Candidate-gene association analysis of response to risperidone in African-American and white patients with schizophrenia.

Clinical trial data were evaluated for the association between 22 single-nucleotide polymorphisms (SNPs) and response in acutely ill patients diagnosed with schizophrenia, schizoaffective disorder or schizophreniform disorder, who were treated with oral risperidone. All patients in the exploratory (78 African Americans) and validation (65 whites) data sets received risperidone 2-6 mg per day over 2-12 weeks. Two SNPs were found to have significant associations with response to risperidone over 2-12 weeks in both African-American and white patients and had a consistent direction of effect in both cohorts. Metabotropic glutamate receptor (GRM3) SNP, rs724226, was associated with a change in the positive and negative syndrome scale (PANSS) total response. Catechol-O-methyltransferase (COMT) SNP, rs165599, was moderately associated with a change in the PANSS Negative score. The greater prevalence of poor-responder GRM3 and COMT alleles in white versus African-American patients might have a clinical significance in evaluating the ethnic-specific response to risperidone.

The influence of low blood lead concentrations on the cognitive and physical development of primary school children in Malaysia.

This study aimed to determine the relationship between blood lead (BPb) concentrations and cognitive and physical development in school children. A total of 169 urban children and 100 industrial children of Malay ethnicity, in the age range of 6(1/2) to 8(1/2) years, were selected. BPb was determined using GF atomic absorption spectrophotometer. The mean cognitive score (102.55) of the children from the industrial area was significantly higher than that of the urban children (95.09; P < .001). However, no significant differences were found in the BPb levels between the 2 groups (industrial, 3.75 microg/dL; urban, 3.56 microg/dL). There was significant inverse correlation between BPb and cognitive scores for all children (P < .05). The cognitive scores for all children were influenced by BPb after adjustments (P < .05). The urban children had significantly better Weight for Height and Left Arm Circumference values than those from industrial area. There was no significant correlation between BPb and the anthropometric measurements. In conclusion, low BPb influenced the cognitive development, whereas physical development was not affected.

Carbon monoxide exposure assessment among toll operators in Klang Valley, Kuala Lumpur, Malaysia.

A comparative cross-sectional study was conducted to determine tollbooth carbon monoxide (CO) levels and carboxyhaemoglobin (COHb) levels among the tollbooth operators and office workers in the Klang Valley, Kuala Lumpur. All tollbooths were equipped with well functioning air-conditioning. The total number of respondents was 180: 90 toll operators and 90 office workers aged between 19 and 52 years. The highest peak of CO level recorded was 61 ppm. The highest average peak CO level within a shift was 30 ppm. The CO level was higher during peak traffic at 6.00 - 8.00 a.m. There was no significant correlation between average peak CO level with vehicle load (r = -0.007, p = 0.474). The toll operators' median COHb level (1.0%, IQR = 0.8%) was significantly higher (p = 0.008) compared to office workers (0.7%, IQR = 0.8). There was a weak and significant correlation between COHb levels with average peak CO levels (r = 0.228, p = 0.031). In conclusion, tollbooth operators were chronically exposed to CO leading to higher COHb levels compared to office workers.

CD44 expression in fetal rat bone: in vivo and in vitro analysis.

Knowledge of the expression pattern of the cell surface glycoprotein CD44 in the development and differentiation of bone is limited. We investigated CD44 expression (a) in bone sections of 21-day-old fetal rat calvaria (RC), metatarsals, and tibiae, (b) in primary cultures of RC cells undergoing differentiation in vitro, and (c) in three rat osteosarcoma cell lines: ROS 17/2.8, UMR 106.01, and UMR 106.06. By immunocytochemistry, Western, Northern and reverse transcription polymerase chain reaction analyses, we found that osteoblastic cells express the 'hematopoietic' or 'standard' CD44 (CD44s) isoform. Osteoblastic cells in vivo and in vitro stained at all detectable stages of differentiation, but intercellular heterogeneity of CD44s staining was evident, with lesser staining in preosteoblastic cells and greater staining in mature osteoblasts and osteocytes. As cells in RC cultures differentiated and formed bone in vitro, CD44s mRNA and protein levels as measured on immunoblots were invariant. All three osteosarcoma cell lines expressed CD44s mRNA and protein. The synthetic glucocorticoid dexamethasone, which stimulates osteogenesis in RC cells in vitro and regulates a number of osteoblast-associated genes, had no apparent effect on either CD44s protein or mRNA levels. The widespread presence of CD44s in osteoblastic cells at various maturational stages suggests that further analyses will be required to determine what role CD44s may play in osteogenesis and in bone tissue organization.

Activated ras and src induce CD44 overexpression in rat intestinal epithelial cells.

CD44 is an adhesion molecule that is involved in the progression of several tumor types, including those originating in the intestine. There are several alternatively spliced forms of CD44. Here we show that intestinal epithelial cells express the standard form of CD44 (CD44s). The same form of CD44 is found in IEC-18, a cell line derived from normal rat intestinal crypts. Upon transfection of IEC-18 cells with ras or src, two oncogenes that are frequently activated in intestinal tumors, a significant induction of CD44s is observed. A causal role for ras in this induction is shown by using IEC clones transfected with an inducible ras expression vector. The oncogene-transformed IEC clones display a high degree of hyaluronic acid-dependent cell-cell adhesion that is not observed in the parental IEC-18 cells suggesting that ras- and src-induced overexpression of CD44 can alter the adhesion properties of intestinal cells.

Detection of occult lymphoma in the peripheral blood and bone marrow of patients with untreated early-stage and advanced-stage follicular lymphoma.

PURPOSE: The object of this study was to compare the relative sensitivities of morphologic, immunophenotypic, gene rearrangement, cytogenetic, and polymerase chain reaction (PCR) analyses in the detection of lymphoma cells in the bone marrow and peripheral blood of patients with follicular lymphoma. PATIENTS AND METHODS: Bone marrow and peripheral-blood samples from 28 newly diagnosed patients with follicular lymphoma referred from several different medical centers were assessed. Routine morphologic assessment was performed initially and the remainder of the sample was aliquoted for DNA extraction to be used for gene rearrangement and PCR analyses and for immunophenotypic and cytogenetic analyses where a sufficient amount of sample remained. RESULTS: Morphologic assessment of the bone marrow was positive for lymphoma cells in 11 of 28 patients. PCR amplification of t(14;18) breakpoint DNA detected lymphoma cells in 17 of 24 patients assessed. Morphologic assessment detected lymphoma cells in three bone marrow samples that were negative by PCR. PCR analysis was the only method able to detect circulating lymphoma cells in peripheral blood at diagnosis and was positive in 15 of 24 samples. The other methods of assessment did not show lymphoma in any samples in which lymphoma was not detected by morphologic or PCR analysis. Lymphoma cells were found in the bone marrow and/or peripheral blood as frequently in early-stage patients as in advanced-stage patients. CONCLUSION: PCR amplification of t(14;18) breakpoint DNA together with morphologic assessment had the highest yield of detecting lymphoma cells in the bone marrow and/or peripheral blood of our population of newly diagnosed patients with follicular lymphoma. The clinical significance and prognostic importance of lymphoma cells detected by PCR in the bone marrow and/or peripheral blood of newly diagnosed follicular lymphoma patients awaits long-term follow-up data of these and additional patients.

Sensitive and reproducible detection of occult disease in patients with follicular lymphoma by PCR amplification of t(14;18) both pre- and post-treatment.

The t(14;18) chromosomal translocation occurs in most follicular non-Hodgkin's lymphomas and places the Bcl-2 gene on chromosome 18q21 into the immunoglobulin JH region on chromosome 14q32. This translocation can be exploited to detect clonal malignant cells bearing this genetic alteration. A polymerase chain reaction (PCR) assay amplifying over the major breakpoint region (mbr) and minor cluster region (mcr) was developed and optimized. In this report, the sensitivity and reproducibility of this semiquantitative assay, performed on a relatively large number of clinical samples is shown. A titration curve of DNA made from a t(14;18)- cell line admixed with increasing ratios of a t(14;18)+ cell line was used to demonstrate that one t(14;18)+ cell in 100,000 t(14;18)- cells could reproducibly be detected. Occult lymphoma cells, not detected by standard morphologic analysis, were demonstrated in almost two-thirds of the bone marrow and peripheral blood specimens obtained from untreated patients with follicular lymphoma. Of 11 bone marrow samples assessed, seven were positive for occult disease by PCR amplification over the mbr and one was positive over the mcr. Of these six positive marrow samples, only three had been reported positive by standard morphologic criteria. In addition, seven of nine peripheral blood samples assessed were positive over the mbr and one additional sample was positive over the mcr. None of these were morphologically positive. Seven of the above patients would have been upstaged if these results were utilized for staging, including two of three patients with stage I or stage II disease. PCR-detectable occult disease persisted in four of four patients assessed both pre- and post-treatment, even after aggressive multi-drug combination chemotherapy in two of these patients. The clinical significance of detecting this occult disease must await the study of larger numbers of patients and the clinical outcomes of patients with occult disease and patients without occult disease.