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Biomedical subjects

K M Weiss

Publications and source records attributed to K M Weiss.

At least 19 recordsLinked to original sources
PubMed1992

Visual information decoding deficits in schizophrenia.

Schizophrenic and control subjects were tested on two-flash fusion (TFF) and visual backward masking (VBM) tasks in a repeated measures design. Each subject was tested in a single session. Both tasks used the same equipment and stimuli. There was no difference between the groups in their ability to detect the presence of two separate stimuli in the TFF task. Schizophrenic subjects did require longer interstimulus intervals (ISI) than control subjects to accurately report one of the two targets in the VBM task. Analysis of individual targets reveals that the VBM deficit is a function of the similarity of the target and mask. The more feature detail discrimination necessary, the longer an ISI is required in VBM. The data are interpreted as supporting the conclusion that since the groups did not differ in their performance of the TFF task, which would also have been affected by a sensory abnormality, the deficit in VBM must be explained by reference to a higher level of information processing. The VBM deficit is a failure to decode the target stimulus, and is not simply a function of abnormalities due to an overactive transient channel system.

Adult↗
PubMed1992

Native American mitochondrial DNA analysis indicates that the Amerind and the Nadene populations were founded by two independent migrations.

Mitochondrial DNAs (mtDNAs) from 167 American Indians including 87 Amerind-speakers (Amerinds) and 80 Nadene-speakers (Nadene) were surveyed for sequence variation by detailed restriction analysis. All Native American mtDNAs clustered into one of four distinct lineages, defined by the restriction site variants: HincII site loss at np 13,259, AluI site loss at np 5,176, 9-base pair (9-bp) COII-tRNA(Lys) intergenic deletion and HaeIII site gain at np 663. The HincII np 13,259 and AluI np 5,176 lineages were observed exclusively in Amerinds and were shared by all such tribal groups analyzed, thus demonstrating that North, Central and South American Amerinds originated from a common ancestral genetic stock. The 9-bp deletion and HaeIII np 663 lineages were found in both the Amerinds and Nadene but the Nadene HaeIII np 663 lineage had a unique sublineage defined by an RsaI site loss at np 16,329. The amount of sequence variation accumulated in the Amerind HincII np 13,259 and AluI np 5,176 lineages and that in the Amerind portion of the HaeIII np 663 lineage all gave divergence times in the order of 20,000 years before present. The divergence time for the Nadene portion of the HaeIII np 663 lineage was about 6,000-10,000 years. Hence, the ancestral Nadene migrated from Asia independently and considerably more recently than the progenitors of the Amerinds. The divergence times of both the Amerind and Nadene branches of the COII-tRNA(Lys) deletion lineage were intermediate between the Amerind and Nadene specific lineages, raising the possibility of a third source of mtDNA in American Indians.

Asian People↗
PubMed1992

On the distinctions between diagnosis, description and measurement of schizophrenia.

The distinctions between diagnostic classification of schizophrenia, the description of the characteristics and course of schizophrenia, and measurement of its severity are discussed. There is confusion among these three categories by both researchers and clinicians. The causes for this confusion are discussed, and it is noted that there are few appropriate measures of cognitive function in schizophrenics. It is proposed that the research design used in most schizophrenia research does not lend itself to the development of more informative interval scales. It is proposed that rather than using performance as a dependent measure with a task of fixed level of difficulty, a 'threshold design' should be used, where the environmental factors are varied to produce a given performance level.

Female↗
PubMed1991

Genetic variation of the mitochondrial DNA genome in American Indians is at mutation-drift equilibrium.

Several surveys have found evidence for founder effects in Amerindian mitochondrial DNA because of the existence of rare Asian morphs in high frequencies in some Amerindian populations and the occurrence of several new morphs not seen elsewhere in the world. These reports, however, do not address whether or not the present genetic variation in the mtDNA genome in Amerindians has reached the steady-state distribution predicted by the mutation-drift theory of population genetics. The present work suggests that in three Amerindian populations (Pima, Maya, and Ticuna) a steady state has apparently been reached, and hence the initial founder effect has probably dissipated during the evolution of Amerindians in the New World. This result is consistent with the genetic variation in nuclear genes in similar populations, shown through surveys of protein variation in earlier work and, more recently, in studies of restriction fragment length polymorphisms.

DNA, Mitochondrial↗
PubMed1991

Genetic studies of human apolipoproteins. XVI. APOE polymorphism and cholesterol levels in the Mayans of the Yucatan Peninsula, Mexico.

Structural variation at the APOE locus is a major determinant of interindividual differences in cholesterol levels in populations at large. We have determined APOE structural polymorphism and estimated its impact on total cholesterol in the Mayans of the Yucatan Peninsula from Mexico. A unique pattern of APOE allele frequency distribution was observed, with no example of the APOE*2 allele and a relatively low incidence (9%) of the APOE*4 allele, giving rise to the lowest average heterozygosity at the APOE locus observed to date. The reported elevating affect of the APOE*4 allele on cholesterol has been found to be absent in the Mayans; several possible explanations which may account for the absence of this affect are discussed. In addition to APOE the gene products of five other apolipoprotein loci were screened and low frequency variation, possibly due to European admixture, was observed in two systems (APOH and APOA-IV).

Alleles↗
PubMed1991

DNA polymorphisms of the apolipoprotein AI/CIII/AIV gene cluster influence plasma cholesterol and triglyceride levels in the Mayans of the Yucatán Peninsula, Mexico.

The purpose of this work was to examine the influence of apolipoprotein gene variation on plasma lipid levels in a population of Mayan Indians of the Yucatán Peninsula, Mexico. Four restriction enzymes: XmnI, PstI, SstI, and PvuII, were used to detect restriction fragment length polymorphisms (RFLP) within the region of the apolipoprotein AI/CIII/AIV gene cluster. The frequencies of these polymorphisms in this Mayan population were similar to those reported for other Amerindian populations, but differed widely from those reported for Caucasian populations. The XmnI and SstI RFLPs were informative for association studies in this population, and we analyzed their influence on the quantitative variation of plasma cholesterol and triglycerides. Using a nonparametric analysis of variance, it is shown that the presence of the XmnI restriction site had a significant effect in lowering plasma cholesterol, whereas the presence of the restriction site for SstI had a significant effect in raising plasma triglycerides. Consequently, genetic indicators of both low and high risk for lipid-related diseases, such as atherosclerosis and coronary heart disease, seem to be present within the same gene region in this Mayan population.

Adult↗
PubMed1991

Studies of three Amerindian populations using nuclear DNA polymorphisms.

Three Amerindian populations, two from Rondônia, Brazil (Karitiana and Rondônia Suruí), and one from Campeche, Mexico (Mayan), were typed for up to 30 nuclear restriction fragment length polymorphisms (RFLPs). Heterozygosities, both observed and expected, were compared with those of Europeans. Average heterozygosity is reduced among these Amerindians (relative to that of Europeans) by 7.0% (Mayan) to 27.1% (Karitiana). This amount of heterozygosity in the nuclear DNA is nevertheless high enough that it is unlikely that there was a severe or prolonged bottleneck.

Alleles↗
PubMed1990

Advantages of reconceptualizing schizophrenia in clinical practice.

Weiss (1989) has proposed abandoning symptom-based diagnosis for schizophrenia research. It is proposed that such a system confuses treatment of symptoms with treatment of the underlying process from which it emanates. Furthermore, it proposes that while a symptom-based system is striving for clarity and objectivity, it is conceptually barren and, thus, offers no treatment framework. A proposed, heuristic model by which to conceptualize major psychiatric disorders is discussed. It is argued that it would have clinical advantages of greater patient acceptance, less social stigma, provide a treatment agenda, allow objective measurement of deficits along a continuum, be more comprehensible by both patient and family, and be more relevant to daily living.

Antipsychotic Agents↗
PubMed1990

Cancer models and cancer genetics.

There have been many attempts to develop stochastic multistage models for cancer. The models relate hypothesized biological processes occurring at the cellular level to the occurrence of tumors at the experimental or epidemiologic level of individuals in a population. The existing models fit a variety of data, but none is fully satisfactory and they are in some ways inconsistent with each other. Recently, substantial new data have become available on the nature of cancer-associated mutations observed directly at the cellular level. These data suggest that the number of stages may be greater and more variable among individual tumors of the same organ than has been thought. There may be many pathways to cancer, and the mutations responsible may not constitute a fixed set or sequence. This pattern resembles the genetics of quantitative rather than qualitative traits, and may also be consistent with the variable histology and behavior of tumors of a given organ. Simulations using such models suggest that cancer in the general population may have such heterogeneous etiology, a possibility that has important implications for screening, risk projection, and prevention. Risk-generating processes of a rather generic kind may generate similar hazard functions for diverse chronic diseases in the age ranges often used in epidemiologic studies. This phenomenon raises questions about the purpose and interpretation of statistical epidemiologic models.

Humans↗
PubMed1990

Genetic studies of human apolipoproteins. XIII. Quantitative polymorphism of apolipoprotein C-III in the Mayans of the Yucatán Peninsula.

Apolipoprotein C-III (APO C-III) is a structural component of very-low-density and high-density lipoprotein particles and is an inhibitor of lipoprotein lipase. In a study of genetic variation of apolipoproteins in the Mayan population of the Yucatán peninsula, we observed a quantitative polymorphism in APO C-III levels. This polymorphism is expressed as variation in immunoblot staining intensity following isoelectric focusing and as variation in plasma levels of APO C-III determined by radial immunodiffusion. This variation is consistent with the presence in Mayans of an allele associated with low levels of plasma APO C-III which we have designated APO C-III*D. Analysis of the distribution of APO C-III levels yields a gene frequency estimate for the deficiency allele of 0.59. There is a significant positive correlation between total plasma APO C-III levels and total plasma cholesterol and triglyceride levels, the lowest levels of cholesterol and triglycerides being seen in individuals homozygous for the deficiency allele. This observation is consistent with the proposed role of APO C-III in lipoprotein metabolism. Family data to determine whether this deficiency allele is due to mutation at the APO C-III structural locus were not available. However, molecular analysis using cloned probes from the APO A-I/C-III/A-IV gene cluster revealed no gross DNA rearrangement or deletion of sequences in this region in homozygous deficient individuals.

Apolipoprotein C-III↗
PubMed1990

Amerindian mitochondrial DNAs have rare Asian mutations at high frequencies, suggesting they derived from four primary maternal lineages.

The mitochondrial DNA (mtDNA) sequence variation of the South American Ticuna, the Central American Maya, and the North American Pima was analyzed by restriction-endonuclease digestion and oligonucleotide hybridization. The analysis revealed that Amerindian populations have high frequencies of mtDNAs containing the rare Asian RFLP HincII morph 6, a rare HaeIII site gain, and a unique AluI site gain. In addition, the Asian-specific deletion between the cytochrome c oxidase subunit II (COII) and tRNA(Lys) genes was also prevalent in both the Pima and the Maya. These data suggest that Amerindian mtDNAs derived from at least four primary maternal lineages, that new tribal-specific variants accumulated as these mtDNAs became distributed throughout the Americas, and that some genetic variation may have been lost when the progenitors of the Ticuna separated from the North and Central American populations.

Asia↗
PubMed1990

The biodemography of variation in human frailty.

A population is composed of individuals who are heterogeneous in their susceptibility to death and disease. This heterogeneity is reflected in the age-specific incidence or mortality (hazard) function. This variation has typically been hidden--that is, not measured directly--and has generally been modeled in a purely empirical statistical way, because there is no theory in demography for the distribution of frailty. A substantial fraction of variation in frailty, however, has an underlying genetic basis, for which there is a formal theory. This theory, based on evolutionary biology and on the nature of mendelian transmission, provides prior constraints on the distribution of variation in the population as well as providing methods for identifying genes involved in many important diseases. The accumulating effects of environmental exposures with age are another major component of variation in frailty. In some important instances, this variation and its effect on the age-specific hazard function can also be understood in terms of cause-specific biological processes. These biological considerations may enable demographers to model frailty, and thus mortality, in a better way.

Disease Susceptibility↗
PubMed1989

Advantages of abandoning symptom-based diagnostic systems of research in schizophrenia.

An alternative is suggested to the symptom-based diagnostic conceptualizations of schizophrenia that are now general. Using a different methodological philosophy, it would investigate empirically determined underlying structure. It is proposed that studies should be more clearly directed toward linking symptoms, underlying processes, and etiology.

Humans↗