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Biomedical subjects

R M Young

Publications and source records attributed to R M Young.

At least 37 records · Page 2Linked to original sources

Association of the D2 dopamine receptor A1 allele with alcoholism: medical severity of alcoholism and type of controls.

D2 dopamine receptor (DRD2) A1 allele frequency was determined in alcoholics of varying medical severity from three different inpatient settings and in various controls. A1 frequency was .15 in 68 alcoholics in a detoxification unit (group A), .19 in 90 alcoholics in a rehabilitation unit (group B), and .31 in 43 alcoholics in a gastroenterology unit (group C). Group C had a higher A1 frequency than group B (p = .045) or group A (p = .005) alcoholics. In 46 controls (group D), A1 frequency was .18. In subsets of these controls, A1 frequency was .14 in 39 subjects with a negative family history (FH-) of alcoholism (group E), .06 in 34 subjects without previous hazardous alcohol consumption (group F), and .05 in 30 subjects with FH- and without previous hazardous alcohol consumption (group G). A1 frequency was significantly higher in group C alcoholics than group F (p = .0002) or group G (p = .0002) controls; however, no A1 frequency difference was found among group A alcoholics and any of the control groups. The severity of alcoholism and the type of controls used are important determinants of DRD2 A1 allele association with alcoholism.

Alcohol Drinking↗

Work-place screening of mine employees using the alcohol use disorders identification test (AUDIT) and alcohol breathalyzation.

Although public health campaigns focusing on alcohol in the work-place are receiving increasing attention, there is little empirical evidence regarding the use of screening. In this work-place study, 152 mining personnel (67% of the work-force) completed a self report screen using the Alcohol Use Disorders Identification Test (AUDIT). One hundred and thirty-three of these (58.5% of the work-force) also consented to be breathalysed and one (0.75%) recorded a BAC just over threshold for detection. Forty-eight males (37.7% of the male work-force) recorded AUDIT scores of eight or more consistent with hazardous alcohol use and one female registered a cumulative score above the female cut-off level for hazardous alcohol use. Eighty males (67% of the work-force), recorded binge drinking at least monthly and 81 males recorded a cumulative AUDIT score of less than eight; however, on item analysis, 64 (83%) of these recorded binge drinking at least sometimes. There is substantial hazardous alcohol use in this sample work group and younger males had higher alcohol consumption, more adverse consequences and higher total AUDIT scores identifying them as particularly at risk. The Cronbach & AUDIT was 0.72, confirming adequate internal consistency.

Journal Article↗

Rotational dynamics of luteinizing hormone receptors and MHC class I antigens on murine Leydig cells.

We have examined the molecular motions of luteinizing hormone (LH) receptor and the Major Histocompatibility Complex Class I antigen on murine Leydig cells. Using time-resolved phosphorescence anisotropy methods, erythrosin (ErITC)-derivatized ovine luteinizing hormone (oLH) bound to the LH receptor appears rotationally mobile with rotational correlation times of 19.6 +/- 1.3 microseconds, 13.3 +/- 2.4 microseconds, 9.5 +/- 0.7 microseconds and 4.7 +/- 0.5 microseconds at 4 degrees C, 15 degrees C, 25 degrees C and 37 degrees C, respectively. Rotational correlation times for human chorionic gonadotropin (hCG)-occupied LH receptors were similar to those of the ErITC-oLH occupied receptor at each temperature. In addition, both oLH- and hCG-occupied LH receptors were laterally mobile in fluorescence photobleaching recovery experiments with diffusion coefficients at 29 degrees C of (5.8 +/- 0.9) x 10(-10) cm2 s-1 and (2.9 +/- 0.4) x 10(-10) cm2 s-1, respectively. We also measured the rotational correlation time of Class I antigen on murine Leydig cells using ErITC-derivatized 34-12-2S, an anti-Class I monoclonal antibody. Because there was no decay of the anisotropy function at 4 degrees C, 15 degrees C, 25 degrees C or 37 degrees C in the absence of oLH or following preincubation of Leydig cells with 1 nM oLH, it appears that Class I is rotationally immobile on the 1 ms timescale of our experiments. This result is consistent with the presence of Class I antigen in large molecular weight structures and may be the result of Class I self-aggregation. Further, treatment of cells with anti-Class I antibody had no effect on either basal or oLH-stimulated testosterone secretion. Thus, it appears that this anti-Class I antibody is not LH-mimetic on murine Leydig cells.

Animals↗

Bromocriptine in the treatment of alcoholics with the D2 dopamine receptor A1 allele.

Various types of alcoholics have been described and heredity has been shown to be involved in some of these types. An important role of the mesolimbic dopamine system has been suggested in the reinforcing effects of alcohol and recent molecular genetic studies are implicating the gene for the D2 dopamine receptor (DRD2) in alcoholism. In a double-blind study, bromocriptine, a DRD2 agonist, or placebo was administered to alcoholics with either the A1 (A1/A1 and A1/A2 genotypes) or only the A2 (A2/A2 genotype) allele of the DRD2 gene. The greatest improvement in craving and anxiety occurred in the bromocriptine-treated A1 alcoholics and attrition was highest in the placebo-treated A1 alcoholics. The feasibility of a pharmacogenetic approach in treating certain types of alcoholics is suggested.

Adult↗

Analyte detection with DNA-labeled antibodies and polymerase chain reaction.

We demonstrate immuno-polymerase chain reaction (PCR) assays for two clinical analytes--human thyroid-stimulating hormone and chorionic gonadotropin (hTSH, hCG)--using DNA-labeled antibodies and PCR for amplification of assay response. DNA-antibody conjugates were synthesized by using heterobifunctional cross-linker chemistries to covalently attach single- or double-stranded DNA labels through amine or sulfhydryl groups on the analyte antibodies. These approaches yielded molecular chimeras possessing both analyte-specific antibody binding and nucleic acid amplification functionalities. Dose-response relationships were demonstrated for immuno-PCR assays of both analytes in a microtiter plate-based, two-antibody sandwich assay format. Detection limits for hTSH (1 x 10(-19) mol, < 1.4 mIU/L) and hCG (5 x 10(-18) mol, 0.025 IU/L) exceeded those of conventional enzyme immunoassays by 2-3 orders of magnitude. We also evaluated various DNA design factors influencing label amplification and assay performance, such as primer sequence, strand number, and DNA length. Our findings, in concert with previous reports, suggest that this hybrid technology could provide the basis for a new generation of ultra-sensitive immunoassays offering multianalyte capabilities.

Antibodies↗

Quantitation of fluorescence energy transfer between cell surface proteins via fluorescence donor photobleaching kinetics.

We describe practical aspects of photobleaching fluorescence energy transfer measurements on individual living cells. The method introduced by T. M. Jovin and co-workers (see, most recently, Kubitscheck et al. 1993. Biophys. J. 64:110) is based on the reduced rate of irreversible photobleaching of donor fluorophores when acceptor fluorophores are present. Measuring differences in donor photobleaching rates on cells labeled with donor only (fluorescein isothiocyanate-conjugated proteins) and with both donor and acceptor (tetramethylrhodamine-conjugated proteins) allows calculation of the fluorescence energy transfer efficiency. We assess possible methods of data analysis in light of the underlying processes of photobleaching and energy transfer and suggest optimum strategies for this purpose. Single murine B lymphocytes binding various ratios of donor and acceptor conjugates of tetravalent concanavalin A (Con A) and divalent succinyl Con A were examined for interlectin energy transfer by these methods. For Con A, a maximum transfer efficiency of 0.49 +/- 0.02 was observed. Under similar conditions flow cytometric measurements of donor quenching yielded a value of 0.54 +/- 0.03. For succinyl Con A, the maximum transfer efficiency was 0.36. To provide concrete examples of quantities arising in such energy transfer determinations, we present examples of individual cell data and kinetic analyses, population rate constant distributions, and error estimates for the various quantities involved.

Animals↗

Structure of the MAST with an Australian sample of alcoholics.

The dimensionality of the Michigan Alcoholism Screening Test (MAST) was examined utilizing an Australian sample (n = 196) of alcoholics. This study was specifically designed to overcome some of the problems with sampling and analytic techniques used in previous studies. Three moderately intercorrelated factors were revealed which covered (a) alcohol-related disabilities; (b) help-seeking behaviour and (c) recognition of a drinking problem. These factors were found to be internally consistent as shown by moderate to high alpha coefficients. Results indicate that the additive system of scoring all 24 items may result in an underestimation of the information afforded by the MAST.

Journal Article↗

Rapid and sensitive pollutant detection by induction of heat shock gene-bioluminescence gene fusions.

Heat shock gene expression is induced by a variety of environmental stresses, including the presence of many chemicals. To address the utility of this response for pollutant detection, two Escherichia coli heat shock promoters, dnaK and grpE, were fused to the lux genes of Vibrio fischeri. Metals, solvents, crop protection chemicals, and other organic molecules rapidly induced light production from E. coli strains containing these plasmid-borne fusions. Introduction of an outer membrane mutation, tolC, enhanced detection of a hydrophobic molecule, pentachlorophenol. The maximal response to pentachlorophenol in the tolC+ strain was at 38 ppm, while the maximal response in an otherwise isogenic tolC mutant was at 1.2 ppm. Stress responses were observed in both batch and chemostat cultures. It is suggested that biosensors constructed in this manner may have potential for environmental monitoring.

Bacterial Outer Membrane Proteins↗

Xanthoderma: an unusual presentation of hypothyroidism.

A young woman presented with progressive yellowing of her skin over a period of six months. Liver function tests were requested by her general practitioner and the results prompted the Chemical Pathology Department to instigate further tests to reach the final diagnosis. Hypercarotenaemia had caused her yellow skin, and various other biochemical abnormalities pointed towards primary hypothyroidism as an underlying cause. Thyroxine replacement treatment successfully corrected all the biochemical abnormalities including hypercarotenaemia. As far as is known, yellow skin as a sole presenting feature of hypothyroidism is extremely rare.

Adult↗

Genetic mapping of mutations using phenotypic pools and mapped RAPD markers.

Genetic markers facilitate the study of inheritance and the cloning of genes by genetic approaches. Molecular markers detect differences in DNA sequence, and are thus less ambiguous than phenotypic markers, which require gene expression. We have demonstrated a molecular approach to the mapping of mutant genes using RAPD markers and pooling of individuals based on phenotype. To map genes by phenotypic pooling a strain carrying a mutation is crossed to a strain that is homozygous for the wild-type allele of the corresponding gene. A set of primers corresponding to mapped RAPDs distributed throughout the genome and in coupling phase with respect to the wild type parent is then used to amplify DNA from wild type and mutant pools of F2 individuals. Linkage between the mutant gene and the RAPD markers is visualized by the absence of the corresponding RAPD DNA bands in the mutant pool. We developed a mathematical model for calculating the probability of linkage between RAPDs and target genes and we successfully tested this approach with the model plant Arabidopsis thaliana.

Arabidopsis↗

Hypogammaglobulinemia in asthmatic patients.

We measured quantitative immunoglobulins (IgG, IgA, IgM, and IgG subclasses) in 101 unselected asthmatic patients. We identified hypogammaglobulinemia in 12 patients primarily involving IgG (dose-related) without a strong prediction for any IgG subclass. IgA and IgM were also suppressed but to a lesser extent. This prevalence of hypogammaglobulinemia (.12 +/- standard error of .03) is significantly greater than that seen in the normal population (approximately .025 +/- .017, P = .01). Hypogammaglobulinemia was strongly associated with use of systemic corticosteroids (P = .0001). A cumulative steroid dose of greater than or equal to 5 mg/day for at least 2 years was found in 10/12 patients with hypogammaglobulinemia compared with 37/89 patients without hypogammaglobulinemia (P = .024). No significant increase in the number of infectious episodes was seen in the hypogammaglobulinemic patients. To assess the significance of hypogammaglobulinemia in asthmatics, we assessed responses to tetanus and pneumococcal vaccine in three groups of asthmatics: (1) those with total IgG less than 400 mg/dL who had been on chronic oral steroids, (2) those with total IgG between 855 and 1199 mg/dL who were currently receiving oral steroids, and (3) those with total IgG between 855 and 1199 mg/dL who were not receiving oral steroids. All patients responded normally to tetanus vaccine, but three of eight patients in the hypogammaglobulinemic group showed impaired responses to pneumococcal vaccine. Patients with impaired pneumococcal responses were not clearly distinguishable on the basis of sinus disease or pneumonia. We conclude that although many patients with severe, steroid-dependent asthma experience repeated episodes of bronchitis or exacerbations of sinusitis, these problems are rarely associated with an impairment in specific antibody production. IgG subclass deficiencies are not common in this patient population. A very small subgroup of patients manifest a more severe hypogammaglobulinemia (IgG less than 400 mg/dL) or an inordinate frequency of infectious episodes. Given that bronchitis or sinusitis can be attributed to factors other than hypogammaglobulinemia in these patients, an assessment of specific antibody production in response to pneumococcal vaccination is warranted. A small but significant percentage of such patients will demonstrate impaired responses. These patients should be considered at increased risk for bacterial infections and should, therefore, be monitored closely for infectious episodes.

Adolescent↗

Cognitive processes and cognitive behavior therapy in the treatment of problem drinking.

Cognitive behavior Therapy has been shown to be an effective therapy for a wide range of clinical problems. However, the efficacy of CBT on addictive behavior is still unknown. This paper reviews the evidence for the efficacy of cognitive behavior therapy treatment for problem drinkers and examines its relationship with cognitive models of problem drinking. A computer search of the literature showed that only 13 studies met the criteria for inclusion in this review. This review indicated that there is evidence to show that cognitive behavior therapy can be successfully applied to addictive behaviors, in particular, problem drinking. However, there is lack of evidence to show that cognitive behavior therapy supports cognitive models of problem drinking. Future direction for research in this area is suggested.

Alcoholism↗

Elevated plasma aluminum levels in normal infants receiving antacids containing aluminum.

Aluminum toxicity is a documented cause of encephalopathy, anemia, and osteomalacia. Excretion is primarily renal; therefore, patients with renal insufficiency are at risk for aluminum accumulation and toxicity. This has been demonstrated in uremic children treated with aluminum-containing antacids. The purpose of this study was to determine whether plasma aluminum levels were elevated in infants with normal renal function during prolonged aluminum-containing antacid use. Ten study infants (mean age = 5.8 months), who had been receiving antacids for at least 1 week, were compared with 16 control infants (mean age = 9.8 months) not receiving antacids. The study patients consumed 123 +/- 16 mg/kg per day (mean +/- SEM) of elemental aluminum for an average of 4.7 weeks. Their plasma aluminum level (37.2 +/- 7.13 micrograms/L) was significantly greater than that of the control group (4.13 +/- 0.66 micrograms/L) (P less than .005). It is concluded that plasma aluminum levels may become elevated in infants with normal renal function who are consuming high doses of aluminum-containing antacids. The safety of antacids containing aluminum should not be assumed and they should be used judiciously in infants, with careful monitoring of the aluminum dose and plasma level.

Aluminum↗

The tension reduction hypothesis revisited: an alcohol expectancy perspective.

The tension reduction hypothesis has been historically and cross-culturally a predominant explanation of alcohol's effects. However, its validation has been inconsistent. One speculative reason for this inconsistency is a failure to control for preheld alcohol expectancies. Past research may have confounded results due to studying populations mixed regarding their expectations of alcohol's tension reducing effects. Only two studies could be found which have comprehensively attempted to control for tension reduction expectancies, both supporting a modified tension reduction hypothesis which does not offer tension reduction as the only explanation of drinking behaviour. The interaction of pharmacology, expectancy, gender role and situation suggest that tension reduction is of major importance in understanding the drinking of many, but not all, individuals. This is consistent with recent 'metatheories' of alcohol use which emphasize the complexity and multiplicity of alcohol's effects. Future theoretical and clinical implications of the revised tension reduction hypothesis and expectancies are briefly discussed.

Alcohol Drinking↗