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Biomedical subjects

M Litt

Publications and source records attributed to M Litt.

At least 127 records · Page 7Linked to original sources
PubMed1989

Localization of a human brain sodium channel gene (SCN2A) to chromosome 2.

A DNA probe derived from a human genomic library has been used to localize on human chromosomes a gene coding for the alpha-subunit of the brain type II sodium channel (SCN2A). Hybridization of the probe to Southern blots made with DNAs from a rodent-human somatic cell hybrid panel indicates localization to the long arm of human chromosome 2. In situ hybridization to metaphase chromosomes confirms this assignment and indicates regional localization to 2q21-q33. The probe also reveals a frequent two-allele HaeIII RFLP.

Animals↗
PubMed1989

Assignment of the gene for complete X-linked congenital stationary night blindness (CSNB1) to Xp11.3.

X-linked congenital stationary night blindness (CSNB) is a nonprogressive retinal disorder characterized by a presumptive defect of neurotransmission between the photoreceptor and bipolar cells. Carriers are not clinically detectable. A new classification for CSNB includes a complete type, which lacks rod function by electroretinography and dark adaptometry, and an incomplete type, which shows some rod function on scotopic testing. The refraction in the complete CSNB patients ranges from mild to severe myopia; the incomplete ranges from moderate hyperopia to moderate myopia. To map the gene responsible for this disease, we studied eight multigeneration families, seven with complete CSNB (CSNB1) and one with incomplete CSNB, by linkage analysis using 17 polymorphic X-chromosome markers. We found tight genetic linkage between CSNB1 and an Xp11.3 DNA polymorphic site, DXS7, in seven families with CSNB1 (LOD 7.35 at theta = 0). No recombinations to CSNB1 were found with marker loci DXS7 and DXS14. The result with DXS14 may be due to the small number of scored meioses (10). No linkage could be shown with Xq loci PGK, DXYS1, DXS52, and DXS15. Pairwise linkage analysis maps the gene for CSNB1 at Xp11.3 and suggests that the CSNB1 locus is distal to another Xp11 marker, TIMP, and proximal to the OTC locus. Five-point analysis on the eight families supported the order DXS7-CSNB1-TIMP-DXS225-DXS14. The odds in favor of this order were 9863:1. Removal of the family with incomplete CSNB (F21) revealed two most favored orders, DXS7-CSNB1-TIMP-DXS255-DXS14 and CSNB1-DXS7-TIMP-DXS255-DXS14. Heterogeneity testing using the CSNB1-M27 beta and CSNB1-TIMP linkage data (DXS7 was not informative in F21) was not significant to support evidence of genetic heterogeneity (P = 0.155 and 0.160, respectively).

Alleles↗
PubMed1989

Rapid human chromosome aberration analysis using fluorescence in situ hybridization.

We have used in situ hybridization of repeat-sequence DNA probes, specific to the paracentromric locus 1q12 and the telomeric locus 1p36, to fluorescently stain regions that flank human chromosome 1p. This procedure was used for fast detection of structural aberrations involving human chromosome 1p in two separate experiments. In one, human lymphocytes were irradiated with 0, 0.8, 1.6, 2.4 and 3.2 Gy of 137Cs gamma-rays. In the other, human lymphocytes were irradiated with 0, 0.09, 0.18, 2.0, 3.1 and 4.1 Gy of 60Co gamma-rays. The frequencies (per cell) of translocations and dicentrics with one breakpoint in 1p and one elsewhere in the genome were determined for cells irradiated at each dose point. These frequencies both increased with dose, D, in a linear-quadratic manner. The delta, alpha, and beta coefficients resulting from a fit of the equation f(D)=delta + alphaD + betaD2 to the translocation frequency dose-response data were 0.0025, 0.0027 and 0.0037 for 137Cs gamma-rays, and 0.0010, 0.0041, and 0.0057 for 60Co gamma-rays. The delta, alpha, and beta coefficients resulting from a fit to the dicentric frequency dose-response data were 0.0005, 0.0010 and 0.0028 for 137Cs gamma-rays and 0.0001, 0.0002 and 0.0035, for 60Co gamma-rays. Approximately 32,000 metaphase spreads were scored in this study. The average analysis rate was over two metaphase spreads per minute. However, an experienced analyst was able to find and score one metaphase spread every 10s. The importance of this new cytogenetic analysis technique for biological dosimetry and in vivo risk assessment is discussed.

Cesium Radioisotopes↗
PubMed1989

Preservation of coronary flow reserve in stunned myocardium.

Microvascular obstruction and persistent focal ischemia have been suggested as a possible cause of myocardial dysfunction (stunning) after brief coronary occlusion. Microvascular occlusion should result in a reduction in maximal coronary flow reserve, although resting transmural coronary flow may be maintained by release of local vasodilators, such as adenosine. To test the microvascular occlusion hypothesis, coronary flow reserve was measured in 14 anesthetized dogs, before and after myocardial stunning produced by 10 min of ischemia. Intracoronary adenosine infusion (5,900 microM/min) increased coronary flow to the same degree in normal [195 +/- 20 (SE) ml/min] and stunned (212 +/- 23 ml/min) myocardium. Peak hyperemic flow after 100 s of coronary occlusion was also similar in normal (205 +/- 25 ml/min) and stunned (218 +/- 23 ml/min) myocardium. The adenosine antagonist 8-phenyltheophylline (5 mg/kg) reduced the flow response to exogenous adenosine, but neither resting coronary flow nor peak hyperemic flow in stunned myocardium was altered. In stunned myocardium, myocardial shortening at rest (0.2 +/- 2.0%) increased during reactive hyperemia (to 13.8 +/- 2.5%, P less than 0.01), but shortening promptly returned to basal levels after each hyperemia. These findings indicate that fixed microvascular occlusion is unlikely to be an important factor in the pathogenesis of stunned myocardium and that local adenosine release does not appear to have a compensatory role in coronary vasoregulation in stunned myocardium.

Adenosine↗
PubMed1989

A hypervariable microsatellite revealed by in vitro amplification of a dinucleotide repeat within the cardiac muscle actin gene.

The human genome contains approximately 50,000 copies of an interspersed repeat with the sequence (dT-dG)n, where n = approximately 10-60. In humans, (TG)n repeats have been found in several sequenced regions. Since minisatellite regions with larger repeat elements often display extensive length polymorphisms, we suspected that (TG)n repeats ("microsatellites") might also be polymorphic. Using the polymerase chain reaction to amplify a (TG)n microsatellite in the human cardiac actin gene, we detected 12 different allelic fragments in 37 unrelated individuals, 32 of whom were heterozygous. Codominant Mendelian inheritance of fragments was observed in three families with a total of 24 children. Because of the widespread distribution of (TG)n microsatellites, polymorphisms of this type may be generally abundant and present in regions where minisatellites are rare, making such microsatellite loci very useful for linkage studies in humans.

Actins↗
PubMed1989

The human dopamine D2 receptor gene is located on chromosome 11 at q22-q23 and identifies a TaqI RFLP.

Human dopaminergic neurons are involved in the control of hormone secretion, voluntary movement, and emotional behavior. Mediating these effects are the dopamine D1 and D2 receptors. These macromolecules belong to a large family of related sequences known as the G protein-coupled receptors. The D2 receptors have been of special interest because they bind, with high affinity and specificity, many of the commonly prescribed antipsychotic drugs. We previously isolated a full-length cDNA clone of the rat D2 receptor. When a chromosome mapping panel was probed with the rat D2 receptor cDNA a 15-kb EcoRI restriction fragment was identified and localized to human chromosome 11. The rat cDNA was also used to clone a human genomic fragment, lambda hD2G1, which contains the last coding exon of the D2 receptor gene (DRD2) and 16.5 kb of 3' flanking sequence. Hybridization of lambda hD2G1 to a chromosome 11 regional mapping panel localized DRD2 to 11q. In situ hybridization of lambda hD2G1 to metaphase chromosomes refined this assignment to the q22-q23 junction of chromosome 11. A search for RFLPs associated with D2DR identified a frequent two-allele TaqI RFLP.

Chromosome Mapping↗
PubMed1989

Population genetics of the highly polymorphic locus D16S7 and its use in paternity evaluation.

We have developed a DNA RFLP test to resolve paternity cases in which the accused man is included at a low probability of paternity by conventional testing. The DNA probe p79-2-23 was used to determine the allele frequency distribution for the locus D16S7 in the North American black, Caucasian, and Hispanic racial groups. Approximately 3,500 TaqI-digested DNAs were analyzed from the three populations studied. An apparent continuum of alleles was detected varying in size from 2.9 kb to 8.3 kb. Estimates of the average probability of exclusion were found to be .90 and .79 for the North American black and Caucasian populations, respectively. Gene frequency data for common and rare alleles indicated a potential paternity index ranging from 2 to 450.

Alleles↗
PubMed1988

A mapped set of DNA markers for human chromosome 17.

We have developed and mapped by genetic linkage a primary set of markers for chromosome 17. The map consists of 21 loci derived from 27 probe/enzyme systems, including eight highly informative markers at loci containing a variable number of tandemly repeated DNA sequences (VNTRs). The map is continuous from the telomeric region of the short arm to the telomeric region of the long arm, covering estimated genetic distances of 218 cM in males and 279 cM in females. The average heterozygosity among all 21 loci in the population sample analyzed is 58%; 77% heterozygosity was observed among the eight VNTR markers that were highly informative. This map will make it possible to detect by linkage the location of genetic defects associated with chromosome 17 and will also provide anchor points for a high-resolution map of this chromosome.

Algorithms↗
PubMed1988

Seven polymorphic loci mapping to human chromosomal region 11q22-qter.

Seven polymorphic loci that map to human chromosomal region 11q22-qter are revealed by DNA probes isolated from a chromosome-specific phage library constructed from a human X mouse somatic cell hybrid that has retained an 11q;16q translocation as the only human DNA. Three probes, each of which reveals a two-allele polymorphism, and four probes, each of which detects two linked RFLPs, have been characterized. Using a somatic cell hybrid mapping panel that divides 11q into four discrete sections, the seven clones have been localized to specific chromosomal regions. Localization of one of the clones has been confirmed and refined by in situ hybridization.

Animals↗
PubMed1988

Theory and design of disposable clinical blood viscometer.

A disposable clinical whole blood viscometer which can produce viscosity measures over a wide range of shear rates in a single rapid determination has been developed and is currently under test. The design is based upon the time varying flow of blood through a capillary. The flow is driven by the pressure in a fixed volume air chamber and transmitted to the sample through a compliant membrane. The time varying pressure in the air chamber is measured by a suitable transducer. The instantaneous shear stress of the blood in the capillary is proportional to the air pressure, while the instantaneous shear rate is proportional to the pressure-time derivative. Proper design ensures that the system operates as a first order dynamic system with flow resistance entirely determined by the nonlinear sample viscosity. By constructing the air chamber in two parts coupled by a quick disconnect fitting the design can allow for the blood-containing part of the instrument to be discarded, eliminating handling and cleaning of blood contacted components. The entire determination is completed in less than a minute, so that anticoagulants are not necessary. Tests on a prototype show that the instrument gives results in excellent agreement with those obtained on a cone-plate rheogoniometer.

Blood Viscosity↗