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Biomedical subjects

B Clark

Publications and source records attributed to B Clark.

At least 109 records · Page 6Linked to original sources
PubMed1985

Occupational risk of hepatitis B infection in hospital workers.

To estimate the risk of hepatitis B virus (HBV) infection among hospital workers, we measured the prevalence of HBV infection in employees in five hospitals in different parts of the country and examined the effect of occupational and non-occupational factors on HBV prevalence. Among 5,697 persons studied, serologic markers of HBV infection were found in 807 (14%). Prevalence of infection was strongly related to race (Asian greater than Black greater than White), sex (male greater than female) and increasing age. Risk related to health occupation, studied by examining the change in HBV prevalence with duration in occupational group, was most strongly correlated with frequency of contact with blood during work. Workers having frequent blood contact had the highest estimated infection rate (1.05 per 100 person-years) and those with moderate contact an intermediate infection rate, compared to a negligible infection rate in workers with no blood contact. Frequency of needle accidents had an independent, positive effect on HBV infection rates, while degree of patient contact had no effect. Infection risk was uniform among all hospitals for groups with frequent blood contact. Among different occupation groups, risk of HBV infection also correlated closely with degree of blood-needle contact during daily work. This study provides a general approach to assessing risk of HBV infection in hospital personnel, and indicates that risk may be most easily estimated by quantitating degree of blood-needle contact during daily work.

Adolescent↗
PubMed1985

Regional distribution of calmodulin activity in rat brain.

Calmodulin activity in 68 discrete areas of rat brain, obtained by micropunch technique, was assessed by its capacity to activate a calmodulin-sensitive form of phosphodiesterase. In general, the activity of calmodulin was higher in the telencephalon, limbic system, and hypothalamus than in the mesencephalon, pons, cerebellum, and medulla. However, there were substantial differences in calmodulin activity in discrete nuclei of each region. The regional distribution of calmodulin activity in rat brain does not appear to correlate with that of any of the known putative neurotransmitters or peptides.

Animals↗
PubMed1985

Synthesis of gamma-glutamyldopamine and other peptidoamines in the nervous system of Aplysia californica.

The synthesis of a series of gamma-glutamyl amines (gamma-Glu-amines), including gamma-Glu-dopamine, gamma-Glu-5-hydroxytryptamine, gamma-Glu-octopamine, gamma-Glu-tryptamine, gamma-Glu-tyramine, and gamma-Glu-phenylethylamine, by nervous tissue of the marine mollusc Aplysia californica is described. After ganglia were incubated in vitro with 14C-amines, the unchanged amine and a new 14C-labeled product, identified as the gamma-Glu conjugate of the amine, were isolated from the tissue extracts. Identification was made by comparing the chromatographic properties (HPLC, TLC, and LC) of the isolated conjugates with chemically synthesized gamma-Glu-amines before and after acid hydrolysis.

Animals↗
PubMed1985

Canine bombesin-like gastrin releasing peptides stimulate gastrin release and acid secretion in the dog.

The synthetic mammalian bombesin-like peptides, canine gastrin releasing peptide 27, 23 and 10, and porcine gastrin releasing peptide 27 were compared with amphibian bombesin 14 and 10 during intravenous infusions into six conscious dogs with chronic gastric cannulae. Gastrin and gastrin releasing peptide were measured in peripherally sampled venous blood by radioimmunoassay and gastric acid secretions were collected. All forms of gastrin releasing peptide stimulated gastrin release and gastric acid secretion in a dose-dependent manner. The larger canine and porcine peptides were more potent than the decapeptide. Bombesin 14 was more potent than bombesin 10. A rise in the venous concentration of immunoreactive gastrin releasing peptide of only 20 fmol ml-1 stimulated gastrin release to about 50% of maximal. Gastrin releasing peptide 10 was cleared from the circulation three times faster than the larger forms and this may account for the apparent differences in potency.

Animals↗
PubMed1985

Use of simple analgesics in rheumatoid arthritis.

The usefulness of anti-inflammatory drugs in rheumatoid arthritis (RA) is beyond dispute. The role of simple analgesics is less clear and has been disputed. A survey of 21 rheumatologists indicated that a majority sometimes supplemented anti-inflammatory treatment of RA with simple analgesics. A random sample of 120 RA patients treated by the same doctors revealed that 47% ranked pain relief as the most desirable objective of their treatment and 54% were taking analgesics regularly. Of those receiving analgesics as well as non-steroidal anti-inflammatory drugs 48% considered the former to be the more effective preparations. Almost half the patients on analgesics were taking drugs without the knowledge of the rheumatologists, who may have underestimated their patients' desire for pain relief.

Acetaminophen↗
PubMed1985

Differential dosing study of pirazolac, a new non-steroidal anti-inflammatory agent, in patients with rheumatoid arthritis.

Twenty-four patients with classical or definite rheumatoid arthritis participated in a 4-week double-blind crossover study to compare the effectiveness of two different dosage regimens of pirazolac. Patients were allocated at random to receive 2-weeks' treatment with either 300 mg pirazolac in the morning and 600 mg at night or 450 mg pirazolac given morning and evening, and were then crossed over to the alternative regimen for a further 2 weeks. Physician assessments of disease activity were carried out on entry and at the end of each treatment period, and patients kept a daily record of visual analogue scale scores for pain and stiffness. The results showed that both dosage regimens of pirazolac produced a significant improvement in the parameters assessed, but the difference between the two regimens was not significant. However, overall assessment at the end of the trial by the 23 patients who completed the study showed that 14 preferred the 300/600 mg regimen compared with 7 who preferred the 450/450 mg regimen: 2 patients considered both regimens equally effective. Pirazolac was relatively well tolerated, only a few patients reporting gastro-intestinal (2) and skin (3) side-effects during the trial period.

Adult↗
PubMed1984

Alpha 2-adrenoceptors in human lymphocytes: direct characterisation by [3H]yohimbine binding.

[3H]yohimbine, a potent and selective alpha 2-adrenergic antagonist was used to label alpha-adrenoceptors in intact human lymphocytes. Binding of [3H]yohimbine was rapid (t1/2 1.5 -2.0 min) and readily reversed by 10 microM phentolamine (t1/2 = 5 - 6 min) and of high affinity (Kd = 3.7 +/- 0.86 nM). At saturation, the total number of binding sites was 19.9 +/- 5.3 fmol/10(7) lymphocytes. Adrenergic agonists competed for [3H]yohimbine binding sites with an order of potency: clonidine greater than (-) epinephrine greater than (-) norepinephrine greater than (+) epinephrine much greater than (-) isoproterenol; adrenergic antagonists with a potency order of yohimbine greater than phentolamine greater than prazosin. These results indicate the presence of alpha 2-adrenoceptors in human lymphocytes.

Adrenergic alpha-Agonists↗
PubMed1984

RECFIT: a microcomputer-based nonlinear regression curve-fitting package for the quantitative resolution of beta-adrenoceptor subtypes and estimation of nonspecific binding.

A dedicated nonlinear regression based curve-fitting packages has been developed for quantitative analysis of beta-adrenoceptor subtypes. A feature of this package is the provision to obtain initial parameter estimates using a conversational graphical technique where the user is prompted for parameter estimates, and the resulting curve is displayed over the data. Data are then fitted to a one- or two-binding site model with user-selected weighting and constraints on the parameters. A novel feature is the provision to estimate the nonspecific binding component in the assays as a parameter in the model. The printout for each model consists of the parameters and their standard deviations, estimates of the goodness of fit, an analysis of residuals, and a graph of the data points overlayed with the fitted curve. The nonlinear regression algorithm is based on that of Gauss-Newton. When unweighted, the values determined by RECFIT are essentially the same as those found using the BMDPAR programs on an ICL 2976 mainframe computer. The implementation is reasonably efficient; a typical run for a two-site fit, using nine data points and estimating nonspecific binding, took a total time of about 8 min, excluding data entry and derivation of initial estimates, 4 min for the fitting, 30 sec for graph generation, and 2-3 min for printing of the graph and data.

Binding Sites↗
PubMed1984

Circadian variation in number and affinity of beta 2-adrenoceptors in lymphocytes of asthmatic patients.

To determine whether circadian variation in adrenoceptor function might underlie the 'morning dip' in peak expiratory flow (PEF) rate and its abolition by salbutamol we measured indices of beta-adrenoceptor function (Bmax. and Kd), the ratio FEV1/FVC, and plasma cortisol at 08.00 and 18.00 hours on and off salbutamol (4 mg given orally every 4 h) in five extrinsic asthmatic patients and five normal volunteers. There was a significant circadian variation in receptor numbers (Bmax.) in both the control and asthmatic groups which was not abolished on treatment with salbutamol. Both groups appeared to compensate for loss of receptor number induced by salbutamol administration by increasing receptor affinity. For comparable combinations of drug/time, there was no significant difference between the control and asthmatic groups. We conclude that the 'morning dip' observed in asthmatic patients cannot simply be explained by changes in cell receptor number or affinity, as our results suggest that both groups have intact beta-adrenoceptor function. Nevertheless, our observations of the normal circadian rhythm has important implications for future studies of beta-adrenoceptors in asthmatic patients.

Albuterol↗
PubMed1984

Binding potencies of 3 new beta 2 specific blockers to beta receptors in the ciliary processes and the possible relevance of these drugs to intraocular pressure control.

The binding potencies of 3 new beta 2 blocking drugs to beta receptors in the ciliary processes were studied by means of radioligand techniques. The drugs studied were IPS339, ICI118,551, and Sandoz L1 32-468. The order of potency of these drugs was IPS339 greater than Sandoz L1 32-468 greater than ICI118,551. The beta 2 dissociation constants (KDs) for these drugs were 0.90 nM, 6.60 nM, and 55 nM respectively. These results are compared with those for other adrenergic agents, including timolol. The potential role of topical beta 2 blockers in glaucoma is discussed.

Adrenergic beta-Antagonists↗
PubMed1984

Pharmacokinetics and toxicity testing.

The pharmacokinetic basis for the design of toxicity tests is discussed with reference to the absorption and clearance of drugs. The absorption and clearance of a wide range of drugs by laboratory animals and man has been examined and reviewed to provide a firm basis against which new drugs can be compared. Some pitfalls in either the empirical approach to toxicology or the incorrect interpretation of kinetic data are highlighted. An approach is outlined for the rational application of animal pharmacokinetic data in the assessment of the safety in man of a new therapeutic agent.

Administration, Oral↗
PubMed1983

Development of the cytosolic defence system against microsomal lipid peroxidation in rat liver.

Ascorbate-induced lipid peroxidation in rat liver microsomes reaches the adult level in 2-3 days. NADPH-induced peroxidation develops more gradually, in parallel with the activity of NADPH-cytochrome P-450 reductase, attaining adult levels by 10-12 days. The glutathione-dependent cytosolic enzyme activity which inhibits peroxidation is inhibited by bromosulphophthalein. The development of this system lags behind the development of microsomal lipid peroxidation between the ages of 2 and 20 days, allowing peroxidation to proceed.

Aging↗
PubMed1983

Microprocessor assisted handling of oestrogen receptor assays.

The use of an Apple II microcomputer equipped with a light-pen for interactive analysis of steroid receptor data is described. Processing times have been reduced to less than 5 minutes per patient from around 45-60 minutes by the manual method. Graphical outputs using full and part data sets with derived results are printed for subsequent verification by the Consultant Medical Biochemist. Data processing backlogs have been completely eliminated by this system. The program has, of course, general applicability to any analyses producing a linear correlation between the x and y parameters, and its use in oestrogen receptor analysis is detailed principally because of a considerable and increasing demand for such assays in our department.

Biopsy↗
PubMed1983

Amino acid sequences of three bombesin-like peptides from canine intestine extracts.

Amino acid sequences of three canine bombesin-like peptides were determined after sequential purification of an extract obtained from 820 g of intestinal muscle. These three peptides contained 27, 23, and 10 amino acid residues. The sequences of the two shorter forms were identical to the corresponding carboxyl-terminal sequence of the heptacosapeptide. The sequence of the largest peptide is H2N-Ala-Pro-Val-Pro-Gly-Gly-Gln-Gly-Thr-Val-Leu-Asp-Lys-Met-Tyr-Pro-Arg-Gly-Asn - His(Trp-Ala-Val-Gly-His-Leu-Met-CONH2). The sequence of the 23-residue peptide is H2N-Gly-Gly-Gln-Gly-Thr-Val-Leu-Asp-Lys-Met-Tyr-Pro-Arg-Gly-Asn-His-Trp-Ala- Val-Gly(His-Leu-Met-CONH2). The sequence of the decapeptide is: H2N-Gly-Asn-His-Trp-Ala-Val-Gly-His-Leu-Met-CONH2. Comparison of the 27-residue peptide with the known structure of porcine gastrin-releasing peptide, another bombesin-like heptacosapeptide, reveals four amino acid substitutions: canine bombesin-like peptide had Pro 4, Gly 5, Gln 7, Asp 12, whereas porcine gastrin-releasing peptide had Ser 4, Val 5, Gly 7, Ala 12. Radioimmunoassay of brain extracts after similar purification revealed the presence of similar large and small forms of immunoreactive bombesin peptides, but with apparent tissue concentrations of about 4% of those present in intestinal muscle. Canine bombesin-like peptides represent another example of mammalian neuropeptides existing in more than one biologically active molecular form.

Amino Acid Sequence↗
PubMed1983

Failure of sodium aurothiomalate and triethyl phosphine gold to cause renal tubular injury in rheumatoid arthritis: implications for the aetiology of gold-related nephropathy.

The urinary excretion of two proteins, B-2-microglobulin (beta 2M) and N-acetyl-B-D-glucosaminidase (NAG) was measured in 25 patients with rheumatoid arthritis (RA) on nonsteroidal anti-inflammatory drugs (NSAID). Although beta 2M excretion was normal NAG excretion was raised. As NAG excretion by a group of osteoarthritis patients receiving similar doses of NSAIDs was normal, it is concluded that rheumatoid disease per se may be associated with mild renal tubular dysfunction. Twelve of the above 25 patients were then given oral triethylphosphine-gold (auranofin) 6 mg daily and urinary beta 2M and NAG were measured after 6 months' treatment. Urinary excretion of beta 2M and NAG was also measured in 13 patients with RA established on intramuscular sodium aurothiomalate (MGST) and NSAIDs. Neither auranofin nor myocrisin were found to further significantly increase beta 2M and NAG excretion. These results suggest that gold compounds are not toxic to renal tubular epithelium.

Acetylglucosaminidase↗