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Biomedical subjects

R Watts

Publications and source records attributed to R Watts.

At least 37 records · Page 2Linked to original sources
PubMed1999

Daily variation of particulate air pollution and poor cardiac autonomic control in the elderly.

examined the cardiac autonomic response to daily variations in PM in 26 elderly (mean age 81) individuals for 3 consecutive weeks. Several standardized methods were used to measure 24-hr average PM concentrations prior to the clinical test inside (indoor PM2.5) and immediately outside (outdoor PM2.5 and PM2.5-10) of participants' residences. Resting, supine, 6-min R wave to R wave (R-R) interval data were collected to estimate high frequency (0.15-0.40 Hz) and low frequency (0.04-0.15 Hz) powers and standard deviation of normal R-R intervals (SDNN) as cardiac autonomic control indices. Participant-specific lower heart rate variability days were defined as days for which the high-frequency indices fell below the first tertile of the individual's high-frequency distribution over the study period. Indoor PM2.5 > 15 microg/m3 was used to define high pollution days. Results show that the odds ratio (95% confidence interval) of low heart rate variability high frequency for high (vs. not high) pollution days was 3.08 (1.43, 6.59). The ss-coefficients (standard error) from mixed models to assess the quantitative relationship between variations in indoor PM2.5 and the log-transformed high frequency, low frequency, and SDNN were: -0.029 (0.010), -0.027 (0.009), and -0.004 (0.003), respectively. This first study of cardiac autonomic control response to daily variations of PM2.5 indicates that increased levels of PM2.5 are associated with lower cardiac autonomic control, suggesting a possible mechanistic link between PM and cardiovascular disease mortality.

Aged↗
PubMed1998

Water hyacinths.

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Africa↗
PubMed1998

Gastro-oesophageal reflux disease in primary care: an international study of different treatment strategies with omeprazole. International GORD Study Group.

OBJECTIVE: To assess the efficacy of omeprazole in patients presenting with troublesome reflux symptoms. DESIGN: Randomized, double-blind, parallel-group, placebo-controlled comparison. SETTING: Primary care. SUBJECTS: Patients were recruited using a symptom-based questionnaire for diagnosis of gastro-oesophageal reflux disease. INTERVENTIONS: After endoscopy, patients without endoscopic oesophagitis were randomized to omeprazole 20 mg (Ome20), omeprazole 10 mg (Ome10) or placebo once daily for 4 weeks (n = 261) and those with oesophagitis (except circumferential/ulcerative) were randomized to receive either Ome20 or Ome10 once daily for 4 weeks (n = 277). Patients not symptom-free at 4 weeks received open treatment with Ome20 once daily for a further 4 weeks. Those symptom-free at 4-8 weeks were followed up for 6 months off treatment, to see whether their symptoms recurred. MAIN OUTCOME MEASURE: Complete upper GI symptom relief during week 4 on Ome20 or Ome10 in patients with or without endoscopic oesophagitis. RESULTS: Forty one percent of all patients on Ome20 and 35% on Ome10 reported complete relief from upper GI symptoms during week 4, whilst 73% of the patients on Ome20 and 62% on Ome10 obtained sufficient control. Complete relief during week 4 was reported by 19% of endoscopy-negative patients on placebo, and sufficient control by 35%. Endoscopic healing at 4 weeks occurred in 76% of oesophagitis patients on Ome20 and in 56% on Ome10. After 6 months off treatment, 90% of patients with oesophagitis and 75% of endoscopy-negative patients reported symptomatic relapse. CONCLUSION: Both 10 mg and 20 mg of omeprazole gave effective relief of symptoms, although 20 mg gave superior healing in patients with oesophagitis. After cessation of treatment, symptomatic relapse was rapid and frequent in both endoscopy-positive and endoscopy-negative patients.

Adolescent↗
PubMed1997

A dominant negative mutant of jun blocking 12-O-tetradecanoylphorbol-13-acetate-induced invasion in mouse keratinocytes.

We previously reported that induced activator protein-1 (AP-1) transcriptional activity appears to be required for tumor promoter-induced transformation in mouse epidermal JB6 cells. To extend this investigation to a keratinocyte culture model and a transgenic mouse model, we constructed K14TAM67, a keratin 14 promoter-controlled version of the dominant negative jun mutant to directly block AP-1 activity and possibly indirectly block NF kappa B activity in basal squamous epithelia. This study was directed at characterizing TAM67 expression and biological activity in the mouse cell line 308, a keratinocyte model for studying carcinogenesis. Cotransfection of K14TAM67 with luciferase plasmid reporter DNAs produced inhibition of basal and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced AP-1 and NF kappa B activity but had no effect on p53-dependent transcriptional activity. In an in vitro invasion assay, stable expression of TAM67 in 308 cells blocked TPA-induced Matrigel invasion. This suggests that blocking TPA-induced AP-1- or NF kappa B-regulated gene expression by TAM67 inhibits TPA-induced progression. Recombinant tissue inhibitor of metalloproteinase 1 reduced TPA-induced in vitro invasion, thus implicating metalloproteinases at least in part in the transcription factor-dependent process. Analysis of mRNA levels for members of the matrix metalloproteinase (MMP) family, however, revealed that the expression of any single MMP family member did not correlate with regulation of AP-1 or NF kappa B activity. However, the combination of substantial levels of mRNA for stromelysin-1, stromelysin-2, collagenase, membrane type 1 MMP, and gelatinase A occurred only in TPA-treated cells in the absence of TAM67. These results suggest that the action of the dominant negative jun mutant on AP-1 and NF kappa B gene regulation results in complex alterations in the levels of downstream effector genes, such as the metalloproteinases, that effect TPA-induced cellular invasion.

Animals↗
PubMed1997

Lessons from syphilis.

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Acquired Immunodeficiency Syndrome↗
PubMed1997

Fluorine-18-FPCT: a PET radiotracer for imaging dopamine transporters.

UNLABELLED: Fluorine-18-labeled 2 beta-carbomethoxy-3 beta-(4-chlorophenyl)-8-[-3-fluoropropyl) nortropane (FPCT) has been synthesized as a new dopamine transporter imaging agent. METHODS: Fluorine-18 was introduced into 2 beta-carbomethoxy-3 beta-(4-chlorophenyl)-8-[-3-fluoropropyl) nortropane by preparation of 1-[18F]fluoro-3-iodopropane followed by alkylation of 2 beta-carbomethoxy-3 beta-(4-chlorophenyl)nortropane. RESULTS: Tissue distribution studies in rats with [18F]FPCT showed high striatal uptake (0.70% dose/g at 60 min; 0.38% dose/g at 120 min) and good striatal-to-cerebellum ratios (5.5 at 60 min; 6.2 at 120 min). Imaging studies in rhesus monkeys (n = 2) with [18F]FPCT showed high uptake and retention in the putamen (P) (P = 0.03%-0.12% dose/g; at 115 min) and good putamen-to-cerebellum ratios of 3.40-3.43 at 115 min. Plasma metabolites were analyzed in rhesus monkeys (n = 2) by ether extraction and HPLC. The radioactivity in the ether-extractable fraction displayed a single peak that corresponded on HPLC to unmetabolized authentic FPCT. CONCLUSION: These results suggest that [18F]FPCT is an excellent candidate for PET imaging of dopamine transporters.

Animals↗
PubMed1997

Attitudes of rural general practitioners towards undergraduate medical student attachments.

OBJECTIVE: Increasing exposure of undergraduate medical students to rural practice is a key component of the national effort in Australia to redress the rural workforce shortage. For this exposure to be successful, willing cooperation of current rural general practitioners is essential. To date there has been no formal assessment of rural general practitioners' attitudes to having undergraduate medical students attached to their practice. METHOD: A descriptive survey, using a mailed questionnaire was sent to all 316 general practitioners currently practising in rural areas of South Australia, as identified from the database maintained by the South Australian Rural Practice Training Unit. RESULTS: A 71.5% response rate (n = 225) was achieved, of which 203 were eligible for inclusion. Of these, 176 doctors had medical student attachments in their practice on at least one occasion; 74.4% of whom (n = 131) perceived the attachments to have a positive experience on their continuing medical education experience, and 81.1% (n = 142) described a positive experience on their professional development. However, 52.6% (n = 92) felt the attachments had a negative effect on their income. Almost all the doctors who were included in the survey (94.6%, n = 192) were willing to have students attached to their practice in the future for between one to two weeks. Of these, 169 wanted quality assurance points, 112 wanted financial reimbursement, and 108 wanted 'academic status' with a university. CONCLUSION: The results suggest that rural general practitioners are willing to have students attached to their practice for periods between one to two weeks, providing they receive quality assurance points, and to a lesser extent, financial reimbursement and academic status.

Attitude of Health Personnel↗
PubMed1996

The need for acute hospitals to provide counselling following motor vehicle accidents.

This paper examines the need for a systematic way of detecting individuals likely to encounter moderate to severe psychological sequelae after being injured in a motor vehicle accident. It presents the findings of assessments of consecutive adult admissions during a six-month period to the Accident and Emergency Department of Royal Melbourne Hospital, a major acute hospital in Melbourne, within two days of being injured in a motor vehicle accident. Seventy of the 250 subjects surveyed completed the General Health Questionnaire 12 and the Impact of Event Scale questionnaire, with 77 per cent found likely to have had a psychiatric disorder. Seventy-four per cent had at least moderate levels of intrusion or avoidance phenomena. Forty-four per cent had severe levels of one or the other. Prevalence of these psychological sequelae was greater than that found in several recent studies on the effects of motor vehicle accidents. A small number (11-15 per cent) sought or received professional counselling within the first three months. This group did not differ, according to levels of intrusion, avoidance, or scores on the GHQ 12, to subjects who did not seek or receive such assistance. Results identify the necessity of investigating and implementing methods of detecting and treating the many who apparently sustain significant psychological sequelae following injury in a motor vehicle accident.

Accidents, Traffic↗
PubMed1995

Molecular cloning of mouse tissue inhibitor of metalloproteinases-3 and its promoter. Specific lack of expression in neoplastic JB6 cells may reflect altered gene methylation.

Mouse tissue inhibitor of metalloproteinases-3 (mTIMP-3), a gene specifically not expressed in neoplastic JB6 cells, have been isolated recently through the use of the mRNA differential display technique (Sun, Y., Hegamyer, G., and Colburn, N. H. (1994) Cancer Res. 54, 1139-1144). We report here the full-length mTIMP-3 cDNA sequence, the promoter sequence and partial characterization, expression and induction of TIMP-3, and the possible molecular basis for the lack of mTIMP-3 expression in neoplastic JB6 cells. There are three transcripts arising from alternative polyadenylation of mouse TIMP-3 gene, having sizes of 4.6, 2.8, and 2.3 kilobase pairs, respectively. All three TIMP-3 transcripts are expressed in preneoplastic but not neoplastic JB6 cells. Computer analysis of cloned TIMP-3 promoter revealed six AP-1 binding sites, two NF-KB sites, a c-Myc site, and two copies of a p53 binding motif separated by eight base pairs with two mismatches at the second motif, along with many other cis elements. TIMP-3 gene expression was inducible by AP-1 and NF-KB activators, 12-O-tetradecanoylphorbol-13-acetate, and tumor necrosis factor-alpha only in preneoplastic cells with an induction peak at 2 h post-treatment, suggesting classification of mTIMP-3 as a member of the immediate early gene family. Southern blot, mutational analysis, and transient transcriptional activation experiments revealed that the lack of expression of mTIMP-3 in neoplastic JB6 cells was due neither to gross deletion nor to promoter mutation of the gene, nor was there a lack of transcription factors required for transcriptional activation. Instead, the lack of TIMP-3 expression in neoplastic JB6 cells may reflect an abnormal methylation of the gene. Both hyper- and hypomethylation of the mTIMP-3 gene are associated with complete down-regulation of gene expression in neoplastic JB6 cell lines. Treatment of neoplastic cells with the methylase inhibitor 5-azacytidine caused reexpression of the mTIMP-3 gene in a tumor cell line that showed hypermethylation but not in another that showed hypomethylation of the gene, suggesting a complex role for methylation in the silencing of gene expression.

Animals↗