A combined analysis of D22S278 marker alleles in affected sib-pairs: support for a susceptibility locus for schizophrenia at chromosome 22q12. Schizophrenia Collaborative Linkage Group (Chromosome 22).

Several groups have reported weak evidence for linkage between schizophrenia and genetic markers located on chromosome 22q using the lod score method of analysis. However these findings involved different genetic markers and methods of analysis, and so were not directly comparable. To resolve this issue we have performed a combined analysis of genotypic data from the marker D22S278 in multiply affected schizophrenic families derived from 11 independent research groups worldwide.

Effect of altitude on spirometric parameters and the performance of peak flow meters.

Background: Portable peak flow meters are used in clinical practice for measurement of peak expiratory flow (PEF) at many different altitudes throughout the world. Some PEF meters are affected by gas density. This study was undertaken to establish which type of meter is best for use above sea level and to determine changes in spirometric measurements at altitude.

Preferential transmission of the high activity allele of COMT in schizophrenia.

Catechol-O-methyl transferase (COMT) metabolizes a variety of catecholamines such as dopamine, adrenaline and noradrenaline. It exists in common high and low activity forms. The low activity form is the result of an amino acid substitution (val-108-met) which reduces the thermostability of the enzyme [Lotta et al.

Linkage analysis of the fragile X gene FMR-1 and schizophrenia: no evidence for linkage but report of a family with schizophrenia and an unstable triplet repeat.

We have examined 23 families multiply affected with schizophrenia for linkage to the FMR-1 gene on the X chromosome. Alleles at the FMR-1 CGG triplet repeat were analysed by the polymerase chain reaction, and methylation status at the FMR-1 locus in individuals with evidence of expanded or unstable repeats was analysed by Southern hybridization. Two-point LOD score analyses with a range of X-linked single gene models and a non-parametric affected sib-pair method revealed no evidence for linkage.

Association between clozapine response and allelic variation in the 5-HT2C receptor gene.

A cysteine to serine substitution at amino acid 23 in the 5-HT2C receptor gene alters the pharmacological properties of the protein. We investigated this polymorphism in subjects with schizophrenia resistant to conventional neuroleptic drugs, and analysed our data for allelic association between the disease state or clinical response to the atypical antipsychotic drug, clozapine. Ninety percent of subjects who had one or more 5-HT2Cser alleles (19/21) were classified as clozapine responders compared with 59% (84/141) without this allele (chi 2 = 7.

Analysis of clozapine response and polymorphisms of the dopamine D4 receptor gene (DRD4) in schizophrenic patients.

We have examined the hypothesis that a variable number of tandem repeats in the third cytoplasmic loop of the dopamine D4 receptor influences clinical response to clozapine using a sample of 189 schizophrenic patients. Alleles of the 48-bp repeat, which range from two to ten copies in the normal human population, were analysed by the polymerase chain reaction using genomic DNA as template. Association between these alleles and response to clozapine was tested using the difference in pre- and post-treatment GAS scores as a measure of response.

Changes in respiration and chemical content during autumnal senescence of Populus tremuloides and Quercus rubra leaves.

Changes in respiration rate, chemical content and chemical concentration were measured in leaves of field-grown Populus tremuloides Michx. and Quercus rubra L. trees throughout the growing season and autumnal senescence.

Evaluation of the pharmacokinetic interaction between cimetidine or famotidine and cyclosporine in healthy men.

Objective: To investigate the potential interaction between cimetidine or famotidine and cyclosporine in healthy men.

Design: All subjects received oral cyclosporine at baseline, after the first week of 1 histamine2 (H2)-blocker, and a third time after a 1-week washout plus 1 week of the second H2-blocker. Blood samples were collected just before each dose of cyclosporine and for up to 36 hours afterward for pharmacokinetic analysis.

No evidence for linkage between the X-chromosome marker DXS7 and schizophrenia.

DeLisi et al. (1994b) have examined the X and Y chromosomes for linkage to schizophrenia in 126 small families and report a small positive LOD score for the marker DXS7, adjacent to the MAO locus at Xp11.4-11.

Systematic search for major genes in schizophrenia: methodological issues and results from chromosome 12.

We describe a method of systematically searching for major genes in disorders of unknown mode of inheritance, using linkage analysis. Our method is designed to minimize the probability of missing linkage due to inadequate exploration of data. We illustrate this method with the results of a search for a locus for schizophrenia on chromosome 12 using 22 highly polymorphic markers in 23 high density pedigrees.

Schizophrenia and the androgen receptor gene: report of a sibship showing co-segregation with Reifenstein syndrome but no evidence for linkage in 23 multiply affected families.

Crow et al. [1993: Am J Med Genet (Neuropsychiatr Genet) 48:159-160] have reported excess sharing of alleles by male sibling pairs with schizophrenia, at a triplet repeat marker within the androgen receptor gene, indicating that mutations at or near this gene may be a risk factor for males. In this report, we describe a pair of male siblings concordant for both schizophrenia and Reifenstein syndrome, which is caused by a mutation in this gene.

Suggestive evidence for linkage of schizophrenia to markers on chromosome 13q14.1-q32.

Family, twin and adoption studies highlight the influence of genes in the aetiology of schizophrenia, though the mode of inheritance is unclear. We have been conducting a systematic search for major genes in schizophrenia using a series of multiply affected families and report preliminary results of linkage under heterogeneity with markers on chromosome 13. A lod2 score of 1.

Association between clozapine response and allelic variation in 5-HT2A receptor gene.

We report allelic association between a polymorphism (T102C) within the coding region of the 5-HT2A gene (HTR2A, 13q14-21) and response to clozapine in schizophrenic patients. Homozygosity for the C102 allele was more frequent (30/57, 53%) among patients who did not respond to clozapine than in those who responded (23/92, 25%). This finding is evidence that allelic variation of genes which encode neurotransmitter receptors can influence clinical response to antipsychotic drugs.

Inter and intraobserver variability of total skin thickness score (modified Rodnan TSS) in systemic sclerosis.

Objective: Assessment of the inter and intraobserver variability of the modified Rodnan (m-Rodnan) total skin thickness score by clinical palpation [a commonly used outcome measure in trials of systemic sclerosis (SSc)].

Methods: Skin thickness was assessed by clinical palpation of 17 body areas on 0 to 3 scale (normal, mild, moderate, severe). The m-Rodnan total skin thickness score was derived by summation of the scores from all 17 body areas.

Linkage studies on chromosome 22 in familial schizophrenia.

As part of a systematic search for a major genetic locus for schizophrenia we have examined chromosome 22 using 14 highly polymorphic markers in 23 disease pedigrees. The markers were distributed at an average distance of 6.6 cM, covering 70-80% of the chromosome.

Cytochrome P4502D6 genotype does not determine response to clozapine.

1. The atypical antipsychotic drug clozapine, used in the treatment of resistant schizophrenia, is metabolized partly by the hepatic cytochrome P450 enzyme CYP2D6. Two phenotypes with respect to the activity of the enzyme are recognized (extensive metabolisers (EM) and poor metabolisers (PM)), resulting from allelic variation in the gene, CYP2D6.

[Ag(I)(Et(2)PCH(2)CH(2)PPh(2))(2)]NO(3): An Antimitochondrial Silver Complex.

The silver(I) complex [Ag(eppe)(2)]NO(3) (eppe = Et(2)PCH(2)CH(2)PPh(2)) is shown by X-ray crystallography to be tetrahedral with Ag - PEt(2) and Ag - P Ph(2) bond lengths of 2.482 and 2.518 A, respectively.

Chromosome 22 markers demonstrate transmission disequilibrium with schizophrenia.

Previously we reported evidence for genetic linkage between markers on chromosome 22q12 and schizophrenia in 23 multiply affected pedigrees. As part of further investigation of this region, we have applied the transmission disequilibrium test (TDT) to the genotype data. The TDT is a test for both linkage and linkage disequilibrium, and is based on the unequal probability of transmission of two different marker alleles from parents to affected offspring.

Developmental shifts in the ability of infants with Down syndrome to produce treadmill steps.

Background And Purpose: In this study, we used a dynamic systems strategy to examine longitudinally the ability of infants with Down syndrome to produce alternating steps when supported on a motorized treadmill.

Subjects: Seven infants participated, ranging in age from 8 to 11 months at entry into the study and 13 to 29 months at their final session.

Methods: Data were collected in the infants' homes on a monthly basis.

Functional neuroimaging and pharmacogenetic studies of clozapine's action at dopamine receptors.

The factors that influence response to neuroleptic drugs are poorly understood. These factors may include clinical variables such as length of illness before treatment, age at onset, and the presence of negative symptoms; and pharmacologic factors such as rates of drug metabolism. For example, pharmacodynamic differences in therapeutic response to haloperidol have been observed between Chinese and Caucasian patients.

Expression of Escherichia coli SecB in Bacillus subtilis facilitates secretion of the SecB-dependent maltose-binding protein of E. coli.

Less than 20% of the Escherichia coli maltose-binding protein (MBP) synthesized in Bacillus subtilis is exported. However, a portion of the secreted MBP was processed cotranslationally. Coexpression of SecB, a secretion-related chaperone of E.