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Biomedical subjects

D M Gorman

Publications and source records attributed to D M Gorman.

At least 55 records · Page 3Linked to original sources
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

Data collection in studies of life events and the harmful use of alcohol.

Although stressful life events have been found to play a role in the development of a number of physical and psychiatric disorders, the research into their influence upon the harmful use of alcohol has been inconsistent. The published studies are reviewed in terms of the methods employed in data collection. It is concluded that a true test of the hypothesis that life events play an aetiological role in the development of the harmful use of alcohol has yet to be carried out, since valid and reliable techniques have not been used in assessing both life events and the onset of harmful use in any one study. Alternative procedures are suggested for use in future research.

Journal Article↗
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↗
PubMed1987

Relationship between alcohol abuse and low back pain.

One hundred and forty-two consecutive referrals attending a low back pain clinic were assessed with questionnaires and blood tests for their alcohol consumption and the severity of their low back pain. Alcohol abuse was found by questionnaires in 11% of patients and 24% had abnormal blood tests. These are higher than reported in the general population. However, the level of alcohol consumption or presence of abnormal tests did not correlate with the severity of the low back pain as assessed by the degree of disability. Nevertheless, the increased consumption of alcohol may contribute to the syndrome complex.

Adolescent↗
PubMed1985

Attitudes and treatment expectancies of patients and general hospital staff in relation to alcoholism.

Attitudes to treatment were investigated in medical and nursing staff and alcoholic patients at a district general hospital. Significant differences were found between the two groups, indicating that patients prefer a strict medical approach to their problems rather than a psychological one. The implications of these findings for the planning of therapeutic strategies for alcoholics are discussed.

Alcoholism↗
PubMedDate not supplied

The use of the Severity of Alcohol Dependence Questionnaire (SADQ) on a sample of problem drinkers presenting at a district general hospital.

Severity of alcohol dependence and patients' consistency of responses to the Severity of Alcohol Dependence Questionnaire (SADQ) were investigated in a sample of 127 problem drinkers, presenting to either medical or psychiatric services of a district general hospital. Nearly 2/3 of the sample were found to be mild to moderate drinkers. Intercorrelations of the sections of the questionnaire were highly significant for the total sample. However, in mildly dependent drinkers, consistency between sections was less marked. Implications for treatment and research are discussed.

Adolescent↗
PubMedDate not supplied

The perception of problem drinkers by general hospital staff, general practitioners and alcoholic patients.

A sample of 275 subjects (general hospital staff, general practitioners and alcoholic patients) was investigated regarding their perception of problem-drinkers. A set of semantic differential scales was used, and subjects were asked to evaluate the concepts of "problem drinker," "self" and "ideal self." Psychological distance was measured in terms of bipolar personality constructs between each of the above concepts. Significant differences were found between the groups in terms of concept evaluation and psychological distance. The implications of these findings for both research and treatment are discussed.

Alcoholism↗