Search PubMed⌕ Search

Biomedical subjects

J Bryan

Publications and source records attributed to J Bryan.

At least 55 records · Page 3Linked to original sources
PubMed1997

Malaria in Honiara, Solomon Islands: reasons for presentation and human and environmental factors influencing prevalence.

During February and March 1995, out-patients attending health clinics and the Central Hospital in East Honiara, Guadalcanal, Solomon Islands, were surveyed with the aim of determining factors influencing the differing rates of malaria, the proportion of transmission occurring within the town, and the reasons for presentation. Three hundred and nine adult patients, who were sick and had blood smears taken, were asked about their general knowledge of malaria transmission. Of those interviewed, 120 were visited at their home in East Honiara, to determine variables. EpiInfo 5.1 was used in analysis. A history of fever alone was not a good indicator of parasitemia. Most precautions, including bed nets, window screens and personal precautions were of little benefit. Significant protection was afforded individuals and families with indoor kitchens. Patients not completing their antimalarial treatment fared worse in terms of parasitemia and malaria history. Most malaria/parasitemia was indigenous to Honiara. Many patients had a good knowledge of malaria transmission and mosquitos, but this did not translate into a lower rate of parasitemia or malaria.

Adolescent↗
PubMed1996

Growth of molluscum contagiosum virus in a human foreskin xenograft model.

Molluscum contagiosum virus (MCV) is a common pathogen causing a troublesome skin condition in many immunocompetent individuals and a widespread, disfiguring affliction in many patients with AIDS. We have successfully infected human foreskin fragments with a patient-derived isolate of MCV. This was demonstrated by exposing the foreskin pieces to a patient lesion extract and implanting the tissue under the renal capsule of athymic mice. Light and electron microscopic examination of infected implants showed the presence of cytoplasmic inclusions containing typical poxvirus particles within 2-3 weeks of implantation. Replication of MCV was established by demonstrating that viable virus was required to produce the cytopathologic effects, and viral DNA replication was demonstrated by incorporation of bromodeoxyuridine into cytoplasmic inclusions. Four additional patient extracts (representing both described MCV types) were also used to successfully infect foreskin implants. A limited number of attempts to pass virus from one infected implant to another were not successful. This system is the most rapid and reproducible for growing MCV that has been reported to date.

Animals↗
PubMed1996

The high-affinity sulfonylurea receptor: distribution, glycosylation, purification, and immunoprecipitation of two forms from endocrine and neuroendocrine cell lines.

The high-affinity sulfonylurea receptor, a novel member of the ATP-binding cassette superfamily, is one component of the ATP-sensitive K+ channel. The protein is critical for regulation of insulin secretion from pancreatic beta-cells, and mutations in the receptor have been linked to familial hyperinsulinemia, a disorder characterized by unregulated insulin release despite severe hypoglycemia. The sulfonylurea receptor is present in membranes from a number of endocrine and neuroendocrine cell lines, including HIT-T15, RINm5f, alpha TC-6, AtT-20, and GH3 cells. Two forms of the receptor are present in RINm5f and alpha TC-6 cells, with apparent SDS gel molecular masses of 140 and 150 kDa. The two forms have equally high affinity, KD approximately 3 nM, for an iodinated derivative of glyburide, an anti-diabetic sulfonylurea. The receptor is a glycoprotein; treatment of RINm5f or alpha TC-6 cells with tunicamycin reduces the 140 and 150 kDa species to a single approximately 137 kDa protein. The 140 and 150 kDa receptors bind differentially to concanavalin A and wheat germ agglutinin, and lectin-affinity chromatography is ideal for the initial stages of receptor purification. After lectin-affinity chromatography, the same methods can be applied for purifying the 150 kDa form as for the 140 kDa receptor. A transiently expressed receptor with a histidine-tagged carboxy-terminus was purified by Ni-agarose chromatography, and this variant was used to demonstrate that the 140 kDa polypeptide is full length. Anti-peptide antibodies directed against the amino-terminus of the receptor and antibodies against the nucleotide binding folds immunoprecipitate both receptor forms. The results indicate the 140 and 150 kDa receptors are differentially glycosylated forms of the same polypeptide chain.

ATP-Binding Cassette Transporters↗
PubMed1996

Expression of the calcium-binding protein, parvalbumin, in cultured cortical neurons using a HSV-1 vector system enhances NMDA neurotoxicity.

Calcium-binding proteins (CaBPs) are a family of proteins having a unique distribution in the brain and are thought to be important in buffering intracellular calcium. Glutamate neurotoxicity is a process by which the over-activation of glutamate receptors can cause the influx of excessive extracellular calcium and neuronal cell death. It has been proposed that neurons containing CaBP may be more resistant to glutamate neurotoxicity due to their increased ability to buffer calcium. Using a herpes simplex virus-1 (HSV-1) vector system we packaged the CaBP gene, parvalbumin, or the marker gene, beta-galactosidase (beta-gal), correctly in viron particles, which were found upon infection to express mRNA specific to these vectors. PC12 and neocortical cultures showed strong immunohistochemical staining for either beta-gal or parv. The cortical cultures stained positively for endogenous glutamate decarboxylase, a marker for GABAergic neurons, but not for endogenous parvalbumin, indicating that parvalbumin was being expressed ectopically from the HSV-1 vector. Interestingly, the expression of parvalbumin increased cortical culture's susceptibility to N-methyl-D-aspartate-induced neurotoxicity. This increase in neurotoxicity was not due to the wild-type virus or the helper virus which accompanies the packaging of these vectors. We speculate that the ectopic expression of parvalbumin in cortical cultures may be increasing glutamate release which in turn increases cell death.

Animals↗
PubMed1996

Adenosine diphosphate as an intracellular regulator of insulin secretion.

Adenosine triphosphate (ATP)-sensitive potassium (KATP) channels couple the cellular metabolic state to electrical activity and are a critical link between blood glucose concentration and pancreatic insulin secretion. A mutation in the second nucleotide-binding fold (NBF2) of the sulfonylurea receptor (SUR) of an individual diagnosed with persistent hyperinsulinemic hypoglycemia of infancy generated KATP channels that could be opened by diazoxide but not in response to metabolic inhibition. The hamster SUR, containing the analogous mutation, had normal ATP sensitivity, but unlike wild-type channels, inhibition by ATP was not antagonized by adenosine diphosphate (ADP). Additional mutations in NBF2 resulted in the same phenotype, whereas an equivalent mutation in NBF1 showed normal sensitivity to MgADP. Thus, by binding to SUR NBF2 and antagonizing ATP inhibition of KATP++ channels, intracellular MgADP may regulate insulin secretion.

ATP-Binding Cassette Transporters↗
PubMed1996

Association of human papillomavirus type 11 DNA with squamous cell carcinoma of the tongue.

A 47-year-old man with a history of a benign papilloma of the tongue 5 years earlier was treated for a squamous cell carcinoma of the tongue with surgical resection. An analysis of the tumor DNA using several methods showed the presence of human papillomavirus (HPV) type 11 sequences that migrated with the high molecular weight cellular DNA, suggesting integration of viral DNA into the cellular genome. A segment of the HPV DNA was cloned from the lesion and shown to be similar to prototype HPV 11 DNA, except for some variability in the viral long control region. The proviral DNA contained part of the L1 region, all of the viral long control region, the entire E6 and E7 open-reading frames, and at least a portion of the E1 region; the E4 region appeared to be deleted. The integration sites of the HPV DNA could not be specifically identified. An analysis of the p53 tumor suppressor gene region of the tumor DNA showed no evidence of mutation. These results suggest that the HPV 11 DNA may have had a role in the origin of the cancer in this patient.

Blotting, Southern↗
PubMed1996

A family of sulfonylurea receptors determines the pharmacological properties of ATP-sensitive K+ channels.

We have cloned an isoform of the sulfonylurea receptor (SUR), designated SUR2. Coexpression of SUR2 and the inward rectifier K+ channel subunit Kir6.2 in COS1 cells reconstitutes the properties of K(ATP) channels described in cardiac and skeletal muscle. The SUR2/Kir6.2 channel is less sensitive than the SUR/Kir6.2 channel (the pancreatic beta cell KATP channel) to both ATP and the sulfonylurea glibenclamide and is activated by the cardiac K(ATP) channel openers, cromakalim and pinacidil, but not by diazoxide. In addition, SUR2 binds glibenclamide with lower affinity. The present study shows that the ATP sensitivity and pharmacological properties of K(ATP) channels are determined by a family of structurally related but functionally distinct sulfonylurea receptors.

ATP-Binding Cassette Transporters↗
PubMed1996

Speed of information processing as a mediator between age and free-recall performance.

A combined experimental and individual differences approach was used to investigate the mediating role of task-specific and task-independent speed of information processing measures in the relationship between age and free-recall performance. Thirty-six younger adults (mean age = 21 years) and 36 older adults (mean age = 73 years) participated. Participants were required to encode 3 lists of words for immediate recall, by rehearsing the words aloud, twice, and 3 times. Participants' speed of information processing was assessed by 3 measures: rehearsal time, articulation speed, and scores on the Digit Symbol Substitution Test (DSST; Wechsler, 1981). Working memory was also assessed by a backward word-span measure. As predicted, younger adults recalled more words after rehearsing words 3 times rather than once, whereas older adults' recall did not increase with increasing numbers of rehearsals. Younger adults were faster on all speed-of-processing measures and had higher backward word span than did older adults. Task-independent speed of processing, measured by DSST scores and articulation speed, mediated the relationship between age and free recall. Scores on the DSST appear to reflect a fundamental difference between younger and older adults that influences recall performance.

Adolescent↗
PubMed1996

The day-to-day variation (test-retest reliability) of residual urine measurement.

OBJECTIVE: To determine the variation in repeated measurements of post-void residual urine volume (PVR), determined by transabdominal ultrasonography (TAUS), within an individual over time (test-retest reliability). PATIENTS AND METHODS: Forty men with symptomatic benign prostatic hyperplasia and awaiting transurethral resection of the prostate were studied over 3 months. Each underwent TAUS to determine both pre- and post-micturition residual volumes on six occasions within the study period. RESULTS: Although one-third of the patients had approximately constant residual volumes (variation in range < 120 mL), two-thirds had wide intra-individual variations over time (variation in range 150-670 mL). The values were log transformed to give a normal distribution and subjected to analysis of variance; there was a wide variation between and also within individuals. The larger the mean PVR, the larger was the overall variation in time. For those with a mean PVR of < 100 mL, the variation was less marked and these patients showed a more consistent test-retest repeatability. CONCLUSIONS: Although the PVR determined by TAUS may be useful to indicate aspects of bladder dysfunction or outlet obstruction, the wide variation in repeated measurements in the same individual limits its use for any clinical purpose that requires repeated assessment, e.g. in monitoring the response to treatment. There is poor test-retest reliability and PVRs cannot be determined reliably from a single measurement.

Aged↗
PubMed1996

beta-Catenin associates with the actin-bundling protein fascin in a noncadherin complex.

Catenins were first characterized as linking the cytoplasmic domains of cadherin cell-cell adhesion molecules to the cortical actin cytoskeleton. In addition to their essential role in modulating cadherin adhesivity, catenins have more recently been indicated to participate in cell and developmental signaling pathways. beta-Catenin, for example, associates directly with at least two receptor tyrosine kinases and transduces developmental signals within the Wnt pathway. Catenins also complex with the tumor suppressor protein adenomatous polyposis coli (APC), which appears to have a role in regulating cell proliferation. We have used the yeast two-hybrid method to reveal that fascin, a bundler of actin filaments, binds to beta-catenin's central Armadillo repeat domain. Western blotting of immunoprecipitates from cell line and mouse and rat brain extracts indicate that this interaction exists in vivo. Fascin and beta-catenin's association was further substantiated in vitro using purified proteins isolated from recombinant bacterial and baculoviral sources. Immunoprecipitation analysis indicates that fascin additionally binds to plakoglobin, which is highly homologous to beta-catenin but not to p120cas, a newly described catenin which contains a more divergent Armadillo-repeat domain. Immunoprecipitation, in vitro competition, and domain-mapping experiments demonstrate that fascin and E-cadherin utilize a similar binding site within beta-catenin, such that they form mutually exclusive complexes with beta-catenin. Immunofluorescence microscopy reveals that fascin and beta-catenin colocalize at cell-cell borders and dynamic cell leading edges of epithelial and endothelial cells. In addition to cell-cell borders, cadherins were unexpectedly observed to colocalize with fascin and beta-catenin at cell leading edges. It is conceivable that beta-catenin participates in modulating cytoskeletal dynamics in association with the microfilament-bundling protein fascin, perhaps in a coordinate manner with its functions in cadherin and APC complexes.

Actins↗
PubMed1996

Mutations in the sulonylurea receptor gene are associated with familial hyperinsulinism in Ashkenazi Jews.

Familial hyperinsulinism (HI) is a disorder of pancreatic beta-cell function characterized by persistent hyperinsulinism despite severe hypoglycemia. To define the molecular genetic basis of HI in Ashkenazi Jews, 25 probands were screened for mutations in the sulfonylurea receptor (SUR1) gene by single-strand conformation polymorphism (SSCP) analysis of genomic DNA and subsequent nucleotide sequence analyses. Two common mutations were identified: (I) a novel in-frame deletion of three nucleotides (nt) in exon 34, resulting in deletion of the codon for F1388 (delta F1388) and (II) a previously described g-->a transition at position-9 of the 3' splice site of intron 32 (designated 3992-9g-->a). Together, these mutations are associated with 88% of the HI chromosomes of the patients studied. 86Rb+ efflux measurements of COSm6 cells co-expressing Kir6.2 and either wild-type or delta F1388 SUR1 revealed that the F1388 mutation abolished ATP-sensitive potassium channel (KATP) activity in intact cells. Extended haplotype analyses indicated that the delta F1388 mutation was associated with a single specific haplotype whereas the 3992-9g-->a mutation was primarily associated with a single haplotype but also occurred in the context of several other different haplotypes. These data suggest that HI in Ashkenazi Jews is predominantly associated with mutations in the SUR1 gene and provide evidence for the existence of at least two founder HI chromosomes in this population.

Animals↗
PubMed1996

Sequence variants in the sulfonylurea receptor (SUR) gene are associated with NIDDM in Caucasians.

NIDDM is a common heterogeneous disorder, the genetic basis of which has yet to be determined. The sulfonylurea receptor (SUR) gene, now known to encode an integral component of the pancreatic beta-cell ATP-sensitive potassium channel, IKATP, was investigated as a logical candidate for this disorder. The two nucleotide-binding fold (NBF) regions of SUR are known to be critical for normal glucose regulation of insulin secretion. Thus, single-strand conformational polymorphism analysis was used to find sequence changes in the two NBF regions of the SUR gene in 35 NIDDM patients. Eight variants were found; and three were evaluated in two Northern European white populations (Utah and the U.K.): 1) a missense mutation in exon 7 (S1370A) was found with equal frequency in patients (n = 223) and control subjects (n = 322); 2) an ACC-->ACT silent variant in exon 22 (T761T) was more common in patients than in control subjects (allele frequencies 0.07 vs. 0.02, P = 0.0008, odds ratio (OR) 3.01, 95% CI 1.54-5.87); and 3) an intronic t-->c change located at position -3 of the exon 24 splice acceptor site was also more common in patients than in control subjects (0.62 vs. 0.46, P < 0.0001, OR 1.91, 95% Cl 1.50-2.44). The combined genotypes of exon 22 C/T or T/T and intron 24 -3c/-3c occurred in 8.9% of patients and 0.5% of control subjects (P < 0.0001, OR 21.5, 95% CI 2.91-159.6). These results suggest that defects at the SUR locus may be a major contributor to the inherited basis of NIDDM in Northern European Caucasians.

ATP-Binding Cassette Transporters↗
PubMed1996

Longitudinal changes in peritoneal kinetics: the effects of peritoneal dialysis and peritonitis.

BACKGROUND: Peritoneal infection and poor ultrafiltration continue to be the major causes of treatment failure in CAPD. The combined effects of peritonitis and the continuous exposure to dialysis fluid remain the most likely candidates affecting the peritoneum in the long term. The purpose of this study was to observe the effects of peritonitis and dialysis on longitudinal peritoneal function. METHODS: The peritoneal equilibration test (PET) was utilized to quantify longitudinal changes in low-molecular-weight solute transfer (D/P(creat)) and ultrafiltration (UF) in 233 patients treated with CAPD. Of these, 166 represented an unselected cohort (Group 1) studied prospectively from commencing treatment for up to 54 months, and 67 were selected patients (Group 2) with PET data available at commencement of the study, having been on dialysis for a minimum of 18 months. PETs were performed either 6-monthly or following peritonitis episodes. RESULTS: Data on the short-term effect of peritonitis kinetics were pooled for groups 1 and 2. Single, isolated episodes (n = 86) had no significant effect on D/P(creat) or UF, whereas recurrences or clusters of infection (n = 70) caused increases in D/P(creat) and reductions in UF, the significance of which increased with the number of episodes. There were significant correlations between both changes in D/P(creat) and UF with the cumulative dialysate leukocyte count, regardless of infecting organism, suggesting that intensity of peritoneal inflammation is also important. Those organisms associated with greater change in peritoneal kinetics, e.g. S. aureus, Pseudomonas, also had the highest neutrophil counts. The longitudinal changes in peritoneal kinetics were analysed for patients in group 1 only. There was a highly significant increase in D/P(creat) after 6 months treatment; this increased further with time on treatment, reaching further significance at 42 and 48 months. There was an associated reduction in UF. In view of the short-term effects of peritonitis on kinetics group 1 was further subdivided into patients who were either peritonitis free or only experienced isolated infections, group 1a, and those that had multiple infection episodes, group 1b. Treatment drop-out, due to death or technical failure occurred at double the rate in group 1b, who also had significantly higher D/P(creat) and lower UF at 1, 6, 12, 18 and 24 months of treatment. Group 1a subsequently caught up, however, indicating that peritonitis is not the only factor influencing long-term changes in peritoneal kinetics. CONCLUSIONS: These data suggest that solute transfer increases and UF declines with time on peritoneal dialysis. This process is exacerbated and accelerated by peritonitis, and appears to be proportional to the degree of associated inflammation and number of infections in close proximity.

Adolescent↗
PubMed1996

Impact of peritoneal absorption of glucose on appetite, protein catabolism and survival in CAPD patients.

Dietary protein and calorie intake, protein catabolism and peritoneal kinetics were measured in 97 CAPD patients to establish the effect of peritoneal glucose absorption on appetite and survival. There was a large variability in the number of calories obtained from the dialysate, mean 5.89 cal/kg (median 5.43 cal/kg), with a skewed distribution, due to the increased requirement for hypertonic solutions by patients with more rapid glucose absorption and poor ultrafiltration. On average calories derived from peritoneal absorption accounted for 19% of the total energy intake which in itself was well below that recommended. Patients with > 6 cal/kg, obtained from the dialysate (top 20th percentile, n = 19) were compared with those with < 6 cal/kg, but no significant differences in oral protein or calorie intake, protein catabolism or total calorie intake were found. Age, body mass index (BMI) and KT/V were also similar in both groups. Patients were followed-up prospectively for a minimum of 24 months and a comparison made of actuarial survival. Patients with high peritoneal calorie intake tended to survive longer but this was not significantly different (p = 0.25). This study suggests that calories derived from the peritoneum in CAPD patients do not suppress appetite, provide a useful and significant proportion of the total energy intake, that does not cause excessive obesity or have a negative effect on patient survival.

Absorption↗
PubMed1996

The predictive value of KT/V and peritoneal solute transport in CAPD patients is dependent on the type of comorbidity present.

Comorbidity, age, dialysis dose (KT/V(urea)), plasma albumin, and peritoneal function (D/P(creat) were measured cross-sectionally in 228 continuous ambulatory peritoneal dialysis (CAPD) patients, who were then followed up for a mean of two years. Comorbidity, utilizing a semi-quantitative score described previously, was the most powerful predictor of mortality in both univariate and multivariate analysis. Using univariate analysis, all the variables predicted outcome with statistical significance, mortality being associated with lower KT/V and plasma albumin and a higher D/P(creat). On multivariate analysis only comorbidity, age, and KT/V remained independent predictors. Data was further analyzed on the basis of type of comorbid condition. In those patients without comorbid disease (n = 127) neither KT/V, albumin nor D/P(creat) predicted outcome. In patients with clinical evidence of ischemic heart disease the KT/V was a significant predictor of favorable outcome. In those with clinical evidence of left ventricular function, mortality was significantly and independently associated with low plasma albumin, high D/P(creat), and KT/V. It is suggested that the concept of treatment adequacy in CAPD patients must include both measures of dialysis dose and peritoneal function, particularly in the context of the patient's comorbidity.

Adolescent↗
PubMed1995

Reconstitution of IKATP: an inward rectifier subunit plus the sulfonylurea receptor.

A member of the inwardly rectifying potassium channel family was cloned here. The channel, called BIR (Kir6.2), was expressed in large amounts in rat pancreatic islets and glucose-responsive insulin-secreting cell lines. Coexpression with the sulfonylurea receptor SUR reconstituted an inwardly rectifying potassium conductance of 76 picosiemens that was sensitive to adenosine triphosphate (ATP) (IKATP) and was inhibited by sulfonylureas and activated by diazoxide. The data indicate that these pancreatic beta cell potassium channels are a complex composed of at least two subunits--BIR, a member of the inward rectifier potassium channel family, and SUR, a member of the ATP-binding cassette superfamily. Gene mapping data show that these two potassium channel subunit genes are clustered on human chromosome 11 at position 11p15.1.

ATP-Binding Cassette Transporters↗