Large decreases in alcohol-related problems following a slight reduction in alcohol consumption in Ontario 1975-83.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to R E Mann.
Explore the source record for details and available documents.
Antiprotein monoclonal antibodies derived from mice inoculated with Rickettsia rickettsii heated at 56 degrees C for 15 min are of two types: one is type specific for epitopes denatured by moderate temperatures, and the other is specific for epitopes resistant to 100 degrees C for 5 min. The heat-resistant epitopes are found by immunoblotting on multiple polypeptides after solubilization of the rickettsiae at temperatures of 56 degrees C or higher. Most, but not all, antibodies to the heat-sensitive epitopes passively protected mice against two 50% lethal doses of R. rickettsii, whereas none of the antibodies to heat-resistant epitopes did.
Analysis of 15 spotted fever group (SFG) and 2 typhus group strains of rickettsiae with a panel of monoclonal antibodies revealed a number of shared and unique epitopes of the 120- and 155-kilodalton surface proteins. All of the SFG strains but neither of the typhus group strains reacted with antibody to the lipopolysaccharidelike antigen of Rickettsia rickettsii; possibly the lipopolysaccharidelike antigen is the common antigen which defines the SFG. North Carolina and Montana strains of R. rickettsii known to differ slightly in virulence for guinea pigs differed in at least one epitope of the 120-kilodalton protein.
In an effort to decrease alcohol-related driving accidents and fatalities among youth, many school-based programmes to prevent drinking and driving have been developed. These programmes would seem to have many important advantages, including being able to foster appropriate attitudes and behaviours at critical times before and during the formation of driving behaviours and drinking behaviours. The didactic assumptions of these programmes are examined in this paper, and evaluations are reviewed. Programmes based on accurate provision of information and non-threatening attempts to change attitudes, and on behavioural peer intervention techniques, consistently demonstrate knowledge gains, and in some cases appropriate changes in attitudes and self-reported behaviours, immediately following programme exposure. These effects often tend to dissipate with time. Since the impact of these programmes on traffic safety measures has not been examined, their development should be carefully monitored and evaluated until traffic safety benefits can be documented.
Previously it has been reported that strains of Rickettsia rickettsii that differ greatly in their ability to cause disease in guinea pigs are similar by serological and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analyses. In this study, we used monoclonal antibodies to the virulent R and the relatively avirulent HLP strains to investigate strain differences which might account for the disparate behavior of the strains in guinea pigs. Coomassie blue-stained sodium dodecyl sulfate-polyacrylamide gel electrophoresis profiles of the R and HLP strains were nearly identical for polypeptides with apparent molecular weights greater than 32 kilodaltons (kDa). All of the monoclonal antibodies to a lipopolysaccharide-like antigen reacted equally well with antigen from both strains by immunoblotting. None of the antibodies to the lipopolysaccharide-like antigen protected mice against challenge with viable rickettsiae. Some antibodies reacted with both 120- and 155-kDa polypeptides of both strains in radioimmune precipitation and immunoblotting tests, and other antibodies reacted only with the homologous strain. The monoclonal antibodies cross-reacted with the heterologous strain in the enzyme-linked immunosorbent assay essentially either completely or not at all. The ability of the monoclonal antibodies to the 120- and 155-kDa polypeptides to protect mice against the two strains was correlated with the ability of the antibodies to react with the antigens in the enzyme-linked immunosorbent assay and radioimmune precipitation or immunoblotting tests. These results demonstrate that R and HLP antigens which appear identical in molecular weight differ in their compositions of antigenic determinants.
The test-retest reliability of a brief, easily administered questionnaire to assess family history of drinking problems was studied. Twenty alcoholic and twenty non-alcoholic volunteers completed the questionnaire on each of two occasions separated by about 2 weeks. The reliability of classification of first- and second-degree relatives as problem drinkers or alcoholics was examined, using both liberal and conservative diagnostic criteria. In general, both sets of criteria produced satisfactory test-retest reliability; one possible exception occurred when alcoholics' second-degree relatives were classified using the conservative criteria. The liberal criteria seemed to provide a more sensitive index of familial alcoholism.
Interviews with 104 youths convicted of an underage alcohol offence (young drinking offenders), 30 youths convicted of an offence not involving alcohol (delinquents) and 31 youths with no convictions (comparison group) were conducted. Young drinking offenders and delinquents differed from the comparison group, but not each other, on measures of attitude, drinking behaviour and problems, other drug use and previous criminal activities. However, the young drinking offenders did differ from the delinquents on measures of social environment. The high levels of alcohol consumption and alcohol problems reported by the young drinking offenders and delinquents reveal large numbers of problem drinkers in these two groups. It is proposed that the deviant behaviour displayed by these two groups may be a result of similar underlying processes, which can be modified by social environment factors.
Hybridomas producing monoclonal antibodies to Rickettsia rickettsii were prepared from mice to investigate the function of rickettsial antigens. Of the 31 reactive hybridoma lines thus far tested for immunoglobulin subclasses, 11 belonged to the IgG2A subclass, 9 to the IgG2B subclass, and 7 to the IgG3 subclass; four did not react with any of the isotyping sera. Five of the antibodies recognized epitopes present on molecules that were presumed to be polysaccharide and heterogeneous in molecular weight. Twenty monoclonal antibodies reacted with a 170,000-dalton antigen, and six precipitated both the 133,000- and 32,000-dalton polypeptides. Only those antibodies to the 170,000- and 133,000-dalton antigens protected mice from challenge with R. rickettsii. Antibodies to these same antigens were detected in sera from patients convalescing from Rocky Mountain spotted fever. All monoclonal antibodies reacted with antigens apparently located on the rickettsial surface. The protective activity of these antibodies was not correlated with their reactivity in complement fixation, enzyme-linked immunosorbent assay, and immunofluorescence tests.
Two experiments are reported in which retrograde enhancement of human memory by alcohol was observed. In both studies male undergraduate volunteers performed an immediate free recall task before and after consuming either alcohol (0.66 abs alc/kg) or placebo. About two hours later, many words as they could delayed free recall was tested when subjects were asked to write down as many words as they could remember from the free recall trials in the session. Subjects given alcohol recalled significantly more words from lists heard before drinking than subjects given placebo; this effect appeared more pronounced for words from the primacy portion of the lists. The possibility that this retrograde enhancement effect is due to alcohol's effects on brain reward systems is raised.
Six strains of Rickettsia rickettsii from Montana and North Carolina were examined in an effort to identify rickettsial constituents associated with virulence. Fever responses, scrotal reactions, and mortalities of male guinea pigs inoculated intraperitoneally with 1,000 PFU of rickettsial strains revealed that the two Montana patient strains ( Sheila Smith and Norgaard ) and one Montana strain ( Sawtooth female 2) from the wood tick, Dermacentor andersoni, could be placed in the group of highest virulence, the two North Carolina strains (Morgan and Simpson) in the group of lesser virulence, and the Montana strain (HLP) from the rabbit tick, Haemaphysalis leporispalustris , in the group of lowest virulence. The HLP strain was differentiated from the other strains by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by staining with Coomassie brilliant blue or with silver. The patient strains could not be differentiated from each other by these procedures. All of the strains apparently had three heat-modifiable proteins. Analysis of proteinase K-digested rickettsial lysates by sodium dodecyl sulfate-polyacrylamide gel electrophoresis suggested that the strains had a complex mixture of polysaccharides. These putative polysaccharides probably were not related to the differences in virulence of the strains, since the patterns for all of the strains were identical. At least five antigens (molecular weights of 128,000, 105,000, 84,000, 30,500, and 20,500) were demonstrated by radioimmune precipitation tests employing extracts from radioiodine-labeled rickettsiae and antibodies from infected guinea pigs. With these same sera a minimum of 14 antigens was detected in these strains by an immunoblotting procedure. The apparent molecular weights of several of the HLP antigens differed from those of the presumed corresponding antigens of the other strains. The electrophoretic techniques utilized in this study were not sufficiently sensitive to demonstrate compositional differences in the patient strains which differed in their virulence for guinea pigs.
Because of the potential significance of external components of the obligate intracellular parasite Rickettsia rickettsii in host-parasite interactions, we have begun the first phase of a study to isolate and characterize surface antigens of this organism. An antiserum to a rickettsial surface component was obtained from rabbits inoculated with immune precipitates prepared by crossed immunoelectrophoresis of Triton X-100 extracts of R. rickettsii strain R. This antiserum (i) protected guinea pigs inoculated with 10,000 guinea pig 50% infectious doses of R. rickettsii against fever, (ii) prevented death of mice challenged with 2 50% lethal doses of R. rickettsii, and (iii) reacted in the microimmunofluorescence test with 9 of 13 spotted fever group serotypes tested. The location of this antigen on the rickettsial surface was demonstrated by immunoelectron microscopy with ferritin-labeled antibodies.
Self-reports of cognition differentiated subjects given alcohol or a placebo, and were associated with the speed of acquisition of tolerance to the effects of alcohol on pursuit-rotor performance.
The development of tolerance to alcohol was examined in two experiments with nonalcoholic drinkers. In both experiments, male undergraduates received pretraining on a pursuit rotor task and were then randomly assigned to either alcohol or placebo conditions. In the first experiment, monetary and performance feedback reinforcement for pursuit rotor performance were provided to both groups over four drinking sessions. In the second experiment, two final drinking sessions were added where no reinforcement was provided to either the alcohol or placebo subjects, and an additional alcohol group received no reinforcement throughout the six drinking sessions. Tolerance to the impairing effects of alcohol on pursuit rotor performance developed only for the reinforced alcohol subjects; withdrawal of reinforcement from tolerant subjects resulted in a return of impaired performance, i.e. tolerance was extinguished. Impairment remained consistently high in the non-reinforced alcohol subjects throughout all six drinking sessions. The results provide support for the learning hypothesis of behavioural tolerance by demonstrating that its acquisition and extinction may be controlled by reinforcement.
Explore the source record for details and available documents.
Areas under the fever curves of guinea pigs inoculated with Rocky Mountain spotted fever vaccine over a restricted dose range and infected with a standardized dose of Rickettsia rickettsii varied linearly with log10 dose of vaccine. A calculator was programmed to plot fever curves and calculate the vaccine dose that reduced the fever of infected animals by 50%.
The properties of Rickettsia rickettsii purified from infected chicken yolk sacs or mouse L cell cultures by sucrose density gradient centrifugation in a zonal rotor were examined in various ways. Rickettsiae derived from both L cells and yolk sacs had similar compositions: about 12% nitrogen, 1.5% phosphorus, 5% carbohydrate, and 30% fatty acids. On a dry-weight basis, purified rickettsiae were at least 2,000 times as effective as a commercial spotted fever vaccine in protecting guinea pigs against infection with spotted fever rickettsiae and mice against death from toxin of R. rickettsii. Gradient-purified rickettsiae (0.6 mug) induced a serological response in guinea pigs of the same magnitude as that stimulated by 1,600 mug of the commercial vaccine. Gradient-purified rickettsiae had little group reactivity in complement fixation tests but became anti-complementary upon storage. Microagglutination and hemagglutination tests with the purified antigen gave promise of usefulness in diagnosis of spotted fever. These results suggest that zonal centrifugation may be a valuable procedure for the preparation of R. rickettsii vaccine and diagnostic reagent.
Explore the source record for details and available documents.
Footpads of mice sensitized by oil-treated Bacillus Calmette-Guérin (BCG) cell walls given either intravenously, subcutaneously, intradermally, intraperitoneally, or intramuscularly became swollen and reddened after injection of purified protein derivative (PPD). This reaction, greatest after intradermal and subcutaneous sensitization, generally reached a maximum about 24 hr after challenge and was still marked at 48 hr. The histological response was characterized by infiltration with both polymorphonuclear and mononuclear cells. The proportion of mononuclear cells increased with time and they predominated at 48 hr. The footpad reaction could be detected as early as 1 week after sensitization and persisted for at least 37 weeks. Footpad sensitivity to PPD and acquired resistance to airborne infection with Mycobacterium tuberculosis H37Rv were correlated in that (i) both reached a peak approximately 1 month after sensitization of the mouse, and (ii) cell walls treated with NaOH or given without oil neither protected mice against challenge infection nor sensitized them to PPD. Although, as we reported previously, mice vaccinated subcutaneously or intradermally exhibited little or no enhanced resistance to experimental infection, mice given oil-treated cell walls by these routes were highly sensitive to footpad inoculation of PPD. Therefore, the footpad test cannot be used to determine immunity of the mouse to pulmonary infection with tubercle bacilli.