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Biomedical subjects

D M Gorman

Publications and source records attributed to D M Gorman.

At least 19 recordsLinked to original sources
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

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↗
PubMed1990

Cloning and expression of a gene encoding an interleukin 3 receptor-like protein: identification of another member of the cytokine receptor gene family.

Using a monoclonal antibody to the interleukin 3 (IL-3) receptor (anti-Aic2), we isolated a cDNA (AIC2B) from a mouse mast cell line which is homologous to the previously characterized gene for the IL-3 receptor (AIC2A). This cDNA encodes a polypeptide of 896 amino acid residues and has 91% amino acid sequence identity with the IL-3 receptor. A consensus sequence defining an additional cytokine receptor family is present in this clone. Compared to the AIC2A clone, the AIC2B cDNA encodes a protein with amino acid substitutions, insertions, and deletions dispersed throughout the entire protein. Oligonucleotide probes specific for each cDNA hybridized with different genomic fragments, indicating that the AIC2A and AIC2B proteins are encoded by two distinct genes. Fibroblasts transfected with the AIC2B cDNA expressed the protein at the cell surface as determined by binding with the anti-Aic2 antibody but did not bind IL-3 or other cytokines, including IL-2, IL-4, granulocyte-macrophage colony-stimulating factor, erythropoietin, and IL-9 (p40) at concentrations between 1 and 10 nM. An S1 nuclease protection assay was used to discriminate between the AIC2A and AIC2B transcripts. We found that the AIC2B gene was coexpressed with the AIC2A gene. These results suggest a potential involvement of AIC2B in cytokine signal transduction.

Amino Acid Sequence↗
PubMed1990

Molecular cloning of a second subunit of the receptor for human granulocyte-macrophage colony-stimulating factor (GM-CSF): reconstitution of a high-affinity GM-CSF receptor.

Using the mouse interleukin 3 (IL-3) receptor cDNA as a probe, we obtained a homologous cDNA (KH97) from a cDNA library of a human hemopoietic cell line, TF-1. The protein encoded by the KH97 cDNA has 56% amino acid sequence identity with the mouse IL-3 receptor and retains features common to the family of cytokine receptors. Fibroblasts transfected with the KH97 cDNA expressed a protein of 120 kDa but did not bind any human cytokines, including IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF). Interestingly, cotransfection of cDNAs for KH97 and the low-affinity human GM-CSF receptor in fibroblasts resulted in formation of a high-affinity receptor for GM-CSF. The dissociation rate of GM-CSF from the reconstituted high-affinity receptor was slower than that from the low-affinity site, whereas the association rate was unchanged. Cross-linking of 125I-labeled GM-CSF to fibroblasts cotransfected with both cDNAs revealed the same cross-linking patterns as in TF-1 cells--i.e., two major proteins of 80 and 120 kDa which correspond to the low-affinity GM-CSF receptor and the KH97 protein, respectively. These results indicate that the high-affinity GM-CSF receptor is composed of at least two components in a manner analogous to the IL-2 receptor. We therefore propose to designate the low-affinity GM-CSF receptor and the KH97 protein as the alpha and beta subunits of the GM-CSF receptor, respectively.

Amino Acid Sequence↗
PubMed1990

Expression cloning of a cDNA encoding the murine interleukin 4 receptor based on ligand binding.

Interleukin 4 (IL-4) is a potent mediator of growth and differentiation for various lymphoid and myeloid cells. To isolate a cDNA encoding the murine IL-4 receptor, we have developed an expression cloning method that uses biotinylated ligand as a probe and that may be generally applicable to cloning of receptor genes. COS-7 cells transiently transfected with the cloned full-length cDNA bind murine IL-4 specifically with a Kd = 165 pM. Crosslinking of 125I-labeled IL-4 to COS-7 cells transfected with the cDNA reveals binding to proteins of 120-140 kDa. IL-4-responsive cells also express IL-4-binding proteins of 120-140 kDa but show additional bands at 60-70 kDa; the relationship of the smaller proteins to the larger ones is unclear. The nucleotide sequence indicates that the full-length cDNA encodes 810 amino acids including the signal sequence. While no consensus sequence for protein kinases is present in the cytoplasmic domain, a sequence comparison with the erythropoietin receptor, the IL-6 receptor, and the beta chain of the IL-2 receptor reveals a significant homology in the extracellular domain, indicating that the IL-4 receptor is a member of a cytokine receptor family.

Amino Acid Sequence↗
PubMed1990

Molecular cloning of a cDNA encoding the human interleukin 4 receptor.

Using the mouse interleukin 4 (IL-4) receptor cDNA as a probe, we isolated a cDNA encoding the human IL-4 receptor (hIL-4 receptor) from a multifactor-responsive human myeloid cell line, TF1. The cDNA encodes for an open reading frame of 825 amino acids including a signal sequence (25 amino acids), the external domain (207 amino acids), a transmembrane domain (24 amino acids), and a large cytoplasmic domain (569 amino acids). The human IL-4 receptor has a 65% identity with the mouse IL-4 receptor at the nucleic acid level and retains the typical structural motif of the previously described cytokine receptor family. COS7 cells transfected with the full-length cDNA expressed high levels (140,000 sites/cell) of IL-4 binding sites, with a Kd = 80 pM, an affinity identical to that of the original TF1 cells. Similar to IL-4 responsive cells, cross-linking of [125I]IL-4 to COS7 cells transfected with the cDNA showed a major protein of 130-150 kd and minor species of 55-85 kd.

Amino Acid Sequence↗
PubMed1990

Types of life events and the onset of alcohol dependence.

Data concerning the occurrence of life events in the year before onset of alcohol dependence were collected from 23 patients recruited from a district general hospital. Both male and female alcohol dependent cases reported significantly more severe life events in the year preceding onset of the disorder than did members of a community comparison group over the same 12-month period. Events were also classified according to the dimensions of 'loss' and 'danger', and 'independence'. The study suggests that individuals may enter the initial stages of alcohol dependence in response to stressful life events.

Adult↗
PubMed1990

Evaluation of an alcohol education package for non-specialist health care and social workers.

A quasi-experimental non-equivalent control group design was used to assess the influence of a two-day experiential alcohol education package for non-specialist health care and social workers. Four pairs of teams took part in the study: general practice; accident and emergency; medicine for the elderly; and social work. The dual foci of the evaluation were agents' knowledge and attitudes, and these were assessed using a modified version of the Alcohol and Alcohol Problems Perception Questionnaire (AAPPQ). For both variables, the one-month follow-up scores of the education teams were significantly higher than those of the comparisons, although the effect was stronger in the case of therapeutic attitudes than knowledge. There were also significant differences in improvement in attitude scores, with significant effects being observed in the general practice, medicine for the elderly and social work teams but not the accident and emergency. At 6 months, the level of fall-off in improvement varied and this, along with the pattern of change evident in the five components which comprise the AAPPQ attitude scale, was examined and discussed in relation to previous research in this field of inquiry.

Adult↗
PubMed1989

Level of agreement between questionnaire measures of alcohol dependence, alcoholism and problem drinking in a sample presenting at a specialist alcohol treatment service.

Two questionnaire measures of the alcohol dependence syndrome, one of alcoholism, and one of alcohol-related problems were compared in a sample of 101 subjects attending a specialist alcohol treatment unit. There was substantial agreement between the two measures of alcohol dependence, and lesser agreement between any other pairing. The measures of alcohol dependence also showed the strongest correlation with reported weekly alcohol consumption. The findings are compared with previous research, and the suitability of the various questionnaires as case-defining instruments in empirical investigations is discussed.

Adult↗
PubMed1989

Is 'disease model' an appropriate term to describe the alcohol dependence syndrome?

Caetano (Concepts of alcohol dependence: the two worlds of research and treatment. Alcohol and Alcoholism 23, 225-227, 1988) has suggested that in the U.S.A. opposition from the disease model has been the main reason for the limited application of the alcohol dependence syndrome. In Britain, the charge that the syndrome is a poorly disguised version of the disease model has had a similar effect. This paper describes the main features of the crude biomedical disease model, which critics equate with the alcohol dependence syndrome. It is concluded that the alcohol dependence syndrome does not conform to this, in that it is not presented by its proponents as a discrete entity identified by a core psycho-biological pathology and carries no built-in assumptions about causal processes. It is argued that instead of setting-up and championing competing all-embracing conceptual models, both clinicians and researchers should be flexible and imaginative in their use of concepts.

Alcohol Drinking↗
PubMed1989

Is the 'new' problem drinking concept of Heather & Robertson more useful in advancing our scientific knowledge than the 'old' disease concept?

Heather & Robertson maintain that the problem drinking concept represents a shift from a 'pre-scientific' to a 'scientific' paradigm within the field of alcohol studies. They consider that the usefulness of a concept can best be assessed in terms of the extent to which it facilitates the testing of hypotheses. The disease concept is of no value when judged in these terms due to the aetiological assumptions that are built into it. It is argued that since Heather & Robertson's 'new' approach incorporates a set of assumptions parallel to those of the disease concept it is equally tautological, and therefore does not represent the type of change in paradigm they propose.

Alcohol Drinking↗
PubMed1988

Employment, stressful life events and the development of alcohol dependence.

Features of employment structures and occupational environments are considered to increase risk of alcohol dependence amongst both males and females, although the mechanisms whereby this operates are not clearly understood. The present retrospective case-control study examined the way in which factors related to employment and occupation facilitated the development of alcohol dependence following the occurrence of a stressful life event. Results showed that for males, there were certain occupational risk factors that were conducive to the development of alcohol dependence, and that risk was especially high for those working in such occupations who experienced a stressful event. For females, there was some evidence to suggest that full-time employment increased risk of alcohol dependence, at least for married women. It is suggested that, in order to better understand the factors of employment conducive to the development of female alcohol dependence, measures focussed specifically on work environments, such as those used in the present study of males should be developed.

Adolescent↗
PubMed1988

Alcohol consumption by patients attending outpatient clinics.

Three hundred and twenty nine (329) patients aged between 18 and 60 years attending the diabetic, hypertension and fracture clinics were studied with regard to their alcohol consumption. The findings confirm the general view that a considerable number of patients attending the general medical services may be considered as problem drinkers, a factor which may contribute to their overall medical complaint.

Adolescent↗