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Biomedical subjects

W J Brown

Publications and source records attributed to W J Brown.

At least 19 recordsLinked to original sources
PubMed1998

Evidence that phospholipase A2 activity is required for Golgi complex and trans Golgi network membrane tubulation.

Membrane tubules of uniform diameter (60-80 nm) and various lengths (up to several micrometers) emanate from elements of the Golgi stack and trans Golgi network (TGN). These organelle membrane tubules are thought to be involved in membrane trafficking and maintenance of Golgi/TGN architecture. The number of these tubules, and their frequency of formation, can be greatly enhanced by the fungal metabolite brefeldin A (BFA), an inhibitor of Golgi/TGN-associated coated vesicle formation. We show here that BFA stimulation of Golgi and TGN membrane tubulation, and the resultant retrograde transport of resident Golgi enzymes to the endoplasmic reticulum, was potently inhibited by a number of membrane-permeant antagonists of phospholipase A2 (PLA2; EC 3.1.1.4) activity. In addition, PLA2 inhibitors on their own caused a reversible fragmentation of the Golgi complex into juxtanuclear, stacked cisternal elements. We conclude from these observations that tubulation of Golgi complex and TGN membranes requires a PLA2 activity, and that this activity may participate not only in Golgi tubule-mediated retrograde trafficking to the endoplasmic reticulum, but also in the maintenance of Golgi complex architecture.

Animals↗
PubMed1998

What is a healthy weight for middle aged women?

OBJECTIVE: To explore associations between body mass index (BMI) and selected indicators of health and well-being and to suggest a healthy weight range (based on BMI) for middle aged Australian women. DESIGN: Population based longitudinal study (cross-sectional baseline data). SUBJECTS: 13431 women aged 45-49 y who participated in the baseline survey for the Australian Longitudinal Study on Women's Health. RESULTS: Forty-eight percent of women had a BMI>25 kg/m2. Prevalence of medical problems (for example, hypertension, diabetes), surgical procedures (cholescystectomy, hysterectomy) and symptoms (for example, back pain) increased monotonically with BMI, while indicators of health care use (for example, visits to doctors) showed a 'J' shaped relationship with BMI. Scores for several sub-scales of the MOS short form health survey (SF36) (for example, general health, role limitations due to emotional difficulties, social function, mental health and vitality) were optimal when BMI was around 19-24 kg/m2. After adjustment for area of residence, education, smoking, exercise and menopausal status, low BMI was associated with fewer physical health problems than mid-level or higher BMI, and the nationally recommended BMI range of 20-25 was associated with optimum mental health, lower prevalence of tiredness and lowest use of health services. CONCLUSIONS: Acknowledging the limitations of the cross-sectional nature of these data, the results firmly support the benefits of leanness in terms of reducing the risk of cardiovascular disease, diabetes and gall bladder disease. The findings are moderated, however, by the observation that both low and high BMI are associated with decreased vitality and poorer mental health. The optimal range for BMI appears to be about 19-24 kg/m2. From a public health perspective this study provides strong support for the recommended BMI range of 20-25 as an appropriate target for the promotion of healthy weight in middle aged Australian women.

Australia↗
PubMed1998

Retrograde trafficking of both Golgi complex and TGN markers to the ER induced by nordihydroguaiaretic acid and cyclofenil diphenol.

Previous studies have shown that the Golgi stack and the trans-Golgi network (TGN) may play a role in capturing escaped resident endoplasmic reticulum (ER) proteins, and directing their retrograde transport back to that organelle. Whether this retrograde movement represents a highly specific or more generalized membrane trafficking pathway is unclear. To better understand both the retrograde and anterograde trafficking pathways of the secretory apparatus, we examined more closely the in vivo effects of two structurally unrelated compounds, the potent lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA), and the non-steroidal estrogen cyclofenil diphenol (CFD), both of which are known to inhibit secretion. In the presence of these compounds, transport of vesicular stomatitis virus G membrane glycoprotein from the ER to the Golgi complex, and from the TGN to the cell surface, was inhibited potently and rapidly. Surprisingly, we found that NDGA and CFD stimulated the rapid, but not concomitant, retrograde movement of both Golgi stack and TGN membrane proteins back to the ER until both organelles were morphologically absent from cells. Both NDGA- and CFD-stimulated TGN and Golgi retrograde membrane trafficking were inhibited by microtubule depolymerizing agents and energy poisons. Removal of NDGA and CFD resulted in the complete, but not concomitant, reformation of both Golgi stacks and their closely associated TGN compartments. These studies suggest that NDGA and CFD unmask a generalized bulk recycling pathway to the ER for both Golgi and TGN membranes and, further, that NDGA and CFD are useful for investigating the molecular mechanisms that control the formation and maintenance of both the Golgi stack proper and the TGN.

Adaptor Proteins, Vesicular Transport↗
PubMed1997

Secretory immunoglobulin A blocks hypoxia-augmented bacterial passage across Madin-Darby canine kidney cell monolayers.

OBJECTIVE: To study the relative impact of previous hypoxic exposure and the addition of secretory immunoglobulin A (IgA) on bacterial translocation. DESIGN: In vitro randomized experimental study. MATERIALS AND METHODS: Transfected Madin-Darby canine kidney epithelial cells were grown as monolayers in a two-chamber tissue culture system. Stationary growth phase Escherichia coli M14 were inoculated in the apical chamber with medium or medium containing polymeric secretory IgA. Tissue culture dishes were then placed in a 21 or 5% O2 incubator environment for 90 minutes followed by a 21% O2 environment. Medium from the basal compartment was then obtained at timed intervals for bacterial culture. MEASUREMENT AND MAIN RESULTS: Bacterial translocation increased with time in co-culture. Previous hypoxic exposure augmented translocation across the monolayers. The addition of IgA blocked translocation under both normoxic and hypoxic conditions. CONCLUSION: Secretory IgA is important in mucosal defense under both normal and shock conditions.

Animals↗
PubMed1997

Splanchnic ischemia and bacterial translocation in the abdominal compartment syndrome.

BACKGROUND AND METHODS: Major trauma or abdominal injury may lead to the development of increased intra-abdominal pressure (IAP) and the onset of the abdominal compartment syndrome. Although the effect of raised IAP on systemic and splanchnic hemodynamics have been described, the consequences of the resultant gut hypoperfusion in this setting are unknown. Bacterial translocation (BT) occurs after a period of splanchnic ischemia and may contribute to later organ failure. A rodent model was used to examine the effect of raised IAP on ileal mucosal blood flow (MBF) and BT. IAP was increased to 25 mm Hg for 60 minutes and mean arterial blood pressure was maintained with fluid. Animals were killed 24 hours later and examined for BT. RESULTS: Increased IAP resulted in a decrease of MBF to 63% of baseline despite maintaining normal mean arterial blood pressure. BT occurred principally to the mesenteric lymph nodes after 60 minutes of IAP at 25 mm Hg. CONCLUSIONS: Increased IAP leads to decreased MBF and to BT, which may contribute to later septic complications and organ failure.

Abdomen↗
PubMed1997

The health of Filipinas in the Hunter region.

An interview survey found life-style behaviours (including risk factors and screening), social support and psychological health (GHQ-12) among a sample of 198 Filipina-Australians to be conducive to good health. Knowledge of local health services was good, and most women expressed general satisfaction with all aspects of life in Australia, except in the area of employment prospects. Despite these indications of good health in the group, there remains a need for health service providers to be aware of the difficulties faced by a proportion of Filipina migrants to Australia.

Adult↗
PubMed1996

Gallbladder and biliary tract candidiasis.

BACKGROUND: The clinical significance of Candida spp isolated from the gallbladder on the biliary tract is relatively unknown. METHODS: To provide this information, patients with Candida spp isolated from gallbladder and other biliary tract sources during a 10-year period were identified through the records of our clinical microbiology laboratory. Medical records were analyzed for biliary disease causes, culture data, treatment, and outcome. RESULTS: Twenty-seven patients were identified. Five of seven patients with cholecystitis were critically ill intensive care unit (ICU) patients in whom the mortality rate was 100%. Gallstone pancreatitis was found in four patients and was fatal in one patient with a pancreatic abscess and ongoing retroperitoneal sepsis. An external biliary shunt/endoprosthesis was placed in 16 patients to relieve biliary obstruction. Cholangitis was present in 14 patients, and most bile cultures contained Candida as part of a mixed flora. Only 3 of 27 patients had candidemia, and 22 of 27 patients were colonized with Candida at other sites. CONCLUSIONS: (1) The ICU patient with Candida cholecystitis has a grave prognosis. (2) Patients with Candida isolated from biliary stents placed for obstruction and cholangitis should be treated with both antifungal and broad spectrum antimicrobial agents. (3) Candidemia is not frequently seen in this setting.

Adult↗
PubMed1996

Women's health: consumer views for planning local health promotion and health care priorities.

A random door knock survey was conducted in five metropolitan postcode areas with a high proportion of low-income households to establish: 1. the health problems experienced by women, 2. the problems with which women would have liked more help, and 3. women's perceptions of how their health care experiences might have been improved. In all, 214 women were interviewed. Across all age groups the most common problems were tiredness, premenstrual syndrome, stress, being overweight and disturbed sleep. Premenstrual syndrome, tiredness and arthritis were the most commonly experienced problems among younger, middle-aged and older women respectively. In general, women were satisfied with the help available to them for their health problems, but one in five would have liked more help to cope with stress, and one in six said they would like help to address the issue of quality of medical care. In relation to health care services, suggestions for improvement included the provision of better health information from doctors and other health care professionals, and more opportunities for counselling and self-help. The project findings will be used to influence the development of local policies and services, and will form the focus for local women's health promotion programs.

Adult↗
PubMed1996

A collaborative approach to cervical cancer screening.

OBJECTIVE: The main objective of this project was to evaluate a collaborative nurse and general practitioner approach to improve screening for cervical cancer. DESIGN: Multiple group time series design. SETTING: Six postal areas in the Hunter Valley of New South Wales, Australia, chosen as intervention sites because of very low Pap test rates compared with the rest of NSW (fewer than 50% of women screened). Six regions of similar size and with similar baseline screening levels were selected as comparison sites. SUBJECTS: All women selected in the resident postal areas. INTERVENTIONS: Women's health nurses worked in collaboration with general practitioners within the communities selected from within the Hunter area to promote and provide screening for cervical cancer. MAIN OUTCOME MEASURES: Qualitative information on initial expectations and impressions of the collaborative processes were collected at the start of the project period. Process data on client characteristics and Pap test results were obtained from minimum data collections; client satisfaction was assessed from client surveys. Outcome data on the increase in the number of women in each community who were screened for cervical cancer were obtained from Health Insurance Commission claims for screening Pap tests (and from nurses' records where Pap tests were examined under block funding arrangements). RESULTS: This project showed that nurses and general practitioners can collaborate to provide appropriate and highly acceptable cervical cancer screening services for women. Many of the women screened by the nurses were in the high risk age range for cervical cancer (40 years and older) and had only basic education levels, thus representing women who are most likely to have poor screening rates. Further, 33.1% of the women screened had not had a Pap test in the past four years or had never been screened. The number of women having a Pap test during the first six months of the project, compared with the number expected from preintervention patterns, was significantly greater in four intervention areas (P < 0.01). No corresponding increase was seen in comparison areas with similar screening rates at baseline. CONCLUSIONS: There is great potential for nurses to work in collaboration with general practitioners to improve the availability and coverage of community cervical cancer screening programmes.

Australia↗
PubMed1995

Characterization of a cytosolic activity that induces the formation of Golgi membrane tubules in a cell-free reconstitution system.

Using a cell-free reconstitution system, we have characterized a cytosol- and ATP-dependent process that leads to the formation of membrane tubules from isolated Golgi complexes. These membrane tubules are uniform in diameter (50-70 nm) and morphologically identical to ones normally seen in cells and to those which are enhanced following brefeldin A treatment. Tubulation was strictly dependent on an activity present in an organelle-free extract of bovine brain cytosol and hydrolyzable ATP. Tubule formation was saturable with respect to both cytosol and ATP with half-maximal induction occurring at approximately 0.5 mg/mL cytosol and 10-20 microM ATP. Mild proteolytic treatment of Golgi membranes significantly reduced the extent of tubulation to subsequently added cytosol, suggesting that the tubulation activity interacts with Golgi-associated membrane proteins. The cytosolic tubulation activity was heat-labile, nondialyzable, and precipitated in ammonium sulfate. This activity could be followed through various chromatographic steps to yield fractions enriched in a major 40 kDa protein and several other minor proteins of approximately 80, 60, and 30 kDa. Monospecific antibodies against the 40K protein inhibited the cytosol-dependent tubulation of Golgi membranes in the cell-free system. Gel filtration chromatography suggests that the tubulation activity has a native molecular weight of approximately 125,000-140,000. These results establish the existence of cytosolic protein factors that regulate the formation of Golgi membrane tubules, and will provide the means for a biochemical dissection of membrane tubulation.

Adenosine Triphosphate↗
PubMed1995

Role for phosphatidylinositol 3-kinase in the sorting and transport of newly synthesized lysosomal enzymes in mammalian cells.

Previous work with the yeast Saccharomyces cerevisiae has demonstrated a role for a phosphatidylinositol-specific PI 3-kinase, the product of the VPS34 gene, in the targeting of newly synthesized proteins to the vacuole, an organelle functionally equivalent to mammalian lysosomes (Schu, P. V., K. Takegawa, M. J. Fry, J. H. Stack, M. D. Waterfield, and S. D. Emr. 1993. Science [Wash. DC]. 260:88-91). The activity of Vps34p kinase is significantly reduced by the PI 3-kinase inhibitors wortmannin, a fungal metabolite, and LY294002, a quercetin analog (Stack, J. H., and S. D. Emr. 1994. J. Biol. Chem. 269:31552-31562). We show here that at concentrations which inhibit VPS34-encoded PI 3-kinase activity, wortmannin also inhibits the processing and delivery of newly synthesized cathepsin D to lysosomes in mammalian cells with half-maximal inhibition of delivery occurring at 100 nM wortmannin. As a result of wortmannin action, newly synthesized, unprocessed cathepsin D is secreted into the media. Moreover, after accumulation in the trans-Golgi network (TGN) at 20 degrees C, cathepsin D was rapidly missorted to the secretory pathway after addition of wortmannin and shifting to 37 degrees C. At concentrations that inhibited lysosomal enzyme delivery, both wortmannin and LY294002 caused a highly specific dilation of mannose 6-phosphate receptor (M6PR)-enriched vesicles of the prelysosome compartment (PLC), which swelled to approximately 1 micron within 15 min after treatment. With increasing time, the inhibitors caused a significant yet reversible change in M6PR distribution. By 3 h of treatment, the swollen PLC vacuoles were essentially depleted of receptors and, in addition, there was a fourfold loss of receptors from the cell surface. However, M6PRs were still abundant in the TGN. These results are most consistent with the interpretation that PI 3-kinase regulates the trafficking of lysosomal enzymes by interfering with a M6PR-dependent sorting event in the TGN. Moreover, they provide evidence that trafficking of soluble hydrolases to mammalian lysosomes and yeast vacuoles rely on similar regulatory mechanisms.

Acridine Orange↗
PubMed1995

A role for calmodulin in organelle membrane tubulation.

Membrane tubules of uniform diameter (60-80 nm) and variable lengths have been seen to extend from the main bodies of the Golgi complex, trans Golgi network (TGN), and endosomes. In the case of endosomes, these tubules appear to mediate membrane and receptor recycling events. Brefeldin A (BFA) is a potent drug that completely blocks coated vesicle formation from the Golgi complex and TGN, but at the same time causes the enhanced formation of membrane tubules from these same organelles. Recently, experiments have shown that calmodulin antagonists inhibit the transport of receptors out of endosomes, perhaps by inhibiting the formation of recycling tubules. Using the potent calmodulin-specific antagonists N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide (W-13), and N-(4-aminobutyl)-5-chloro-1-naphthalenesulfonamide (C-1), we found that the recycling of transferrin from endosomes to the cell surface was significantly inhibited, resulting in the formation of enlarged endosomal vacuoles. In addition, these same calmodulin antagonists also potently inhibited the formation of BFA-stimulated membrane tubules from the Golgi complex, TGN, and endosomes. In the case of the Golgi complex, failure to form tubules resulted in the inhibition of BFA-stimulated retrograde transport to the endoplasmic reticulum. These results suggest that calmodulin is a general regulator of membrane tubulation and is capable of influencing the morphology of several organelles.

Animals↗
PubMed1995

Inpatient cervical screening: a survey of patient acceptability.

Offering Pap tests to hospital inpatients could increase cervical screening rates. A survey to examine the acceptability of this concept was conducted with female inpatients in a rural public hospital. A large majority reported that they would find hospital Pap tests acceptable. Acceptability was not related to Pap test status, attitudes, or knowledge of cervical cancer. This strategy may provide access to cervical screening for underscreened groups.

Adolescent↗
PubMed1995

Setting targets: a three-stage model for determining priorities for health promotion.

This paper describes a three-stage model for setting targets for health promotion. The model was developed in 1992 in response to the need to identify priority areas for health promotion for women in the Hunter Region of New South Wales. The approach enabled epidemiological data and views from the community to be synthesised and integrated with those of experts from health and social services (key informants), using a nominal group process. The reliability of the method was investigated by replicating the process with two groups of key informants. There was considerable commonality in the targets generated by the two groups. The process resulted in the identification of seven targets that reflected the concerns of the community and local experts as well as the health priorities suggested by local epidemiological data. The model used could be adapted for determining priorities in a wide range of health and health care settings, where available resources restrict the range of services or activities which can be offered.

Consumer Organizations↗
PubMed1995

A comparison of bronchoscopic vs blind protected specimen brush sampling in patients with suspected ventilator-associated pneumonia.

BACKGROUND: Pneumonia is a common complication in patients undergoing mechanical ventilation and increases ICU mortality. The clinical diagnosis of ventilator-associated, however, pneumonia is unreliable, and many consider bronchoscopic-directed protected specimen brush sampling and quantitative culture the diagnostic method of choice. Bronchoscopy, however, is expensive and not readily available in many ICUs. OBJECTIVE: To test the hypothesis that "blind" protected specimen brush (PSB) sampling may produce results similar to that of bronchoscopic-directed sampling. SETTING: The medical ICU of a university-affiliated teaching hospital. INTERVENTION: Patients with suspected ventilator-associated pneumonia (VAP) who had not received antibiotics for at least 48 h underwent "blind" and bronchoscopic-directed PSB sampling with quantitative culture. RESULTS: Fifty-five paired PSB specimens were obtained from 53 patients. There was an 85% quantitative agreement between the blind and bronchoscopic-directed specimens. The agreement was independent of the bronchopulmonary segment from which the bronchoscopic sampling was directed. CONCLUSION: The results of this study are consistent with the notion that blind PSB sampling and quantitative culture may prove to be a useful, cost-effective, and minimally invasive method of diagnosing VAP.

Adult↗