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S Leach

Publications and source records attributed to S Leach.

34 records · Page 2Linked to original sources

Analysis of coccal cell formation by Campylobacter jejuni using continuous culture techniques, and the importance of oxidative stress.

Campylobacter jejuni is an important human gastrointestinal pathogen. In hostile environments it may adapt its physiology to prolong survival, potentially including the adoption of a viable, non-culturable form and a change to coccal cell morphology. By independently controlling the individual parameters of continuous cultures of Camp. jejuni (e.g. pH, nutrient limitation, growth rate, etc.), coccal cell formation was shown to be elicited only be high oxygen tension in conjunction with reduced carbon concentration. Electron microscopy revealed degradative changes in these cells. This occurred as a transient response over 48 h coincident with a large reduction in maximum growth rate and viable count. Kinetic analysis of the biomass reduction of the cultures demonstrated that significant underlying growth was maintained, with the subsequent selection of a more oxygen-resistant population of cells and reversion to spiral morphology. Coccal cells appear to be predominantly a degenerate form of Camp. jejuni resulting from oxidative damage. While some of these coccal cells may recover, the more interesting population of cells is probably that which retains, or regains, spiral morphology during adaptation to oxidative stress.

Campylobacter jejuni↗

Functional characterization of alternatively spliced human SERCA3 transcripts.

The sarcoplasmic (or endoplasmic) reticulum Ca2+-ATPase (SERCA)-3 has been implicated in the possible dysregulation of Ca2+ homeostasis that accompanies the pathology of hypertension and diabetes. We report the molecular cloning of two alternatively spliced transcripts from the human SERCA3 gene, ATP2A3, that encode proteins that differ at their carboxy termini by 36 amino acids. SERCA3 transcripts were most abundantly expressed in lymphoid tissues, intestine, pancreas, and prostate. The two human SERCA3 proteins encoded by alternatively spliced transcripts were recognized by the monoclonal antibody PL/IM430 and demonstrated Ca2+ uptake and ATPase activity with an apparent Ca2+ affinity 0.5 pCa unit lower than that of other SERCA gene products. The subcellular distribution of SERCA3 protein was indistinguishable from that of SERCA2b, with expression in the nuclear envelope and in the endoplasmic reticulum throughout the cell. Two variant SERCA3 constructs, huS3-I and huS3-II, were isolated that encode proteins with three amino acid differences: Ala-673 (in huS3-I) substituted for Thr (in huS3-II), Ile-817 substituted for Met, and an insertion of Glu-994. huS3-I displayed a 10-fold lower capacity to transport Ca2+ than huS3-II.

Alternative Splicing↗

Changes with growth rate in the membrane lipid composition of and amino acid utilization by continuous cultures of Campylobacter jejuni.

Methods and media (defined and complex) are described which permit studies designed to determine the influence of single environmental factors on the survival and virulence of Campylobacter jejuni. The effect of growth rate on selected physiological traits (amino acid utilization, membrane lipid composition, motility, cell morphology) was studied in continuous culture. In both media, growth was at the expense of amino acid (serine, aspartate, glutamate and proline) catabolism. Slow growth in the complex medium shifted amino acid utilization from more (serine and aspartate) to less preferred substrates (glutamate, proline and possibly amino acids from the proteolysis of peptones). Low growth rates promoted the conversion of unsaturated 11-octadecenoic acid substituted phosphatidyl ethanolamines to corresponding 11-methylene substituted species, a feature correlated with stationary phase and exposure to environmental stress in other organisms. During continuous growth, cells lost motility although they still possessed flagella. Slow growth resulted in longer cells. Future studies will investigate the independent effects of nutrient stress and growth rate on the virulence and persistence of cells.

Acetates↗

In my time: scenes of scientific life.

A narrative account of the ingredients in the making of a young scientist, his wartime science in England, and subsequent career in France, where, starting in molecular electronic spectroscopy, he has grown older and has expanded his horizons to address problems of astrophysical, nonlinear optical, and biological interest, using, with the aid of many good scientists, a variety of techniques, mainly of optical and mass spectroscopies and with synchrotron radiation as an important excitation source. He has plans to continue.

Journal Article↗

Degradation of Altosid XR briquets under field conditions in Minnesota.

Incomplete degradation of control products and subsequent carryover of active ingredient to the next year are operational concerns for control agencies. Altosid XR briquets were weighed before and after 6-18 months of exposure in temporary wetlands to determine the rate of physical degradation of the briquets. Degradation rate was influenced mainly by the number of days a briquet remained under water. The average briquet degraded to 19% of its weight within 150 days of immersion and was completely degraded after 1.5 yr under water. The active ingredient (methoprene) content of briquets declined faster among those exposed to air and more slowly among those that were immersed.

Biodegradation, Environmental↗

Twenty-four hour urinary nitrate excretion in 48 populations from 30 countries: an ECP-INTERSALT collaborative study.

BACKGROUND: There is considerable interest in the possible role of nitrate in gastric carcinogenesis, but little information on nitrate intake around the world. This is the first study to give comprehensive standardised data on nitrate excretion as a marker of intake, using 48 worldwide population samples. METHODS: Urinary nitrate excretion has been shown to be a valid measure of nitrate intake in people under 50. This report presents data on 24-hour urinary nitrate excretion from urine collections obtained in the INTERSALT study, based on random samples of men and women aged 20-49 from each of 48 population samples in 30 countries. RESULTS: There was large variation in urinary nitrate excretion both within and between samples; within-sample (individual) distributions tended to be skewed towards higher values. Median values of the samples ranged from 0.42 mmol/day (Labrador, Canada) to 3.52 (Beijing, People's Republic of China) in men and 0.44 mmol/day (Colombia) to 3.44 (Beijing) in women. Overall, median values were higher in men than women by 11% on average (higher in men in 37 of 48 population samples). Comparison by geographical region of median values for men and women combined showed relatively low values in the samples in North America and Northern Europe (range 0.46-0.88 mmol/day), slightly higher values in Western Europe and Africa (0.68-1.11), and intermediate to high values in Southern Europe, Eastern and Central Europe and India (0.86-2.47). The highest median values were found in the Far Eastern samples (up to 3.48). Median values in the Central and South American samples ranged from 0.48 mmol/day (Colombia) to 1.37 (Xingu Indians of Brazil, and Argentina). CONCLUSIONS: For the first time, these data give standardized information on urinary nitrate excretion from different geographical regions of the world, and provide a basis for the further exploration of the role of nitrate in the aetiology of disease in human populations.

Adult↗

Schizophrenia-associated chromosome 11q21 translocation: identification of flanking markers and development of chromosome 11q fragment hybrids as cloning and mapping resources.

Genetic linkage, molecular analysis, and in situ hybridization have identified TYR and D11S388 as markers flanking the chromosome 11 breakpoint in a large pedigree where a balanced translocation, t(1;11)(q43;q21), segregates with schizophrenia and related affective disorders. Somatic cell hybrids, separating the two translocation chromosomes from each other and from the normal homologues, have been produced with the aid of immunomagnetic sorting for chromosome 1- and chromosome 11-encoded cell-surface antigens. The genes for two of these antigens map on either side of the 11q breakpoint. Immunomagnetic bead sorting was also used to isolate two stable X-irradiation hybrids for each cell-surface antigen. Each hybrid carries only chromosome 11 fragments. Translocation and X-irradiation hybrids were analyzed, mainly by PCR, for the presence of 19 chromosome 11 and 4 chromosome 1 markers. Ten newly designed primers are reported. The X-irradiation hybrids were also studied cytogenetically, for human DNA content, by in situ Cot1 DNA hybridization and by painting the Alu-PCR products from these four lines back onto normal human metaphases. The generation of the translocation hybrids and of the chromosome 11q fragment hybrids is a necessary preliminary to determining whether a schizophrenia-predisposition gene SCZD2 is encoded at this site.

Animals↗

Nitrate and N-nitrosoproline excretion in two Italian regions with contrasting rates of gastric cancer: the role of nitrate and other factors in endogenous nitrosation.

Exposure to nitrate and propensity for endogenous nitrosation were examined in 80 healthy males, aged 25-40 years, residing in areas of Italy with long-standing high (Florence) and low (Cagliari) rates of gastric cancer. Nitrate exposure was assessed by measurement of urinary nitrate excretion over 12 hr, and endogenous nitrosation was assessed using the N-nitrosoproline test (NPRO-test). Our hypothesis was whether the geographic variation in cancer rate correlated with nitrate exposure or nitrosating ability. Exposure to background sources of NPRO was significantly higher in the high-risk subjects (phi = 0.04) whereas no differences were found in exposure to nitrate or in urinary NPRO levels after L-proline loading (test NPRO levels). The regional difference in test NPRO was almost completely accounted for by background NPRO exposure. Examination of individual rather than grouped data revealed that exposure to nitrate was a major factor in NPRO formation. No other factors studied (age, dietary-questionnaire-assessed intake of anti-oxidant vitamins) had a significant effect. Geographical variation in gastric cancer risk did not, therefore, correlate with either nitrate exposure or propensity for endogenous nitrosation of L-proline.

Adult↗

N-nitrosoproline excretion in the presence and absence of gastric disease.

N-nitrosoproline (NPRO) excretion, an indicator of endogenous nitrosation, was measured in a group of hospital inpatients who were identified by endoscopy and gastric biopsy as either having gastric lesions or having healthy stomachs. NPRO was assayed in background 24-hour urine samples and samples collected after loading doses of nitrate and L-proline. The presence of gastric lesions was associated with altered gastric pH and concomitant changes in gastric juice nitrate and nitrite concentration. Gastric juice pH increased with increasing severity of gastric disease (P = 0.031) and patients with normal stomachs had a lower gastric pH than those with chronic atrophic gastritis (CAG) (3.0 vs. 6.5, P = 0.017). The changes in gastric juice nitrate concentration were in the reverse direction (P = 0.002 for trend) with normal patients having higher mean levels than CAG patients (12.7 vs. 5.5 micrograms/ml, P less than 0.0001). Nitrite concentration increased with severity of gastric disease but the results were not significant (normal, 82.9 vs. CAG, 223.4 ng/ml, P = 0.069). No association was found between the presence of gastric lesions and increased urinary NPRO excretion. Mutagenic activity was not detected in any of the gastric juice samples.

Adult↗

Use of a modified N-nitrosoproline test to show intragastric nitrosation in patients at risk of gastric cancer.

Intragastric nitrosation has been implicated in the pathogenesis of gastric cancer and in precancerous conditions such as pernicious anaemia and the post-gastrectomy state. Intragastric nitrosation was assessed in at-risk patients by N-nitrosoproline (NPRO) excretion using both a conventional and a modified test. Twenty-four hour urinary excretion of NPRO was measured after oral administration of sodium nitrate (300 mg) and L-proline (500 mg) as an indirect indicator of intragastric nitrosation. In the conventional test no differences in intragastric nitrosation were found between at-risk patients and controls. In the modified test the loading dose of sodium nitrate was omitted and urinary NPRO levels were found to be significantly increased in Polya partial gastrectomy patients (P = 0.003) and post-vagotomy patients (P = 0.03) compared to controls. In pernicious anaemia patients NPRO levels were also higher than in controls but just failed to reach statistical significance. This study has confirmed that hypochlorhydria results in increased intragastric nitrosation, thus facilitating the formation of potentially carcinogenic N-nitroso compounds.

Adult↗

N-nitrosoproline excretion in patients with gastric lesions and in a control population.

N-Nitrosoproline (NPRO) excretion was measured in a group of hospital in-patients who were identified as either bearing gastric lesions or having apparently healthy stomachs. NPRO was assayed in background 24-h urine samples and then in urines collected after loading doses of nitrate and proline. The presence of gastric lesions was associated with altered gastric juice pH and nitrite concentration, but not with NPRO excretion. The significance of NPRO excretion as a marker of endogenous nitrosation is dependent on the interpretation of this result.

Adult↗

Adverse drug reactions: an investigation on an acute geriatric ward.

A total of 521 patients consecutively admitted to an acute geriatric unit were kept under surveillance by one observer during their stay. All drugs given to them and the occurrence of adverse events were recorded. One hundred and seventeen adverse drug reactions occurred in 94 patients representing 18.8% of the 500 patients receiving drugs. Thirteen of these reactions were considered severe. Each patient received an average of 6.1 drugs, not necessarily simultaneously. Altogether 212 different drug preparations were used. Diamorphine and insulin had the highest adverse reaction rates, diamorphine having the highest risk of a severe adverse reaction. Antibiotics and diuretics caused the most adverse reactions, and were by far the most commonly prescribed drugs (26.5% of the sample). Of the patients receiving eight or more drugs, 41% suffered an adverse drug reaction.

Age Factors↗

Significant endogenous synthesis of nitrate does not appear to be a feature of influenza A virus infection.

There is much concern about the role of nitrate in the formation of carcinogenic N-nitroso compounds. There has been renewed interest in the endogenous formation of nitrate arising as a host response to infection. This study was designed to investigate whether the large increases in nitrate excretion rate reported (6-15-fold) for certain infectious diseases is also a feature of systemic influenza infections. Volunteers were challenged either with an attenuated strain of influenza A virus or with saline; and excreted nitrate was measured in subsequent 24-h urine samples. Both with and without adjustment for potential confounding by dietary and other factors, it was clear that neither mild nor moderate influenza A virus infection resulted in substantial endogenous nitrate biosynthesis since all the variation in urinary nitrate excretion observed was within the range of normal daily fluctuations. It remains possible that a stronger and more consistent nitrate excretion response might be observed in other infectious illnesses with greater systemic disturbance.

Adult↗