Coculture cells that express leukemia inhibitory factor (LIF) enhance mouse blastocyst developmentin vitro

Purpose Leukemia inhibitory factor is a cytokine that plays an important role in implantation and enhances mouse preimplantation embryo development in vitro.Since leukemia inhibitory factor enhances early embryo development, we tested the hypothesis that coculture cells that express leukemia inhibitory factor would enhance mouse blastocyst development in vitro.In this study, Northern analysis for leukemia inhibitory factor was performed on total RNA extracted from Vero cells, human embryonic, fibroblasts, and human placental fibroblasts.Methods Two-cell mouse embryos were cultured to blastocyst in Ham's F-10 with 15% human cord serum (control) or with the coculture cells. Northern analysis demonstrated expression of LIF mRNA in Vero cells and embryonic fibroblasts but not in placental fibroblasts. Development to blastocyst was significantly enhanced in two-cell embryos cultured with Vero cells (86%, 140/163) and embryonic fibroblasts (83%, 118/142) when compared to controls (71%, 67/94, P<0.05) or placental fibroblasts (71%, 95/134), P<0.05).Conclusion These data suggest that coculture cells that express leukemia inhibitory factor may be superior to nonleukemia inhibitory factor expressing cells for early preimplantation embryo development.Presented at the 50th Annual Meeting of the American Fertility Society, San Antonio, Texas, November 5–10, 1994.     

Inaccessible information is useless information: addressing the knowledge gap

The burdens of increasing information overload, time constraints, and the high human and financial costs of medical error, mean that doctors cannot practice high quality evidence-based medicine without the aid of decision support systems at the point of care. The physician's role is to formulate a management plan based on clinical judgment, the patient's unique circumstances and preferences, and the best available evidence. Clineguide is a clinical knowledge system that will integrate into the workflow to improve patient outcomes, reduce variability of care, and promote efficiency in the health care process. This article discusses some of the issues surrounding the provision of rapid, accurate, and accessible information to health care professionals.     

Phase II trial of pyrazoloacridine in advanced non-small cell carcinoma of the lung--a Kansas Cancer Institute and Thompson Cancer Survival Center Study

Background: More active agents areneeded in the treatment of metastaticnon-small cell lung cancer. Pyrazoloacridine (PZA) is a 9-methoxyacridine compound containing a reducible5-nitro substituent. Although themechanism of action of PZA is unknown, theacridine compounds are known to causecytotoxicity by interaction with DNA andRNA. Methods: Eighteen patients withmetastatic non-small cell lung carcinomawere treated with pyrazoloacridine.Pyrazoloacridine was administered as athree-hour infusion at 750 mg/M² every21 days. Results: There were no objectiveresponses. One patient maintained stabledisease for 20 months. Median survival was4.8 months. The primary toxicity wasgranulocytopenia with 5 patientsexperiencing severe infections. Conclusions: Pyrazoloacridine has nodemonstrable activity in patients withmetastatic non-small cell carcinoma of thelung when given at this dose andschedule.     

Bioterrorism-related anthrax surveillance,Connecticut, September-December, 2001

On November 19, 2001, a case of inhalational anthrax was identified in a 94-year-old Connecticut woman, who later died. We conducted intensive surveillance for additional anthrax cases, which included collecting data from hospitals, emergency departments, private practitioners, death certificates, postal facilities, veterinarians, and the state medical examiner. No additional cases of anthrax were identified. The absence of additional anthrax cases argued against an intentional environmental release of Bacillus anthracis in Connecticut and suggested that, if the source of anthrax had been cross-contaminated mail, the risk for anthrax in this setting was very low. This surveillance system provides a model that can be adapted for use in similar emergency settings.     

Design and synthesis of dipeptide nitriles as reversible and potent Cathepsin S inhibitors

The specificity of the immune response relies on processing of foreign proteins and presentation of antigenic peptides at the cell surface. Inhibition of antigen presentation, and the subsequent activation of T-cells, should, in theory, modulate the immune response. The cysteine protease Cathepsin S performs a fundamental step in antigen presentation and therefore represents an attractive target for inhibition. Herein, we report a series of potent and reversible Cathepsin S inhibitors based on dipeptide nitriles. These inhibitors show nanomolar inhibition of the target enzyme as well as cellular potency in a human B cell line. The first X-ray crystal structure of a reversible inhibitor cocrystallized with Cathepsin S is also reported.     

Parent-child conflict and the comorbidity among childhood externalizing disorders

BACKGROUND: Previous research has suggested that substantial comorbidity exists among childhood externalizing disorders, specifically attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and conduct disorder (CD). Moreover, parent-child conflict predicts each of these disorders. Our goals were to determine whether parent-child conflict was associated with the comorbidity among ADHD, CD, and ODD, and to explicitly examine the etiology of this association via a genetically informative design. METHODS: We compared the fit of the following 2 biometric models: the 2-factor common-pathway model, which examined genetic and environmental contributions to the relationship between conflict and the covariation among the 3 disorders, and the Cholesky model, which examined the relationship between conflict and each disorder individually. The sample consisted of 808 same-sex 11-year-old twin pairs from the Minnesota Twin Family Study, a population-based sample of Minnesota twins and their families. Main outcome measures included symptom counts for ADHD, CD, and ODD, obtained from structured interviews administered to twins and their mothers. Parent-child conflict was assessed via mother and twin reports of the Parental Environment Questionnaire. RESULTS: The 2-factor model provided a better fit to the data. These results indicated that conflict accounted for 33% of the covariation among the disorders, via genetic and environmental factors. CONCLUSIONS: Parent-child conflict appears to act as a common vulnerability that increases risk for multiple childhood disorders. Furthermore, this association is mediated via common genetic and environmental factors. These findings support the idea that the comorbidity among these disorders partially reflects core psychopathological processes in the family environment that link putatively separate psychiatric disorders.     

Bone density assessments of dental implant sites: 1. Quantitative computed tomography

PURPOSE: This study was designed to evaluate variations of bone density in designated implant sites using quantitative computed tomography (QCT) and to compare the QCT measurements to subjective evaluation of bone density. MATERIALS AND METHOD: Sixty-two designated implant sites in jaws of 9 human cadavers were used. Indicator rods, 2 mm in diameter, were placed in all sites. CT images representing 1-mm buccolingual slices immediately mesial and distal to the rods were selected. Bone density (in Hounsfield units) was assessed in a standardized implant area superimposed on the images and was also subjectively evaluated by 2 independent examiners using the Lekholm and Zarb classification. RESULTS: QCT results demonstrated that bone densities may vary markedly when different areas of a designated implant site are compared. The Lekholm and Zarb ratings for the 2 examiners showed coefficients of correlation ranging between 0.5 to 0.7 for the relationships with the QCT values. Within each of the scores used for the subjective classification, however, a wide range of QCT values was observed. DISCUSSION: The results emphasize the importance of the use of radiographic methods prior to implant placement that allow topographically precise assessments of bone density in the region of interest. CONCLUSION: Access to QCT values should constitute a valuable supplement to subjective bone density evaluations prior to implant placement.