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Biomedical subjects

A Smith

Publications and source records attributed to A Smith.

At least 127 records · Page 7Linked to original sources
PubMed2003

Induction by sphingomyelinase of shiga toxin receptor and shiga toxin 2 sensitivity in human microvascular endothelial cells.

Shiga toxin-producing enterohemorrhagic Escherichia coli is the major cause of acute renal failure in young children. The interaction of Shiga toxins 1 and 2 (Stx1 and Stx2) with endothelial cells is an important step in the renal coagulation and thrombosis observed in hemolytic uremic syndrome. Previous studies have shown that bacterial lipopolysaccharide and host cytokines slowly sensitize endothelial cells to Shiga toxins. In the present study, bacterial neutral sphingomyelinase (SMase) rapidly (1 h) sensitized human dermal microvascular endothelial cells (HDMEC) to the cytotoxic action of Stx2. Exposure of endothelial cells to neutral SMase (0.067 U/ml) caused a rapid increase of intracellular ceramide that persisted for hours. Closely following the change in ceramide level was an increase in the expression of globotriaosylceramide (Gb3), the receptor for Stx2. A rapid increase was also observed in the mRNA for ceramide:glucosyltransferase (CGT), the first of three glycosyltransferase enzymes of the Gb3 biosynthetic pathway. The product of CGT (glucosylceramide) was also increased. In contrast, mRNA for the third enzyme of the pathway, Gb3 synthase, was constitutively produced and was not influenced by SMase treatment of HDMEC. These results describe a rapid response mechanism by which extracellular neutral SMase derived from either bacteria or eukaryotic cells may signal endothelial cells to become sensitive to Shiga toxins.

Cells, Cultured↗
PubMed2003

Molecular characteristics of human immunodeficiency virus type 1 subtype C viruses from KwaZulu-Natal, South Africa: implications for vaccine and antiretroviral control strategies.

The KwaZulu-Natal region of South Africa is experiencing an explosive outbreak of human immunodeficiency virus type 1 (HIV-1) subtype C infections. Understanding the genetic diversity of C viruses and the biological consequences of this diversity is important for the design of effective control strategies. We analyzed the protease gene, the first 935 nucleotides of reverse transcriptase, and the C2V5 envelope region of a representative set of 72 treatment-naïve patients from KwaZulu-Natal and correlated the results with amino acid signature and resistance patterns. Phylogenetic analysis revealed multiple clusters or "lineages" of HIV-1 subtype C that segregated with other C viruses from southern Africa. The same pattern was observed for both black and Indian subgroups and for retrospective specimens collected prior to 1990, indicating that multiple sublineages of HIV-1 C have been present in KwaZulu-Natal since the early stages of the epidemic. With the exception of three nonnucleoside reverse transcriptase inhibitor mutations, no primary resistance mutations were identified. Numerous accessory polymorphisms were present in the protease, but none were located at drug-binding or active sites of the enzyme. One frequent polymorphism, I93L, was located near the protease/reverse transcriptase cleavage site. In the envelope, disruption of the glycosylation motif at the beginning of V3 was associated with the presence of an extra protein kinase C phosphorylation site at codon 11. Many polymorphisms were embedded within cytotoxic T lymphocyte or overlapping cytotoxic T-lymphocyte/T-helper epitopes, as defined for subtype B. This work forms a baseline for future studies aimed at understanding the impact of genetic diversity on vaccine efficacy and on natural susceptibility to antiretroviral drugs.

AIDS Vaccines↗
PubMed2003

Birth prevalence of Prader-Willi syndrome in Australia.

This is the first population based study to estimate the birth prevalence of DNA proven Prader-Willi syndrome. Thirty infants were reported to the Australian Paediatric Surveillance Unit between 1998 and 2000, a prevalence of 4 per 100,000 live births or approximately 1/25,000 live births per annum.

Adolescent↗
PubMed2003

Interventions for post-traumatic stress disorder and psychological distress in emergency ambulance personnel: a review of the literature.

A literature review was carried out to establish the extent of the literature on interventions for psychological distress and post-traumatic stress disorder in emergency ambulance personnel. A total of 292 articles were identified. Of these, 10 were relevant to this review. The primary intervention used with this population was critical incident stress debriefing, although there was some debate in the literature about the effectiveness of this intervention and the quality of the research conducted. More high quality research is needed on critical incident stress debriefing before being confident of its effectiveness.

Crisis Intervention↗
PubMed2003

Outcome of diabetic patients treated in the prehospital arena after a hypoglycaemic episode, and an exploration of treat and release protocols: a review of the literature.

OBJECTIVES: This review examines current treat and release protocols adopted by the ambulance service, and factors that may predispose patients to hypoglycaemia. METHODS: Online database searches and hand searches of journals led to 241 articles being found, of which eight were used for this article. RESULTS: Out of hospital treatment of hypoglycaemia is safe for most patients, but further studies are needed if positive improvements are to be made. DISCUSSION: There is potential for further research in this area and clarification is needed in the treat and release debate. A definitive set of protocols would be beneficial to the ambulance service.

Clinical Protocols↗
PubMed2003

Intermittent enteral nutrition--a comparative study examining the effect on gastric pH and microbial colonization rates.

In a prospective randomized study we aimed to examine the effect on gastric pH and microbial colonization of enteral nutrition (EN) delivered both by intermittent and continual infusion. Forty-three mechanically ventilated patients were randomized to receive EN by one of three methods, intermittent or continual gastric or continual jejunal. We sampled gastric aspirate for pH and culture in all patients at 0600 hours and pH in gastric intermittent feeders at 2200 hours daily. Patients were studied for 12 days or until extubated. Data was obtained on 41 patients, of whom 73% had a diagnosis of trauma. Median APACHE II score was 17 and ventilation time 11 days. Twelve patients received gastric continuous, 15 gastric intermittent and 14 jejunal nutrition. No significant difference was observed between the three groups with regard to median 0600 pH (P = 0.16). This was lowest in the jejunal group (3.2) followed by the gastric intermittent group (4.0) and then gastric continuous group (5.0). With overnight cessation of EN in the gastric intermittent group, the median pH fell from 5.2 at 2200 to 4.0 at 0600 (P = 0.01) with no effect on gastric colonization. The probability of gastric colonization over time however was significantly lower in the jejunal group compared with the two gastric groups (Log rank test, P = 0.02). These results demonstrate that in a patient population consisting predominantly of trauma, overnight cessation of EN made no overall difference to 0600 gastric pH or colonization rates. The preservation of pH and lowered colonization in those given jejunal feeding may have implications in the pathogenesis of ventilator-associated infection and may warrant further study using larger patient numbers.

APACHE↗
PubMed2003

Exhaled breath condensate pH is a robust and reproducible assay of airway acidity.

Exhaled breath condensate (EBC) pH is low in several lung diseases and it normalises with therapy. The current study examined factors relevant to EBC pH monitoring. Intraday and intraweek variability were studied in 76 subjects. The pH of EBC collected orally and from isolated lower airways was compared in an additional 32 subjects. Effects of ventilatory pattern (hyperventilation/hypoventilation), airway obstruction after methacholine, temperature (-44 to +13 degrees C) and duration of collection (2-7 min), and duration of sample storage (up to 2 yrs) were examined. All samples were collected with a disposable condensing device, and de-aerated with argon until pH measurement stabilised. Mean EBC pH (n=76 subjects, total samples=741) was 7.7+/-0.49 (mean+/-SD). Mean intraweek and intraday coefficients of variation were 4.5% and 3.5%. Control of EBC pH appears to be at the level of the lower airway. Temperature of collection, duration of collection and storage, acute airway obstruction, subject age, saliva pH, and profound hyperventilation and hypoventilation had no effect on EBC pH. The current authors conclude that in health, exhaled breath condensate pH is slightly alkaline, held in a narrow range, and is controlled by lower airway source fluid. Measurement of exhaled breath condensate pH is a simple, robust, reproducible and relevant marker of disease.

Acid-Base Equilibrium↗
PubMed2003

Implanon: user views in the first year across three family planning services in the Trent Region, UK.

OBJECTIVE: Implanon (NV Organon, Oss, The Netherlands) was released in the United Kingdom towards the end of 1999. This survey elicited the experiences of women who had the new implant inserted in three family planning services in North Trent, UK during the first year after its introduction. METHOD: A previously piloted questionnaire was sent to all Implanon users who had the devices fitted in the three services between December 1999 and December 2000. Returned questionnaires were analyzed. RESULTS: Health-care providers and friends or family were the main sources of information about the single-rod contraceptive implant for the survey population. Women considered themselves informed about the method prior to insertion irrespective of whether they continued to use the method or requested early removal. Ease of use was the most common reason for choosing Implanon and one of the best-liked features. Bleeding irregularities were the most commonly reported side-effect, followed by weight gain, moods and headaches. Bleeding problems led to the majority of removal requests; the wish for pregnancy was not stated at all. The single-rod implant compared favorably with most responders' experiences with other methods of contraception. Further research into motivation and perceptions regarding modern contraceptives may be required in different populations.

Adult↗
PubMed2003

Outbreak of hepatitis A infection among intravenous drug users in Suffolk and suspected risk factors.

A prolonged outbreak of hepatitis A infection amongst drug users in Suffolk prompted a study of the natural immunity against hepatitis A in this population, and a retrospective analysis of the relationship between specific drug-taking behaviours and the risk of hepatitis A infection. Prior to the outbreak, age-specific seroprevalence of hepatitis A IgG in drug users was similar to that amongst blood donors in the region. Of those without effective immunity, intravenous drug users, multiple drug users and those injecting frequently were more likely to have developed hepatitis. The reported frequency of equipment sharing and the number of injecting partners were not related to the risk of infection. The potential for blood-to-blood, and a suggested faecal-blood transmission were considered to be important in propagating the outbreak in this population. We suggest that a single dose of hepatitis A vaccine administered opportunistically should be used in outbreaks involving drug users.

Adult↗
PubMed2002

Measurements of inclusive B-->psi production.

Using the combined CLEO II and CLEO II.V data sets of 9.1 fb(-1) at the Upsilon(4S), we measure properties of psi mesons produced directly from decays of the B meson, where "B" denotes an admixture of B+, B-, B0, and B;(0), and "psi" denotes either J/psi(1S) or psi(2S). We report first measurements of psi polarization in B-->psi(direct)X: alpha(psi(1S))=-0.30(+0.07)(-0.06)+/-0.04 and alpha(psi(2S))=-0.45(+0.22)(-0.19)+/-0.04. We also report improved measurements of the momentum distributions of psi produced directly from B decays, correcting for measurement smearing. Finally, we report measurements of the inclusive branching fraction for B-->psiX and B-->chi(c1)X.

Journal Article↗
PubMed2002

Measurement of B(D+-->K(*0)l(+)nu(l)).

Using 13.53 fb(-1) of CLEO data, we have measured the ratios of the branching fractions R(+)(e),R(+)(mu) and the combined branching fraction ratio R(+)(l), defined by R(+)(l)=[B(D+-->K(*0)l(+)nu(l))]/[B(D+-->K-pi(+)pi(+))]. We find R(+)(e)=0.74+/-0.04+/-0.05, R(+)(mu)=0.72+/-0.10+/-0.05, and R(+)(l)=0.74+/-0.04+/-0.05, where the first and second errors are statistical and systematic, respectively. The known branching fraction B(D+-->K-pi(+)pi(+)) leads to B(D+-->K(*0)e(+)nu(e))=(6.7+/-0.4+/-0.5+/-0.4)%, B(D+-->K(*0)mu(+)nu(mu))=(6.5+/-0.9+/-0.5+/-0.4)%, and B(D+-->K(*0)l(+)nu(l))=(6.7+/-0.4+/-0.5+/-0.4)%, where the third error is due to the uncertainty in B(D+-->K-pi(+)pi(+)).

Journal Article↗
PubMed2002

Observation of the decay Omega(0)(c)-->Omega(-)e(+)nu(e).

Using the CLEO detector at the Cornell Electron Storage Ring we have observed the Omega(0)(c) (css ground state) in the decay Omega(0)(c)-->Omega(-)e(+)nu(e). We find a signal of 11.4+/-3.8(stat) events. The probability that we have observed a background fluctuation is 7.6x10(-5). We measure B(Omega(0)(c)-->Omega(-)e(+)nu(e)).sigma(e(+)e(-)-->Omega(0)(c)X)=(42.2+/-14.1(stat)+/-5.7(syst)) fb and R=[Gamma(Omega(0)(c)-->Omega(-)pi(+))]/[Gamma(Omega(0)(c)-->Omega(-)enu(e))]=00.41+/-0.19(stat)+/-0.04(syst). This is the first statistically significant observation of an individual decay mode of the Omega(0)(c) in e(+)e(-) annihilation and the first example of a baryon decaying via beta emission, where no quarks from the first generation participate in the reaction.

Journal Article↗
PubMed2002

Potential role of endocrine gastrin in the colonic adenoma carcinoma sequence.

The role of hyper-gastrinaemia in the incidence of colonic cancer remains to be clarified. The aim of this study was to determine whether cholecystokinin-2 (CCK-2) receptor expression predicts the sensitivity of human colonic adenomas to the proliferative effects of serum hyper-gastrinaemia. Gene expression of the classical (74 kDa) CCK-2 receptor in human colonic adenoma specimens and cell lines, was quantified by real-time PCR. Western blotting, using a CCK-2 receptor antiserum, confirmed protein expression. A transformed human colonic adenoma was grown in SCID mice, with hyper-gastrinaemia induced by proton pump inhibitors. CCK-2 receptor blockade was achieved by using neutralising antiserum. Both human colonic adenoma cell lines and biopsies expressed CCK-2 receptor mRNA at levels comparable with CCK-2 receptor transfected fibroblasts and oxyntic mucosa. Western blotting confirmed immunoreactive CCK-2 receptor bands localised to 45, 74 and 82.5 kDa. Omeprazole and lansoprazole-induced hyper-gastrinaemia (resulting in serum gastrin levels of 34.0 and 153.0 pM, respectively) significantly increased the weight of the human adenoma grafts (43% (P=0.016) and 70% (P=0.014), respectively). The effect of hypergastrinaemia on tumour growth was reversed by use of antiserum directed against the CCK-2 receptor. Hyper-gastrinaemia may promote proliferation of human colonic adenomas that express CCK-2 receptor isoforms.

Adenocarcinoma↗
PubMed2002

Transgenic tilapia and the tilapia genome.

The tilapia fish (Oreochromis niloticus) has an important place in the aquaculture of the developing world. It is also a very useful laboratory animal, and readily lends itself to the transgenic technology. Through the use of reporter genes, a range of potential gene promoters have been tested in tilapia, both through transient and stable expression of the reporter construct. Using the transgenic technology, growth enhanced lines of tilapia have been produced. These fish have no abnormalities and offer a considerable growth advantage for future exploitation. It is however crucial that transgenic fish, to be exploited in aquaculture, be sterile, and various methods of achieving sterility are considered. These include triploidy, gene knock out of crucial hormone encoding genes via homologous recombination, and knock down of the function of the same genes via ribozyme or antisense technologies. Transgenic tilapia also offer the potential for exploitation as biofactories in the production of valuable pharmaceutical products, and this is also discussed.

Animals↗
PubMed2002

Improved measurement of /V(cb)/ using B-->D*l nu decays.

We determine the weak coupling /V(cb)/ between the b and c quarks using a sample of 3 x 10(6) BB; events in the CLEO detector at the Cornell Electron Storage Ring. We determine the yield of reconstructed B-->D*l nu; decays as a function of w, the boost of the D* in the B rest frame, and from this we obtain the differential decay rate d Gamma/dw. By extrapolating d Gamma/dw to w=1, the kinematic end point at which the D* is at rest relative to the B, we extract the product /V(cb)/F(1), where F(1) is the form factor at w=1. Combined with theoretical results for F(1) we determine /V(cb)/=0.0469+/-0.0014(stat)+/-0.0020(syst)+/-0.0018(theor).

Journal Article↗