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Biomedical subjects

R H Smith

Publications and source records attributed to R H Smith.

At least 91 records · Page 5Linked to original sources
PubMed1988

A controlled trial of GL enzyme in the treatment of acute myocardial infarction.

GL enzyme (hyaglosidase) is a highly purified component enzyme of hyaluronidase. A therapeutic trial was carried out in the treatment of suspected myocardial infarction among 1,488 patients presenting within 6 h of the onset of symptoms. No significant reduction in mortality at 6 months was observed in the GL group (15.7%) compared with the placebo group (16.4%). Mortality at 2 weeks was also unaffected by treatment (GL 10.3%; placebo 10.9%).

Clinical Trials as Topic↗
PubMed1987

In vitro proliferation of lymphocytes from cyclophosphamide-pretreated mice immunized with antigen mixed with dimethyl dioctadecyl ammonium bromide.

A blastogenesis assay employing lymphocytes from cyclophosphamide-pretreated mice immunized with antigen mixed with the immunopotentiating compound dimethyl dioctadecyl ammonium bromide is described. The model antigen used for determining the assay parameters was inactivated purified measles virus. The optimal time for removal of immunologically primed T cells was 7 days after immunization of mice pretreated 2 days previously with 200 mg of cyclophosphamide/kg. The peak lymphoproliferative response was found to occur after 3-5 days in culture, depending on the concentration of antigen used. Although fetal bovine serum and syngeneic mouse serum each worked well as a medium supplement, significantly higher specific and lower non-specific lymphoproliferation were obtained when the mouse serum was used. Most of the lymphocytes responding to antigen were of the Ly 1.2 phenotype. Specificity of the blastogenic response was shown by a lack of cross-reactivity among measles virus, herpes simplex virus type 1 and vesicular stomatitis virus antigens. This approach to a mouse blastogenesis assay involves an easy way to induce strong T cell priming in mice, while still providing an assay which has an ideal combination of low non-specific and high antigen-specific responses.

Adjuvants, Immunologic↗
PubMed1987

Tumors in F344 rats by oral administration of 1,3-diethyltriazene.

A group of 20 male F344 rats was given by gavage a solution of 2.5 mg of 1,3-diethyltriazene in 0.2 ml corn oil twice a week for 20 weeks. Diethyltriazene is very unstable in hydroxylic solvents, but when administered in oil by gavage it induced tumors in almost all of the treated animals, 16 of which had neoplasms of the forestomach; 13 of which were carcinomas. In addition 9 rats had adenomas of the nasal mucosa, two had alveolar-bronchiolar adenomas of the lung, one had a carcinoma of the esophagus and one an adenocarcinoma of the ileum. Half of the rats had died by week 56 of the experiment, the first at week 40 and the last at week 73. The induction of tumors at sites distant from the stomach indicate that diethyltriazene is more stable in the body than would be predicted from its chemical behavior. Although diethyltriazene is a protected alkyldiazonium ion, its carcinogenic effects in rats differ from ethylnitrosoureas, which are also ethylating agents.

Administration, Oral↗
PubMed1987

Studies of rumen function in an in vitro continuous culture system.

An in vitro continuous culture system to simulate processes in the rumen is described. This comprises a culture vessel (Fig. 2) fed continuously with pelleted solid feed (Fig. 1); artificial saliva also enters the vessel while effluent leaves it continuously in two streams, one is filtered and the other simply overflows (Fig. 1). In this way liquid and solid turnover times may be manipulated independently; in a trial experiment the former and latter were 6.3% and 3.4% per hour respectively. In four replicated experiments a steady-state was achieved in 5-6 days with a feed of barley, tapioca, fishmeal, urea and straw and maintained for a further 7 to 14 days. During a steady-state period, rumen characteristics in terms of protozoal count, pH, redox potential, total volatile fatty acid concentration and ammonia concentration were stable and similar to those found in the rumens of animals given similar diets. Flows of microbial N compounds were assessed by infused Na2H32PO4 with the artificial saliva and estimating the 32P label incorporated in bacterial fractions. The system demonstrably provided a satisfactory means for studying many aspects of rumen function.

Animal Feed↗
PubMed1987

T cell cross-reactivity among viruses of the paramyxoviridae.

Blastogenesis and delayed-type hypersensitivity assays were used to examine mouse T cell responses to five viruses representing the three genera of the Paramyxoviridae. Cross-reactive T cell responses were observed in a lympho-proliferative assay for measles, mumps, respiratory syncytial, canine distemper and parainfluenza type 3 virus. Confirmation of T cell cross-reactivity among measles, mumps and respiratory syncytial virus was obtained with a delayed-type hypersensitivity test. These results show that T cell cross-reactivity is common for Paramyxoviridae viruses, even though these viruses show virtually no inter-genus antibody cross-reactivity. The cross-reactivity among respiratory syncytial, measles and mumps virus at the T cell level may have implications for usage of the attenuated measles/mumps/rubella (MMR) vaccine. Respiratory syncytial virus is contacted by many children before they receive the MMR vaccine and T cells induced by respiratory syncytial virus may influence subsequent development of immunity to measles and/or mumps virus.

Animals↗
PubMed1986

Characterization of the plasma membrane bound GTPase from rabbit neutrophils. I. Evidence for an Ni-like protein coupled to the formyl peptide, C5a, and leukotriene B4 chemotaxis receptors.

We have characterized the GTPase activity of the Ni-like guanine-nucleotide-binding regulatory protein in rabbit neutrophil plasma membranes. The low Km (3.64 +/- 0.87 X 10(-7) M) GTPase copurified with the formyl peptide receptor in the plasma membrane fraction obtained by discontinuous sucrose density gradient centrifugation. The Vmax (23.9 +/- 2.91 pmol/mg/min) and Km of the unstimulated enzyme were similar to those reported for Ni in other cell types. The activity of the unstimulated enzyme was both magnesium and sodium dependent and linear over the first 4 min of the assay. The chemoattractants, formyl-methionyl-leucyl-phenylalanine (fMLP), C5a, and leukotriene B4 (LTB4) stimulated the GTPase in purified neutrophil plasma membrane preparations, whereas other secretagogues, such as A23187 and PMA, were without effect. Lineweaver-Burk analysis showed an fMLP-induced increase in Vmax (31.94 +/- 4.80 pmol/mg/min) (33.1 +/- 9.5%) but not in Km. The dose-response curve for fMLP stimulation showed an ED50 of 4.1 +/- 1.0 X 10(-8) M and an overall 22.2 +/- 3.1% maximal stimulation. C5a (30 micrograms/ml) increased the activity of the GTPase 21.3 +/- 5.7% and 10(-7) M LTB4 produced a 32.2 +/- 5.4% increase. Activated pertussis toxin treatment of neutrophil plasma membranes inhibited by 72.5 +/- 14.3% the stimulation of GTPase activity induced by fMLP; however, activated cholera toxin had no effect on the inhibition of fMLP stimulation, suggesting a direct role for an Ni-like protein in the coupling process. In contrast to the lack of inhibition of fMLP stimulation by activated cholera toxin treatment of plasma membranes, both pertussis toxin and to a lesser extent cholera toxin treatment reduced fMLP, C5a, and LTB4 stimulation of the GTPase in sonicates prepared from pretreated whole cells. Pertussis toxin inhibited fMLP stimulation of the GTPase by 75 +/- 7%, C5a stimulation was inhibited by 83 +/- 13%, and LTB4 stimulation was inhibited completely. Sonicates prepared from neutrophils treated similarly with cholera toxin showed a smaller inhibition of GTPase activity (50 +/- 4% and 14 +/- 9% for fMLP and LTB4, respectively) with the exception of C5a, where CT inhibition (81 +/- 32%) equaled pertussis toxin inhibition. Similarly, pertussis toxin completely inhibited the release of the granule enzyme N-acetyl-glucosaminidase by all three chemoattractants, whereas cholera toxin, except with C5a stimulation, had little or no effect.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

The critical micelle concentration of some physiologically important fatty acyl-coenzyme A's as a function of chain length.

The critical micelle concentration (CMC) of a series of saturated fatty acyl-CoAs have been determined using a fluorescent titration method with 2-toluidinylnaphthalene-6-sulfonate as a probe. The CMC was found to be a function of the number of carbon atoms in the acyl chain over the range tested (12 to 18). A double bond has the effect on the CMC of decreasing the acyl chain by 1.6 carbon atoms. Knowledge that the CMC of each of these fatty acyl-CoAs is a function of the acyl chain length and the availability of a simple and appropriate method for the estimation of this property under other conditions should be of importance in designing and interpreting in vitro experiments with these compounds.

Acyl Coenzyme A↗
PubMed1986

Selection of imagery in the relief of chronic and acute clinical pain.

This study examined the effects of pleasant imagery and type of pleasant imagery on the relief of acute and chronic pain. Two images were used in alternation, both selected from five images generated by the patient. The first image was the one most preferred by the patient; the second was the one determined by the experimenter to represent the most successful mastery of developmental stages according to the schemata outlined by Erickson (International Encyclopedia of Social Sciences, Vol. 9, McMillan, 1968). It was hypothesized that an image associated with successful phases of life would be less likely to provoke anxiety disruptive of the relaxation procedure and thus be more effective in the relief of pain. Both images were successful in reducing reported pain relief over a three-day period, but as predicted, the developmentally-selected image was more effective. The general effectiveness of these images held only for patients with acute pain.

Acute Disease↗
PubMed1986

Exchanges of water and certain water-soluble minerals during passage of digesta through the stomach compartments of young ruminating bovines.

1. Four ruminating bull calves were provided with cannulas in the rumen and abomasum and a sleeve sutured at the omosal-abomasal orifice that permitted digesta flowing from the omasum to be diverted and collected. 2. The calves were each given in turn a high-roughage (HR) and high-concentrate (HC) diet consisting mainly of dried grass and flaked maize in the proportions 3:2 and 1:2 by weight respectively. Water-soluble non-absorbable marker (polyethylene glycol) was also given and the diets were sometimes supplemented with magnesium sulphate. For each diet (HR(0), HR(Mg), HC(0), HC(Mg], collections were made from the rumen, reticulum, omasal outflow and abomasum, and flows of water, sodium, potassium and chloride calculated at these sites relative to intakes. 3. The general pattern of net exchange was similar for all the diets. Substantial additions of water and Na, a small addition of K and a small absorption of Cl occurred between mouth and reticulum. Substantial (approximately 40-60%) absorption of water and Na, a small absorption of K and considerable secretion of Cl occurred in the omasum. Quantitative comparisons indicated that addition of water and Na up to the reticulum, presumably in saliva, was significantly greater for the HR than the HC diets. Addition of Mg appeared to stimulate absorption of Na and water up to the reticulum for unknown reasons. Re-absorption of these components in the omasum varied for different calves and diets but appeared to be influenced primarily by a positive linear relation between amounts of digesta flowing into the omasum and amounts of water and Na absorbed from it. The proportion of water absorbed also increased with increasing entry rates of water. 4. Other findings showed that pH values rose slightly (about 0.2 pH units) but significantly in the reticulum compared with the rumen and that the value fell again by about the same amount during the passage of digesta through the omasum. Changes between omasal outflow and the abomasum were as expected, with marked additions of Cl, Na and water and a fall in pH.

Abomasum↗
PubMed1986

Exchanges of magnesium and phosphorus at different sites in the ruminant stomach.

Three ruminating calves were each provided with a rumen cannula (from which reticulum samples could be obtained), an abomasal cannula and a sleeve sutured at the omasal-abomasal orifice that permitted digesta flowing from the omasum to be diverted and collected. The calves were each given in turn a high roughage (HR) and high concentrate (HC) diet consisting mainly of dried grass and flaked maize in the proportions by weight of 3:2 and 1:2 respectively. A water soluble non-absorbable marker (polyethylene glycol) and a particulate marker (103Ru-phenanthroline complex) were also given and the diets were sometimes supplemented with MgSO4. For each diet (HR(O), HR(Mg), HC(O), HC(Mg)) samples were taken from the reticulum and omasal outflow. Magnesium, phosphorus, PEG and 103Ru were measured in the samples as taken and liquid-rich and solid-rich fractions prepared from them. From their distributions relative to the two markers, Mg and P flows into and out of the omasum were estimated. Results were too few to show significant differences in absorption efficiency between diets but overall approximately 10-40% of the Mg entering the omasum was absorbed as a net effect implying that this organ may be the major site of Mg absorption in young cattle. For P also substantial amounts entering the omasum (approximately 10-40%) were absorbed in that organ.

Animals↗
PubMed1986

Physiological Changes in Cultured Sorghum Cells in Response to Induced Water Stress : II. Soluble Carbohydrates and Organic Acids.

Eight cultivars Sorghum bicolor (L.) Moench were grown as callus cultures under induced, prolonged water stress (8 weeks), with polyethylene glycol in the medium. Concentrations of soluble carbohydrates and organic acids in callus were measured at the end of the growth period to determine differences in response to prolonged water stress. Sucrose, glucose, fructose, and malate were the predominant solutes detected in all callus at all water potentials. All cultivars had high levels of solutes in the absence of water stress and low levels in the presence of prolonged water stress. However, at low water potentials, low levels of solutes were observed in drought-tolerant cultivar callus and high solute levels were observed in drought-susceptible cultivar callus. Estimated sucrose concentrations were significantly higher in water-stressed, susceptible cultivar callus. Large solute concentrations in susceptible cultivar callus were attributed to osmotic adjustment and/or reduced growth during water stress.

Journal Article↗
PubMed1986

Effects of selenazofurin and ribavirin and their 5'-triphosphates on replicative functions of influenza A and B viruses.

We studied the effects of selenazofurin alone and in combination with ribavirin on replication of influenza A and B viruses. These drugs showed little cytotoxicity as measured by leucine incorporation into protein in MDCK cells, although they were potent inhibitors of viral replication in the same cells. Selenazofurin inhibited growth of influenza A and B viruses at concentrations (50% inhibitory dose = 25 and 19 microM, respectively) which were similar to those at which growth was inhibited by ribavirin (50% inhibitory dose = 50 and 30 microM, respectively). The inhibition of replication of either influenza A or B virus was additive for any combination of ribavirin and selenazofurin. The effects of the 5'-triphosphate of selenazofurin on two replicative functions associated with the influenza virus RNA-dependent RNA polymerases, primer generation (initiation of transcription) and its subsequent elongation, were measured. Elongation was more sensitive to selenazofurin 5'-triphosphate than was primer generation, and the effects of this drug on these functions were approximately the same as those of ribavirin 5'-triphosphate. The activities of ribavirin triphosphate and selenazofurin triphosphate were additive, and combinations did not potentiate the individual inhibitory effects of these drugs on elongation.

Animals↗
PubMed1986

Protection of mice from lethal influenza virus infection with high dose-short duration ribavirin aerosol.

An aerosol generated from a reservoir containing 60 mg of ribavirin per ml given for 2 h twice daily for 4 days afforded the same high level of protection against lethal influenza virus infection of mice as a longer, conventional treatment schedule (20 mg/ml given for 11 h daily for 4 days). Incremental decreases in ribavirin concentration made while maintaining the 2-h intermittent schedule provided progressively less protection of mice. Mice exposed to the 60-mg/ml doses had significantly increased pulmonary and serum drug levels when compared with mice given 20 mg of drug per ml, these increases were transient, and no evidence of pulmonary intolerance was detected. These studies suggest that protective effects of ribavirin against influenza virus infection can be achieved without untoward effects if higher doses and shorter periods of administration are used.

Aerosols↗
PubMed1986

Cocaine users seen in medical practice.

Cocaine use and the public's awareness of cocaine abuse problems have escalated sharply in the past several years and yet little is known of the users direct contact with medical providers. A questionnaire was designed, mailed to 2,422 physicians in general and family practice, internal medicine, emergency medicine, and psychiatry. The results indicated that many more cocaine users were presently being seen than had been seen in the same month in the previous year. Most of the cocaine patients were seen by psychiatrists, and contrary to popular myth, only a small percentage had high incomes. Most were young male, polydrug users who had been using for more than several months. Few seemed to want treatment. The responding physicians who saw cocaine patients almost always commented on how they managed such patients. Physician involvement varied from almost none (drug use was seen as incidental) to brief advice, referral, or direct treatment. Physician's comments provide a mirror of problems and feelings surrounding this patient population. Contrasts and similarities with hotline data are discussed. The growth of physician recognition of this problem population clearly indicates a treatment need.

Adult↗
PubMed1986

Cyclophosphamide and dimethyl dioctadecyl ammonium bromide immunopotentiate the delayed-type hypersensitivity response to inactivated enveloped viruses.

Immunization of BALB/c mice with measles virus inactivated with beta-propiolactone and mixed with 100 micrograms of the cationic surface-active lipid dimethyl dioctadecyl ammonium bromide (DDA) primes for a strong virus-specific delayed-type hypersensitivity (DTH) response that peaks 1 week later. Optimal immunization and challenge doses were found to be 8 and 4 micrograms/mouse, respectively, and pretreatment with 200 mg of cyclophosphamide/kg 2 days prior to immunization significantly enhanced the DTH response. When compared to Freund's complete and incomplete adjuvants, DDA was superior for induction of DTH to inactivated purified measles virus. As DDA could be administered to animals at a site different from the measles virus antigens, or 1 day previously, and still significantly enhance the DTH response, DDA is probably acting more as an immune modulator than as a simple adjuvant. The conditions for an optimal DTH response to measles virus were also shown to be applicable to other enveloped viruses, for example, a strong DTH response was similarly generated to inactivated purified influenza PR8 virus and to herpes simplex virus type I antigens present in plasma membranes isolated from infected Vero cells.

Adjuvants, Immunologic↗