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R Leach

Publications and source records attributed to R Leach.

At least 37 records · Page 2Linked to original sources
PubMed1994

High-resolution genomic mapping of the three human replication protein A genes (RPA1, RPA2, and RPA3).

Human replication protein A (RPA) is a three-subunit protein that plays a central role in eukaryotic DNA replication, homologous recombination, and excision repair. We have previously reported the cloning and bacterial overexpression of the three RPA genes and have mapped them to chromosome 1 (RPA2), chromosome 7 (RPA3), and chromosome 17 (RPA1). We have now obtained yeast strains with artificial chromosomes carrying the three human RPA genes and report the more detailed genomic mapping of RPA. RPA1 was mapped to chromosome 17p13.3 using a combination of PCR amplification of somatic cell hybrids and radiation hybrids containing chromosome 17 fragments. RPA2 was mapped to chromosome 1p35 by PCR amplification of somatic cell hybrids of chromosome 1 and by fluorescence in situ hybridization. RPA3 was mapped to chromosome 7p22 by Southern analysis and PCR amplification of somatic cell hybrids of chromosome 7 as well as fluorescence in situ hybridization. Since RPA is an essential component of major metabolic events affecting DNA, the physical mapping of the genes for it may help elucidate the biochemical basis of genetic disorders involving DNA metabolism.

Blotting, Southern↗
PubMed1994

Effect of lesion size on the metabolic activity of tibial dyschondroplastic chondrocytes.

Experiments were conducted to determine the influence of lesion size and method of producing tibial dyschondroplasia on metabolic activity of cultured chondrocytes. Genetic selection was one method used to produce a high incidence of tibial dyschondroplasia. Chondrocytes obtained from severe lesions exhibited reduced mitogenic activity (3H-thymidine incorporation) and ability to synthesize matrix proteoglycans (35SO4 incorporation) when compared with normal growth plate and smaller lesions. When a commercial broiler strain was used, all chondrocytes isolated from lesions induced by feeding thiram had reduced metabolic activity. Similar results were observed with severe lesions obtained from copper-deficient chicks. It is concluded that lesion size is an important factor in determining subsequent metabolic activity of chondrocytes isolated from tibial dyschondroplastic lesions.

Animals↗
PubMed1993

Fibrinolytic parameters in women undergoing ovulation induction.

OBJECTIVE: The purpose of this study was to evaluate the effect of elevated levels of circulating estradiol on the clotting and fibrinolytic system in patients undergoing controlled ovarian hyperstimulation. STUDY DESIGN: Fifty-two patients undergoing controlled ovarian hyperstimulation with human menopausal gonadotropins or urofollotropin were asked to participate. Blood for hemostasis parameters was obtained on the days that patients returned for estradiol sampling. Sample days were identified as cycle days 1 to 5 (baseline), 6 to 9, and 10 to 14. Each factor was analyzed by repeated-measures analysis of variance and correlation analysis. RESULTS: A significant decline was observed for tissue plasminogen activator antigen and plasminogen activator inhibitor type 1 activity from baseline to cycle days 10 to 14. As serum estradiol levels increased throughout each phase (maximum mean estradiol 739.8 pg/ml), a significant linear decrease was observed for both tissue plasminogen activator antigen and plasminogen activator inhibitor type 1 activity, whereas thrombin-antithrombin III complexes did not change significantly. A significant positive correlation was also observed for plasminogen activator inhibitor activity and tissue plasminogen activator antigen level over all cycle days examined. CONCLUSION: Down-regulation of the fibrinolytic system was observed as estradiol levels increased. However, thrombin formation did not change, thus suggesting that elevated circulating estradiol alone does not predispose to a thromboembolic event.

Adult↗
PubMed1992

Future directions in reproductive medicine.

Major advances in assisted reproductive technology and fertility enhancement in the last decade are discussed in this article. Sustained research efforts have led to refinement in in vitro fertilization and related technologies. Other therapeutic innovations such as the use of newer pharmacologic agents and surgical procedures to preserve reproduction function are highlighted. Future directions and anticipated developments are briefly reviewed.

Fertilization in Vitro↗
PubMed1989

Two NF1 translocations map within a 600-kilobase segment of 17q11.2.

Balanced translocations, each involving chromosome 17q11.2, have been described in two patients with von Recklinghausen neurofibromatosis (NF1). To better localize the end points of these translocation events, and the NF1 gene (NF1) itself, human cosmids were isolated and mapped in the immediate vicinity of NF1. One cosmid probe, c11-1F10, demonstrated that both translocation breakpoints, and presumably NF1, are contained within a 600-kilobase Nru I fragment.

Animals↗
PubMed1989

Non-steroidal anti-inflammatory drug ingestion: retrospective study of 272 bleeding or perforated peptic ulcers.

The ingestion of non-steroidal anti-inflammatory drugs (NSAID) in 272 patients with bleeding or perforated peptic ulcer was compared with 272 age/sex matched controls. A significantly higher proportion of patients with gastric ulcers had received NSAID than those with duodenal ulcers. Twelve of 90 (13%) patients admitted with bleeding duodenal ulcers had received NSAID compared with 11 of 26 (42%) patients with bleeding gastric ulcers (P = 0.003). Sixteen of 132 (12%) patients with perforated duodenal ulcer were taking NSAID compared with 8 of 24 (33%) patients with perforated gastric ulcer. Thirty eight percent of patients with both bleeding and perforated gastric ulcers had received NSAID compared with 13% bleeding and perforated duodenal ulcers (P less than 0.002). This study confirms the association of NSAID and complicated peptic ulcer in patients of over 65 years and highlights the particular susceptibility of the gastric mucosa to their injurious effect.

Adult↗
PubMed1988

Supplemental oxygen and exercise ability in chronic obstructive airways disease.

The influence of supplemental oxygen on exercise performance was assessed in 17 patients with severe airflow obstruction. Exercise capacity was measured by the six minute walking distance, by an endurance walking test, and by an endurance cycling test and comparison was made with performance when the patient was breathing air. In addition, the relation between the flow rate of supplemental oxygen and cycling endurance time was studied. Portable oxygen (41 min-1) carried by the patient increased the mean endurance walking time by 59% and the six minute walking distance by 17%. The endurance time for cycling at a constant work load was increased by 51% with oxygen at a flow rate of 21 min-1, by 88% at 41 min-1, and by 80% at 61 min-1. Supplemental oxygen prolonged the length of time that the patients were able to walk at a fixed speed. It also increased the mean speed achieved during a six minute walk but this was variable and did not occur in all the subjects. The benefit from supplemental oxygen was not cancelled by the effort of carrying the portable cylinder.

Adult↗
PubMed1988

Perforated duodenal ulcer and cigarette smoking.

Whilst the association between smoking and peptic ulceration has been reported previously, the relationship between smoking and the complications of ulcers, such as perforation, bleeding or acute painful exacerbation, has not been examined. In a retrospective study comparing 275 emergency admissions for peptic ulcer with 275 controls, cigarette smoking was significantly more common only in those with a perforated duodenal ulcer. Of 128 patients with perforated duodenal ulcers, 110 (86%) were cigarette smokers compared with 65 (51%) of the 128 matched controls (X2, P less than 0.01). Cigarette smoking in patients with bleeding or acutely exacerbated ulcers was not significantly more common than in controls. These findings strongly suggest a particular association between smoking and perforated duodenal ulcer.

Duodenal Ulcer↗
PubMed1987

Purification of an IgM antibody response-enhancing factor to the alpha 1-6 epitope of native dextran from serum and supernatants from T-cell hybridomas.

We have found that some hybrids produced by fusing AKR thymoma BW 5147 with spleen cells from Dx-hyperimmunized CBA mice produce factors that affect the primary CBA IgM PFC response. By the use of HPLC-DEAE chromatography, sometimes combined with affinity chromatography, we have purified from hyperimmune anti-Dx serum, from ascites-growing T hybrids, and from normal CBA serum a family of factors that specifically enhance the anti-Dx IgM response. They show specificity for either Dx or anti-Dx, they may contain an Iak determinant, and they are genetically restricted in their function. The factors from all three sources are found in the same fractions after separation and move in fractions without Ig contamination. The affinity-purified factor was eluted at an NaCl concentration of 0.15-0.20 M. On the basis of these characteristics we believe that we have separated a class of T cell-derived helper factors from serum. The concentration of the factor in serum increases after hyperimmunization with Dx. As a specificity control we show that the same sera contain a natural anti-SRBC IgM response-enhancing factor. It co-separates with the anti-Dx-enhancing factor, but they can be distinguished by their preferential binding to their own antigens.

Animals↗
PubMed1986

Construction of a map of the short arm of human chromosome 6.

Four DNA sequences that reveal restriction fragment length polymorphisms (RFLPs) on the short arm of human chromosome 6 have been identified. Two of these sequences were isolated from recombinant DNA libraries enriched for DNA from human chromosome 6, one was isolated as a subclone from a human DNA segment having homology to an HLA class I sequence, and one was isolated by virtue of its homology to part of the insulin gene. Genetic linkage was determined among these four polymorphic sequences and several genes known to be on chromosome 6: glyoxylase I (GLO1), HLA-DR alpha, HLA-DQ alpha, and HLA-B. Additionally, two of the four RFLPs were regionally localized by using 53 deletion cell lines that had been typed for HLA-A, -B, and -DR, and for glyoxylase I. A genetic map of the short arm of chromosome 6 has been constructed on the basis of linkage studies with the eight markers. The map spans a minimum of 60 recombinational units and will be useful in the study of HLA-associated diseases.

Chromosome Mapping↗
PubMed1986

Arbovirus infection in a Murray Valley community.

Serum antibodies to Ross River virus and Murray Valley encephalitis virus were measured during 1974-1975 in residents of Echuca, an urban Murray Valley community. A representative group of volunteers was obtained by random selection of households. The prevalence of antibodies to both viruses increased progressively with age. Prevalence was equal in both sexes for both viruses in all age groups, indicating that the risk of infection was mainly determined by geography rather than by personal activities. Antibody levels remained unchanged in the following year when there was no disease activity in the area. The stability of antibody levels permitted retrospective estimates of mean rates of infection. These were approximately 0.4% per annum for both viruses when age was used as the index for years of exposure. With allowance for other factors, the best estimate for both virus infections is probably closer to 1%. The morbidity rate for Ross River virus infection appeared to be low. It is concluded that infection with Ross River virus and with Murray Valley encephalitis-related viruses is endemic in the Murray Valley.

Adolescent↗
PubMed1985

Deletion mapping of HLA and chromosome 6p genes.

We have analyzed a set of heterozygous mutants with deletions that encompass parts of HLA and surrounding regions of chromosome 6p. By a combination of Southern blotting, serologic, enzymatic, and cytogenetic analyses, we have ordered eight independent deletion break points into a sequence that divides chromosome 6p into six regions. The deletion mutants have been used in conjunction with the Southern blot technique to map HLA and other 6p gene probes into those regions. On the basis of these and other data we propose a genetic and physical map of HLA and surrounding regions of chromosome 6p. We find that for HLA probes, most of which hybridize with more than one gene, the multiple copies recognized by single probes map to single regions. Any chromosome 6p gene can now be regionally mapped by using these mutants.

Chromosome Deletion↗
PubMed1985

Alpha 1-antitrypsin deficiency and liver cirrhosis in adults.

Although cirrhosis of the liver caused by alpha 1-antitrypsin deficiency is not uncommon in children, only a few cases have been described in adults. We have seen three such patients--one man and two women, ranging in age from 57 to 66 years. These cases show the wide spectrum of this genetically influenced disease.

Adult↗
PubMed1984

Isolation and regional localization of DNA segments revealing polymorphic loci from human chromosome 13.

A recombinant DNA library enriched for portions of human chromosome 13 has been constructed from a hamster-human somatic cell hybrid that contained human chromosomes 13, 12, and 6p. A total of 733 phages were identified that contain human DNA inserts, and 46 single-copy subfragments have been derived and used as probes on Southern transfers of genomic DNA isolated from unrelated individuals. From this set, nine fragments revealing polymorphic loci (RFLP) in Msp I- or Taq I-digested DNA have been identified, of which three are polymorphic with both enzymes. Six of these probes have been shown to segregate concordantly with human chromosome 13 in a somatic cell hybrid mapping panel, and the RFLPs at these loci have been shown to behave as codominant Mendelian alleles. Additionally, hybridization to DNA isolated from cells containing various deletions of chromosome 13 has allowed regional localization. This recombinant DNA library will be useful in the study of retinoblastoma as well as in the study of the mechanisms responsible for abnormalities of this autosome.

Animals↗