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D M Gorman

Publications and source records attributed to D M Gorman.

At least 37 records · Page 2Linked to original sources
PubMed1996

Applications of retrovirus-mediated expression cloning.

We have recently established a novel expression cloning system using retroviral vectors. The system is based on a high-efficiency packaging cell line, BOSC23, and a simplified retroviral vector, pBabeX, carrying no selection marker. cDNA libraries, constructed in the pBabeX vector, are transiently transfected into BOSC23 cells. The supernatant contains more than 3X10(6)/mL, which would cover large complexities of cDNA libraries. The retrovirus stock gave 100% infection efficiency in NIH3T3 cells and 5-40% infection efficiency in various hematopoietic cell lines. In contrast to the conventional expression cloning system, in which it is necessary to transfect cDNA libraries transiently into particular cell types such as COS cells, retrovirus-mediated expression cloning allows us to transduce cDNAs into a wide variety of cell types. This method therefore makes it possible to select cells expressing a cDNA of interest by various functional assays. When combined with polymerase chain reaction (PCR)-driven random mutagenesis, this system is also useful in searching for mutations of various molecules that will result in alterations of their functions.

3T3 Cells↗
PubMed1995

Impaired interleukin-3 (IL-3) response of the A/J mouse is caused by a branch point deletion in the IL-3 receptor alpha subunit gene.

Interleukin-3 (IL-3) alone does not support hematopoietic colony formation of bone marrow cells from the A/J mouse. To elucidate the molecular lesion in A/J mice, we examined expression of the alpha and beta subunits of the IL-3 receptor (IL-3R). While IL-3R beta was normally expressed, IL-3R alpha was not detectable on the surface of A/J-derived cells by antibody staining. Genetic linkage analysis using recombinant inbred mouse strains between A/J and IL-3-responsive C57BL/6 indicated that the IL-3R alpha gene locus was responsible for the impaired IL-3 response in A/J mice. Molecular cloning and characterization of A/J-derived IL-3R alpha cDNA revealed that it lacked the sequence corresponding to exon 8, which encodes 10 amino acid residues in the extracellular domain. The aberrant splicing was due to a 5 base pair deletion at the branch point in intron 7 and was reproduced in heterologous cells by transfecting with an IL-3R alpha minigene carrying the deleterious intron. The A/J-specific abnormal form of IL-3R alpha was localized inside the cells, but not on the cell surface, providing the molecular basis for the impaired IL-3 response in the A/J mouse.

Amino Acid Sequence↗
PubMed1994

Subset of CD4+ T cell clones expressing IL-3 receptor alpha-chains uses IL-3 as a cofactor in autocrine growth.

In this paper we demonstrate that IL-3 can act as a cofactor for the growth of some CD4+ T cells. This lymphokine synergized with IL-4 to induce both a unique set of protein tyrosine phosphorylations and the vigorous proliferation of the keyhole limpet hemocyanin-specific and I-Ab-restricted CD4+ Th0 cell clone, E6. In addition, neutralizing anti-IL-3 Abs specifically inhibited the growth of E6 T cells to Ag or anti-CD3 mAb stimulation. Finally, this T cell clone was shown to express both the IL-3R alpha-chain and an IL-3R beta-chain (AlC2A). An examination of other CD4+ T cell clones determined that one Th1 clone (A.E7), two Th0 clones (16B.2 and L9A.1), and one Th2 clone (D10.G4.1) were not influenced by the addition of rIL-3. However, proliferation of the Th2 clones CDC25 and CDC35 to CD3-stimulation was significantly enhanced by IL-3. The sensitivity of these latter two clones to IL-3 was also found to be associated with expression of IL-3R alpha-chains. Because E6 T cells are highly dependent on IL-4 for autocrine growth similar to Th2 cells, these results suggest that IL-3 may synergize with IL-4 to enhance the proliferation of a subset of IL-4-dependent CD4+ T cells, and the study indicates that IL-3R alpha-chain expression may be a specific marker of this CD4+ T cell subset.

Animals↗
PubMed1994

Measuring factors that influence the response of medical practitioners and social workers to problem drinkers: a pilot study.

It is increasingly recognized that factors such as professionals' empathy, willingness to intervene, self-efficacy and role legitimacy influence the initial engagement of clients into treatment and the nature of any subsequent therapeutic relationship. These factors are difficult to measure using questionnaires, and for this reason qualitative research techniques are frequently used in this field of inquiry. The present methodological study is based on in-depth interviews conducted with 16 medical practitioners and 12 social workers, and attempts to overcome one of the main limitations associated with qualitative data-that is, the difficulty of reducing such complex material to a numerical value suitable for quantitative analysis. The interview technique and rating system described were most successful in achieving this in the case of self-efficacy and least successful in the case of empathy. Possible reasons for this are discussed. It is concluded that the technique described has the potential to elicit detailed data concerning the interactions of medical practitioners and social workers with problem drinkers, and that this material can be reliably rated in a manner that is not unduly time-consuming and burdensome to researchers.

Journal Article↗
PubMed1994

Alcohol misuse and the predisposing environment.

In recent years, the aetiology of alcohol misuse has come to be conceptualised in terms of risk factor models. Risk can emanate from a number of sources ranging from the genetic to the sociostructural. This chapter reviews the major environmental risk factors under two broad headings--those that affect the availability of the agent and those that affect the vulnerability of the host. The former include a variety of economic, social and physical factors such as price, advertising and licensing laws. The latter include broad socioeconomic and sociocultural factors, as well as interpersonal influences such as family, peers, employment and stress. Practitioners (as distinct from policy-makers) concerned with prevention and treatment of alcohol misuse can most effectively intervene at the interpersonal level, and the paper concludes with a discussion of the implications for clinical practice of the research reviewed in this domain.

Alcoholic Beverages↗
PubMed1993

"War on drugs" continues in United States under new leadership.

Criticism of the "war on drugs" pursued under Republican administrations has grown in the United States. With the election of Bill Clinton many experts expected a shift from law enforcement policies to an approach favouring treatment and prevention. The budget announced in April, however, revealed no such shift in allocation of resources. Although the war on drugs has apparently failed to reduce the supply of cheap heroin and cocaine to the United States, the prevention strategy favoured by its opponents--school based prevention programmes--has not yet been shown to be effective in dealing with the concentration of drug misuse among the socially disadvantaged. In looking for new strategies Clinton must satisfy both liberals and conservatives in Congress, and community policing might therefore prove to be a politically expedient option.

Drug and Narcotic Control↗
PubMed1993

A review of studies comparing checklist and interview methods of data collection in life event research.

This article is concerned with the relative merits of checklists and interviews as techniques for collecting data in the study of life events. It presents a detailed review of studies that have directly compared checklists and interviews. The author's conclusion is that the two techniques should not be seen as equivalent in the assessment of life events. Virtually all of the studies reviewed showed a marked tendency to overreport on checklists. The method appears inadequate in distinguishing truly stressful events from trivial occurrences. In contrast, the in-depth interview is sensitive to the subtleties of life events and should be the preferred method when data of any precision and accuracy are required in an empirical study.

Data Collection↗
PubMed1993

A theory-driven approach to the evaluation of professional training in alcohol abuse.

This paper begins by observing that, to date, evaluations of brief training courses in alcohol abuse for non-specialist professionals indicate that they have little influence on attitudes and behaviour. The reasons why this is so have not been studied in detail, and such training courses continue to be widely used despite their minimal effects. It is argued that the failure of this field of inquiry to develop beyond this point is due to the fact that, with only a very few exceptions, it has not been informed by theoretical concerns. The research in this area is discussed in terms of the types of models tested and the research designs typically used in evaluations. This is followed by a detailed description of the 'theory driven approach' to evaluation. It is proposed that the use of such an approach by those concerned with the development and evaluation of training in alcohol abuse for non-specialists would increase the likelihood of identifying the real effects of such programmes and the processes that mediate their successful implementation. This would result in a more purposeful use of educators' and evaluators' energies and skills.

Alcoholism↗
PubMed1992

Chromosomal localization and organization of the murine genes encoding the beta subunits (AIC2A and AIC2B) of the interleukin 3, granulocyte/macrophage colony-stimulating factor, and interleukin 5 receptors.

Chromosomal genes for two mouse homologous beta subunits (AIC2A and AIC2B) of the interleukin-3, granulocyte/macrophage colony-stimulating factor, and interleukin-5 receptors were characterized. Both AIC2A and AIC2B genes were present on a 250-kilobase MluI restriction fragment and were mapped on murine chromosome 15 (these loci were provisionally designated as Il3rb-1 (AIC2A) and Il3rb-2 (AIC2B)), closely linked to the c-sis locus. Both genes consist of 14 exons and span about 28 kb each. The major transcription initiation sites of both genes were mapped at 194 bp from the initiation codon. These genes are 95% identical up to 700 bp from the transcription initiation sites. Potential recognition sequences for hemopoietic transcription factors including GATA-1 and PU.1 in addition to a TATA-like sequence are present in the 5'-flanking region. A stretch of 20 bp including the initiation site is homologous to the corresponding region of the erythropoietin receptor and the interleukin-7 receptor genes and to the initiator sequence of the adeno-associated virus P5 promoter, suggesting a possible role in transcription initiation. Comparison of the exon/intron boundaries of AIC2A and AIC2B genes with those of other members of the cytokine receptor superfamily reveals a conserved evolutionary structure. Isolation of various forms of AIC2 cDNAs reveals differential splicing of the transcripts.

Animals↗
PubMed1992

Distinguishing primary and secondary disorders in studies of alcohol dependence and depression.

This paper is concerned with the relationship between alcohol dependence and depression, and more specifically with the issue of which criteria should be used in distinguishing primary and secondary disorders. The data presented indicate that borderline or subclinical depression frequently precedes the onset of alcohol dependence. This finding is discussed in terms of previous studies, which show that depression is generally secondary to alcohol dependence. Such studies have focused almost exclusively on severe forms of depressive disorder, and, it is argued, used inappropriate criteria to designate the onset of alcohol dependence (e.g. withdrawal phenomena and alcohol-related problems). In contrast to previous studies, the present paper indicates that subclinical episodes of depression should be assessed by clinicians as possible predisposing factors in the development of alcohol dependence. In addition, it is argued that research designed to establish whether alcohol dependence is a primary or secondary disorder when it occurs in the presence of an accompanying psychiatric disorder should measure onset in terms of changes in behaviour such as giving-up existing interests in order to spend time drinking and consuming more alcohol than former companions.

Journal Article↗
PubMed1992

Recent developments in life-event research and their relevance for the study of addictions.

The idea that stressful life events can on occasions contribute to the development of addictive disorders is fairly well-accepted within both clinical and research communities. However, little support is available: research is sparse and investigators have generally neglected methodological refinements and innovations in the broader field of life-event research. Some of these developments are discussed, especially as they relate to the measurement of the meaning of life events. Findings from research based on such techniques are summarized, and their relevance for the study of addictions discussed under three headings: specification of life events, vulnerability, and diagnostic specificity.

Adaptation, Psychological↗
PubMed1992

Using theory and basic research to target primary prevention programs: recent developments and future prospects.

This paper is concerned with recent attempts within the field of primary prevention to use theory and basic research to develop intervention programs. It starts by reviewing a number of recent large scale studies based upon the dominant theoretical perspective within this field--the social influences model. It argues that the results of such evaluations suggest that a 'universal' prevention strategy (i.e. one aimed in an undifferentiated manner at all individuals within a given population) is out of touch with our current knowledge concerning the etiological processes underlying substance use and misuse. As an alternative, it is suggested that prevention programs be developed according to a number of 'specific' strategies (i.e. ones targeted at vulnerable subgroups within larger populations). The rationale underlying this approach, as well as a number of theoretical models upon which such interventions might be developed, is then outlined.

Alcoholism↗
PubMed1992

Reports of physical symptoms and alcohol use: findings from a primary health care sample.

The relationship between alcohol consumption and physical health was examined in a primary health care sample of 366 adults. Unlike many previous studies that relied on static measures of medical diagnoses, the data reported here are repeated assessments of self-reported symptoms and alcohol use over 12 months. The results suggest, first, that drinking patterns in non-alcoholic samples fluctuate over time, and, second, that abstainers who have more prior illnesses or worse current health consistently report the greatest number of physical symptoms. The data highlight the importance of accounting for the health status of abstainers before comparing them with users of alcohol, and suggest that the presence of physical symptoms in addition to objective indices of health (e.g. the need for medication) may play a role in the initiation or maintenance of abstinence.

Aged↗
PubMed1991

Implications of using the composite and short versions of the Alcohol and Alcohol Problems Perception Questionnaire (AAPPQ).

The Alcohol and Alcohol Problems Perception Questionnaire (AAPPQ) has often been used in studies seeking to understand or change the attitudes of workers towards alcohol abusers. Data are normally presented in terms of either individual subscales or as a composite scale, and recently a short version of the composite scale has been proposed. Using data from a quasi-experimental community intervention the information provided by the summary scales is compared with that from the individual subscales. The analysis suggests that there are two systems within the data--a role security/basic role requirements system and a therapeutic commitment system. Both summary scales are misleading in that they reflect the role security/basic role requirements system scales and not those measuring therapeutic commitment. It is concluded that the summary scales should only be used when the underlying data structure is understood.

Adult↗
PubMed1990

Cloning of an interleukin-3 receptor gene: a member of a distinct receptor gene family.

Interleukin-3 (IL-3) binds to its receptor with high and low affinities, induces tyrosine phosphorylation, and promotes the proliferation and differentiation of hematopoietic cells. A binding component of the IL-3 receptor was cloned. Fibroblasts transfected with the complementary DNA bound IL-3 with a low affinity [dissociation constant (Kd) of 17.9 +/- 3.6 nM]. No consensus sequence for a tyrosine kinase was present in the cytoplasmic domain. Thus, additional components are required for a functional high affinity IL-3 receptor. A sequence comparison of the IL-3 receptor with other cytokine receptors (erythropoietin, IL-4, IL-6, and the beta chain IL-2 receptor) revealed a common motif of a distinct receptor gene family.

Amino Acid Sequence↗