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Biomedical subjects

J Noel

Publications and source records attributed to J Noel.

At least 19 recordsLinked to original sources
PubMed1997

Outbreak of viral gastroenteritis due to a contaminated well. International consequences.

CONTEXT: Small round-structured viruses (SRSVs) are known to cause viral gastroenteritis, but until now have not been confirmed in the implicated vehicle in outbreaks. OBJECTIVE: Investigation of a gastroenteritis outbreak. DESIGN: After applying epidemiologic methods to locate the outbreak source, we conducted environmental and laboratory investigations to elucidate the cause. SETTING: Tourists traveling by bus through Alaska and the Yukon Territory of Canada. PARTICIPANTS: Staff of a restaurant at a business complex implicated as the outbreak source, convenience sample of persons on buses that had stopped there, and bus employees. MAIN OUTCOME MEASURES: Odds ratios (ORs) for illness associated with exposures. Water samples from the restaurant and stool specimens from tourists and restaurant staff were examined by nucleic acid amplification using reverse transcription polymerase chain reaction and sequencing of viral amplification products. RESULTS: The itineraries of groups of tourists manifesting vomiting or diarrhea were traced back to a restaurant where buses had stopped 33 to 36 hours previously. Water consumption was associated with illness (OR, 5.3; 95% confidence interval [CI], 2.3-12.6). Eighteen of 26 employees of the business complex were ill; although not the index case, an employee ill shortly before the outbreak lived in a building connected to a septic pit, which was found to contaminate the well supplying the restaurant's water. Genotype 2/P2B SRSV was identified in stool specimens of 2 tourists and 1 restaurant employee. Stools and water samples yielded identical amplification product sequences. CONCLUSIONS: The investigation documented SRSVs in a vehicle epidemiologically linked to a gastroenteritis outbreak. The findings demonstrate the power of molecular detection and identification and underscore the importance of fundamental public health practices such as restaurant inspection, assurance of a safe water supply, and disease surveillance.

Base Sequence↗
PubMed1997

Pre-steady-state study of recombinant sesquiterpene cyclases.

An Escherichia coli expression system was used to generate hexahistidyl-tagged plant sesquiterpene cyclases, which were readily purified by a single affinity chromatographic step. Genes for Hyoscyamus muticus vetispiradiene synthase (HVS), a chimeric 5-epi-aristolochene synthase (CH3), and a chimeric sesquiterpene cyclase possessing multifunctional epi-aristolochene and vetispiradiene activity (CH4) were expressed in bacterial cells, which resulted in the sesquiterpene cyclases accumulating to 50% of the total protein and 35% of the soluble protein. From initial velocity experiments, the Michaelis constant for HVS was 3.5 microM, while CH3 and CH4 exhibited smaller values of 0.7 and 0.4 microM, respectively. Steady-state catalytic constants were from 0.02 to 0.04 s-1. A combination of pre-steady-state rapid quench experiments, isotope trapping experiments, and experiments to measure the burst rate constant as a function of substrate concentration revealed that turnover in all three cyclases is limited by a step after the initial chemical step involving rupture of the carbon-oxygen bond in farnesyl diphosphate (FPP). Rate constants for the limiting step were 10-70-fold smaller than for the initial chemical step. Dissociation constants for the enzyme-substrate complex (20-70 microM) were determined from the pre-steady-state experiments and were significantly larger than the observed Michaelis constants. A mechanism that involves an initial, rapid equilibration of enzyme with substrate to form an enzyme-substrate complex, followed by a slower conversion of FPP to an enzyme-bound hydrocarbon and a subsequent rate-limiting step, is proposed for the three enzymes. Interestingly, the multifunctional chimeric enzyme CH4 exhibited both a tighter binding of FPP and a faster conversion of FPP to products than either of its wild-type parents.

Alkyl and Aryl Transferases↗
PubMed1996

The changing epidemiology of astrovirus-associated gastroenteritis: a review.

Our understanding of the epidemiology of astrovirus-associated gastroenteritis has changed markedly with each improvement in detection method. In early surveys based on electronmicroscopy (EM), astroviruses appeared to be a rare cause of gastroenteritis, being found in fewer than 1% of children with diarrhea, usually in small outbreaks of disease and primarily during the winter season. The development and use of monoclonal antibodies and enzyme immunoassays (EIA) to detect astroviruses led to reports of a higher prevalence (2.5%-9%) of astrovirus infection among patients hospitalized with diarrhea. Astroviruses appeared second only to rotaviruses as a cause of hospitalization for childhood viral gastroenteritis. Studies based on EIA detection of astroviruses indicate that astroviruses are common causes of diarrhea in children worldwide, and that most children are infected during their first two years of life. The elderly and the immunocompromised represent high-risk groups as well. The observations that newborns monitored prospectively rarely have repeat disease and that the rate of detection decreases with increasing age suggest that immunity to astroviruses, as immunity to rotaviruses, may develop early in life. The cloning and sequencing of astroviruses have led to more sensitive assays to detect the viruses by reverse transcription, polymerase chain reaction (RT-PCR). Application of RT-PCR for detection of astroviruses in children in day-care centers showed a marked increase in the detected prevalence of astrovirus-associated diarrhea, the rate of asymptomatic infection, and the duration of shedding of virus among those infected, when compared with studies that used other methods. As with rotaviruses, neither the mode of transmission nor the reservoir of astrovirus infection has been identified. Both immune and molecular-based assays to detect astrovirus serotypes indicate that serotype 1 is most common worldwide, although the predominant serotypes may vary by region and time. In the absence of obvious strategies to prevent astrovirus-associated diarrhea, vaccines might be considered if further studies establish that the disease burden would render such a vaccine cost-effective.

Animals↗
PubMed1996

Differential localization of Na+/H+ exchanger isoforms (NHE1 and NHE3) in polarized epithelial cell lines.

Na+/H+ exchangers (NHEs) are transporters that exchange sodium and proton ions across the plasma membrane at the expense of their chemical gradient. In higher eukaryotes these transporters exist as multiple specialized isoforms. For example, NHE1, the ubiquitously expressed form is a major pH-regulating system whereas the epithelial NHE3 isoform is specialized in transepithelial Na+ transport. NHE1 and NHE3 can be very well distinguished pharmacologically with the HOE694 specific inhibitor and immunologically with specific polyclonal and monoclonal antibodies. With these molecular tools we investigated the specific steady state expression of the two NHE isoforms in polarized epithelial cells in culture. Endogenous NHE3 in OK cells or NHE3-VSVG transfected in either OK or MDCK cells showed an exclusive expression of the transporter at the apical membrane. Overexpression of NHE3 did not result in any spill over on the basal lateral side. These results obtained by functional measurement of NHE3 activity were fully consistent with its detection only at the apical side by immunofluorescence and confocal microscopy. By contrast, using the same cells, the same culture conditions and the same detection methods, we clearly detected NHE1 at both specialized membranes of four different polarized epithelial cell lines. Furthermore, biotinylation of cell surface proteins of MDCK, OK and HT-29 cells followed by immunoprecipitation of NHE1 revealed expression of the transporter at both sides of the polarized epithelial cells. Interestingly, the cell surface expression correlated well with the corresponding NHE1 activities. In addition, immunodetection by fluorescence microscopy was found to be qualitatively consistent with the above-reported results. We therefore conclude that the epithelial and more specialized NHE3 isoform is exclusively restricted to the apical side of epithelial cells. In marked contrast, both endogenous or ectopically expressed NHE1 isoform, have the capacity to be expressed in both the apical and basal lateral membranes of polarized cells in cultures.

Amino Acid Sequence↗
PubMed1995

The poster assignment: a connected teaching strategy for increasing student comfort with issues of sexuality.

The poster assignment has proven to be the most successful strategy designed by a group of nurse educators seeking to facilitate nursing student comfort and confidence with sexuality related content. Through the use of a process involving both structured and informal interaction opportunities, the context was set for students to build knowledge, examine values and attitudes, and develop helping skills, necessary building blocks for preparing students to assist patients with sexual problems and concerns. The process is described and discussed with specific examples given from the authors' experiences with this non-traditional learning activity.

Attitude of Health Personnel↗
PubMed1995

Mechanisms of proximal proton secretion in BBM of herbivorous, omnivorous, and carnivorous species.

The mechanisms of proton secretion by the proximal brush-border membrane (BBM) were compared in carnivorous (dog), omnivorous (human, pig, rat), and herbivorous (rabbit, hamster) species. The activity of the proton pump (V-type bafilomycin-sensitive H(+)-adenosinetriphosphatase) and of the Na+/H+ exchanger (amiloride-sensitive quenching of acridine orange fluorescence), the two major proton secretion mechanisms, was measured. The enzymatic activity of the H(+)-adenosinetriphosphatase activity was measured in intact (endosomes) and solubilized (0.1% deoxycholate or Triton X-100) BBM vesicles isolated by conventional Mg2+ precipitation techniques. In all species, but not in humans, the fraction of the ATP turnover energizing the proton pump (bafilomycin-sensitive respiration) was also measured in isolated proximal tubules. Significant differences in acid transport mechanisms were noted between species, with the proton pump predominating in the BBM of carnivorous species and the Na+/H+ exchanger predominating in the BBM of herbivorous species. The fraction of respiration suppressible by bafilomycin in proximal tubules was also different in all the species considered. This may indicate a different organization of proximal H+ transport related to the species-specific menace to acid-base balance.

Animals↗
PubMed1994

Identification of adenoviruses in faeces from patients with diarrhoea at the Hospitals for Sick Children, London, 1989-1992.

Faecal samples from 137 patients that had been shown to contain adenoviruses by electron microscopy were identified in a series of enzyme immunoassays (EIA) using a single monoclonal antibody (Mab) to adenovirus 40 and four different Mabs to adenovirus 41. Adenoviruses were partially characterised by restriction enzyme analysis (REA) of DNA extracts using SmaI. Samples were also run in a commercial EIA (Adenovirus IDEIA; Dako, Ltd.) which detects group antigen. The majority (84%) of adenoviruses were subgenus F: adenovirus type 41, 87 (64%) and adenovirus type 40, 28 (20.4%). Subgenus A viruses were identified in ten, (7%) patients, eight were type 31, and two type 12. The adeno IDEIA test was sensitive and specific, detecting 127 of 131 positives and giving no false-positive results with other enteric viruses. Use of monoclonal-based EIAs showed significant differences depending on which adeno 41 Mab was used, although the restriction patterns obtained using SmaI appeared to be identical for 66 of 69 samples that produced recognisable bands. The Mab that performed best, M 4.3.1, was raised against strains obtained from children in England and detected 83 of 84 (99%) of the adenovirus 41 samples tested. In contrast Mab JH/41 raised against the prototype strain of adenovirus 41 (Tak) detected only 69 of 87 (79%).

Adenoviruses, Human↗
PubMed1994

Identification of astrovirus serotypes from children treated at the Hospitals for Sick Children, London 1981-93.

An enzyme immunoassay (EIA) for astrovirus type 1 together with immune electronmicroscopy (IEM) was used to type a collection of 162 astroviruses obtained from 1981-93 from children with diarrhoea. The EIA was found to be specific for astrovirus type 1. Astrovirus types 2-4 were typed by IEM. Astrovirus type 1 was the prevalent serotype 107/125 (86%), followed by type 3 (8%), type 4 (6%) and type 2 (1%). Six samples containing astrovirus could not be typed or detected by EIA because they were coated with coproantibodies; 11 others were not identified. Virus particles could no longer be detected in 15/162 (9%) samples following storage for > or = 2 years. Selected samples containing astrovirus types 1-4 were passaged in CaCO2 cells and their identity confirmed by one or both assays. One sample was shown to have remained viable for 10 years when stored as an aqueous suspension at -20 degrees C. Two patients with severe combined immune deficiency disease (SCID) were shown to be excreting astrovirus type 1 for 32 and 102 days respectively. One child was simultaneously shedding rotavirus and the other child was excreting adenovirus.

Child↗
PubMed1993

Restless legs syndrome in the elderly.

The prevalence and significance of restless legs syndrome was assessed in 307 patients presenting to an acute-care geriatric medical service. Fifteen patients (5%) had restless legs syndrome; 13 (87%) of these patients had insomnia and 10 (67%) reported troublesome or frequent leg symptoms. Of 147 patients with current insomnia, iron deficiency (serum ferritin < 18 ng/ml) was present in 4/13 (31%) patients with restless legs and 8/134 (6%) patients without restless legs (P < 0.025). Improvement in symptoms of restless legs was noted with iron repletion. These findings suggest that restless legs syndrome is relatively common in the elderly and causes significant discomfort and sleep disturbance. Iron deficiency is a common and treatable cause.

Aged↗
PubMed1993

Cardiopulmonary resuscitation preferences in the elderly.

OBJECTIVE: Many studies have examined the attitudes of elderly Americans towards cardiopulmonary resuscitation. A less formal approach to resuscitation decisions is usual in Europe, but few comparable studies have been reported in elderly European populations. We studied the views on resuscitation in a prospective series of elderly Irish patients. METHODS: We administered a standardized questionnaire to 100 elderly patients who did not have cognitive impairment, depression or terminal or life-threatening illness. Patients were asked if they could wish to be resuscitated following a cardiac arrest in their present state of health and in a number of hypothetical clinical situations. RESULTS: All of our patients would reject resuscitation in the event of severe functional or mental impairment. Even in their present state of health, only three patients would definitely opt for resuscitation, 74 patients would reject resuscitation, and the remainder would leave the decision to their family or doctor. CONCLUSIONS: These results suggest that there are substantial differences in attitudes to resuscitation between Irish and American elderly patients. Further studies in other European populations are necessary.

Aged↗
PubMed1992

Oscillations of cytosolic free calcium concentration in the presence of intracellular antibodies to phosphatidylinositol 4,5-bisphosphate in voltage-clamped guinea-pig hepatocytes.

In liver cells, the stimulation of alpha 1-adrenoceptors by noradrenaline induces the production of Ins(1,4,5)P3 through the degradation of membrane polyphosphoinositides [PtdIns(4,5)P2]. InsP3 evokes in turn the release of Ca2+ from internal stores. Our results show that the internal perfusion of single guinea-pig hepatocytes with monoclonal anti-PtdInsP2 antibody blocks the rise in cytosolic free Ca2+ concn. ([Ca2+]i) evoked by noradrenaline, an InsP3-dependent agonist, but not by the monohydroxylated bile acid taurolithocholate 3-sulphate, which is known to permeabilize the endoplasmic reticulum. In these conditions, the bile acid elicited either fast or slow fluctuations of [Ca2+]i independently of any InsP3 production. The responses to the bile acid were also observed in the absence of external Ca2+. The presence of intracellular anti-PtdInsP2 antibody does not affect the response to a photolytic release of InsP3 (1.5 microM final concn.) from a caged precursor.

Animals↗
PubMed1991

Cyclic AMP-evoked oscillations of intracellular [Ca2+] in guinea-pig hepatocytes.

The effects of the beta-adrenoceptor agonist isoprenaline and cyclic AMP (cAMP) on cytosolic free Ca2+ ([Ca2+]i) were studied in the single guinea-pig hepatocyte. In common with InsP3-dependent agonists such as noradrenaline or angiotensin II, isoprenaline (0.5-10 microM) and cAMP (50-100 mM, perfused into the cell via the patch-pipette), were able to generate fast and slow fluctuations of [Ca2+]i. Responses to isoprenaline and cAMP also were observed in the absence of external Ca2+. Isoprenaline-evoked [Ca2+]i rises were not blocked by the intracellular perfusion of heparin, suggesting that these fluctuations are independent of the binding of InsP3 to its receptor.

Angiotensin II↗
PubMed1991

Evidence for bile acid-evoked oscillations of Ca2(+)-dependent K+ permeability unrelated to a D-myo-inositol 1,4,5-trisphosphate effect in isolated guinea pig liver cells.

In single liver cells, the D-myo-inositol 1,4,5-triphosphate (InsP3)-dependent agonists such as noradrenaline and angiotensin II evoke oscillations in intracellular calcium [Ca2+]i resulting mostly from the periodic release and reuptake of calcium from intracellular stores. In the present work, we have reexamined the effects of these agonists and investigated whether the natural bile acid taurolithocholic acid 3-sulfate (TLC-S), which permeabilizes the endoplasmic reticulum, could initiate oscillations of [Ca2+]i. Oscillations of [Ca2+]i were monitored with the Ca2(+)-dependent K+ permeability in whole-cell voltage-clamped guinea pig liver cells. Our results confirm the presence of two types of oscillations induced by hormones. They could be distinguished by their frequency periods. The fast (type I) had periods ranging from 5 to 12 s and the slow (type II) from 60 to 240 s. They have been respectively attributed to second messenger- and receptor-controlled oscillations, respectively. Our results also show that TLC-S, as noradrenaline and angiotensin II, induced the activation of this Ca(+)-dependent K+ current and was able to reproduce both types of oscillations. The bile acid effect was not blocked by intracellular perfusion of heparin known to inhibit both InsP3 binding and InsP3-evoked Ca2+ release in several tissues. In these conditions, TLC-S only evoked type I oscillations, suggesting that these fluctuations could originate from a mechanism that is independent of InsP3 and is an intrinsic property of internal Ca2+ stores.

Angiotensin II↗
PubMed1988

Use of short-chain cyclopentano-phosphatidylcholines to probe the mode of activation of phospholipase A2 from bovine pancreas and bee venom.

A great mystery in the mechanism of phospholipase A2 (PLA2) and many other lipolytic enzymes is the "interfacial activation" induced by micellar but not monomeric substrates. Equally mysterious is the lack of interfacial activation in bee venom PLA2, as opposed to PLA2s from pancreas and other sources. We have probed these problems using the conformationally restricted short-chain cyclopentano-analogues of diacylphosphatidylcholine (Cp-DCnPC, all-trans isomer). In the reaction catalyzed by bovine pancreatic PLA2, Cp-DC8PC behaved differently from DC8PC in that its monomers and micelles showed comparable activities (but lower than the activity of DC8PC). This result suggests that the activity of PLA2 can be regulated by substrate conformation and supports the "substrate conformation model" (Wells, M. A. (1974) Biochemistry 13, 2248-2257), but raises a question as to whether Cp-DC8PC mimics monomers or micelles of DC8PC. Conformational analysis by 1H NMR revealed that monomeric Cp-DC8PC was conformationally restricted near the carbonyl region, a property characteristic of micelles. Thus, monomeric CP-DC8PC can be considered as a conformational analogue of micelles, but the important structural feature lies in the CH2COO region instead of the glycerol backbone. CP-DC8PC was then used to test a previous proposal that the bee venom PLA2 hydrolyzes monomers but not micelles (which would predict little or no activity for Cp-DC8PC since its conformation is micelle-like whether below or above its critical micelle concentration). The results showed that Cp-DC8PC is a relatively good substrate for the bee venom PLA2 in comparison with the pancreatic PLA2. This and other evidence together suggest that the bee venom PLA2 is not sensitive to the conformation of monomeric and micellar substrates and hydrolyzes both monomers and micelles. The results in both PLA2s demonstrate the usefulness of cyclopentano-phospholipids in probing the mechanism of phospholipases and the roles of substrate conformation in the catalysis of PLA2.

Animals↗
PubMed1988

Chronic dose urinary and serum pharmacokinetics of norfloxacin in the elderly.

1. Norfloxacin was administered as two daily 400 mg oral doses to eight elderly patients requiring treatment for urinary tract infections. Blood specimens were obtained for pharmacokinetic profiles following the first and fifteenth doses. Further specimens were obtained before each morning's dose of norfloxacin. Specimens of urine were obtained to ascertain if adequate antimicrobial concentrations were reached in these patients with diminished renal function. 2. Norfloxacin half-life was consistent with that expected in mild renal impairment and was not different between the first and fifteenth doses. Based on ratios of AUC values, accumulation is probably related to renal function, being greatest for creatinine clearance values below 30 ml min-1. 3. On the great majority of occasions, the urinary concentrations of norfloxacin exceeded 20 micrograms ml-1. On days 2-7, the mean percentage 12 h renal elimination of norfloxacin was 18.6 +/- 1.47 (mean of 82 separate observations). Norfloxacin 400 mg twice daily was well tolerated in this group of elderly patients and produced adequate antimicrobial concentrations in urine.

Aged↗
PubMed1988

Characterization and metabolism of canine proximal tubules, thick ascending limbs, and collecting ducts in suspension.

Preparations of distinct nephron segments were obtained from dog kidneys by collagenase treatment. Four morphologically different tissues were isolated: glomeruli, proximal tubules, thick ascending limbs, and papillary collecting ducts. Each segment possessed a characteristic assay of membrane-bound and cytoplasmic enzymes. Specific metabolic characteristics also were found: gluconeogenesis and ammoniagenesis in proximal tubules, glycolytic aerobic metabolism in thick ascending limbs, and glycolytic anaerobic metabolism in papillary collecting ducts. The assay of Na+ -K+ ATPase, H+ -ATPase, and Ca2+ -ATPase activities in these nephron segments demonstrated a specific enrichment of Na+ -K+ ATPase in thick ascending limbs, and of H+ -ATPase in proximal tubules and papillary collecting ducts. Tubular respiration in the absence or presence of ouabain, 1,3-dicyclohexylcarbodiimide, or furosemide demonstrated that the respiration of each segment could be correlated to the activity of specific ion motive ATPases. Furthermore, a tight coupling between ion transport, ATP turnover, and substrate oxidation was demonstrated. These isolated tubular structures are thus viable and capable of transepithelial transport. Our preparation provides large amounts of defined population of tubules and are thus useful for the study of biochemical and functional heterogeneity along the nephron.

Adenosine Monophosphate↗