Search PubMedSearch

Biomedical subjects

M J Clark

Publications and source records attributed to M J Clark.

At least 19 recordsLinked to original sources

Review of the literature and report of a case of a dermoid cyst.

This article presents a large dermoid cyst discovered in the floor of the mouth of a young male patient. The lesion was clinically detected by manual palpation and confirmed by the use of magnetic resonance imaging. Treatment of this case was by surgical removal of the dermoid cyst. The patient recovered without any complications or evidence of re-occurrence of the cyst.

Child

Drosophila abl tyrosine kinase in embryonic CNS axons: a role in axonogenesis is revealed through dosage-sensitive interactions with disabled.

During Drosophila embryogenesis, the Abelson tyrosine kinase (abl) is localized in the axons of the central nervous system (CNS). Mutations in abl have no detectable effect on the morphology of the embryonic CNS, and the mutant animals survive to the pupal and adult stages. In the absence of abl function, however, heterozygous mutations or deletions of disabled (dab) exert dominant effects, disrupting axonal organization and shifting the lethal phase of the animals to embryonic and early larval stages. Embryos that are homozygous mutant for both abl and dab fail to develop any axon bundles in the CNS, although the peripheral nervous system and the larval cuticle appear normal. The genetic interaction between these two genes begins to define a process in which both the abl tyrosine kinase and the dab gene product participate in establishing axonal connections in the embryonic CNS of Drosophila.

Animals

Relationship between opioid-receptor occupancy and stimulation of low-Km GTPase in brain membranes.

Treatment of rat brain membranes with the irreversible opioid ligand cis-3-methylfentanylisothiocyanate (Superfit) was used to reduce gradually the number of available binding sites for the delta-selective agonist [3H][D-Ser2,Leu5]enkephalin-Thr6 ([ 3H]DSLET). Subsequently, the correlation between ligand binding and low-Km GTPase was investigated. Alkylation with 10 microM and 25 microM Superfit inactivated 66% and 71% of high-affinity (KD, 1 nM) binding sites without decreasing the affinity of the remaining sites and the stimulation of low-Km GTPase by DSLET. Following exposure of the membranes to 50 microM and 75 microM Superfit, ligand binding was confined to the low-affinity (KD, 20 nM) sites. In these membranes, the delta-agonists DSLET and [D-Pen2,D-Pen5]enkephalin still stimulated low-Km GTPase, and these effects were blocked by ICI 174864 (N,N-diallyl-Tyr-AIB-AIB-Phe-Leu-OH; AIB, alpha-aminoisobutyric acid), a delta-selective antagonist. A similar relationship between low-affinity ligand binding and GTPase stimulation was observed following alkylation of the delta-opioid receptor with the non-selective irreversible antagonist beta-chlornaltrexamine in the presence of protective concentrations of DSLET. The results reveal spare receptor sites in the coupling of the delta-opioid receptor to low-Km GTPase in brain and identify low-affinity ligand binding as a functional component in the process.

Animals

Evaluating nursing productivity in child health.

As nurses are increasingly concerned with assessing and improving their productivity in a variety of settings, they must make systematic use of an evaluation model. The Discrepancy Evaluation Model (DEM) was used to evaluate the productivity of nurses in child health clinics in five centers in the southeastern United States. The first step in any evaluation is to identify standards against which performance can be measured. In this project, no standards were available, and creating them was the first task. Standards for productivity in child health were developed that accounted for differences in clients and the experience level of nurses, while maintaining quality of care. They were situation specific and allowed for the constraints operating in each of the five centers. Discrepancies between the standards and observed performance were identified and underlying factors examined, resulting in a number of recommendations that could streamline the provision of services and improve nursing productivity. The evaluation process can be applied to public health nursing services in a variety of settings.

Ambulatory Care Facilities

Is the mode of action of almitrine bismesylate dose dependent?

In order to assess whether different doses and/or plasma levels of almitrine bismesylate (ABM) could induce preferential effects on ventilation or on lung perfusion, we performed a single-blind placebo-controlled study of ABM treatment with different dosages (0.75, 1.5 and 2.25 mg.kg-1 single oral dose) in 26 patients suffering from chronic obstructive pulmonary disease (COPD). All measurements were performed according to the same time table. At control and at three 1.5-hour intervals, we measured alveolar-arterial (A-a) differences, alveolar dead space, total ventilation and ABM plasma levels. The effect on ventilation was estimated using changes in ventilatory parameters and (A-a)O2 differences. The effect on perfusion was indirectly estimated by analysis of arterial-end-tidal (a-ET)CO2 difference and alveolar dead space. The response to treatment was significant for the 1.5- and the 2.25-mg.kg-1 ABM groups, but not for the 0.75 mg.kg-1 ABM and the placebo group. A ventilatory response was often present in both 1.5- and 2.25-mg.kg-1 ABM groups, but a nonventilatory effect was present only at the highest dose according to the Severinghaus and Stupfel concept. Only the parameters reflecting an effect of the distribution of perfusion (a-ET)CO2 difference and alveolar dead space were significantly correlated with ABM plasma levels. The results suggest that a dose-dependent effect of ABM on lung perfusion may explain the controversial data in the literature about the mode of action of ABM.

Administration, Oral

An open multiple dose study of Optrex Eye Lotion in eye irritation due to hayfever.

Twenty-four patients consulting their general practitioner with eye irritation due to hayfever entered a seven-day open, multiple dose study of a newly formulated Optrex Eye Lotion. Patients self-administered Optrex by irrigation into their left eye three times daily for seven days, with an option to use the same preparation in their right eye if they thought this to be of benefit. Assessment was by means of daily diary cards completed by the patient each evening for the seven-day period. Following the first instillation, the treated eye felt significantly better at 20 seconds and at four minutes when compared with the untreated eye. Differences between the eyes for degree of redness, comfort and clearness of vision were not significant, but 15 patients (63 per cent) optionally used Optrex in their right eye. Seventeen patients (71 per cent) reported that they derived overall benefit from the use of Optrex Eye Lotion during the study period. Two patients reported side effects during the study but, in each case, the investigator did not consider the event to be therapy related. One patient withdrew on Day 7 of the trial due to worsening of their allergic conjunctivitis. It can be concluded that some subjective benefit was gained by the majority of patients in that a considerable number of them chose to treat both eyes for the duration of the study.

Administration, Topical

Selectivity of ligand binding to opioid receptors in brain membranes from the rat, monkey and guinea pig.

Conditions for the equilibrium binding to opioid receptor of [3H]sufentanil (mu selective), [3H][D-Pen2,D-Pen5]enkephalin (delta selective), and [3H]U69,593 (kappa selective) were established in membranes from rat brain cerebrum, monkey cortex, or guinea pig cerebellum. The selectivity index of various opioid alkaloids and peptides in binding to the mu, delta, or kappa opioid receptors was expressed as the ratio of their EC50 values in displacing two selective radiolabeled ligands: [3H]sufentanil/[3H](D-Pen2,D-Pen5)enkephalin (selectivity: mu/delta), [3H]sufentanil/[3H]U69,593 (selectivity: mu/kappa), or [3H][D-Pen2,D-Pen5]enkephalin/[3H]U69,593 (selectivity: delta/kappa). High resolution in binding selectivity was observed: in rat brain the mu/delta selectivity for Tyr-D-Ala-Gly-(Me)Phe-Gly-ol and sufentanil were 0.02 and 0.03, whereas for [D-Pen2,D-Pen5]enkephalin and ICI 174,864 they were 1,200 and 998. Compared to mu opiates, the specific binding of delta and kappa agonists was less sensitive to sodium. The results describe a routinely applicable methodological approach for the assessment of selective ligand binding to the mu, delta and kappa opioid receptors in rodent and monkey brain membranes.

Analgesics, Opioid

Wet and dry deposition of Chernobyl releases.

The passage of the Chernobyl plume over the United Kingdom in May 1986 led to the deposition of radionuclides on the ground by wet and dry deposition processes. Here we analyse rainfall during the passage of the plume and the published monitoring data obtained afterwards, and show that levels of deposited 137Cs can be closely related to rainfall intercepting the plume. 137Cs was present in the atmosphere mostly as particulate species with wet deposition mechanisms dominating. In contrast, 131I was present as particulate and vapour phase material, and reported levels on grass and in cow's milk show that both wet and dry deposition mechanisms were important. 131I on grass and in cow's milk therefore shows a different geographic pattern to 137Cs, and is not so closely related to rainfall. We have calculated washout factors for locations where there are data on deposition, rainfall and air concentrations during the passage of the Chernobyl plume. From these factors and interpolated concentrations in the atmosphere, the total deposition of 137Cs has been estimated at each of 4,000 rain gauge stations in the United Kingdom. The results are presented as deposition contours and have been compared with measurements in parts of the country. Estimates of the total deposition of 131I and 137Cs show that less than or equal to 1% of the estimated total releases from Chernobyl were deposited on the United Kingdom.

Accidents

Characterization of the human homolog of the rat MRC OX-2 membrane glycoprotein.

The MRC OX-2 antigen is a membrane glycoprotein present on rat thymocytes, neurons, follicular dendritic cells, endothelium, and some smooth muscle. The sequence of 248 amino acids has similarities to Ig domains organized with one V-like domain, one C-like domain, and transmembrane and cytoplasmic regions. Thus it resembles a T-cell receptor chain but shows no sequence divergence. We report the characterization of the human gene for this molecule. Its exon organization is similar to that found for immunoglobulins although the region with similarities to Ig J regions is found within the same exon as the V-like domain. Human MRC OX-2 is expressed at the mRNA level in brain and B-cell lines but not detected in liver or T-cell lines. It does not obviously correspond to any previously defined leukocyte antigen. The sequence homology for the human and rat MRC OX-2 molecules is higher for the Ig-related region (75%) than for many other Ig-related molecules and very high in the transmembrane region (96%), implying a functional role other than simply its anchoring into the membrane.

Amino Acid Sequence

Coupling of multiple opioid receptors to GTPase following selective receptor alkylation in brain membranes.

Opioid agonists of the mu, kappa and delta types stimulated low-Km guanosine triphosphatase (GTPase) in membranes, from the brain of the rat by up to 34%, with potencies the rank order of which corresponded to the respective binding affinities to opioid receptor. In general, kappa ligands stimulated GTPase to a lesser degree than mu or delta opiates. The coupling of a given type of opioid receptor to GTPase was resolved by direct or protective alkylation of the other receptors. Treatment of the membranes with beta-funaltrexamine abolished the stimulation of GTPase by sufentanil and levorphanol (mu), but not by bremazocine (kappa) or DSLET (delta). On the other hand, prior incubation with Superfit, an alkylating agent with selectivity for the delta opioid receptor, specifically eliminated the effect of DSLET. Partial alkylation by increasing concentrations of Superfit gradually reduced the extent of stimulation of GTPase by DSLET. The successive treatment of membranes with Superfit and beta-funaltrexamine blocked the actions of DSLET, sufentanil and levorphanol, but had no effect on the stimulation of the GTPase by bremazocine. Selective coupling of an opioid receptor to GTPase was also obtained after incubation of membranes with beta-chlornaltrexamine in the presence of protective concentrations of mu, kappa or delta opioid ligands. Alkylation resolved the coupling of the non-selective opiate etorphine: the sum of stimulation of GTPase in the receptor-selective membranes equalled maximal stimulation of enzyme in untreated membranes. Naloxone blocked the stimulation of GTPase by mu, kappa or delta agonists, but ICI-174,864 specifically inhibited the effect of DSLET.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkylation

Physiologic responses to heavy-resistance exercise with very short rest periods.

Heavy-resistance exercise utilizing very short rest periods is commonly used by body builders to prepare for competition. The purpose of this study was to compare the acute responses of this type of heavy-resistance exercise protocol in competitive body builders (BB) and power lifters (PL). Nine male BB and eight PL were matched for age, size and experience. A ten-station heavy-resistance exercise protocol was used. Each subject performed three sets of 10 repetition maximum (RM) with 10-s rest between sets and alternated 30-s and 60-s rest periods between exercises. No differences were observed in total work between the groups, but BB used a significantly (P less than 0.05) higher percentage of their 1 RM in the bench press and leg press exercises. Heart rate, ratings of perceived exertion (RPE), and lactate levels were obtained during the exercise protocol; significant (P less than 0.05) increases were observed above rest for these variables. RPE was significantly correlated with lactate levels (r = 0.84). Plasma epinephrine, norepinephrine, dopamine, cortisol, and lactate levels significantly increased from pre- to 5 min post-exercise. Mean plasma volumes were reduced -16.6 (+/- 3.64)% and -20.6 (+/- 8.32)% following the exercise protocol for BB and PL, respectively. Significant (P less than 0.05) decreases in eosinophil counts were observed following exercise. No significant differences were observed between BB and PL for any of the physiologic responses measured. PL exhibited a higher incidence (100%) of clinical symptoms of dizziness and nausea compared to BB (11.1%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Evidence for coupling of the kappa opioid receptor to brain GTPase.

In membranes from guinea pig cerebellum, a tissue which predominantly contains kappa opioid receptors, exogenous and endogenous kappa-selective opioid agonists stimulated low-km GTPase activity by 11-20% with concentrations for half-maximal stimulation of 3-23 microM. Opioid ligands of the mu and delta type had no effect on GTPase in these membranes. Similar stimulation of GTPase by kappa opiates was obtained in rat and monkey brain membranes pretreated with beta-funaltrexamine (beta-FNA) and cis-(+/-)-3-methylfentanyl isothiocyanate (superfit) to alkylate the mu and delta receptors, respectively. The stimulation of brain GTPase by kappa opiates in both types of membranes was inhibited by naloxone with IC50's of 0.35 microM and 0.40 microM. The results demonstrate the coupling of the kappa opioid receptor to high affinity GTPase, the Ni regulatory protein of the adenylate cyclase complex.

Alkylation

The distribution of [14C]acrylamide in male and pregnant Swiss-Webster mice studied by whole-body autoradiography.

Male and 13.5- and 17.5-day pregnant Swiss-Webster mice were administered 120 mg/kg [2,3-14C]acrylamide orally. The male mice were frozen 0.33, 1, 3, 9, 24, 72, and 216 hr later, and the pregnant mice at each gestational period were frozen at 3 and 24 hr. Whole-body autoradiographs from the male mice at early time intervals revealed accumulation of radioactivity in the contents of the gastrointestinal tract, liver, pancreas, testis, brain and gallbladder, and epithelia of oral cavity, esophagus, and bronchi. The distribution appears to be similar in the male and pregnant mice. Absorption from the stomach was virtually complete by 3 hr; renal and hepatic elimination was essentially complete at 24 hr. Radioactivity in the male reproductive tract appeared in the parenchyma of the testis at 1 hr, moved to the seminiferous tubules and head of the epididymis at 9 hr, and by 9 days remained only in the tail of the epididymis and the crypts of the epithelium of the glans penis. This movement parallels that of spermatids. The 13.5-day fetuses were uniformly labeled except for a slightly increased uptake in fetal brain. The distribution of radioactivity in the 17.5-day fetal tissues resembled that in maternal tissues; the remarkable exception was an intense accumulation in fetal skin. This study indicates that acrylamide is efficiently absorbed from the stomach and eliminated by the liver, kidney, and possibly the pancreas. A previously unrecognized affinity of acrylamide or a metabolic product was demonstrated for fetal skin in late gestation and for adult epithelia of oral cavity, esophagus, forestomach, and bronchi. Also, acrylamide or a metabolite appears to bind to spermatids at a specific stage near maturation.

Acrylamide

Evaluation of bidirectional aluminum transfer across hollow fiber dialyzers.

The ultrafiltrable fraction of plasma aluminum (UFAl) determined utilizing the hollow fiber dialyzer is variable and ranges from 10% to 50%. This extreme variability in UFAl led us to examine the possibility of Al binding to the hollow fiber dialyzer. Ultrafiltrate of aqueous Al solutions was obtained by applying a negative pressure of 250 mm Hg to a hollow fiber dialyzer (TriEx-1). In the first of three experimental protocols, Al was measured before and after recirculation of solutions containing 344 to 9244 micrograms/L Al through a hollow fiber dialyzer until the entire volume was collected as ultrafiltrate. UFAl ranged from 0.9% to 37.6% and did not correlate with the initial Al concentration. Total Al binding ranged from 42 micrograms to 1.3 mg. In the second, 16 L of aqueous AlCl3 solution (n = 3), containing from 205 to 411 micrograms/L Al were passed through the blood compartment of a hollow fiber dialyzer. The percentage of UFAl ranged from 4.1% to 17.3% during the first 20 minutes and 79.3% to 81.8% at 120 minutes. Finally, to investigate Al transfer from dialysate, 16 L of deionized distilled water were passed through the blood compartment while 16 L of AlCl3 solutions of 330 micrograms/L and 398 micrograms/L AI passed through the dialysate compartment. Samples were collected from blood and dialysate outflow ports every 20 minutes for 120 minutes. The transfer of Al from dialysate to blood compartment increased with time. However the concentration of Al at the blood outflow port never reached that at the dialysate outflow port.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum

The effect of cigarette smoking during pregnancy on the cholinergic system in isolated term human placental tissue.

Mothers who smoke cigarettes during pregnancy give birth to babies with lower birth weights than do nonsmoking mothers. One hypothesis to explain this finding is that nicotine depresses the activity of the placental cholinergic system, which has been linked to the placental transport of amino acids and other substances. The levels and activities of several components of the term placental cholinergic system were determined in smokers and nonsmokers to investigate whether this system is involved in the effect of smoking. There were no statistically significant differences in the levels, synthesis or release of acetylcholine in the tissues from smoking and nonsmoking mothers, nor in the activities of the choline uptake system or the enzymes choline acetyltransferase, cholinesterase or sodium/potassium adenosine triphosphatase. The results do not support the hypothesis that the lower birth weights of babies born to smoking mothers is mediated by an effect of nicotine or other tobacco components on the placental cholinergic system.

Acetylcholine