Lack of association between the hOGG1 gene Ser326Cys polymorphism and gastric cancer risk: evidence from a case-control study and a meta-analysis.

The association between the human 8-oxoguanine glycosylase 1 (hOGG1) gene Ser326Cys polymorphism (rs1052133) and gastric cancer has been widely evaluated, yet a definitive answer to whether this association exists is lacking. We first conducted a case-control study to assess this association in a large Han Chinese population, and then performed a meta-analysis to further address this issue. This case-control study involved 448 patients clinically diagnosed with gastric cancer and 372 cancer-free control individuals from China. Genotyping was conducted using the polymerase chain reaction-ligase detection reaction method. Meta-analysis was performed by the STATA software. Data and study quality were assessed in duplicate. Our case-control association study indicated that there were no significant differences in the genotype and allele distributions of the Ser326Cys polymorphism between gastric cancer patients and controls (P = 0.8026 for genotype, and P = 0.5857 for allele), consistent with the results of the subsequent meta-analysis involving 2745 patients and 4588 controls under both allelic [odds ratio (OR) = 1.02; 95% confidence interval (CI) = 0.91-1.14; P = 0.739] and dominant (OR = 0.97; 95%CI = 0.78-1.21; P = 0.803) models. Further subgroup analyses by ethnicity, source of controls, and sample size also did not detect any positive associations in this meta-analysis. Overall, our study in the Han Chinese population, along with the meta-analysis, failed to confirm the association of the hOGG1 gene Ser326Cys polymorphism with gastric cancer risk, even across different ethnic populations.

Pediatric education and managed care: a literature review.

Managed care is becoming the dominant form of health care delivery and financing in the United States, necessitating changes in pediatric education. This transition is redefining the questions of what needs to be taught, who should be teaching it, where it should be taught, and how to pay for this education. We performed a literature review and examined reports from policy and professional groups to seek answers to these questions. We have identified curricular, administrative, and financial challenges to pediatric education in managed care. Although road maps for innovation have been described, there is a deficiency of research and information in key areas of pediatric education in the managed care environment.

Intention to practice primary care by pediatric residents: nature or nurture?

Factors associated with the intention to practice primary care were examined in a survey of a national sample of PL-2 residents (n = 98). Socioemotional orientation (nature), faculty and peer encouragement (nurture), and clinical experiences during residency (nurture) were independently associated with a primary care career choice. For residents who changed career intentions to primary care from a nonprimary care preference, gender, encouragement by faculty and peers, and outpatient experiences during residency were associated with the change. Encouragement by both faculty and peers had the strongest influence on primary care career choice for all residents.

The eosin-5-maleimide binding site on human erythrocyte band 3: investigation of membrane sidedness and location of charged residues by triplet state quenching.

The triplet probe eosin-5-maleimide (EMA) is a specific inhibitor of anion transport mediated by the erythrocyte membrane protein, band 3. It was previously shown that the eosin moiety is located close to the anion binding site when EMA is covalently bound to band 3 [Pan, R.-j., and Cherry, R. J. (1995) Biochemistry 34, 4880-4888]. In the present study the electrostatic properties and membrane sidedness of the EMA binding site of band 3 were further investigated by triplet state quenching. A series of stable nitroxyl free radicals, which are characterized by different charges, and I- were used as the quenchers. Time-resolved laser spectroscopy was employed to measure the triplet lifetime of EMA. It was found that the quenching reaction between the quenchers and band 3-bound EMA follows a linear Stern-Volmer plot. The quenching rate constants (Kq) of the quenchers are in the order of NH3+-TEMPO (Kq = 6.34 x 10(6) M-1 s-1) > TEMPO-Choline+ (Kq = 2.18 x 10(6) M-1 s-1) > TEMPO (Kq = 1.13 x 10(6) M-1 s-1) > I- (Kq = 2.46 x 10(5) M-1 s-1) > pyrroline-COO- (Kq = 2.18 x 10(4) M-1 s-1). Experiments with resealed ghosts and inside-out vesicles revealed that negatively charged quenchers can only access the EMA binding site from the extracellular side of the membrane while the positively charged quenchers acted from the cytoplasmic side. The ionic strength dependence of the quenching rate constants and the effects of pH on the quenching reaction were also studied. For both TEMPO-Choline+ and I-, the Kq values decreased as the ionic strength increased, but quenching by TEMPO was independent of the ionic strength variation over the same range. It was also found that at lower pH, the I- quenching rate constant increases but the TEMPO-choline+ quenching rate constant decreases. In both cases, the dependence of quenching on pH exhibited an apparent pKa of about 6.5, which suggests the involvement of one or more histidine residues. This notion gained further support from the finding that modification of His residues of band 3 by DEPC reduced I- quenching at pH 6. On the basis of these results, it is proposed that eosin is located in the anion transport channel such that it is accessible from both sides of the membrane. Histidine residues, which have previously been proposed to lie in the anion channel, probably are located on either side of the eosin probe where they contribute to electrostatic interactions which determine the Kq values for the charged quenchers.

Evidence that eosin-5-maleimide binds close to the anion transport site of human erythrocyte band 3: a fluorescence quenching study.

The interaction between eosin-5-maleimide (EMA), an inhibitor of the anion transport protein, band 3, and I-, a transportable substrate, was investigated by fluorescence quenching. The Stern-Volmer plot for the quenching reaction between EMA-labeled band 3 and I- exhibits downward curvature both in human erythrocyte ghosts and in purified band 3. The quenching reaction is insensitive to the viscosity of the bulk phase. The shape of the Stern-Volmer plot becomes more linear with increasing temperature. Following the approach of Blatt et al. [(1986) Biophys. J. 50, 349-356], we have developed a binding-diffusion model which is in good agreement with the quenching data. The model supposes that EMA is located in a compartment or "pocket" in band 3 which is separate from the bulk phase and contains a binding site or sites for the quencher. Quenching of band 3-bound EMA fluorescence by I- is inhibited by DIDS and by the transportable anions Cl-, HCO3-, and Br-. Analysis of these experiments yields dissociation constants for the anions which are in reasonable agreement with those determined from transport kinetics and by NMR. We thus deduce that the quencher binding site is the anion binding/transport site on band 3. We propose that EMA is located in the wall of the anion access channel such that it does not inhibit anion binding. The methods described in this report should facilitate detailed studies of anion binding to the transport site on band 3 under a variety of experimental conditions.

Views of managed care--a survey of students, residents, faculty, and deans at medical schools in the United States.

BACKGROUND AND METHODS: Views of managed care among academic physicians and medical students in the United States are not well known. In 1997, we conducted a telephone survey of a national sample of medical students (506 respondents), residents (494), faculty members (728), department chairs (186), directors of residency training in internal medicine and pediatrics (143), and deans (105) at U.S. medical schools to determine their experiences in and perspectives on managed care. The overall rate of response was 80.1 percent. RESULTS: Respondents rated their attitudes toward managed care on a 0-to-10 scale, with 0 defined as "as negative as possible" and 10 as "as positive as possible." The expressed attitudes toward managed care were negative, ranging from a low mean (+/-SD) score of 3.9+/-1.7 for residents to a high of 5.0+/-1.3 for deans. When asked about specific aspects of care, fee-for-service medicine was rated better than managed care in terms of access (by 80.2 percent of respondents), minimizing ethical conflicts (74.8 percent), and the quality of the doctor-patient relationship (70.6 percent). With respect to the continuity of care, 52.0 percent of respondents preferred fee-for-service medicine, and 29.3 percent preferred managed care. For care at the end of life, 49.1 percent preferred fee-for-service medicine, and 20.5 percent preferred managed care. With respect to care for patients with chronic illness, 41.8 percent preferred fee-for-service care, and 30.8 percent preferred managed care. Faculty members, residency-training directors, and department chairs responded that managed care had reduced the time they had available for research (63.1 percent agreed) and teaching (58.9 percent) and had reduced their income (55.8 percent). Overall, 46.6 percent of faculty members, 26.7 percent of residency-training directors, and 42.7 percent of department chairs reported that the message they delivered to students about managed care was negative. CONCLUSIONS: Negative views of managed care are widespread among medical students, residents, faculty members, and medical school deans.