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Biomedical subjects

S Williams

Publications and source records attributed to S Williams.

At least 217 records · Page 12Linked to original sources

Cell salvage in obstetrics: an evaluation of the ability of cell salvage combined with leucocyte depletion filtration to remove amniotic fluid from operative blood loss at caesarean section.

During 27 elective caesarean sections, operative blood loss was collected and processed using the Haemonetics Cell Saver 5 and filtered by Pall RC 100 leucocyte depletion filtration. The efficiency of removal of amniotic fluid, and the degree. of contamination with fetal red cells were assessed in the resulting 'cleaned' blood. Cell saver processing effectively removed alpha-fetoprotein from the red cells of 14 patients whose amniotic fluid was removed by separate suction and from nine of the 13 patients whose amniotic fluid was aspirated into the cell saver along with operative blood loss. Cell saver processing and leucocyte depletion filtration completely removed trophoblastic tissue and white cells, but fetal squames were still clearly present in 10, and possibly in 14 samples after processing and fully removed in only two specimens. Amorphous debris was present in all samples after processing. The maximum mass of fetal red cells contaminating any patient's total salvaged blood was 19 ml (range 2-19 ml). Had this been re-transfused into a rhesus-incompatible mother it would have required 2500 i.u. (500 microg) anti-D immunoglobulin to prevent rhesus-immunization of the mother. Contamination of processed caesarean section blood with fetal red cells and fetal squames is defined and its clinical implications discussed, with an overview of the development and current status of cell salvage. Autotransfusion by cell salvage with leucocyte depletion filtration should be considered in life-threatening obstetric haemorrhage and offered to Jehovah's Witnesses.

Journal Article↗

Observations on the effect of abolishing analgesic abuse and reducing smoking on cancers of the kidney and bladder in New South Wales, Australia, 1972-1995.

OBJECTIVES: We have assessed the effect on the rates of cancers of the kidney and bladder of measures undertaken by the government in 1979-1983 to limit smoking and analgesic abuse in New South Wales (NSW). Sale of phenacetin-containing analgesics, previously available without restriction and regularly taken by 11-13% of women and 4-9% of men in NSW, was prohibited from 1979. The prevalence of current smokers among adult Australian men had fallen from 72% in 1945 to 43% in 1980 and to 28% in 1992. In women the corresponding figures were 26%, 31% and 24%. METHODS: Incidence and mortality data from the New South Wales Central Cancer Registry for the period 1972 to 1995 were analyzed, by sex and age, for trends over time. Relative survival was calculated for cases diagnosed in the period 1980-94 and followed until the end of 1996. RESULTS: Significant trends evident from these data were: throughout the period of review a rising incidence of, and to a lesser extent mortality from, renal parenchymal cancer for which relative survival has steadily improved; falling mortality from bladder cancer throughout the period of review, but more rapid after 1985; a reversal of the earlier increasing incidence of, and mortality from, cancer of the renal pelvis; and relative survival for bladder and renal pelvic cancers which was worse in women than men. Changes in registration practice in 1985 and 1993 introduced artifacts into the trends in incidence of bladder cancer. CONCLUSIONS: Improvements in the trends of incidence and mortality of cancers of the renal pelvis and bladder in the mid-1980s are interpreted, in the light of registration and clinical practice, to indicate a beneficial effect of regulations which virtually abolished analgesic abuse and, less certainly, a contribution from measures restricting smoking, in New South Wales. However, renal parenchymal cancer continues to increase, although there has been some apparent benefit of earlier detection.

Adult↗

Psychologists in medical schools in 1997. Research brief.

The activities, income, and medical staff membership and limitations on that membership for psychologists working in U.S. medical school settings in 1997 were examined. A total of 1,938 psychologists responded to a survey conducted by the Research Office of the American Psychological Association, in conjunction with the Association of Medical School Psychologists. Some of the most salient findings were that (a) the largest number of psychologists was involved in research activities, (b) just over half of medical school psychologists were required to generate all or part of their own income through clinical work and research, and (c) the majority of these psychologists were members of a medical staff but were not extended full medical staff privileges. These and other results are discussed in the context of academic rank, tenure status, and other relevant factors.

Humans↗

Differential cognitive response to a mood challenge following successful cognitive therapy or pharmacotherapy for unipolar depression.

This study examined the nature of cognitive reactivity to mood changes in formerly depressed patients. Patients who recovered either through cognitive-behavior therapy (CBT; N = 25) or through pharmacotherapy (PT; N = 29) completed self-reported ratings of dysfunctional attitudes before and after a negative mood induction procedure. In response to similar levels of induced sad mood, PT patients showed a significant increase in dysfunctional cognitions compared with patients in the CBT group. To evaluate the effects of such cognitive reactivity on the subsequent course of depression, follow-up analyses reassessed 30 patients several years after initial testing. Results indicated that patients' reactions to the mood induction procedure were predictive of depressive relapse. These findings argue for differential effects of treatment on cognitive reactivity to mood induction and for the link between such reactivity and risk for later depressive relapse.

Adult↗

Crosstalk between cAMP-dependent kinase and MAP kinase through a protein tyrosine phosphatase.

The haematopoietic protein tyrosine phosphatase (HePTP) is a negative regulator of the MAP kinases Erk1, Erk2 and p38. HePTP binds to these kinases through a kinase-interaction motif (KIM) in its non-catalytic amino terminus and inactivates them by dephosphorylating the critical phosphorylated tyrosine residue in their activation loop. Here we show that cyclic-AMP-dependent protein kinase (PKA) phosphorylates serine residue 23 in the KIM of HePTP in vitro and in intact cells. This modification reduces binding of MAP kinases to the KIM, an effect that is prevented by mutation of serine 23 to alanine. The PKA-mediated release of MAP kinase from HePTP is sufficient to activate the kinase and to induce transcription from the c-fos promoter. Expression of a HePTP serine-23-to-alanine mutant inhibits MAP-kinase dissociation and activation and induction of transcription from the c-fos promoter. We conclude that HePTP not only controls the activity of MAP kinases, but also mediates crosstalk between the cAMP system and the MAP-kinase cascade.

Alanine↗

Cancer mortality in East and Southeast Asian migrants to New South Wales, Australia, 1975-1995.

Routinely collected data for New South Wales were used to analyse cancer mortality in migrants born in East or Southeast Asia according to duration of residence in Australia. A case-control approach compared deaths from cancer at particular sites with deaths from all other cancers, adjusting for age, sex and calendar period. Compared with the Australian-born, these Asian migrants had a 30-fold higher risk of dying from nasopharyngeal cancer in the first 2 decades of residence, falling to ninefold after 30 years, and for deaths from liver cancer, a 12-fold risk in the first 2 decades, falling to threefold after 30 years. The initial lower risk from colorectal, breast or prostate cancers later converged towards the Australian-born level, the change being apparent in the third decade after migration. The relative risk of dying from lung cancer among these Asian migrants was above unity for each category of duration of stay for women, but at or below unity for men, with no trend in risk over time. An environmental or lifestyle influence for nasopharyngeal and liver cancers is suggested as well as for cancers of colon/rectum, breast and prostate.

Adolescent↗

Predicting BMI in young adults from childhood data using two approaches to modelling adiposity rebound.

OBJECTIVE: To identify the age of adiposity rebound and the value of its associated BMI and examine their association with BMI at ages 18 and 21 y for males and females. DESIGN: A longitudinal study of a large cohort of people born in Dunedin, New Zealand between 1972-1973. SUBJECTS: Four hundred and seventy-four males and 448 females aged between birth and 21 y. MEASUREMENTS: BMI was derived from measurements of weight and height made when the participants were born and at intervals from age 3-21 y. RESULTS: When a random coefficients model was fitted to the data for those who had five or more measures of BMI between age 3 and age 18y, adiposity rebound occurred at 6.0 y of age for boys and 5.6y for girls. The values of BMI associated with these were 15.7 kg/m2 for boys and 15.5 kg/m2 for girls. The correlations between age at adiposity rebound and BMI at ages 18 and 21 y were between -0.72 and -0.65 for boys and -0.59 and -0.47 for girls. These were higher than those derived from fitting individual curves or from deriving the adiposity rebound from data collected up to age 11 y. The correlation between BMI at age 7y and BMI at ages 18 and 21 y were 0.70 and 0.61 for boys and 0.56 and 0.52 for girls. The correlations between measures of skeletal maturity at age 7y and adiposity rebound were statistically significant for boys but not for girls. CONCLUSIONS: BMI in early adulthood was associated with both age of adiposity rebound and BMI at that age. As the correlations between BMI at age 7 y and BMI at ages 18 and 21 y were similar in magnitude, BMI at age 7 y may be a more practical way of predicting BMI in early adulthood.

Adipose Tissue↗

Complexity- and risk-adjusted model for measuring surgical outcome.

BACKGROUND: Although currently available surgical scoring systems have good outcome predictive power, their use is often limited by complexity and their non-dynamic nature. The aim of this study was to develop and test a risk adjustment for general surgical audit which is both simple and dynamic, while preserving a high predictive power for surgical morbidity. METHODS: Twelve easily measured, well defined prognostic variables for morbidity were identified from the Otago Surgical Audit data collection form and stratified into suitable categories. Logistic regression was used to adjust for confounding between factors, identifying risk factors with the strongest prognostic value for the outcome of severe and intermediate complications. The resulting model was tested by back-validation and validation. RESULTS: The derived risk adjustment included all 12 variables. Adjusted odds ratios for all variables were markedly lower than unadjusted values. After logistic regression, the strongest predictors of postoperative morbidity were duration of operation, operation category, inpatient status and organ system in which the procedure was carried out. The area under the receiver operating characteristic curve was 0.86. CONCLUSION: A simple dynamic model for surgical morbidity has been developed which is comparable to previously published surgical scoring systems in terms of predictive power. This risk adjustment tool can be incorporated into the existing audit system, enabling comparison of surgical unit performance.

Adolescent↗

Reduced toxicity of expression, in Escherichia coli, of antipollutant antibody fragments and their use as sensitive diagnostic molecules.

Single-chain antibody fragments (scAb), specific for the chlorophenoxy acid herbicide mecoprop, have been expressed and purified from the bacterium Escherichia coli. Co-expression with the colE1-compatible, arabinose-inducible, skp expression vector pHELP1 prevented bacterial lysis and significantly increased both total and functional expression yield. The periplasmic protein, SKP, may have a role as a generic detoxification protein. Surface plasmon resonance (BIAcore 2000) analysis confirmed that the purified scAb retained similar binding kinetics to the monoclonal antibody (Mab) from which it was cloned. In competition ELISA, the bacterial scAb showed the same specificity for mecoprop and a related herbicide, MCPA, as the Mab but an increase in sensitivity for free antigen in all ELISA formats. Bacterially expressed antibody fragments provide a simple, sensitive and cost-effective alternative to the traditional production of diagnostic Mabs via tissue culture.

2-Methyl-4-chlorophenoxyacetic Acid↗

A novel isoform of the low molecular weight phosphotyrosine phosphatase, LMPTP-C, arising from alternative mRNA splicing.

The low molecular weight protein tyrosine phosphatase (LMPTP) is an 18-kDa enzyme that it distantly related to other protein tyrosine phosphatases. The single gene for LMPTP is known to undergo an alternative splicing event in which exon 3 or exon 4 is excised, resulting in two isoforms termed A and B; the latter is more mobile in SDS/PAGE. In this paper we report the existence of a third isoform, which we call C, in which both exons 3 and 4 are lacking. We find the resulting mRNA to be ubiquitously expressed at levels that exceed those of the mRNAs for isoforms A and B. This mRNA was reverse-transcribed, cloned and sequenced, confirming the direct splicing of exon 2 to exon 5. In-vitro transcription and translation of the cDNA for the novel isoform resulted in the expected 16 kDa protein. This protein was also detected in Jurkat T cells using an antipeptide antiserum. LMPTP-C immunoprecipitated from transfected cells, as well as bacterially produced recombinant LMPTP-C, lacked phosphatase activity. Unlike LMPTP-B, LMPTP-C was not phosphorylated on tyrosine when coexpressed with Lck despite the presence of the two acceptor tyrosines. Finally, whereas c-fos induction by platelet-derived growth factor was inhibited by LMPTP-B, LMPTP-C augmented it. These results suggest that the lack of the 38-amino acid fragment encoded by exon 3 or 4 results in a protein product with a different three-dimensional folding, that lacks a functional catalytic pocket and that may function as a natural antagonist of isoforms A and B.

Alternative Splicing↗

Mood and organizational citizenship behavior: the effects of positive affect on employee organizational citizenship behavior intentions.

This study, involving 139 employees from a variety of industries, organizations, and positions in Singapore, measured the effects of mood on the intentions of employees to contribute actions that are organizationally desirable but are not part of their formal job requirements (organizational citizenship behavior). After effects of established patterns of historical organizational citizenship behavior, demographic characteristics, and employee positive and negative affectivity had been controlled, stepwise regression analysis revealed that the amount of positive affect currently experienced by an employee significantly influenced the employee's intention to perform specific acts of organizational citizenship.

Administrative Personnel↗

The effects of mood on managerial risk perceptions: exploring affect and the dimensions of risk.

The effects of managerial mood on situational risk perceptions were tested among 85 managers from a variety of organizations, industries, and positions in Singapore. A risk-assessment scenario was developed that systematically varied the risk dimensions of outcome uncertainty, potential gains and losses, situational framing, and personal expectations. Negative, neutral, and positive moods were induced by having managers recall and describe work events. As affective state became more positive, managers perceived situational framing as more positive, and their beliefs that they could influence risky outcomes increased. Additionally, positive affect increased the likelihood that people who perceived situations as risky would select riskier courses of action.

Adult↗

Effect of gender, treatment site and psychiatric comorbidity on quality of life outcome in substance dependence.

Patients receiving treatment for substance dependence frequently endorse high rates of psychological impairment and other measures of reduced quality of life. We conducted a baseline and six-month follow-up study of a series of one hundred and three unselected patients receiving treatment for a substance abuse or dependence problem. Women and patients requiring in-patient detoxification demonstrated the most psychological impairment at baseline, as measured by the mental component summary of the SF-36. Inpatient site of treatment was associated with continued psychological impairment six months following treatment. More aggressive psychiatric and psychological interventions may be indicated for women and for inpatient substance dependence populations.

Adult↗

A study of artefacts in simultaneous PET and MR imaging using a prototype MR compatible PET scanner.

We have assessed the possibility of artefacts that can arise in attempting to perform simultaneous positron emission tomography (PET) and magnetic resonance imaging (MRI) using a small prototype MR compatible PET scanner (McPET). In these experiments, we examine MR images for any major artefacts or loss in image quality due to inhomogeneities in the magnetic field, radiofrequency interference or susceptibility effects caused by operation of the PET system inside the MR scanner. In addition, possible artefacts in the PET images caused by the static and time-varying magnetic fields or radiofrequency interference from the MR system were investigated. Biological tissue and a T2-weighted spin echo sequence were used to examine susceptibility artefacts due to components of the McPET scanner (scintillator, optical fibres) situated in the MR field of view. A range of commonly used MR pulse sequences was studied while acquiring PET data to look for possible artefacts in either the PET or MR images. Other than a small loss in signal-to-noise using gradient echo sequences, there was no significant interaction between the two imaging systems. Simultaneous PET and MR imaging of simple phantoms was also carried out in different MR systems with field strengths ranging from 0.2 to 4.7 T. The results of these studies demonstrate that it is possible to acquire PET and MR images simultaneously, without any significant artefacts or loss in image quality, using our prototype MR compatible PET scanner.

Artifacts↗

Dose control with cell lines used for encapsulated cell therapy.

Cell therapy-use of cells to deliver active factors-is an emerging technique in treatment of neurodegenerative disease. Successful devices maintain cell viability and functionality over extended implant periods. Use of dividing cell lines to deliver therapeutic factors has been studied extensively. One emerging issue is the tendency of cells to continue proliferation within the intracapsular environment-potentially outstripping nutrient supply. This work presents a method of controlling proliferation and delivering therapeutic molecules within a dose range. The method entails encapsulation into a hollow fiber device of discrete numbers of cell-containing microcarriers. Proliferation control is attained by embedding cell-containing microcarriers in nonmitogenic hydrogels. PC-12 cells secreting L-dopa and dopamine was the model cell line tested. Feasibility of the method in controlling growth of normally rapidly dividing cells in the intracapsular environment was demonstrated in vitro and in vivo. Control nonmicrocarrier PC-12 cell devices had approximately fourfold greater expansion in cell number compared to experimental microcarrier-containing devices over 4 weeks in vitro and in vivo after implant into rat striatum. Ability to control dose released over a several-fold range was demonstrated with encapsulated PC-12 cells delivering neurotransmitters and C2C12 mouse myoblast cells delivering neurotrophic factors (CNTF).

Animals↗

An estimation of selenium requirements for New Zealanders.

BACKGROUND: Current US dietary recommendations for selenium are based on maximization of plasma glutathione peroxidase (GSHPx) activity according to data from one study of Chinese men. OBJECTIVE: The effect of various amounts of supplemental selenium on GSHPx activities in blood of New Zealand adults was investigated to calculate a selenium requirement for New Zealanders. The effect on plasma selenoprotein P and thyroid hormones was also investigated. DESIGN: Fifty-two adults with low blood selenium concentrations ingested a placebo or 10, 20, 30, or 40 microgram Se as L-selenomethionine daily for 20 wk. RESULTS: Plasma and whole-blood GSHPx activities increased in all supplemented groups but reached a plateau only in the group receiving 40 microgram Se, as determined by statistical analysis. Increases in selenoprotein P were greater than those for selenium and GSHPx at all supplement intakes. Thyroxine concentrations decreased in supplemented groups but the decrease was significantly different from that in the control group only for the 10-microgram group and for all supplemented groups combined. CONCLUSIONS: An upper estimated requirement of 90 microgram Se/d was calculated as the intake necessary for maximization of plasma GSHPx activity, as used in the derivation of the US recommended daily allowance. Our lower estimated requirement of 39 microgram Se/d was the intake necessary to reach two-thirds of maximal GSHPx activity, as was used in calculating the World Health Organization normative requirement. The lower estimate is a realistic goal for New Zealand but the upper estimate could be achieved only with regular inclusion of high-selenium foods.

Adult↗

The identification of [2-(14)C]2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine metabolites in humans.

[2-(14)C]2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine ([14C]PhIP), a putative human carcinogenic heterocyclic amine found in well-done cooked meat, was administered orally to three colon cancer patients undergoing a partial colonectomy. Forty-eight to seventy-two hours prior to surgery, subjects received a 70-84 microg dose of 14C. Urine and blood were analyzed by HPLC for PhIP and PhIP metabolites. Metabolites were identified based on HPLC co-elution with authentic PhIP metabolite standards, mass spectral analysis and susceptibility to enzymatic cleavage. In two subjects, approximately 90% of the administered [14C]PhIP dose was eliminated in the urine, whereas in the other, only 50% of the dose was found in the urine. One subject excreted three times more radioactivity in the first 4 h than did the others. Twelve radioactive peaks associated with PhIP were detected in the urine samples. The relative amount of each metabolite varied by subject, and the amounts of each metabolite within subjects changed over time. In all three subjects the most abundant urinary metabolite was identified as 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine-N2-glucuron ide (N-hydroxy-PhIP-N2-glucuronide), accounting for 47-60% of the recovered counts in 24 h. PhIP accounted for <1% of the excreted radiolabel in all three patients. Other metabolites detected in the urine at significant amounts were 4-(2-amino-1-methylimidazo[4,5-b]pyrid-6-yl)phenyl sulfate, N-hydroxy-PhIP-N3-glucuronide and PhIP-N2-glucuronide. In the plasma, N-hydroxy-PhIP-N2-glucuronide accounted for 60, 18 and 20% of the recovered plasma radioactivity at 1 h post PhIP dose in subjects 1, 2 and 3 respectively. Plasma PhIP was 56-17% of the recovered dose at 1 h post exposure. The relatively high concentration of N-hydroxy-PhIP-N2-glucuronide and the fact that it is an indicator of bioactivation make this metabolite a potential biomarker for PhIP exposure and activation. Determining the relative differences in PhIP metabolites among individuals will indicate metabolic differences that may predict individual susceptibility to carcinogenic risk from this suspected dietary carcinogen.

Administration, Oral↗

Glucuronidation of 2-hydroxyamino-1-methyl-6-phenylimidazo[4, 5-b]pyridine by human microsomal UDP-glucuronosyltransferases: identification of specific UGT1A family isoforms involved.

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine is a heterocyclic aromatic amine found in cooked meats and dietary exposure to PhIP has been implicated in the etiology of colon cancer in humans. PhIP, along with other heterocyclic aromatic amines, requires metabolic activation to exhibit genotoxic effects. PhIP is initially oxidized by the activity of cytochrome P4501A2 to produce 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine (N-OH-PhIP), a reaction occurring primarily in the liver. Whereas subsequent biotransformation of N-OH-PhIP via acetylation or sulfation can produce reactive electrophiles that readily bind to DNA, N-glucuronidation, catalyzed by UDP-glucuronosyltransferases (UGTs), functions as a detoxification mechanism. Although hepatic glucuronidation of N-OH-PhIP has been well characterized, the extrahepatic metabolism of this compound is poorly understood. Studies in our laboratory now indicate that the intestinal tract, and particularly the colon, is a significant site of glucuronidation of N-OH-PhIP. When assays were performed with microsomes prepared from the mucosa of the intestinal tract, it was determined that glucuronidation of N-OH-PhIP occurs throughout the intestinal tract, with activity approximately three times higher in the colon as that found in the upper intestine. Glucuronidation rates from colon microsomes showed considerable interindividual variability and incubation with N-OH-PhIP yielded two glucuronides. HPLC analysis showed that the predominant product formed is the N-OH-PhIP-N2-glucuronide, while the N3-glucuronide accounts for <10% of the total glucuronidation product. These rates approach the rates found in human liver microsomes, demonstrating the significance of extrahepatic metabolism of this food-borne carcinogen. Subsequent assays with human recombinant UGTs demonstrated that at least four human UGT isoforms, all from the UGT1A subfamily, are capable of catalyzing the biotransformation of N-OH-PhIP. Members of the UGT2B family available for this study did not conjugate N-OH-PhIP, although immunoinhibition studies in human liver microsomes strongly suggest the involvement of a UGT2B isoform(s) in this organ.

Animals↗