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Biomedical subjects

J Watson

Publications and source records attributed to J Watson.

At least 127 records · Page 7Linked to original sources
PubMed1997

Effectiveness of antismoking telephone helpline: follow up survey.

OBJECTIVE: To evaluate the effectiveness of an antismoking campaign conducted by the Health Education Board for Scotland. DESIGN: Descriptive survey of adult callers to a telephone helpline (Smokeline) for stopping smoking; panel study of a random sample of adult callers; assessment of changes in prevalence of smoking in Scotland before and after introduction of the helpline. SETTING: Telephone helpline. SUBJECTS: Callers to Smokeline over the initial one year period. Detailed information was collected on a 10% sample (n = 8547). A cohort of adult smokers who called Smokeline (total n = 848) was followed up by telephone interview three weeks, six months, and one year after the initial call. MAIN OUTCOME MEASURES: Numbers of adult smokers calling helpline; changes in smoking behaviour, especially stopping smoking among cohort members; and changes in prevalence of smoking in the general population. RESULTS: An estimated 82782 regular adult smokers made genuine contact with Smokeline over the year, representing about 5.9% of all adult smokers in Scotland. At one year 143 of the cohort of 848 callers (23.6%; 95% confidence interval 20.2% to 27.0%) reported that they had stopped smoking and 534 (88.0%; 85.4% to 90.6%) reported having made some change. About 19500 (16700 to 22350) adult smokers, equivalent to 1.4% (1.2% to 1.6%) of the mean adult smoking population, stopped smoking with direct help from Smokeling. During the second year of the campaign (1994) smoking prevalence among 25-65 year olds in Scotland was 6% (2.0% to 10.0%) lower than it had been before the start of the campaign. CONCLUSION: The Health Education Board for Scotland's antismoking campaign reached a high number of adult smokers, was associated with a highly acceptable quit rate among adults given direct help through Smokeline, and contributed considerably to an accelerated decline in smoking prevalence in Scotland.

Adolescent↗
PubMed1997

Young people, alcohol, and designer drinks: quantitative and qualitative study.

OBJECTIVE: To examine the appeal of "designer drinks" to young people. DESIGN: Qualitative and quantitative research comprising group discussions and questionnaire led interviews with young people accompanied by a self completion questionnaire. SETTINGS: Argyll and Clyde Health Board area, west Scotland. SUBJECTS: Eight groups aged 12-17 years; 824 aged 12-17 recruited by multistage cluster probability sample from the community health index. RESULTS: Young people were familiar with designer drinks, especially MD 20/20 and leading brands of strong white cider. Attitudes towards these drinks varied quite distinctly with age, clearly reflecting their attitudes towards and motivations for drinking in general. The brand imagery of designer drinks-in contrast with that of more mainstream drinks-matched many 14 and 15 year olds' perceptions and expectations of drinking. Popularity of designer drinks peaked between the ages of 13 and 16 while more conventional drinks showed a consistent increase in popularity with age. Consumption of designer drinks tended to be in less controlled circumstances and was associated with heavier alcohol intake and greater drunkenness. CONCLUSIONS: Designer drinks are a cause for concern. They appeal to young people, often more so than conventional drinks, and are particularly attractive to 14-16 year olds. Consumption of designer drinks is also associated with drinking in less controlled environments, heavier drinking, and greater drunkenness. There is a need for policy debate to assess the desirability of these drinks and the extent to which further controls on their marketing are required.

Adolescent↗
PubMed1997

Protein expression of the epsilon subspecies of protein kinase C ceases as Swiss 3T6 fibroblasts increase in cell density even though message for the protein is still present.

We have noted previously that growth of C6 glioma cells from low cell density to confluency and quiescence in serum is accompanied by changes in protein content of different protein kinase C (PKC) subspecies. Here we show that the same occurs as non-contact-inhibiting Swiss 3T6 fibroblasts grow to high density in the presence of serum. Protein expression of PKC subspecies alpha and delta increases as the cells increase in density while that of PKC-zeta remains the same. Unusually, protein expression of PKC-epsilon is completely down-regulated as cells grow beyond about 50% confluency and no PKC-epsilon protein can be detected in 3T6 fibroblasts at high density by Western blotting. However, mRNA for PKC-epsilon is expressed at all stages of fibroblast growth as revealed by RT-PCR. When high-density 3T6 fibroblasts are passaged to low density in fresh medium, re-expression of PKC-epsilon protein is observed within 15 min and becomes down-regulated again as cells become more dense. This very rapid synthesis of PKC-epsilon is not blocked by the transcription inhibitor actinomycin D but is inhibited by cycloheximide. PKC-epsilon has some characteristics of a novel 'early response' protein whose synthesis in newly passaged 3T6 cells is regulated at the translational level.

3T3 Cells↗
PubMed1997

Clinical outcome of hypogammaglobulinaemic patients following outbreak of acute hepatitis C: 2 year follow up.

In 1994, an outbreak of hepatitis C virus (HCV) infection, genotype 1a, occurred in 30 hypogammaglobulinaemic patients in the UK from one batch of contaminated anti-HCV screened intravenous immunoglobulin. This study aimed to study prospectively the outcome of HCV in hypogammaglobulinaemic patients, and to assess the response to early treatment with interferon-alpha, 6 million units three times weekly for 6 months. Data were collected using standardized questionnaires. Five patients with secondary hypogammaglobulinaemia due to lymphoid malignancy were not treated and all have died of their primary malignancy. Of 25 patients with primary hypogammaglobulinaemia, one resolved HCV infection before treatment, 17 commenced on treatment, and seven declined or treatment was contra-indicated. Thirteen of 17 patients completed therapy and seven (54%) have a sustained response (normal transaminases, negative serum HCV RNA) at 6 and 12 months after treatment. Two of the 12 patients with primary hypogammaglobulinaemia, who were not treated or failed to complete treatment, have cleared the virus. Liver biopsy was performed in patients not clearing HCV and was abnormal in all. Four patients developed liver failure within 2 years, of whom three have died and one has been successfully transplanted. In conclusion, HCV can cause rapid severe liver disease in hypogammaglobulinaemic patients. Early treatment with high-dose interferon-alpha results in a high clearance of HCV.

Acute Disease↗
PubMed1997

Apoptosis through CD95 (Fas/APO-1), but not a CD40/CD95 chimeric receptor, is inhibited by phorbol-12-myristate-13-acetate.

CD95 (Fas/APO-1)-mediated apoptosis appears to be regulated by positive and negative signaling molecules. A human CD40/CD95 chimeric receptor was stably transfected into CD95-expressing human Jurkat T cells, and signaling through native and chimeric CD95 was compared in the same cell type to assess contributions of the CD95 extracellular and intracellular domains. Apoptosis was induced in these transfectants by soluble CD40 ligand and also by the anti-CD40 monoclonal antibodies (mAb) M2 and M3. The M2 mAb was more effective than M3 in these transfectants. In contrast to apoptosis mediated through native CD95, CD40/CD95-mediated apoptosis was not inhibited by phorbol-12-myristate-13-acetate (PMA). The apoptotic response to the anti-CD40 mAb M3, but not M2, was enhanced by PMA and dibutyryl cyclic adenosine monophosphate (db-cAMP), which also increased mRNA levels and surface expression of CD40/CD95. The enhancing effects of PMA, but not those of db-cAMP, were sensitive to cycloheximide. The M2 and M3 mAbs appeared to have virtually identical binding affinities but, when added to cells together, M3 inhibited M2-induced apoptosis. These mAbs may bind neighboring epitopes, but M2 induces a more effective signaling-competent conformation upon the chimeric receptor. These data suggest that dimerization, however only in a signaling-competent conformation, was sufficient to induce apoptosis. When expressed as a chimera with the CD40 extracellular domain, the CD95 intracellular domain was not inhibited by protein kinase C (PKC)-dependent pathways, suggesting that the CD95 extracellular domain is required for association with a molecule that inhibits the apoptotic signal.

Antibodies, Monoclonal↗
PubMed1997

Sexual dysfunction in primary medical care: prevalence, characteristics and detection by the general practitioner.

BACKGROUND: Despite the recent focus on sexual behaviour and AIDs, there are almost no data on the prevalence of sexual dysfunction within primary care settings. METHOD: One hundred and seventy patients attending a general practice participated in a questionnaire survey of the prevalence and characteristics of sexual problems. The detection rate of the general practitioners (GPs) and indicators in the patient notes were also investigated. RESULTS: Thirty five per cent of the men (n = 22) reported some form of specific sexual dysfunction: premature ejaculation was identified in 31 per cent of the men; 17 per cent experienced erectile dysfunction, which was associated with current medication, a high mean annual attendance and increasing age. The prevalence of sexual dysfunction in the women was 42 per cent (n = 41); vaginismus was reported by 30 per cent of the sample; 23 per cent of the women suffered from anorgasmia. General sexual dissatisfaction was more common than specific dysfunction; 68 per cent (n = 66) of the women and 75 per cent (n = 54) of the men reported at least one problem with dissatisfaction, avoidance, infrequency or non-communication. The large majority of the sample (70 per cent) considered sexual matters to be an appropriate topic for the GP to discuss. Despite this, sexual problems were recorded in only 2 per cent of the GP notes. CONCLUSIONS: This study confirms the high prevalence of sexual disorders in the population. Many of these problems are concealed from GPs. Predictors in patients' notes could help GPs to detect those patients with more serious problems.

Adolescent↗
PubMed1997

Driving with an internal defibrillator: legal, ethical, and quality-of-life issues.

Patients with internal cardioverter-defibrillators experience many issues after implantation. One issue is operating a motor vehicle. This issue has many ethical, legal and quality-of-life concerns that must be addressed by the patient, health care providers, and society. The legal and ethical issues surrounding patients with internal cardioverter-defibrillators will be explored using an ethically based theoretical framework.

Accidents, Traffic↗
PubMed1997

Expression of the Wilms' tumour gene WT1 in the developing human and in paediatric renal tumours: an immunohistochemical study.

AIMS: The Wilms' tumour gene (WT1) product is expressed during the development of the urogenital system. This study was undertaken to evaluate four anti-WT1 antibodies and use the most specific one to examine the expression of WT1 in formalin fixed, paraffin wax embedded tissues from human embryos, fetuses, and paediatric renal neoplasms. METHODS: The antibodies were assessed on paraffin sections of fetal kidney and by western blotting. Immunohistochemical techniques were optimised and performed on a range of embryonic, fetal, and infant tissues from 35 days post-conception to three months of age, and on a selection of paediatric renal neoplasms. RESULTS: The antibodies tested were found to vary in their specificity. Anomalous expression in smooth muscle was seen with one batch of a commercial polyclonal antibody. WT1 protein was detected in both the metanephros and the mesonephros, the spleen, the gonads, and in the peritoneal mesothelium in fetuses. WT1 was expressed in nuclei and was strongest in the podocytes of fetal kidney. The podocytes of infant glomeruli were also positive. There was focal positive staining in Wilms' tumours, nephrogenic rests, and in a cystic partially differentiated nephroblastoma. Staining of nuclei was seen in one of two rhabdoid tumours of the kidney. No positive staining was seen in other renal tumours. CONCLUSIONS: WT1 is detected readily in formalin fixed material. There were differences in specificity between batches of the polyclonal antibodies used. The distribution of the WT1 gene product in tissues and tumours reflected previous findings with in situ hybridisation studies of WT1 mRNA.

Antibodies↗
PubMed1997

Effect of CP101,606, a novel NR2B subunit antagonist of the N-methyl-D-aspartate receptor, on the volume of ischemic brain damage off cytotoxic brain edema after middle cerebral artery occlusion in the feline brain.

BACKGROUND AND PURPOSE: The purpose of this study was to test the hypothesis that the neuroprotective compound CP101,606 will ameliorate the increase in lactate, retard the development of cytotoxic edema, and decrease the infarct volume after ischemic stroke. METHODS: Seventeen adult cats were allocated to control (n = 7) and CP101,606-treated groups (n = 10). Transorbital middle cerebral artery occlusion was performed under anesthesia. Extracellular fluid lactate by microdialysis as well as infarct volume measurement by triphenyltetrazolium chloride (TTC)-stained section, with and without neuroprotective agents, was used to determine the value of these potential "surrogate markers" of ischemic damage. RESULTS: The control group showed an increased dialysate lactate (15.5% increase) at 30 minutes and a peak (332.0% increase) in dialysate lactate at 1 hour after middle cerebral artery occlusion compared with the drug-treated group. Significant differences between control and drug-treated groups were seen in the rate of fall of the apparent diffusion coefficient at both 1 and 5 hours. A close correlation was seen between the 1- and 5-hour apparent diffusion coefficient maps and the TTC-stained sections. There was a significantly smaller lesion in the CP101,606-treated group (62.9% reduction in infarct size compared with the control group; P < .001). CONCLUSIONS: CP101,606 ranks very highly among the current neuroprotection candidates for clinical trials, and its excellent safety record in both animals and phase II studies in conscious, moderate head injury patients suggests that it will be highly effective in human occlusive stroke.

Animals↗
PubMed1996

Functional comparison of spleen dendritic cells and dendritic cells cultured in vitro from bone marrow precursors.

We have compared dendritic cells (DC) isolated from mouse spleen, or generated in vitro from bone marrow (BM) precursors cultured in granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin-4 (IL-4), for the ability to process and present soluble antigen and stimulate major histocompatibility complex (MHC) Class II-restricted T cells. DC from spleen or BM cultures were equally able to stimulate the in vitro proliferation of allogeneic T cells or of antigen-specific T-cell receptor (TCR)-transgenic T cells. Both DC populations also induced comparable levels of IL-2 secretion by a T-cell hybridoma. Therefore, splenic and BM-derived DC express comparable levels of (Antigen + MHC Class II) ligands and/or costimulatory molecules and have comparable ability to stimulate T-cell responses. When presentation of a native protein antigen, rather than peptide, was evaluated, BM-derived DC were at least 50 times better than splenic DC at stimulating the proliferation of TCR-transgenic T cells. The antigen processing ability of the two populations was similar only when splenic DC were used immediately ex vivo. Therefore, unlike spleen DC, BM-derived DC maintain the capacity to process protein antigen for MHC Class II presentation during in vitro culture. Due to these characteristics, BM-derived DC may represent a useful tool in immunotherapy studies, as they combine high T-cell stimulatory properties with the capacity to process and present native antigen.

Amino Acid Sequence↗
PubMed1996

Broad spectrum antiemetic effects of CP-122,721, a tachykinin NK1 receptor antagonist, in ferrets.

The potent, selective, tachykinin NK1 receptor antagonist, CP-122,721 ([(+)-(2S,3S)-3-(2-methoxy-5-trifluoromethoxybenzyl)amino-2- phenylpiperidine]), at 0.01-1 mg/kg, s.c. reduced retching and vomiting elicited by loperamide, copper sulfate, ipecac syrup and cisplatin in a dose-dependent manner. ID50 values after subcutaneous administration ranged from 0.02 mg/kg (loperamide) to 0.08 mg/kg (ipecac). Oral CP-122,721 reduced cisplatin-induced emesis with an ID50 of approximately 0.08 mg/kg. The less active (2R, 3R)-enantiomer, CP-132.687, did not significantly suppress retching or vomiting induced by any of the emetogens. These data support the hypothesis that CP-122,721 blocks emesis by a specific action at tachykinin NK1 receptors. Its broad spectrum of antiemetic activity suggests a central site of action.

Animals↗
PubMed1996

pLEF, a novel vector for expression of glutathione S-transferase fusion proteins in mammalian cells.

An expression vector, pLEF, has been used to produce the intracellular domain (IC) of the human CD95 (Fas/APO-1) apoptosis receptor as a glutathione S-transferase (GST) fusion protein in murine L929 fibroblasts. GST::CD95IC was affinity-purified in a single step using glutathione-Sepharose. Purification of GST::CD95IC from 32P-labelled L929 cells and cleavage with thrombin revealed that CD95IC was phosphorylated in vivo when produced as a GST fusion protein. Therefore, pLEF may facilitate the mapping of in vivo-modified sites of eukaryotic proteins.

Amino Acid Sequence↗