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Biomedical subjects

E Wright

Publications and source records attributed to E Wright.

At least 127 records · Page 7Linked to original sources
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

Massive schwannoma of the nose and paranasal sinuses.

Schwannomas, uncommon tumors of the nose and paranasal sinuses, are discovered late in their clinical course because of their obscure anatomic location. In this report, we have described the clinical findings in a massive nasal schwannoma (neurilemoma) that obstructed both nares, the left maxillary sinus, and the ethmoid sinuses, and protruded from the oropharynx and nose. The preoperative work-up included both computerized tomographic and magnetic resonance imaging studies.

Diagnosis, Differential↗
PubMed1987

Quantitative analyses of the binding of soluble complement-fixing antibody/dsDNA immune complexes to CR1 on human red blood cells.

We have used direct binding isotherm analyses to measure the association constant (Ka) and number of binding sites for the binding of prepared complement-fixing antibody (Ab)/dsDNA immune complexes (IC) to human red blood cells (RBC). In order to generalize this study we have examined the binding reaction for a number of different anti-dsDNA Ab (from systemic lupus erythematosus plasmas), complement sources, RBC donors, and dsDNA sizes. The affinity of the IC for the RBC is quite high, and the Ka values fall within a narrow range (5 to 14 X 10(10) liter/mol). Similarly, the limiting stoichiometries for the number of IC bound per RBC were between 40 and 91. The very high affinity and limiting stoichiometries both suggest that the IC bind to the RBC via multiple contacts with clusters of complement receptor type 1 (CR1). Furthermore, we have used three specific monoclonal AB (mAb) to quantitate CR1 on human RBC in the presence and absence of bound IC. One of these Ab, mAb 1B4, is blocked from binding to the RBC if IC are previously bound, and we have used this observation to verify the multivalent nature of the interaction of complement-fixing IC with CR1 on human RBC.

Antibodies, Antinuclear↗
PubMed1987

Gene for von Recklinghausen neurofibromatosis is in the pericentromeric region of chromosome 17.

Linkage analysis of 15 Utah kindreds demonstrated that a gene responsible for von Recklinghausen neurofibromatosis (NF) is located near the centromere on chromosome 17. The families also gave no evidence for heterogeneity, indicating that a significant proportion of NF cases are due to mutations at a single locus. Further genetic analysis can now refine this localization and may lead to the eventual identification and cloning of the defective gene responsible for this disorder.

Centromere↗
PubMed1987

Further linkage data on Norrie disease.

We obtained a LOD score of +1.61 using DNA marker L1.28 in 5 generations of a family with Norrie disease, raising the total LOD score to +5.42. There have been no recombinations between the 2 loci in any family to date, making the marker useful for genetic counseling.

Blindness↗
PubMed1987

Repair and fixation of potentially lethal damage (PLD) as demonstrated by delayed plating or incubation with araA in contact inhibited refed plateau-phase C3H mouse embryo 10 T1/2 cells grown in the presence of BrdUrd.

C3H mouse 10 T1/2 cells showing strong inhibition of growth at confluency were grown under daily refeeding in the presence of BrdUrd (from 0 to 1 microM) and exposed to gamma-rays either while exponentially growing or in the plateau phase. An increase in radiosensitivity was observed in both growth conditions mainly reflected by a reduction in Dq. Greater radiosensitization was observed in exponentially growing than in plateau-phase cells, and 3-4 times higher BrdUrd concentrations were required in plateau-phase cells for similar potentiation in killing. This effect could not be entirely attributed to a reduction in BrdUrd incorporation since measurements with 3H-BrdUrd showed reductions in incorporation between only 17-47% in plateau-phase cells. The rate of repair of potentially lethal damage (PLD) as demonstrated by delayed plating was not affected by the incorporation of BrdUrd, but the amount of repair (measured as the relative increase in cell survival) was higher for BrdUrd-containing cells. Post-irradiation treatment of cells in the plateau-phase (no BrdUrd) with 9-beta-D-arabinofuranosyladenine (araA) caused fixation of radiation-induced PLD. AraA treatment of cells grown in the presence of various amounts of BrdUrd also caused fixation of PLD, but resulted in survival levels similar to those observed with cells growing in BrdUrd-free medium. This result indicates that BrdUrd mediated radiosensitization cannot be observed when cells are prevented from repairing PLD by postirradiation incubation with araA. Based on these findings we propose that the mechanism of radiosensitization by BrdUrd incorporation might be, by increasing probability of fixation, mediated by the postirradiation progression of cells through the cycle, of a sector of PLD also sensitive to post-irradiation treatment with araA. For this sector of PLD the term alpha-PLD has been proposed.

Animals↗
PubMed1987

Genetic analysis of NF1: identification of close flanking markers on chromosome 17.

The gene causing von Recklinghausen neurofibromatosis, or NF1, has been more precisely localized in the pericentromeric region of chromosome 17. Narrowing of the location for the disease became possible through the identification of eight new DNA probe genetic markers in the centromeric region. Markers that closely flank the centromere also closely flank the NF1 gene. Although there was evidence against this localization in one recombinant, a review of the clinical records revealed a borderline diagnosis of NF1. Significant sex differences in recombination were observed in the pericentric region, and odds for different orders were less discriminating when sex differences were considered in multilocus analyses. The location of the NF1 gene with respect to the centromere could not be determined because recombinants between NF1 and the centromere were not detected in the set of families tested.

Animals↗
PubMed1987

Possible importance of PLD repair in the modulation of BrdUrd and IdUrd-mediated radiosensitization in plateau-phase C3H10T1/2 mouse embryo cells.

C3H10T1/2 mouse embryo cells exhibiting strong contact inhibition of growth at confluency were grown in the presence of 5-bromodeoxyuridine (BrdUrd) or 5-iododeoxyuridine (IdUrd) (0-1.2 microM) with daily refeeding and exposed to gamma-rays (6 Gy) either in the logarithmic or the plateau phase of growth. Sensitization to radiation was observed in both growth states with increasing concentration of BrdUrd or IdUrd but the degree of sensitization achieved was lower for plateau-phase cells. Because the degree of [H3]BrdUrd incorporation was found to be similar in exponentially growing and plateau-phase cells, it is hypothesized that the radiosensitization caused by pyrimidine analogues may be affected by the physiological state of the cells at the time of irradiation. Delayed plating of plateau-phase cells (6 h) caused an increase in survival, indicating repair of potentially lethal damage (PLD). A greater increase in cell survival was observed in cells that had been grown in the presence of BrdUrd and IdUrd and it was found to increase with increasing concentrations. This analogue-concentration dependent PLD repair activity resulted in an almost complete loss of the radiosensitizing effect in delayed plated plateau-phase cells up to a concentration of about 0.6 microM of BrdUrd and IdUrd. Both compounds, but especially BrdUrd, caused a relaxation in the mechanism of contact inhibition and led to higher cell densities in the plateau phase. The results suggest that repair and/or expression of PLD might be involved in the mechanism underlying BrdUrd and IdUrd-mediated radiosensitization and point out the potential importance of PLD repair in the modulation of the radiosensitizing effect of these compounds in their clinical application.

Animals↗
PubMed1987

A genomic search for linkage of neurofibromatosis to RFLPs.

Our initial attempt to map NF was directed towards chromosomes 4 and 19, both of which had provided positive evidence for linkage in previous reports. This analysis showed no evidence in support of either hypothesis. Our second attempt at mapping NF was a general search of the genome, analysing a set of markers selected according to their degree of polymorphism, chromosomal location, ease of use, and availability. Data for linkage analysis were obtained from 17 multiplex families which are segregating a gene for NF. Linkage analyses were performed using PAP. Of note is the lod score of +1.17 at a recombination fraction of 0.1 between NF and the centromere of chromosome 17.

Chromosome Mapping↗
PubMed1986

The kinetics of clearance of human antibody/dsDNA immune complexes from rabbit circulation. Effects of dsDNA size, rheumatoid factor, and reduction and alkylation of the antibodies.

We have conducted in vivo investigations of the rate of clearance of prepared antibody/dsDNA immune complexes from the circulation of rabbits and have correlated the results with some in vitro immunologic properties of the complexes. Those complexes that fix complement most efficiently in vitro (as manifested by their complement-mediated binding to human red blood cells or rabbit platelets) are cleared most rapidly. Factors that decrease this binding such as reduction and alkylation of the antibodies or the use of dsDNA of a lower m.w. also tend to prolong the circulation times for the complexes. This study provides additional evidence in support of a complement-mediated platelet immune complex clearance mechanism in non-primates that parallels the erythrocyte immune complex clearance mechanism in primates first described by He bert. Finally, the implications of our findings with respect to the importance of dsDNA size in the pathogenesis of systemic lupus erythematosus are discussed.

Alkylation↗
PubMed1986

Evidence for differences among the sectors of potentially lethal damage expressed by hypertonic treatment in plateau-phase V79 cells after exposure to neutrons or gamma rays: the importance of distinction between alpha and beta-PLD forms.

Expotentially growing and plateau-phase V79 cells were exposed to various doses of neutrons and plated either immediately or after treatment in hypertonic medium (250-500 mM NaCl) to express radiation-induced potentially lethal damage (PLD). Postirradiation treatment of exponentially growing cells in hypertonic medium (500 mM) resulted in a decrease in both Dq and D0, whereas postirradiation treatment of plateau-phase cells in hypertonic medium (in the range between 200 to 1,500 mM) resulted mainly in a reduction of Dq. This difference in response between exponentially growing and plateau-phase cells may reflect differences in the chromatin structure in cells at various stages of the cell cycle, affecting fixation of radiation-induced damage. Exposure of plateau-phase cells to gamma rays, on the other hand, resulted in a treatment time and salt concentration-dependent decrease in Dq along with a decrease in D0. Repair of neutron-induced, hypertonic treatment-sensitive PLD, measured by delaying treatment for various periods after irradiation, was found to proceed with a t1/2 of about 1 h. This is similar to the repair kinetics obtained by delaying treatment of plateau-phase cells with 150 microM beta-D-arabinofuranosyladenine (araA) after exposure to gamma rays or neutrons and contrasts the repair kinetics observed after exposure of cells to gamma rays. In this case, hypertonic treatment was found to affect a form of PLD repaired with a t1/2 of 10-15 min (beta-PLD) and araA, a different form of PLD, repaired with a t1/2 of about 1 h (alpha-PLD). Based on these results it is hypothesized that the sector of lesions affected by hypertonic treatment and araA coincides after exposure to neutrons (effect on alpha-PLD) but only partly overlaps after exposure to gamma rays (due to the effect on beta-PLD of hypertonic treatment). The results presented, together with previously published observations, suggest a differential induction and/or fixation by hypertonic medium of the alpha- and beta-PLD forms as the LET of the radiation increases. Furthermore, they indicate that direct comparison of the effects of a postirradiation treatment, as well as of the repair kinetics obtained by its delayed application after exposure to radiations of various LET, should be made with caution.

Animals↗