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M J Smith

Publications and source records attributed to M J Smith.

At least 181 records · Page 10Linked to original sources
PubMed1994

Faecal dry weight and potassium are related to faecal sodium and plasma aldosterone in rats chronically fed on varying amounts of sodium or potassium chlorides.

Recent studies have shown that faecal residue (dry weight) and Na and K increase with increasing levels of dietary fibre, an effect which may be related to unstirred layers that slow absorption and the flow rate of chyme through the gastrointestinal tract. Salts of Na are the primary osmotic components of chyme and influence both retention of fluid in the bowel and transit of fluid from the small to the large intestine. The present study examines the chronic effects of dietary Na and K intake on faecal Na, K and residue excretion. Male Sprague-Dawley rats were given 12-13 g feed/d (control (g/kg): Na 4, K 8.5) for 1 week, followed by a 4-week period where Na or K intake was altered (0.01-3 times control levels). These diets altered chronic (> 1 week) faecal residue excretion and affected Na and K excretion by 8-, 310- and 2100-fold respectively. Low dietary Na reduced faecal Na and residue; K excretion was doubled during week 1, but fell over weeks 2-4 despite a 4-5-fold increase in plasma aldosterone. Chronic high dietary Na increased faecal Na, residue and K despite a 60% decrease in plasma aldosterone. Chronic low dietary K decreased faecal Na, K and residue and plasma aldosterone. Chronic high dietary K did not alter faecal Na and K despite increased faecal residue and a 4-5-fold increase in plasma aldosterone. Faecal water was unchanged by diet, paralleling changes in faecal residue. Analyses of the results provide systematic models of chronic regulation of faecal Na, K and residue excretions. When plasma aldosterone is low (< 160 ng/l), weekly faecal residue excretion is equal to 3.6 g (fibre intake was 2.6-2.7 g/week)+2.6 g/mmol Na, and K excretion is equal to 0.55 mmol/mmol Na. When plasma aldosterone is high (> 1500 ng/l) weekly faecal residue excretion is equal to 2.3 g + 2.6 g/mmol Na, and K excretion is equal to 0.7 mmol/week + 0.55 mmol/mmol Na.

Aldosterone↗
PubMed1994

Surfactant protein A-directed toxin gene kills lung cancer cells in vitro.

Human surfactant protein A (SPA) expression is considered a marker of respiratory epithelial differentiation. Non-small cell lung cancers (NSCLC) are respiratory epithelial derivatives, and it was previously shown that a minority of these cancers expressed SPA, presumably a consequence of their respiratory epithelial origin. In the studies reported here, SPA-I gene transcriptional regulatory sequences were localized to a 2.75-kb genomic 5'-flanking region fragment obtained by screening a human genomic library. The 2.75-kb fragment was used to direct a luciferase coding sequence transcriptionally within a plasmid construct. In plasmid transduction experiments, the SPA-directed luciferase plasmid produced significant luciferase activity in the SPA-expressing NSCLC cell line, H441, but only background levels in the non-SPA-expressing A549 cells. Because Northern blot analysis of resected NSCLC showed that the majority expressed SPA, an SPA-transcriptional targeting strategy was investigated using chimeric toxin genes comprising the coding sequence for herpes simplex virus thymidine kinase (HSV-TK) under transcriptional control of SPA or SV40 regulatory sequences. As expected, transduction of the constitutive, SV40-directed plasmid followed by ganciclovir treatment reduced numbers of both the A549 and H441 cells. In contrast, the SPA-directed plasmid reduced only the SPA-expressing H441 cells and had no significant effect on the A549 cells. The results of these in vivo experiments suggest the concept of transcriptionally directing toxin genes with SPA can produce targeted toxicity in NSCLC.

Carcinoma, Non-Small-Cell Lung↗
PubMed1994

MIC2R: a transcribed MIC2-related sequence associated with a CpG island in the human pseudoautosomal region.

Sequences related to exons 1, 4 and 5 of the human pseudoautosomal gene MIC2 have been detected on the X and Y chromosomes of humans and other primate species. Isolation of these sequences has defined a new transcribed locus, MIC2R (MIC2-related) which is associated with the second most proximal CpG-rich island in the human pseudoautosomal region. Genomic sequences from the MIC2R locus show that it is composed of a single sequence related to exon 1 and at least four tandem copies of sequences related to exons 4 and 5 of MIC2. Comparison of the four exon 4- and 5-related sequences suggest that they are the result of sequential duplication of a 2.8 kb region during evolution. Transcripts from the MIC2R locus have been detected in all tissues analysed and a number of different transcripts appear to be generated by alternative RNA splicing. However, as none of the transcripts analysed to date contain a significant open reading frame, the function of the MIC2R locus remains unknown.

12E7 Antigen↗
PubMed1994

Hypoglycemia counterregulation in elderly humans: relationship to glucose levels.

This study was designed to define the effect of human aging on hypoglycemia counterregulatory mechanisms. A hyperinsulinemic (2 mU.kg-1.min-1) glucose clamp procedure was used to control glucose and insulin levels during stepwise lowering of plasma glucose. Counterregulatory hormones, hepatic glucose production (HGP), glucose utilization, and symptoms of hypoglycemia were studied in 13 healthy young [age 24 +/- 1 (SE) yr] and 11 healthy old (age 65 +/- 1 yr) nondiabetic volunteers on two occasions: 1) at matched euglycemia and 70 and 60 mg/dl (study 1) and 2) at matched euglycemia and 60 and 50 mg/dl (study 2). The old had consistently lower epinephrine (P < 0.005), glucagon (P < 0.02), cortisol (P < 0.05), and pancreatic polypeptide (P < 0.02) responses at the 60-mg/dl glucose step in study 1. However, these differences were no longer detectable at the more severe hypoglycemic stimulus of 50 mg/dl in study 2. A consistent increase in HGP occurred in both groups only at the 50-mg/dl glucose step (study 2) and was not different between young and old. There were also no differences in symptom responses between young and old. In summary, we found that elderly individuals have a subtle impairment of the glucose counterregulatory response during moderate hypoglycemia, but this impairment is no longer detectable during more severe hypoglycemia.

Adult↗
PubMed1994

Abnormal insulin secretion, not insulin resistance, is the genetic or primary defect of MODY in the RW pedigree.

Maturity-onset diabetes of the young (MODY) is a form of non-insulin-dependent diabetes mellitus (NIDDM) associated with autosomal-dominant inheritance. In the RW pedigree, MODY is associated with polymorphic DNA markers on chromosome 20q. To determine the early abnormalities of insulin action and insulin secretion in MODY, we studied nondiabetic members of the RW pedigree with and without the gene marker. Six nondiabetic marker-negative and 5 nondiabetic marker-positive members of the RW pedigree were studied, as were 4 diabetic marker-positive family members. Unrelated, young, healthy subjects served as comparison groups. Insulin action and insulin secretion were assessed with a frequently sampled intravenous glucose tolerance test. Insulin secretion was further assessed during constant glucose infusion by deconvolution of plasma C-peptide and by pulse analysis. The nondiabetic marker-positive group had normal sensitivity to insulin and unimpaired acute insulin response to intravenous glucose (AIRglu). However, the nondiabetic marker-positive group had decreased mean plasma C-peptide concentration and reduced absolute amplitude of insulin secretory oscillations during prolonged glucose infusion. These responses to prolonged glucose infusion were similar to those observed in the diabetic group. No alterations of insulin secretion were observed in the nondiabetic marker-negative family members. Deranged and deficient insulin secretion, and not insulin resistance, appears to be the genetic or primary abnormality that characterizes nondiabetic individuals who are predisposed to MODY in the RW pedigree.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Mini-dose (1-microCi) 14C-urea breath test for the detection of Helicobacter pylori.

OBJECTIVES: To develop and evaluate a mini-dose (1-microCi) 14C-urea breath test (UBT), using a simplified protocol. METHODS: Fasting patients (n = 95) were given a drink of 1 microCi (37 kBq) of 14C-urea. Samples of breath carbon dioxide (2 mmol) were collected at 10, 20, and 30 min later by trapping in hyamine solution; 14C activity was measured by liquid scintillation counting. Results were expressed as "CO2 recovery," i.e., [(% of administered dose recovered/mmol CO2 trapped) x body weight (kg)]. Reproducibility of the test was assessed by repeat studies on two consecutive days in 11 volunteers. All breath test results were compared with culture for Helicobacter pylori. In 27 patients, results also were compared with 13C-urea breath test (European protocol). RESULTS: Using receiver operator characteristic (ROC) analysis, we selected a cut-off value of 0.55 at 20 min to separate those positive and negative for H. pylori. Sensitivity and specificity were 98% and 87%, respectively. Among four patients with negative culture but positive 14C-breath tests, three had evidence of infection by serology or 13C-UBT. Assuming that these three were genuinely positive, the recalculated specificity improved to 97%, sensitivity remaining at 98%. The reproducibility of the test was good, with only a minor day-to-day variation. Concordance with the 13C-UBT was excellent: there was 100% agreement in the diagnostic classification of all 27 patients (19 positive, eight negative). CONCLUSIONS: The mini-dose 14C-urea breath test has a high diagnostic accuracy (sensitivity 98%, specificity 97%) with minimal radiation exposure. It is simple, rapid, and convenient for a busy general hospital.

Breath Tests↗
PubMed1994

Anticholinergic premedication for fibreoptic bronchoscopy.

Atropine is routinely used as part of the premedication regimen for fibreoptic bronchoscopy. This study was performed, firstly, to evaluate the effect of anticholinergic agents on the ease of bronchoscopy, haemodynamic parameters and patient comfort during the procedure; and secondly, to compare atropine with glycopyrrolate, a newer acetylcholine antagonist which is claimed to cause less tachycardia and sedation, whilst suppressing salivation more effectively. One hundred and ninety consecutive patients were randomly allocated to three treatment groups: diazepam 5 mg; diazepam 5 mg + atropine 600 micrograms; and diazepam 5 mg + glycopyrrolate 300 micrograms. Diazepam was given orally one hour before bronchoscopy, and glycopyrrolate/atropine intramuscularly 30 min before bronchoscopy. All patients received thalamonal intravenously, lignocaine gel into one nostril, and lignocaine by transtracheal injection just prior to the procedure. The incidence of bronchoscopy related haemodynamic problems was similar in all three groups. Troublesome coughing, as observed by the operator, was less frequent with glycopyrrolate (control 51%, atropine 42%, glycopyrrolate 30%), as was patient movement (40%, 32%, 19%, respectively). Uncomfortable dryness of the mouth was most common with glycopyrrolate (37%, 32%, 66%, respectively), but overall assessment of discomfort, and the number of patients who would agree to a repeat bronchoscopy (73%, 76%, 70%, respectively) were very similar in all three groups. In conclusion, the differences between the three groups were slight. Glycopyrrolate made the bronchoscopy slightly easier for the operator because of significantly improved cough and movement suppression, though atropine was marginally preferable in terms of patient comfort.

Administration, Oral↗
PubMed1993

The isolation and identification of 6-hydroxycyclohepta-1,4-dione as a novel intermediate in the bacterial degradation of atropine.

Growth of Pseudomonas AT3 on the alkaloid atropine as its sole source of carbon and nitrogen is nitrogen-limited and proceeds by degradation of the tropic acid part of the molecule, with the metabolism of the tropine being limited to the point of release of its nitrogen. A nitrogen-free compound accumulated in the growth medium and was isolated and identified as 6-hydroxycyclohepta-1,4-dione. This novel compound is proposed as an intermediate in tropine metabolism. It served as a growth substrate for the organism and was also the substrate for an NAD(+)-linked dehydrogenase present in cell extracts. The enzyme was induced during the tropine phase of diauxic growth on atropine or during growth on tropine alone.

Alcohol Oxidoreductases↗
PubMed1993

The phylogeny of echinoderm classes based on mitochondrial gene arrangements.

Previous analyses have demonstrated that, among the echinoderms, the sea star (class: Asteroidea) mitochondrial genome contains a large inversion in comparison to the mitochondrial DNA of sea urchins (class: Echinoidea). Polymerase chain reaction amplification, DNA cloning, and sequencing have been used to examine the relationships of the brittle stars (class: Ophiuroidea) and sea cucumbers (class: Holothuroidea) to the sea stars and sea urchins. The DNA sequence of the regions spanning potential inversion junctions in both brittle stars and sea cucumbers has been determined. This study has also revealed a highly modified tRNA cluster in the ophiuroid mitochondrial genome. Our data indicate mitochondrial gene arrangement patterns that group the sea cucumbers with sea urchins and sea stars with brittle stars. This use of molecular characters clarifies the relationships among these classes.

Amino Acid Sequence↗
PubMed1993

Aldosterone secretion and the mechanism of potassium adaptation in rats.

In order to better understand the cellular mechanism of potassium (K+) adaptation, the sensitivity of aldosterone secretion to acute changes in extracellular K+ concentration was studied in freshly dissected adrenal capsules of rats adapted to diets of high or low K+ content, of rats adapted to low or high sodium (Na+) diets, and also of control rats. In control tissues, the aldosterone secretion from the capsules of an individual animal averages 0.44 +/- 0.05 nmol/h, increasing 4.4-fold between 2 and 8 mM K+ but decreasing between 8 and 10 mM K+. Although a high K+ diet increases aldosterone secretion by only 34% at 4 mM K+, the rate of secretion increases 3.7-fold more steeply than control as the K+ concentration increases. This change is equivalent to a parallel 3.1-fold increase in the effective number of T- and L-type calcium (Ca2+) channels, accompanied by a 1.3-fold increase in the K(+)-insensitive rate of aldosterone secretion. In contrast, after Na+ restriction, aldosterone secretion is about 3 times the control rate for all K+ concentrations tested, equivalent to an increase in the basal rate and the effective number of L-channels. Thus, the alteration in the number of effective T-channels is specific to diets of increased K+ content, not simply an effect of increased secretory capacity. After a low K+ diet, aldosterone secretion is 18% of control at 4 mM K+ and changes little with the K+ concentration, consistent with a 94% to 96% decrease in the effective number of T- and L-channels plus a 77% decrease in the K(+)-insensitive rate of aldosterone secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed1993

Children with disabilities and the Children Act: who will assess their needs?

The Children Act focuses attention on meeting the assessed needs of children with disabilities. General practitioners (GPs) and Community Child Health (CCH) doctors in one health district were asked by postal questionnaire who it was who currently assessed such needs and who would do so in the future. The involvement of GPs (15) varied from none (1) to regular reassessment (3). Nearly all (14) treated acute illnesses but educational assessments were assigned to CCH doctors. Community doctors (9) had a clearer idea of their role including regular reassessment (9), education assessment (9) and interagency liaison (3). Both groups complained of poor communication with each other and with hospital services. To fulfil the requirements of the Children Act, community child health services, family health services authorities and district health authorities will have to specify how and by whom children with disabilities are identified and assessed. Arrangements will vary according to local service development. These arrangements, and the resulting liaison with other agencies, should be specified in National Health Service contracts, thus improving communication and cooperation.

Child↗
PubMed1993

Alteration within a discrete region of the H-2Ld alpha 1 helix upon association with human beta 2 microglobulin.

The utilization of the beta 2-microglobulin (B2m) exchange assay allowed for the association of H-2Ld with human B2m. Upon association with H-2Ld, human B2m induces structural alterations in H-2Ld that appear dependent upon xenogeneic B2m amino acid sequence variability. In this regard, xenogeneic B2m exchange is used as a tool to induce structural alterations in class I as a means of analysing the structural-functional relationship of B2m/class I association. Incorporating H-2Ld site-directed mutants into the experimental approach provided strong evidence that B2m makes indirect contact with discrete class I specific amino acid positions located in the helical region of the alpha 1 domain.

Amino Acid Sequence↗
PubMed1993

The genomic organisation of the human pseudoautosomal gene MIC2 and the detection of a related locus.

The human pseudoautosomal gene MIC2 encodes a 185 amino acid cell surface antigen recognised by the monoclonal antibody 12E7. The gene is abundantly expressed in all tissues tested and a role in cell-cell interactions has been suggested. We describe here the isolation of 95kb of genomic DNA encompassing the entire MIC2 gene. The gene is 52kb in size and orientated towards the centromere. As predicted by previous genetic studies, the 5' end of MIC2 is located 95kb from the pseudoautosomal boundary and confirming that the elevated rate of recombination in pseudoautosomal region is continuous up to the boundary. The gene is divided into ten exons which show correlation with predicted domains of the protein and are considerably smaller than the average for mammalian genes. Evolutionary studies indicate that the gene can be detected by DNA hybridisation only in primates, however genomic probes for both exons 1 and 5 detect related locus present on both the human X and Y chromosomes.

12E7 Antigen↗
PubMed1993

Histocompatibility antigens and La Crosse encephalitis.

Major histocompatibility complex antigens (HLA-ABC and -DR loci) on lymphocytes from 79 patients with La Crosse encephalitis were compared with those of 69 control subjects. Nine patients (11%) and none of the control population had HLA-B49 (P < .01, uncorrected for multiple comparisons). Of La Crosse encephalitis patients with acute-phase seizures, only 2 (7%) were positive for HLA-DR5, whereas 16 (37%) of nonseizure patients were positive for that antigen (P < .025). These findings suggest that susceptibility and complications associated with this disease may have an immunogenetic component.

Encephalitis Virus, California↗
PubMed1993

Intraspecific DNA sequence variation of the mitochondrial control region of white sturgeon (Acipenser transmontanus).

Intraspecific sequence variation in the D-loop region of mtDNA in white sturgeon (Acipenser transmontanus), a relict North American fish species, was examined in 27 individuals from populations of the Columbia and Fraser rivers. Thirty-three varied nucleotide positions were present in a 462-nucleotide D-loop sequence, amplified using the polymerase chain reaction. Bootstrapped neighbor-joining and maximum-parsimony trees of sequences from 19 haplotypes suggest that the two populations have recently diverged. This is consistent with the hypothesis that the Columbia River, a Pleistocene refugium habitat, was the source of founders for the Fraser River after the last glacial recession. On the basis of a divergence time of 10-12 thousand years ago, the estimated substitution rate of the white sturgeon D-loop region is 1.1-1.3 x 10(-7) nucleotides/site/year, which is comparable to rates for hypervariable sequences in the human D-loop region. Furthermore, the ratio of mean percent nucleotide differences in the D-loop (2.27%) to that in whole mtDNA (0.54%, as estimated from restriction-enzyme data) is 4.3, which is similar to the fourfold-to-fivefold-higher substitution rate estimated for the human D-loop. The high nucleotide substitution rate of the hypervariable region indicates that the vertebrate D-loop has potential as a genetic marker in molecular population studies.

Animals↗
PubMed1993

Physical, subjective, and social availability: their relationship to alcohol consumption in rural and urban areas.

The alcohol availability literature indicates that under some conditions, physical availability is positively associated with per capita alcohol consumption. Smart (1980) suggested that at the individual level, subjective and social aspects of availability may mediate and outweigh the influence of physical availability. The study described here examined the simultaneous effects of physical, subjective, and social availability on alcohol consumption. Standardized telephone interviews were conducted with 781 adult drinkers. As hypothesized, physical availability was not a significant multivariate predictor of alcohol consumption for residents of high, medium, and low alcohol outlet density counties in Michigan (USA). Subjective and social availability indicators were significant predictors of alcohol consumption. Similar patterns of results were found in multiple regression analyses for blacks and whites and women and men, although blacks and women consumed less alcohol than did whites and men. The theoretical and practical implications of these results are discussed.

Adult↗
PubMed1993

Chemotactic signalling in Rhodobacter sphaeroides requires metabolism of attractants.

Rhodobacter sphaeroides showed chemotaxis towards L-alanine but not towards the analog 2-aminoisobutyrate. 2-Aminoisobutyrate and alanine were shown to share a common transport system, but 2-aminoisobutyrate was not metabolized. Chemotaxis towards alanine was inhibited by structurally unrelated metabolites, suggesting cross-inhibition by common metabolic intermediates.

Alanine↗