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Biomedical subjects

M H Skolnick

Publications and source records attributed to M H Skolnick.

At least 91 records · Page 5Linked to original sources
PubMed1989

The influence of electrical variables on analgesia produced by low current transcranial electrostimulation of rats.

Pulsed low current transcranial electrostimulation (TE) has been shown to induce analgesia in rats as measured by the wet tail flick test. This study investigates the effect of varying stimulus frequency, pulse width, charge balance and polarity, as well as the influence of electrode placement and time of day at which stimulus occurred. A biphasic, charge balanced waveform with a first phase duration of 2 msec, current 10 microA and repetition rate 10 Hz was found to induce maximum tail flick latency changes. The effects of morning or nighttime stimulation were statistically indistinguishable, as were the differences between monophasic and biphasic stimulation. Analgesia was maximized when a positive first phase was delivered into the right ears of the rats, but monolateral stimulation with both electrodes on either the left or the right ear produced no measurable effect. Examination of TE responses in sham and stimulated populations reveals normal response distributions with the stimulated group skewed toward a positive effect.

Analgesia↗
PubMed1988

Common inheritance of susceptibility to colonic adenomatous polyps and associated colorectal cancers.

We studied 670 persons in 34 kindreds by flexible proctosigmoidoscopic examination (60 cm) to determine how frequently colorectal adenomas and cancers result from an inherited susceptibility. Kindreds were selected through either a single person with an adenomatous polyp or a cluster of relatives with colonic cancer. The kindreds all had common colorectal cancers, not the rare inherited conditions familial polyposis coli and nonpolyposis inherited colorectal cancer. Likelihood analysis strongly supported the dominant inheritance of a susceptibility to colorectal adenomas and cancers, with a gene frequency of 19 percent. According to the most likely genetic model, adenomatous polyps and colorectal cancers occur only in genetically susceptible persons; however, the 95 percent confidence interval for this proportion was 53 to 100 percent. These results suggest that an inherited susceptibility to colonic adenomatous polyps and colorectal cancer is common and that it is responsible for the majority of colonic neoplasms observed clinically. The results also reinforce suggestions that first-degree relatives of patients with colorectal cancer should be screened for colonic tumors. This evidence of an inherited susceptibility to a cancer with well-recognized environmental risk factors supports the hypothesis that genetic and environmental factors interact in the formation and transformation of polyps.

Adenomatous Polyposis Coli↗
PubMed1988

Prevalence of hemochromatosis among 11,065 presumably healthy blood donors.

There is evidence that iron loading and organ damage can be prevented in patients with hemochromatosis if prophylactic phlebotomy is employed early in the disease--findings emphasizing the importance of early detection before clinical signs occur. This study was designed to determine the efficacy of transferrin saturation as a screening tool for hemochromatosis and to assess the frequency of homozygosity for the HLA-linked hemochromatosis gene in a healthy population. We screened 11,065 presumably healthy blood donors (5840 men and 5225 women). Donors with transferrin saturations of 62 percent or more after an overnight fast were considered potential homozygotes and were asked to undergo liver biopsy and pedigree analysis. The frequency of values for transferrin saturation of 62 or higher in men was 0.008 and in women 0.003. Thirty-eight persons with values higher than 62 were studied in detail; 35 underwent liver biopsy. Liver iron stores ranged from normal to markedly increased. Twelve siblings with an identical HLA match to a proband underwent liver biopsy, and 11 had increased liver iron stores. According to likelihood analysis of the pedigrees, 26 of the 38 probands were homozygotes, and 12 were heterozygotes. The estimated frequency of homozygosity was based on the data in men, because the threshold value of 62 for the transferrin saturation identified only half as many female homozygotes as expected. The frequency of homozygosity was 0.0045, corresponding to a gene frequency of 0.067. The value of population screening is demonstrated in these studies by the detection of homozygotes before clinical manifestations of hemochromatosis occur.

Adolescent↗
PubMed1988

Segregation and linkage analysis of nine Utah breast cancer pedigrees.

The analysis of nine Utah families that were ascertained for clusters of breast cancer cases is reported. Segregation analysis of an inherited susceptibility to breast cancer shows two distinct maximum likelihood solutions that have almost equal likelihood. One model indicates that most females had zero risk for breast cancer, but 10% of the female population had risks much greater than the Utah age-specific incidence rates. The other model indicates that most females have a risk defined by the Utah rates for breast cancer, but a rare dominant gene is segregating for increased susceptibility to breast cancer. Our analysis shows that linkage results under the two models are consistent in sign but not in magnitude. No evidence for linkage was found with the 14 marker loci examined. In addition to demonstrating distortion of linkage results from ignoring sporadic cases, this analysis shows the inherent difficulty of obtaining parameter estimates for segregation analysis when families are ascertained from a cluster of cases.

Breast Neoplasms↗
PubMed1988

Auricular microelectrostimulation: naloxone-reversible attenuation of opiate abstinence syndrome.

This study evaluated the effects in rats of very low amplitude (10 mu amp) charge-balanced 10-Hz stimulation delivered bilaterally to low impedance points on the outer ear. This microelectrostimulation markedly and significantly reduced the number of opiate abstinence signs observed following a week of continuous morphine infusion. This effect was prevented by subcutaneous injection of 3 mg/kg naloxone, suggesting that stimulation of endogenous opioid activity plays a major role in the actions of auricular microelectrostimulation.

Animals↗
PubMed1988

HGDBMS: a human genetics database management system.

Human genetics research involves a large number of complex data sets naturally organized in hierarchical structures. Data collection is performed on different levels, e.g., the project level, pedigree level, individual level, and sample level. Different aspects of a study utilize different views of the data, requiring a flexible database management system (DBMS) which satisfies these different needs for data collection and retrieval. We describe HGDBMS, a comprehensive relational DBMS, implemented as an application of the GENISYS I DBMS, which allows embedding the hierarchical structure of pedigrees in a relational structure. The system's file structure is described in detail. Currently our Melanoma and Chromosome 17 map studies are managed with HGDBMS. Our initial experience demonstrates the value of a flexible system which supports the needs for data entry, update, storage, reporting, and analysis required during different phases of genetic research. Further developments will focus on the integration of HGDBMS with a human genetics expert system shell and analysis programs.

Computer Systems↗
PubMed1988

Simultaneous analysis of multiple polymorphic loci using amplified sequence polymorphisms (ASPs).

In this paper we present a systematic approach to gene mapping and genotyping based on the simultaneous analysis of multiple amplified sequence polymorphisms (ASPs). These genetic markers measure variation in DNA sequences which have been amplified by a polymerase and/or a ligase. The amplified sequence lengths are determined by appropriate choice of oligonucleotides used in the amplification reaction. We describe three classes of ASPs: restriction site polymorphisms, sequence length polymorphisms, and DNA base pair changes not associated with restriction sites. Simultaneous analysis of multiple ASPs using a modified automated DNA sequencing apparatus should be possible because amplification with oligonucleotides provides control over the fragment lengths generated. Development of an automated ASP technology is therefore the next logical step for efficient gene mapping and genotyping of individuals. With this technology, one gel would be sufficient to indicate the most probable locations of a gene and a second gel would permit the selection of the correct location while simultaneously providing a fine structure map.

Chromosome Mapping↗
PubMed1986

Linkage analysis of Von Recklinghausen neurofibromatosis: chromosomes 4 and 19.

This report describes a study that examines the hypotheses of genetic linkage between the autosomal dominant disorder neurofibromatosis (NF) and loci on human chromosomes 4 and 19. Twelve Utah families were evaluated for evidence of possible linkage of NF to six known markers on chromosome 4 and five markers on chromosome 19. Due to previous reports suggesting tight linkage of NF to the GC locus on chromosome 4 and the C3 (linked to myotonic dystrophy) locus on chromosome 19, these two markers were of particular interest. For the Utah families the cumulative LOD score for GC was -4.81 (r = 0.05). Cumulative LOD scores were -0.90 (r = 0.05) and -1.01 (r = 0.05) for C3 serum determinations and a C3 DNA polymorphism respectively. Linkage data is also included on all individual informative families for the GC and C3 loci to specifically address the question of heterogeneity. Linkage data is consistent with, but does not strongly support, the existence of heterogeneity implicating both the GC locus on chromosome 4 and the C3 locus on chromosome 19. A compilation of cumulative LOD scores from this and other current linkage studies produces values that in the absence of heterogeneity refute previous reports for tight linkage of NF to GC and to C3.

Adolescent↗
PubMed1986

Detection of restriction fragment length polymorphisms at the centromeres of human chromosomes by using chromosome-specific alpha satellite DNA probes: implications for development of centromere-based genetic linkage maps.

We describe a general strategy for the detection of high-frequency restriction fragment length polymorphisms in the centromeric regions of human chromosomes by molecular analysis of alpha satellite DNA, a diverse family of tandemly repeated DNA located near the centromeres of all human chromosomes. To illustrate this strategy, cloned alpha satellite repeats isolated from two human chromosomes, 17 and X, have been used under high-stringency conditions that take advantage of the chromosome-specific organization of this divergent repeated DNA family. Multiple high-frequency restriction fragment length polymorphisms are described for the centromeric region of both chromosome 17 and X chromosome. Mendelian inheritance of the variants is demonstrated. The X-linked alpha satellite polymorphisms in particular are highly informative and constitute a virtually unique centromeric DNA marker for each X chromosome examined. Since the strategy we describe is a general one, the alpha satellite family of DNA should provide a rich source of molecular variation in the human genome and should contribute to the development of centromere-based genetic linkage maps of human chromosomes.

Centromere↗