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Biomedical subjects

P Williams

Publications and source records attributed to P Williams.

At least 289 records · Page 16Linked to original sources

Physiological factors associated with falls in older community-dwelling women.

OBJECTIVE: To determine the prevalence of impaired vision, peripheral sensation, lower limb muscle strength, reaction time, and balance in a large community-dwelling population of women aged 65 years and over, and to determine whether impaired performances in these tests are associated with falls. DESIGN: One-year prospective study. SETTING: Conducted as part of the Randwick Falls and Fractures Study, in Sydney, Australia. PARTICIPANTS: Four hundred fourteen women aged 65 to 99 years (mean age 73.7 years, SD = 6.3) were randomly selected from the community; 341 of these women were included in the 1-year prospective study. MAIN RESULTS: The prevalence of impairment in all tests increased with age. In the year following assessment, 207 subjects (60.7%) experienced no falls, 63 subjects (18.5%) fell one time only, and 71 subjects (20.8%) fell on two or more occasions. After controlling for age, multiple falling was associated with low contrast visual acuity and contrast sensitivity, poor vibration sense and proprioception, reduced lower limb strength, slow reaction time, and impaired balance, as indicated by four sway tests and two clinical stability measures. Discriminant function analysis identified visual contrast sensitivity, proprioception in the lower limbs, quadriceps strength, reaction time, and sway on a compliant (foam rubber) surface with the eyes open as the variables that significantly discriminated between subjects who experienced multiple falls and subjects who experienced no falls or one fall only (Wilks' lambda = 0.73 (P < 0.001), canonical correlation = 0.52). This procedure correctly classified 75% of subjects into multiple faller or nonmultiple faller groups. CONCLUSIONS: These findings support previous results conducted in retirement village and institutional setting and indicate that the test procedure aids in the identification of older community-dwelling women at risk of falls.

Accidental Falls↗

Identification and characterization of an iron-regulated hemopexin receptor in Haemophilus influenzae type b.

Heme can serve Haemophilus influenzae as a source of both essential porphyrin and iron. In extracellular mammalian body fluids neither free heme nor free iron is available, since they are tightly bound to hemopexin and transferrin, respectively. Since H. influenzae grows in the presence of iron-transferrin and heme-hemopexin and is known to express a saturable receptor for transferrin, we investigated the process by which this pathogen acquired heme from hemopexin for use as an iron source. The ability of human and rabbit hemopexin to donate heme as a source of iron to H. influenzae type b strains was demonstrated by plate bioassays. With a dot enzyme assay with biotinylated hemopexin as ligand, H. influenzae bound heme-hemopexin and apo-hemopexin following growth in iron-restricted, but not in iron-sufficient, medium. Competitive binding studies with heme-hemopexin and apo-hemopexin demonstrated saturability of binding. Neither heme, protoporphyrin IX, hemoglobin, nor transferrin blocked the binding of hemopexin to whole cells, demonstrating the specificity of binding. Treatment of whole H. influenzae cells with trypsin abolished binding. Taken together, these observations suggest that H. influenzae type b expresses an outer membrane protein(s) which acts as a receptor for hemopexin and which is regulated by the availability of iron in the growth medium. In iron-restricted media, H. influenzae 706705 and DL42 did not express the 100-kDa hemopexin-binding protein previously reported (M.S. Hanson, S.E. Pelzel, J. Latimer, U. Muller-Eberhard, and E.J. Hansen, Proc. Natl. Acad. Sci. USA 89:1973-1977, 1992). The putative iron-regulated hemopexin receptor was solubilized from cell envelopes of H. influenzae 706705, DL42, and Eagan with the detergent CHAPS (3-[(3-cholamidopropyl)-dimethyl-ammonio]-1-propanesulfonate) and isolated by affinity chromatography on heme-hemopexin-Sepharose 4B. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the proteins bound to the affinity resin revealed three proteins of 29, 38, and 57 kDa, of which the 57- and 29-kDa proteins bound hemopexin after Western blotting (immunoblotting). A monoclonal antibody to the 57-kDa hemopexin-binding protein of 706705 recognized a 57-kDa protein on Western blots of the cell envelope proteins of 706705, DL42, and Eagan; no reaction was observed with the 100-kDa hemopexin-binding protein of DL42. These data suggest that some H. influenzae strains possess at least two hemopexin receptors, the expression of which is determined by the prevailing growth environment.

Aerobiosis↗

Staphylococci express a receptor for human transferrin: identification of a 42-kilodalton cell wall transferrin-binding protein.

Staphylococcus aureus and the coagulase-negative staphylococci are commonly responsible for peritonitis in renal patients undergoing continuous ambulatory peritoneal dialysis. To simulate growth conditions in vivo, staphylococci isolated from peritoneal infections were cultured in used human peritoneal dialysate (HPD). Immunoblotting experiments using cell wall preparations from these staphylococci revealed the presence of the host iron-binding glycoprotein transferrin bound to S. aureus, S. epidermidis, S. capitis, S. haemolyticus, and S. hominis but not to S. warneri or S. saprophyticus. Similar results were obtained by incubating broth-grown staphylococci with human transferrin, although, in contrast to S. aureus, the coagulase-negative staphylococci bound more transferrin after growth in iron-restricted broth. To determine whether the staphylococci express a saturable specific receptor for human transferrin, the interaction of human 125I-transferrin with the staphylococci was examined. Both S. aureus and S. epidermidis bound the radiolabelled iron-saturated ligand in a time- and concentration-dependent manner. From competition binding assays, the affinity (Kd) and number of receptors were estimated for S. epidermidis (Kd, 0.27 microM; 4,200 receptors per cell) and S. aureus (Kd, 0.28 microM; 4,200 receptors per cell). S. epidermidis but not S. aureus receptor activity was partially iron regulated. Human apotransferrin and iron-saturated transferrin and rabbit and rat transferrins competed equally well for the staphylococcal receptor. Bovine and porcine transferrins and ovotransferrin as well as human and bovine lactoferrins were much less effective at competing with human transferrin. Treatment of whole staphylococci with protease abolished transferrin binding, indicating the involvement of cell surface protein. Western blots (immunoblots) of cell wall preparations probed with human transferrin revealed the presence of a 42-kDa transferrin-binding protein common to both S. aureus and S. epidermidis. On Western strip blots, the binding of human transferrin to this protein was blocked by labelled human transferrin but not by albumin, immunoglobulin G, or bovine transferrin or ovotransferrin. To assess the conservation of the 42-kDa transferrin-binding protein, cell wall proteins of S. epidermidis, S. haemolyticus, S. capitis, S. hominis, S. warneri, and S. saprophyticus were Western blotted and probed with human transferrin. Only S. warneri and S. saprophyticus lacked the 42-kDa wall protein, consistent with their inability to bind transferrin. These data show that the staphylococci express a specific receptor for human transferrin based at least in part on a common 42-kDa cell wall protein.

Animals↗

Comparison of acetylcholine-dependent relaxation in large and small arteries of rat mesenteric vascular bed.

The relative contributions of nitric oxide (NO) to in vitro relaxation responses elicited by acetylcholine (ACh) were compared in vessels of different sizes from the rat mesenteric vascular bed. ACh elicited an endothelium-dependent relaxation in phenylephrine-contracted superior mesenteric arteries (SMA, unstretched luminal diam 650 microns), which was blocked by compounds that inhibited NO, such as hemoglobin (10 microM), methylene blue (10 microM), and NG-monomethyl-L-arginine (1 mM). In contrast, the endothelium-dependent relaxation induced by ACh in phenylephrine-contracted mesenteric resistance arteries (MRA, unstretched luminal diam 200 microns) was not blocked by hemoglobin, methylene blue, or NG-monomethyl-L-arginine. KCl (25 mM) partially inhibited the ACh-dependent relaxation in MRA. Furthermore, the ACh-dependent relaxation in MRA was selectively inhibited by the Ca(2+)-activated K+ channel blocker charybdotoxin (0.1 microM). In contrast, the ATP-sensitive K+ channel blocker glibenclamide (50 microM) did not block the ACh-dependent relaxation in MRA. We conclude that 1) NO is a major component of the ACh-dependent relaxation in SMA and 2) the ACh-dependent relaxation of MRA is resistant to NO inhibitors but sensitive to a Ca(2+)-activated K+ channel blocker. This suggests that an endothelium-derived hyperpolarization factor may be involved in the relaxation of MRA.

Acetylcholine↗

Effect of acute ethanol intoxication on glucoregulation during prolonged insulin-induced hypoglycemia.

This study examined the interaction of acute ethanol administration on glucose homeostasis during insulin-induced hypoglycemia (IIH). Glucose kinetics and net hepatic balances of alanine, glycerol, and lactate were estimated in three groups of dogs: group I underwent 3 h of IIH; group II received a continuous ethanol infusion in addition to IIH; group III received ethanol for 3 h. In group I, IIH resulted in a sustained twofold increase in glucose rate of appearance (Ra) and net hepatic uptake (NHU) of glycerol and lactate but no change in NHU of alanine. In group II, glucose Ra rose transiently, NHU of alanine and glycerol increased two- and fivefold, respectively, whereas NHU of lactate dropped 60%. In group III, no alterations in plasma glucose levels, glucose Ra, and NHU of alanine and glycerol were observed, but NHU of lactate switched to a net output. These results demonstrate that ethanol alone or with IIH exclusively inhibited NHU of lactate, and this was responsible, in a stoichiometric fashion, for the failure of the delayed increase in glucose Ra during IIH.

Alanine↗

Food service trends in NSW hospitals, 1986-1993.

In 1993 a survey of the food service departments in 159 hospitals in New South Wales was carried out using a mailed questionnaire, and the results were compared with those of a similar survey in 1986. The results reveal that over the past seven years there has been a significant increase in the proportion of hospitals using cook-chill systems, from 5 per cent in 1986 to 18 per cent in 1993. Hospitals with cook-chill systems do not appear to be operating more efficiently than those with conventional catering systems: in cook-chill hospitals the mean food service staffing ratio was 7.1 beds/full-time equivalent (FTE) compared to 7.8 beds/FTE in hospitals with cook-serve systems. Most hospitals in New South Wales still use traditional hot food delivery to the wards, and more of these are now using effective heat maintenance systems for patient meals. The proportion of special diet meals has increased over the past seven years to 17.1 per cent in public hospitals. The percentage of food service departments with an unqualified person in charge fell from 47 per cent in 1986 to 22 per cent in 1993. Meal times remain largely unchanged, with more than 90 per cent of hospitals still serving the evening meal before 5.30pm.

Food Handling↗

Transnational criminal organizations and drug trafficking.

Transnational criminal organizations, particularly drug-trafficking organizations, operate unrestricted across international borders. They are very similar in kind to legitimate transnational corporations in structure, strength, size, geographical range and scope of their operations. Above all other features they engage in unregulated forms of capitalist enterprise. To fully understand transnational criminal organizations it is necessary to examine them as organizations responding to economic opportunities and focus on the factors that influence their emergence. Those factors can be understood as a result of the confluence of opportunities, pressures, incentives and resources at the global and national level. The present article identifies the key environmental factors relevant to the emergence of transnational criminal organizations, and explores the intrinsic relationship between those organizations, their home States and host States. It is those conditions which not only give rise to transnational criminal organizations, but also help to sustain them.

Crime↗

Assessment of the possible role of iron and copper in cisplatin-induced nephrotoxicity in the rat.

Nephrotoxic lesions induced by cisplatin in rats are characterized by acute tubular necrosis in the outer stripe of the medulla. The purpose of this study was to examine the potential role of changes in metal binding proteins, and iron and copper content in urine and renal tissue in cisplatin-induced nephrotoxicity. Cisplatin was administered intravenously to groups of 20 rats at single doses of 0, 1, 2.5, and 5 mg/kg and rats were sacrificed at 1, 2, 3 and 6 days after treatment. Increased serum BUN and creatinine were observed at a dose of 5 mg/kg cisplatin on day 2 through day 6. Increased urinary copper excretion coincided with necrosis and increased BUN and creatinine on day 3 in the high-dose group. Evidence of renal injury was apparent histologically as karyomegaly at all dose levels as early as 48 hours after injection of cisplatin, prior to increases in urinary copper levels. No change in the distribution of metal binding proteins (transferrin, ferritin, ceruloplasmin, and metallothionein) evaluated by immunohistochemical staining, was seen. Based upon these results, it is unlikely that changes in metal excretion play a primary role in cisplatin-induced nephrotoxicity however, changes in nuclear function indicated by karyomegaly may be involved in early renal injury.

Animals↗

Hearing impairment and hearing aid use in women over 65 years of age. Cross-sectional study of women in a large urban community.

OBJECTIVES: (i) To describe the prevalence of self-reported hearing impairment and level of hearing aid use in women aged 65 years and over living in the community; (ii) to provide comparison findings from the National Health Survey and the Survey of Disability and Ageing undertaken by the Australian Bureau of Statistics. DESIGN: Cross-sectional study of a large community population. SETTING: Conducted as part of the Randwick Falls and Fractures Study, in Randwick a surburban area in eastern Sydney. PARTICIPANTS: Four hundred and ninety-six women aged between 65 and 99 years (mean age, 74.6 years) took part in the study. The sample was representative of the population from which it was drawn. RESULTS: We found a higher level of hearing difficulty than the levels reported in the Australian Bureau of Statistics surveys for women of comparative ages, which may reflect differences in the questions posed. The proportions with a hearing aid in the Randwick study and the Survey of Disability and Ageing were very similar (7.1% and 7.3% respectively). Of the one-third of the Randwick sample who reported a hearing difficulty, only half had been referred for audiometry and a quarter had been prescribed an aid. Only slightly more than a third of those who received an aid were regularly wearing it. Among the women with hearing difficulties, not using an aid was not associated with age, cognitive status or subjective health. There was a trend suggesting that those who did not use an aid had increased use of community support services. Women who had not received assistance with their hearing impairment had more difficulty shopping and relied more on family members. CONCLUSION: Almost two-thirds of people prescribed a hearing aid were not wearing it regularly, denying themselves proven benefits in communication, social involvement and life satisfaction. The prescribing of these unused aids represents a huge waste of health resources. A program to increase hearing aid use by hearing impaired people may reduce the waste of health resources and the need for community support services. Such a program may greatly increase the life satisfaction for this very large group of disabled older people.

Aged↗

Hormonal and metabolic effects of neuroglucopenia.

We examined the role of central neuroglucopenia, induced by intracerebroventricular (i.c.v.) administration of 2-deoxyglucose (2-DG), on glucose and amino acid kinetics in conscious dogs. Group 1 received i.c.v. 2-DG at 2.5 mg.kg-1 x min-1 for 15 min. Group 2 received an equal intravenous (i.v.) amount of 2-DG. In the i.c.v. group, plasma glucose levels rose from 106 +/- 4 mg/dl to a peak of 204 +/- 12 mg/dl by 90 min. Blood lactate increased from 689 +/- 1 to 2,812 +/- 5 mumol/l and blood alanine not change from basal (256 +/- 41 mumol/l). The rate of hepatic glucose production, determined isotopically, was increased 2-fold over basal (P < 0.01). Significant increases (P < 0.001) over basal were also noted in plasma epinephrine, norepinephrine, insulin, glucagon and cortisol. Leucine rate of appearance (Ra) showed a 30% decrease from basal to 2.4 +/- 0.05 mumol.kg-1 x min-1 (P < 0.01). In group 2 plasma glucose levels were not altered but plasma cortisol and glucagon showed a modest transient increase above basal (P < 0.05). No significant changes were noted in amino acid kinetics. These findings suggest that periventricular neuroglucopenia, in the absence of peripheral glucose deprivation, is accompanied by hyperglycemia secondary to enhanced hepatic glucose production with decreased glucose utilization and by increased hepatic uptake of gluconeogenic precursors. These, however, were not accompanied by increased whole body proteolysis as was previously seen with generalized glucopenia resulting from insulin-induced hypoglycemia.

Alanine↗

Antigenic relationships of transferrin-binding proteins from Neisseria meningitidis, N. gonorrhoeae and Haemophilus influenzae: cross-reactivity of antibodies to NH2-terminal peptides.

The NH2-terminal amino sequence through the first 20 amino acids was obtained for transferrin-binding protein (TBP)1 from three strains of Neisseria meningitidis. These were identical except for a glutamine to a glycine substitution at residue 6 in one case. The sequences of the NH2-terminal 20 amino acids of TBP2 from the same three strains were also determined; one TBP2 had a M(r) of 68,000 and the other two of 78,000. Sequences were identical up to residue 13 in all three proteins. Peptides based on the NH2-terminal sequences of TBP1 and 2 were synthesized, linked to Keyhole Limpet haemocyanin and used to raise antibodies in rabbits. Anti-peptide antibodies cross-reacted on immunoblotting with the respective TBPs from all meningococcal strains tested, as well as with those from N. gonorrhoeae, suggesting that the NH2-terminals of these proteins are well conserved in the Neisseria. Neither anti-peptide serum reacted with the analogous TBP1 and 2 from Haemophilus influenzae, although common epitopes have previously been shown to exist.

Amino Acid Sequence↗

A method for the enumeration of bacterial adhesion to epithelial cells using image analysis.

Computerised image analysis was utilised to enumerate the attachment of Staphylococcus epidermidis to HEp2 cell monolayers. A differential staining technique was employed such that individual staphylococcal cells stood out in sharp contrast against the uneven cell surface and granular contents of the epithelial cells. The primary image analysis operation involved subtracting an out-of-focus image from an in-focus image of the bacteria on the monolayer, thereby accentuating the bacterial image. Enumeration, using a particle counting routine, was rapid and reproducible, facilitating counting in excess of 700 bacteria per field at x 500 magnification. The computerised programme compared favourably with manual counting and would provide a rapid, objective and morphologically discriminatory method for evaluating bacterial attachment to various tissues.

Bacterial Adhesion↗

Control of epidemic group A meningococcal disease in Auckland.

AIM: To study group A meningococcal vaccine delivery to infants less than 2 years of age in Auckland in 1987 to control epidemic disease. METHODS: Mechanisms of vaccine delivery and its facilitation are described. A detailed audit of delivery of vaccine to children less than two years using signed consent forms determined delivery source. This was the age group at highest risk, and poorly covered by routine childhood vaccines. Primary health care source of children presenting with disease was determined by telephone. RESULTS: The epidemic of group A meningococcal disease in the winters of 1985 and 1986 abated most likely due to the vaccination of high risk children (3 months-13 years) in 1987. 90% of the target population were vaccinated. In south Auckland the majority (92%) of vaccine doses for children less than two years of age was delivered by the Plunket Society with Department of Health backing aided by community health workers. By contrast delivery by, general practitioners was greater in north-west and central Auckland (approximately 25%, of dose 1), especially after the publicity over possible side effects (approximately 50% of dose 2). Coverage for dose 1 of children < 2 years was similar (89%) in south Auckland. Of children presenting with meningococcal disease 1 in 4 did not have an identifiable general practitioner. CONCLUSIONS: Vaccines to prevent serious paediatric illness are known to be highly cost effective. The best method of delivery of vaccinations may vary from area to area. Major community involvement including community health workers for the Maori and Pacific Island communities may have facilitated the dissemination of information in this campaign.

Adolescent↗

In vivo evaluation of protein adsorption to sterically stabilised colloidal carriers.

A diffusion chamber implanted intraperitoneally in the rabbit was employed as an in vivo model to evaluate the interaction of peritoneal proteins with block copolymer (poloxamer and poloxamine)-coated polystyrene microspheres (PS). Using a desorption technique followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, six proteins of 94, 86, 66, 53, 40, and 20 kDa were desorbed from the carrier systems after incubation with peritoneal fluid in vitro. The 40- and 20-kDa proteins dominated the protein profile. A similar pattern was observed when proteins were desorbed from PS microspheres removed after 24-h implantation in chambers in the peritoneal cavity, although the protein profile was dominated by the 94- and 53-kDa proteins. In general, coating of PS with block copolymers reduced the amount of protein bound to the microspheres in vitro and in vivo but did not change the types of proteins bound.

Adsorption↗