Biomedical subjects
Publications and source records attributed to D Wood.
A case of acute oliguric renal failure due to bilateral renal artery occlusion is described. The renal function was restored to normal 36 h after the embolic event by revascularization with streptokinase.
We abstracted 752 randomly selected records of 2-year-old children at 5 public health centers in Los Angeles. Only 27% of the children were up-to-date in their vaccinations by 2 years of age. Being up-to-date was strongly associated with the number of missed opportunities to vaccinate and number of well child visits. Missed opportunities to vaccinate occurred during 52% of all visits and were associated with minor illness diagnoses and inaccurate immunization status assessment by nurses. Frequent missed opportunities to vaccinate and inadequate numbers of well child visits may result in low immunization levels among children attending public health clinics.
OBJECTIVE: To identify factors associated with undervaccination at 3 months and 24 months among low-income, inner-city Latino and African-American preschool children. DESIGN: Interviews with a representative sample of inner-city families using a cross-sectional, multi-stage, cluster-sample design combined with a replicated quota sampling approach. SETTING: South Central and East Los Angeles areas in inner-city Los Angeles. POPULATION: Eight hundred seventeen Latino and 387 African-American families with children between 12 and 36 months of age. MAIN OUTCOME VARIABLES: Being fully immunized or up-to-date (UTD) at 3 months (1 diphtheria-tetanus-pertussis vaccine and 1 oral polio vaccine) and 24 months of age (4 diphtheria-tetanus-pertussis vaccines, 3 oral polio vaccines, and 1 measles-mumps-rubella vaccine). METHODS: Logistic regressions of UTD immunization status at 3 and 24 months by population and health care system factors. RESULTS: Seventy percent of Latino children and 53% of African-American children were UTD at 3 months of age. At 24 months of age, 42% of Latino children and 26% of African-American children were UTD on their immunizations. Receipt of the first immunizations by 3 months was associated with smaller family size, and evidence of connection to prenatal care. Latino children were less likely to be UTD at 24 months if they obtained well child care from private providers versus public clinics (odds ratio [OR] = 0.45, 95% confidence interval [CI] = 0.26, 0.79). There was also a trend for Latino children to be less well immunized if they were in health maintenance organizations versus public clinics (0.31, 0.05 < P < .1). African-American children were more likely to be UTD at 24 months if they were UTD at 3 months (OR = 5.56, 95% CI = 1.43, 21.6), had more health visits (OR = 1.13, 95% CI = 1.01, 1.27), and were less likely to be UTD at 24 months if they were on Medicaid versus private insurance (OR = 0.26, 95% CI = 0.08, 0.90). IMPLICATIONS: Both African-American and Latino children in inner-city Los Angeles have low immunization rates at 3 and 24 months. Prenatal care and family size are strongly associated with being UTD by 3 months; however, family and child characteristics are relatively unimportant predictors of being UTD at 24 months of age. Important risk factors for underimmunization at 2 years of age in the inner-city, low-income communities studied include type of health insurance and source of well child care, with the public sector having higher rates than private doctors' offices or health maintenance organization/managed care plans.
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This is a two-year progress report on a life span dose-response study of brain tumor risk at moderate to high doses of energetic protons. It was initiated because a joint NASA/USAF life span study of rhesus monkeys that were irradiated with 55-MeV protons (average surface dose, 3.5 Gy) indicated that the incidence of brain tumors per unit surface absorbed dose was over 19 times that of the human tinea capitis patients whose heads were exposed to 100 kv x-rays. Examination of those rats that died in the two-year interval after irradiation of the head revealed a linear dose-response for total head and neck tumor incidence in the dose range of 0-8.5 Gy. The exposed rats had a greater incidence of pituitary chromophobe adenomas, epithelial and mesothelial cell tumors than the unexposed controls but the excessive occurrence of malignant gliomas that was observed in the monkeys was absent in the rats. The estimated dose required to double the number of all types of head and neck tumors was 5.2 Gy. The highest dose, 18 Gy, resulted in high mortality due to obstructive squamous metaplasia at less than 50 weeks, prompting a new study of the relative biological effectiveness of high energy protons in producing this lesion.
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California plans to enroll half of its Medicaid population, 75 percent of which are children, into managed care. To measure the impact of managed care on utilization of preventive services, we surveyed 867 families in two inner-city areas of Los Angeles and assessed the relationship between insurance type, source of care, and access to immunization services. Compared to children in public health clinics, those in private physicians' offices or health maintenance organizations (HMOs) had odds of being up-to-date on immunizations of 0.43 (p < .01) and 0.24 (p < .01), respectively. We conclude that in the absence of meaningful financial incentives to encourage private physicians and HMOs to provide immunizations to inner-city children, managed care is unlikely to improve immunization rates among this vulnerable population.
OBJECTIVE: The United States is a highly mobile society, with family relocation rates double those of Great Britain and Germany. The objective of this study was to describe the impact of frequent family moves on reported rates of delay in growth or development, learning disorders, school failure, and frequent behavioral problems in US school-age children. DESIGN AND SETTING: We analyzed data on 9915 six- to 17-year-old children of families responding to the 1988 National Health Interview Survey, a nationally representative sample of families and children. OUTCOME MEASURES: Parents were asked to report the total number of moves the index child had experienced during his or her lifetime. Total moves were adjusted for the child's age in years. Children were divided into two groups: never moved/infrequent relocation (below the 90th percentile for age-adjusted moves) and frequent relocation (above the 90th percentile for age-adjusted moves). The parent was asked if the child had ever had a learning disability or a delay in growth or development, had ever failed a grade, or had four or more frequently occurring behavioral problems as described by a behavioral problems checklist. RESULTS: The measures of both child dysfunction and family relocation were independently associated with multiple sociodemographic characteristics such as poverty, race, and family structure. Frequent relocation was associated with higher rates of all measures of child dysfunction; 23% of children who moved frequently had repeated a grade vs 12% of children who never or infrequently moved. Eighteen percent of children who moved frequently had four or more behavioral problems vs 7% of children who never or infrequently moved. Use of logistic regression to control for potential confounding covariates demonstrated that children who moved frequently were 77% more likely to be reported to have four or more behavioral problems (odds ratio, 1.77; 95% confidence interval, 1.37 to 2.29) and were 35% more likely to have failed a grade (odds ratio, 1.35; 95% confidence interval, 1.06 to 1.72), but no more likely to have had delays in growth or development or a learning disorder. CONCLUSIONS: After adjusting for other covariates, frequent family relocation was associated with an increased risk of children failing a grade in school and four or more frequently occurring behavioral problems.
A microbial screen using a yeast strain with conditional deficiency in the GPA1 gene was carried out to search for inhibitors of protein farnesyltransferase (PFT). A strain of Streptomyces was found to produce active compounds named UCF1-A, UCF1-B, and UCF1-C. Structural determination of these compounds revealed that UCF1-C is identical to the known antibiotic, manumycin, whereas UCF1-A and UCF1-B are structurally related to manumycin. All three UCF1 compounds suppress the lethality of gpa1 disruption, with UCF1-C exhibiting the strongest activity. UCF1 inhibits yeast as well as rat brain PFT. Fifty percent inhibition of yeast PFT activity is observed with 5 microM UCF1-C. Kinetic analyses of the inhibition suggest that UCF1-C acts as a competitive inhibitor of PFT with respect to farnesyl pyrophosphate, exhibiting a Ki of 1.2 microM, whereas the same compound appears to act as a noncompetitive inhibitor of PFT with respect to the farnesyl acceptor, the Ras protein. UCF1-C shows significant activity to inhibit the growth of Ki-ras-transformed fibrosarcoma, raising the possibility of its use as an antitumor drug.
The fluorescent Dye H33342 (H342) is a bis-benzimidazole used for intravital fluorescent staining. In this report, we found that H342 completely abolished histone 2a mRNA but had no effect on alkaline phosphatase gene expression and protein synthesis in UMR 106-01 rat osteoblast-like cells. The complete loss of histone 2a mRNA occurred after only 20 min of treatment with H342. This effect is unlikely to be a result of inhibition of DNA synthesis, which was only partly suppressed. The mechanism of the action of H342 on histone 2a mRNA is presently unknown.
The folding pathway for a 150-amino acid recombinant form of the dimeric cytokine human macrophage colony-stimulating factor (M-CSF) has been studied. All 14 cysteine residues in the biologically active homodimer are involved in disulfide linkages. The structural characteristics of folding intermediates blocked with iodoacetamide reveal a rapid formation of a small amount of a non-native dimeric intermediate species followed by a slow progression via both monomeric and dimeric intermediates to the native dimer. The transition from monomer to fully folded dimer is complete within 25 h at room temperature at pH 9.0. The blocked intermediates are stable under conditions of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and thus represent various dimeric and folded monomeric species of the protein with different numbers of disulfide bridges. Peptide mapping and electrospray ionization mass spectrometry revealed that a folded monomeric species of M-CSF contained three of the four native disulfide bridges, and this folded monomer also showed some biological activity in a cell-based assay. The results presented here strongly suggest that M-CSF can fold via two different pathways, one involving monomeric intermediates and another involving only dimeric intermediates.
The type 2 live-attenuated vaccine strain of poliovirus (P2/Sabin) is associated with rare cases of poliomyelitis in vaccinees or their contacts. Recombinants were generated between infectious clones of a neurovirulent isolate from one such case (P2/117) and P2/Sabin and neurovirulence assays suggested that a maximum of six nucleotide differences between the two strains were responsible for their phenotypic difference. Site-directed mutagenesis of P2/Sabin showed that mutations at just two positions, at 481 in the 5' non-coding region and at VP1-143 in the capsid proteins, resulted in a highly neurovirulent virus. Other nucleotide changes may have weaker phenotypic effects. These results are consistent with those reported in the mouse model by Ren et al. [J. Virol. 65, 1377, (1991)] indicating that, for P2/Sabin at least, the same determinants of attenuation are important in both primates and transgenic mice expressing the poliovirus receptor. Sequence analysis of isolates from other vaccine-associated cases of poliomyelitis and from healthy vaccinees showed that both major determinants of attenuation are unstable on human passage, although selection pressures against an A at 481 are stronger than those against an Ile at 1143.