Search PubMed⌕ Search

Biomedical subjects

J Bryan

Publications and source records attributed to J Bryan.

At least 37 records · Page 2Linked to original sources
PubMed2001

Of mice and men: K(ATP) channels and insulin secretion.

K(ATP) channels are a unique, small family of potassium (K+)-selective ion channels assembled from four inward rectifier pore-forming subunits, K(IR)6.x, paired with four sulfonylurea receptors (SURs), members of the adenosine triphosphate (ATP)-binding cassette superfamily. The activity of these channels can be regulated by metabolically driven changes in the ratio of adenosine diphosphate (ADP) to ATP, providing a means to couple membrane electrical activity with metabolism. In pancreatic beta cells in the islets of Langerhans, K(ATP) channels are part of an ionic mechanism that couples glucose metabolism to insulin secretion. This chapter 1) briefly describes the properties of K(ATP) channels; 2) discusses data on a genetically recessive form of persistent hyperinsulinemic hypoglycemia of infancy (PHHI), caused by loss of beta-cell K(ATP) channel activity; and 3) compares the severe impairment of glucose homeostasis that characterizes the human phenotype with the near-normal phenotype observed in K(ATP) channel null mice.

Animals↗
PubMed2001

Gender, mosquitos and malaria: implications for community development programs in Laputta, Myanmar.

This paper examines the gender roles linked to division of labor and potential exposure to mosquitos and malaria prevention activities. A "Human Development Initiative" (HDI) Project has been launched in Laputta, a mangrove delta region of Myanmar assisted by United Nations Development Program since 1994. The project aims to improve rural community access to primary health care and provide micro-credit programs, income generation schemes, and educational opportunities as a basis for community empowerment. Women and children of low-income households are the target beneficiaries. Prior to self-care training program and distribution of self-care manuals, altogether 20 focus group discussions (separately assigned to men and women) were conducted in eight study villages between January to February 2000. The primary vector for malaria in study area is Anopheles sundaicus. Rural women were prone to malaria due to exposure to mosquitos within the peak biting period at night because of their gender assigned roles. Both men and women perceived that mosquitos commonly bite before midnight, more at dusk. Lack of awareness of correlation between mosquitos and malaria together with lack of affordability enhance either non-use or shared use of bed-nets at home. Rural women did not consider destruction of breeding places of mosquitos as their major concern. Thus, it is essential for program planners to motivate local women for more active participation in vector control measures within and beyond their households in the context of community development programs.

Animals↗
PubMed2000

Hetero-concatemeric KIR6.X4/SUR14 channels display distinct conductivities but uniform ATP inhibition.

K(IR)6.1 and K(IR)6.2 are the pore-forming subunits of K(NDP)(,) the nucleotide-diphosphate-activated K(ATP) channels, and classical K(ATP) channels, respectively. "Hybrid" channels, in which the structure is predetermined by concatemerizing K(IR)6.1 and K(IR)6.2, exhibit distinct conductivities specified by subunit number and position. Inclusion of one K(IR)6.2 is sufficient to open K(IR)6. X-X-X-X/SUR1(4) in the absence of nucleotide stimulation through sulfonylurea receptor-1 (SUR1). ATP inhibited the spontaneous bursting of hybrid channels with an IC(50(ATP)) approximately 10(-)(5) m, similar to that of K(IR)6.2(4)-containing channels. These findings and a transient increase in K(NDP) channel activity following rapid wash-out of MgATP suggested that K(IR)6.1 is not ATP-insensitive as previously believed. We propose that SUR-dependent, inhibitory ATP-enhanced interactions of the cytoplasmic domains of both K(IR)6.1 and K(IR)6.2 stabilize a closed form of the M2 bundle in the gating apparatus.

ATP-Binding Cassette Transporters↗
PubMed2000

Characterization of human retinal fascin gene (FSCN2) at 17q25: close physical linkage of fascin and cytoplasmic actin genes.

Retinal fascin is a newly identified photoreceptor-specific paralog of the actin-bundling protein fascin. Fascins crosslink f-actin into highly ordered bundles within dynamic cell extensions such as neuronal growth cone filopodia. We have isolated cDNA and genomic clones of human retinal fascin and characterized the structure of the human retinal fascin gene (FSCN2). The cDNA predicts a protein of 492 amino acids and molecular mass 55,057 that shows 94% identity to bovine retinal fascin and 56% identity to human fascin. Promoter analysis reveals a consensus retinoic acid response element and several potential binding sites for transcription factors Crx and Nrl, which correlates with the retina-specific expression of FSCN2 mRNA. Fluorescence in situ hybridization analysis and genomic clone sequencing indicate that the FSCN2 gene lies within 200 kb of the actin gene ACTG1 at 17q25. Database searches revealed that the human fascin gene FSCN1 and actin gene ACTB at 7p22 also coexist within a 200-kb genomic clone. The close physical linkage of these fascin/actin gene pairs suggests that they derive from a common gene duplication event and allows comparison of fascin and actin phylogenetic analyses. Finally, a possible link to the retinitis pigmentosa 17 allele (RP17) at distal 17q was excluded by demonstration of multiple independent segregation events in two RP17 kindreds. Informative FSCN2 polymorphisms were identified and will serve as useful markers in future linkage studies. The likely function of retinal fascin, in light of known fascin roles in other cell types, is to assemble actin microfilaments in support of photoreceptor disk morphogenesis.

Actins↗
PubMed2000

Sur1 knockout mice. A model for K(ATP) channel-independent regulation of insulin secretion.

Sur1 knockout mouse beta-cells lack K(ATP) channels and show spontaneous Ca(2+) action potentials equivalent to those seen in patients with persistent hyperinsulinemic hypoglycemia of infancy, but the mice are normoglycemic unless stressed. Sur1(-/-) islets lack first phase insulin secretion and exhibit an attenuated glucose-stimulated second phase secretion. Loss of the first phase leads to mild glucose intolerance, whereas reduced insulin output is consistent with observed neonatal hyperglycemia. Loss of K(ATP) channels impairs the rate of return to a basal secretory level after a fall in glucose concentration. This leads to increased hypoglycemia upon fasting and contributes to a very early, transient neonatal hypoglycemia. Whereas persistent hyperinsulinemic hypoglycemia of infancy underscores the importance of the K(ATP)-dependent ionic pathway in control of insulin release, the Sur1(-/-) animals provide a novel model for study of K(ATP)-independent pathways that regulate insulin secretion.

ATP-Binding Cassette Transporters↗
PubMed2000

Pharmaco-topology of sulfonylurea receptors. Separate domains of the regulatory subunits of K(ATP) channel isoforms are required for selective interaction with K(+) channel openers.

The differential responsiveness of (SUR1/K(IR)6.2)(4) pancreatic beta-cell versus (SUR2A/K(IR)6.2)(4) sarcolemmal or (SUR2B/K(IR)6. 0)(4) smooth muscle cell K(ATP) channels to K(+) channel openers (KCOs) is the basis for the selective prevention of hyperinsulinemia, myocardial infarction, and acute hypertension. KCO-stimulation of K(ATP) channels is a unique example of functional coupling between a transport ATPase and a K(+) inward rectifier. KCO binding to SUR is Mg-ATP-dependent and antagonizes the inhibition of (K(IR)6.0)(4) pore opening by nucleotides. Patch-clamping of matched chimeric human SUR1-SUR2A/K(IR)6.2 channels was used to identify the SUR regions that specify the selective response of sarcolemmal versus beta-cell channels to cromakalim or pinacidil versus diazoxide. The SUR2 segment containing the 12th through 17th predicted transmembrane domains, TMD12-17, confers sensitivity to the benzopyran, cromakalim, and the pyridine, pinacidil, whereas an SUR1 segment which includes TMD6-11 and the first nucleotide-binding fold, NBF1, controls responsiveness to the benzothiadiazine, diazoxide. These data are incorporated into a functional topology model for the regulatory SUR subunits of K(ATP) channels.

ATP-Binding Cassette Transporters↗
PubMed2000

Measures of fluency as predictors of incidental memory among older adults.

This study investigated fluency performance as a mediator of age-related declines in incidental memory performance as both are thought to rely on strategic retrieval processes. A large sample of community dwelling older adults completed a battery of tests assessing fluency, verbal knowledge, speed of information processing, and incidental recall. Fluency measures included initial and excluded letter fluency and the Uses for Objects Test, and they were assumed to reflect increasing reliance on strategic retrieval search. Speed emerged as the best mediator of age-related variance in incidental recall, and Uses for Objects Test performance added to the variance after controlling for verbal knowledge and speed. The results suggest that age-related decline in incidental recall is largely due to speed and the strategic search of memory.

Age Factors↗
PubMed2000

Familial hyperinsulinism and pancreatic beta-cell ATP-sensitive potassium channels.

Familial hyperinsulinism, also known as persistent hyperinsulinemic hypoglycemia of infancy (PHHI), is a genetic disease characterized by mild to severe hypoglycemia in the presence of inappropriately high levels of insulin. The recessive form is caused by mutations in the adenosine 5'-triphosphate (ATP)-sensitive K+ channel (KATP channel) present in the plasma membrane of pancreatic beta-cells. This channel is formed by two subunits, the high-affinity sulfonylurea receptor, SUR1, and KIR6.2, a member of the inwardly rectifying family of K+ channels. KATP channels regulate insulin secretion by linking membrane excitability with glucose metabolism. Approximately 50 mutations, in both channel subunits, that abolish or alter the regulation of beta-cell KATP channels have been identified in patients with the recessive form of PHHI.

Adenosine Triphosphate↗
PubMed2000

Measurement of executive function: considerations for detecting adult age differences.

This review considers the validity and suitability of neuropsychological and other tests of executive function for the detection of adult age differences in executive function. Executive function is typically assessed using tests which have been found to be sensitive to frontal lobe dysfunction because theory links executive function with the frontal lobes. However, any age-related decline in executive function is expected to be mild, or sub-clinical, compared to the deficits shown among those with frontal lesions. Therefore, in order to detect the type of mild executive dysfunction expected among older adults we need to employ tests sensitive enough to detect any age-related deficit, yet which are not too stressful or tiring for older adults to perform. This review discusses some commonly used neuropsychological tests of executive function as well as tests devised to assess theoretical aspects of executive function. Indications are given throughout as to which tests appear to be most suitable for detecting age differences in executive function.

Adult↗