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Biomedical subjects

D R Smith

Publications and source records attributed to D R Smith.

At least 235 records · Page 13Linked to original sources
PubMed1988

Polymorphisms in mitochondrial DNA of European and Africanized honeybees (Apis mellifera).

This study demonstrates polymorphisms in both the length and in the restriction enzyme cleavage sites of honeybee mitochondrial DNA (mtDNA). The levels of variation are typical of those found in other metazoan species. These polymorphisms are potentially useful for the identification of Africanized bees in the western hemisphere and for study of honeybee phylogenetics.

Animals↗
PubMed1988

Photoimmunology: the mechanisms involved in immune modulation by UV radiation.

Ultraviolet radiation (UVR) may be the most prevalent agent that man encounters in his environment. As a result, certain biological adaptations take advantage of the beneficial effects of UVR exposure, e.g. the photoactivation steps involved in vitamin D metabolism. In this regard, UVR plays an important role in maintaining our good health; however, it must be noted that UVR is potentially the most harmful naturally occurring agent in our environment. Thus, it appears that several mechanisms have evolved to protect us against the detrimental effects of UVR overexposure. Although epidermal melaninization or "tanning" may be the most obvious example of these processes, we would argue that adoptive mechanisms within the immune system also provide protection against UVR-induced skin damage. It is now known that UVR affects the distribution and functional activities of various immunocompetent cells within the skin, as well as modifying the production of inflammatory and hematopoietically active cytokines. This review will focus on the known mechanisms involved in the immune modulatory effects of UVR and how adoptive immune responses to UVR-induced skin damage contribute to specific pathological processes.

Immune System↗
PubMed1988

Coronary artery calibre after direct intra-arterial infusion of epoprostenol (prostacyclin).

Because epoprostenol (prostacyclin) is a prostaglandin that causes vasodilatation and inhibits platelet function it may be of benefit during coronary artery angioplasty. The safety and capacity of intracoronary epoprostenol to dilate coronary arteries were assessed in 16 patients undergoing routine coronary angiography. The view that best displayed the left epicardial coronary arteries was selected as a control for each patient. Intracoronary epoprostenol was then given and the angiogram was repeated in the chosen view. The procedure was repeated twice: once with a higher dose of epoprostenol and once after intracoronary isosorbide dinitrate. Angiograms were coded and analysed by an observer who was unaware of the treatment. The calibre of the arteries was measured from traced projections of the angiograms. The blood pressure, heart rate, and electrocardiogram were recorded throughout. The first two patients were given epoprostenol infusions of 2.5 and 5.0 ng/kg per minute to assess safety, and there were no untoward reactions. The next ten patients had epoprostenol infusions of 5.0 and 7.5 ng/kg per minute followed by intracoronary isosorbide dinitrate. No haemodynamic disturbances occurred and coronary luminal calibre did not change with epoprostenol (mean (SD) luminal diameter: 2.85 (0.62) mm control, 2.80 (0.61) mm at 5.0 ng/kg, and 2.80 (0.54) mm at 7.5 ng/kg), but it did increase significantly with isosorbide dinitrate (to 3.17 (0.36) mm). The last four patients had epoprostenol infusions of 7.5 and 10 ng/kg followed by intracoronary isosorbide dinitrate and two of them became hypotensive (one after epoprostenol and one after isosorbide dinitrate). Coronary luminal calibre did not change significantly (3.5 (0.45) mm control, 2.96 (0.81) mm at 7.5 ng/kg, 3.45 (0.96) mm at 10 ng/kg, and 3.20 (0.61) mm with isosorbide dinitrate). Eight patients developed tall T waves on the electrocardiogram during epoprostenol infusion but none had arrhythmias. The results indicate that clinically tolerable doses of intracoronary epoprostenol do not significantly dilate the epicardial coronary arteries. This route of administration is therefore unlikely to be of use during coronary angioplasty, although the antiplatelet action of intravenous epoprostenol might help to prevent restenosis.

Coronary Angiography↗
PubMed1988

QSAR studies of hydrazone uncouplers of oxidative phosphorylation.

Semiempirical molecular orbital calculations have been performed on a series of hydrazone uncouplers of mitochondrial oxidative phosphorylation which show insecticidal activity. Regression analysis yielded significant correlations between uncoupling activity, insecticidal potency and such physicochemical or theoretically-derived parameters as lipophilicity, pKa and atom charges.

Adenosine Diphosphate↗
PubMed1988

Tissue pressure management in the vocational setting.

A significant problem that confronts a spinal cord injured person who returns to work is how to design the work station and tasks so that pressure sores do not develop and compromise the worker's productivity. In this study, reach was investigated as a mechanism to cause weight shift during task execution. It is shown that by using an extended reach motion, it is possible to cause effective weight redistribution. By incorporating this type of motion in task design for mobility impaired workers, it should be possible to reduce their risk of developing pressure sores with a minimal effect on job performance.

Arm↗
PubMed1987

Comparison of angiotensinogen and tetradecapeptide as substrates for human renin. Substrate dependence of the mode of inhibition of renin by a statine-containing hexapeptide.

The kinetic properties of two different substrates for human renin, a synthetic tetradecapeptide and the natural substrate human angiotensinogen, have been compared. While the Vmax was similar for the two substrates, the Km values differed by a factor of 10, i.e., 11.7 +/- 0.7 microM (tetradecapeptide) and 1.0 +/- 0.1 microM (angiotensinogen). The mode of inhibition of renin by a statine (Sta)-containing hexapeptide, BW897C, that is a close structural analog of residues 8-13 of human angiotensinogen (Phe-His-Sta-Val-Ile-His-OMe), was determined for the two substrates. Competitive inhibition was observed when tetradecapeptide was the substrate (Ki = 2.0 +/- 0.2 microM), but a more complex mixed inhibition mode (Ki = 1.7 +/- 0.1 microM, Ki' = 3.0 +/- 0.23 microM) was found with angiotensinogen as substrate. This mixed inhibition probably results from the formation of an enzyme-inhibitor-substrate or enzyme-inhibitor-product complex and reflects the more extensive interactions that the protein angiotensinogen, as opposed to the small tetradecapeptide substrate, can make with renin. We conclude that the mixed inhibition observed when angiotensinogen is used as renin substrate could be important in the clinical application of renin inhibitors because it is less readily reversed by increased concentrations of substrate than is simple competitive inhibition.

Amino Acids↗
PubMed1987

A genetic linkage map of the human genome.

We report the construction of a linkage map of the human genome, based on the pattern of inheritance of 403 polymorphic loci, including 393 RFLPs, in a panel of DNAs from 21 three-generation families. By a combination of mathematical linkage analysis and physical localization of selected clones, it was possible to arrange these loci into linkage groups representing 23 human chromosomes. We estimate that the linkage map is detectably linked to at least 95% of the DNA in the human genome.

Chromosome Mapping↗
PubMed1987

Hepatic estrogen and androgen receptors and binding proteins in streptozotocin-diabetic male Wistar rats.

We have previously shown that there are decreases in the sex differences seen in certain hepatic drug and steroid metabolising enzymes in rats with early (4 day) streptozotocin-induced diabetes. We postulated that hepatic sex hormone receptors or binding proteins might be involved in modulation of the sex differences noted in metabolism. In the present study, we measured the binding kinetics of the hepatic cytosolic estrogen receptor and androgen receptor, along with the high capacity-low affinity estrogen binding protein. At 4 or 10 days post-streptozotocin (60 mg/kg intravenously), there was no change in the maximum binding capacity of the estrogen receptor, nor in the hormone affinity of any of the three proteins. However, the binding capacity of the androgen receptor and estrogen binding protein in the diabetic animals was decreased to less than half of control levels. This effect could not be reversed by hormone replacement with any of the following regimens: protamine zinc insulin, 10 U/kg subcutaneously once a day; Toronto insulin, 15 U/kg subcutaneously twice a day; testosterone enanthate, 1 mg/kg s.c. once a day; triiodothyronine, 30 micrograms/kg s.c. daily; ovine growth hormone: 0.02 U/h s.c., 30 micrograms s.c. 7 times daily, 30 micrograms i.v. 4 times daily; or various combinations of these hormones. Stress, such as 4 intravenous injections of saline per day, was noted to decrease the binding capacity of the estrogen binding protein. Therefore, we measured the basal serum corticosterone levels, which were not significantly different from control values in untreated or insulin-treated diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Purified scrapie prions resist inactivation by procedures that hydrolyze, modify, or shear nucleic acids.

Prions were purified from scrapie-infected hamster brains and incubated for 24 hr at 65 degrees with 2 mM Zn2+ or 5 mM Mg2+; no loss of infectivity was observed. Bacteriophage M13, tobacco mosaic virus (TMV), potato virus X, and potato spindle tuber viroid were all inactivated by divalent metal ions under these conditions. Prions also resisted inactivation by prolonged digestions with DNase I, RNases A and T1, and micrococcal nuclease. Prions were resistant to psoralen photoadduct formation using high concentrations of psoralens; in contrast, M13 bacteriophage was inactivated by low concentrations of all these psoralens. Hydroxylamine failed to inactivate prions even after lengthy exposures to concentrations as high as 1 M, while TMV and M13 were both inactivated. Sonication of prions failed to decrease infectivity even though rod-shaped aggregates were disrupted while both M13 and TMV lost infectivity.

Animals↗
PubMed1987

Lithium and haloperidol differentially alter the dynorphin A (1-8) and enkephalin levels in the neurointermediate lobe of rat pituitary.

Repeated administration of the antimanic drug lithium (4 mEq/kg/day for 2, 4 or 6 days, i.p.) to rats produced a progressive decline and eventual depletion of dynorphin-A (1-8) (DYN) concentration whereas Met5-enkephalin (ENK) was only marginally decreased in the neurointermediate lobe of the pituitary (NIL). Administration of a neuroleptic haloperidol neither affected ENK and DYN levels nor influenced lithium-induced changes. The study reveals that lithium produces a preferential perturbation in the dynorphin system relative to the enkephalin system. These results taken together with other evidence, indicate that dynorphin is possibly coreleased with vasopressin following lithium administration and provide a pharmacological support to the previously described colocalization and corelease of these endogenous peptides in the NIL.

Animals↗
PubMed1987

Use of the maximal ST/HR slope to estimate myocardial ischaemia after recent myocardial infarction.

Fifty two patients were examined 4-6 weeks after myocardial infarction to assess whether factors other than coronary artery narrowing affect the maximal ST/HR slope which is used as an index of myocardial ischaemia. The slope was compared with indices of myocardial scarring or cardiac enlargement derived from x ray and echocardiographic and angio-cardiographic investigations. In 35 (67%) patients the slope failed to predict the severity of myocardial ischaemia attributable to coronary artery narrowing: in 14 (27%) patients the slope overestimated the findings of coronary angiography and in 21 (40%) patients the slope underestimated the findings of coronary angiography. In the remaining 17 (33%) patients the slope accorded with the assessment of myocardial ischaemia by coronary angiography. Underestimation by the slope was associated with significantly poorer left ventricular function and a lower ejection fraction, indicating a greater degree of myocardial scarring. To assess whether overestimation was related to cardiac enlargement with better preservation of ventricular function a follow up examination was performed six months after infarction. In the overestimated group 11 patients were followed up and seven of them showed a reduction in the maximal ST/HR slope which correlated with a reduction in the cardiothoracic ratio. This suggested that cardiac enlargement had contributed to myocardial ischaemia. The results suggest that if the maximal ST/HR slope is an index of exercise induced myocardial ischaemia after recent infarction, it is subject to the influences of coronary artery narrowing as well as those of scarring and cardiac enlargement.

Adult↗
PubMed1986

Assessment of the effect of nifedipine on myocardial ischaemia by using the ST segment/heart rate slope.

Nifedipine is used in patients with stable angina of effort and any resulting change in symptoms is attributed to several effects of nifedipine. However, there have been indications in such patients that one effect of nifedipine could be an increase in the severity of myocardial ischaemia, and the present report involves a trial the results of which could explain this effect. In the present trial, the effect of nifedipine on myocardial ischaemia was assessed by using the maximal ST/heart rate slope. This slope was used as an index of myocardial ischaemia because, in our hands in patients with angina, an increase or a decrease in the value of the slope respectively indicated an increase or a decrease in the severity of myocardial ischaemia as assessed by coronary arteriography. The maximal ST/heart rate slope was obtained at least twice in each of 23 patients with stable angina, with and without nifedipine; two patients were examined twice and three other patients were examined after an increased dose. Nifedipine resulted in an increase in the slope in 24 of the 28 comparisons, no change in three and a decrease in one comparison; there was a statistically significant (P less than 0.005; n = 28; paired t-test) increase in the maximal ST/heart rate slope. A further increase in the slope was obtained by increasing the dose of nifedipine in two out of three patients. The increase in the maximal ST/heart rate slope occurred in the absence of any effect of nifedipine on the initial level of ST segment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗