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Biomedical subjects

H Smith

Publications and source records attributed to H Smith.

At least 469 records · Page 26Linked to original sources

Genome differences among varicella-zoster virus isolates.

The DNAs of 17 isolates of varicella-zoster virus (VZV) were analysed by restriction endonuclease cleavage and agarose gel electrophoresis. By comparing gel patterns of DNAs cleaved with only a few enzymes, all epidemiologically distinct isolates were shown to be unique. Two isolates recovered from members of a family infected in a common-source outbreak were identical to each other (4/4 enzymes) but distinct from the other strains. In addition, three isolates recovered at different times during the course of a single episode of zoster in another individual were identical by endonuclease analysis (4/4 enzymes) but once again were distinct from all other isolates. The differences that have been recognized in cleavage profiles of all VZV strains reported thus far map into four regions of the viral genome. Two of these variable regions lie within the long unique sequences while the other differences appear to map in each of the inverted repeat sequences.

Base Sequence↗

The similar interaction of ferret alveolar macrophages with influenza virus strains of differing virulence at normal and pyrexial temperatures.

The possibility that ferret lung macrophages may be one factor operating in vivo to prevent infection of susceptible alveolar cells (as demonstrated by organ cultures) by both virulent and attenuated strains of influenza virus has been investigated. Phagocytosis of four strains of influenza virus [A/PR/8/34 (H1N1) and clone 64d (attenuated for ferrets) and clones 64c and 7a (virulent for ferrets) of the recombinant virus A/PR/8/34-A/England/939/69 (H3N2)] by ferret alveolar macrophages in vitro showed that all strains, whether virulent or attenuated, attached equally well (72 to 93%). Recoveries of virus were similar (17 to 44%) whether phagocytosis occurred at the normal temperature of the ferret (39 degrees C) or at pyrexial temperatures induced during infection (40 degrees C for A/PR/8/34 and clone 64d; 41 degrees C for clones 7a and 64c). Thus, alveolar macrophages probably contribute to the lack of alveolar infection observed in vivo.

Animals↗

Cytotoxicity of Neisseria gonorrhoeae for human peripheral blood phagocytes.

The toxicity of gonococci [strain BS4 (agar)] for human peripheral blood polymorphonuclear phagocytes, infected in vitro, was assessed by light microscopic examination of Giemsa stained cell deposits of polymorphonuclear phagocytes which had ingested these bacteria. The cytotoxicity elicited by viable gonococci, assessed by percentage lysis and concomitant reduction in the number of polymorphonuclear phagocytes increased as the ratio of gonococci to phagocytes in the original suspension mixture was raised. Pretreatment of viable gonococci with antiserum raised to whole organisms increased the cytotoxic effect produced by the organisms. Killed (heat or UV irradiation) gonococci caused little or no cytotoxicity, even when the organisms were pretreated with specific antiserum. Hence, the lysis of polymorphonuclear phagocytes appears to be caused by a factor or factors produced by viable gonococci and not by LPS per se.

Cytotoxins↗

Deficiencies of clinical trials of alcohol withdrawal.

Eighty-one therapeutic trials of alcohol withdrawal were found that have been published in English since 1954; controls were randomized in 29 (RCTs). Two thousand three hundred thirteen patients were randomized. Variable pretreatment description prevented estimates of delirium tremens and convulsion prevalence, but only four deaths were reported. Endpoints were thus entirely subjective in these moderately ill patients. Protocol quality of the RCTs was graded by a previously developed system for evaluating adequacy of descriptions, blinding, and essential measurements. Mean score obtained was .49 +/- .03 (1 SE). (A perfect paper would score 1.00.) Data presentations and statistical analyses scored .18 +/- .03. There was little evidence of improvement of scores over time. Papers lacked confidence intervals, proper handling of dropouts, and adequate details of side effects. In five RCTs, six comparisons showed that benzodiazepines are clearly superior to placebo (p less than .001), but conclusions about comparisons with other drugs were not possible. In none of eight "negative" comparisons was the probability of a type II error (beta) considered. Discovery of more effective symptomatic agents or methods of reducing the death rate will require more rigid protocols and analyses as well as larger studies to allow the use of more critical endpoints such as occurrence of delirium tremens, convulsions, or death.

Alcohol Withdrawal Delirium↗

Transformation in Bacillus subtilis: properties of DNA-binding-deficient mutants.

Transformation-deficient mutants of Bacillus subtilis were selected after replica plating on agar plates containing transforming DNA. Out of 24 mutants tested, 3 showed highly reduced abilities to bind donor DNA; the residual levels of binding were similar to those of noncompetent cells. Transformation and transfection were reduced to nondetectable levels in the mutants. However, transduction with phage SPP1 occurred at normal frequencies. The nuclease activities involved in entry of donor DNA were present in the mutants. Comparison of protein patterns by two-dimensional gel electrophoresis revealed the absence of one major protein in the mutants as compared with the wild-type strain. This protein (molecular weight, approximately 18,000; isoelectric point, 5.0) appeared to be membrane associated. The protein was specific for competent cells, suggesting that it is involved in the binding of donor DNA.

Bacillus subtilis↗

Transformation in Bacillus subtilis: purification and partial characterization of a membrane-bound DNA-binding protein.

In DNA binding-deficient mutants of Bacillus subtilis a competence-specific protein with a subunit molecular weight of 18,000 was absent. The native protein containing this subunit was purified from B. subtilis membranes by chromatography on hydroxyapatite, DEAE-cellulose, and Sephacryl S-200. This protein appeared to be complexed with a second protein of slightly lower molecular weight (17,000) and a different isoelectric point. The native protein complex (apparent molecular weight, 75,000) contained approximately equal amounts of the two polypeptides and showed a strong DNA-binding activity. Incubation of the complex with plasmid and bacteriophage DNA revealed nuclease activity, specifically directed toward double-stranded DNA. Predominantly single-stranded nicks and a limited number of double-stranded breaks were introduced in the presence of Mg2+ ions. In the presence of Mn2+ ions the complex produced low-molecular-weight breakdown products from the DNA.

Bacillus subtilis↗

Electrocardiographic changes after streptokinase-induced recanalization in patients with acute left anterior descending artery obstruction.

ECG changes were assessed in 15 patients in whom intracoronary streptokinase recanalized a totally occluded left anterior descending artery during acute myocardial infarction. These results were compared retrospectively with those in 22 comparable conventionally treated patients who underwent catheterization during the acute stage of infarction. Before angiography no significant differences were found in the sum of ST elevation (sigma ST increase V1-V6), the sum of R waves (sigma RV1-V6), or the number of Q waves (nQV1-V6) in leads V1 through V6. sigma ST increase V1-V6 was significantly lower in the streptokinase group than in control patients at all times after angiography. sigma RV1-V6 declined and nQV1-V6 increased in both groups during the first 12 hr, but there was no further change in the control group, whereas in the streptokinase group a significant increase in sigma RV1-V6 and decrease in nQV1-V6 followed. There was a significant correlation between long-term electrocardiographic (sigma RV1-V6; nQV1-V6) and angiographic findings (ejection fraction, akinetic segment length). Thus, the Q wave regression and increase in sigma RV1-V6 after streptokinase suggest, in accordance with angiographic findings, that jeopardized myocardium was salvaged by reperfusion.

Aged↗

The role of naturally-acquired bacterial infection in influenza-related death in neonatal ferrets.

Concomitant, naturally-acquired bacterial infection was the cause of some deaths occurring in neonatal ferrets infected with the attenuated influenza virus A/Puerto Rico/8/34, these being prevented by antibiotic therapy. Bacterial infection played an insignificant role in the greater number of deaths following inoculation with the virulent clone 7a (of the recombinant influenza virus A/Puerto Rico/8/34-A/England/939/69/(H3N2]. As seen previously with clone 7a some ferret neonates infected with A/PR/8/34 died either from obstruction in the upper respiratory tract or from viral pneumonia, but with the latter virus, both types of lesion were probably attributable to the bacterial superinfection.

Animals↗

Sensitivity and specificity of clinical trials. Randomized v historical controls.

The relative accuracy of randomized control trials (RCTs) and historical control trials (HCTs) in determining effective therapies has not been compared since there is no external verification of efficacy. We reviewed six therapies studied by both methods. Most HCTs concluded therapy was better than control, but few RCTs agreed. We calculated sensitivity and specificity for each type of trial by combining published results with all possible combinations of effectiveness. The sensitivity of HCTs was 0.80 to 1.00 (mean, 0.90) and specificity was 0.0 to 0.27 (mean, 0.11). The sensitivity of RCTs was 0.0 to 0.27 (mean, 0.12) and specificity was 0.67 to 1.00 (mean, 0.88). Defects of RCTs are more easily corrected than those of HCTs. Readers should consider trial design and the probability of errors when deciding how much credence to give to a clinical trial.

Clinical Trials as Topic↗

Changes in left ventricular ejection fraction after intracoronary thrombolytic therapy. Results of the Registry of the European Society of Cardiology.

Changes of left ventricular ejection fraction (delta EF) determined by monoplane contrast angiography before intracoronary streptokinase infusion and in the chronic stage of infarction before hospital discharge were assessed in 125 patients. Preintervention EF was .49 +/- .136 and chronic EF was .025 +/- .118 higher (p = .02) in the total group. Some subgroups had an improved EF: patients with collaterals (delta EF = .046 +/- .106, p less than .01, n = 42), patients with incomplete obstruction before intervention (delta EF = + .076 +/- .141, p = .03, n = 19) and patients in whom complete obstruction was permanently recanalized (delta EF = .024 +/- .113, p = .04, n = 89). A continuous model relating delta EF to both duration of infarct symptoms before hospital admission and to preintervention EF showed a decline in EF improvement over time in the subgroup that was admitted within less than 6 hours after the onset of chest pain and successfully recanalized (n = 72).

Cardiac Output↗

Differentiation of extracellular from ingested Candida albicans blastospores in phagocytosis tests by staining with fluorescein-labelled concanavalin A.

In phagocytosis tests with human polymorphonuclear (PMN) cells, extracellular blastospores of Candida albicans could be distinguished microscopically from ingested blastospores mor easily than with methods used previously by staining phagocyte monolayers with fluorescent-labelled concanavalin A. This stain reacted with the cell wall mannan of extracellular blastospores but seemed unable to reach that of the ingested blastospores. This technique both improves determination of phagocytic indices and checks that extracellular blastospores have been washed away before assessment of intracellular survival and growth.

Candida albicans↗

Inosiplex for SSPE.

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Clinical Trials as Topic↗

The role of microbial interactions in infectious disease.

The occurrence of infectious disease is affected by interaction between microorganisms in three ways. The indigenous flora (commensal microorganisms) of some mucous surfaces provide one of the main protective mechanisms against infection by pathogens (disease-producing microbes). The commensal populations interfere with the establishment of pathogens on mucous membranes by evoking anaerobic conditions, by competing for space and nutrients and by producing inhibitors. How, at the beginning of successful infection, pathogens in relatively small numbers overcome this protective activity of the commensal population is unknown. Although not a general phenomenon, some pathogens exacerbate the effects of others. The best examples are the potentiation of bacterial infections by existing viral infections: mucosal adherence and penetration by bacteria are enhanced and phagocytic defences against them weakened. Some microorganisms that are unable to produce significant disease on their own may combine with others to cause serious sickness. The harmful effects of these combinations of microorganisms can be explained by the multifactorial nature of pathogenicity (virulence), i.e. the capacity to produce disease. Although each member of the mixed population cannot alone produce the full complement of factors needed for disease production, the complement can be attained by combining contributions from different members.

Bacteria↗