Comparison of local risk factors for children's atopic symptoms in Hanoi, Vietnam.

BACKGROUND: A 1999 study in Hanoi, Vietnam using the International Study on Asthma and Allergies in Childhood (ISAAC) questionnaire showed a high prevalence of atopic symptoms. Identifying risk factors for symptoms in these children may help in understanding the causes for these high estimates. METHODS: An ISAAC questionnaire with supplemental questions on environmental variables was distributed to 5495 school children in Hanoi and a suburban district, Dong Anh. The response rate was 65.7%. RESULTS: In Dong Anh, the following were among the significant age and gender adjusted associations: pig ownership [odds ratio (OR) (95% confidence interval), OR = 1.79 (1.18-2.70) for doctor-diagnosed asthma (DDA), OR = 1.72 (1.08-2.78) for doctor diagnosed hay fever (DDHF)] and farming [OR = 1.67 (1.27-2.19) for ever asthma, OR = 1.51 (1.09-2.09) for DDHF]. In multivariate models, tuberculosis (TB) was a significant predictor of atopic symptoms [Hanoi: OR = 3.09 (1.10-8.70) for DDA, Dong Anh: OR = 3.71 (1.40-9.84) for DDA, OR = 4.66 (1.88-11.57) for DDHF]. CONCLUSIONS: These findings are contrary to the "hygiene hypothesis". Recent immunologic and epidemiologic studies refute the inverse association between allergy and TB and may be one explanation for the positive association in this study. The positive association with pig ownership and farming may be because of exposures on farms in a developing country that may be different from exposures in farms of developed countries.

An occupational risk survey of a refractory brick company in Ha Noi, Viet Nam.

Viet Nam has an increasing need for building materials, including refractory bricks. Little is known regarding the occupational hazards incurred in brick manufacturing. To determine the occupational health hazards posed by a refractory brick operation in Ha Noi, Viet Nam, a cross-sectional occupational risk survey was conducted, focusing on respirable dust hazards. It included an industrial hygiene walk-through and gravimetric dust analysis. Noise, heat, lack of head protection, and dust exposure were hazards identified at the brick-manufacturing site. Respiratory protection involved a three-layer cloth mask that had not been tested for efficacy. Silica dust exposure levels exceeded the Vietnamese permissible exposure level by almost fivefold based on gravimetric assessment and estimated silica content. This brick manufacturing site contains significant injury and respiratory illness hazards. Further investigations are necessary to begin to develop occupational safety measures at the site.

Pediatric environmental health: perceptions from a survey questionnaire.

To expand the base of knowledge regarding perceptions about potential environmental threats to children's health, a survey was conducted in the Northwest United States. Samples of Head Start parents, PTA presidents, public health officials, school nurses, naturopathic physicians, family practitioners, and pediatricians were mailed a questionnaire inquiring into the nature and degree of concerns about pediatric environmental health. The response rate was 24%. Trends in the data showed disparities in perceptions regarding levels of concern and exposure concerns between respondent categories. Disparities also existed regarding information resources used for children's environmental health. Recognizing differences in perceptions of children's environmental health, as demonstrated in these results, may be useful for risk communication and resource allocation, especially in the context of the wide variety of health belief models. Such knowledge may help clarity situations with environmental health risk concerns, including clinical, public health, and educational circumstances.

Constitutive activation of JAKs and STATs in BCR-Abl-expressing cell lines and peripheral blood cells derived from leukemic patients.

An important step in the oncogenic transformation of hemopoietic cells and the subsequent development of leukemia is the proliferation of tumor cells in the absence of exogenous growth factors. In most cases of chronic myelocytic leukemia and in some cases of acute myelocytic leukemia and acute lymphocytic leukemia, the bcr-abl oncogene is involved in this process. Although the BCR-Abl oncoprotein demonstrates enhanced tyrosine kinase activity in leukemic cells, the mechanism by which this leads to growth factor independence remains poorly defined. One proposed mechanism is the activation of cytokine signal transduction pathways, possibly by an autocrine loop involving IL-3 and/or granulocyte-macrophage CSF. Examination of several different cell lines expressing BCR-Abl demonstrates that some of these cells have constitutive activation of the JAK/STAT signaling pathway. We have found the constitutive activation of STAT5 in most, but not all, cell lines expressing BCR-Abl. This constitutive activation of STAT5 is variably associated with a corresponding activation of JAK kinases. Ab blocking studies show that the activation of STAT5 in these cell lines cannot be attributed to the activation of an IL-3/granulocyte-macrophage CSF-driven autocrine loop. Interestingly, samples of peripheral blood cells derived from patients with acute myelocytic leukemia and chronic myelocytic leukemia, which express BCR-Abl, demonstrate constitutive activation of STAT family members. These studies suggest that in a variety of leukemic states, BCR-Abl may use a bypass mechanism to activate cytokine signal transduction pathways.

VHDJH gene sequences and antigen reactivity of monoclonal antibodies produced by human B-1 cells: evidence for somatic selection.

To understand whether the distinct VHDJH gene utilization by natural polyreactive Abs reflects the developmentally restricted Ig VHDJH rearrangements putatively expressed by B-1 cells, we generated 11 (8 IgM, 1 IgG3, 2 IgA1), 7 (6 IgM, 1 IgG1), and 7 (2 IgM, 3 IgG1, 2 IgG3) mAb-producing lines using B-1a (surface CD5+, CD45RAlow), B-1b (surface CD5-, CD45RAlow, CD5 mRNA+), and B-2 (surface CD5-, CD45RAhigh, CD5 mRNA-) cells, respectively, sorted from adult human peripheral blood. Most B-1a and B-1b, but no B-2, cell-derived mAbs were polyreactive; i.e., they bound different self and foreign Ags with different affinities. B-1a and B-2 mAbs preferentially utilized VH4 (p = 0.003) and VH3 (p = 0.010) genes, respectively. All three mAb populations utilized DXP, DLR, DN DH genes, and JH6, but no mAb utilized DHQ52. There were fewer unencoded nucleotide (N) additions in the VHDJH junctions of B-1b (3.00 +/- 2.52, mean +/- SD) than of B-1a (12.45 +/- 3.93, p = 1.23 x 10(-5)) or B-2 (8.29 +/- 4.75, p = 0.020) mAbs. Partly due to the fewer N additions and a paucity of D-D fusions, the B-1b mAb CDR3s were significantly shorter than the B-1a mAb CDR3s (p = 0.013), which contained a nonrandom Tyr distribution (p = 0.003). Finally, all but two B-1 cell-derived mAbs were mutated, in a fashion similar to that of the Ag-selected B-2 mAbs. Thus, in the human adult, B-1 cells that make natural polyreactive Abs may not be representative of the predominantly B-1 developmental waves of colonization of the fetal and neonatal B cell repertoires, and are somatically selected.

Subtypes of losartan-sensitive angiotensin receptor in the rabbit pulmonary artery.

1. The short rabbit pulmonary artery was denuded of endothelium and divided into three sections, the cardiac end (cardiac), middle and pulmonary end (pulmonary) sections, respectively. Des-Asp-angiotensin I attenuated the contractions of the cardiac and middle sections to transmural nerve stimulation but potentiated the contractions in the pulmonary section. 2. The actions of the nonapeptide were inhibited completely by 10(-6) M losartan; however, a similar concentration of PD123319 had no effect. Indomethacin (10(-6) M) also inhibited completely the attenuation in the cardiac and middle sections but had no effect on the potentiation seen in the pulmonary section. 3. The data suggest that the two differential responses of the pulmonary artery to des-Asp-angiotensin I are mediated by two separate subtypes of the losartan-sensitive angiotensin AT1 receptor.

Immunogenic properties of multiple antigen peptide systems containing defined T and B epitopes.

Immunization with chemically defined synthetic polymers, multiple Ag peptide (MAP) systems, containing T and B epitopes of the circumsporozoite protein of P. berghei induce high levels of circulating antibodies that are detectable several months after boosting. The anti-MAP secondary antibody response is characterized by an increase in the levels of circulating IgG and a concomitant decrease in the IgM levels. In vitro and in vivo experiments indicated that Th epitopes included in the MAP are recognized by T cells induced after immunization with the native protein and, also, that MAP-induced T cells can recognize the native protein. In addition to high levels of anti-B epitope antibodies, MAP immunization also induces antibodies against the T epitope. This anti-T epitope immune response does not affect the generation of the anti-B epitope antibodies. Immunization of different strains of mice revealed that the antibody response is consistent with the genetically restricted pattern of recognition of the T epitope. There are, however, significant differences in the levels of antibody responses observed among responder strains. The findings of this study indicate that MAP are potent immunogens capable of inducing immunologic memory and are, thus, good candidates for the development of subunit vaccines designed to induce high levels of circulating antibodies.