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S Matthysse

Publications and source records attributed to S Matthysse.

At least 37 records · Page 2Linked to original sources
PubMed1989

Simulation of pedigree genotypes by random walks.

A random walk method, based on the Metropolis algorithm, is developed for simulating the distribution of trait and linkage marker genotypes in pedigrees where trait phenotypes are already known. The method complements techniques suggested by Ploughman and Boehnke and by Ott that are based on sequential sampling of genotypes within a pedigree. These methods are useful for estimating the power of linkage analysis before complete study of a pedigree is undertaken. We apply the random walk technique to a partially penetrant disease, schizophrenia, and to a recessive disease, ataxia-telangiectasia. In the first case we show that accessory phenotypes with higher penetrance than that of schizophrenia itself may be crucial for effective linkage analysis, and in the second case we show that impressionistic selection of informative pedigrees may be misleading.

Ataxia Telangiectasia↗
PubMed1988

A single dominant gene can account for eye tracking dysfunctions and schizophrenia in offspring of discordant twins.

Eye movement dysfunctions (EMDs), detectable during smooth pursuit, occur in a majority of schizophrenics and in 45% of their first-degree relatives. Previous data suggest that they represent a biologic marker for schizophrenia. To determine the mode of transmission of the schizophrenia-EMD complex, the eye movements of offspring of monozygotic and dizygotic twins were recorded. One group of twins was discordant for schizophrenia; the other group for manic depression or reactive psychosis. The data suggest that EMDs and at least some schizophrenias can be considered expressions of a single underlying trait that is transmitted by an autosomal dominant gene.

Affective Disorders, Psychotic↗
PubMed1987

Schizophrenic thought disorder: a model-theoretic perspective.

Model theory is a branch of mathematics that treats such abstruse questions as "is there another number system, different from 0,1,2, ... that satisfies all the axioms of arithmetic?" (yes), and "can every mathematical hypothesis be proved true or false?" (no). It would not seem likely that any contribution could be made to our understanding of though disorder in schizophrenia from such a remote quarter. The detailed results of model theory obviously will not apply; but I believe certain ways of thinking common in that field, but not in psychology, may help lead us toward explanations.

Humans↗
PubMed1987

Genetics, chance, and morphogenesis.

We posit that chance plays a major role in the occurrence of many common malformations that cluster in families but recur less frequently than expected for simple Mendelian traits. Once the role of random effects is accepted, the segregation of such malformations may be explained on the basis of Mendelian transmission of a single abnormal gene that predisposes to, but does not always result in, the abnormal phenotype. We apply a stochastic (probabilistic) single-gene model to the occurrence of malformations in mouse and man. The stochastic single-gene model suggests the feasibility of isolating individual genes that determine morphogenesis and sets limits on the precision with which the recurrence of malformations can be predicted.

Animals↗
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

Geometrical correspondence between phenazocine and the enkephalins.

Calculations have been performed on phenazocine using Allinger's MM2 (molecular mechanics II) program with full energy minimization. The N-phenethyl group was found to have considerable flexibility with a number of low-energy conformers. The best N-phenethyl axial conformer was 1.6 kcal/mol higher in energy than the best equatorial one. Calculations were also performed on the beta isomer of phenazocine with the result that the energy difference between the best equatorial and axial conformers rose to a substantial 4.6 kcal/mol. The hypothesis that opiate agonism requires an N substituent in the axial position does not appear to be consistent with the increased potency of beta isomers in which axial N substituents are thermodynamically more unstable. Comparisons have also been made between the low-energy conformers of phenazocine and those that have been observed or proposed for the enkephalins. One conformation of the tyrosine portion of the enkephalins that was observed by X-ray crystallography by Karle et al. was found to be a good fit to morphine-like opiates. The backbone conformer suggested by Gorin et al. was found to be the best fit to the two phenyl rings of phenazocine.

Enkephalins↗
PubMed1985

Increased adhesiveness of trisomy 21 cells and atrioventricular canal malformations in Down syndrome: a stochastic model.

Based on the finding that fetal trisomy 21 fibroblasts explanted from lungs and endocardial-cushion-derived structures appear more adhesive in vitro than those from normal control individuals, we present a stochastic model for atrioventricular (AV) canal malformations in Down syndrome (DS). Computer simulations were performed to model the normal anatomic sequences of cushion-to-cushion and cushion-to-septum fusion in AV canal development. In these simulations, random-walking endocardial cells were allowed to migrate, divide, and adhere with programmable probabilities. Low values of intercellular adhesiveness engendered simulations resembling normal AV canal development; higher values of adhesiveness yielded deficiencies of AV canal development as seen in DS. Moderately high levels of adhesiveness resulted in abnormalities in only a proportion of multiple, independently performed simulations. The model successfully predicts the temporospatial sequence of anatomic events in cushion-to-septum fusion, clinical variability among individuals with the same genotype based on chance alone, and amplified developmental instability as observed in individuals with DS.

Cell Adhesion↗
PubMed1985

Stochastic branching model for hemopoietic progenitor cell differentiation.

We present algebraic expressions describing the predictions of a stochastic branching model for differentiation of hemopoietic progenitor cells. The model assumes that there is a fixed probability, p (0 less than or equal to p less than or equal to 1), that commitment to a differentiative event occurs per progenitor cell division for each daughter cell. The model describes properties of in vitro hemopoietic cell differentiation including the population structure at the time the first progenitor cell becomes committed, the number of committed progenitor cells engendered by a single progenitor cell, and the probability of eventual commitment of all daughter cells derived from a single progenitor or stem cell. Application of the model to experimental data obtained from erythroid cultures suggests that the observed data can be explained by the stochastic branching model alone without making the deterministic assumption that there is a differentiative hierarchy in the lineage of the progenitors of erythropoiesis (BFU-E). The qualitative and quantitative aspects of the proposed stochastic model are discussed in conjunction with other analogous stochastic branching models.

Cell Division↗
PubMed1985

Genetics of congenital heart malformations: a stochastic model.

A stochastic model is proposed to explain how alterations in the properties of developing endocardial cells could control the outgrowth of endocardial cushions in normal persons, in subjects from families with a predisposition to congenital heart defects, and in subjects with trisomy 21. Normal and abnormal outgrowth of the endocardial cushions of the atrioventricular (AV) canal were modeled by computer simulations. Computer simulations depicted not only the sequence of normal AV valve development, but also illustrated how increased cellular adhesiveness of fibroblasts from the endocardial cushions of the AV canal--which we have observed in vitro among cultured cells from Down syndrome abortuses--may result in AV canal defects. The stochastic model so elaborated demonstrates how single gene changes may result in abnormalities in only a proportion of subjects carrying mutant alleles, yielding inheritance patterns characterized previously as being "multifactorial" in origin.

Cell Adhesion↗
PubMed1983

Morphometric analysis of granule cell dendrites in the mouse dentate gyrus.

We devised a computer program to analyze the dendritic geometry of dentate granule cells as seen in rapid Golgi impregnations from the mouse. Three dimensional coordinates were recorded by using a computer-assisted microscope. Geometric parameters are of two general types: (1) LINEAR parameters include the number of dendritic segments per branch order and their individual and aggregate lengths. (2) ANGULAR parameters define the spatial relationships of branch points and segment terminals with each other and with the axis of symmetry derived for all the dendrites. We find that values for linear parameters are highly variable and more susceptible to artifacts. Values for most angular parameters are more highly constrained and are presumably the best descriptors of the class-characteristic conical shape of granule cell dendrites. Additional features which are necessary to describe granule cell dendrites fully are: (1) Branching frequency is highest proximal to the cell soma, (2) deviant segments are kept "on course" to ensure axial symmetry, and (3) terminal segments end at the plane of the cortical surface. A critical analysis of the various parameters suggests the hypothesis that the characteristic and uniform geometry of granule cell dendrites is controlled largely by factors residing in the molecular layer where growth and differentiation are sustained. An additional finding of potential interest is that there are two subpopulations of granule cells with a twofold difference in spine density.

Animals↗
PubMed1983

Conformational properties of butaclamol and isobutaclamol. Regularities in the structures of semirigid neuroleptics.

Conformational energy calculations have been performed on butaclamol and isobutaclamol using Allinger's MM2 (Molecular Mechanics II) program. Cis arrangements of rings D and E were found to be preferred by 1.4-1.9 kcal/mole for both compounds. Nevertheless, based on a molecular comparison with a number of semirigid neuroleptics, most notably loxapine and octoclothepin, it is suggested that trans arrangements are required for neuroleptic activity in the two compounds. However, trans conformer B of butaclamol, which was previously postulated as the biologically active form, was found to be 4.1 kcal/mole higher in energy, suggesting that it is less likely to play a significant pharmacological role. The biologically active forms are identified as trans conformer A for butaclamol and trans conformer B for isobutaclamol. Certain regularities in the structures of the semirigid neuroleptics are noted. It is also speculated that the cis conformers of protonated butaclamol may have unfavorable geometries for ion solvation, which would account for the anomalously low pKa measured for the compound. A similar explanation would also account for a trans conformer being found in the crystal structures of the bromide salts of butaclamol and dexaclamol.

Antipsychotic Agents↗