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Biomedical subjects

N Barton

Publications and source records attributed to N Barton.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1989

Neurologic complications in long-standing nephropathic cystinosis.

The central nervous system has been considered to be uninvolved in nephropathic cystinosis. Survival into adulthood, following renal dialysis and transplantation, has brought attention to the sequelae of long-standing cystinosis. We examined 14 patients with cystinosis, 12 of whom had undergone renal transplantation. Two patients had neurologic symptoms. One patient had progressive bradykinesia, dementia, and spasticity with computed tomographic scan evidence of cerebral atrophy and multifocal mineralization in bilateral internal capsules and periventricular white matter. One patient had behavioral and, to a lesser extent, cognitive disturbance and computed tomographic scan evidence of marked, progressive cerebral atrophy. Although the remaining patients had normal results of neurologic examinations, 11 had roentgenographic evidence of generalized cerebral atrophy; 2 of these had abnormal electroencephalograms, 1 had borderline-deficient intellectual function, and 2 had computed tomographic scan evidence of multifocal, intracerebral mineralization. The patients with nervous system abnormalities were not distinguished by patterns of medication use, demographic or laboratory features, or the relative severity of cystinosis. Although the neurologic involvement in these patients suggests that cystinosis may eventually involve the central nervous system, the differential diagnosis must include other complications from renal failure, dialysis, and immunosuppression.

Adolescent↗
PubMed1989

The divergence of a polygenic system subject to stabilizing selection, mutation and drift.

Polygenic variation can be maintained by a balance between mutation and stabilizing selection. When the alleles responsible for variation are rare, many classes of equilibria may be stable. The rate at which drift causes shifts between equilibria is investigated by integrating the gene frequency distribution W2N II (pq)4N mu-1. This integral can be found exactly, by numerical integration, or can be approximated by assuming that the full distribution of allele frequencies is approximately Gaussian. These methods are checked against simulations. Over a wide range of population sizes, drift will keep the population near an equilibrium which minimizes the genetic variance and the deviation from the selective optimum. Shifts between equilibria in this class occur at an appreciable rate if the product of population size and selection on each locus is small (Ns alpha 2 less than 10). The Gaussian approximation is accurate even when the underlying distribution is strongly skewed. Reproductive isolation evolves as populations shift to new combinations of alleles: however, this process is slow, approaching the neutral rate (approximately mu) in small populations.

Alleles↗
PubMed1989

Inference from clines stabilized by frequency-dependent selection.

Frequency-dependent selection against rare forms can maintain clines. For weak selection, s, in simple linear models of frequency-dependence, single locus clines are stabilized with a maximum slope of between square root of s/square root of 8 sigma and square root of s/square root of 12 delta, where sigma is the dispersal distance. These clines are similar to those maintained by heterozygote disadvantage. Using computer simulations, the weak-selection analytical results are extended to higher selection pressures with up to three unlinked genes. Graphs are used to display the effect of selection, migration, dominance, and number of loci on cline widths, speeds of cline movements, two-way gametic correlations ("linkage disequilibria"), and heterozygote deficits. The effects of changing the order of reproduction, migration, and selection, are also briefly explored. Epistasis can also maintain tension zones. We show that epistatic selection is similar in its effects to frequency-dependent selection, except that the disequilibria produced in the zone will be higher for a given level of selection. If selection consists of a mixture of frequency-dependence and epistasis, as is likely in nature, the error made in estimating selection is usually less than twofold. From the graphs, selection and migration can be estimated using knowledge of the dominance and number of genes, of gene frequencies and of gametic correlations from a hybrid zone.

Computer Simulation↗
PubMed1989

Fractures of the scaphoid.

We may think that we know all we need to know about fractures of the scaphoid. The reverse is true. Most of what we have been taught (and which we therefore believe we know) is unproved and much of it is actually untrue. Many of the key questions about diagnosis and management remain unanswered.

Bone Transplantation↗
PubMed1988

Polyclonal B-cell lymphocytosis and hypergammaglobulinemia in patients with Gaucher disease.

Sera from 23 individuals with Gaucher disease (GD) were analyzed for hypergammaglobulinemia and oligoclonal and monoclonal gammopathies. Serum IgG level was elevated in 15/23 (65%) patients, and a diffuse hypergammaglobulinemia was present in 10/23 (43%) patients. An oligoclonal gammopathy was noted in six patients, and a monoclonal gammopathy in two. Lymphocyte subset analysis was also carried out in eight individuals with GD. Four of five individuals showed increased surface Ig-positive lymphocytes, while 7/7 were positive for either increased CD19- and/or CD20-positive lymphocytes. An eighth patient was found to have a B-cell leukemia. Statistical analysis of kappa and lambda histograms were suggestive of a monoclonal excess. However, restriction enzyme analysis of four individuals with GD and increased B cells failed to show any evidence of Ig gene rearrangements. Serum Ig abnormalities and perhaps B-cell lymphocytosis appear to be common in the GD patient population and are not associated with circulating monoclonal lymphocytes.

Adult↗
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↗
PubMed1987

Niemann-pick variant disorders: comparison of errors of cellular cholesterol homeostasis in group D and group C fibroblasts.

Fluorescence microscopic examination of filipin-stained cultured skin fibroblasts derived from two brothers with group D Niemann-Pick disease revealed abnormal storage of low density lipoprotein (LDL)-derived cholesterol. LDL stimulation of intracellular cholesteryl ester synthesis was severely compromised in the Niemann-Pick D fibroblasts, as it also was in fibroblasts obtained from Niemann-Pick C patients. Cholesteryl ester synthesis was intermediately deficient in cells derived from an obligate group-D heterozygous carrier. Activity of acyl-CoA:cholesterol acyltransferase was within the normal range in cell-free extracts of both LDL-depleted and LDL-supplemented cultures of Niemann-Pick C and D fibroblasts. Incubation of Niemann-Pick D fibroblasts with LDL did not lead to as high a level of intracellular cholesterol accumulation as the excessive storage observed with Niemann-Pick C fibroblasts. These findings suggest that the Niemann-Pick variant disorders may represent a family of specific and possibly individual mutations that disrupt cellular cholesterol homeostasis.

Adult↗
PubMed1987

Does the use of the operating microscope improve the results of peripheral nerve suture?

Twenty-four cases of complete division of median or ulnar nerves were assessed on two occasions after direct suture, with an interval of three years between assessments. Clinical, electrophysiological and timed functional tests were used. All the operations had been performed by one surgeon, using the operating microscope for approximately half the cases but not for the other half. The results were analysed, and the patient's age, any delay between injury and suture, and the duration of follow-up were all found to exert strong and consistent effects on the scores obtained. After controlling for these factors, there was no consistent difference between the results of the two surgical methods. It is concluded that, at least in the hands of one particular surgeon, the use of the operating microscope gives no better results than careful epineural suture performed without it.

Adult↗
PubMed1987

Toxoplasma encephalitis in patients with acquired immune deficiency syndrome: diagnosis and response to therapy.

Although Toxoplasma gondii is the most commonly recognized cause of central nervous system mass lesions in patients with acquired immune deficiency syndrome, published investigations have provided little information about criteria for diagnosis of toxoplasmosis or the response to therapy. In this series the method of diagnosis and response to therapy were assessed in 14 patients who had evidence for toxoplasmosis based on routine histopathology, immunoperoxidase staining, or mouse inoculation. These patients presented with clinical and radiologic findings that did not clearly distinguish them from patients with other infectious or neoplastic processes. Excisional biopsies usually showed tachyzoites on routine histology, but needle biopsies were usually negative unless mouse inoculation or immunoperoxidase staining was employed. Response to pyrimethamine and sulfadiazine therapy was often prompt, but therapy had to be continued for long periods of time to maintain a clinical response, and no alternative regimen of one or more drugs appeared to be effective in patients unable to tolerate both pyrimethamine and sulfadiazine.

Acquired Immunodeficiency Syndrome↗