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Biomedical subjects

B H Chang

Publications and source records attributed to B H Chang.

48 records · Page 3Linked to original sources
PubMed1994

Contrasting rates of nucleotide substitution in the X-linked and Y-linked zinc finger genes.

We have sequenced the entire exon (approximately 1.180 bp) encoding the zinc finger domain of the X-linked and Y-linked zinc finger genes (ZFX and ZFY, respectively) in the orangutan, the baboon, the squirrel monkey, and the rat; a total of 9,442 bp were sequenced. The ratio of the rates of synonymous substitution in the ZFY and ZFX genes is estimated to be 2.1 in primates. This is close to the ratio of 2.3 estimated from primate ZFY and ZFX intron sequences and supports the view that the male-to-female ratio of mutation rate in humans in considerably higher than 1 but not extremely large. The ratio of synonymous substitution rates in ZFY and ZFX is estimated to be 1.3 in the rat lineage but 4.2 in the mouse lineage. The former is close to the estimate (1.4) from introns. The much higher ratio in the mouse lineage (not statistically significant) might have arisen from relaxation of selective constraints. The synonymous divergence between mouse and rat ZFX is considerably lower than that between mouse and rat autosomal genes, agreeing with previous observations and providing some evidence for stronger selective constraints on synonymous changes in X-linked genes than in autosomal genes. At the protein level ZFX has been highly conserved in all placental mammals studied while ZFY has been well conserved in primates and foxes but has evolved rapidly in mice and rats, possibly due to relaxation of functional constraints as a result of the development of X-inactivation of ZFX in rodents. The long persistence of the ZFY-ZFX gene pair in mammals provides some insight into the process of degeneration of Y-linked genes.

Animals↗
PubMed1994

Intronic gene conversion in the evolution of human X-linked color vision genes.

Human red and green visual pigment genes are X-linked duplicate genes. To study their evolutionary history, introns 2 and 4 (1,987 and 1,552 bp, respectively) of human red and green pigment genes were sequenced. Surprisingly, we found that intron 4 sequences of these two genes are identical and that the intron 2 sequences differ by only 0.3%. The low divergences are unexpected because the duplication event producing the two genes is believed to have occurred before the separation of the human and Old World monkey (OWM) lineages. Indeed, the divergences in the two introns are significantly lower than both the synonymous divergence (3.2% +/- 1.1%) and the nonsynonymous divergence (2.0% +/- 0.5%) in the coding sequences (exons 1-6). A comparison of partial sequences of exons 4 and 5 of human and OWM red and green pigment genes supports the hypothesis that the gene duplication occurred before the human-OWM split. In conclusion, the high similarities in the two intron sequences might be due to very recent gene conversion, probably during evolution of the human lineage.

Animals↗
PubMed1993

Male-driven evolution of DNA sequences.

It is commonly believed that the mutation rate is much higher in the human male germ line than in the female germ line because the number of germ-cell divisions per generation is much larger in males than in females. But direct estimation of mutation rates is difficult, relying mainly on sex-linked genetic diseases, so the ratio (alpha m) of male to female mutation rates is not clear. It has been noted that if alpha m is very large, then the rate of synonymous substitution in X-linked genes should be only 2/3 of that in autosomal genes, and comparison of human and rodent genes supported this prediction. As the number of X-linked genes used in the study was small and the X-linked and autosomal sequences were non-homologous, and given that the synonymous rate varies among genes, we sequenced the last intron (approximately 1 kb) of the Y-linked and X-linked zinc-finger-protein genes (ZFY and ZFX) in humans, orang-utans, baboons and squirrel monkeys. The ratio Y/X of the substitution rate in the Y-linked intron to that in the X-linked intron is approximately 2.3, which is close to that estimated from synonymous rates in the ZFY and ZFX genes and implies alpha m approximately 6. This estimate of alpha m supports the view that the evolution of DNA sequences in higher primates is male-driven. It is, however, much lower than the previous estimate and therefore raises a number of issues.

Animals↗
PubMed1993

Potential problems in estimating the male-to-female mutation rate ratio from DNA sequence data.

It is commonly believed that the rate of mutation is much higher in males than in females because the number of germ-cell divisions per generation is much larger in males than in females. However, the precise magnitude of the male-to-female mutation rate ratio (alpha m) remains unknown. Recently there have been efforts to estimate alpha m by using DNA sequence data from different species. We have studied the potential problems in such an approach. We found that the rate of synonymous substitution varies about fivefold among X-linked genes, as large as the variation among autosomal genes. This large variation makes the assumption of selective neutrality of synonymous changes dubious, so one should be cautious in using the synonymous rates in X-linked and autosomal genes to estimate alpha m. A similar difficulty was also observed in using nonhomologous intron sequences to estimate alpha m. Contrary to the expectation that X-linked sequences should evolve more slowly than autosomal sequences, the Alu repeat in the last intron of the X-linked zinc finger gene has evolved faster than the four autosomal Alu repeats used in this study. It appears that the best way to estimate alpha m is to use homologous sequences. However, such sequences may be involved in gene conversion events. In fact, we found evidence that the Y-linked and X-linked zinc finger genes have been involved in multiple conversion events during primate evolution. Thus, the possibility of gene conversion should be considered when using homologous sequences to estimate alpha m.

Animals↗
PubMed1993

A new method for making interstate comparisons of highway fatality rates.

Highway fatality rates vary significantly among jurisdictions. Before attributing these variations to policy differences, it is important to account for exogenous factors (e.g. weather) that are beyond the control of policy makers. A new method is developed to identify states that are doing better or worse than expected. The method is applied to the 48 contiguous American states using highway fatality data for the years 1975 to 1986. A fixed effects linear model is used to estimate the fatality rate for each state, taking into account exogenous factors. Results indicate that many states have higher or lower fatality rates than is expected based on a ranking of states according to crude fatality rates. Policy implications are discussed.

Accidents, Traffic↗
PubMed1993

The essential mitotic target of calmodulin is the 110-kilodalton component of the spindle pole body in Saccharomyces cerevisiae.

Two independent methods identified the spindle pole body component Nuf1p/Spc110p as the essential mitotic target of calmodulin. Extragenic suppressors of cmd1-1 were isolated and found to define three loci, XCM1, XCM2, and XCM3 (extragenic suppressor of cmd1-1). The gene encoding a dominant suppressor allele of XCM1 was cloned. On the basis of DNA sequence analysis, genetic cosegregation, and mutational analysis, XCM1 was identified as NUF1/SPC110. Independently, a C-terminal portion of Nuf1p/Spc110p, amino acid residues 828 to 944, was isolated as a calmodulin-binding protein by the two-hybrid system. As assayed by the two-hybrid system, Nuf1p/Spc110p interacts with wild-type calmodulin and triple-mutant calmodulins defective in binding Ca2+ but not with two mutant calmodulins that confer a temperature-sensitive phenotype. Deletion analysis by the two-hybrid system mapped the calmodulin-binding site of Nuf1p/Spc110p to amino acid residues 900 to 927. Direct binding between calmodulin and Nuf1p/Spc110p was demonstrated by a modified gel overlay assay. Furthermore, indirect immunofluorescence with fixation procedures known to aid visualization of spindle pole body components localized calmodulin to the spindle pole body. Sequence analysis of five suppressor alleles of NUF1/SPC110 indicated that suppression of cmd1-1 occurs by C-terminal truncation of Nuf1p/Spc110p at amino acid residues 856, 863, or 881, thereby removing the calmodulin-binding site.

Binding Sites↗
PubMed1992

Poorer is riskier.

To examine the relationship between economic well being and health status, two economic concepts were explored: the permanent-income hypothesis and the transitory-income hypothesis. A regression analysis of time-series mortality data for the period of 1950-1988 was conducted. The regression results indicated that the total mortality rate is negatively associated with permanent income and positively associated with the transitory income. Results are also reported for the 8 major causes of death in the United States. The implications for risk analysis are discussed.

Health Status↗
PubMed1991

The cost of medical care for injuries to children.

STUDY OBJECTIVES: To estimate the mean cost of initial medical treatment for a variety of injury types and injury causes and project the national cost of initial medical care for injuries to children. DESIGN: We combined injury incidence data from the Massachusetts Statewide Childhood Injury Prevention Project (SCIPP) with a claims data set (1987 charges) from the Health Data Institute, Lexington, Massachusetts. SETTING AND STUDY POPULATION: SCIPP incidence data were obtained from hospital emergency department and inpatient facilities for a population of 87,000 Massachusetts children 0 to 19 years old between 1979 and 1982. Health Data Institute charge data for children were derived from insurance claims for 3% of all privately insured patients throughout the United States. RESULTS: The estimated mean cost of initial hospitalization for injury was $5,094, while ED care was $171. Projected annual cost for initial medical care of injury to children for the nation was $5.1 billion, which was about equally divided between cases seen in EDs and those requiring inpatient care. Although there was little difference in mean cost between the genders, mean cost increased with age. Because of both a higher injury incidence and a greater mean cost per injury, the projected initial cost of injuries to teenagers 15 to 19 years old was much higher than that of younger children. CONCLUSION: Expenditures for medical care of injured children, particularly adolescents, are great. The prevention of childhood injuries should become a higher priority in the United States. To improve the quality of national estimates of the incidence and cost of injury, a national surveillance system for nonfatal injuries should be developed. Such a system should include information on the major causes of injury and their costs.

Adolescent↗
PubMed1989

Prevention of childhood injuries: evaluation of the Statewide Childhood Injury Prevention Program (SCIPP).

We evaluated the effectiveness of a community-based injury prevention program designed to reduce the incidence of burns, falls in the home, motor vehicle occupant injuries, and poisonings and suffocations among children ages 0-5 years. Between September 1980 and June 1982, we implemented five injury prevention projects concurrently in nine Massachusetts cities and town; five sites, matched on selected demographic characteristics, were control communities. An estimated 42 percent of households with children ages 0-5 years were exposed to one or more of the interventions over the two-year period in the nine communities. Participation in safety programs increased three-fold in the intervention communities and two-fold in the control communities. Safety knowledge and practices increased in both intervention and control communities. Households that reported participatory exposure to the interventions had higher safety knowledge and behavior scores than those that received other community exposure or no exposure to intervention activities. We found a distinct reduction in motor vehicle occupant injuries among children ages 0-5 years in the intervention compared with control communities, associated with participatory exposure of about 55 percent of households with children ages 0-5 years. We have no evidence that the coordinated intervention programs reduced the other target injuries--although exposure to prevention messages was associated with safety behaviors for burns and poisonings.

Accident Prevention↗
PubMedDate not supplied

Risk adjustment for measuring health outcomes: an application in VA long-term care.

An empirically derived risk adjustment model is useful in distinguishing among facilities in their quality of care. We used Veterans Affairs (VA) administrative databases to develop and validate a risk adjustment model to predict decline in functional status, an important outcome measure in long-term care, among patients residing in VA long-term care facilities. This model was used to compare facilities on adjusted and unadjusted rates of decline. Predictors of decline included age, time between assessments, baseline functional status, terminal illness, pressure ulcers, pulmonary disease, cancer, arthritis, congestive heart failure, substance-related disorders, and various neurologic disorders. The model performed well in the development and validation databases (c statistics, 0.70 and 0.68, respectively). Risk-adjusted rates and rankings of facilities differed from unadjusted ratings. We conclude that judgments of facility performance depend on whether risk-adjusted or unadjusted decline rates are used. Valid risk adjustment models are therefore necessary when comparing facilities on outcomes.

Aged↗