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Biomedical subjects

J Bryan

Publications and source records attributed to J Bryan.

At least 55 records · Page 3Linked to original sources
PubMed2000

Queenslanders' use of personal strategies to minimise risk of mosquito-borne disease.

OBJECTIVE: To describe Queenslanders' awareness, knowledge and attitudes towards mosquito-borne diseases and their transmission, and to determine which factors influence the adoption of effective individual prevention strategies. METHODS: In 1995-6, cross-sectional surveys of adult residents in the western suburbs of Brisbane and registered voters in Cairns were conducted. Forced entry logistic regression was used to predict use of personal protection and elimination of domestic breeding sites in the two cities. RESULTS: Final sample sizes were 347 in Cairns and 165 in Brisbane with response rates of approximately 70%. RRVD awareness was nearly universal in both cities. A majority of residents (60% in Brisbane and 65% in Cairns) report they are careful to avoid being bitten by mosquitoes. 25% of Cairns residents and 18% of Brisbane residents report always using some method of personal protection. Cairns residents are also more likely to say that they actively prevent mosquitoes from breeding in their yards (76% in Brisbane and 87% in Cairns). Knowledge of mosquitoes and disease transmission was slightly higher in Cairns. In Brisbane, dislike of mosquitoes and being regularly bitten were significant in the multivariate model predicting personal protection, whereas concern for disease and being female were significant in Cairns. Concern about disease was a significant predictor of eliminating breeding sites in both cities. CONCLUSIONS: Raising concern about mosquito-borne disease can increase use of personal prevention strategies. However, providing information on prevention strategies may not be effective. The most effective strategies are not practiced or seen by the public to be related to minimising risk of disease. IMPLICATIONS: Greater emphasis in health promotion campaigns should be placed on encouraging permanent alterations to the domestic environment rather than temporary methods that are difficult to sustain and not effective against the common vectors for mosquito-borne diseases in Queensland. Educational messages should explicitly link preventive behaviours with the reduction in the likelihood of contracting a serious disease.

Adult↗
PubMed2000

Enterobacterial repetitive intergenic consensus polymerase chain reaction typing of isolates of Enterobacter cloacae from an outbreak of infection in a neonatal intensive care unit.

BACKGROUND: Enterobacter cloacae has become a common cause of nosocomial infections. This study was designed to investigate the pattern of spread of E cloacae during an outbreak in a neonatal intensive care unit. METHODS: Enterobacterial repetitive intergenic consensus polymerase chain reaction was used to examine 111 E cloacae isolates from 17 patients, including 81 from surveillance cultures, 23 from endotracheal tubes, 3 from eyes, and 1 each from blood, urine, skin, and throat. Antibiotic susceptibility profiles were also obtained. RESULTS: Infection with E cloacae resulted from endogenous bacteria and from horizontal transmission. One group of 61 isolates, a third of which were obtained from clinical specimens, was uniformly susceptible to imipenem and ciprofloxacin only. A second group of 50 isolates, only 18% of which were obtained from clinical specimens, was susceptible to all antibiotics tested except for aminopenicillins and first-generation cephalosporins. CONCLUSION: These data indicate that (1) patient-to-patient spread is an important cause of E cloacae infection in the neonatal intensive care unit and (2) highly antibiotic-resistant E cloacae may emerge during an outbreak.

Academic Medical Centers↗
PubMed2000

Interactive medical data on demand: a high-performance imaged-based approach across heterogeneous environments.

Medical data in image format continues to increase in both size and complexity. We have integrated advanced techniques in visualization, networked computing, and interface design to improve methods for accessing medical data comprising high-resolution images for reconstructions into three-dimensional volumetric representations. We present two approaches to handle the range of low to high-end client platforms, support visualization functionality, and provide the ability to manipulate very large data over heterogeneous computing and networking environments. We present examples of its use for clinical, research, and educational purposes and discuss future extensions.

Computer Communication Networks↗
PubMed2000

Virtual temporal bone dissection simulation.

We have developed a working prototype system for the virtual simulation of temporal bone dissection. The system offers a paradigm from traditional practices by integrating technological advances to provide a safer and more cost effective way to learn fundamental techniques used in temporal bone surgeries. We present our methods to provide a real-time interactive volumetric system that obviates the need for physical materials in initial training, and provides a more accessible way for residents to practice and to increase exposure to pathological variance. Finally, we discuss ways to extend this work to more advanced resident training, presurgical planning, and surgical documentation.

Aged↗
PubMed1999

Sulfonylurea receptors: ABC transporters that regulate ATP-sensitive K(+) channels.

The association of sulfonylurea receptors (SURs) with K(IR)6.x subunits to form ATP-sensitive K(+) channels presents perhaps the most unusual function known for members of the transport ATPase family. The integration of these two protein subunits extends well beyond conferring sensitivity to sulfonylureas. Recent studies indicate SUR-K(IR)6.x interactions are critical for all of the properties associated with native K(ATP) channels including quality control over surface expression, channel kinetics, inhibition and stimulation by Mg-nucleotides and response both to channel blockers like sulfonylureas and to potassium channel openers. K(ATP) channels are a unique example of the physiologic and medical importance of a transport ATPase and provide a paradigm for how other members of the family may interact with other ion channels.

ATP-Binding Cassette Transporters↗
PubMed1999

The tolbutamide site of SUR1 and a mechanism for its functional coupling to K(ATP) channel closure.

Micromolar concentrations of tolbutamide will inhibit (SUR1/K(IR)6. 2)(4) channels in pancreatic beta-cells, but not (SUR2A/K(IR)6.2)(4) channels in cardiomyocytes. Inhibition does not require Mg(2+) or nucleotides and is enhanced by intracellular nucleotides. Using chimeras between SUR1 and SUR2A, we show that transmembrane domains 12-17 (TMD12-17) are required for high-affinity tolbutamide inhibition of K(ATP) channels. Deletions demonstrate involvement of the cytoplasmic N-terminus of K(IR)6.2 in coupling sulfonylurea-binding with SUR1 to the stabilization of an interburst closed configuration of the channel. The increased efficacy of tolbutamide by nucleotides results from an impairment of their stimulatory action on SUR1 which unmasks their inhibitory effects. The mechanism of inhibition of beta-cell K(ATP) channels by sulfonylureas during treatment of non-insulin-dependent diabetes mellitus thus involves two components, drug-binding and conformational changes within SUR1 which are coupled to the pore subunit through its N-terminus and the disruption of nucleotide-dependent stimulatory effects of the regulatory subunit on the pore. These findings uncover a molecular basis for an inhibitory influence of SUR1, an ATP-binding cassette (ABC) protein, on K(IR)6.2, a ion channel subunit.

ATP-Binding Cassette Transporters↗
PubMed1999

The C terminus of SUR1 is required for trafficking of KATP channels.

In beta cells from the pancreas, ATP-sensitive potassium channels, or KATP channels, are composed of two subunits, SUR1 and KIR6.2, assembled in a (SUR1/KIR6.2)4 stoichiometry. The correct stoichiometry of channels at the cell surface is tightly regulated by the presence of novel endoplasmic reticulum (ER) retention signals in SUR1 and KIR6.2; incompletely assembled KATP channels fail to exit the ER/cis-Golgi compartments. In addition to these retrograde signals, we show that the C terminus of SUR1 has an anterograde signal, composed in part of a dileucine motif and downstream phenylalanine, which is required for KATP channels to exit the ER/cis-Golgi compartments and transit to the cell surface. Deletion of as few as seven amino acids, including the phenylalanine, from SUR1 markedly reduces surface expression of KATP channels. Mutations leading to truncation of the C terminus of SUR1 are one cause of a severe, recessive form of persistent hyperinsulinemic hypoglycemia of infancy. We propose that the complete loss of beta cell KATP channel activity seen in this form of hyperinsulinism is a failure of KATP channels to traffic to the plasma membrane.

ATP-Binding Cassette Transporters↗
PubMed1999

Two regions of sulfonylurea receptor specify the spontaneous bursting and ATP inhibition of KATP channel isoforms.

KATP channels are heteromultimers of KIR6.2 and a sulfonylurea receptor, SUR, an ATP binding cassette (ABC) protein with several isoforms. KIR6.2 forms a channel pore whose spontaneous activity and ATP sensitivity are modulated by the receptor via an unknown interaction(s). Side by side comparison of single-channel kinetics and steady-state ATP inhibition of human beta-cell, SUR1/KIR6.2, versus cardiac, SUR2A/KIR6.2 channels demonstrate that the latter have a greater mean burst duration and open probability in the absence of nucleotides and approximately 4-fold higher IC50(ATP). We have used matched chimeras of SUR1 and SUR2A to show that the kinetics, which determine the maximal open probability (Pomax), and the ATP sensitivity are functionally separable and to identify the two segments of SUR responsible for these isoform differences. A region within the first five transmembrane domains specifies the interburst kinetics, whereas a C-terminal segment determines the sensitivity to inhibitory ATP. The separable effects of SUR on ATP inhibition and channel kinetics implies that the cytoplasmic C terminus of SUR either directly modulates the affinity of a weak ATP binding site on the inward rectifier or affects linkage between the binding site and the gate. This is the first identification of parts of an ABC protein that interact with an ion channel subunit to modulate the spontaneous activity and ATP sensitivity of the heteromeric channel.

ATP-Binding Cassette Transporters↗
PubMed1999

Sulfonylurea receptors set the maximal open probability, ATP sensitivity and plasma membrane density of KATP channels.

KATP channels are heteromultimers of SUR and KIR6.2. C-terminal truncation of KIR6.2 allows surface expression of the pore. KIR6.2deltaC35 channels display approximately 7-fold lower maximal open probability, approximately 35-fold reduced ATP sensitivity, reduced mean open time, a markedly increased transition rate from a burst into a long-lived closed state, and have no counterpart in vivo. SUR1 and SUR2A restore wild-type bursting, ATP sensitivity and increase channel density in the plasma membrane. The high IC50(ATP) of approximately 4 mM for KIR6.2deltaCK185Q channels results from the additive effects of SUR removal and KIR6.2 modification. The results demonstrate allosteric interaction(s) are essential for normal intrinsic activity, ATP inhibition, and trafficking of KATP channels.

ATP-Binding Cassette Transporters↗
PubMed1999

The N-terminus of KIR6.2 limits spontaneous bursting and modulates the ATP-inhibition of KATP channels.

KATP channels are heteromultimers of a sulfonylurea receptor SUR and KIR6.2 with the inward rectifier forming the pore which is regulated by SUR. We have examined the contributions of the cytoplasmic domains of KIR6.2 to control of spontaneous bursting and ATP-inhibition in human SUR1/KIR6.2 KATP channels. Truncations of the N-terminus of KIR6.2 nearly eliminate transitions to interburst closed states without affecting the open or intraburst closed states, thus producing SUR1/DeltaNKIR6.2 channels with an extremely high open probability in the absence of nucleotides. These channels have a decrease apparent ATP-sensitivity which is consistent with the involvement of the N-terminus in a transition to an interburst closed state that preferentially binds inhibitory ATP. Mutations in both the N- and proximal C-termini of KIR6.2 can synergistically attenuate the ATP-inhibition. The results identify the N-terminus of KIR6.2 as a determinant of the interburst kinetics of KATP channels and suggest that the two cytoplasmic domains of KIR6.2 participate in ATP-inhibitory gating through distinct mechanisms.

ATP-Binding Cassette Transporters↗
PubMed1999

Carbohydrate-deficient glycoprotein syndrome in a newborn with an unbalanced chromosomal translocation.

UNLABELLED: Carbohydrate-deficient glycoprotein syndromes may occur as a primary result of distinct genetic disruption of the enzymes involved in processing the carbohydrate moeities of glycoproteins. They may also occur due to a number of secondary defects in glycosylation. CONCLUSION: A female infant with an unbalanced chromosomal translocation [46,XX,der(21)t(17;21) (p13.1;q22.11)mat.ish der(21)t(17;21) (D17S375 x 3, D21S65-)] and with biochemical and clinical features of a carbohydrate deficient glycoprotein syndrome is reported. This chromosomal disruption is another secondary cause of the disorder.

Congenital Disorders of Glycosylation↗