Search PubMed⌕ Search

Biomedical subjects

A Bailey

Publications and source records attributed to A Bailey.

At least 55 records · Page 3Linked to original sources

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↗

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↗

Relationship of neuropsychological and MRI measures to age of onset of schizophrenia.

Age of onset of schizophrenia (AOS) may be largely determined by neurobiological factors. We examined in a diverse sample of schizophrenia out-patients the relationships of AOS with neuropsychological abilities and structural brain abnormalities as measured on cerebral magnetic resonance imaging (MRI). A total of 82 out-patients meeting DSM-III-R criteria for schizophrenia were evaluated with a comprehensive neuropsychological battery and semi-automated quantitatively analysed cerebral MRI. Earlier AOS correlated with poorer performance in learning and abstraction/cognitive flexibility, and with larger volumes of caudate and lenticular nuclei, and smaller volume of thalamus on MRI. A model for predicting AOS consisting of abstraction and thalamic and caudate volumes remained significant after controlling for duration of illness, current age and daily neuroleptic dose. In conclusion, AOS may be related to specific rather than general measures of cognitive performance and structural brain abnormalities.

Adult↗

Systematic gain-of-function genetics in Drosophila.

A modular misexpression system was used to carry out systematic gain-of-function genetic screens in Drosophila. The system is based on inducible expression of genes tagged by insertion of a P-element vector carrying a GAL4-regulated promoter oriented to transcribe flanking genomic sequences. To identify genes involved in eye and wing development, the 2300 independent lines were screened for dominant phenotypes. Among many novel genes, the screen identified known genes, including hedgehog and decapentaplegic, implicated in these processes. A genetic interaction screen for suppressors of a cell migration defect in a hypomorphic slow border cells mutant identified known genes with likely roles in tyrosine kinase signaling and control of actin cytoskeleton, among many novel genes. These studies demonstrate the ability of the modular misexpression system to identify developmentally important genes and suggest that it will be generally useful for genetic interaction screens.

Animals↗

Validity of specific subscales of the positive and negative symptom scales in older schizophrenia outpatients.

We investigated the construct validity of subscales of the Scale for the Assessment of Positive Symptoms (SAPS) and the Scale for the Assessment of Negative Symptoms (SANS) along with other measures of psychopathology in 109 schizophrenia outpatients aged 45-84 years. Scores on subscales of the SAPS, SANS and Brief Psychiatric Rating Scale (BPRS) and on the Hamilton Depression Scale (HAM-D) were subjected to a principal components analysis and orthogonal rotation followed by an extension analysis. In both analyses, three of four SAPS subscales had their highest loading on the positive symptom factor and four of five SANS subscales had their highest factor loading on the negative symptom factor. The SAPS bizarre behavior subscale, however, had a much higher loading on the depressive symptom factor than on the positive symptom factor, and the SANS avolition-apathy subscale had moderate loadings on both the negative symptom factor and the depressive symptom factor. The use of SAPS and SANS subscales to represent two constructs was largely (but not entirely) validated among middle-aged and elderly schizophrenia outpatients. The SAPS bizarre behavior subscale and, to a lesser extent, the SANS avolition-apathy subscale appear to represent in this older population a separate construct which may be related to depressive symptoms.

Age Factors↗

Neuroleptic dose reduction in older psychotic patients.

We conducted a non-randomized, rater-blind study to safely determine the lowest effective neuroleptic dosage in older psychotic patients and to evaluate the clinical, neuropsychological, and psychosocial effects of neuroleptic dosage reduction. Twenty-seven carefully selected patients with schizophrenia and related psychotic disorders over the age of 45 had their dosage tapered by 25% each month to determine their lowest effective dosage. These patients were compared with patients similar in age, gender, and education who were currently off neuroleptics (n = 19) or maintained on neuroleptics (n = 22). All groups were followed for 11 months. Over the follow-up period, 29% of patients in the taper group, 8% of neuroleptic-free patients, and 0% of patients in the maintenance group experienced some increase in psychopathology, although there was no significant change in mean PANSS score in any group, and no patient required hospitalization. Patients in the taper group were maintained on approximately 60% of their original neuroleptic dosage after restabilization. Extrapyramidal symptoms continued to improve over time in the taper group. Neuropsychological testing did not change significantly over time except for those in the taper group who experienced a decrease in memory-retention on the Hopkins Verbal Learning Test and a significant improvement in digit vigilance and Stroop Interference Index. Carefully selected middle-aged and elderly psychotic patients can have their neuroleptic medications reduced without a significant change in psychopathology. Extrapyramidal symptoms may continue to improve gradually over time. The impact on cognition functioning needs further investigation.

Age Factors↗

Census tract analysis of lead exposure in Rhode Island children.

There has been increasing interest in a targeted approach to the screening and prevention of lead exposure in children. Targeted screening requires an understanding of variation in lead exposure in individual children or by region. In order to better understand variation by region, we studied Rhode Island lead poisoning screening data, examining average lead exposure to children living in 136 Providence County census tracts (CTs). The study population included 17,956 children aged 59 months and under, who were screened between May 1, 1992, and April 30, 1993. We evaluated the relationship between the percentage of children with blood lead > or = 10 micrograms/dL (pe10) and sociodemographic and housing characteristics, derived from United States 1990 Census data, of these CTs. CT descriptors included population density, percentage of households receiving public assistance income, median per capita income, percentage of households female headed, percentage of houses owner occupied, percentage of houses built before 1950, percentage of houses vacant, percentage of population Black, percentage of recent immigrants, and intraurban mobility. On average, 109 children were screened in each census tract; mean screening rate was 44%. There was wide variation in average lead exposure among census tracts, with pe10 ranging from 3 to 60% of screened children (mean 27%). Individual census variables explained between 24 and 67% of the variance in pe10 among CTs. A multiple regression model including percentage screened, percentage of households receiving public assistance, percentage of houses built before 1950, In (percentage of houses vacant), and percentage of recent immigrants explained 83% of variance in pe10. The percentage of houses built before 1950, a variable which models the presence of lead paint in old houses, displayed the largest adjusted effect on pe10 over the range observed for that variable in RI CTs. The percentage of houses vacant was also a highly significant and robust predictor; we suggest that vacancy is an ecological marker for the deterioration of leadbased paint, with higher vacancy neighborhoods containing houses in poorer condition. In Rhode Island, census tracts with high vacancy rates also have high rates of recent immigration, making immigrant groups vulnerable to lead exposure. Small-areas analysis may be useful in directing resources to high risk areas, explaining the sociocultural forces which produce such exposure and analyzing the effects of housing policy over time in states with high screening penetration.

Child, Preschool↗

Carbon regulation of the cuticle-degrading enzyme PR1 from Metarhizium anisopliae may involve a trans-acting DNA-binding protein CRR1, a functional equivalent of the Aspergillus nidulans CREA protein.

The pr1 gene of the entomopathogenic fungus Metarhizium anisopliae encodes a serine protease that is highly active towards the insect cuticle and whose synthesis is subject to both carbon and nitrogen repression. The pr1 promoter region was sequenced revealing the presence of putative CREA- and AREA-binding sites. In vitro bandshift experiments demonstrated that an Aspergillus nidulans GST-CREA fusion protein was capable of binding to two of the three putative CREA sites. Using a PCR-based strategy the M. anisopliae crr1 gene was identified; it encodes a putative C2H2-type DNA-binding protein with significant sequence similarity to A. nidulans CREA. Complementation experiments with an A. nidulans strain carrying creA204 demonstrated that CRR1 can partially substitute for CREA function.

Amino Acid Sequence↗

The role of alpha-2 adrenoceptors in the regulation of oxytocin neurones in the suckled rat.

The role of alpha-2 adrenoceptors in the milk-ejection reflex was investigated by making electrophysiological recordings from oxytocin neurones in the supraoptic nucleus of urethane-anaesthetised rats. Systemic administration of the alpha-2 adrenoceptor antagonist. Idazoxan (0.5 mg/kg, i.v.), temporarily suppressed OT cell bursting activity, while having no consistent action on basal neuronal activity. Clonidine (25 micrograms/kg, i.v.) caused an immediate increase in the frequency and amplitude of oxytocin cell bursting, coincident with a fall in basal activity. A higher dose of clonidine (50 micrograms/kg, i.v.), inhibited both bursting and basal activity. These results indicate that alpha-2 adrenoceptors are essential for the normal functioning of the milk-ejection reflex and may be involved in the facilitatory and inhibitory regulation of suckling-evoked bursting in oxytocin neurones.

Adrenergic alpha-Agonists↗

Somatostatin receptor subtype 2 knockout mice are refractory to growth hormone-negative feedback on arcuate neurons.

The pulsatile nature of GH release is apparently regulated by alternating sequential changes in two hypothalamic hormones, GH releasing hormone (GHRH) and somatostatin. Entrainment of this pulsatility appears to involve GH-mediated negative feedback. Recently a new receptor involved in GH release was cloned. Activation of this receptor by GH-releasing peptides and MK-0677 initiates and amplifies GH pulsatility and is associated with increased Fos immunoreactivity and electrical activity in GHRH containing arcuate neurons. We show that pretreating mice with GH blocks activation of these neurons by MK-0677. Similarly, octreotide inhibited the action of MK-0677. To determine whether this GH-mediated negative feedback on GHRH neurons was direct, or by GH stimulation of somatostatin release from periventricular neurons, we selectively inactivated the gene for one of the five specific somatostatin receptor subtypes (subtype 2). In the knockout mice, both GH and octreotide failed to inhibit MK-0677 activation of arcuate neurons. GH did, however, increase Fos immunoreactivity in the periventricular nucleus, consistent with GH stimulation of somatostatin release from periventricular neurons. Thus, GH-mediated negative feedback involves signaling between periventricular and arcuate neurons with the signal being transduced specifically through somatostatin subtype 2 receptors.

Animals↗

Vectorette PCR isolation of microsatellite repeat sequences using anchored dinucleotide repeat primers.

We have developed a vectorette PCR approach to provide an improved method for isolation of microsatellite repeats. The modified procedure relies on PCR amplification using a vectorette-specific primer in combination with one of a panel of anchored dinucleotide repeat primers. The target DNA to be screened for microsatellite sequences can be from YAC, P1, cosmid, bacteriophage or plasmid clones. We have used this technique to isolate novel, polymorphic microsatellite repeats from clones containing the amelogenin gene (AMGX) located on human chromosome Xp22.3.

Amelogenin↗

Yeast artificial chromosome cloning and chromosomal localization of the abundant odontogenic keratocyst protein elafin.

An imbalance in human leucocyte elastase (HLE) activity is widely recognized to play an important pathological role in a number of human diseases. An earlier report has described greater transcription of elafin, an endogenous inhibitor of HLE, in epithelia of odontogenic keratocysts of the jaw than in normal oral mucosa. The elafin gene was now localized to chromosome 20q11.2-13.1 using a combination of somatic cell-hybrid panel screening and fluorescence in situ hybridization using a biotinylated DNA probe prepared from isolated yeast artificial chromosomes. No other positive fluorescent signals were observed. This eliminates the elafin gene as a candidate gene for naevoid basal-cell carcinoma syndrome, as the gene for this syndrome localizes to chromosome 9q23.1-31. The elafin yeast artificial chromosome DNA is to be subcloned to identify polymorphic microsatellite markers that will establish whether this gene is frequently amplified in oral neoplastic tissue.

Basal Cell Nevus Syndrome↗

Validating specific psychopathology scales in older outpatients with schizophrenia.

To our knowledge, there have been no published studies validating commonly used psychopathology rating scales in older outpatients with schizophrenia. We studied specific psychopathology rating scales (three subscales of the Brief Psychiatric Rating Scale: positive symptoms, negative symptoms, and depression subscales; the Scale for Assessment of Positive Symptoms; the Scale for the Assessment of Positive Symptoms; the Scale for the Assessment of Negative Symptoms; and the Hamilton Depression Rating Scale) in 101 (age > 45 years) DSM-III-R-diagnosed schizophrenia outpatients. We found high interrater reliability (intra-class correlated coefficient > or = .77) on these scales. Using principal components analysis, we demonstrated satisfactory construct validity, suggesting three factors-positive symptoms, negative symptoms, and depressive symptoms.

Age Factors↗