Asthma & elderly people.
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Administration, Inhalation↗
Biomedical subjects
S Smith
Publications and source records attributed to S Smith.
A comparison of two different shuttle run tests for the estimation of VO2max.
The aims of this experiment were twofold. The first was to determine whether there was a significant difference between two types of 20-m shuttle run test used to estimate VO2max, these being the Canadian version (CT) and the European versione (ET). The second aim was to determine which of the two tests best estimated direct VO2 measurement in our laboratory. To accomplish the first aim, 500 schoolchildren aged 12 to 16 years were randomly chosen from schools within Tasmania to undertake the two tests within seven days of each other. On the day of testing the children were assigned to one of the two tests and had no knowledge as to which test was being undertaken. Half of the children underwent the CT test first while the other half undertook the ET test first. Seven days after the first test was completed the appropriate second test was undertaken. The instructions to each child centred around the necessity to complete as many shuttles as possible staying in time with a pre-recorded signal. A relationship between the two sets of shuttle run data indicated that there was a significant correlation between the ET and CT, r = 0.834 (p < 0.0001). A Student's "t" test revealed that when the estimates of VO2max were compared however, there was a significant difference between the two tests (p < 0.0001). The ET estimated (Mean +/- SEM) VO2max at 34.9 +/- 0.45 ml.kg-1.min-1 whereas the CT estimated VO2max at 43.3 +/- 0.40 ml.kg-1.min-1. When this data was correlated, the co-efficient dropped to r = 0.761 which was still significant (p < 0.001). In order to accomplish the second aim, fifty children were chosen at random to undertake a VO2max test (DM) which was conducted via standard open circuit spirometry using a Quinton Metabolic Cart (QMC). The highest correlation was DM:ET being r = 0.93 whereas DM:CT was r = 0.87, both being significant at p < 0.001. When the data was compared there was a significant (p < 0.05) difference between DM and ET. DM measured VO2max as 37.6 +/- 0.37 ml.kg-1.min-1 whereas ET underestimated DM and measured VO2max at 34.7 +/- 0.56 ml.kg-1.min-1. The CT (41.9 +/- 0.62 ml.kg-1.min-1) over estimated DM by 11.4% however, the difference here also being significant (p < 0.01). This results of this study would suggest that teachers and coaches should use either one test or the other in the estimation of VO2max as the two tests differ significantly in their estimation. Of these two test versions, the ET underestimates direct VO2max measurement but is more accurate than the CT, so we feel this is the test of choice.
Adolescent↗
Birth stools. In harmony with gravity.
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Delivery, Obstetric↗
Phase I study of N-(phosphonacetyl)-L-aspartate with fluorouracil and with or without dipyridamole in patients with advanced cancer.
We conducted a combined biochemical modulation trial of N-(phosphonacetyl)-L-aspartate (PALA), dipyridamole (DP), and fluorouracil (5-FU) in patients with cancer. Eighty-eight patients with advanced cancer were entered into this Phase I trial. During the first part of the study, four doses of PALA (125, 250, 500, and 1000 mg/m2, administered on day 1) were evaluated to determine the PALA dose with maximal suppression of aspartate transcarbamylase (ATCase) activity that was clinically tolerable. Patients were randomized to receive DP (or no DP), 50 mg/m2, p.o. every 6 h on days 1-6, and all patients received 5-FU, 400 mg/m2, by bolus administration on days 2-5. Prior to and during therapy, WBCs were collected and assayed for ATCase activity. After the maximally tolerated PALA dose with 400 mg/m2 5-FU +/- 50 mg/m2 DP was defined, the 5-FU dose was escalated using the same administration schedule of 5-FU, PALA, and DP. The dose of 5-FU was escalated by 25% in each of the DP cohorts until dose-limiting toxicity was reached. ATCase activity was inhibited in a dose-dependent manner with PALA doses of 125, 250, 500, and 1000 mg/m2, resulting in 0, 13, 17, and 49% inhibition of ATCase activity. Only at the higher PALA doses (i.e., 500 and 1000 mg/m2) was ATCase activity suppressed during days 2-5, but the activity returned to pretreatment levels by day 15. Based on the clinical tolerance and significant suppression of ATCase activity, a PALA dose of 500 mg/m2 was selected for the 5-FU dose escalation phase. At a 5-FU dose of 625 mg/m2, dose-limiting toxicity (leukopenia, stomatitis, and diarrhea) occurred in both DP cohorts. We recommend that for this monthly treatment schedule, 500 mg/m2 PALA and 500 mg/m2 5-FU, with or without 50 mg/m2 DP, be used in subsequent Phase II trials.
Adult↗
Cloning and sequencing of a gene encoding pyruvate kinase from Schizosaccharomyces pombe; implications for quaternary structure and regulation of the enzyme.
A cDNA encoding pyruvate kinase from Schizosaccharomyces pombe has been isolated from a lambda ZAPII library. This cDNA was sequenced and found to contain an open reading frame of 1524 nucleotides, giving a predicted protein subunit M, of 55470. The sequence shows a high degree of identity with other pyruvate kinase sequences, with residues implicated in the binding of substrate and metal ion co-factors conserved. However, there are significant differences in the putative subunit interface and effector binding regions which may account for the unusual quaternary structure and regulatory properties of the S. pombe enzyme.
Amino Acid Sequence↗
The tolerability and pharmacokinetics of N-butyl-deoxynojirimycin in patients with advanced HIV disease (ACTG 100). The AIDS Clinical Trials Group (ACTG) of the National Institute of Allergy and Infectious Diseases.
Twenty-nine patients were enrolled in a phase I dose-escalating tolerance trial of N-butyl-deoxynojirimycin, an alpha-glucosidase I inhibitor that inhibits human immunodeficiency virus (HIV)-1 replication by altering glycosylation of gp120. Dosing was begun at 8 mg/kg/day and subsequent doses were 16, 32, 48, and 64 mg/kg/day. The maximum tolerated dose was not achieved because of slow accrual and because the study was stopped after the finding of cataracts in initial long-range rat toxicology studies. These cataracts were later shown to be transient and not found in other animals. The most common side effects were gastrointestinal, with diarrhea and flatulence occurring in most subjects, which seemed to partially improve on a modified diet that excluded complex carbohydrates. Grade III elevations in liver function tests were seen in two patients. Grade III leukopenia and neutropenia were seen in seven patients, but were only severe enough in two to require discontinuation. No significant trends in CD4 cell counts or HIV-1 p24 levels were noted.
1-Deoxynojirimycin↗
Screening for diabetic retinopathy. GPs in south London have direct access to screening service.
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Diabetic Retinopathy↗
Increased retinoic acid receptor gamma expression suppresses the malignant phenotype and alters the differentiation potential of human neuroblastoma cells.
Human neuroblastoma (NB) tumor cell lines treated in vitro with the retinoid, all-trans-retinoic acid (aRA), form neurites and undergo growth arrest. Retinoids exert their diverse morphologic effects through a signalling pathway which involves the nuclear retinoid receptors. Defective retinoic acid receptor (RAR) function contributes to the malignant phenotype of several human and experimental tumors. Considerable evidence from gene disruption studies now suggests that one of the RARs, RAR gamma, may directly mediate some retinoid effects on embryonic and malignant cells. We, firstly, examined primary NB tumor tissue for a correlation between endogenous RAR gamma expression and clinical stage of the tumor and secondly, the effects of exogenous over-expression of the RAR gamma gene on a human NB tumor cell line. RAR gamma mRNA expression in 32 primary NB tumor tissue samples were significantly higher in clinically localised tumors compared with advanced or disseminated tumors. The human NB tumor cell line, BE(2)-C, was stably transfected with a mammalian expression vector (pREP4) over-expressing the human RAR gamma cDNA. Two selected clones over-expressing RAR gamma (BE/G1 and 2) exhibited a reduced growth rate compared to control cells. Tumorigenicity was inhibited for BE/G1 cells and there was a delayed onset to tumor formation for BE/G2 cells. aRA caused growth inhibition but not neuritic differentiation of the BE/G clones, while 9-cis-retinoic acid caused both growth arrest and neuritic differentiation. Taken together these results suggest that reduced endogenous RAR gamma expression may contribute to the malignant phenotype of human NB. In NB cells the retinoid signalling pathway for neuritic differentiation may be distinct from that causing growth inhibition.
Adrenal Glands↗
A single ataxia telangiectasia gene with a product similar to PI-3 kinase.
A gene, ATM, that is mutated in the autosomal recessive disorder ataxia telangiectasia (AT) was identified by positional cloning on chromosome 11q22-23. AT is characterized by cerebellar degeneration, immunodeficiency, chromosomal instability, cancer predisposition, radiation sensitivity, and cell cycle abnormalities. The disease is genetically heterogeneous, with four complementation groups that have been suspected to represent different genes. ATM, which has a transcript of 12 kilobases, was found to be mutated in AT patients from all complementation groups, indicating that it is probably the sole gene responsible for this disorder. A partial ATM complementary DNA clone of 5.9 kilobases encoded a putative protein that is similar to several yeast and mammalian phosphatidylinositol-3' kinases that are involved in mitogenic signal transduction, meiotic recombination, and cell cycle control. The discovery of ATM should enhance understanding of AT and related syndromes and may allow the identification of AT heterozygotes, who are at increased risk of cancer.
Amino Acid Sequence↗
Community study of role of viral infections in exacerbations of asthma in 9-11 year old children.
OBJECTIVE: To study the association between upper and lower respiratory viral infections and acute exacerbations of asthma in schoolchildren in the community. DESIGN: Community based 13 month longitudinal study using diary card respiratory symptom and peak expiratory flow monitoring to allow early sampling for viruses. SUBJECTS: 108 Children aged 9-11 years who had reported wheeze or cough, or both, in a questionnaire. SETTING: Southampton and surrounding community. MAIN OUTCOME MEASURES: Upper and lower respiratory viral infections detected by polymerase chain reaction or conventional methods, reported exacerbations of asthma, computer identified episodes of respiratory tract symptoms or peak flow reductions. RESULTS: Viruses were detected in 80% of reported episodes of reduced peak expiratory flow, 80% of reported episodes of wheeze, and in 85% of reported episodes of upper respiratory symptoms, cough, wheeze, and a fall in peak expiratory flow. The median duration of reported falls in peak expiratory flow was 14 days, and the median maximum fall in peak expiratory flow was 81 l/min. The most commonly identified virus type was rhinovirus. CONCLUSIONS: This study supports the hypothesis that upper respiratory viral infections are associated with 80-85% of asthma exacerbations in school age children.
Asthma↗
Levels of p53 antigen in the plasma of patients with adenomas and carcinomas of the colon.
Plasma levels of p53 protein were examined by an enzyme linked immunosorbent assay in 184 patients enrolled in a colonoscopy study. The mean levels among 47 individuals with normal colonoscopic examinations and no prior history of colonic neoplasia (0.12 ng/ml) and among 61 individuals with normal colonoscopic examinations and a prior history of colonic neoplasia (0.09 ng/ml) were similar. However, the mean levels among 54 individuals with newly diagnosed colonic adenomas (0.44 ng/ml) and 22 individuals with newly diagnosed colonic carcinomas (0.55 ng/ml) were statistically significantly elevated compared to the normal controls (P < 0.02). Among these tumor patients, the plasma levels tended to increase with increasing adenoma size and with increasing carcinoma stage, although these trends were not statistically significant. Defining a significant positive plasma level as any value greater than ten times background, the percentage of positive samples increased from 4% in the controls to 20% in the adenoma cases to 32% in the carcinoma cases. These results demonstrate that plasma p53 protein levels are elevated in a subgroup of individuals with colonic neoplasia.
Adenoma↗
Familial inverted duplication 7p.
A 10-month-old female with developmental delay and failure to thrive was referred for genetic evaluation as part of an adoption assessment. Physical exam showed a mildly beaked nose and clinodactyly, but otherwise nothing remarkable. Chromosome analysis showed an inverted duplication of the p12.2-->p13 portion of chromosome 7[(46,XX, dup(7)(p13p12.2)]. The proposita's older brother, mother, and grandmother were cognitively delayed and had the same chromosome 7 duplication. A review of the literature showed no other cases involving this exact duplication.
Chromosome Inversion↗
Cloning and sequence analysis of an ERG24 homolog from Schizosaccharomyces pombe.
The Schizosaccharomyces pombe (Sp) erg24 cDNA, encoding C-14 sterol reductase (erg24p), has been cloned and sequenced. The nucleotide sequence of Sp erg24 contains an open reading frame encoding a 424-amino-acid protein. The deduced aa sequence of Sp erg24 shows significant homology with Saccharomyces cerevisiae (Sc) Erg24p, as well as with other members of a larger gene family that includes yeast C-24(28) sterol reductase (Erg4p) and a vertebrate inner nuclear membrane protein, the lamin B receptor (LBR).
Amino Acid Sequence↗
Interleukin-10 administration decreases survival in murine recipients of major histocompatibility complex disparate donor bone marrow grafts.
Studies in mice and humans have indicated that the predominance of interleukin-4 (IL-4)- and IL-10-producing T-helper type 2 (Th2) cells may serve to downregulate acute graft-versus-host disease (GVHD) reactions, whereas IL-2-producing Th1 cells have been implicated in facilitating acute GVHD. We explored the possibility that the in vivo infusion of IL-10 would inhibit acute GVHD induced by fully allogeneic donor grafts. Unexpectedly, IL-10 infusions resulted in a dose-dependent increase in GVHD-induced mortality. The acceleration of lethal GVHD by IL-10 occurred in irradiated recipients of T-cell-depleted bone marrow (BM) plus 5, 15, or 25 x 10(6) splenocytes but did not influence the post-BM transplantation (post-BMT) survival rate of recipients of BM without splenocytes, suggesting that the IL-10 effects were not due to toxicity. Antimurine IL-10-neutralizing monoclonal antibody injections, administered to diminish endogenous IL-10, reduced GVHD-associated mortality and improved the clinical appearance of the recipients. For BM graft rejection studies, IL-10 was infused into sublethally irradiated recipients of anti-Thy 1.2 + C' T-cell-depleted, fully allogeneic BM grafts. In a short-term (day 7) in vivo assay, IL-10 infusions significantly inhibited allogeneic (but not syngeneic) BM proliferation in vivo, indicative of increased graft rejection. In long-term chimerism experiments, IL-10 infusions caused a significant increase in early post-BMT mortality caused by a profound anemia typically associated with graft rejection and aplasia. A slightly higher irradiation dose (650 cGy v 600 cGy) eliminated the anemia but did not reverse the graft rejection process associated with IL-10 administration. We conclude that the in vivo infusion of exogenous IL-10 in recipients of fully allogeneic donor grafts results in accelerated GVHD and graft rejection in the strain combinations tested to date.
Animals↗
The relationship of the skin conductance and finger pulse amplitude components of the orienting response to season of birth in schizophrenia and depression.
Schizophrenia is said to be associated with a modest excess of winter births. We examined relations of season of birth (SOB) to the skin conductance response (SCR) and finger pulse amplitude response (FPAR) components of the orienting response (OR) in 83 schizophrenic patients, 59 depressed patients, and 81 normal controls. SCR-OR nonresponding was more prevalent among depressed patients regardless of SOB, whereas only winter-born schizophrenics showed significantly more frequent electrodermal nonresponding than controls. However, this latter relation was not confirmed with log linear analysis. No other relations of SOB to SCR-OR or FPAR-OR nonresponding were significant. Our data do not support the view that nonresponding in the SCR or FPAR components of the OR is associated with winter birth either in schizophrenia or depression.
Adolescent↗
Deletion detection in the dystrophin gene by multiplex gap ligase chain reaction and immunochromatographic strip technology.
The purpose of this study is to demonstrate the value of a multiplex amplification and readout system. The validation was done using as a model system the detection of deletions in nine possible dystrophin exons: 4, 8, 12, 17, 19, 44, 45, 48, and 51. The amplification system was gap ligase chain reaction, adapted to amplify selected regions of multiple exons simultaneously. The amplified products were read out with an immunochromatographic methodology, adapted from that used in the Abbott product line commercialized under the name Test Pack Plus. In each amplification, the beta-globin gene was incorporated and served as a procedural control. The complete process takes < 3 hr from DNA sample to result. The procedure is therefore rapid and simple, as well as being potentially very cost effective. The combination of these two technologies is shown to be a useful tool for the determination of deletions in the nine exons of the dystrophin gene. The results of a 100-patient sample study showed concordance with cDNA and PCR in current use. Equivalent performance at two sites was shown.
Base Sequence↗