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Biomedical subjects

R Tate

Publications and source records attributed to R Tate.

At least 19 recordsLinked to original sources
PubMed1999

Molecular cloning and demonstration of an aminopeptidase activity in a filarial nematode glycoprotein.

ES-62 is an abundant phosphorylcholine-containing secreted glycoprotein of the filarial nematode Acanthocheilonema viteae. Using an antiserum directed against the parasite molecule, 3 cDNAs of size, approximately 1.5-1.6 kbp were isolated from an A. viteae expression library. Sequence analysis in combination with N-terminal amino acid sequencing of purified ES-62 revealed that each clone contained a full-length cDNA for ES-62 corresponding to 474 amino acid residues but differed in their 5' and 3' untranslated regions. Characterisation of the 5' end of ES-62 mRNA using 5' rapid amplification of cDNA ends showed that it coded for a signal sequence. Several tryptic peptides were independently sequenced using quadruple-time-of-flight mass spectrometry and used to confirm the cDNA sequence. The mature protein was found to contain three potential N-linked glycosylation sites. Comparison of the derived amino acid sequence of ES-62 with the SwissProt database identified a sequence (between amino acid residues approximately 250 and 350 of mature ES-62) with significant similarity to several bacterial/fungal aminopeptidases. Incubation of ES-62 with leucine-7-amino-4-methylcoumarin as substrate confirmed that ES-62 possessed aminopeptidase activity.

Amino Acid Sequence↗
PubMed1999

Upper airway resistance syndrome: effect of nasal dilation, sleep stage, and sleep position.

BACKGROUND: The upper airway resistance syndrome (UARS) is one of the mild variants of obstructive sleep disordered breathing. Nasal obstruction is proposed as one of the mechanisms that lowers intrapharyngeal pressure and hence increases airway collapsibility. OBJECTIVE: We evaluated the effect of external nasal dilation and sleep position on sleep in UARS. METHOD: A double blind, randomized, controlled study with a crossover design (using therapeutic and placebo dilators) was conducted in 18 consecutive patients with UARS. Each patient had two overnight sleep studies one to two weeks apart. Cardiorespiratory parameters (AHI, percentage of time that SaO2 was more than 2% below awake [desaturation time] and mean overnight heart rate), sleep architecture (sleep stages, sleep efficiency, and arousal index), and body position were determined. RESULTS: Application of the external nasal dilator resulted in a significant increase in the nasal cross-sectional area (p < 0.001). Treatment reduced stage 1 sleep (as a percent of total sleep time) from 8.6 +/- 0.8% to 7.1 +/- 0.7 (SEM), p = 0.034). Desaturation time was significantly lower with treatment (12.2 +/- 2.2% on placebo versus 9.1 +/- 1.3 on treatment, p = 0.04). There were no additional significant effects on the cardiorespiratory parameters, sleep architecture, or MSLT when the entire night was examined. Controlling for interactions of sleep stage and position and treatment we found that treatment reduced desaturation time (p = 0.03) but not AHI or arousal index. AHI was significantly lower in the lateral position compared to the supine (p = 0.0001) and in NREM sleep compared to REM (p = 0.001). Desaturation time was significantly lower on the lateral compared to the supine position (p = 0.002) and in NREM sleep compared to REM (p = 0.006). Arousal index was highly dependent on sleep stage (p = 0.0001): the index was higher in stage 2 compared to slow wave sleep and REM. Sleep position and treatment had no significant effect on arousals. CONCLUSIONS: External nasal dilation reduced stage 1 sleep, an indirect marker of disrupted sleep, and desaturation time. There were no additional effects on sleep architecture or sleep disordered breathing. Both sleep position and sleep stage had a significant effect on sleep disordered breathing in UARS.

Airway Resistance↗
PubMed1999

Sphingosine 1-phosphate stimulation of the p42/p44 mitogen-activated protein kinase pathway in airway smooth muscle. Role of endothelial differentiation gene 1, c-Src tyrosine kinase and phosphoinositide 3-kinase.

We report here that cultured airway smooth muscle cells contain transcripts of endothelial differentiation gene 1 (EDG-1), a prototypical orphan Gi-coupled receptor whose natural ligand is sphingosine 1-phosphate (S1P). This is consistent with data that showed that S1P activated both c-Src and p42/p44 mitogen-activated protein kinase (p42/p44 MAPK) in a pertussis toxin (PTX)-sensitive manner in these cells. An essential role for c-Src was confirmed by using the c-Src inhibitor, PP1, which markedly decreased p42/p44 MAPK activation. We have also shown that phosphoinositide 3-kinase (PI-3K) inhibitors (wortmannin and LY294002) decreased p42/p44 MAPK activation. An essential role for PI-3K was supported by experiments that showed that PI-3K activity was increased in Grb-2 immunoprecipitates from S1P-stimulated cells. Significantly, Grb-2 associated PI-3K activity was decreased by pretreatment of cells with PTX. Finally, we have shown that the co-stimulation of cells with platelet-derived growth factor (PDGF) and S1P (which failed to stimulate DNA synthesis) elicited a larger p42/p44 MAPK activation over a 30 min stimulation compared with each agonist alone. This was associated with a S1P-dependent increase in PDGF-stimulated DNA synthesis. These results demonstrate that S1P activates c-Src and Grb-2-PI-3K (intermediates in the p42/p44 MAPK cascade) via a PTX-sensitive mechanism. This action of S1P is consistent with the stimulation of EDG-1 receptors. S1P might also function as a co-mitogen with PDGF, producing a more robust activation of a common permissive signal transduction pathway linked to DNA synthesis.

Animals↗
PubMed1998

DRG cost weights--getting it right.

Inadequate cost weights are a major problem in casemix funding systems. Clinicians should understand the basis for the cost weights underpinning the hospital payment system in their State and their own hospital. Clinician managers need valid patient costing data if they are to benchmark and improve cost-effectiveness while maintaining and enhancing quality. The cost model approach for determining cost weights has inherent limitations, and, the alternative, detailed patient costing, requires efficient hospital information technology systems. A simplified approach to patient costs, which uses existing hospital data systems, may be useful for smaller hospitals. A better classification system and funding formulas incorporating reliable cost weights derived from patient costing should overcome many of the deficiencies in the current casemix payments systems.

Australia↗
PubMed1998

Causes of staff abuse in health care facilities. Implications for prevention.

Verbal and physical abuse of health care workers (HCWs) is prevalent and costly. A 3 month prospective study was conducted to characterize precipitating conditions and the perpetrators of abusive incidents reported by HCWs at a large inner city hospital. Sixty-six HCWs reporting 102 incidents were interviewed by a research nurse within 48 hours of the incident. Abusive incidents resulted from 55 different patients and 11 visitors. Verbal abuse accounted for 42 incidents (41%) and 60 (59%) involved physical abuse. Two thirds of the abuse occurred on psychiatric wards, 20% on inpatient wards, and 13% in other settings. Overall, twice as many abusive incidents were inflicted by males as females. Cognitive impairment accounted for 19% of the incidents and one abuser was intoxicated at the time. Rule enforcement precipitated abuse in 70% of incidents. Researchers concluded that reviewing rules that apply to patients, how HCWs are trained to enforce rules, how to respond when service requested cannot be provided promptly, and how HCWs can protect themselves when performing a service were important elements in the prevention of staff abuse.

Causality↗
PubMed1997

Differential effect of finasteride on the tissue androgen concentrations in benign prostatic hyperplasia.

OBJECTIVE: The 5 alpha-reductase inhibitor, finasteride, provides a logical medical treatment for benign prostatic hyperplasia (BPH). However, the effects of chronic finasteride treatment on prostatic androgen levels, 5 alpha-reductase activity and tissue prostatic specific antigen (PSA) have not been studied. We have examined prostate tissue androgen concentrations and 5 alpha-reductase activity of the gland in men with BPH treated with the drug for 3 months. DESIGN AND PATIENTS: Twenty-eight patients with clinically diagnosed BPH, awaiting transurethral resection of the prostate, were entered in a double-blind placebo controlled study. Nineteen patients were randomly allocated to treatment with finasteride (5 mg daily) and 9 received placebo for 3 months. MEASUREMENTS: Prostate specimens were collected immediately following surgery and analysed for testosterone, dihydrotestosterone (DHT), androstenedione, 5 alpha-reductase activity and PSA. Blood specimens obtained before the start and immediately following treatment were also tested for steroid hormone concentrations and PSA levels. RESULTS: There was no significant difference in the median levels of intraprostatic testosterone (P = 0.77), DHT (P = 0.46) and androstenedione (P = 0.09) between the finasteride and placebo groups. However, the 5 alpha-reductase activity of the placebo group (237.9 pmol DHT/g tissue/30 min) was approximately 10 times that of the finasteride group (21.5 pmol DHT/g tissue/30 min; P = 0.0008). Although we were unable to detect any differences in the PSA concentrations of the prostate glands, there was a significant difference (P = 0.0002) in the median percentage change of serum PSA concentrations for the two patient groups. Serum DHT levels were also depleted (P = 0.038) whilst serum testosterone was increased (P = 0.054) in the finasteride patients when compared to the placebo group. Furthermore our study demonstrated no correlation between the in vitro 5 alpha-reductase activity of the gland and tissue DHT concentrations. CONCLUSIONS: Whilst finasteride treatment induced a reduction in serum dihydrotestosterone and prostatic specific antigen levels with a concomittant increase in blood testosterone concentrations, the impact of the drug on tissue androgen concentrations varied considerably from one patient to another. The differential effect of the drug on tissue androgen concentrations suggests that in the human prostate there are possibly more than one isoform of 5 alpha-reductase responsible for the accumulation of DHT in the gland.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1997

A cysG mutant strain of Rhizobium etli pleiotropically defective in sulfate and nitrate assimilation.

By its inability to grow on sulfate as the sole sulfur source, a mutant strain (CTNUX8) of Rhizobium etli carrying Tn5 was isolated and characterized. Sequence analysis showed that Tn5 is inserted into a cysG (siroheme synthetase)-homologous gene. By RNase protection assays, it was established that the cysG-like gene had a basal level of expression in thiosulfate- or cysteine-grown cells, which was induced when sulfate or methionine was used. Unlike its wild-type parent (strain CE3), the mutant strain, CTNUX8, was also unable to grow on nitrate as the sole nitrogen source and was unable to induce a high level of nitrite reductase. Despite its pleiotropic phenotype, strain CTNUX8 was able to induce pink, effective (N2-fixing) nodules on the roots of Phaseolus vulgaris plants. However, mixed inoculation experiments showed that strain CTNUX8 is significantly different from the wild type in its ability to nodulate. Our data support the notion that sulfate (or sulfite) is the sulfur source of R. etli in the rhizosphere, while cysteine, methionine, or glutathione is supplied by the root cells to bacteria growing inside the plant.

Amino Acid Sequence↗
PubMed1996

Upper limb repetitive strain injuries in Manitoba.

A review of workers' compensation board (WCB) claims in Manitoba, Canada identified an estimated 382 upper limb repetitive strain injury (RSI) claims or 9.3% of all upper limb WCB claims accepted in 1991. Tendonitis and carpal tunnel syndrome (CTS) were the most frequent diagnoses (27.5% and 19.3%, respectively). Rates of RSI were not significantly different by gender and age. RSI claimants had been experiencing symptoms for an average of 8 months prior to filing a compensation claim. While clerical occupations accounted for 13.6% of all upper limb RSI claims, the rates for RSIs in these occupations were low (0.67/1,000 workers), in contrast to occupations with the highest RSI rates: food, beverage, and related processing occupations (14.68/1,000 workers) and fabricating, assembling, and repairing of metal products (9.32/1,000). The highest risk industries were meat and poultry processing-related (23.48/1,000) and the manufacturing of airplanes (9.06/1,000). RSI claims were significantly more costly (+5,569 vs. +2,480, p < 0.0001) and required more time loss (71.4 vs. 33.6 d, p < 0.0001) than similar musculoskeletal non-RSI claims. Similarly, RSI claimants were less likely to return to the same job (67.3% vs. 81.0%, p < 0.0001) than non-RSI claimants. It was concluded that the cost and severity of RSI claims militate for intensified preventive measures.

Absenteeism↗
PubMed1995

Human prostatic steroid 5 alpha-reductase isoforms--a comparative study of selective inhibitors.

The present study describes the independent expression of the type 1 and 2 isoforms of human 5 alpha-reductase in the baculovirus-directed insect cell expression system and the selectivity of their inhibition. The catalytic properties and kinetic parameters of the recombinant isozymes were consistent with published data. The type 1 isoform displayed a neutral (range 6-8) pH optimum and the type 2 isoform an acidic (5-6) pH optimum. The type 2 isoform had higher affinity for testosterone than did the type 1 isoform (Km = 0.5 and 2.9 microM, respectively). Finasteride and turosteride were selective inhibitors of the type 2 isoform (Ki (type 2) = 7.3 and 21.7 nM compared to Ki (type 1) = 108 and 330 nM, respectively). 4-MA and the lipido-sterol extract of Serenoa repens (LSESr) markedly inhibited both isozymes (Ki (type 1) = 8.4 nM and 7.2 micrograms/ml, respectively; Ki (type 2) = 7.4 nM and 4.9 micrograms/ml, respectively). The three azasteroids were competitive inhibitors vs substrate, whereas LSESr displayed non-competitive inhibition of the type 1 isozyme and uncompetitive inhibition of the type 2 isozyme. These observations suggest that the lipid component of LSESr might be responsible for its inhibitory effect by modulating the membrane environment of 5 alpha-reductase. Partially purified recombinant 5 alpha-reductase type 1 activity was preserved by the presence of lipids indicating that lipids can exert either stimulatory or inhibitory effects on human 5 alpha-reductase.

Animals↗
PubMed1995

Early intervention for back-injured nurses at a large Canadian tertiary care hospital: an evaluation of the effectiveness and cost benefits of a two-year pilot project.

This study evaluated a two-year multidisciplinary early intervention pilot programme for back-injured nurses employed at a large teaching hospital, using a pre- versus post-programme analysis. The purpose was to ascertain whether this programme could reduce the incidence, morbidity, time lost and cost due to back injuries in the 250 nurses employed on ten targeted high-risk wards. Injuries in the remaining 1395 nurses employed on the other 45 wards were monitored concurrently for comparison. The programme consisted of prompt assessment, treatment and rehabilitation through modified work. Evaluative data were gathered by one research nurse on standardized forms at the time of injury, weekly until return to work, and at a six-month follow-up. Time lost and cost data for up to one-year post-injury were derived from workers' compensation statements. Compared to the two years prior to introduction of the programme, the rates of back injuries and lost-time back injuries decreased by 23% and 43%, respectively, on the targeted wards, while these increased on the control wards. Combined expenditure was 32% lower per injury and 34% lower per lost-time injury for those in the targeted group who consented to take part in the programme compared to their counterparts on the control wards, as the increased assessment and treatment costs per case attributable to the programme were more than offset by the savings in lower compensation (wage loss) costs. This programme thus reduced the incidence and time lost due to back injuries and was cost-beneficial.

Back Injuries↗
PubMed1995

The epidemiology of back injuries in nurses at a large Canadian tertiary care hospital: implications for prevention.

Two years of prospective data on 416 back injuries were gathered at a 1100-bed acute and tertiary care hospital to assist target prevention efforts. The rate of injury among 1645 nurses was found to be highest for those working on orthopaedic, medicine, neurology, spinal and surgery wards, indicating priorities for prevention. In fact, 51% of the orthopaedic nurses sustained at least one back injury during the two-year period. Gender did not significantly affect the risk of back injury; however, injuries were slightly more common in nurses with less seniority and younger nurses were found to be at significantly increased risk of back injury. Almost 63% of the back injuries which occurred in nurses working 8 h shifts on the high-risk wards occurred during the first two hours of the shift. Lifting and transferring patients with assistance were the two most common mechanisms for back injury (22.6% and 23.3%, respectively). In total, injured nurses attributed 52.3% of their injuries to inadequate training; inadequate staffing was given as the primary reason for 13.8% of the injuries. The results suggest that training in the indications for and use of mechanical devices for lifting/transferring patients requires intensification, and a 'warm-up' period should also be considered in the face of injuries occurring early in the shift if work activities cannot be evenly planned.

Adult↗
PubMed1995

A survey of dentists and the services they provide to disabled people in the Province of Manitoba.

Persons with disabilities occasionally report that dentists are reluctant to provide them with either dental care or necessary services. There is very little information about the kinds of services that Canadian dentists provide to disabled people. To answer this question, a mail survey, following Dillman's Total Design Method, was undertaken in Manitoba. Questionnaires were mailed to all dentists licensed to practise in Manitoba in 1990. A total of 342 surveys were returned, representing a 62 per cent response rate. In all, 259 (76 per cent) of respondents reported regularly providing dental care to disabled people of all ages who were afflicted by a broad range of disabling conditions. The private dental office was the primary location in which this dental care was provided, but 65 dentists (25 per cent) reported providing dental care in hospitals or other institutions such as nursing homes. Forty per cent of the dentists who reported treating disabled people were willing to accept referrals of new patients with disabilities. Dentists reported providing a full range of dental services to disabled people, and using similar modes of pain control for both disabled and non-disabled patients. The primary mechanism of payment was social assistance programs. Dentists reported that they received adequate compensation (defined as their usual and customary fee) in only 50 per cent of the cases in which they provided dental care to disabled patients. However, 27 per cent of the respondents reported always receiving their customary fee, and 52 per cent indicated that they would be willing to attend continuing education courses offered in the area of special patient care.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Cancer mortality in workers employed at a transformer manufacturing plant.

This study examined mortality to December 31, 1989 in a cohort of 2,222 males employed between 1947 and 1975 at a transformer manufacturing plant in Canada, where there had been extensive use of transformer fluid, some containing polychlorinated biphenyls (PCBs). A combined cohort list of 2,222 names was independently obtained from plant management and union officials. Mortality of 1,939 workers with known birthdates was ascertained by record linkage with the Canadian Mortality Data-base. Standardized mortality ratios (SMRs) for different criteria for acceptance of the death certificate link and for cohort membership (based on work history) ranged from .71-1.05. There was no significant increase in overall cancer deaths. The only significant site-specific increased mortality was pancreatic cancer (11 deaths), with SMRs ranging from 2.92-7.64 and higher mortality risk in those who entered the cohort prior to 1960. All but one of these deaths had a latency period of at least 10 years, and greatest SMRs were found in departments with the greatest exposure to transformer fluid. Several previous studies have found excess pancreatic cancers in association with oil exposures and electrical equipment manufacturing. The need to further investigate pancreatic cancer in transformer manufacturing and related exposures is evident.

Canada↗
PubMed1993

Absence of 5 alpha-reductase activity in the gubernaculum during descent of the fetal pig testis.

To evaluate the hypothesis that testicular descent is mediated by the action of high local concentrations of dihydrotestosterone in the gubernaculum, testis, or epididymis, we obtained tissues from 30 male pig fetuses between 63 and 101 days of gestation. We assayed the 5 alpha-reductase activity in homogenates of pooled tissue by following the conversion of (3H)testosterone to (3H)dihydrotestosterone. The 5 alpha-reductase activity in the urethra and prostate increased prior to and during, but decreased after, the period of testicular descent. The 5 alpha-reductase activity in the gubernaculum remained constant throughout gestation and was not significantly higher than the background activity found in umbilical cord, testis plus epididymis, striated thigh muscle and heat inactivated samples of prostate and urethra. Prior to testicular descent, the 5 alpha-reductase activity was approximately 60 to 300 times higher in the urethra than in the gubernaculum, and approximately 20 to 55 times higher in the prostate than in the gubernaculum. These findings indicate that local conversion of testosterone to dihydrotestosterone in the gubernaculum or epididymis does not play a role in the mediation of testicular descent in the pig fetus.

Animals↗