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Biomedical subjects

M Jarvis

Publications and source records attributed to M Jarvis.

At least 37 records · Page 2Linked to original sources
PubMed1992

Effect of transdermal nicotine patches on cigarette smoking: a double blind crossover study.

The effect of transdermal nicotine patches on ad libitum cigarette smoking was examined in 30 subjects by measuring behavioural, biochemical and subjective aspects of smoking during a week of smoking without patches, and then a week each of nicotine and placebo patches in a randomised double blind crossover design. While wearing nicotine patches the subjects did not reduce the number of cigarettes smoked, but their expired carbon monoxide was reduced by 14%, they obtained less satisfaction from their cigarettes, and reported fewer and weaker urges to smoke. Down-regulation of nicotine intake from cigarettes was imprecise, such that when subjects wore nicotine patches their post-cigarette plasma nicotine concentration increased to an average of 45 ng/ml compared with 37 ng/ml in both no patch and placebo patch conditions. As the nicotine patches produced a plasma nicotine concentration of 15.9 ng/ml in abstinent subjects, this suggests a 22% reduction in nicotine intake from cigarettes while wearing nicotine patches. No serious symptoms of nicotine overdose were reported. It is suggested that the continuous absorption of nicotine from the patch may cause a build-up of acute tolerance to both toxic and pleasant subjective effects from smoking.

Administration, Cutaneous↗
PubMed1992

A prospective study of obesity, lipids, apolipoproteins and ischaemic heart disease in women.

The aim of the study was to examine the relationships of obesity, lipids and apolipoproteins with the risk for subsequent ischaemic heart disease in middle-aged women, using a case-control study nested within a cohort study. A total of 3634 women aged 26-88 were recruited in Guernsey between 1977 and 1985 and followed until June 1986 by abstraction of their general practitioners' records. Fifty-one cases of incident ischaemic heart disease (11 myocardial infarction, 40 angina) were identified. For each case up to 4 controls were selected, matched for age and date at recruitment. Odds ratios for the development of ischaemic heart disease in the middle and upper thirds of the distribution for each variable in the controls, relative to the lowest third (and two-sided P-values for linear trends), were: 3.0, 2.6 (0.015) for Quetelet's index; 3.3, 5.1 (0.003) for total cholesterol; 0.5, 0.6 (0.102) for apolipoprotein A-I; 1.8, 2.4 (0.015) for apolipoprotein B; 1.3, 2.1 (0.155) for apolipoprotein(a). The increased risks associated with increased Quetelet's index and total cholesterol were independent of each other and these variables were more strongly related to myocardial infarction than to angina. The relationships of risk with serum cotinine, fatty acids, dehydroepiandrosterone sulphate and sex hormone binding globulin were weak and did not approach statistical significance.

Adult↗
PubMed1991

Adolescent smokers seen in general practice: health, lifestyle, physical measurements, and response to antismoking advice.

OBJECTIVE: To compare physical, lifestyle, and health characteristics of adolescent smokers and non-smokers and their initial response to anti-smoking counselling. DESIGN: Adolescents aged 13, 15, and 17 years were identified from age-sex registers and invited by letter for a general practice health check. SETTING: Three general practices in the MRC general practice research framework. MAIN OUTCOME MEASURES: Blood pressure, body mass index, saliva cotinine concentration, peak flow rate, alcohol consumption, exercise, duration of sleep, and stated persistent health problems. RESULTS: 73% of the adolescents (491) attended for the health check. A total of 68 (14%) were regular smokers. By age 17 those who smoked regularly had a significantly lower systolic blood pressure than those who had never smoked regularly (by 6 mm Hg; p = 0.025) despite a significantly higher body mass index (by 1.5; p <0.001) [corrected]. Cotinine concentrations increased with smoking exposure, from 0.7 ng/ml when no family member smoked to 155 ng/ml in active smokers of six or more cigarettes a week. Significantly more regular smokers than never regular smokers drank greater than or equal to 8 g alcohol a day (chi 2 = 15.2 adjusted for age and sex p less than 0.001); regular smokers exercised less (1.0 hrs/week in boys and 0.8 hrs/week in girls v 3.4 hrs/week in boys and 2.2 hrs/week in girls; p less than 0.001) and slept less (8.0 hrs/night v 8.5 hrs/night at age 17; p less than 0.005). Persistent health problems, mostly asthma or allergic symptoms, were reported by 25% (17/68) of the smokers and 16% (60/381) of the non-smokers. Of the smokers given counselling, 60% (26/43) made an agreement with the practice doctor or nurse to give up smoking. CONCLUSION: General practice is an appropriate setting for adolescents to receive advice on healthy lifestyle, which should not focus solely on smoking.

Adolescent↗
PubMed1991

Risk of strangulation in groin hernias.

Although the elective repair of groin hernias is advised to prevent strangulation, the likelihood of this complication occurring is unknown. To quantify this risk, the cumulative probability of strangulation in relation to the length of history has been calculated for inguinal and femoral hernias presenting to this hospital between 1987 and 1989. Of 476 hernias (439 inguinal, 37 femoral), there were 34 strangulations (22 inguinal, 12 femoral). After 3 months the cumulative probability of strangulation for inguinal hernias was 2.8 per cent, rising to 4.5 per cent after 2 years. For femoral hernias the cumulative probability of strangulation was 22 per cent at 3 months and 45 per cent at 21 months. The rate at which the cumulative probability of strangulation increased was in both cases greatest in the first 3 months, suggesting that patients with a short history of herniation should be referred urgently to hospital and given priority on the waiting list.

Adolescent↗
PubMed1991

Renal actions of a new adenosine agonist, CGS 21680A selective for the A2 receptor.

This study compares the renal actions of the A2 selective adenosine agonist, CGS 21680A, with the A1 selective adenosine agonist, N6-cyclopentyladenosine (CPA), and the nonselective agonist, 5'-N-ethylcarboxamide adenosine (NECA), in the anesthetized dog. Initial receptor binding studies in dog brain demonstrated that CPA and CGS 21680A were selective for the A1 and A2 adenosine receptor, respectively, whereas NECA displayed slightly greater affinity for A1 than A2 adenosine receptors in the canine brain. Intravenous infusion of CGS 21680A (0.25 and 2.5 micrograms/kg/min) decreased blood pressure (BP) and increased heart rate (HR). CGS 21680A transiently increased renal blood flow (RBF) and either did not change or, at the highest dose infused, decreased glomerular filtration rate (GFR). Both urine volume (UV) and urinary sodium excretion (UNaV) also were decreased by CGS 21680A. At the lowest infusion rate (0.025 micrograms/kg/min) CGS 21680A produced a slowly developing increase in RBF, no change in GFR and a significant decrease in sodium excretion. Intravenous infusion of CPA (15 micrograms/kg/min) lowered BP and HR RBF and GFR. UNaV, UV and renin release also were inhibited by CPA. At a lower infusion rate (2.5 micrograms/kg/min), CPA markedly inhibited UNaV in the absence of a significant change in either BP or renal hemodynamic parameters. Infusion of NECA (0.01 and 0.1 micrograms/kg/min) lowered BP but did not change HR. Furthermore, RBF was increased by NECA, whereas UV and UNaV were inhibited in the absence of a change in GFR. These results may be explained by the relative selectivity of each analog for A1 or A2 adenosine receptors.

Adenosine↗
PubMed1987

Differences in the chemical and catalytic characteristics of two crystallographically 'identical' enzyme catalytic sites. Characterization of actinidin and papain by a combination of pH-dependent substrate catalysis kinetics and reactivity probe studies targeted on the catalytic-site thiol group and its immediate microenvironment.

The characteristics of actinidin (EC 3.4.22.14) and papain (EC 3.4.22.2), two cysteine proteinases whose catalytic-site regions appear to superimpose to a degree that approaches atomic co-ordinate accuracy of both crystal structures, were evaluated by determining (a) the pH-dependence in acid media of the acylation process of the catalytic act (k+2/Ks) using N alpha-benzoyl-L-arginine p-nitroanilide (L-Bz-Arg-Nan) as substrate and (b) the sensitivity of the reactivity of the catalytic-site thiol group and its pH-dependence to structural change in small, thiol-specific, two-protonic-state reactivity probes (2,2'-dipyridyl disulphide and methyl 2-pyridyl disulphide) where enzyme-probe contacts should be restricted to areas close to the catalytic site. Distortion of the catalytic sites of the two enzymes at pH less than 4 was evaluated over time-scales appropriate for both stopped-flow reactivity probe kinetics (less than or equal to 1-2 s) and steady-state substrate catalysis kinetics (3-5 min) by using the 2,2'-dipyridyl disulphide monocation as a titrant for non-distorted catalytic sites. This permitted a lower pH limit to be defined for valid kinetic analysis of both types. The behaviour of the enzymes at pH less than 4 requires a kinetic model in which the apparently biomolecular reaction of enzyme with probe reagent is separated from the process leading to loss of conformational integrity by a potentially reversible step. The acylation of actinidin with L-Bz-Arg-Nan in acidic media occurs in two protonic states, one produced by raising the pH across pKa less than 4 which probably characterizes the formation of -S-/-ImH+ ion pair (pKa approx. 3) and the other, of higher reactivity, produced by raising the pH across pKa 5.5, which may characterize rearrangement of catalytic-site geometry. The pH-dependence of the acylation of papain by L-Bz-Arg-Nan is quite different and is not influenced by protonic dissociation with pKa values in the range 5-6. The earlier conclusion that the acylation of papain depends on two protonic dissociations each with pKa approx. 4 was confirmed. This argument is now more firmly based because titration with 2,2'-dipyridyl disulphide permits the loss of conformational integrity to be taken into account in the analysis of the kinetic data at very low pH. Methyl 2-pyridyl disulphide was synthesized by reaction of pyridine-2-thione with methyl methanethiolsulphonate and its pKa at I = 0.1 was determined by spectral analysis at 307 nm to be 2.8.(ABSTRACT TRUNCATED AT 400 WORDS)

Acylation↗
PubMed1987

Subjective effects of cigarette smoking in adolescents.

Eighty-two per cent of a sample of 170 female adolescent smokers reported experiencing one or more of five specified subjective effects of smoking. Feeling calmer was the most frequently reported effect and daily smokers were more likely to report this than non-daily smokers (64% versus 38%, P less than 0.001). Self-reports of cigarette consumption and depth of inhalation and measures of smoke intake (salivary cotinine and expired-air carbon monoxide levels) were positively related to the report of feeling calmer when smoking and negatively related to feeling dizzy/light-headed and sick when smoking. The likelihood of experiencing at least one withdrawal effect when trying to quit was greater amongst those who reported feeling calmer when smoking (82% versus 40%, P less than 0.001). These results indicate that subjective effects of smoking are commonly reported by children and it is possible that pharmacological factors are implicated alongside psychosocial ones even at this early stage.

Adolescent↗
PubMed1987

Nucleotide sequence of the immunity and lysis region of the ColE9-J plasmid.

We have determined the nucleotide sequence of a 1500 bp fragment of the ColE9-J plasmid which encodes colicin E9 immunity and colicin E5 immunity and contains two lys genes. Open reading frames corresponding to the four genes have been located and their position confirmed by transposon mutagenesis of sub-clones of the ColE9-J plasmid. The E9imm gene shows 69% homology at both the nucleotide and the amino acid level to the previously sequenced E2imm gene. The E5imm gene shows little homology to any other E colicin immunity gene which has been sequenced. The lys gene distal to the 3' end of the E5imm gene shows considerable sequence homology to all other previously sequenced E colicin lys genes. The lys gene distal to the 3' end of the E9imm gene is identical to the pColE2 and pColE3 lys genes for the first 59 nucleotides but encodes a much smaller gene product than any other lys gene which has been sequenced. The two lys genes sequenced here are exceptions to Shepherd's rule concerning the number of RNY codons in the three possible reading frames.

Base Sequence↗
PubMed1986

The structure and transcription start site of a major potato tuber protein gene.

We have isolated recombinant lambda clones containing intact major tuber protein (patatin) genes and flanking sequences from the commercial tetraploid variety Maris Piper. The gene is composed of seven exons and six introns, spread over 4 kb of DNA. Nuclease mapping defined the 5' end of the mRNA approximately 45 bp upstream of the initiation codon. The 5' end of the gene is preceeded by a canonical TATA box sequence. The three known patatin genes encode proteins of nearly identical Mr but very different isoelectric points. The sequence of the gene does not indicate a role for patatin as one of the globulin class of plant storage proteins.

Amino Acid Sequence↗
PubMed1986

Chymopapain A. Purification and investigation by covalent chromatography and characterization by two-protonic-state reactivity-probe kinetics, steady-state kinetics and resonance Raman spectroscopy of some dithioacyl derivatives.

Chymopapain A was isolated from the dried latex of papaya (Carica papaya) by ion-exchange chromatography followed by covalent chromatography by thiol-disulphide interchange. The latter procedure was used to produce fully active enzyme containing one essential thiol group per molecule of protein, to establish that the chymopapain A molecule contains, in addition, one non-essential thiol group per molecule and to recalculate the literature value of epsilon 280 for the enzyme as 36 000 M-1 X cm -1. The Michaelis parameters for the hydrolysis of L-benzoylarginine p-nitroanilide and of benzyloxy-carbonyl-lysine nitrophenyl ester at 25 degrees C, and I 0.1 at several pH values catalysed by chymopapain A, papaya proteinase omega, papain (EC 3.4.22.2) and actinidin (EC 3.4.22.14) were determined. Towards these substrates chymopapain A has kcat./km values similar to those of actinidin and of papaya proteinase omega and significantly lower than those of papain or ficin. The environment of the catalytic site of chymopapain A is markedly different from those of other cysteine proteinases studied to date, as evidenced by the pH-dependence of the second-order rate constant (k) for the reaction of the catalytic-site thiol group with 2,2'-dipyridyl disulphide. The striking bell-shaped component that is a characteristic feature of the reactions of S-/ImH+ (thiolate/imidazolium) ion-pair components of many cysteine-proteinase catalytic sites with the 2,2'-dipyridyl disulphide univalent cation is not present in the pH-k profile for the chymopapain A reaction. The result is consistent with the presence of an additional positive charge in, or near, the catalytic site that repels the cationic form of the probe reagent. Resonance Raman spectra were collected at pH values 2.5, 6.0 and 8.0 for each of the following dithioacyl derivatives of chymopapain A: N-benzoylglycine-, N-(Beta-phenylpropionl)glycine- and N-methoxycarbonylphenylalanylglycine-. The main conclusion of the spectral study is that in each case the acyl group binds as a single population known as conformer B in which the glycinic N atom is in close contact with the thiol S atom of the catalytic-site cysteine residue, as is the case also for papain and other cysteine proteinases studied. Thus the abnormal catalytic-site environment of chymopapain A detected by the reactivity-probe studies, which may have consequences for the acylation step of the catalytic act, does not perturb the conformation of the bound acyl group at the acyl-enzyme-intermediate stage of catalysis.

2,2'-Dipyridyl↗
PubMed1986

Cigarette withdrawal symptoms in adolescent smokers.

One hundred and sixteen female adolescent smokers were asked about withdrawal symptoms experienced during past attempts to give up smoking for good. Sixty-three percent reported difficulties during abstinence of the kind experienced by adult smokers. Daily smokers were more likely to report withdrawal effects than non-daily smokers (74% versus 47%, P less than 0.005). Reported experience of withdrawal symptoms was positively related to self-reports of cigarette consumption and depth of inhalation and nicotine intake as indexed by salivary cotinine concentrations. Reported occurrence of at least one withdrawal effect correlated positively with nicotine intake after controlling for behavioural variables. Our results indicate that teenage smokers are likely to suffer withdrawal symptoms when they try to give up. Behavioural factors and expectations based on observations of adults may have played a part in their experience of withdrawal, but it is also likely that pharmacological factors are implicated even at this early stage.

Adolescent↗
PubMed1984

An evaluation of the intervention against smoking in the multiple risk factor intervention trial.

The results of the Multiple Risk Factor Intervention Trial showed no significant difference in mortality from coronary heart disease between intervention and control groups despite an apparent success of the intervention against cigarette smoking. A reanalysis of the published data indicates that the effectiveness of the smoking intervention may have been overestimated. The researchers counted those who smoked pipes or cigars at screen as nonsmokers and attempted to classify cigarette smokers who switched to pipes or cigars during the trial as successes whether or not they continued to inhale the smoke. It is unreasonable to assume a priori that inhaling pipe or cigar smoke is less dangerous than cigarette smoke. Moreover, attempting to include pipe and cigar smokers, who may have been inhaling smoke, among the successes makes biochemical validation of claims of abstinence overly lenient. When levels of serum thiocyanate are used to obtain an objective index of smoking reduction, it appears that the effect of intervention was considerably smaller than has been reported, and failed to reach design goals over the first 4 years. This could help to explain the disappointing mortality results.

Carbon Monoxide↗
PubMed1984

Biochemical markers of smoke absorption and self reported exposure to passive smoking.

One hundred non-smoking patients attending hospital outpatient clinics reported their degree of passive exposure to tobacco smoke over the preceding three days and provided samples of blood, expired air, saliva, and urine. Although the absolute levels were low, the concentration of cotinine in all body compartments surveyed was systematically related to self reported exposure. Salivary nicotine concentration also showed a linear increase with degree of reported exposure, although this measure was sensitive only to exposure on the day of testing. Measures of carbon monoxide, thiocyanate, and plasma nicotine concentrations were unrelated to exposure. The data indicate that cotinine provides a valid marker of the dose received from passive smoke exposure. The non-invasive samples of urine and saliva are particularly suited to epidemiological investigations. Detailed questionnaire items may also give valuable information.

Absorption↗