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Biomedical subjects

J Smith

Publications and source records attributed to J Smith.

At least 577 records · Page 32Linked to original sources
PubMed1995

People nominated as wise: a comparative study of wisdom-related knowledge.

This study examined whether our conception of wisdom has a psychological bias, by focusing on a group of distinguished individuals nominated as being wise. The comparison groups included older clinical psychologists and highly educated old and young control groups. Wisdom-related knowledge was assessed by 2 tasks and evaluated with a set of 5 wisdom criteria. First, old wisdom nominees performed as well as clinical psychologists who in past research had shown the highest levels of performance. Second, wisdom nominees excelled in the task of existential life management and the criterion of value relativism. Third, up to age 80, older adults performed as well as younger adults. If there is a psychological bias to our conception of wisdom, this does not prevent nonpsychologists from being among the top performers.

Adaptation, Psychological↗
PubMed1995

The structure of calcyclin reveals a novel homodimeric fold for S100 Ca(2+)-binding proteins.

The S100 calcium-binding proteins are implicated as effectors in calcium-mediated signal transduction pathways. The three-dimensional structure of the S100 protein calcyclin has been determined in solution in the apo state by NMR spectroscopy and a computational strategy that incorporates a systematic docking protocol. This structure reveals a symmetric homodimeric fold that is unique among calcium-binding proteins. Dimerization is mediated by hydrophobic contacts from several highly conserved residues, which suggests that the dimer fold identified for calcyclin will serve as a structural paradigm for the S100 subfamily of calcium-binding proteins.

Amino Acid Sequence↗
PubMed1995

The strategic planning of health management information systems.

This paper discusses the roles and functions of strategic planning of information systems in health services. It selects four specialised methodologies of strategic planning for analysis with respect to their applicability in the health field. It then examines the utilisation of information planning in case studies of three health organisations (two State departments of health and community services and one acute care institution). Issues arising from the analysis concern the planning process, the use to which plans are put, and implications for management.

Australia↗
PubMed1995

Temperament and stress resilience in school-age children: a within-families study.

OBJECTIVE: Stress resilience was assessed in 81 school-age children, from within 32 families acknowledging severe psychosocial stress. Resilient and nonresilient children, identified via competence and behavior disorder measures from school and home, were compared. METHOD: Parents and teachers completed questionnaires and rating scales, and children were observed and assessed at home on attributes of temperament, self-esteem, ability, gender, and mother-child warmth. RESULTS: Individual differences in child and family attributes that were predictive of competent child functioning varied according to the outcome measure used. Teachers' ratings of positive temperament (low emotional reactivity, high social engagement) best discriminated children showing resilience on all indicators, i.e., behavioral and social competence both at home and at school, with maternal warmth and the number of adverse life events the child had recently experienced also contributing. Level of maternal stress and individual differences in child intelligence were related to academic adjustment, but the child's age, sex, ability, and self-concept were not significant discriminators of behavioral adjustment. CONCLUSIONS: The findings emphasize the salience of a positive temperament as a resilience factor as well as the need to consider different estimates and contexts in assessing resilience for children growing up in stressful situations.

Adaptation, Psychological↗
PubMed1995

Antagonism of the effects of clonidine by the alpha 2-adrenoceptor antagonist, fluparoxan.

1. The effects of fluparoxan, an alpha 2-adrenoceptor antagonist, on the pharmacodynamic changes induced by clonidine were investigated in this placebo-controlled, double-blind, two-period, cross-over study in 16 healthy male volunteers (aged 19 to 44 years). 2. Subjects received either fluparoxan or placebo, twice-daily for 5 1/2 days (11 doses). One hour after the first and last dose of each treatment period, clonidine (200 micrograms) was infused intravenously over 5 min. 3. Indices of clonidine-mediated pharmacodynamic responses (growth hormone secretion, bradycardia, hypotension, xerostomia and sedation) were taken before and after clonidine infusion. Growth hormone secretion was assessed by quantifying serum growth hormone concentrations; sedation was assessed by both visual analogue scales (VAS) and by a visual psychomotor response meter, measuring critical flicker fusion (CFF). 4. The majority of subjects reported minor adverse events such as lethargy, headache and dry mouth following clonidine infusion. All adverse events were likely to be related to clonidine, as they occurred consistently between treatment groups. Fluparoxan has, however, in previous studies been reported to cause headache and light-headedness. 5. Prior to the clonidine infusion, fluparoxan caused small but statistically significant increases in systolic blood pressure (4 mm Hg) and salivary flow (approximately 30%) after both single and repeated doses. A small increase in heart rate (2 beats min-1) was seen after a single dose which was also statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1995

Increase in non-melanoma skin cancer--the King's College Hospital experience (1970-92).

A retrospective study of the number of patients with non-melanoma skin cancer treated over a 22-year period at King's College Hospital was carried out. There was a threefold rise in the number of patients with basal cell carcinoma and a 10-fold rise in the number of patients with squamous cell carcinoma from 1970 to 1992. This study demonstrates a marked increase in the number of patients with non-melanoma skin cancers presenting to the Department of Dermatology and reflects a national trend which underlines the need for skin cancer services to be prepared for a growing workload in this area.

Age Distribution↗
PubMed1995

Australasian multicentre phase II study of paclitaxel (Taxol) in relapsed ovarian cancer.

BACKGROUND: Until recently there has been no effective therapy for patients with relapsed ovarian carcinoma following standard platinum based chemotherapy. Paclitaxel has recently been approved for clinical use in this malignancy. AIMS: To evaluate the objective response rate and toxicity of paclitaxel in patients with relapsed ovarian cancer. METHODS: Paclitaxel was given on an outpatient basis as a three hour infusion every 21 days for a maximum of ten cycles to 72 patients with advanced ovarian cancer previously treated with at least one platinum containing regimen. The starting dose was either 175 mg/m2 (patients with one or two prior chemotherapy regimens) or 135 mg/m2 (three previous regimens). Premedication was given because of the documented risk of hypersensitivity reactions to paclitaxel. RESULTS: The overall response rate was 22% (95% confidence interval [CI] 13% to 34%) in the 72 patients enrolled in the study: four patients had a complete response. Three patients (4%) ceased treatment due to hypersensitivity reactions. Other significant (WHO grade 3 or 4) toxicities included neutropenia (51%), myalgia (14%), neurological (3%), alopecia (93%) and nausea and vomiting (3%). The estimated median survival of all patients was 9.8 months (95% CI: 9.1-13.0 months) with 44% alive at one year (standard error [SE] 7%). CONCLUSIONS: This study confirms that paclitaxel given as a three hour infusion has significant activity and acceptable toxicity in advanced ovarian carcinoma previously treated with platinum regimens.

Adolescent↗
PubMed1995

Cognitive function, thyroid status and postpartum depression.

Impairment of cognitive function can occur with thyroid disorder and also with depression. Since depression occurs in conjunction with postpartum autoimmune thyroiditis, the question arises as to whether any impairment of cognitive function in postpartum women is related to change in thyroid status or to depressed mood. A total of 242 women (110 thyroid antibody-positive and 132 antibody-negative) were assessed at 8, 12, 20 and 28 weeks postpartum in the outpatients of a district general hospital. Thyroid antibody levels (antimicrosomal and antithyroglobulin) were monitored at monthly intervals, together with plasma T3, T4 and thyroid-stimulating hormone. The main outcome measures were Research Diagnostic Criteria for depression, the 17-item Hamilton Depression Rating Scale and the Edinburgh Postnatal Depression Scale, together with reaction time and digit span. Subjects with postnatal depression showed detectable cognitive impairment independent of thyroid antibody status and actual thyroid dysfunction.

Antibodies↗
PubMed1995

Antibody responses to suspected periodontal pathogens in elderly subjects with periodontal disease.

Little is known about the relationship of aging to periodontal disease. The immune response undergoes aging-related changes resulting in loss of functional capacity. The aim of this study was to investigate the relationship between levels of serum IgG antibodies against suspected periodontal pathogenic microorganisms to the presence or absence of periodontal disease in an elderly (65-75 yrs) population. From this study, we obtained information concerning: (1) the ability to differentiate elderly individuals without disease from those with disease by their levels of antibodies against periodontal pathogens and (2) which periodontal pathogen(s) triggered those responses. IgG anti- Porphyromonas gingivalis (strains W83 and 381) levels in the serum of elderly patients with severe periodontal disease were the only antibody responses measured which were elevated compared to the elderly control group of subjects with no periodontal disease. Anti- Prevotella intermedia IgG levels in both elderly patient groups were depressed compared to anti- P. intermedia levels in the young normal control subjects. Serum IgG antibody levels to six other plaque microorganisms did not differentiate between diseased and normal, elderly or young subjects. This data suggested that P. gingivalis was associated with periodontal disease in this elderly group of individuals and that those elderly individuals were able to respond with a normal IgG immune response.

Adult↗
PubMed1995

Gray-to-white matter ratios of HMPAO in the human brain.

The gray-to-white matter ratio of technetium 99m-hexamethylpropyleneamine oxime (99mTc-HMPAO) in 14 anesthetized patients undergoing partial brain resection for treatment of complex partial seizures. The gray-to-white matter ratio of 99mTc-HMPAO was 1.8:1 (standard deviation 0.6) in the temporal lobe. Many of the biopsied specimens demonstrated histopathological abnormalities.

Adult↗
PubMed1995

Different forms of streptolysin O produced by Streptococcus pyogenes and by Escherichia coli expressing recombinant toxin: cleavage by streptococcal cysteine protease.

To resolve apparent discrepancies in the literature, N-terminal sequences of the active high- and low-molecular-weight (high- and low-M(r)) forms of native streptolysin O (nSLO) purified from Streptococcus pyogenes culture supernatants and of the similar-size high- and low-M(r) forms of recombinant SLO (rSLO) found in the periplasm of Escherichia coli expressing a cloned slo gene were determined. The high-M(r) forms of nSLO and rSLO are identical, reflecting removal of a 31-residue signal peptide, but the similar-size low-M(r) forms are very different. Removal of C-terminal sequences by proteases in the E. coli periplasm produces an inactive low-M(r) form of rSLO. In contrast, an active low-M(r) form of nSLO is produced by proteolytic cleavage between the N-terminal residues Lys-77 and Leu-78, which was shown to correspond to an extremely sensitive cleavage site for the pyrogenic exotoxin B-derived streptococcal cysteine protease.

Amino Acid Sequence↗
PubMed1995

Detection of human immunodeficiency virus type 1 proviral DNA by PCR using an electrochemiluminescence-tagged probe.

We have developed a rapid, pseudohomogeneous assay for the detection of PCR amplicons, based on the use of electrochemiluminescence generated from a Tris-bipyridine ruthenium(II) label. PCR amplification of highly conserved human immunodeficiency virus type 1 (HIV-1) gag gene sequences was performed with SK38 and SK39 primers, the latter of which was 5' biotinylated. Post-PCR reaction mixtures were combined with 10(12) copies of the SK19 probe-Tris-bipyridine ruthenium(II) conjugate, denatured by heating at 100 degrees C for 5 min, and hybridized at 55 degrees C for an additional 15 min. Hybridization to the biotinylated strand of the amplified DNA was determined by the addition of streptavidin-conjugated magnetic particles and analyzed by using an Origen-1 electrochemiluminescence analyzer. Our results demonstrated a sensitivity of fewer than five copies of HIV-1 (pre-PCR), by using either purified plasmid DNA containing one complete copy of the HIV-1 cDNA genome or lysed, proteinase K-treated 8E5 cells as the starting material. In an evaluation of actual clinical specimens (peripheral blood monocytes from both healthy and HIV-1-infected children), the electrochemiluminescent detection assay correlated 100% with both our standard method (solution hybridization with a radiolabeled probe followed by polyacrylamide gel electrophoresis [PAGE] and autoradiography) and a commercial method (Roche Amplicor). The electrochemiluminescent method was substantially easier to perform than either the PAGE or microtiter plate assays and was considerable faster to perform than either of these alternative formats.

Child↗
PubMed1995

A mutation in the gene encoding the Saccharomyces cerevisiae single-stranded DNA-binding protein Rfa1 stimulates a RAD52-independent pathway for direct-repeat recombination.

In the yeast Saccharomyces cerevisiae, recombination between direct repeats is synergistically reduced in rad1 rad52 double mutants, suggesting that the two genes define alternate recombination pathways. Using a classical genetic approach, we searched for suppressors of the recombination defect in the double mutant. One mutation that restores wild-type levels of recombination was isolated. Cloning by complementation and subsequent physical and genetic analysis revealed that it maps to RAF1. This locus encodes the large subunit of the single-stranded DNA-binding protein complex, RP-A, which is conserved from S. cerevisiae to humans. The rfa1 mutation on its own causes a 15-fold increase in direct-repeat recombination. However, unlike most other hyperrecombination mutations, the elevated levels in rfa1 mutants occur independently of RAD52 function. Additionally, rfa1 mutant strains grow slowly, are UV sensitive, and exhibit decreased levels of heteroallelic recombination. DNA sequence analysis of rfa1 revealed a missense mutation that alters a conserved residue of the protein (aspartic acid 228 to tyrosine [D228Y]). Biochemical analysis suggests that this defect results in decreased levels of RP-A in mutant strains. Overexpression of the mutant subunit completely suppresses the UV sensitivity and partially suppresses the recombination phenotype. We propose that the defective complex fails to interact properly with components of the repair, replication, and recombination machinery. Further, this may permit the bypass of the recombination defect of rad1 rad52 mutants by activating an alternative single-stranded DNA degradation pathway.

Amino Acid Sequence↗
PubMed1995

Non-invasive detection of bladder cancer by identification of abnormal CD44 proteins in exfoliated cancer cells in urine.

Aims-To investigate the expression of CD44 proteins in exfoliated urothelial cells and in tumour tissues from bladder cancer patients. A further objective was to evaluate the diagnostic potential of the changes observed in the expression of these proteins as a marker for non-invasive detection of bladder cancer.Methods-Naturally voided urine specimens were collected from 47 patients with bladder cancer or severe urothelial dysplasia (n=3) and from a control group of 43 people with no evidence of neoplastic disease. Exfoliated urothelial cells floating in the urine were pelleted by centrifugation and lysed, and their constituent proteins extracted. The pattern of expression of CD44 proteins in each sample was examined by western blot analysis using a monoclonal antibody, Hermes 3, which recognises an epitope on the polypeptide backbone of the CD44 protein. Immunohistochemical studies were performed on neoplastic (n=10) and normal (n=4) bladder tissue specimens which were snap frozen in liquid nitrogen before examination with antibodies to CD44 gene products (CD44s and CD44v6).Results-Western blot analysis revealed several high molecular weight CD44 isoforms > 160 kDa in urine cell lysates from 75% of patients with histologically confirmed bladder cancer and in two of the three patients with severe dysplasia. Such patterns were not detected in the urine cell pellets from any persons in the control group. Immunohistochemical studies of the tissue distribution of CD44s and CD44v6 showed that the differentiation and maturation of the epithelial cells in the normal bladder mucosa is accompanied by a decrease in CD44 protein expression. However, carcinoma cells overexpress standard and variant CD44 isoforms and continue to do so as they proceed through the thickened epithelial layer to the luminal surface and after they are shed into the urine.Conclusions-The abnormal expression of CD44 proteins in exfoliated cancer cells may be a useful marker for the noninvasive diagnosis of bladder cancer.

Journal Article↗
PubMed1995

Insulin-like growth factor II prevents apoptosis in a human teratoma derived cell line.

Aim-To study how insulin-like growth factor II (IGF-II) affects the behaviour of human teratoma cells.Methods-The human pluripotential teratoma cell line Tera 2 was cultured under serum-free conditions in the presence or absence of IGF-II. Effects on cell proliferation and apoptosis as well as on the expression of the proto-oncogene c-myc were studied.Results-In this study we show that Tera 2 cells deprived of serum undergo programmed cell death (apoptosis). The onset of nuclear fragmentation was observed 12 hours after serum withdrawal. The morphological changes of the Tera 2 cell nuclei were confirmed by the occurrence of a nucleosome ladder. However, the constitutive expression of the proto-oncogene c-myc was not decreased in parallel with initiation of apoptosis. The apoptotic response to serum withdrawal could be counteracted by simultaneous addition of IGF-II. In addition it was found that human testicular tumours (seminoma and embryonal carcinoma) contain raised levels of insulin-like growth factors.Conclusions-The precise roles of IGF-I and IGF-II have been unclear, and there is overwhelming evidence against these factors as primarily transforming agents. The finding that IGF-II apparently counteracts apoptosis in vitro may well explain its effects on tumours in vivo.

Journal Article↗
PubMed1995

Comparison of patients' needs for information on prostate surgery with printed materials provided by surgeons.

OBJECTIVES: To identify strengths, weaknesses, and omissions in existing leaflets and factsheets on prostatectomy given by surgeons to patients. DESIGN: Comparison of content of leaflets and factsheets with patients' needs and discontents in a questionnaire survey as part of the national prostatectomy audit. SETTING: All NHS and independent hospitals performing prostatectomy in four health regions. SUBJECTS: 87 surgeons, 53 of whom used printed material to inform patients about their operations; a total of 25 different factsheets being used. 5361 men undergoing prostatectomy were sent a closed response questionnaire about their treatment; 4226 men returned it completed. A random sample of 2000 patients was asked for further comments, of whom 807 supplied pertinent comments. MAIN MEASURES: Content of the 25 factsheets compared with patients' needs identified in the questionnaires. RESULTS: Much of the information distributed had considerable shortcomings: it lacked uniformity in form and content, topics of relevance to patients were omitted, terminology was often poor, and patients' experience was at variance with what their surgeons said. For example, only one factsheet discussed the potential consequences of malignancy. Patients wanted more information on prostate cancer (1250(29%)) and some thought that the explanation of biopsy results was inadequate (29(4%)). Only six factsheets discussed the possible changes in sexual sensation after transurethral resection of the prostate, stating that patients would feel no change. However, 1490(35%) patients reported a change and 500(12%) were worried about it. CONCLUSION: Current standards of printed information do not meet the needs and requirements of patients undergoing prostatectomy.

General Surgery↗
PubMed1995

Salmeterol inhaler using a non-chlorinated propellant, HFA134a: systemic pharmacodynamic activity in healthy volunteers.

BACKGROUND: Metered dose inhalers for the treatment of asthma use chlorofluorocarbons as propellants. These face an international ban due to their effect on the ozone layer. Salmeterol has been reformulated using the non-chlorinated propellant Glaxo inhalation grade HFA134a. METHODS: The safety, tolerability and systemic pharmacodynamic activity of the salmeterol/HFA134a inhaler, the current salmeterol inhaler, and placebo (HFA134a) were compared in 12 healthy volunteers in a double blind, randomised crossover study using a cumulative dosing design. RESULTS: Safety and tolerability were similar and the response was related to the dose over the range used (50-400 micrograms) with both salmeterol inhalers. The salmeterol/HFA134a inhaler showed no differences from the current inhaler for pulse rate, blood pressure, tremor, QTc interval, and plasma glucose levels. The salmeterol/HFA134a inhaler had significantly less effect on plasma potassium levels. CONCLUSIONS: In healthy volunteers the salmeterol/HFA134a inhaler is at least as safe and well tolerated as the current salmeterol inhaler, and has similar systemic pharmacodynamic activity.

Administration, Inhalation↗