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Biomedical subjects

A Bailey

Publications and source records attributed to A Bailey.

At least 91 records · Page 5Linked to original sources
PubMed1994

Cell type specific regulation of expression from the Ad40 E1b promoter in recombinant Ad5/Ad40 viruses.

The defective growth of the enteric adenovirus type 40 (Ad40) in HeLa cells can only be overcome by supplying an E1B 55K function in trans, and it has been demonstrated that expression of Ad40 E1B mRNA is poor in these cells (V. Mautner et al., 1990, Virology 171, 618-622). To study the control of expression from the Ad40 E1B region in greater detail, two Ad5/Ad40 recombinant viruses were constructed containing the Ad40 E1B region in place of the equivalent Ad5 region, under either the control of the Ad40 E1B promoter (sub40P) or that of Ad5 (sub5P). For both recombinants, E1B mRNAs similar to those seen in a wt Ad40 infection were detected, with late splicing (post DNA replication) occurring predominantly via the Ad40 14S splice acceptor. However, the level of expression from the substituted E1B region differs markedly between the two recombinants, and synthesis of E1B mRNA and proteins was impaired in sub40P-infected cells. In 293 and KB16 cells, expression from the Ad40 E1B promoter was reduced 10- to 20-fold compared with the Ad5 promoter. In HeLa cells, the reduction was 80-fold and mirrored the poor expression of E1B mRNA in Ad40-infected HeLa cells. Furthermore, in contrast to the 293 cells, early expression of E1B proteins could not be detected in sub40P- or wt Ad40-infected HeLa cells. The experiments demonstrate the low activity of the Ad40 E1B promoter and that this promoter is regulated in a cell type specific manner.

Adenovirus E1B Proteins↗
PubMed1994

Systematic underestimation of association between serum cholesterol concentration and ischaemic heart disease in observational studies: data from the BUPA study.

OBJECTIVE: To estimate the size of the association between serum concentration of low density lipoprotein cholesterol and mortality from ischaemic heart disease. DESIGN: Prospective study of total serum cholesterol concentration and mortality from ischaemic heart disease in 21,515 men (538 deaths) and study of total cholesterol concentration measured on two occasions an average of three years apart in 5696 men in whom low density lipoprotein cholesterol concentration was also measured on the second occasion. SUBJECTS: Men who attended the medical centre of the British United Provident Association (BUPA) in London between 1975 and 1982. MAIN OUTCOME MEASURE: The difference in mortality from ischaemic heart disease for a 0.6 mmol/l difference in concentration of low density lipoprotein cholesterol after adjustment for, firstly, regression dilution bias, which arises from the random fluctuation of serum cholesterol concentration in people over time, and, secondly, the surrogate dilution effect, which arises because differences in total cholesterol concentration between people reflect smaller differences in low density lipoprotein cholesterol concentration. RESULTS: The observed difference in mortality from ischaemic heart disease associated with a difference of 0.6 mmol/l in total serum cholesterol concentration was 17% but increased to 24% after correction for the regression dilution bias and to 27% (95% confidence interval 21% to 33%) after adjustment for both sources of underestimation, which provides an estimate of the difference in mortality for a true difference of 0.6 mmol/l in low density lipoprotein cholesterol concentration. The association was greater at younger ages. The estimated decrease in mortality from all causes was 6% before and 10% (1% to 17%) after adjustment for the two sources of underestimation. There was no excess mortality from any cause associated with low cholesterol concentration. CONCLUSIONS: The association between serum cholesterol concentration and ischaemic heart disease is materially stronger than directly inferred from prospective studies. This has important implications for the health benefit of achieving low cholesterol concentrations.

Adult↗
PubMed1994

Apolipoproteins and ischaemic heart disease: implications for screening.

Apolipoproteins and lipids are established risk factors of ischaemic heart disease (IHD) but their efficacy as screening tests is not known. We therefore examined the mortality from IHD and serum concentrations of lipids and apolipoproteins in a prospective study of 21,520 men aged 35-64 years. Serum apo B was the apolipoprotein most strongly associated with IHD risk; a decrease in apo B of 10% was associated with 22% lower risk of IHD. However, measurement of apo B alone detected only 17% of all IHD deaths at the cost of a 5% false-positive rate. Combining apo B with apo AI and apo (a) increased the detection rate to 19%. With systolic blood pressure, smoking, and family history of IHD the detection rate increased to 28%. We conclude that screening for IHD by measuring apo B alone or with apo AI and apo (a) is too poor to discriminate between recommending drug therapy or lifestyle change for some and not others. It is not advisable to screen for IHD by measuring any combination of cholesterol, apo B, apo AI, apo (a) and the other risk factors. The primary aim in prevention of ischaemic heart disease should be to lower the risk factors in the population.

Adult↗
PubMed1994

Phylogenetic relationships among adenovirus serotypes.

Phylogenetic comparisons of adenovirus DNA sequences, including the recently completed genomic sequences of Ad40 and Ad12, have been performed in order to investigate the evolutionary relationships among the various serotypes. Phylogenetic trees were constructed from sequence data for the ITR, E1a, E1b, E2a, E3b, major late promoter, hexon, protease, and fiber regions of the genome using programs contained in the PHYLIP (Phylogeny Inference) package. In general the branching pattern of the human serotypes at each locus correlated well with the classification of the human serotypes into six subgenera (A-F). However, a close evolutionary relationship was inferred between Ad4 (the only member of subgenus E) and the subgenus B viruses Ad3, Ad7, and Ad35, and challenges the placement of Ad4 in a subgenus of its own. In addition, the human viruses of subgenera A (Ad12, Ad18, and Ad31) and F (Ad40 and Ad41), as well as the simian adenoviruses SAV16 (SA7) and SAV8 (SV30), all of which are associated with infections of the gastrointestinal tract, were found to cluster together. The results suggest that these viruses have followed a course of evolution distinct from those of the other subgenera which largely infect the respiratory tract. Analysis of genetic variability between the four complete genomic sequences (Ad2, Ad5, Ad12, and Ad40) identified three regions subject to more rapid change, corresponding to the hexon-, fiber- and E3a-coding regions. Genetic variability at the E3a locus is particularly striking and may relate to the pathogenicity of the various serotypes.

Adenoviridae↗
PubMed1994

Statistical methods for clinical trials.

The object of this paper is to describe the essential features for the design and conduct of clinical trials. We include aspects of patient eligibility, random allocation to treatment including the principle of uncertainty, assessment of endpoints including those observed at different time points for each patient and trial size. Indications of appropriate methods of analysis are given, and the intention to treat principle is discussed. Some pointers to difficulties associated with data collection and management are included.

Clinical Trials as Topic↗
PubMed1994

Neuroleptic treatment of HIV-associated psychosis. HNRC group.

The aim of this rater-blinded randomized study was to evaluate the efficacy and side effects of haloperidol and thioridazine in the treatment of new-onset psychosis in HIV-positive individuals. Participants were 13 men who had no history of psychosis prior to infection with HIV, and whose psychosis was not attributable to delirium or to non-HIV-related organic factors. Participants were evaluated at baseline after at least one month without neuroleptic treatment and then weekly for six weeks of the experimental treatment using several rating scales. The mean daily dose in chlorpromazine equivalents was 124 mg. Both neuroleptics produced modest but significant reduction in overall level of psychosis and in positive symptoms, but not in negative symptoms. All the haloperidol-treated patients developed extrapyramidal side effects and required treatment with anticholinergic medication, whereas three of the five thioridazine-treated patients had noticeable side effects. We make recommendations for the treatment of HIV-associated psychosis with neuroleptics.

AIDS Dementia Complex↗
PubMed1994

Phase 2 study of prolonged administration of oral etoposide in combination with weekly cisplatin in advanced non-small cell lung cancer.

We administered chemotherapy consisting of a 21-day course of oral etoposide (50 mg/m2/day) and a 3-weekly dose of cisplatin (30-33 mg/m2/week) to 23 chemotherapy-naive patients with advanced non-small cell lung cancer (NSCLC). Six patients achieved a partial response (28.6%; 95% confidence interval, 11.3-52.2%), with a median response duration of 4 months and a median overall survival of 5 months. Besides alopecia, myelosuppression was the most significant drug-related toxicity. Observed side effects in 59 cycles of chemotherapy were granulocytopenia (< 1,000/microliters) in 23% of the treatment cycles, thrombocytopenia (< 75,000/microliters) in 25%, anemia (< 10 g/dl) in 64%, and nausea-vomiting (grades > or = 2) in 8%. Mild renal insufficiency (serum creatinine, 1.5-2.1 mg/dl) occurred in six patients. Three toxic deaths were observed during or immediately after cycle 1, and were related to granulocytopenia. We conclude that this regimen has modest activity in advanced NSCLC; but this therapeutic approach does not appear to produce a major improvement in the treatment of this disease. Thus, in advanced NSCLC, continued evaluation of new chemotherapeutic agents should remain the major emphasis of investigational therapy.

Administration, Oral↗
PubMed1994

Autism and known medical conditions: myth and substance.

There is general agreement that autism has an organic basis but there is less agreement on the frequency with which it is associated with known medical conditions. The evidence in the literature on the latter point is reviewed and it is concluded that the rate of known medical conditions in autism is probably about 10%; however the rate appears to be higher in cases of autism associated with profound mental retardation and in cases of atypical autism.

Autistic Disorder↗
PubMed1994

A case-control family history study of autism.

Family history data on 99 autistic and 36 Down's syndrome probands are reported. They confirmed a raised familial loading for both autism and more broadly defined pervasive developmental disorders in siblings (2.9% and 2.9%, respectively, vs 0% in the Down's group) and also evidence for the familial aggregation of a lesser variant of autism, comprising more subtle communication/social impairments or stereotypic behaviours, but not mental retardation alone. Between 12.4 and 20.4% of the autism siblings and 1.6% and 3.2% of the Down's siblings exhibited this lesser variant, depending on the stringency of its definition. Amongst autistic probands with speech, various features of their disorder (increased number of autistic symptoms; reduced verbal and performance ability) as well as a history of obstetric complications, indexed an elevation in familial loading. No such association was seen in the probands without speech, even though familial loading for the lesser variant in this subgroup, was significantly higher than in the Down's controls. The findings suggest that the autism phenotype extends beyond autism as traditionally diagnosed; that aetiology involves several genes; that autism is genetically heterogeneous; and that obstetric abnormalities in autistic subjects may derive from abnormality in the foetus.

Adolescent↗
PubMed1994

Early course of new-onset tardive dyskinesia in older patients.

The risk of neuroleptic-induced tardive dyskinesia (TD) in older patients is known to be high, yet the course of TD in older patients has not been systematically studied. We followed 69 middle-aged and elderly outpatients newly diagnosed with TD in a naturalistic, longitudinal, prospective fashion. Standardized assessment instruments were administered to measure psychopathology, cognitive impairment, and abnormal movements. We observed a highly fluctuating early course of TD. Although the cumulative proportion of patients whose TD partially remitted was quite high (56% at 3 months, and 80% at 6 months), the cumulative proportion of patients whose TD relapsed (post-remission) was also high (33% at 3 months and 54% at 6 months). These findings may have clinical as well as theoretical implications for TD in older subjects.

Aged↗
PubMed1993

CACC box and enhancer response of the human embryonic epsilon globin promoter.

The functional interaction between the human epsilon globin promoter and an erythroid-specific transcription enhancer, 5' HS-2, has been analyzed by transient expression assay. While stepwise deletion of DNA sequences between -852 and -122 had only small effects, removal of the CACC box at position -111 greatly decreased epsilon-globin promoter activity, as well as its response to the enhancer function of 5' HS-2 in erythroid cells. Our data demonstrated that the three ubiquitous promoter elements, the CACC, CCAAT, and TATA boxes, of the epsilon-globin-encoding gene together form a minimal promoter that would interact efficiently with 5' HS-2, and that at least the CACC box is an essential functional component of this enhancer-promoter interaction.

Base Sequence↗
PubMed1993

Enteric adenovirus type 40: expression of E1B proteins in vitro and in vivo.

The genes encoding the enteric adenovirus type 40 E1B proteins designated 19K, 55K, and 15K (55K related) have been cloned into the pET3a expression vector and synthesized by in vitro transcription and translation and by in vivo expression after induction in bacteria. The 19K product expressed in bacteria is recognized by anti-peptide sera specific for the C-terminal region of the open reading frame and has the same M(r) as 19K protein immunoprecipitated from virus-infected cells. The 55K protein synthesized in bacteria is insoluble except under extreme denaturing conditions, but after in vitro transcription followed by translation, a polypeptide of the predicted size is obtained. The 15K protein, equivalent to the first 73 and last 29 of the 476-residue 55K protein with an internal deletion of 374 amino acids, is expressed to a high level in bacteria in a soluble form and interacts weakly but specifically with N- and C-terminal anti-peptide sera. The bacterially expressed 15K protein was used to raise antibodies in rabbits. This serum precipitates the 55K protein expressed by in vitro translation, but only the 15K product can be immunoprecipitated from virus-infected cells. The same antiserum, however, detects the 55K protein in infected cells by Western blotting, at a time broadly coinciding with the onset of DNA replication. This is the first identification of Ad40 55K protein in infected cells and confirms that the Ad40 22S mRNA can be utilized in vivo. The question of whether this protein is functional can now be addressed.

Adenovirus E1B Proteins↗
PubMed1993

Differentiation of constrictive pericarditis from restrictive cardiomyopathy by Doppler transesophageal echocardiographic measurements of respiratory variations in pulmonary venous flow.

OBJECTIVES: The purpose of this study was to test the utility of measuring respiratory variation in pulmonary venous flow by transesophageal echocardiography. BACKGROUND: Respiratory variation of atrioventricular and central venous flow velocities by Doppler echocardiography has been used to differentiate constrictive pericarditis from restrictive cardiomyopathy. METHODS: We performed pulsed wave Doppler transesophageal echocardiography of the left or right pulmonary veins in 31 patients with diastolic dysfunction. Fourteen patients had constrictive pericarditis, and 17 had restrictive cardiomyopathy. We measured the pulmonary venous peak systolic and diastolic flow velocities and the systolic/diastolic flow ratio with transesophageal echocardiography during expiration and inspiration. The percent change in Doppler flow velocity from expiration to inspiration (%E) was calculated. RESULTS: Pulmonary venous peak systolic flow in both inspiration and expiration was greater in constrictive pericarditis than in restrictive cardiomyopathy. The %E for peak systolic flow tended to be higher in constrictive pericarditis (19% vs. 10%, p = 0.09). In contrast, pulmonary venous peak diastolic flow during inspiration was lower in constrictive pericarditis than in restrictive cardiomyopathy. The %E for peak diastolic flow was larger in constrictive pericarditis (29% vs. 16%, p = 0.008). The pulmonary venous systolic/diastolic flow ratio was greater in constrictive pericarditis in both inspiration and expiration. The combination of pulmonary venous systolic/diastolic flow ratio > or = 0.65 in inspiration and a %E for peak diastolic flow > or = 40% correctly classified 86% of patients with constrictive pericarditis. CONCLUSIONS: The relatively larger pulmonary venous systolic/diastolic flow ratio and greater respiratory variation in pulmonary venous systolic, and especially diastolic, flow velocities by transesophageal echocardiography can be useful signs in distinguishing constrictive pericarditis from restrictive cardiomyopathy.

Blood Flow Velocity↗
PubMed1993

XASH1, a Xenopus homolog of achaete-scute: a proneural gene in anterior regions of the vertebrate CNS.

The pro-neural achaete-scute complex (ASC) of Drosophila encodes four homologous proteins, each containing a basic helix-loop-helix (bHLH) domain, characteristic of a large family of transcription factors. We have isolated XASH1, a Xenopus homolog of achaete-scute. The XASH1 protein is very similar to the ASC proteins of Drosophila and the rat homolog, MASH1. XASH1 is expressed in the embryonic anterior central nervous system in a dynamic sequence, first in the midbrain, then in the forebrain, and then in the eye and hindbrain. In the larva, XASH1 expression correlates with regions of continued neurogenesis in the CNS, revealing the pattern of rhombomeres in the hindbrain, and other proliferative zones in the eye and midbrain. As a heterodimer with the bHLH protein E12, XASH1 binds specifically to an enhancer sequence derived from the promoter of the proneural achaete gene of Drosophila. This binding is inhibited by the extramacrochaete protein, a negative regulator of ASC gene function and neurogenesis in Drosophila. The combined evidence described in this paper strongly suggests that XASH1 plays a role in Xenopus neurogenesis similar to that played by the ASC genes in Drosophila.

Amino Acid Sequence↗
PubMed1993

Vitamin C intake and plasma ascorbic acid concentration in adolescents.

The relationship between vitamin C intake and status was investigated in a group of adolescents (13-14 years old). Dietary intakes were assessed using a 7 d weighted dietary record method, coupled with the collection of duplicate diets. Vitamin C intakes calculated using food composition tables were compared with values obtained by direct analysis of duplicate diets. Vitamin C status was judged via measurement of plasma ascorbic acid (AA) concentration in blood samples taken after a 12-15 h fast. The relationship between calculated and analysed vitamin C intake and plasma AA concentration was examined. Average daily calculated vitamin C intakes, for the group (n 54) as a whole over a 7 d period, gave a good estimate of intake, as judged by prompt analysis of duplicate diets. However, analysed v. calculated intakes were significantly different for approximately one-third of subjects when data were examined on an individual basis. Large discrepancies between analysed and calculated values could not be accounted for on a food group basis. In all but two individuals, calculated vitamin C intake was in excess of the new reference nutrient intake (RNI, part of the new daily reference values (Department of Health and Social Security, 1991)) of 40 mg and all plasma AA concentrations were well above those used to indicate even a moderate risk of deficiency. A relationship between vitamin C intake and plasma AA was observed for both males (n 19) and females (n 35). However, the relationship was much stronger for males who showed a wider range of both intake and plasma AA values.

Adolescent↗
PubMed1993

Prevalence of the fragile X anomaly amongst autistic twins and singletons.

Early screening studies of autistic individuals suggested that up to one-quarter of cases were associated with the Fragile X anomaly. Recent studies find that the usual behavioural phenotype of the Fragile X anomaly is distinct from autism as usually defined, and that a variety of methodological factors contribute to the variability of the prevalence estimates. We report the prevalence of the Fragile X anomaly, using strict cytogenetic criteria, in a large sample of autistic individuals whose diagnosis was confirmed using a standardised diagnostic instrument. The anomaly was detected in 1.6% of tested autistic individuals from a combined sample of: autistic twins; clinic attenders; and, individuals from families multiplex for autism or related cognitive phenotypes. The anomaly was not detected in greater than 2.5% of any of the constituent samples and accounted for only a small proportion of the genetic influences amongst concordant twins and multiplex families. The anomaly was detected in 5% of the 40 tested autistic females, confirming reports that the prevalence of the anomaly is similar amongst autistic individuals of both sexes.

Adult↗