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Biomedical subjects

W Hsiao

Publications and source records attributed to W Hsiao.

11 recordsLinked to original sources
PubMed1998

Transformation of ministries of health in the era of health reform: the case of Colombia.

Ministries of health are being called upon to lead major health reforms; at the same time they must reform themselves to become more modern institutions and assume new and different functions and roles in the more dynamic reformed system. The literature on public administration and on health reform has recommended many processes of institutional reform and development, building on private sector management techniques, popularized by 'reinventing government' and 'total quality management'. More recently, thoughtful insights have emphasized improving public management through a focus on creating 'public value'; on political, as well as administrative, leadership; improving institutional performance through strengthening the 'task networks' of organizations needed to achieve strategic objectives; and creating a learning culture within the organization. This article applies these recent approaches to the specific needs of ministries of health in order to improve their capacity to lead major health reforms. This combined approach is then used to analyze and make recommendations to the Ministry of Health in Colombia where the authors were providing technical support for a major new health reform.

Colombia↗
PubMed1994

Ethnic distribution of the glutathione transferase Mu 1-1 (GSTM1) null genotype in 1473 individuals and application to bladder cancer susceptibility.

Polycyclic aromatic hydrocarbons, found in cigarette smoke, food and industrial materials, are potential human carcinogens. Deficiency of detoxifying enzymes, such as glutathione transferases, may affect the metabolic fates of these chemicals and raise cancer risks in exposed individuals. The GSTM1 null genotype is a common form of glutathione transferase deficiency. Because knowledge of its ethnic distribution would be useful in epidemiologic studies, we measured the frequencies of the GSTM1 null genotype among healthy blacks, whites, Asian Indians, Chinese, Japanese, Koreans, Filipinos, Samoans and Hispanics. Rapid genotyping was done by use of a PCR assay, with dried blood spots on blotter paper as DNA templates. The frequency of the null genotype ranged from 0.31 among blacks to 0.88 among Samoans. The PCR assay was also applied to a pilot study of 114 bladder cancer cases from Kaiser Permanente Medical Center, Harbor City, California. DNA for these cases was obtained from paraffin-embedded surgical specimens. The overall odds ratio for bladder cancer with the GSTM1 null genotype was 1.4 (95% confidence interval 0.94-2.1), indicating no statistical difference in null genotype frequencies among bladder cancer patients compared to a healthy population. Large epidemiologic studies, which can be accomplished with dried blood spots or paraffin-embedded tissue specimens, may be useful for further assessment.

Adolescent↗
PubMed1992

Small-group judgment methods for determining resource-based relative values.

National telephone surveys used in the Resource-Based Relative Value Scale Study produce reliable and valid relative values of work, but phone surveys are expensive and time consuming. We evaluated three small-group processes as alternatives. We compared national survey work estimates for 38 surgical services to those generated by panels of 11 and 19 highly qualified general surgeons using 1) single-round mail survey; 2) Delphi multiple-round ratings; and 3) modified Delphi with face-to-face discussion. Single-round mail-survey ratings were closest to the national survey; average differences were 11.0% and 12.6%. Delphi feedback led to increased differences: typical values differed by 14.6% and 15.2%. Face-to-face discussion led to still further divergence (21.0%). Single-round mail survey of a small number of experts provides relative work values that compare more favorably to those of the national survey than those obtained from Delphi multiple-round ratings or modified Delphi with face-to-face discussion.

Data Collection↗
PubMed1990

Influence of cholesterol oxides on endocytosis of cultured endothelial and smooth muscle cells.

Human umbilical vein endothelial cells and rabbit aortic smooth muscle cells in culture were incubated for intervals up to 24 hrs with varying concentrations of cholesterol, 7-ketocholesterol, 25-hydroxycholesterol, cholestane-3 beta,5 alpha,6 beta-triol or cholesterol-5 alpha, 6 beta-epoxide. Endocytosis, as measured by uptake of horseradish peroxidase (HRP), was inhibited in a dose and time dependent manner in both endothelial and smooth muscle cell cultures by cholestane-3 beta,5 alpha,6 beta-triol and 25-hydroxycholesterol. Inhibition by 7-ketocholesterol in endothelial cells occurred only at higher concentrations, and cholesterol and cholesterol epoxide showed no significant inhibitory effects. The viability of the cells exposed to the cholesterol oxides at the concentrations that inhibited the uptake of HRP was not changed. Cholesterol oxides induce functional endothelial injury, not morphologically apparent, which may be involved in atherogenesis.

Animals↗
PubMed1986

Studies on the mechanism of action of protein kinase C and the isolation of molecular clones encoding the enzyme.

Protein kinase C (PKC) plays an important role in signal transduction and the action of phorbol ester tumor promoters, and it is of interest to isolate the coding sequence of this enzyme. Using a 53-base pair synthetic oligonucleotide probe that corresponds to an 18-amino acid peptide obtained from rat brain PKC, we have isolated rat brain cDNA clones corresponding to PKC. We have also isolated several closely related clones. Partial nucleotide sequence analysis of one of the PKC clones (RP41) identifies a 224-amino acid region with approximately 40% homology to the carboxy terminal and catalytic domains of both the cAMP-dependent and cGMP-dependent protein kinases. The levels of mRNA homologous to RP41 are very high in brain; very low but detectable levels are present in heart and liver. A second cDNA (RP16) was only partially sequenced, and based on its predicted amino acid sequence, it shares 65% homology with the corresponding region of the PKC clone RP41. The levels of mRNA corresponding to RP16 are also highest in rat brain, but they are of a different size than those detected with RP41. These and additional results indicate that the gene for the enzyme PKC shares considerable homology with other protein kinases and that PKC itself may belong to a new multigene family. The availability of these cDNA clones should greatly facilitate further studies on the role of PKC in growth control, differentiation, and multistage carcinogenesis.

Amino Acid Sequence↗
PubMed1985

Mechanisms of multistage chemical carcinogenesis and their relevance to respiratory tract cancer.

The evolution of a fully malignant tumor is a multistep process resulting from the action of multiple factors, both environmental and endogenous, and involves alterations in the function of multiple cellular genes. Chemical carcinogens that initiate this process appear to do so by damaging cellular DNA. In addition to producing simple point mutations, this damage appears to induce the synthesis of a transacting factor that can induce asynchronous DNA replication. This response may result in gene amplification and/or gene rearrangement. This phenomenon may also play a role in synergistic interactions between chemicals and viruses in the causation of certain cancers. The primary target of the tumor promoters TPA, teleocidin, and aplysiatoxin appears to be cell membranes. All three of these agents act, at least in part by, enhancing the activity of the phospholipid-dependent enzyme PKC. We have proposed a stereochemical model to explain the interaction of these amphiphilic compounds with the PKC system. We have found that TPA and teleocidin markedly enhance the transformation of C3H10T1/2 mouse fibroblasts when these cells are transfected with the cloned H-ras human bladder cancer oncogene. Thus, tumor promoters can act synergistically with an activated oncogene to enhance cell transformation. Furthermore, carcinogen-transformed rodent cells display aberrations in the expression of various endogenous retrovirus-related sequences. Activation of some of these sequences may lead to insertion mutations and further aberrations in gene expression. These findings are discussed in terms of a multistep model that involves progressive changes in cellular oncogenes and aberrations in the function of DNA transcription enhancer sequences. It will be of interest to determine to what extent these concepts apply to the etiology of cancers of the respiratory tract.

Animals↗
PubMed1984

Cellular targets and host genes in multistage carcinogenesis.

Recent studies indicate that although cellular DNA is the critical target in the action of initiating carcinogens, specific membrane-associated receptors mediate the actions of certain tumor promoters. A stereochemical model is presented to explain how three different types of tumor promoters (phorbol esters, indole alkaloids, and polyacetates) can interact with the same class of cellular receptors. Multistage chemical carcinogenesis might involve progressive alterations in the expression of cellular DNA sequences homologous to oncogenes and regulatory sequences in certain retroviruses. We found that the oncogene c-mos is not rearranged or expressed in a series of carcinogen-transformed murine C3H 10T112 cells. These cells do express, however, a unique set of poly(A)+ RNAs that contain sequences homologous to the Moloney leukemia virus long terminal repeat sequence. Studies are in progress to determine the significance of this finding with respect to the carcinogenic process.

Animals↗