Circumcision debate. Task Force on Circumcision, 1999-2000.
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Academies and Institutes↗
Biomedical subjects
A Bailey
Publications and source records attributed to A Bailey.
Association analysis of the vitamin D receptor gene, the type I collagen gene COL1A1, and the estrogen receptor gene in idiopathic osteoarthritis.
OBJECTIVE: Evidence has accumulated supporting a role for genes in the etiology of osteoarthritis (OA). Several candidates have been targeted as potential susceptibility loci including genes that are involved in the regulation of bone density. Genetic association analysis has suggested a role for the vitamin D receptor gene (VDR) and the estrogen receptor gene (ER) in susceptibility. Such findings must be tested in additional independent cohorts. We tested for association of these 2 genes, plus a third gene implicated in bone density, COL1A1, with idiopathic OA. METHODS: A case-control cohort of 371 affected probands and 369 unaffected spouses was used. Association was tested using 4 intragenic single nucleotide polymorphisms (SNP), one each for the VDR and COL1A1 genes, and 2 for the ER gene. The VDR and ER SNP are the same SNP that have been associated with OA. All 4 SNP affect restriction enzyme sites and were genotyped using polymerase chain reaction and enzyme digestion. Allele and genotype distributions for each SNP were compared between cases and controls and analyzed using Fisher's exact test. RESULTS: There was no evidence of association of the VDR or the ER gene SNP to OA. There was weak evidence of association of the COL1A1 SNP in female cases (p = 0.017), reflected by a difference in the distribution of genotypes at this SNP between female cases and controls (p = 0.027). However, when corrected for multiple testing, these results were not significant. CONCLUSION: If the VDR, ER, or COL1A1 genes do encode predisposition to OA then the 4 SNP tested are not associated with major susceptibility alleles at these 3 loci.
Aged↗
Variable expression of the autism broader phenotype: findings from extended pedigrees.
Factors influencing the rate, form, and severity of phenotypic expression among relatives of autistic probands are examined. Family history data on 3095 first- and second-degree relatives and cousins from 149 families with a child with autism and 36 families with a child with Down syndrome are studied. The results provide further evidence of an increased risk among autism relatives for the broadly defined autism phenotype. Of proband characteristics, severity of autism and obstetric optimality were confirmed as being related to familial loading for probands with speech. There was little variation in loading among probands lacking speech. The type of phenotypic profile reported in relatives appeared little influenced by characteristics of the relative or the proband, except for variation by degree of relative, parental status of relative, and perhaps proband's birth optimality score. Phenotypic rates among parents suggested reduced fitness for the severest and more communication-related forms of expression but not for the more mild and social forms of expression. Patterns of expression within the families did not support a simple X-linked nor an imprinted X-linked mode of inheritance. The basis for sex differences in rates of expression is discussed.
Autistic Disorder↗
Targeted gene delivery: a two-pronged approach.
The success of gene therapy relies on the ability of gene delivery systems to selectively deliver therapeutic genes to a sufficient number of target cells yielding expression levels that impact the diseased state. The gene delivery systems can be divided into two classes: viral and nonviral (or plasmid DNA-based). The present gene delivery technology being used in clinics today can be considered first generation, in that they possess the ability to transfect or infect target cells through their inherent chemical, biochemical, and molecular biological properties. Relying on these sole properties, however, limits therapeutic applications. Expansion of therapeutic applications or increased effectiveness of current therapies can be achieved by increasing the number of cells and cell types susceptible to gene transfer. This can be achieved through physical targeting and molecular biological targeting. Physical targeting relies on the attachment to the delivery vehicle of ligands that bind to cell surface receptors unique to the target cells. Molecular biological targeting refers to selective expression of the therapeutic gene by the target cell through the use of selective promoters. Selective expression can be further achieved by the use of expression systems controlled by extrinsic induction molecules. This review will describe in detail the advances that have been made in each of these areas of gene targeting.
Animals↗
Properties of the adenovirus type 40 E1B promoter that contribute to its low transcriptional activity.
The adenovirus type 5 (Ad5) E1B promoter contains two elements essential for maximal activity, a TATA box and a GC box. The enteric adenovirus type 40 (Ad40) E1B promoter has a TATA box sequence identical to that of Ad5 and a GC box that fits the Sp1 binding site consensus. Nevertheless, Ad40 E1B RNA synthesis is severely impaired in HeLa cells, attributable in part at least to the weak transactivating activity of Ad40 E1A. However, the responsiveness of Ad40 early promoters to E1A transactivation has not been directly demonstrated. Using a transient expression assay with a chloramphenicol acetyl transferase (CAT) reporter gene, the Ad40 E1B promoter was very poorly transactivated by E1A of both Ad40 and Ad5 and showed only a limited response to the promiscuous varicella zoster virus transactivator p140. Construction of Ad5 recombinant viruses expressing the CAT gene under the control of the Ad5 or Ad40 E1B promoter allowed detection and measurement of expression from the Ad40 E1B promoter in a well-defined background and showed that overall activity is some 100-fold lower than for the Ad5 E1B promoter. Deletion analysis revealed that sequences upstream of the Sp1 binding site down-modulated Ad40 E1B promoter responsiveness, and two protein binding sites, identified by DNase footprinting and gel retardation assay, may be implicated in this effect. Gel shift analysis also showed that the Ad40 Sp1 binding site had a reduced affinity for Sp1 protein, relative to the Ad5 site, and that the context as well as the core sequence had an influence on Sp1 recognition.
Adenovirus E1B Proteins↗
Serotonin transporter (5-HTT) and gamma-aminobutyric acid receptor subunit beta3 (GABRB3) gene polymorphisms are not associated with autism in the IMGSA families. The International Molecular Genetic Study of Autism Consortium.
Previous studies have suggested that the serotonin transporter (5-HTT) gene and the gamma-aminobutyric acid receptor subunit beta3 (GABRB3) gene, or other genes in the 15q11-q13 region, are possibly involved in susceptibility to autism. To test this hypothesis we performed an association study on the collection of families from the International Molecular Genetic Study of Autism (IMGSA) Consortium, using the transmission disequilibrium test. Two polymorphisms in the 5-HTT gene (a functional insertion-deletion polymorphism in the promoter and a variable number tandem repeat in the second intron) were examined in 90 families comprising 174 affected individuals. Furthermore, seven microsatellite markers spanning the 15q11-q13 region were studied in 94 families with 182 affected individuals. No significant evidence of association or linkage was found at any of the markers tested, indicating that the 5-HTT and the GABRB3 genes are unlikely to play a major role in the aetiology of autism in our family data set.
Autistic Disorder↗
Antagonists of the platelet P2T receptor: a novel approach to antithrombotic therapy.
The platelet P2T receptor plays a major role in platelet aggregation, and its antagonists are predicted to have significant therapeutic potential as antithrombotic agents. We have explored analogues of adenosine triphosphate (ATP), which is a weak, nonselective but competitive P2T receptor antagonist. Modification of the polyphosphate side chain to prevent breakdown to the agonist adenosine diphosphate (ADP) and substitution of the adenine moiety to enhance affinity and selectivity for the P2T receptor led to the identification of 10e (AR-C67085MX), having an IC50 of 2.5 nM against ADP-induced aggregation of human platelets. Compound 10e was the first very potent antagonist of the P2T receptor, with a selectivity for that subtype of the P2 receptor family of >1000-fold. Further modification of the structure produced compound 10l (AR-C69931MX) having an IC50 of 0.4 nM. In vivo, at maximally effective antithrombotic doses, there is little prolongation of bleeding time (1.4-fold), which is in marked contrast to the 5-6-fold found with GPIIb/IIIa antagonists.
Adenosine Monophosphate↗
A comparative evaluation of a fibromyalgia rehabilitation program.
OBJECTIVE: To compare an evidence-based clinical fibromyalgia program, referred to as Fibro-Fit, with results of controlled clinical trials. METHODS: An interdisciplinary group education and exercise program with 36 sessions over 12 weeks was used. Demographic, clinical, and outcome variables were collected on 149 participants, of whom 71% completed the program. Outcomes included measures of self-efficacy, pain, physical fitness, function, and coping skills. RESULTS: Results of the prospective before-after evaluation showed statistically significant (P < 0.005) improvements in all outcomes except for grip strength. These results were comparable with controlled clinical trials found in the literature. Data suggest that smoking, fibromyalgia support groups, and medications may be important modifiable factors. CONCLUSIONS: Results suggest that Fibro-Fit was effective in improving physical impairments and function. Further investigation is required to refine the effective components of these programs and determine how modifiable factors can be used to improve outcomes.
Activities of Daily Living↗
Semiquantitative polymerase chain reaction enzyme immunoassay for the diagnosis of pertussis.
The two most commonly used targets for diagnosis of pertussis by the polymerase chain reaction have been the pertussis toxin promoter and the repeated insertion sequence IS481. A comparative assessment of these primers was performed on routinely collected nasopharyngeal swabs, stored at -20 C, using novel semiquantitative enzyme immunoassays. Both sets of primers behaved similarly with bacterial suspensions, and the 17 culture-positive nasopharyngeal swabs were also positive with the pertussis toxin promoter primers, with one exception, which had been subject to prolonged storage. Significantly more of the 69 culture-negative swabs were positive with the pertussis toxin promoter primers (n = 36) than with the IS481 primers (n = 18). To determine the effect of inhibitors, a comparative assessment of three primer pairs against human DNA (beta-globin and glyceraldehyde-3-phosphate dehydrogenase) was also performed.
Child↗
High throughput detection of retrovirus-associated reverse transcriptase using an improved fluorescent product enhanced reverse transcriptase assay and its comparison to conventional detection methods.
The development and application of a novel, sensitive TaqMan fluorescent probe-based product enhanced RT test (F-PERT) for the detection of retrovirus are described. The assay allows discrimination between the amplification signals generated by genuine positive signals that result from retroviral RT activity and the RT-like activity from DNA polymerases. The RT-like activity from DNA polymerases was suppressed by the addition of activated calf-thymus DNA with no reduction in the RT activity. A linear relationship between threshold cycle (C(T)) and the number of virus particles was demonstrated, allowing quantification of retroviruses in unknown samples. The F-PERT assay was able to detect a wide range of retroviral RT activities, including that from porcine endogenous retrovirus (PoERV), murine leukaemia virus (MLV), simian foamy virus (SFV), simian immunodeficiency virus (SIVmac) and squirrel monkey retrovirus (SMRV). The detection limit of SMRV, MLV and PoERV was approximately 100 virion particles and the test was able to detect at least 10(2) molecules of purified RT enzyme. RT activity was not detected in cellular lysates and supernatants from MRC-5, BT, VERO, or Raji cells, whereas RT activity was detected in C1271, Mus dunni, K-Balb, BHK-21, CHO-K1, SP2/0-Ag14 and NSO cell supernatants. RT activity was also detected in the Spodoptera cell line Sf9.
Animals↗
Lower incidence of tardive dyskinesia with risperidone compared with haloperidol in older patients.
OBJECTIVE: To compare the 9-month cumulative incidence of tardive dyskinesia (TD) with risperidone to that with haloperidol in older patients. DESIGN: A prospective longitudinal study. SETTING: An outpatient psychiatric clinic. PARTICIPANTS: Subjects were middle-aged and older (mean age 66 years) patients with schizophrenia, dementia, mood disorders, or other conditions with psychotic symptoms or severe behavioral disturbances. Sixty-one patients on risperidone were matched with 61 patients from a larger sample of haloperidol-treated patients in regard to age, diagnosis, and length of pre-enrollment neuroleptic intake to create clinically comparable groups. The median daily dose of each medication was 1.0 mg. MEASUREMENTS: Abnormal Involuntary Movement Scale, modified Simpson-Angus' scale for extrapyramidal symptoms, Brief Psychiatric Rating Scale, and Mini-Mental State Examination were administered at baseline, 1 month, and 3, 6, and 9 months. The diagnosis of TD was based on specific research criteria. The raters were blind to the patient's medication status. RESULTS: Life table analysis revealed that patients treated with haloperidol were significantly more likely to develop TD than patients treated with risperidone (P < .05, Peto-Prentice). CONCLUSIONS: The atypical antipsychotic risperidone is significantly less likely to result in TD than the conventional neuroleptic haloperidol in a high-risk group of older patients, at least over a 9-month period.
Aged↗
Depressive symptoms in schizophrenia.
OBJECTIVE: The authors assessed the presence and severity of depressive symptoms, as well as their associations with other clinical measures, in a group of mid- to late-life patients with schizophrenia who were not in a major depressive episode or diagnosed with schizoaffective disorder. METHOD: Sixty outpatients with schizophrenia between the ages of 45 and 79 years and 60 normal comparison subjects without major neuropsychiatric disorders, proportionally matched for age and gender, were studied. Depressive symptoms were rated primarily with the Hamilton Depression Rating Scale. Standardized instruments were also used to measure global psychopathology, positive and negative symptoms, abnormalities of movement, and global cognitive status. RESULTS: Depressive symptoms were more frequent and more severe in schizophrenic patients than in normal comparison subjects; 20% of the women with schizophrenia had a Hamilton depression scale score of 17 or more. Severity of depressive symptoms correlated with that of positive symptoms but not with age, gender, negative symptoms, extrapyramidal symptoms, or neuroleptic dose. CONCLUSIONS: Depressive symptoms are common in older patients with schizophrenia. They may be an independent, core component of the disorder or, alternatively, may be a by-product of severe psychotic symptoms.
Age Factors↗
Autism screening questionnaire: diagnostic validity.
BACKGROUND: Good interview and diagnostic measures for autism and other pervasive developmental disorders (PDDs) are available but there is a lack of a good screening questionnaire. AIMS: To develop and test a screening questionnaire based on items in the best available diagnostic interview--the Autism Diagnostic Interview--Revised (ADI-R). METHOD: A 40-item scale, the Autism Screening Questionnaire (ASQ), was developed and tested on a sample of 160 individuals with PDD and 40 with non-PDD diagnoses. RESULTS: The ASQ has good discriminative validity with respect to the separation of PDD from non-PDD diagnoses at all IQ levels, with a cut-off of 15 proving most effective. The differentiation between autism and other varieties of PDD was weaker. CONCLUSIONS: The ASQ is an effective screening questionnaire for PDD.
Adolescent↗
The pediatric sedation unit: a mechanism for safe pediatric sedation.
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Anesthesiology↗
Isolation of a nitrogen response regulator gene (nrr1) from Metarhizium anisopliae.
Attempts to improve the effectiveness of entomopathogenic fungi as biological control agents require a clear understanding of the pathogenicity determinants at both the biochemical and molecular level. Proteases play a key role in entomopathogenicity, allowing the fungus to penetrate the insect cuticle and rapidly invade the host. The most extensively studied of these protease activities, PR1A and PR2, are both subject to nitrogen derepression. The Metarhizium anisopliae nrr1 (nitrogen response regulator 1) gene was identified using a PCR-based strategy; it encodes a putative DNA-binding protein with a single zinc finger motif defined by the C-X2-C-X17-C-X2-C sequence. M. anisopliae NRR1 shows a significant sequence similarity to Neurospora crassa NIT2. Sequence analysis identified the presence of two introns, suggesting a greater degree of similarity to N. crassa nit2 than to the areA-like genes that have been identified. However, functional equivalence of nrr1 to areA was demonstrated, by co-transformation and complementation of an A. nidulans areA loss-of-function mutant (areA18 argB2 pabaA1 inoB2) with the M. anisopliae nrr1 gene. The areA-/nrr1+ Aspergillus transformants were able to grow on media with nitrate and glutamate as the sole nitrogen source, whereas the areA- strain is unable to grow under these conditions. The possible relevance of nitrogen regulation to pathogenicity is discussed.
Amino Acid Sequence↗
A single amino-acid substitution in the iron-sulphur protein subunit of succinate dehydrogenase determines resistance to carboxin in Mycosphaerella graminicola.
A gene encoding the iron-sulphur protein (Ip) subunit of succinate dehydrogenase (Sdh, EC 1.3.99.1) from Mycosphaerella graminicola (Septoria tritici) has been cloned andsequenced. The deduced amino-acid sequence exhibited a high degree of homology to Ip subunits of Sdh from other organisms; three cysteine-rich clusters associated with the iron-sulphur centres involved in electron transport were particularly conserved. Expression studies using a synthetic green fluorescent protein (SGFP) expression vector demonstrated that the cloned DNA also contained a functional promoter region and confirmed that the deduced initiation codon could act as a translational start site. Mutants resistant to the fungicide carboxin (Cbx), a known inhibitor of Sdh, were found to contain a single amino-acid substitution in the third cysteine-rich domain of the Ip protein. These mutations resulted in the conversion of a highly conserved His residue, located in a region of the protein associated with the [3Fe-4 S] high-potential non-heme iron sulphur-redox (S3) centre, to either Tyr or Leu. AnIp gene containing the His -> Tyr mutation was constructed and shown to confer Cbx resistance following co-transformation into the Cbx-sensitive wild-type strain. This confirmed that the mutation identified by sequence analysis was responsible for determining Cbx resistance.
Alleles↗
Autism: the phenotype in relatives.
There is broad agreement that genetic influences are central in the development of idiopathic autism. Whether relatives manifest genetically related milder phenotypes, and if so how these relate to autism proper, has proved a more contentious issue. A review of the relevant studies indicates that relatives are sometimes affected by difficulties that appear conceptually related to autistic behaviors. These range in severity from pervasive developmental disorders to abnormalities in only one area of functioning, and possibly extend to related personality traits. Issues involved in clarifying the components of milder phenotypes and their relationship to autism are outlined.
Autistic Disorder↗
A clinicopathological study of autism.
A neuropathological study of autism was established and brain tissue examined from six mentally handicapped subjects with autism. Clinical and educational records were obtained and standardized diagnostic interviews conducted with the parents of cases not seen before death. Four of the six brains were megalencephalic, and areas of cortical abnormality were identified in four cases. There were also developmental abnormalities of the brainstem, particularly of the inferior olives. Purkinje cell number was reduced in all the adult cases, and this reduction was sometimes accompanied by gliosis. The findings do not support previous claims of localized neurodevelopmental abnormalities. They do point to the likely involvement of the cerebral cortex in autism.
Adult↗