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Biomedical subjects

G Kennedy

Publications and source records attributed to G Kennedy.

At least 73 records · Page 4Linked to original sources
PubMed1995

Apparent lack of response of salmon affected by pancreas disease to pancreatic enzyme replacement therapy.

A trial was conducted to establish whether there would be any benefit in feeding mammalian pancreatic enzymes to farmed salmon clinically affected by pancreas disease. Pancreatic enzymes were incorporated at a rate of 4 kg/tonne of feed and fed at 0.6 to 0.9 per cent bodyweight/day for 41 days to one cage of salmon. The weights, lengths and condition factors were established for the fish before and after the feeding trial and compared with those for an adjacent cage of untreated fish. Histopathology and blood amylase and lipase activities were monitored weekly. No significant increases in weight or condition factor, and no reduction in mortalities were recorded. Histopathology confirmed the presence of pancreas disease throughout the trial and there were concurrent skeletal and cardiac myopathies. Blood amylase activities showed no significant change and were considered to be within normal ranges; blood lipase activity remained undetectable.

Amylases↗
PubMed1995

Occupational and environmental exposure of automobile mechanics and nonautomotive workers to airborne manganese arising from the combustion of methylcyclopentadienyl manganese tricarbonyl (MMT).

Inhalation exposure to manganese (Mn) was measured for a group of garage mechanics and a control group of nonautomotive workers. The airborne Mn exposure of 35 garage mechanics suspected of being relatively highly exposed to Mn from MMT was measured at the workplace over one-week period. It also was measured for 30 nonautomotive workers at the University of Montreal. The environmental exposure also was measured for the two groups, as was the exposure to three other metals, aluminum (Al), iron (Fe), and zinc (Zn). At work the mechanics were exposed to Mn concentrations varying from 0.010 to 6.673 micrograms m-3 with a mean of 0.45 microgram m-5, while the control group was exposed to concentrations varying from 0.011 to 1.862 microgram m-3 with a mean of 0.04 microgram m-3. The mean environmental exposure for the two groups was similar to the Mn concentrations gathered in Montreal in 1992. Workplace concentrations of Al, Fe, and Zn also were higher for the garage mechanics. The results suggest that less than 10% of the Mn exposure of the garage mechanics was due to MMT. The levels of the metals measured were below the established limits for industrial and even environmental exposure.

Air Pollutants, Occupational↗
PubMed1995

Release of 5-ASA from Pentasa in patients with Crohn's disease of the small intestine.

BACKGROUND: Pentasa is a controlled-release tablet made from semipermeable microspheres and designed to continuously deliver therapeutic quantities of 5-ASA (5-aminosalicylic acid) throughout the gastrointestinal tract. Scintigraphic studies in healthy subjects have documented that 5-ASA release could occur in the small intestine. We tested here the disintegration of Pentasa in the digestive tract of nine patients with Crohn's disease of the small intestine. MATERIALS: Each patient was given, after breakfast, a 250 mg tablet of Pentasa containing samarium-153 oxide. For 8 h the progression of the isotope in the gastrointestinal tract was followed using gamma camera scintigraphy. Plasma measurement of 5-ASA and acetylated 5-ASA was used to verify the liberation and absorption of 5-ASA. RESULTS: The Pentasa tablet appeared completely dissolved in the stomach by 117 +/- 18 min. Samarium oxide was first detected in the small intestine 60 +/- 5 min after its ingestion; it reached the colon after 280 +/- 13 min and it was completely absent from the small intestine at 360 +/- 26 min. Plasma concentrations of 5-ASA started to rise after 67 +/- 7 min and were maximal at 222 +/- 25 min. CONCLUSION: In patients with Crohn's disease of the small intestine, Pentasa microgranules start releasing 5-ASA in the proximal small intestine, acting locally to exert its beneficial effect.

Adult↗
PubMed1995

Smooth muscle myosin: a high force-generating molecular motor.

Smooth muscle generates as much force per cross sectional area of muscle as skeletal muscle with only one-fifth the myosin content. Although this apparent difference could be explained at the tissue or cellular level, it is possible that at the molecular level smooth muscle cross-bridges generate greater average force than skeletal muscle cross-bridges. To test this hypothesis, we used an in vitro motility assay (VanBuren et al., 1994) in which either chicken thiophosphorylated gizzard smooth or pectoralis skeletal muscle monomeric myosin is adhered to a nitrocellulose surface. A fluorescently labeled actin filament, attached to an ultracompliant (50-200 nm/pN) glass microneedle, is brought in contact with the myosin surface. Isometric force, being generated by myosin cross-bridges pulling on the attached actin filament, is calculated from the extent to which the calibrated microneedle is deflected. By measuring the density of myosin adhered to the surface, we estimated the number of myosin cross-bridges that are able to interact with a length of actin filament in contact with the myosin surface. In a direct comparison between smooth and skeletal muscle myosin, the average force per cross-bridge was 0.8 and 0.2 pN, respectively. Surprisingly, smooth muscle myosin generates approximately 4 times greater average force per cross-bridge head than skeletal muscle myosin. Because average isometric force is the product of the cross-bridge unitary force and duty cycle, we are presently using a laser optical trap in an attempt to measure unitary events from single myosin molecules. This approach should allow us to determine whether an increase in unitary force, duty cycle, or both contribute to smooth muscle myosin's enhanced force-generating capacity compared with skeletal muscle myosin.

Actins↗
PubMed1994

Ultrastructural evidence of GABA-ergic inhibition and glutamatergic excitation in the pacemaker nucleus of the gymnotiform electric fish, Hypopomus.

The medullary pacemaker nucleus of Hypopomus triggers each electric organ discharge (EOD) by a single command pulse. It consists of electrotonically coupled 'pacemaker' cells, which generate the rhythm, and 'relay' cells, which follow the pacemaker cells and excite the spinal motoneurons of the electric organ. The pacemaker cells receive two inputs from the complex of the diencephalic prepacemaker nucleus (PPn), a GABA-ergic inhibition and a glutamatergic excitation. Relay cells, on the other hand, receive two glutamatergic inputs, one from a subnucleus of the PPn, the PPn-C, and a second from the sublemniscal prepacemaker nucleus (SPPn). We have labelled afferents to the pacemaker nucleus by injecting HRP to specific sites of the prepacemaker complex. By using immunogold-labelled antibodies and en-grid staining techniques, we demonstrated GABA and glutamate immunoreactivity in labelled synaptic profiles of ultra-thin sections of the pacemaker nucleus. The two types of synapses were interspersed on the surfaces of pacemaker cells, with GABA-immunoreactive synapses apparently representing the GABA-mediated input of the 'PPn-I', an inhibitory subdivision of the PPn, and glutamate-immunoreactive synapses representing the input of the 'PPn-G', an excitatory subdivision of the PPn. Only glutamate-immunoreactive synapses were found on relay cells.

Animals↗
PubMed1994

Occupational and environmental exposure of garage workers and taxi drivers to airborne manganese arising from the use of methylcyclopentadienyl manganese tricarbonyl in unleaded gasoline.

Occupational and environmental exposure to airborne manganese has been measured for two groups of workers in Montreal, taxi drivers and garage mechanics. In Canada methylcyclopentadienyl manganese tricarbonyl (MMT) has replaced lead as an anti-knock agent in gasoline and represents a potentially important source of manganese contamination for the population in general and for the two chosen groups of workers in particular. Twenty workers (10 taxi drivers and 10 garage mechanics) wore a personal air sampler for five consecutive working days and two off-work periods. The amount of total Mn on each filter was determined by neutron activation analysis and then converted to atmospheric Mn concentrations. The values obtained varied from 0.004 microgram m-3 to 2.067 micrograms m-3. At work the garage mechanics were exposed to an average of 0.250 microgram m-3 and the taxi drivers to 0.024 microgram m-3. Off-work, the two groups were exposed respectively to an average of 0.007 microgram m-3 and 0.011 microgram m-3. In the garages there was twice as much Mn in the air on days when the doors were closed compared to days when they were left opened (0.314 micrograms m-3/0.152 microgram m-3). The levels found in this study remain well below the established limits for occupational and environmental airborne exposure. These results will lead to further studies to positively identify the source of Mn as MMT and to explore other pathways leading to the contamination of the general population.

Air Pollutants↗
PubMed1993

Lack of effect of cimetidine on cigarette smoking.

The efficacy of cimetidine as a treatment that could reduce smoking in heavily dependent smokers has been determined. In a randomised, double-blind, double-crossover experiment, 43 heavy smokers were divided into two groups, one receiving cimetidine 400 mg orally three times a day, and the other receiving placebo for two weeks followed by the alternative treatment (placebo or cimetidine). No significant difference in the mean alveolar carbon monoxide, nicotine or cotinine levels was found between the two treatment groups compared to baseline. Since the alveolar carbon monoxide level reflects the intensity of smoking behaviour, the results suggest that no change in smoking behaviour occurred in the subjects. Contrary to our previous findings that cimetidine decreased the total body clearance of nicotine by 30% in a population of non-smokers, in the heavily dependent smokers, cimetidine did not appear to alter nicotine elimination. One possible explanation for the discrepancy is that tobacco smoking is known to induce nicotine metabolism and the induction might have offset any effect of cimetidine on nicotine elimination. Cimetidine does not appear to be a useful treatment leading to a reduction or cessation of cigarette smoking.

Carbon Monoxide↗
PubMed1993

No place for motor speech acts in the assessment of dysphagia? Intelligibility and swallowing difficulties in stroke and Parkinson's disease patients.

Speech and language therapists are increasingly being asked to treat dysphagic patients. Concern has been expressed and surveys have confirmed that radiological assessment procedures are rarely available. Consequently, patients must often be assessed and their treatment planned on the basis of bedside examinations. Despite evidence that swallowing disorders need not be related to problems of articulation, recommendations on the procedure of such examinations frequently include an evaluation of speech and non-speech articulatory movements. A study is reported of patients who exhibit both dysphagia and dysarthria as a result of either stroke or Parkinson's disease. Assessments of the intelligibility of their speech and of their swallowing problems were found to be unrelated. The implications of this finding for the assessment of dysphagia are discussed.

Aged↗
PubMed1993

Cell adhesion receptors and early mammalian heart development: an overview.

Cardiovascular development is the end result of a complex genetic program subject to regulation by signals transmitted between a cell and its extracellular environment. As cells encounter new extracellular matrices or establish new cell-cell interactions, new genes must be activated to accommodate the altered developmental situation within which the cell finds itself. This is likely reflected in a program of adhesion receptor and counter receptor expression on the surface of cells engaged in the morphogenesis. To understand the molecular basis of development, it is necessary to first determine if such a program exists and then to establish the role of various receptors and counter receptors in the particular morphogenetic process under investigation. To this end, we have initiated an investigation into expression of specific adhesion receptors during cardiovascular development in the mouse. Here, we demonstrate that platelet endothelial cell adhesion molecule (PECAM)-1 is an excellent marker for following vascular formation in the mammalian embryo. It is expressed during development in several alternatively spliced forms involving the cytoplasmic domain of the molecule. These forms differ in their ligand binding properties. Thus, a change in the cytoplasmic domain affects the folding of the molecule in such a way as to structurally alter the extracellular domain. Further, several receptors including the laminin receptor, the fibronectin receptor and a hyaluronic acid receptor, display specific expression patterns during heart development. These include differential expression in the endocardium and myocardium, down regulation during endocardial and myocardium, down regulation during endocardial cushion formation and cessation of expression in particular regions of the heart upon maturation. Interference with the function of one of these receptors (the fibronectin receptor) results in aberrant heart formation. These observations strongly support the concept that morphogenesis requires specific cell adhesion molecules that are expressed in precisely choreographed programs.

Animals↗
PubMed1992

Radioactivity of building materials available in Canada.

Concentrations of 232Th, 226Ra, and 40K were measured in 47 samples of seven different building materials available in Canada. The radioactivities were low for woods and natural gypsums and up to 160 Bq kg-1 232Th, 121 Bq kg-1 226Ra, and 990 Bq kg-1 40K for bricks and tiles. Annual gonadal doses generated by these materials vary from 0.01-1.4 mSv.

Canada↗
PubMed1990

A new high performance liquid chromatographic method for the simultaneous measurement of S-adenosylmethionine and S-adenosylhomocysteine. Concentrations in pig tissues after inactivation of methionine synthase by nitrous oxide.

A rapid gradient method has been established to measure simultaneously the tissue levels of S-adenosylmethionine (AdoMet) and S-adenosylhomocysteine (AdoHcy). The method involves application of a 15%-25% linear gradient of methanol over a period of 10 min to an initial mobile phase of 15% methanol with 25 mM sodium phosphate, 10 mM 1-heptanesulfonic acid solution at pH 3.2 and a flow rate of 1 mL/min. AdoHcy elutes at 9.5 min and AdoMet at 12.6 min. The assay has a detection limit of 10 pmol and is linear in the concentration range 30-800 pmol. The method was used to assess changes in AdoMet and AdoHcy concentrations of pig tissues after seven days exposure to the anaesthetic gas nitrous oxide which irreversibly inactivates methionine synthase and induces an inability to recycle homocysteine, particularly in neural tissues. The treatment caused significant alterations in cellular AdoMet:AdoHcy ratios which were principally due to a dramatic rise in AdoHcy concentrations.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed1990

Structure determination of adducts from the reaction of (R)-glycidaldehyde and guanosine.

The structures of the initial adducts formed in the reactions of guanosine or deoxyguanosine with (R)-glycidaldehyde have been determined and compared with those obtained from racemic glycidaldehyde. A new stable adduct has also been identified which is a potential biomarker for glycidaldehyde interactions with DNA. Mechanisms are proposed to account for the formation of all the observed products. The results provide information on the molecular basis for the genotoxicity of glycidaldehyde and compounds which generate this reactive aldehyde in vivo.

Aldehydes↗
PubMed1989

Differential effects of viqualine on alcohol intake and other consummatory behaviors.

Viqualine, a serotonin releaser and uptake inhibitor, was studied for its effects on consummatory behaviors (intake of ethanol and nonalcoholic beverages, cigarette smoking, and changes in body weight) in 29 men who were early-stage problem drinkers between 21 to 55 years of age. Subjects were randomly assigned to receive a placebo and either 100 mg/day viqualine (n = 15) or 200 mg/day viqualine (n = 14) orally in a double-blind crossover study. Viqualine administration and ethanol intake were assessed by self-reports and by measurement of drug and ethanol concentrations in body fluids. Compared with placebo, 100 mg/day viqualine did not decrease ethanol intake. However, 200 mg/day viqualine significantly decreased the total number of drinks consumed in a 14-day period (F1,12 = 5.3; p less than 0.05). An increase in the number of abstinent days was significant only for those subjects who received the placebo first (F1,6 = 11.3, p less than 0.02). Subjects reported a decreased interest in and decreased desire for alcohol during viqualine treatment. Patterns of response varied, but 64% of the subjects decreased the number of alcoholic drinks consumed and/or increased the number of days of abstinence by at least 25% during treatment with 200 mg/day viqualine compared with placebo treatment. Neither dose of viqualine had an effect on cigarette smoking or on consumption of nonalcoholic beverages, but subjects showed significant decreases in body weight with both doses. These findings indicate that viqualine both attenuates ethanol intake and reduces body weight in human beings.

Adult↗