Developmental toxicity of 1,2-dichloropropane (PDC) in rats and rabbits following oral gavage

The ST-16 antigenic specificity of the HLA-B locus is defined as a B39 variant of Mexican-Americans. Nucleotide sequencing of cDNA shows the ST-16 allele (B*3905) differs from B*39011 by a single substitution that substitutes tyrosine for aspartic acid at position 74 of the mature class I heavy chain. The complete coding region sequence for the common caucasoid allele encoding the B38 antigen has been determined. This B*3801 allele differs from B*3802 at two nucleotide substitutions within the Bw4 sequence motif. B*3801 and B*3802 may have been derived independently from B*39011 by conversion events with B alleles donating distinctive Bw4 motifs. A novel allele B*39022 derived from a Colombian Indian differs from the B*39021 allele of Japanese origin at two widely separated silent substitutions. Comparison of sequences for the known B16 alleles suggest that B*39021 and B*39022 were independently derived by recombination from B*39013 and B*39011 respectively.     

Serum HIV-1 RNA levels and time to development of AIDS in the Multicenter Hemophilia Cohort Study

Normal women produce small amounts of active androgens. When androgen levels are elevated, such as for example in the polycystic ovary syndrome, this is followed by the development of male physical characteristics and muscle mass, structure and function as well as android adipose tissue distribution and function. Psychological features and stress reactions also seem similar to those of men. Such women have an increased risk of developing hypertension, non-insulin-dependent diabetes mellitus and cardiovascular disease. Recent data have shown that these physical, and psychological characteristics, as well as risk of ill health, are also found in the population of women selected at random. Women in the lowest quintiles of levels of sex-hormone-binding globulin--an indicator inversely related to active androgens--are at risk of developing hypertension, non-insulin-dependent diabetes mellitus and cardiovascular mortality. The mechanism probably includes muscular insulin resistance, following a relative androgen excess. It is thus apparent that androgens, even within the highest levels of the nonselected population of women, are powerful predictors of serious disease development. The population at risk might be as large as about 20% of middle-aged women. This is an area of female disease risk which requires more attention in screening and intervention procedures.     

Mast cell activation is not required for induction of airway hyperresponsiveness by ozone in mice

Exposure to ambient ozone (O3) is associated with increased exacerbations of asthma. We sought to determine whether mast cell degranulation is induced by in vivo exposure to O3 in mice and whether mast cells play an essential role in the development of pulmonary pathophysiological alterations induced by O3. For this we exposed mast cell-deficient WBB6F1-kitW/kitW-v (kitW/kitW-v) mice and the congenic normal WBB6F1 (+/+) mice to air or to 1 or 3 parts/million O3 for 4 h and studied them at different intervals from 4 to 72 h later. We found evidence of O3-induced cutaneous, as well as bronchial, mast cell degranulation. Polymorphonuclear cell influx into the pulmonary parenchyma was observed after exposure to 1 part/milllion O3 only in mice that possessed mast cells. Airway hyperresponsiveness to intravenous methacholine measured in vivo under pentobarbital anesthesia was observed in both kitW/kitW-v and +/+ mice after exposure to O3. Thus, although mast cells are activated in vivo by O3 and participate in O3-induced polymorphonuclear cell infiltration into the pulmonary parenchyma, they do not participate detectably in the development of O3-induced airway hyperresponsiveness in mice.     

The role of state policies and programs in buffering the effects of poverty on children's immunization receipt

OBJECTIVES: This study assessed the influence of public policies on the immunization status of 2-year old children in the United States. METHODS: Up-to-dateness for the primary immunization series was assessed in a national sample of 8100 children from the 1988 National Maternal and Infant Health Survey and its 1991 Longitudinal Follow-Up. RESULTS: Documented immunization rates of this sample were 33% for poor children and 44% for others. More widespread Medicated coverage was associated with greater likelihood of up-to-dateness among poor children. Up-to-dateness was more likely for poor children with public rather than private sources of routine pediatric care, but all children living in states where most immunizations were delivered in the public sector were less likely to be up to date. Poor children in state with partial vaccine replacement programs were less likely to be up to date than those in free-market purchase states. CONCLUSIONS: While state policies can enhance immunization delivery for poor children, heavy reliance on public sector immunization does not ensure timely receipt of vaccines. Public- and private-sector collaboration is necessary to protect children from vaccine-preventable diseases.     

The material basis for reduced mechanical properties in oim mice bones

Osteogenesis imperfecta (OI), a heritable disease caused by molecular defects in type I collagen, is characterized by skeletal deformities and brittle bones. The heterozygous and homozygous oim mice (oim/+ and oim/oim) exhibit mild and severe OI phenotypes, respectively, serving as controlled animal models of this disease. In the current study, bone geometry, mechanics, and material properties of 1-year-old mice were evaluated to determine factors that influence the severity of phenotype in OI. The oim/oim mice exhibited significantly smaller body size, femur length, and moment of area compared with oim/+ and wild-type (+/+) controls. The oim/oim femur mechanical properties of failure torque and stiffness were 40% and 30%, respectively, of the +/+ values, and 53% and 36% of the oim/+ values. Collagen content was reduced by 20% in the oim/oim compared with +/+ bone and tended to be intermediate to these values for the oim/+. Mineral content was not significantly different between the oim/oim and +/+ bones. However, the oim/oim ash content was significantly reduced compared with that of the oim/+. Mineral carbonate content was reduced by 23% in the oim/oim bone compared with controls. Mineral crystallinity was reduced in the oim/oim and oim/+ bone compared with controls. Overall, for the majority of parameters examined (geometrical, mechanical, and material), the oim/+ values were intermediate to those of the oim/oim and +/+, a finding that parallels the phenotypes of the mice. This provides evidence that specific material properties, such as mineral crystallinity and collagen content, are indicative and possibly predictive of bone fragility in this mouse model, and by analogy in human OI.     

The effects of environmental conditions on the in vitro activity of selected antimicrobial agents against Escherichia coli

Serotonin (5-hydroxytryptamine, 5-HT) may play an important role in the pathogenesis of schizophrenia. Previous studies suggested that the efficacy of atypical neuroleptic drugs (e.g., risperidone and clozapine) on negative symptoms may be related to the 5-HT2a receptor. Although association studies between MspI polymorphism (T102C) and the 5-HT2a receptor gene and schizophrenia have been reported, their results are still controversial. The aim of this study was to examine the association between T102C polymorphism of the 5-HT2a receptor gene and schizophrenia as well as the association between the polymorphism and negative symptoms in a Japanese population (106 patients with schizophrenia and 109 healthy controls). No significant positive associations were observed. Our results suggest that the 5-HT2a receptor gene is not involved in the pathogenesis of schizophrenia or negative symptoms.     

Fat distribution and insulin response in prepubertal African American and white children

Ethnic differences in obesity-related disease prevalence may relate to differences in fat distribution or metabolism. We conducted a study in 73 African American and white children to examine the relation between fat distribution and insulin and to determine whether ethnic differences in fat distribution or in adiposity-insulin relations contribute to differences in insulin concentrations. Fasting and postchallenge insulin concentrations were determined by oral-glucose-tolerance test, total body fat by dual-energy X-ray absorptiometry, and subcutaneous abdominal (SAAT) and intraabdominal (IAAT) adipose tissue by computerized tomography. African Americans had greater fasting insulin (x +/- SD: 79 +/- 37 compared with 55 +/- 23 pmol/L, P < 0.01), incremental 30-min insulin (567 +/- 438 compared with 300 +/- 304 pmol/L, P < 0.001), and incremental area under the insulin curve (AUC; 262 +/- 209 compared with 164 +/- 156 pmol/L, P < 0.01). In multiple linear regression, fasting insulin was independently related to total fat within both ethnic groups (model R2 = 0.42 and 0.52 for African Americans and whites, respectively), incremental 30-min insulin to total fat and IAAT in whites only (model R2 = 0.71), and AUC to SAAT in African Americans only (model R2 = 0.49). Adjusting insulin indexes for adiposity did not eliminate the significant effect of ethnicity. In general, relations between adiposity and insulin were stronger in whites than in African Americans. African American children had higher insulin concentrations than white children after total body fat, IAAT, and SAAT were controlled for. However, strong relations between adiposity (total and abdominal) and insulin in both groups suggest that obesity may contribute to disease risk regardless of ethnicity.