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Biomedical subjects

R Deane

Publications and source records attributed to R Deane.

At least 19 recordsLinked to original sources
PubMed2002

Differences in urinary stress hormones in male and female nurses at different ages.

AIM: The aim of this study was to assess the levels of urinary stress hormones in male and female nurses and to determine their contribution to sex-determined health outcomes. RATIONALE/BACKGROUND: While the use of questionnaires have shown that there is a high degree of stress in health care workers, these results are inconclusive. In this study a more objective approach was used by assessing the levels of urinary stress hormones, adrenaline, noradrenaline and cortisol. In premenopausal women oestrogen may attenuate sympathetic nervous system activity and the secretion of adrenaline and cortisol and therefore lower the stress response and incidence of stress-related illnesses. METHODS: Three hundred and fifteen nurses of both sexes were separated into two age groups, 20-40 and 45-60 years, and for postmenopausal women into those taking or not taking hormone replacement therapy (HRT). Early morning urine sample were collected and stress hormones determined by high performance liquid chromatography (HPLC). RESULTS: Urinary cortisol, adrenaline and noradrenaline levels were all increased with age in both sexes, with a greater difference in the younger age group compared with the older group. These hormones were lower in premenopausal women compared with male nurses of similar age. The difference between the sexes in the high age group was less compared with the lower one. Postmenopausal women on HRT had lower levels of these hormones. CONCLUSION: The age-related changes were surprising but may be because of higher stress levels in the older groups of both sexes. However, the gender difference supports the view that oestrogen reduces sympathetic activity and the secretion of cortisol and adrenaline. HRT reduces the stress response and therefore may have additional benefits by reducing the level of stress-related illnesses. These results were surprising but may suggest that oestrogen reduces the stress response in women and therefore offers protection against stress-related disorders.

Adult↗
PubMed2001

Identification of a novel human tankyrase through its interaction with the adaptor protein Grb14.

Tankyrase is an ankyrin repeat-containing poly(ADP-ribose) polymerase originally isolated as a binding partner for the telomeric protein TRF1, but recently identified as a mitogen-activated protein kinase substrate implicated in regulation of Golgi vesicle trafficking. In this study, a novel human tankyrase, designated tankyrase 2, was isolated in a yeast two-hybrid screen as a binding partner for the Src homology 2 domain-containing adaptor protein Grb14. Tankyrase 2 is a 130-kDa protein, which lacks the N-terminal histidine/proline/serine-rich region of tankyrase, but contains a corresponding ankyrin repeat region, sterile alpha motif module, and poly(ADP-ribose) polymerase homology domain. The TANKYRASE 2 gene localizes to chromosome 10q23.2 and is widely expressed, with mRNA transcripts particularly abundant in skeletal muscle and placenta. Upon subcellular fractionation, both Grb14 and tankyrase 2 associate with the low density microsome fraction, and association of these proteins in vivo can be detected by co-immunoprecipitation analysis. Deletion analyses implicate the N-terminal 110 amino acids of Grb14 and ankyrin repeats 10-19 of tankyrase 2 in mediating this interaction. This study supports a role for the tankyrases in cytoplasmic signal transduction pathways and suggests that vesicle trafficking may be involved in the subcellular localization or signaling function of Grb14.

Adaptor Proteins, Signal Transducing↗
PubMed2000

The use of anthropometric and clinical parameters for early identification and categorisation of nutritional risk in pre-school children in Benin City, Nigeria.

This study was conducted in Benin City, Nigeria between June and August 1996 to assess nutritional status and health risks of three to five-year-old children, with the view to suggesting practical approaches to their early detection and intervention. A total of 165 children comprising 90 males and 75 females was studied. Mid-upper arm circumference (MUAC), weight-for-age (WFA), weight-for-height (WFH) and height-for-age (HFA) z-scores were determined and used to calculate percentage prevalence of malnutrition. Clinical features of macro- and micro-nutrient deficiency were used to develop a clinical scoring system which was subsequently matched with anthropometric z-scores. The results showed that MUAC z-scores (-1.91 SD +/- 0.74) gave the highest percentage prevalence of malnutrition of 45.2% in this population, followed by the WFA (-1.22 SD +/- 1.07) and HFA (-0.84 SD +/- 1.42) z-scores with a percentage prevalence of 23.3% and 20.6% respectively. The WFH z-score (-0.89 SD +/- 1.06) was the least sensitive in detecting malnutrition (14.7% prevalence). The percentage prevalence calculated from MUAC z-scores matched FAO figures (43%) for the sub-Saharan African region in 1996. MUAC z-scores also correlated more closely with the clinical features of malnutrition (R2 = 0.7087). Progressively worsening clinical features were also seen with decreasing z-scores for all variables. Even though moderate differences in clinical and anthropometric variables were detected between the sexes with females fairing better than male subjects, these differences were not statistically significant. Comparisons between anthropometric variables showed only weak correlation, except for WFA vs. HFA z-scores (R2 = 0.5233) and WFH vs. WFA z-scores (R2 = 0.4559) which showed moderately positive correlation. We conclude that whereas MUAC z-scores were most sensitive in detecting the extent of malnutrition in this population, merely using anthropometric variables alone may lead to significant under-reporting of the prevalence of malnutrition in a community. A combination of various anthropometric z-scores with clinical features will however help in the early identification and categorisation of subjects in terms of degree of nutritional risk. The training of field health and nutrition workers should therefore emphasise the routine use and combination of anthropometric and clinical variables in the determination of prevalence of malnutrition and in the formulation of intervention strategies for nutrition rehabilitation.

Analysis of Variance↗
PubMed1998

PCNA and Ki-67 labelling indices in pre-irradiated and post-irradiated astrocytomas: a comparative immunohistochemical analysis for evaluation of proliferative activity.

AIM: To determine the tumour proliferative activity in a series of archival cerebral astrocytomas and compare proliferating cell nuclear antigen (PCNA) and Ki-67 labelling indices in the primary and recurring neoplasms following therapeutic radiation. METHOD: Twenty eight cases of pre-irradiated and post-irradiated astrocytomas (ranging from WHO grades I to IV) were stained immunohistochemically using the avidin-biotin horseradish peroxidase technique. Two antibodies, PC10 and MIB-1, were used to establish the proliferating labelling indices, PC10 identifies PCNA and MIB-1 recognises the Ki-67 antigen. RESULTS: Both antibodies showed significantly higher labelling indices in the post-irradiated specimens. However, in general, the Ki-67 indices were lower than those for PCNA. MIB-1 immunoreactivity showed less variation and was more intense than that seen with PC10. The discrepancy between the labelling indices of the pre-irradiated and post-irradiated samples raises questions about the evolution of astrocytomas and the effects of therapeutic intervention. CONCLUSIONS: The data may represent genetic alterations, the natural tumour course, and/or the effect of radiation. Although both of the antibodies reflected the state of growth of neoplastic cells in astrocytomas, MIB-1 was more reliable. A simple immunohistochemical method using proliferation markers does have an important role in the future care of patients with astrocytoma.

Adult↗
PubMed1997

Yrb4p, a yeast ran-GTP-binding protein involved in import of ribosomal protein L25 into the nucleus.

Gsp1p, the essential yeast Ran homologue, is a key regulator of transport across the nuclear pore complex (NPC). We report the identification of Yrb4p, a novel Gsp1p binding protein. The 123 kDa protein was isolated from Saccharomyces cerevisiae cells and found to be related to importin-beta, the mediator of nuclear localization signal (NLS)-dependent import into the nucleus, and to Pse1p. Like importin-beta, Yrb4p and Pse1p specifically bind to Gsp1p-GTP, protecting it from GTP hydrolysis and nucleotide exchange. The GTPase block of Gsp1p complexed to Yrb4p or Pse1p is released by Yrb1p, which contains a Gsp1p binding domain distinct from that of Yrb4p. This might reflect an in vivo function for Yrb1p. Cells disrupted for YRB4 are defective in nuclear import of ribosomal protein L25, but show no defect in the import of proteins containing classical NLSs. Expression of a Yrb4p mutant deficient in Gsp1p-binding is dominant-lethal and blocks bidirectional traffic across the NPC in wild-type cells. L25 binds to Yrb4p and Pse1p and is released by Gsp1p-GTP. Consistent with its putative role as an import receptor for L25-like proteins, Yrb4p localizes to the cytoplasm, the nucleoplasm and the NPC.

Amino Acid Sequence↗
PubMed1997

Ran-binding protein 5 (RanBP5) is related to the nuclear transport factor importin-beta but interacts differently with RanBP1.

We report the identification and characterization of a novel 124-kDa Ran binding protein, RanBP5. This protein is related to importin-beta, the key mediator of nuclear localization signal (NLS)-dependent nuclear transport. RanBP5 was identified by two independent methods: it was isolated from HeLa cells by using its interaction with RanGTP in an overlay assay to monitor enrichment, and it was also found by the yeast two-hybrid selection method with RanBP1 as bait. RanBP5 binds to RanBP1 as part of a trimeric RanBP1-Ran-RanBP5 complex. Like importin-beta, RanBP5 strongly binds the GTP-bound form of Ran, stabilizing it against both intrinsic and RanGAP1-induced GTP hydrolysis and also against nucleotide exchange. The GAP resistance of the RanBP5-RanGTP complex can be relieved by RanBP1, which might reflect an in vivo role for RanBP1. RanBP5 is a predominantly cytoplasmic protein that can bind to nuclear pore complexes. We propose that RanBP5 is a mediator of a nucleocytoplasmic transport pathway that is distinct from the importin-alpha-dependent import of proteins with a classical NLS.

Amino Acid Sequence↗
PubMed1996

The Quality Cup winner: Fletcher Allen Health Care's early extubation team.

Many organizations are looking for ways to reduce the cost and improve the quality of open-heart surgery. Fletcher Allen Health Care in Burlington, Vermont used a total quality management approach to do just that. The result was a dramatic improvement in outcomes. Fletcher Allen won the 1994 USA Today Quality Cup for its efforts.

Awards and Prizes↗
PubMed1996

Preoperative prediction of postoperative respiratory outcome. Coronary artery bypass grafting.

OBJECTIVE: The hypothesis that traditionally defined preoperative risk factors predict prolonged mechanical ventilation after coronary artery bypass graft surgery (CABG) was tested in our cohort. The predictive power of these factors was quantified, and specific patient subsets destined for prolonged mechanical ventilation after CABG surgery were defined. DESIGN: Five hundred thirteen consecutive patients undergoing CABG were prospectively evaluated. Preoperative pulmonary evaluation included clinical historic data, standard spirometry, and arterial blood gas. Preoperative cardiac parameters included clinical parameters and left ventricular function assessment. Nonthoracic organ (renal, endocrine, pancreas, liver) function was assessed. SETTING: University-based, tertiary referral center. INTERVENTIONS: None (observational only). OUTCOMES MEASURED: Duration of mechanical ventilation, duration of surgical ICU stay, and mortality. RESULTS: Multivariate regression analyses revealed that for the patient undergoing routine elective surgery and the patient undergoing urgent surgery, prolonged mechanical ventilation and death were rare events (8.3% and 2.0%, respectively). The combination of reduced left ventricular ejection fraction and the presence of selected preexisting comorbid conditions (clinical congestive heart failure, angina, current smoking, diabetes) served as modest risk factors for prolonged mechanical ventilation; their absence strongly predicted an uncomplicated postoperative respiratory course. No pulmonary diagnosis, mechanical lung function, or blood gas parameter substantially contributed to predicting adverse outcome. Classification and regression tree subgroup analysis refined specific factors important in specific subgroups. CONCLUSION: With the exception of left ventricular ejection fraction, no preoperative factors emerge as good predictors across all subgroups. This series suggests that pulmonary diagnosis, lung mechanics, and blood gas parameters do not offer the clinician global rules in predicting postoperative respiratory outcome, nor should they be used as exclusion crteria for CABG surgery.

Aged↗
PubMed1992

Overexpression of Mos, Ras, Src, and Fos inhibits mouse mammary epithelial cell differentiation.

Mammary epithelial cells terminally differentiate in response to lactogenic hormones. We present evidence that oncoprotein overexpression is incompatible with this hormone-inducible differentiation and results in striking cellular morphological changes. In mammary epithelial cells in culture, lactogenic hormones (glucocorticoid and prolactin) activated a transfected beta-casein promoter and endogenous beta-casein gene expression. This response to lactogenic hormone treatment was paralleled by a decrease in cellular AP-1 DNA-binding activity. Expression of the mos, ras, or src (but not myc) oncogene blocked the activation of the beta-casein promoter induced by the lactogenic hormones and was associated with the maintenance of high levels of AP-1. Mos expression also increased c-fos and c-jun mRNA levels. Overexpression of Fos and Jun from transiently transfected constructs resulted in a functional inhibition of the glucocorticoid receptor in these mouse mammary epithelial cells. This finding clearly suggests that glucocorticoid receptor inhibition arising from oncogene expression will contribute to the block in hormonally induced mammary epithelial cell differentiation. Expression of Src resulted in the loss of the normal organization and morphological phenotype of mammary epithelial cells in the epithelial/fibroblastic line IM-2. Activation of a conditional c-fos/estrogen receptor gene encoding an estrogen-dependent Fos/estrogen receptor fusion protein also morphologically transformed mammary epithelial cells and inhibited initiation of mammary epithelial differentiation-associated expression of the beta-casein and WDNM 1 genes. In response to estrogen treatment, the cells displayed a high level of AP-1 DNA-binding activity. Our results demonstrate that high cellular AP-1 levels contribute to blocking the ability of mammary epithelial cells in culture to respond to lactogenic hormones. This and other studies indicate that the oncogene products Mos, Ras, and Src exert their effects, at least in part, by stimulating cellular Fos and probably cellular Jun activity.

Animals↗
PubMed1990

Transport of lead-203 at the blood-brain barrier during short cerebrovascular perfusion with saline in the rat.

Lead transport at the blood-brain barrier has been studied by short (less than 1.5 min) vascular perfusion of one cerebral hemisphere of the rat with a buffered physiological salt solution at pH 7.4 without calcium, magnesium, or bicarbonate and containing 203 Pb-labelled lead chloride. In the absence of complexing agents, 203Pb uptake was rapid, giving a space of 9.7 ml/100 g of wet frontal cortex at 1 min. Lead-203 influx was linear with lead concentration up to 4 microM. Five percent albumin, 200 microM cysteine, or 1 mM EDTA almost abolished 203Pb uptake. Lead-203 entry into brain was uninfluenced by varying the calcium concentration or by magnesium or the calcium blocker methoxyverapamil. Similarly, 1 mM bicarbonate or 50 microM 4,4'-diisothiocyanostilbene-2,2'-disulphonic acid was without effect. Increasing the potassium concentration reduced 203Pb uptake. Vanadate at 2 mM, 2 microM carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (a metabolic uncoupler), or 2 microM stannic chloride all markedly enhanced lead entry into brain, as did a more alkaline pH (7.80). In conclusion, there is a mechanism allowing rapid passive transport of 203Pb at the brain endothelium, perhaps as PbOH+. Lead uptake into brain via this system is probably made less important by active transport of lead back into the capillary lumen by the calcium-ATP-dependent pump.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1988

Infrared tympanic thermometer: evaluation of a new clinical thermometer.

We have evaluated a new clinical thermometer for accuracy. It determines temperature by measuring infrared radiation given off by a warm object. It was found to be accurate both in vivo and in vitro over the temperature range of 34.0 degrees to 39.5 degrees C. The in vivo assessment was made in patients in the ICU after their return from open heart surgery. The infrared tympanic thermometer tracked the core temperature (as measured by the thermistor tip of the pulmonary artery catheter) closely, with a correlation coefficient of 0.98, and took less than 2 sec to measure. We found this new thermometer to be accurate and, in our opinion, easily usable in the clinical situation.

Body Temperature↗
PubMed1987

Developmental changes in cerebrospinal fluid pressure and resistance to absorption in rats.

Cerebrospinal fluid (c.s.f.) pressure and resistance to absorption have been studied in exteriorized fetuses (18 to 21 days gestation) from pregnant rats anaesthetised with pentobarbitone and in similarly anaesthetised postnatal rats at 1, 5, 10 and 30 days after birth and in adults. The resting c.s.f. pressure was low in fetuses (17-21 mm H2O) and it rose to 26-27 mm H2O at 1 and 5 days after birth. By 10 days after birth the pressure was 34 mm H2O after which time there was no further change. The plateau pressure response to different infusion rates was linear, but only up to pressures around 7-fold higher than the resting c.s.f. pressure. Hence, resistance to absorption was calculated for plateau pressures up to 140 mm H2O in fetuses, to 200 mm H2O in 1- and 5-day rats and to 240 mm H2O for 10-day, 30-day and adult rats. Resistance to absorption was not significantly different for the two measurement sites (lateral ventricle and subarachnoid space) at any age studied, showing that fluid can move freely through the ventricular system in young rats. The resistance to absorption was low in the fetuses, 10.8 and 16.3 mm H2O min/microliters at 18-19 and 20-21 days gestation, respectively. There was a sharp increase in resistance to 39.2 mm H2O min/microliters at 1 day after birth and thereafter there was a decrease to 6.8 mm H2O min/microliters at 30 days and this was similar to adult values. This decrease in outflow resistance from the first day after birth may be related to the increase in c.s.f. pressure and secretion rate that occur after birth in the rat.

Absorption↗