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Biomedical subjects

A Wilson

Publications and source records attributed to A Wilson.

At least 145 records · Page 8Linked to original sources
PubMed1998

Importance of environmental distractors in the effects of nicotine on short-term memory.

This study examined the role of environmental context in mediating the effects of nicotine on short-term memory performance (i.e., working memory). Male and female smokers (n = 12, overnight tobacco abstinent) and nonsmokers (n = 11) were administered nicotine (20 ug/kg) and a placebo (0 ug/kg) by means of a measured-dose nasal spray procedure on separate days. Participants were tested on a variant of S. Sternberg's (1966) memory search task. Half of the memory task sets involved the presentation of an auditory environmental distraction. Improvements in short-term memory performance with nicotine were primarily seen in smokers and in the presence of the distracting stimuli. These results suggest that environmental conditions, such as the presence of a distracting stimulus, may play an important role in mediating the effects of nicotine.

Adult↗
PubMed1998

Influence of 2-(4-aminophenyl)benzothiazoles on growth of human ovarian carcinoma cells in vitro and in vivo.

2-(4-Aminophenyl)benzothiazole molecules substituted in the 3 position of the phenyl ring with a halogen atom or methyl moiety comprise a group of compounds that potently inhibit specific human ovarian carcinoma cell lines. GI50 values fall within the nM range. Inhibition is highly selective -- whereas the GI50 value in IGROV1 cells consistently lies at < 10 nM, SK-OV-3 presents GI50 values > 10 microM. Biphasic dose-response relationships were observed in sensitive cell lines after 48-h drug exposure. COMPARE analyses revealed the very similar profiles of anti-tumour activity of 3-substituted benzothiazoles and 5-(4-dimethylaminophenylazo)quinoline, with Pearson correlation coefficients > 0.65. Anti-tumour activity extended to preliminary in vivo tests. The growth of OVCAR-3 cells in polyvinylidene fluoride (PVDF) hollow fibres implanted in the peritoneal cavity of mice was inhibited by more than 50% after intraperitoneal (i.p.) administration of 2-(4-amino-3-methylphenyl)benzothiazole (10 mg kg(-1)), 2-(4-amino-3-chlorophenyl)benzothiazole (100 mg kg(-1)) or 2-(4-amino-3-bromophenyl)benzothiazole (150 mg kg(-1)). The growth of OVCAR-3 tumours in subcutaneously (s.c.) implanted hollow fibres was retarded by more than 50% after treatment with 2-(4-amino-3-methylphenyl)benzothiazole (6.7 and 10 mg kg(-1)). In addition, the growth of s.c. OVCAR-3 xenografts was delayed after exposure to DF 203. However, the relationship between drug concentration and growth inhibition was inverse.

Animals↗
PubMed1998

Controlled trial of hypnotherapy for weight loss in patients with obstructive sleep apnoea.

OBJECTIVE: To assess if hypnotherapy assists attempts at weight loss. DESIGN: Randomised, controlled, parallel study of two forms of hypnotherapy (directed at stress reduction or energy intake reduction), vs dietary advice alone in 60 obese patients with obstructive sleep apnoea on nasal continuous positive airway pressure treatment. SETTING: National Health Service hospital in the UK. MEASURES: Weight lost at 1, 3, 6, 9, 12, 15 and 18 months after dietary advice and hypnotherapy, as a percentage of original body weight. RESULTS: All three groups lost 2-3% of their body weight at three months. At 18 months only the hypnotherapy group (with stress reduction) still showed a significant (P < 0.02), but small (3.8 kg), mean weight loss compared to baseline. Analysed over the whole time period the hypnotherapy group with stress reduction achieved significantly more weight loss than the other two treatment arms (P < 0.003), which were not significantly different from each other. CONCLUSIONS: This controlled trial on the use of hypnotherapy, as an adjunct to dietary advice in producing weight loss, has produced a statistically significant result in favour of hypnotherapy. However, the benefits were small and clinically insignificant. More intensive hypnotherapy might of course have been more successful, and perhaps the results of the trial are sufficiently encouraging to pursue this approach further.

Cohort Studies↗
PubMed1998

Fine mapping of the diabetes-susceptibility locus, IDDM4, on chromosome 11q13.

Genomewide linkage studies of type 1 diabetes (or insulin-dependent diabetes mellitus [IDDM]) indicate that several unlinked susceptibility loci can explain the clustering of the disease in families. One such locus has been mapped to chromosome 11q13 (IDDM4). In the present report we have analyzed 707 affected sib pairs, obtaining a peak multipoint maximum LOD score (MLS) of 2.7 (lambda(s)=1.09) with linkage (MLS>=0.7) extending over a 15-cM region. The problem is, therefore, to fine map the locus to permit structural analysis of positional candidate genes. In a two-stage approach, we first scanned the 15-cM linked region for increased or decreased transmission, from heterozygous parents to affected siblings in 340 families, of the three most common alleles of each of 12 microsatellite loci. One of the 36 alleles showed decreased transmission (50% expected, 45.1% observed [P=.02, corrected P=.72]) at marker D11S1917. Analysis of an additional 1,702 families provided further support for negative transmission (48%) of D11S1917 allele 3 to affected offspring and positive transmission (55%) to unaffected siblings (test of heterogeneity P=3x10-4, corrected P=. 01]). A second polymorphic marker, H0570polyA, was isolated from a cosmid clone containing D11S1917, and genotyping of 2,042 families revealed strong linkage disequilibrium between the two markers (15 kb apart), with a specific haplotype, D11S1917*03-H0570polyA*02, showing decreased transmission (46.4%) to affected offspring and increased transmission (56.6%) to unaffected siblings (test of heterogeneity P=1.5x10-6, corrected P=4.3x10-4). These results not only provide sufficient justification for analysis of the gene content of the D11S1917 region for positional candidates but also show that, in the mapping of genes for common multifactorial diseases, analysis of both affected and unaffected siblings is of value and that both predisposing and nonpredisposing alleles should be anticipated.

Chromosome Mapping↗
PubMed1998

Functionally null mutations in patients with the cblG-variant form of methionine synthase deficiency.

Methionine synthase (MS) catalyses the methylation of homocysteine to methionine and requires the vitamin B12 derivative, methylcobalamin, as cofactor. We and others have recently cloned cDNAs for MS and described mutations associated with the cblG complementation group that correspond to MS deficiency. A subset of cblG, known as "cblG variant," shows no detectable MS activity and failure of [57Co]CN cobalamin to incorporate into MS in patient fibroblasts. We report the mutations responsible for three cblG-variant patients, two of them siblings, who presented with neonatal seizures, severe developmental delay, and elevated plasma homocysteine. Cell lines from all three patients were negative by northern blotting, though trace MS mRNA could be detected by means of phosphorimage analysis. Reverse transcriptase-PCR, SSCP, and nucleotide sequence analysis revealed four mutations. All were functionally null, creating either a frameshift with a downstream stop codon or an insert containing an internal stop codon. Of the two mutations found in the siblings, one of them, intervening sequence (IVS)-166A-->G, generates a cryptic donor splice site at position -166 of an intron beginning after Leu113, resulting in a 165-bp insertion of intronic sequence at junction 339/340. The second is a 2-bp deletion, 2112delTC. Mutations in the third patient include a G-->A substitution, well within the intron after Lys203, which results in intronic inserts of 128 or 78 bp in the mRNA. The second mutation is a 1-bp insertion, 3378insA. We conclude that the absence of MS protein in these cblG variants is due to mutations causing premature translation termination and consequent mRNA instability.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed1998

Effectiveness of methylphenidate in Native American children with fetal alcohol syndrome and attention deficit/hyperactivity disorder: a controlled pilot study.

This pilot study was designed to assess the short-term effectiveness and side effects of methylphenidate in treating symptoms of attention deficit hyperactivity disorder (ADHD) in Native American children (5 to 12 years old) with documented fetal alcohol syndrome (FAS) or partial fetal alcohol syndrome. Using strict criteria for the diagnosis of FAS and ADHD, a randomized double-blind cross-over study of two placebos and a fixed dose of methylphenidate was completed in 4 Native American children in a residential school. Each treatment condition lasted 5 days, and daily observational outcome measures, the Conners Parent Rating Scale (CPRS-48), and the Conners Teacher Rating Scale (CTRS-39), were employed. Methylphenidate significantly improved scores of the Hyperactivity Index Scale on the CPRS-48 and the CTRS-39 but not the Daydreaming-Attention score on the CTRS-39. Side effects were similar to those traditionally found in other populations. The promising preliminary results suggest that a more definitive study of methylphenidate in Native and non-Native children with FAS and ADHD is warranted.

Adolescent↗
PubMed1998

The role of the T-cell receptor (TCR) in alpha beta/gamma delta lineage commitment: clues from intracellular TCR staining.

T cells belong to two mutually exclusive lineages expressing either alpha beta or gamma delta T-cell receptors (TCR). Although alpha beta and gamma delta cells are known to share a common precursor the role of TCR rearrangement and specificity in the lineage commitment process is controversial. Instructive lineage commitment models endow the alpha beta or gamma delta TCR with a deterministic role in lineage choice, whereas separate lineage models invoke TCR-independent lineage commitment followed by TCR-dependent selection and maturation of alpha beta and gamma delta cells. Here we review the published data pertaining to the role of the TCR in alpha beta/gamma delta lineage commitment and provide some additional information obtained from recent intracellular TCR staining studies. We conclude that a variant of the separate lineage model is best able to accommodate all of the available experimental results.

Animals↗
PubMed1998

Risk factors for stroke and type of stroke in persons with isolated systolic hypertension. Systolic Hypertension in the Elderly Program Cooperative Research Group.

BACKGROUND AND PURPOSE: We sought to determine risk factors for stroke and stroke type in persons with isolated systolic hypertension (ISH). METHODS: We performed proportional hazards analyses of data from the Systolic Hypertension in the Elderly Program, a double-blind, randomized, placebo-controlled trial of 4736 persons aged > or =60 years with ISH (systolic blood pressure, 160 to 219 mm Hg; diastolic blood pressure, <90 mm Hg). One treatment group received chlorthalidone (12.5 to 25 mg/d) with step-up to atenolol (25.0 to 50.0 mg/d) or reserpine (0.05 to 0.10 mg/d), if needed. The other treatment group received matching placebo. The main outcome measures were stroke, stroke or transient ischemic attack [TIA], and stroke types: ischemic (including lacunar, atherosclerotic, and embolic) and hemorrhagic. RESULTS: During an average follow-up of 4.5 years, 384 strokes or TIAs and 262 strokes (including 217 ischemic, 66 lacunar, 26 atherosclerotic, and 25 embolic strokes) were documented. In multivariate analyses, placebo treatment, older age, smoking, history of diabetes, higher systolic blood pressure, lower HDL cholesterol, and ECG abnormality were significantly associated (P<0.05) with increased incidence of stroke or TIA, stroke, or ischemic stroke. Greater lacunar stroke risk was significantly related to placebo treatment, older age, history of diabetes (relative risk [RR] = 3.03; 95% confidence interval [CI], 1.70 to 5.40), and smoking (RR = 3.04; 95% CI, 1.73 to 5.37). Greater atherosclerotic and embolic stroke risk were significantly related to presence of carotid bruit (RR = 5.75; 95% CI, 2.50 to 13.24) and older age (RR = 1.65 per 5 years; 95% CI, 1.25 to 2.18), respectively. CONCLUSIONS: In older persons with ISH, history of diabetes and smoking are important risk factors for lacunar stroke, whereas carotid bruit and age are important risk factors for atherosclerotic and embolic stroke, respectively.

Aged↗
PubMed1998

Substance use, health and social problems of service users at 54 drug treatment agencies. Intake data from the National Treatment Outcome Research Study.

BACKGROUND: The National Treatment Outcome Research Study (NTORS) is the first large-scale, prospective, multi-site treatment outcome study of drug users in the UK. METHOD: Substance use, health and social problems of 1075 service users were assessed at intake to 54 agencies chosen to be representative of the main national drug treatment modalities. RESULTS: Heroin dependence was the most frequently reported problem often with poly-drug and alcohol problems. Most service users injected drugs and a quarter of the injectors shared injecting equipment. Poly-drug use and heavy drinking were more common among service users admitted to residential treatments. High criminality rates were reported. Psychological and physical health problems were common and many service users had prior contact with psychiatric and medical services. CONCLUSIONS: The range and severity of problems adversely affect individual users, their families, and present a challenge to addiction treatment services. These problems create costs for the health care, social service and criminal justice system responses.

Adolescent↗
PubMed1998

Combination therapy for HIV: the effect on inpatient activity, morbidity and mortality of a cohort of patients.

We set out to quantify the changes in HIV-related morbidity and mortality associated with the clinical use of antiretroviral therapy via prospectively collected patient-related events (admissions, bed days, deaths, WHO stage 3 and 4 events and drug costs) on all HIV patients known to the Regional Infectious Disease Unit (RIDU) from 1 January 1987 to 31 December 1996. The introduction of zidovudine monotherapy in 1987 for those with AIDS was associated with a subsequent decline of inpatient activity for 2 years: in 1989 there was a 23% reduction in bed days but only a 6% reduction in admissions. A further dramatic decline of patient-related events in those with AIDS was noted during 1996 following the introduction of combination therapy, a 39% reduction in admissions, 44% reduction in bed days, 54% reduction in stage 4 events, 33% reduction in WHO stage 3 events and 40% reduction in the death rate. Reductions were also observed for patients without AIDS including a 42% reduction in the rate of patients developing AIDS. Similar reductions were noted when the patients were classified by immunological instead of clinical status although data for 1997 suggest an increase in patient-related activity for those with CD4 counts >200 cells/microl possibly as a result of low levels of anti-HIV therapy. The introduction of combination therapy for HIV has to date led to a minimum saving of one inpatient bed per 100 patient years which helped defray the cost of combination therapy. Although we cannot imply causality from an observational study, dramatic reductions in patient-related activity were associated with the introduction of combination therapy into clinical practice. The ultimate extent and duration of this effect cannot as yet be predicted and caution is required since similar reductions were noted with zidovudine therapy which were unfortunately time limited.

Anti-HIV Agents↗
PubMed1998

Military training at civilian trauma centers: the first year's experience with the Regional Trauma Network.

The Regional Trauma Network was launched in 1996 to provide trauma training opportunities for Army surgeons in the Southeast Regional Medical Command. Training directors at eight civilian level I trauma centers agreed to allow military surgeons to function at the fellowship level of responsibility for up to 30 days at a time. In the first year, 7 surgeons participated in rotations at five different centers and 13 surgeons attended nationally recognized trauma symposia. The response from participating civilian and military participants has been overwhelmingly positive as confidence and enthusiasm for treating seriously injured patients are refreshed. Significant lessons were learned in providing good clinical training experiences, administering a regional program, and measuring the costs and benefits of additional readiness training. Although the data collection processes were devised to capture both the actual and the opportunity costs of training at civilian centers, more participants are needed before a conclusive analysis can be made. A joint services effort on a regional basis and support throughout the chain of command are key to strengthening the surgical readiness training program.

Attitude of Health Personnel↗
PubMed1997

Calmodulin-dependent protein kinase IV during T-cell development.

In a primary cell culture system of fetal rat brain, the calmodulin-dependent protein-kinase IV (CaMKIV) could be induced by the thyroid hormone T3 in a time- and concentration-dependent manner, provided the tissue was excised not later than day 15 of gestation (E15) (Krebs et al., J. Biol. Chem. 271, 11055, 1996). We report here that in the fetal thymus CaMKIV could not be detected earlier than day 16 of gestation and that the expression of this enzyme was fully upregulated at day 18. In mouse fetal thymus organ culture (FTOC) of day 14 embryonic thymus, CaMKIV could not be detected, even after several days of culture if a minimal culture medium lacking fetal calf serum was used. However, after addition of fetal calf serum to the culture medium the expression of CaMKIV could be specifically induced. Furthermore, it could also be shown that during T-cell development in the adult murine thymus the expression of CaMKIV was tightly regulated. Taken together, these results demonstrate that the expression of CaMKIV, an enzyme involved in the regulation of Ca(2+)-dependent gene expression, is itself under stringent regulatory control during tissue development.

Animals↗
PubMed1997

Fas ligand expression is restricted to nonlymphoid thymic components in situ.

The cell surface receptor Fas (Apo-1/CD95) and its ligand (FasL) are mediators of apoptosis that have been shown to be implicated in activation-induced death of mature T cells and in killing mediated by cytolytic T cells. The role of the Fas pathway in apoptosis associated with thymic selection events is, however, controversial. Although Fas and FasL are known to be expressed in the thymus, the nature and in vivo localization of FasL-expressing cells have not been determined. Using recently developed anti-FasL Abs in combination with in situ hybridization on tissue sections, we show in this work that FasL-expressing cells are present in the thymus, particularly within the medulla. FasL mRNA was detected readily in thymic stromal cell extracts, but not in isolated thymocytes. Moreover, immunohistochemical analysis of serial tissue sections stained with Abs against FasL in conjunction with epithelial and dendritic cell markers indicated that both thymic epithelial and dendritic cells express FasL in situ. The coexistence of FasL-expressing stromal cells and Fas-expressing thymocytes may have important implications for the role of the Fas pathway in apoptosis associated with thymic selection events.

Animals↗
PubMed1997

Evaluation of cDNA libraries from different developmental stages of Schistosoma mansoni for production of expressed sequence tags (ESTs).

A comparative study of the gene expression profile in different developmental stages of Schistosoma mansoni has been initiated based on the expressed sequence tag (EST) approach. A total of 1401 ESTs were generated from seven different cDNA libraries constructed from four distinct stages of the parasite life cycle. The libraries were first evaluated for their quality for a large-scale cDNA sequencing program. Most of them were shown to have less than 20% useless clones and more than 50% new genes. The redundancy of each library was also analyzed, showing that one adult worm cDNA library was composed of a small number of highly frequent genes. When comparing ESTs from distinct libraries, we could detect that most genes were present only in a single library, but others were expressed in more than one developmental stage and may represent housekeeping genes in the parasite. When considering only once the genes present in more than one library, a total of 466 unique genes were obtained, corresponding to 427 new S. mansoni genes. From the total of unique genes, 20.2% were identified based on homology with genes from other organisms, 8.3% matched S. mansoni characterized genes and 71.5% represent unknown genes.

Animals↗
PubMed1997

Abnormal T lymphocyte development induced by targeted overexpression of IkappaB alpha.

A role in thymic maturation for factors of the NF-kappaB family has long been suspected, but not yet proven. Transgenic mice with a lymphocyte-specific defect in NF-kappaB activation were produced by targeted expression of human IkappaB alpha. The thymic cellularity of these mice was significantly decreased. The proportion of mature, TCRhigh thymocytes of the alphabeta lineage was reduced, and the remaining TCRhigh population contained an unusually high proportion of double-positive cells. This defect in maturation resulted in a transgene dose-dependent reduction in peripheral T lymphocytes, with the CD8 lineage being more severely affected. These data provide direct evidence for the involvement of NF-kappaB/Rel family proteins in late stages of T lymphocyte development, coincident with positive and negative selection.

Animals↗