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N Barton

Publications and source records attributed to N Barton.

13 recordsLinked to original sources
PubMed1992

The gene for autosomal dominant polycystic kidney disease lies in a 750-kb CpG-rich region.

PKD1, the locus most commonly affected by mutations that produce autosomal dominant polycystic kidney disease (ADPKD), has previously been localized to chromosome 16p13.3. Since no cytogenetic abnormalities have been found in association with ADPKD, flanking genetic markers have been required to define an interval--the PKD1 region--that contains the PKD1 gene. In this report we demonstrate, through the construction of a long-range restriction map that links the flanking genetic markers GGG1 (D16S84) and 26.6PROX (D16S125), that the PKD1 gene lies within an extremely CpG-rich 750-kb segment of chromosome 16p13.3. Approximately 90% of this region has been cloned in three extensive cosmid/bacteriophage contigs. The cloned DNA is a valuable resource for identifying new closer flanking genetic markers and for isolating candidate genes from the region.

Chromosomes, Human, Pair 16↗
PubMed1992

Tophaceous pyrophosphate deposition with extensor tendon rupture.

Tophaceous deposition of calcium pyrophosphate dihydrate (CPPD) crystals is considered unusual as is deposition within tendon sheaths. Associated tendon rupture is described but is rare. We report a lady with tophaceous CPPD deposition at the wrist, a previously unreported site. Contrary to previous cases, this occurred in the setting of symptomatic, polyarticular, pyrophosphate arthropathy. An additional point of interest was development of associated extensor tendon rupture with features favouring a non-inflammatory mechanism of tendon damage.

Aged↗
PubMed1990

Estimates of selection and gene flow from measures of cline width and linkage disequilibrium in heliconius hybrid zones.

Hybrid zones can yield estimates of natural selection and gene flow. The width of a cline in gene frequency is approximately proportional to gene flow (sigma) divided by the square root of per-locus selection (square root of s). Gene flow also causes gametic correlations (linkage disequilibria) between genes that differ across hybrid zones. Correlations are stronger when the hybrid zone is narrow, and rise to a maximum roughly equal to s. Thus cline width and gametic correlations combine to give estimates of gene flow and selection. These indirect measures of sigma and s are especially useful because they can be made from collections, and require no field experiments. The method was applied to hybrid zones between color pattern races in a pair of Peruvian Heliconius butterfly species. The species are Müllerian mimics of one another, and both show the same changes in warning color pattern across their respective hybrid zones. The expectations of cline width and gametic correlation were generated using simulations of clines stabilized by strong frequency-dependent selection. In the hybrid zone in Heliconius erato, clines at three major color pattern loci were between 8.5 and 10.2 km wide, and the pairwise gametic correlations peaked at R approximately 0.35. These measures suggest that s approximately 0.23 per locus, and that sigma approximately 2.6 km. In erato, the shapes of the clines agreed with that expected on the basis of dominance. Heliconius melpomene has a nearly coincident hybrid zone. In this species, cline widths at four major color pattern loci varied between 11.7 and 13.4 km. Pairwise gametic correlations peaked near R approximately 1.00 for tightly linked genes, and at R approximately 0.40 for unlinked genes, giving s approximately 0.25 per locus and sigma approximately 3.7 km. In melpomene, cline shapes did not perfectly fit theoretical shapes based on dominance; this deviation might be explained by long-distance migration and/or strong epistasis. Compared with erato, sample sizes in melpomene are lower and the genetics of its color patterns are less well understood. In spite of these problems, selection and gene flow are clearly of the same order of magnitude in the two species. The relatively high per locus selection coefficients agree with "major gene" theories for the evolution of Müllerian mimicry, but the genetic architecture of the color patterns does not. These results show that the genetics and evolution of mimicry are still only sketchily understood.

Animals↗
PubMed1990

Elective subtotal splenectomy. Indications and results in 33 patients.

Elective subtotal splenectomy was performed in 33 patients (30 children and 3 adults) between 1981 and 1989. Indications for the procedure were (1) prevention of azathioprine-induced neutropenia (n = 20); (2) Type I Gaucher disease (n = 9); and (3) cholesteryl ester storage disease, chronic myelogenous leukemia, thalassemia major, and splenic cyst in one patient each. There were no operative deaths, no reoperations for bleeding, and 30 of 33 (91%) patients had a functioning splenic remnant documented by a postoperative radionuclide spleen scan. One patient developed neutropenia without evidence of viral infection that required temporary cessation of azathioprine and the patient with thalassemia major had only transient improvement in transfusion requirements. All other patients (94%) had control of the underlying condition for which the operation was performed. We conclude that subtotal splenectomy is a safe, effective therapy for a variety of nontraumatic conditions.

Adolescent↗
PubMed1990

Localisation of human PGP and HAGH genes to 16p13.3.

Gene loci for phosphoglycolate phosphatase and hydroxyacyl glutathione hydrolase were localized within human chromosome band 16p13.3. This result was determined by the electrophoretic detection of enzymes from a human x mouse somatic cell panel, the members of which carried portions of human chromosome 16 with precisely defined breakpoints.

Chromosome Mapping↗
PubMed1988

Dystonia with marked diurnal variation associated with biopterin deficiency.

Two pairs of siblings with severe dystonia with marked diurnal fluctuation had both reduced CSF concentration of biopterin and marked symptomatic improvement of the dystonia in response to levodopa. Whether the reduced concentration of biopterin reflects focal abiotrophy of biopterin-containing neurons or deficiency of biopterin synthesis is uncertain. A fifth individual, who had a systemic deficiency of biopterin synthesis, shared the features of reduced biopterin in CSF, marked diurnal variation in the degree of dystonia, and clinical improvement in response to levodopa. Generalized dystonia with marked diurnal fluctuation was therefore shared by the four patients in whom biopterin deficiency was limited to the CNS and the patient with systemic deficiency of biopterin.

Adolescent↗
PubMed1985

High-pressure liquid chromatographic methods for determining arabinosyladenine-5'-monophosphate, arabinosyladenine, and arabinosylhypoxanthine in plasma and urine.

New high-pressure liquid chromatographic methods for determining concentrations of arabinosyladenine (Ara-A), its 5'-monophosphate (Ara-AMP), and arabinosylhypoxanthine (Ara-H) in plasma and urine are presented. A fluorescence detector is used for Ara-A and Ara-AMP, which are first converted to highly fluorescent derivatives with chloroacetaldehyde. This increases sensitivity greatly over previous methods. The sensitivities of the methods (in micrograms per milliliter) are as follows: in plasma, Ara-AMP, 0.002; Ara-A, 0.0015; and Ara-H, 0.35; and in urine, 9 times these values, respectively. Drug concentration data are also presented, which were obtained after doses of Ara-AMP were given intramuscularly to two patients treated with this drug for severe herpes zoster. One patient was given 13 mg of Ara-AMP per kg of body weight once daily, and the other was given 6.5 mg/kg twice daily. Peak Ara-AMP and Ara-A levels in plasma occurred within 1 h after the doses, and neither exceeded 2 micrograms/ml. Ara-AMP and Ara-A concentrations in plasma fell to less than 0.01 micrograms/ml in both patients by 4 to 6 h after the doses. Peak Ara-H concentrations in plasma occurred within 1 to 2 h after doses and were 21 micrograms/ml in patient 1 and 2. The highest concentration of Ara-AMP in urine was 0.09 micrograms/ml. The highest Ara-A concentration in urine was 62 micrograms/ml, and the highest Ara-H concentration in urine was 1,080 micrograms/ml. An interfering substance of unknown nature, cochromatographing with Ara-H, was encountered sporadically in urine samples. An algorithm based on differential spectrophotometry to identify and correct for this problem is described. Estimates of the renal clearances of Ara-AMP, Ara-A, and Ara-H are also given.

Arabinonucleosides↗
PubMed1979

Acyclovir kinetics after intravenous infusion.

The disposition and safety of the antiviral drug acyclovir were studied in 14 subjects with advanced malignancies. Acyclovir was administered by a 1-hr intravenous infusion at doses of 0.5, 1.0, 2.5, and 5.0 mg/kg. At the end of infusion, mean peak plasma levels (+/- SEM), determined by radioimmunoassay, were 6.4 +/- 0.7, 12.1 +/- 2.3, 14.9 +/- 2.7, and 33.7 +/- 7.1 microM. The plasma concentration-time profiles could be described by a biexponential equation. The half-life of acyclovir in the slow disposition phase ranged from 2.2 to 5 hr and the drug was detected in the plasma for at least 18 hr after infusion. The total body clearance ranged from 117 to 396 ml/min/1.73 m2. A proportionality between area under the curve and dose suggests that acyclovir exhibits dose-independent kinetics in the dose range studied. There was wide variation in cumulative urinary excretion of unchanged drug, ranging from 30 to 69% of the dose. From renal clearances of acyclovir, which were higher than creatinine clearances, it appears that both glomerular filtration and tubular secretion contribute to its renal excretion. Analysis of the urine by reverse-phase high-performance liquid chromatography revealed the presence of the metabolite 9-carboxymethoxymethylguanine. There was no indication of toxicity either clinically or from laboratory findings in any of the study subjects. This study demonstrates that in addition to selectivity and low toxicity, the kinetic profile and metabolic disposition of acyclovir make it an attractive candidate for therapy in a variety of herpes infections.

Aged↗
PubMed1977

Fractures of the phalanges of the hand.

A retrospective study has been made of 100 unselected adult finger fractures and a smaller group of similar injuries in children. The principles of treatment are reviewed, a simple practical classification of finger fractures suggested, and the treatment of each type described.

Adolescent↗