Chemical constituents of gentianaceae. IV. New xanthones of Canscora decussata.
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Biomedical subjects
Publications and source records attributed to A Nath.
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Fluorescence spectroscopy is a promising technology for detection of epithelial precancers and cancers. In preparation for a multicenter phase II screening trial, a pilot trial was conducted to test data collection and patient examination procedures, use data forms, time procedures, and identify problems with preliminary data analysis. Women 18 years of age and older underwent a questionnaire, a complete history, and a physical examination, including a pan-colposcopy of the lower genital tract. A fiber-optic probe measured fluorescence excitation-emission matrices at 1-3 cervical sites for 58 women. The data collection procedures, data forms, and procedure times worked well, although collection times for all the clinical data take an average of 28 min. The clinical team followed procedures well, and the data could be retrieved from the database at all sites. The multivariate analysis algorithm correctly identified squamous normal tissue 99% of the time and columnar normal tissue only 7%. The assessment of ploidy from monolayer samples was not accurate in this small sample. The study was successful as a pilot trial. We learned who participated, who withdrew, how often abnormalities were present, and that algorithms that have worked extremely well in previous studies do not work as well when a few study parameters are changed. The current algorithm for diagnosis identified squamous normal tissue very accurately and did less well for columnar normal tissue. Inflammation may be an explanation for this phenomenon. Fluorescence spectroscopy is a promising technology for the detection of epithelial precancers and cancers. The screening trial of fluorescence and reflectance spectroscopy was successful.
Activation and infection by HIV-1 of glial cells and infiltrating macrophages are cardinal features of AIDS-related neurological disease. Tumor necrosis factor-alpha (TNF-alpha) is released by these cell types, and increased TNF-alpha mRNA and protein levels are associated with the development and severity of HIV-induced neurological disease. HIV-1 proteins have been implicated in HIV neuropathogenesis including Tat which has been shown to be a potent inducer of TNF-alpha. We review our data showing the induction of TNF-alpha by Tat in primary human fetal astrocytes, human peripheral blood mononuclear cells, macrophages, and astrocytic and macrophage cell lines. TNF-alpha induction was NF-kappaB dependent and was eliminated by inhibiting protein kinase A, phospholipase C and protein tyrosine kinase activity. In addition, we examined the molecular diversity of the tat genome in the brains of HIV-infected patients from different HIV-1 clades. Comparison of matched brain- and spleen-derived tat sequences indicated that homology among brain-derived clones was greater than that between the brain- and spleen-derived clones. The brain-derived tat sequences were markedly heterogeneous in regions which influence viral replication and intracellular transport. Future studies using Tat, encoded by different sequences, will be necessary to determine the functional significance of tat molecular diversity. Nonetheless, these studies suggest that Tat is an important inducer of TNF-alpha production and thus may play a key role in the pathogenesis of HIV-related neurological disease.
Residency training involves surgery by resident surgeons at various levels of experience and proficiency, supervised by an experienced attending physician. We reviewed the results of strabismus surgery performed at four institutions with two residency training programs. Five hundred twenty-two cases with follow up greater than 6 weeks were evaluated. These cases included 315 attending procedures and 207 resident procedures under direct attending supervision. Success was defined as a strabismic deviation of 8 prism diopters or less. Average postoperative follow-up was 57 weeks and did not differ between groups. There was no statistical difference between the resident success rate of 58% (121/207) and the attending success rate of 69% (217/315) after adjusting for population differences. The average final deviation of the patients postoperatively was 7 delta for the attending group and 10 delta for the resident group. Amblyopia was significantly more frequent in the resident cases (P < .001). Adjustable sutures were used significantly more often in attending cases (P < .0001). This study supports the premise that resident strabismus surgery is as successful as attending surgery.
The genotoxic potentiality of nimesulide was evaluated in vivo in murine bone marrow cells. The human equivalent prophylactic dose of nimesulide (5 mg/kg body wt/day) was given to animals orally, once daily for seven consecutive days. Metaphase chromosome analyses revealed the significant increase in the incidence of chromosomal aberrations with preference to structural over the numerical ones. It therefore suggested the clastogenic effect of the nimesulide. The molecular mechanism of mutagenesis is yet to be determined.