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Biomedical subjects

S Lawrence

Publications and source records attributed to S Lawrence.

At least 19 recordsLinked to original sources
PubMed1992

Construction of a map of chromosome 16 by using radiation hybrids.

A human-hamster cell hybrid carrying a single copy of chromosome 16 as the only human genetic material was irradiated with a single dose of gamma-rays (7000 rads; 1 rad = 0.01 Gy) and then fused with a thymidine kinase-deficient hamster cell line (RJKM) to generate radiation hybrids retaining unselected fragments of this human chromosome. In two experiments, 223 hybrids were isolated in hypoxanthine/aminopterine/thymidine (HAT) medium and screened with 38 DNA probes, corresponding to anonymous DNA or gene sequences localized on chromosome 16. The most likely order and location of the 38 DNA sequences were established by multiple pairwise analysis and scaled to estimate physical distance in megabases. The order and the distances thus obtained are mostly consistent with available data on genetic and physical mapping of these markers, illustrating the usefulness of radiation hybrids for mapping.

Chromosome Mapping↗
PubMed1992

A prospective evaluation of prehospital 12-lead ECG application in chest pain patients.

The objective of this study was to prospectively determine the utility, efficiency, and reliability of early prehospital 12-lead electrocardiogram (ECG) application, the improvement in prehospital diagnostic accuracy, and paramedic and base physician opinions regarding early application of prehospital 12-lead ECGs in a broad range of stable chest pain patients. The patient population consisted of cooperative, stable adult prehospital patients with a chief complaint of nontraumatic chest pain of presumed ischemic origin. From July 17, 1989 through January 1, 1990 paramedics acquired prehospital 12-lead ECGs on 680 stable adult chest pain patients. Factors affecting prehospital 12-lead ECG application were evaluated. Paramedic application of prehospital 12-lead ECGs was found to be efficient and reliable, and it can be applied to most cooperative stable adult prehospital chest pain patients. Prehospital 12-lead ECGs significantly improve base physicians' diagnostic accuracy in myocardial infarction, angina, and nonischemic chest pain patients. Paramedic and base physicians' opinions regarding early application of prehospital 12-lead ECGs during patient evaluation were favorable.

Chest Pain↗
PubMed1992

Algorithms for a location database.

The algorithms that drive the ldb location database are described. The program captures data on genetic and physical maps and combines information from different sources into a summary map. To assure portability it was developed in Fortran on a SUN SPARCStation under Unix. The algorithms, which combine rule-based seriation with a minimum deviance bootstrap, allow investigators and chromosome committees to produce a composite location in Mb that integrates partial maps. The program and manual are now available from the authors.

Algorithms↗
PubMed1992

The AD1 locus in familial Alzheimer disease.

The AD1 locus on chromosome 21 (MIM 104300) maps to the beta-amyloid precursor locus (APP) at approximately 27.7 Mb from pter (10.9 cM in males and 33.9 cM in females), flanked proximally by D21S8 and distally by D21S111, with D21S124 and D21S210 close but of uncertain order. AD1 accounts for 63 +/- 11% of multiplex Alzheimer pedigrees for which lod scores have been reported. Since a much smaller proportion of pedigrees have mutations in the cDNA for beta-amyloid (APP exons 16 and 17), it is likely that the AD1 locus spans controlling elements near those exons. There is no evidence for a second locus on chromosome 21. The remaining pedigrees may include sporadic cases as well as mutations at an AD2 locus on another chromosome.

Alzheimer Disease↗
PubMed1991

Radiation hybrid mapping.

A theory is developed to predict marker retention and conditional retention or loss in radiation hybrids. Applied to multiple pairwise analysis of a human chromosome 21 data set, this theory fits much better than proposed alternatives and gives a physical map consistent with other evidence and robust with respect to errors to typing. Radiation hybrids have great promise to provide order and physical location at two levels of resolution, spanning the techniques of linkage and restriction fragments and not limited to polymorphic loci.

Centromere↗
PubMed1991

Low dose erythropoietin in maintenance haemodialysis: improvement in quality of life and reduction in true cost of haemodialysis.

Human recombinant erythropoietin (r-HuEPO) improves quality of life in patients on maintenance haemodialysis, but the haemoglobin (Hb) level necessary to achieve this improvement is unknown. In this study, quality of life, functional capacity and symptoms of 28 haemodialysis patients with an initial Hb of 67 +/- 2 (mean +/- SEM) g/L were assessed after 0, 6 and 12 months of r-HuEPO, the dose of which was titrated to achieve a stable Hb of between 90 and 100 g/L. At six and 12 months Hb was 97 +/- 2 and 93 +/- 2 g/L, and mean r-HuEPO dose between three and six, and between nine and 12 months was 88 +/- 6 and 62 +/- 9 U/kg/week intravenously respectively. There was a significant improvement in level of activity and satisfaction with various aspects of life, and a reduction in fatigue, weakness, dyspnoea, angina and restless legs. Patients were able to walk 50% further in six minutes. The improvement in quality of life and function was similar to that reported from other centres whose target Hb was between 100 and 120 g/L, and where the r-HuEPO dose was 75% higher than in this study. Costs of r-HuEPO therapy were assessed. The drug itself costs +A3681/yr/patient, to which was added the estimated cost of additional dialyses and medications, bringing the total to +A5177/yr/patient. There was, however, a reduction in both hospitalisation by 8.3 days/yr/patient and medical consultation by 3.9 hours/yr/patient. Five patients commenced full-time work, one took up full-time study aimed at finding work, three transferred to home haemodialysis and six fewer patients drew social security benefits. The net cost saving from using low dose r-HuEPO was more than +A1,000/yr/patient.

Adult↗
PubMed1990

A pseudo-outbreak of Pseudomonas on a special care baby unit.

Following isolation of a multi-antibiotic-resistant pseudomonad from a newborn infant on admission to the Special Care Baby Unit and further isolation of apparently the same organism from two additional infants, a full investigation was instigated in an attempt to discover the source of the organism. This revealed a further 13 infants apparently colonized with the same organism. Repeated screening of the infants with a commercial sterile swab/transport medium failed to isolate the organism. Examination of bottles of the in-house transport medium, which had been stored under a sink, produced further isolates of the same organism. Water splashed from the sink was suspected as the ultimate source of contamination. Biochemical characterization showed that P. pickettii and at least one other Pseudomonas species were involved. The epidemiological, clinical and economic implications of the 'outbreak' are discussed together with the ultimate financial implications for investigation of such incidents.

Cross Infection↗
PubMed1990

Identification and molecular characterization of shrunken-2 cDNA clones of maize.

Mutation at the shrunken-2 (Sh2) locus of maize, a gene described more than 40 years ago, greatly reduces starch levels in the endosperm through its effect on the starch synthetic enzyme ADP-glucose pyrophosphorylase, an enzyme thought to be regulatory in this biosynthetic pathway. Although our previous work has suggested that Sh2 is a structural gene for this enzyme, we have also reported data compatible with Sh2 acting post-transcriptionally. In this study, we took advantage of a transposable element-induced Sh2 allele, its progenitor, and revertants to identify a clone for this locus. Although the cloning and identification were done independently of any knowledge concerning the product of this gene, examination of the deduced amino acid sequence revealed much similarity to known ADP-glucose pyrophosphorylase subunits of plants and bacteria, including regions involved in substrate binding and activator binding. Little sequence similarity, however, was found at the DNA level. These observations provide direct evidence that Sh2 encodes a subunit for endosperm ADP-glucose pyrophosphorylase. Analysis of several phenotypically wild-type alleles arising from a mutable sh2-Ds allele revealed one unexpected case in which DNA sequences of Sh2 were rearranged in comparison with the progenitor Sh2. In contrast to wild type, the Ds-induced sh2 allele conditions at least two transcripts in the endosperm.

Alleles↗
PubMed1990

Prevalence of intestinal parasites in a rural community in north-central Puerto Rico.

A hematology and parasitological survey was conducted in Bayaney, Hatillo, a rural community located in north-central Puerto Rico. A surprising finding was the comparatively high proportion of eosinophilia observed (43 of 83 individuals: 52%). Of these same 83 individuals 16 were found positive for intestinal helminth eggs using the modified Ritchie formol-ether concentration method, which uses 1 gram of feces. When eosinophilia was in the 5 to 10% range, 35% were also found to be infected with one helminth parasite. When eosinophilia was in the 10 + % range, 75% of the individuals were also found to be infected with one helminth parasite. The helminth eggs or larvae found were: hookworm (n = 8), Strongyloides stercoralis (2), Trichuris trichiura (5), and one individual with a combined infection of hookworm and Trichuris. Fifteen of the 16 (94%) individuals with intestinal helminth infections had eosinophilia ranging from 5 to 40%. Of a subgroup of 5th grade school children, 11 of 35 (31%) had eosinophilia ranging from 5 to 17%, but only two of these also had helminth eggs (Trichuris). No intestinal protozoan parasites were found. Although all infected individuals were apparently asymptomatic, they were informed of the results of the survey and contacted for additional medical examination and treatment, where applicable. An ELISA for anti-S. mansoni egg antibodies using a cationic antigen fraction denoted CEF-6 was done with the serum of 44 individuals of which 20 were a high risk group because of frequent water contact. Only one (2%) was found positive by serology and this one was negative for S. mansoni eggs by coprology. Additional studies are warranted to elucidate the etiology of eosinophilia in the absence of helminth infection.

Adolescent↗
PubMed1989

Evaluation of a monoclonal antibody pool for rapid diagnosis of respiratory viral infections.

A pool of monoclonal antibodies (MAbP) was evaluated both as a method of cell culture confirmation and as a rapid diagnostic screen for viral infection in respiratory secretions. The MAbP was used in a two-step fluorescent staining procedure on cells harvested from cultures (phase 1) and on exfoliated nasopharyngeal or tracheal cells (phase 2). Antibodies in the MAbP were directed against respiratory syncytial virus, adenoviruses, parainfluenza virus types 1, 2, and 3, and influenza viruses A and B. Individual antiviral antibody stains were used to identify specific viruses from MAbP-positive specimens. In phase 1 (cell culture confirmation only), 241 respiratory specimens were tested. MAbP sensitivity and specificity were 91 and 94%, respectively. In phase 2, 376 respiratory specimens were evaluated by direct staining of exfoliated cells, and these results were compared with results of cell culture isolation. The sensitivity and specificity of the MAbP used in direct specimen testing were 69 and 97%, respectively. These results indicate that the MAbP is highly specific and fairly sensitive for detection of seven different respiratory viruses in one testing procedure. The MAbP is a rapid screening technique for respiratory secretions and is potentially a cost-effective approach to viral detection.

Adenoviruses, Human↗
PubMed1989

Delayed lung maturation in the macrosomic offspring of genetically determined diabetic (db/+) mice.

We studied a genetically determined diabetes in pregnancy, the heterozygous diabetes (db/+) mouse. We found that fetal mice from these pregnancies are macrosomic with increased body, lung, and placenta wt, have altered organ protein, DNA and phospholipid content, and exhibit abnormal carbohydrate metabolism with increased liver and glycogen content. We further studied the effect of increased substrate availability and utilization on lung growth and maturation in (db/+) fetal mice, by measuring lung phospholipid synthesis as represented by the incorporation of the radiolabeled precursors, [3H]choline and [14C]glycerol, in fetal lung at 18 days' gestation (term = 19). Diabetic fetuses incorporated significantly more [3H]choline into disaturated phosphatidylcholine than controls (1.32 +/- 0.10 X 10(-2) versus 0.78 +/- 0.05 X 10(-2) nmol/g protein/min, mean +/- SE; p less than 0.001), but significantly less [14C]glycerol into phosphatidylglycerol than controls (3.18 +/- 0.38 versus 4.91 +/- 0.53 nmol/g protein/min, mean +/- SE; p less than 0.002), and their phosphatidylglycerol/phosphatidylinositol synthesis ratios were decreased (1.81 +/- 0.18 versus 3.17 +/- 0.14; mean +/- SE; p less than 0.001). Diabetic fetal lungs appeared morphologically less mature than controls at 18 days' gestation, as shown by a significantly decreased air space density (0.27 +/- 0.01 versus 0.43 +/- 0.02, mean +/- SE; p less than 0.001) and alveolar epithelial cell/total tissue ratio (0.54 +/- 0.02 versus 0.66 +/- 0.03, mean +/- SE; p less than 0.01). The increased synthesis of lung disaturated phosphatidylcholine in diabetic fetal mice may reflect the enhancement of body and lung growth in these macrosomic fetuses.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Increased binding of epidermal growth factor to placental membranes of intrauterine growth restricted fetal rats.

To examine the relationship between nutrient supply and fetal and placental growth, we examined epidermal growth factor (EGF) binding to membranes prepared from placentas of growth-restricted fetal rats. Intrauterine growth retardation was accomplished by unilateral ligation of the uterine artery; fetal rats on the contralateral uterine horn served as controls. Fetal growth restriction was accompanied by decreased placental wt at 19 and 20 day's gestation and significantly decreased placental glycogen content at 20 and 21 days, 30% and 15%, respectively. Placental DNA content and protein/DNA ratios were similar in the growth-restricted and control groups. Specific binding of 125I-EGF was increased in growth-restricted placentas at 19 and 20 days' gestation by 32% and 16%, respectively. 125I-EGF binding at 20-21 days increased linearly with the extent of placental growth restriction. Competitive binding experiments yielded linear Scatchard plots with an increased receptor density in growth-restricted placenta at 19 and 20 days' gestation, 74% and 60%, respectively. Binding affinities for the EGF receptor were similar in the two groups. The increased binding of EGF to membranes prepared from growth-restricted fetal rats may serve to enhance nutrient uptake under conditions of decreased uterine blood flow.

Animals↗