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Biomedical subjects

M North

Publications and source records attributed to M North.

At least 37 records · Page 2Linked to original sources

Serum chemokine levels in patients with non-progressing HIV infection.

OBJECTIVE: To evaluate serum chemokines, macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta and RANTES, concentrations in non-progressing HIV-infected patients and AIDS patients. SETTING: University Hospital-based AIDS Clinical Trials Unit. DESIGN/METHODS: Serum MIP-1 alpha, MIP-1 beta and RANTES levels were determined by enzyme-linked immunosorbent assay using archived serum specimens obtained on two occasions at least 1.8 years apart. PATIENT SELECTION: Long-term non-progressing HIV-infected adult patients were identified from clinic records. For each non-progressing patient two adult AIDS patients with initial documentation of seropositivity the same year and the same length of follow-up were selected. RESULTS: Four long-term non-progressing patients and eight AIDS patients were studied. Neither the duration of known HIV positivity at the time of specimen collection nor the length of time between specimen collections differed significantly between non-progressing patients and AIDS patients. Serum levels of MIP-1 alpha, MIP-1 beta and RANTES in specimens obtained either early or later in the course of HIV infection did not differ significantly between non-progressing patients and AIDS patients. In the two patient subsets, significant differences in serum chemokine levels over time were not observed. The rate of change of serum chemokine concentration over time also did not differ between non-progressing patients and AIDS patients. Serum MIP-1 alpha and MIP-1 beta levels did not reach levels reported to suppress HIV proliferation in vitro. When expressed as a quantity per peripheral blood CD8+ lymphocyte, AIDS patients exhibited significantly greater levels of MIP-1 alpha, MIP-1 beta and RANTES than non-progressing HIV patients (P < 0.05). These values did not exhibit a significant variation over time. CONCLUSIONS: Serum MIP-1 alpha, MIP-1 beta and RANTES levels do not distinguish patients with AIDS from patients with non-progressing HIV infection. Variations in levels of these chemokines do not explain individual variation in the natural history of HIV infection.

Acquired Immunodeficiency Syndrome↗

Indication for linkage of the human OB gene region with extreme obesity.

Obesity is one of the most significant risk factors for hypertension, coronary heart disease, and NIDDM (Frayn KN, Coppack SW: Insulin resistance, adipose tissue and coronary heart disease. Clin Sci 82:1-8, 1992; Kaplan NM: The deadly quartet: upper-body obesity, glucose intolerance, hypertriglyceridemia, and hypertension. Arch Intern Med 149:1514-1520, 1989). While family segregation, adoption, and twin studies have indicated that degree of adiposity has a significant genetic component (Stunkard AJ, Harris JR, Pedersen NL, McClearn GE: The body-mass index of twins who have been reared apart. N Engl J Med 322:1483-1487, 1990; Bouchard C, Despres J-P, Mauriege P: Genetic and nongenetic determinants of regional fat distribution. Endocr Rev 14:72-93, 1993), the genes and predisposing mutations remain poorly understood. This is in contrast to several well-defined genetic models for obesity in rodents, particularly the mouse obese (ob) gene, in which loss-of-function mutations cause severe obesity. Recent studies have demonstrated a substantial reduction in body fat when recombinant ob protein (leptin) is administered to mice. To test the relevance of these observations to human obesity, the location of the human homologue (OB) was established by radiation hybrid mapping and eight microsatellite markers spanning the OB gene region (7q3l.3) were genotyped in 101 obese French families. Affected-sib-pair analyses for extreme obesity, defined by BMI >35 kg/m2, revealed suggestive evidence for linkage to three markers located within 2 cM of the OB gene (D7S514, D7S680, and D7S530). The OB gene is therefore a candidate for genetic predisposition to extreme obesity in a subset of these families.

Alleles↗

Effectiveness of computer-generated (virtual reality) graded exposure in the treatment of acrophobia.

OBJECTIVE: The authors' goal was to examine the efficacy of computer-generated (virtual reality) graded exposure in the treatment of acrophobia (fear of heights). METHOD: Twenty college students with acrophobia were randomly assigned to virtual reality graded exposure treatment (N = 12) or to a waiting-list comparison group (N = 8). Seventeen students completed the study. Sessions were conducted individually over 8 weeks. Outcome was assessed by using measures of anxiety, avoidance, attitudes, and distress associated with exposure to heights before and after treatment. RESULTS: Significant differences between the students who completed the virtual reality treatment (N = 10) and those on the waiting list (N = 7) were found on all measures. The treatment group was significantly improved after 8 weeks, but the comparison group was unchanged. CONCLUSIONS: The authors conclude that treatment with virtual reality graded exposure was successful in reducing fear of heights.

Adult↗

Identification of Genes Predisposing to Clinically Severe Obesity: An Approach.

BACKGROUND: Familial correlations, twin studies and adoption studies have all indicated that human obesity has a substantial genetic component. To date, obesity genes have only been identified using mouse models. METHODS: In an attempt to identify human obesity genes large numbers of multigenerational families, in whom extreme obesity segregates, are currently being collected. RESULTS AND CONCLUSIONS: Relative risk estimates and models of genetic heterogeneity indicate that at least 500 affected sibling pairs will need to be collected to identify major genes.

Journal Article↗

Study of B and T cell phenotypes in blood from patients with common variable immunodeficiency (CVID).

B and T cell phenotypes in peripheral blood from 71 CVID patients have been measured in a study using directly conjugated monoclonal antibodies and two colour flow cytometry. Data was compared between different patient groups (based on whether their B cells could secrete IgM or IgG in vitro) and normal donors. There was a clear correlation between abnormalities of both B and T cells and the different patient groups. There were reduced absolute numbers of circulating CD4+ T cells, particularly those of the CD4+.CD45RA+ subset, and of CD19+ B cells in those patients whose B cells failed to secrete IgM or IgG in vitro. This demonstrates an association between B cell lymphopenia, failure of B cell immunoglobulin production in vitro and T cell subset lymphopenia in CVID. It supports the view that this group of CVID patients has a disease involving T cell regulation of B cells of varying severity.

Antibodies, Monoclonal↗

Olfactory receptors: transduction, diversity, human psychophysics and genome analysis.

The emerging understanding of the molecular basis of olfactory mechanisms allows one to answer some long-standing questions regarding the complex recognition machinery involved. The ability of the olfactory system to detect chemicals at sub-nanomolar concentrations is explained by a plethora of amplification devices, including the coupling of receptors to second messenger generation through GTP-binding proteins. Specificity and selectivity may be understood in terms of a diverse repertoire of olfactory receptors of the seven-transmembrane-domain receptor superfamily, which are probably disposed on olfactory sensory neurons according to a clonal exclusion rule. Signal termination may be related to sets of biotransformation enzymes that process odorant molecules, as well as to receptor desensitization. Many of the underlying molecular components show specific expression in olfactory epithelium, with a well-orchestrated developmental sequence of emergence, possibly related to sensory neuronal function and connectivity requirements. A general model for molecular recognition in biological receptor repertoires allows a prediction of the number of olfactory receptors necessary to achieve efficient detection and sheds light on the analogy between the immune and olfactory systems. The molecular cloning and mapping of a human genomic olfactory receptor cluster on chromosome 17 provides insight into olfactory receptor diversity, polymorphism and evolution. Combined with future genotype-phenotype correlation, with particular reference to specific anosmia, as well as with computer-based molecular modelling, these studies may provide insight into the odorant specificity of olfactory receptors.

GTP-Binding Proteins↗

Why patients consult and what happens when they do.

OBJECTIVE: To study patients' perceptions of why they consulted the doctor, how ill they thought they were, and what happened in the consultation. To compare patients' perceptions before and after the consultation and to compare these perceptions with those of the doctor. DESIGN: Patients filled in a questionnaire before and after the consultation. The doctor filled a questionnaire in after the consultation. SETTING: Three general practices in Bedfordshire and one in Hertfordshire. PATIENTS: 500 consecutive patients consulting in each practice. MAIN OUTCOME MEASURES: Changes in patients' perceptions and differences between the perceptions of patients and doctors. RESULTS: Doctors perceived patients to be less ill than the patients themselves did. Patients from social classes IV and V and children perceived themselves to be more ill than the average. Patients perceived themselves to be less ill after the consultation. A third of patients attended because doctors had told them to, and a quarter of patients had already tried to treat their problem themselves when they attended the consultation. Doctors' perceptions of the consultation emphasised listening, supporting, and giving advice. Patients' perceptions emphasised prescribing, reassuring, and referring to a consultant. Doctors perceived that they listened, examined, and gave advice less to social classes IV and V than to social classes I, II, and III and gave explanations more often to men than to women. Patients perceived external factors rather than lifestyle factors as being more important in causing their problems. CONCLUSION: Doctors' perceptions of patients' problems differed from those of patients expressed both before and after their consultation. Doctors' and patients' perceptions also differed about the consultation itself. The consultation reassured some patients.

Attitude to Health↗

Comparison of ZFY and ZFX gene structure and analysis of alternative 3' untranslated regions of ZFY.

We have cloned and sequenced transcripts from the X- and Y-linked zinc-finger genes ZFX and ZFY respectively and discuss a possible mechanism of post-transcriptional control by which these genes can be widely expressed but translated in only specific tissues. We report the identification of a novel 3'UTR (untranslated region) present in ZFY which is highly conserved among primates and contains a series of motifs implicated as mRNA instability determinants. These sequences can be substantially removed by polyadenylation directed from consensus (AATAAA) and non-consensus (AATATAAA) sequences in adult testis. The DNA-binding domains of the ZFY and ZFX proteins are compared using present models for zinc-finger/DNA interactions. Additionally, the genomic organisation of the ZFY coding sequence is presented as compared to that of ZFX.

Amino Acid Sequence↗

A search for retrovirus infection in systemic lupus erythematosus and rheumatoid arthritis.

Evidence for retroviral infection in general and human immunodeficiency virus (HIV) infection in particular was sought in freshly isolated peripheral blood T cells, B cells, and monocyte-macrophages from patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) and also in T cell and B cell lines established from the same source. Similar cells isolated from rheumatoid synovial membrane were also examined. The strategy used for the detection of virus was cocultivation with susceptible cell lines looking for syncytia formation, reverse transcriptase production, and nucleic acid hybridisation with HIV cDNA probes. No evidence for infection was obtained.

Acquired Immunodeficiency Syndrome↗

Role of retroviruses in acquired hypogammaglobulinaemia.

Mononuclear cells were obtained from 42 patients with 'common variable' hypogammaglobulinaemia (CVH) and co-cultured with various cell lines in an attempt to isolate retroviruses. Cultures from only two patients showed evidence of a viral infection, although the virus could not be isolated and characterized in either. Despite the previous isolation of HIV's from two other CVH patients, this data suggests that similar viruses are not etiologically involved in the majority of patients.

Adult↗

Isolation of retroviruses from two patients with "common variable" hypogammaglobulinaemia.

Retroviruses related to human T-lymphotropic virus III/lymphadenopathy-associated virus (HTLV-III/LAV) have been isolated from peripheral-blood mononuclear cells of two patients with "common variable" hypogammaglobulinaemia who were being treated with intravenous gammaglobulin. One has had three different opportunistic infections. In both patients hypogammaglobulinaemia developed within 6 years of a longlasting undiagnosed viral-like illness in adolescence, and it is suggested that the virus causing that illness also gave rise to the hypogammaglobulinaemia. However, iatrogenic infection from intravenous gammaglobulin cannot be ruled out.

Adolescent↗

Characterization of cloned murine cytolytic T cell lines.

Murine cytolytic T lymphocytes can be kept in continuous culture apparently indefinitely by repeated passage in a concanavalin A-induced growth promoting medium. Some of these long-term cell lines maintain their cytolytic activity. Starting from three such populations, several cloned cytolytic T cell lines were derived and subsequently subcloned one or more times. Considerable variation in the levels of cytolytic activity was observed between different subclones; some initially active subclones lost activity with prolonged culture. In addition, one of the clones appeared to progressively lose the relative specificity demonstrated during the earlier passages of the parent cell line.

Animals↗

Why sociology?

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Public Health Nursing↗