Influence of type of dwelling on the prevalence of chronic respiratory diseases in Ho Chi Minh City, Viet Nam.

SETTING and OBJECTIVE: Exposure to pollutants is related to the type of dwelling inhabited. Besides tobacco smoke, indoor air pollution is a significant risk factor for chronic respiratory disease (CRD). The prevalence of CRD by type of dwelling was studied in Ho Chi Minh City, Viet Nam.DESIGN: A total of 1561 people living in four type of dwellings were enrolled. Information on respiratory health, lung function, dwelling characteristics and sources of indoor pollution was obtained using a symptom and demographics questionnaire and spirometry. The two main respiratory health outcomes were clinical chronic CRD (CCRD) and chronic obstructive respiratory disease (CORD) (forced expiratory volume in 1 sec/forced vital capacity <0.7). We used binary logistic regression adjusted for age, sex, time spent at home, smoking status, certain occupational exposures, previous tuberculosis, presence of pets, rats or cockroaches at home, wall dampness, biofuel use and use of airconditioning.RESULTS: The prevalence of CCRD (24.3%) and CORD (5.3%) in the type of dwellings studied were not similar (χ² P < 0.0001). CCRD and CORD prevalence was similar in tube houses and apartments. Compared to people living in apartments, those living in rental single rooms had a 46% higher risk of developing CCRD. The odds ratio of having CORD in people living in rental single rooms and in rural houses were respectively 4.64 (95%CI 1.97-10.5) and 2.99 (95%CI 1.21-7.37).CONCLUSION: Type of dwelling was associated with CCRD and CORD morbidity.

Synthetic radiation-inducible promoters mediated HSV-TK/GCV gene therapy in the treatment of oral squamous cell carcinoma.

OBJECTIVE: To investigate the therapeutic effect of herpes simplex virus thymidine kinase (HSV-TK) gene mediated by synthetic radiation-inducible promoters in the treatment of oral squamous cell carcinoma (OSCC) in vitro and in vivo. METHODS: The plasmids pcDNA3.1(+)E6-HSV-TK were constructed, in which the HSV-TK genes were mediated by synthetic radiation-inducible promoters. The recombined plasmids were transfected into the Tca8113 cells and golden hamster buccal carcinoma, respectively. Low-dose radiotherapy was used to upregulate the HSV-TK genes expression. HSV-TK mRNA was assayed by RT-PCR. Apoptosis and proliferating cell nuclear antigen were detected respectively by in situ end-labeling and immunohistochemical method. RESULTS: Compared with control group, the comparative survival rate of Tca8113 cells in HSV-TK/GCV/IR group was markedly decreased and the golden hamster buccal carcinoma in HSV-TK/GCV/IR group was obviously suppressed. Up-regulation of HSV-TK gene expression was found in the Tca8113 cells and in the golden hamster buccal carcinoma resulting from exposure to low-dose irradiation. The apoptosis indexes in Tca8113 cells or golden hamster buccal carcinoma with irradiation were markedly higher than those without irradiation. At the same time, the proliferation indexes in Tca8113 cells or golden hamster buccal carcinoma with irradiation were markedly lower than those without irradiation. CONCLUSION: The results indicate that the synthetic radiation-inducible promoters can serve as a molecular switch to adjust the expression of HSV-TK gene in the treatment of OSCC, and low-dose induction radiation can significantly improve therapeutic efficiency.

Appropriate use of personal protective equipment among healthcare workers in public sector hospitals and primary healthcare polyclinics during the SARS outbreak in Singapore.

BACKGROUND: Singapore was affected by an outbreak of severe acute respiratory syndrome (SARS) from 25 February to 31 May 2003, with 238 probable cases and 33 deaths. AIMS: To study usage of personal protective equipment (PPE) among three groups of healthcare workers (HCWs: doctors, nurses, and administrative staff), to determine if the appropriate PPE were used by the different groups and to examine the factors that may determine inappropriate use. METHODS: A self-administered questionnaire survey of 14,554 HCWs in nine healthcare settings, which included tertiary care hospitals, community hospitals, and polyclinics, was carried out in May-July 2003. Only doctors, nurses, and clerical staff were selected for subsequent analysis. RESULTS: A total of 10 236 valid questionnaires were returned (70.3% response); 873 doctors, 4404 nurses, and 921 clerical staff were studied. A total of 32.5% of doctors, 48.7% of nurses, and 77.1% of the administrative staff agreed that paper and/or surgical masks were "useful in protecting from contracting SARS". Among this group, 23.6% of doctors and 42.3% of nurses reported working with SARS patients. The view that a paper and/or surgical mask was adequate protection against SARS was held by 33.3% of doctors and 55.9% of nurses working at the A&E unit, 30.5% of doctors and 49.4% of nurses from medical wards, and 27.5% of doctors and 37.1% of nurses from intensive care units. Factors which predicted for agreement that paper and/or surgical masks were protective against SARS, included HCW's job title, reported contact with SARS patients, area of work, and Impact Events Scale scores. CONCLUSION: A variety of factors determine appropriate use of personal protective equipment by HCWs in the face of a major SARS outbreak.

Coping responses of emergency physicians and nurses to the 2003 severe acute respiratory syndrome outbreak.

OBJECTIVES: During the 2003 severe acute respiratory syndrome (SARS) outbreak, health care workers (HCWs) experienced unusual stressors. The study hospital introduced psychosocial interventions to help HCWs. This study aimed to examine the coping strategies adopted by the emergency department (ED) HCWs who cared for the SARS patients. METHODS: In November 2003, a self-administered questionnaire of physicians and nurses was conducted in the hospital ED that is the national SARS screening center in Singapore. Data collected included demographics and responses to these instruments: 1) the Coping Orientation to Problems Experienced (COPE) to assess coping strategies, 2) the Impact of Event Scale (IES) to measure psychological reactions, and 3) the General Health Questionnaire 28 (GHQ 28) to measure psychiatric morbidity. RESULTS: Thirty-eight of 41 (92.7%) physicians and 58 of 83 (69.9%) nurses responded. The respondents reported a preference for problem-focused and emotion-focused coping measures. The physicians chose humor as a coping response significantly more frequently (p < 0.001) than nurses, scoring 9.61/16 (95% CI = 8.52 to 10.69), compared with the nurses' score of 7.05/16 (95% CI = 6.28 to 7.83). The Filipino HCWs turned to religion as a coping response significantly more frequently (p < 0.001) than the non-Filipino HCWs, scoring 14.38/16 (95% CI = 13.33 to 15.42), compared with 9.93/16 (95% CI = 9.00 to 10.87) for the non-Filipinos. Psychiatric morbidity was 17.7% on the IES and 18.8% on the GHQ 28, with the trend for physicians to report lower psychiatric morbidity. CONCLUSIONS: With a supportive hospital environment, ED HCWs chose adaptive coping in response to the outbreak and reported low psychiatric morbidity. Physicians chose humor and Filipinos chose turning to religion as their preferred responses. Psychosocial interventions to help HCWs need to take these preferences into account.

Mapping quantitative trait loci in oligogenic models.

We discuss strategies for mapping quantitative trait loci with emphasis on certain issues of study design that have recently received attention: e.g. genotyping only selected pedigrees and the comparative value of large pedigrees versus sib pairs. We use a standard variance components model and a parametrization of the genetic effects in which the 'segregation' parameters are locally orthogonal to the 'linkage' parameters. This permits simple explicit expressions for the expectation of the score statistic, which we use to compare the power of different strategies. We also discuss robustness of the score statistic.

Modulation of PAX6 homeodomain function by the paired domain.

PAX6 is required for proper development of the eye, central nervous system, and nose. PAX6 has two DNA binding domains, a glycine-rich region that links the two DNA binding domains, and a transactivation domain. There is evidence that the different DNA binding domains of PAX6 have different target genes. However, it is not clear if the two DNA binding domains function independently. We have studied the effect of structural changes in the paired domain on the function of PAX6 mediated through its homeodomain. The R26G and I87R mutations have been reported in different human patients with clinically different phenotypes and are in the N- and the C-terminal halves of the paired domain, respectively. Surprisingly, we found that the I87R mutant protein not only lost the transactivation function but also failed to bind DNA by either of its DNA binding domains. In contrast, the R26G mutant protein lost DNA binding through its paired domain but had greater DNA binding and transactivation than wild-type PAX6 on homeodomain binding sites. Like R26G, the 5a isoform showed higher DNA binding than wild-type PAX6. This study demonstrates that the two subdomains of the paired domain influence the function of the homeodomain differentially and also provides an explanation for the difference in phenotypes associated with these mutations.

Legibility of video-blended TV menus.

This article describes three experiments relating to the legibility of TV menus. Special emphasis is placed on the influence of a relatively new feature in TVs: the possibility to blend graphics and video. Three experiments are presented: one concentrating on the influences of blending level and video content; one concentrating on the influences of content and of colour combinations; and one concentrating on the influences of various font characteristics. The results are interpreted in terms of guidelines for blended TV menus.

Truncation mutations in the transactivation region of PAX6 result in dominant-negative mutants.

PAX6 is a transcription factor with two DNA-binding domains (paired box and homeobox) and a proline-serine-threonine (PST)-rich transactivation domain. PAX6 regulates eye development in animals ranging from jellyfish to Drosophila to humans. Heterozygous mutations in the human PAX6 gene result in various phenotypes, including aniridia, Peter's anomaly, autosomal dominant keratitis, and familial foveal dysplasia. It is believed that the mutated allele of PAX6 produces an inactive protein and aniridia is caused due to genetic haploinsufficiency. However, several truncation mutations have been found to occur in the C-terminal half of PAX6 in patients with Aniridia resulting in mutant proteins that retain the DNA-binding domains but have lost most of the transactivation domain. It is not clear whether such mutants really behave as loss-of-function mutants as predicted by haploinsufficiency. Contrary to this theory, our data showed that these mutants are dominant-negative in transient transfection assays when they are coexpressed with wild-type PAX6. We found that the dominant-negative effects result from the enhanced DNA binding ability of these mutants. Kinetic studies of binding and dissociation revealed that various truncation mutants have 3-5-fold higher affinity to various DNA-binding sites when compared with the wild-type PAX6. These results provide a new insight into the role of mutant PAX6 in causing aniridia.

Dissection of the transactivation function of the transcription factor encoded by the eye developmental gene PAX6.

PAX6 is a transcription activator that regulates eye development in animals ranging from Drosophila to human. The C-terminal region of PAX6 is proline/serine/threonine-rich (PST) and functions as a potent transactivation domain when attached to a heterologous DNA-binding domain of the yeast transcription factor, GAL4. The PST region comprises 152 amino acids encoded by four exons. The transactivation function of the PST region has not been defined and characterized in detail by in vitro mutagenesis. We dissected the PST domain in two independent systems, a heterologous system using a GAL4 DNA-binding site and the native system of PAX6. Our data consistently showed that in both systems all four constituent exons of the PST domain are responsible for the transactivation function. The four exon fragments act synergistically to stimulate transcription, although none of them can function individually as an independent transactivation domain. Combinations of two or more exon fragments can reconstitute substantial transactivation activity when fused to the DNA-binding domain of GAL4, but they surprisingly do not produce much activity in the context of native PAX6, although the mutant PAX6 proteins are stable and their DNA-binding function remains unaffected. Our data suggest that these mutants may antagonize the wild-type PAX6 activity by competing for target DNA-binding sites. We conclude that the PAX6 protein contains an unusually large transactivation domain that is evolutionarily conserved to a high degree and that its full transactivation activity relies on the synergistic action of the four exon fragments.

Functional analysis of paired box missense mutations in the PAX6 gene.

Mutations in the human PAX6 gene produce various phenotypes, including aniridia, Peters' anomaly, autosomal dominant keratitis and familial foveal dysplasia. The various phenotypes may arise from different mutations in the same gene. To test this theory, we performed a functional analysis of two missense mutations in the paired domain: the R26G mutation, previously reported in a case of Peters' anomaly, and an unreported I87R mutation, which we identified in a patient with aniridia. While both the R26 and the I87 positions are conserved in the paired boxes of all known PAX genes, X-ray crystallography has shown that only R26 makes contact with DNA. We showed that the R26G mutant failed to bind a subset of paired domain binding sites but, surprisingly, bound other sites and successfully transactivated promoters containing those sites. In contrast, the I87R mutant had lost the ability to bind DNA at all tested sites and failed to transactivate promoters. Our data support the haploid-insufficiency hypothesis of aniridia, and the hypothesis that R26G is a hypomorphic allele.

[Determination of thermograms of bacterial growth].

The fundamental growth thermograms of bacteria have been determined by using the microcalorimetric method. These perfect thermogram curves reflect the changes of bacterial growth patterns (including the lag phase of growth, log growth, stationary phase and the decline phase of growth). In our experiments, highly characteristic and reproducible growth patterns are observed under the same condition, therefore one can use these thermograms as "finger print" to discriminate bacteria. On the other hand, there thermogram curves contain ample information, which are very significant for the studies on microorganism metabolism, bio-thermokinetic and clinical fields.

Solid-phase radioimmunoassay with protein-A-bearing Staphylococcus aureus cells used to assay a protein (ferritin) and a hapten (digoxin).

We compared use of protein-A-containing Staphylococcus aureus bacteria with conventional ammonium sulfate precipitation and second-antibody methods of separating bound and free antigen in the radioimmunoassay of a hapten (digoxin) and protein (ferritin) in human sera. In each case, values obtained with the heat-killed, formalin-fixed bacteria correlated well with those found by established methods. No matrix effects were detected in either hapten or protein measurements. Because of the affinity of S. aureus for rabbit IgG, rabbit antisera could be used with a small number of bacteria to detect antigen in the presence of 50-fold excess human IgG. The availability of S. aureus and ease of handling make this reagent a rapid, economical alternative of general applicability in radioimmunoassay.