Role of mismatch repair in the Escherichia coli UVM response

Mutagenesis at 3,N4-ethenocytosine (epsilonC), a nonpairing mutagenic lesion, is significantly enhanced in Escherichia coli cells pretreated with UV, alkylating agents, or H2O2. This effect, termed UVM (for UV modulation of mutagenesis), is distinct from known DNA damage-inducible responses, such as the SOS response, the adaptive response to alkylating agents, or the oxyR-mediated response to oxidative agents. Here, we have addressed the hypothesis that UVM results from transient depletion of a mismatch repair activity that normally acts to reduce mutagenesis. To test whether the loss of mismatch repair activities results in the predicted constitutive UVM phenotype, E. coli cells defective for methyl-directed mismatch repair, for very-short-patch repair, or for the N-glycosylase activities MutY and MutM were treated with the UVM-inducing agent 1-methyl-3-nitro-1-nitrosoguanidine, with subsequent transfection of M13 viral single-stranded DNA bearing a site-specific epsilonC lesion. Survival of the M13 DNA was measured as transfection efficiency, and mutation fixation at the lesion was characterized by multiplex sequencing technology. The results showed normal UVM induction patterns in all the repair-defective strains tested. In addition, normal UVM induction was observed in cells overexpressing MutH, MutL, or MutS. All strains displayed UVM reactivation, the term used to describe the increased survival of epsilonC-containing DNA in UVM-induced cells. Taken together, these results indicate that the UVM response is independent of known mismatch repair systems in E. coli and may thus represent a previously unrecognized misrepair or misreplication pathway.     

NIDDM incidence in a tri-ethnic population of diagnosed hypertensives

OBJECTIVE: Significant racial/ethnic differences exist in the prevalence of hypertension (HTN) and non-insulin dependent diabetes mellitus (NIDDM). The purpose of this study was to determine if ethnicity (African-American, Hispanic and non-Hispanic white) was related to NIDDM incidence over a maximum follow-up period of 10 years. DESIGN: Retrospective cohort study. SETTING: A large, urban public health care system serving over 200,000 predominantly minority persons. The system includes nine primary care health centers. PATIENTS: African-American, Hispanic and non-Hispanic white patients with diagnosed hypertension who received primary care in the study setting. METHODS: Medical records of 2,941 hypertensives free of NIDDM at their baseline visit were reviewed to document incident NIDDM during follow-up. Sociodemographic characteristics and physiologic covariates consistently available in the medical record (blood pressure, height, weight, and blood glucose) were also abstracted. RESULTS: The mean age of patients at the baseline visit was 56 years; 67% were female, 63% were African-American. 17% Hispanic, and 20% non-Hispanic white. Two hundred thirty-six incident cases of NIDDM were identified in the cohort. In Cox proportional hazards analysis, the risk of developing NIDDM was not related to ethnicity either in univariate analysis or after adjusting for age, baseline blood glucose, and body mass index (adjusted RR for African Americans compared with whites = .82, 95% CI = .57-1.18; adjusted RR for Hispanics compared with whites = .84, 95% CI = .51-1.38). CONCLUSION: The lack of association between ethnicity and NIDDM risk among hypertensives is unexpected, and may indicate differences in the pathogenetic mechanisms that underlie the development of hypertension and NIDDM in these three ethnic groups.     

Mutation in the prion protein gene at codon 232 in Japanese patients with Creutzfeldt-Jakob disease: a clinicopathological, immunohistochemical and transmission study

The societal and economic forces driving change in medical education are affecting communities as well as universities. Each of the four authors of this paper is deeply involved in one of the components of their locale's well-developed community-based medical educational system, and each describes how change is influencing his role in that system, whether the role be managing a community hospital, directing a local Area Health Education Center, participating as a family medicine faculty member, or being a community preceptor. They agree on some common themes: (1) that it is good that medical students' education is moving into the community (e.g., this validates the importance of the community hospital to medical education, is an acknowledgment of the importance of generalism, and provides students invaluable learning experiences); (2) that educating medical students in the community is expensive, and more funding and resources are needed so that the area's hospitals, community faculty, preceptors, and support services can be fairly compensated for their commitment; and (3) that their community-based education system can no longer absorb the costs of training more medical students. This is not a criticism of academic medical centers, which are under tremendous financial pressures themselves, but is simply to state the community perspective and to urge fairness in the distribution of resources for medical education. Community institutions and academic medical centers will work individually to create their own integrated health care systems but must work together to create a better, more cost-effective system for educating medical students.     

Modeling multimode-input star couplers in polymers

In this paper, we present the first numerical study of highly multimode-input integrated-optic star couplers. Although the design utilizes the physical quantities appropriate for a polymer device, many of the results are applicable to multimode-input star couplers using a wide range of materials. Design parameters explored include the input-port waveguide width, refractive index difference, and insertion angle. The simulation work is done utilizing the beam propagation method. The statistically based scaling parameters for these highly multimode structures are shown to be compatible with the results of an analytical model which is suitable for initial device design     

Nasal polyps in children

The inflammatory nasal polyp is the most common benign or malignant nasal mass seen in children. Nasal polyps in the pediatric population appear to occur as inflammatory responses to bacterial infections. In 33% of the patients with polyps whom we studied, antral choanal polyps were noted, and in 20% of the patients the polyps were unilateral but not antral choanal. In 18% of the patients the polyps were bilateral and in an additional 29% they occurred bilaterally in association with cystic fibrosis. History of an allergy is infrequently associated with nasal polyps; allergies are potentially major contributing factors to nasal polyps only in patients without cystic fibrosis whose nasal polyps are bilateral. Patients with antral choanal polyps are most successfully managed by simultaneous Caldwell-Luc antrostomy and polypectomy. Sixty percent of patients with nasal polyps and cystic fibrosis are adequately managed with a single intranasal polypectomy. Simultaneous sinus surgery and polypectomy should be considered for all patients with recurrent polyps and for all patients with clinical or radiographic evidence of significant sinusitis. Complications, including epistaxis and intranasal synechia, occurred in 3% of the 170 surgical procedures performed.