual basis. From both biological and statistical perspectives, transformations of scale may be more appropriate for analysis than the measurements are themselves. Recent criticism of contemporary models and computational procedures is based on a caricature of path analysis rather than on the method as it is actually practiced. The utility of path analysis is primarily limited by an investigator's biological insight and analytical skill, not by the method's assumptions. Model-free descriptive statistics are inherently inadequate to characterize the stable and autonomous features of the underlying mechanisms that generate observable variation in multifactorial traits. In contrast, path analysis has led to remarkably stable estimates of structural parameters for a wide variety of important biological traits. While exploratory methods can be useful for preliminary data inspection, they cannot substitute for formal tests of hypotheses based on explicit, falsifiable models.

Genetics, Medical↗
PubMed1983

Genetic diversity, genome organization, and investigation of the etiology of psychiatric diseases.

Recent advances in our understanding of the structure and organization of the human genome have strong implications for investigations of the diagnosis and etiology of psychiatric disorders. The concept of human genes as contiguous regions of DNA has been discarded and replaced by the concept of a gene split in separate pieces that must be spliced in order to make its protein products. The 'one gene - one enzyme' concept has also been modified to allow for the observation that many functional proteins are composed of multiple subunits, each coded by separate genes, whose expression is regulated by many other genetic and environmental factors. Consequently, the development of a complex phenotype cannot be predicted from knowledge of even the entire DNA sequence, and exploratory methods that rely entirely on genetic linkage analysis are unlikely to be fruitful. It is recommended that investigations reverse the natural development sequence and begin with studies at a phenotypic level, proceeding down to the genotypic level. Studies at a purely clinical level can define independent familial subtypes, which can in turn be studied at several levels of observation (social, physiological, biochemical, genetic) to identify multiple biosocial risk factors. Recent advances in genetic epidemiology now provide quantitative methods to detect major gene effects, resolve cultural inheritance from biological inheritance, and identify the influence of multiple risk factors on the development and expression of psychiatric disease.

Chromosome Mapping↗
PubMed1982

Pentoxifylline efficacy in the treatment of intermittent claudication: multicenter controlled double-blind trial with objective assessment of chronic occlusive arterial disease patients.

The efficacy, safety, and tolerance of pentoxifylline (Trental, Hoechst-Roussel Pharmaceuticals, Inc.) in the treatment of intermittent claudication associated with chronic occlusive arterial disease (COAD) were evaluated in a double-blind, placebo-controlled, parallel-group, multicenter clinical trial involving a total of 128 outpatients. The response to treatment was ascertained at regular intervals during the trial by measuring the distance walked prior to the onset of claudication when patients were subjected to a standardized treadmill test. Pentoxifylline given orally in doses up to 1200 mg/day was significantly more effective than placebo in increasing both the initial and absolute claudication distances in patients with COAD. Reduction of lower limb paresthesias also suggested greater clinical improvement in the pentoxifylline treated patients. These results support the hypothesis that pentoxifylline reduces blood viscosity by improving red cell flexibility, and thereby enhances blood flow in patients with COAD. White the precise mode of therapeutic action requires clarification, pentoxifylline was well tolerated with minimal unwanted effects.

Aged↗
PubMed1982

Investigation of the membrane-fluidizing properties of porphyrin-inducing drugs.

The objective of this study was to test the hypothesis that porphyrin-inducing drugs act at least in part by disrupting membrane lipids. The porphyrin-inducing steroids, 3 alpha-hydroxy-5 alpha-pregnane-11,20-dione (alfaxalone) and 3 alpha-hydroxy-5 alpha-pregnan-20-one induce considerably greater fluidity changes in spin-labelled phospholipid-cholesterol bilayers than do the corresponding 3 beta-hydroxy steroids which are also less potent as porphyrin inducers. The steroids did not cause any significant change in spin-labelled vesicles lacking cholesterol. The porphyrin-inducing compound 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine and a series of analogues caused fluidity changes in phospholipid bilayers in the presence and absence of cholesterol. The porphyrin-inducing nonplanar 2,2',4,4'-6,6'-hexachlorobiphenyl caused a significant change in bilayer fluidity in phospholipid bilayers in the presence and absence of cholesterol. Since the planar 3,3',4,4'-tetrachlorobiphenyl, allylisopropylacetamide (AIA), and griseofulvin are potent porphyrin-inducing compounds, but do not fluidize a lipid bilayer, it was clear that the original hypothesis required modification. No evidence could be obtained to support the idea that a subset of porphyrin-inducing drugs exists which are membrane fluidizers and whose common mechanism of action as porphyrin-inducers might be revealed by a common pattern of porphyrin accumulation in chick embryo liver cells. It is suggested that those porphyrin-inducing compounds with membrane-fluidizing properties might fluidize the nuclear membrane, thus facilitating the transfer of an induction specific RNA for delta-aminolevulinic acid synthetase from the nucleus to the cytoplasm.

Allylisopropylacetamide↗
PubMed1982

Ascertainment bias for non-twin relatives in twin proband studies.

When families are ascertained through affected twins, as for example when twin probands are selected from a registry and their non-twin relatives studied, a correction for ascertainment bias is needed. It is shown that probandwise counting (where relatives of doubly ascertained twin pairs are counted twice) is the appropriate method. The bias resulting from pairwise counting is given and depends on the genetic model and on the probability of selecting an affected twin as a proband. For the multifactorial and generalized single major locus models the bias is small, and the problems associated with nonindependent ascertainment are negligible in practice.

Chromosome Mapping↗
PubMed1982

Refutation of the general single-locus model for the etiology of schizophrenia.

All published studies on the familial incidence of schizophrenia appropriate for testing the applicability of the general single-locus two-allele model are examined under the assumption of a unitary etiology for all schizophrenia. We show that the single major locus model is inadequate to predict the incidence in four classes of relatives of schizophrenic probands (parents, siblings, monozygotic, and dizygotic cotwins). In addition, the observed proportion of affected offspring from dual matings differ significantly from the model's prediction. The lack of an overall fit between the published familial distributions and the monogenic model suggests that a single major locus is insufficient for the etiology of schizophrenia. Further efforts in examining multifactorial models, mixed models, and other transmission models may be fruitful.

Chromosome Mapping↗
PubMed1981

Inbreeding and the genetic control of nondisjunction.

We have studied the frequency of trisomics in newly formed zygotes and the proportion of trisomics, k, coming from consanguineous marriages by assuming that recessive genes at a single locus or multiple loci are responsible for the induction of nondisjunction. For mitotic nondisjunction, the value of k increases as the magnitude of consanguinity of the parents increases, but the opposite relationship holds for meiotic nondisjunction. Therefore, it is important to distinguish mitotic and meiotic types in the genetic study of nondisjunction. This seems to be one of the simplest tests for detecting the genetic control of nondisjunction.

Consanguinity↗
PubMed1980

Analysis of behavioral traits in the presence of cultural transmission and assortative mating: Applications to IQ and SES.

General linear models of familial resemblance are described which allow for polygenic inheritance, cultural transmission from parent to offspring, phenotypic assortative mating, common environment, and maternal and parental effects. These models use observed phenotypic correlations between multiple classes of relatives and/or correlations between individuals reared in separated and extended family structures to yield maximum likelihood parameter estimates. The models are first applied to American kinship data for IQ, with the variance of IQ partitioned as 30% additive genetic, 29% due to cultural inheritance, 9% due to gene--culture covariance, and 32% due to nontransmissible environment. Under the assumption that the correlations between (nontransmissible) environments of DZ and MZ twins are the same, an approximate treatment of dominance yields an estimate of 23% dominance variation.

Culture↗
PubMed1980

General causal models for sex differences in the familial transmission of multifactorial traits: an application to human spatial visualizing ability.

A general multifactorial model is given for the inheritance of traits that exhibit a sexual dimorphism. The model allows for polygenic inheritance, cultural transmission, phenotypic assortative mating, and a common environment of rearing. Several cultural mechanisms are described for which transmission from parent to offspring is sex-dependent and for which many different patterns of sex-specific correlations can result. A special case of the general model is described in which phenotypic differences between males and females are due only to differences in nontransmissible environmental factors and/or genetic factors that do not contribute to variability within a sex. Application of these models to human spatial visualizing ability, using data reported by others, gives an estimate of 45 per cent for the proportion of the variance that is accounted for by transmissible factors. Neither an X-linked hypothesis nor a sex-specific cultural mechanism is required to explain the transmission of spatial ability.

Female↗