Neodymium:YAG laser optical opening for retained Descemet''s membrane after penetrating keratoplasty

Although the extent of suprathreshold damage to murine lung that results from exposure to pulsed ultrasound increases with time, the threshold level for lung hemorrhage is relatively insensitive to total exposure time. Adult mice were exposed for 20 s and 3 min to 2.3-MHz ultrasound (10-microseconds pulses, 100-Hz pulse repetition frequency) at peak positive pressures ranging up to 3 MPa. Threshold pressures for the two exposure times, 1.6 MPa and 1.4 MPa, respectively, are the same within the statistical significance of the measurements.     

Ureteral Stones Clinical Guidelines Panel summary report on the management of ureteral calculi. The American Urological Association

PURPOSE: The American Urological Association convened the Ureteral Stones Clinical Guidelines Panel to analyze the literature regarding available methods for treating ureteral calculi and to make practice policy recommendations based on the treatment outcomes data. MATERIALS AND METHODS: The panel searched the MEDLINE data base for all articles related to ureteral calculi published from 1966 to January 1996. Outcomes data were extracted from articles accepted after panel review. The data were then meta-analyzed to produce outcome estimates for alternative treatments of ureteral calculi. RESULTS: The data indicate that up to 98% of stones less than 0.5 cm. in diameter, especially in the distal ureter, will pass spontaneously. Shock wave lithotripsy is recommended as first line treatment for most patients with stones 1 cm. or less in the proximal ureter. Shock wave lithotripsy and ureteroscopy are acceptable treatment choices for stones 1 cm. or less in the distal ureter. CONCLUSIONS: Most ureteral stones will pass spontaneously. Those that do not can be removed by either shock wave lithotripsy or ureteroscopy. Traditional blind basket extraction, without fluoroscopic control and guide wires, is not recommended. Open surgery is appropriate as a salvage procedure or in certain unusual circumstances.     

Solution structure of the minor conformer of a DNA duplex containing a dG mismatch opposite a benzo[a]pyrene diol epoxide/dA adduct: glycosidic rotation from syn to anti at the modified deoxyadenosine

Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental contaminants whose metabolism in mammals results in deleterious cell transformation. Covalent modification of DNA by diol epoxides metabolically formed from PAHs such a benzo[a]pyrene (BaP) provides a mechanism for the genotoxicity, mutagenicity, and carcinogenicity of PAHs. We had previously reported NMR evidence for a minor conformer of the duplex d(G1G2T3C4A5*C6G7A8G9).d(C10T11C12G13G14G15A16C17C18) containing a dG14 mismatch opposite a dA5* residue modified at the exocyclic amino group by trans addition to (+)-(7R,8S,9S,10R)-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a] pyrene [Yeh, H.J.C., Sayer, J.M., Liu, X., Altieri, A.S., Byrd, R.A., Lashman, M.K., Yagi, H., Schurer, E.J., Gorenstein, D.G., & Jerina, D.M. (1995) Biochemistry 34, 13570-13581]. In the present work, we describe the structure of this minor conformer (ca. 17% of the total conformer population). This represents the first structural determination of a minor conformer of a carcinogen-lesion DNA adduct. Two-dimensional NOESY, ROESY, TOCSY, and exchange-only spectra at 750 MHz allowed nearly complete sequential assignment of both conformers. In the minor conformer, the adducted base assumes an anti-glycosidic torsion angle whereas in the major conformer it assumes an unusual syn-glycosidic torsion angle. The aromatic hydrocarbon in the minor conformer is intercalated between dG13 and dG14, preserving the energetically favorable stacking interactions found in the major conformer. The major structural differences between the two conformers appear to be near the lesion site as evidenced by the large chemical shift differences between major and minor conformer protons near the lesion site; away from this site, the chemical shifts of the major and minor conformer protons are nearly identical. Because any of the conformations of benzo[a]pyrene diol epoxide-modified DNA may contribute to tumorigenic activity, structural determination of all conformations is essential for the elucidation of the mechanism of cell transformation initiated by covalent modification of DNA by PAHs.     

Relationship between food-specific IgE concentrations and the risk of positive food challenges in children and adolescents

BACKGROUND: The double-blind, placebo-controlled food challenge (DBPCFC) is the "gold standard" for diagnosis of food hypersensitivity. Skin prick tests and RASTs are sensitive indicators of food-specific IgE antibodies but poor predictors of clinical reactivity. Previous studies suggested that high concentrations of food-specific IgE antibody were predictive of food-induced clinical symptoms. Because the CAP System FEIA (Pharmacia Diagnostics, Uppsala, Sweden) provides a quantitative assessment of allergen-specific IgE antibody, this study was undertaken to determine the potential utility of the CAP System FEIA in diagnosis of IgE-mediated food hypersensitivity. METHODS: Sera from 196 patients with food allergy were analyzed for specific IgE antibodies to egg, milk, peanut, soy, wheat, and fish by CAP System FEIA. Sera were randomly selected from 300 stored samples of children and adolescents who had been evaluated by history, skin prick tests, and DBPCFCs. The study population was highly atopic; all patients had atopic dermatitis, and approximately 50% had asthma and allergic rhinitis at the time of initial evaluation. The performance characteristics of the CAP System FEIA were compared with those of skin prick tests and the outcome of DBPCFCs or "convincing" histories of anaphylactic reactions. RESULTS: The prevalence of specific food allergies in the study population varied from 22% for wheat to 73% for egg. Allergy to egg, milk, peanut, and soy accounted for 87% of confirmed reactions. The performance characteristics of skin prick tests and CAP System FEIA (egg, milk, peanut, fish) were comparable, with excellent sensitivity and negative predictive accuracy but poor specificity and positive predictive accuracy. The performance characteristics of the CAP System FEIA for soy and wheat were poor. For egg, milk, peanut, and fish allergy, diagnostic levels of IgE, which could predict clinical reactivity in this population with greater than 95% certainty, were identified: egg, 6 kilounits of allergen-specific IgE per liter (kU[A]/L); milk, 32 kU(A)/L; peanut, 15 kU(A)/L; and fish, 20 kU(A)/L. CONCLUSIONS: When compared with the outcome of DBPCFCs, results of CAP System FEIA are generally comparable to those of skin prick tests in predicting symptomatic food hypersensitivity. Furthermore, by measuring the concentrations of food-specific IgE antibodies with the CAP System FEIA, it is possible to identify a subset of patients who are highly likely (>95%) to experience clinical reactions to egg, milk, peanut, or fish. This could eliminate the need to perform DBPCFCs in a significant number of patients suspected of having IgE-mediated food allergy.     

DNA-damaging steroidal alkaloids from Eclipta alba from the suriname rainforest1

Bioassay-guided fractionation of the MeOH extract of Eclipta alba using three yeast strains (1138, 1140, and 1353) resulted in the isolation of eight bioactive steroidal alkaloids (1-8), six of which are reported for the first time from nature. The major alkaloid was identified as (20S)(25S)-22,26-imino-cholesta-5,22(N)-dien-3beta-ol (verazine, 3), while the new alkaloids were identified as 20-epi-3-dehydroxy-3-oxo-5,6-dihydro-4,5-dehydroverazine (1), ecliptalbine [(20R)-20-pyridyl-cholesta-5-ene-3beta,23-diol] (4), (20R)-4beta-hydroxyverazine (5), 4beta-hydroxyverazine (6), (20R)-25beta-hydroxyverazine (7), and 25beta-hydroxyverazine (8). Ecliptalbine (4), in which the 22,26-imino ring of verazine was replaced by a 3-hydroxypyridine moiety, had comparable bioactivity to verazine in these assays, while a second alkaloid (8) showed good activity against Candida albicans. All the alkaloids showed weak cytotoxicity against the M-109 cell line.     

Activity-based cost management. Part II: Applied to a respiratory protection program

The ability of IL-12 and IL-15 to enhance natural killer (NK) activity and antibody-dependent cellular cytotoxicity (ADCC) of mononuclear cells (MNCs) from HIV+ children and their mothers was investigated. MNCs from HIV+ patients were deficient in NK and ADCC activity compared to control MNCs against several target cells. Overnight incubation with IL-15 or IL-12 augmented NK activity of MNCs from both patients and controls, and the combination of IL-12 and IL-15 resulted in the greatest enhancement. ADCC in HIV+ patients against gp120-coated CEM.NKR cells or chicken erythrocytes could also be enhanced by IL-2 or IL-15 in overnight cultures. Culturing MNCs with either IL-2 or IL-15 for 1 week increased the NK activity in patients to levels of controls treated with these cytokines. However, the response to the combination of IL-12 and IL-15 was less than that to IL-15 alone in 1-week cultures. Culturing MNCs with IL-2 and IL-15 for 1 week also increased the percentage of CD16+/CD56+ cells in both patients and controls. Thus, IL-15 can restore the deficient NK activity in patients and may be a candidate for immunomodulative therapy in HIV+ patients.     

Stress and a glycinergic intervention interact in the modulation of MK-801-elicited mouse popping behavior

Cancer mortality in a population-based cohort of 10,322 parkinsonian patients (448 deaths observed during 1987 to 1994) was compared with that of the Italian province of Rome using the standardized mortality ratio (SMR). The overall cancer mortality risk was lower in this cohort than in the reference population (SMR, 56; 95% CI, 51 to 61). This reduction included most cancer sites as well as both smoking-related (SMR, 51; 95% CI, 42 to 60) and nonsmoking-related cancers (SMR, 58; 95% CI, 52 to 65). The observed reduction in cancer mortality risk in this cohort cannot be explained entirely by the hypothesis that smokers are less likely to develop PD.     

Cardiovascular disease prevention research at the National Heart, Lung, and Blood Institute

The morphology of endothelial cells in vivo depends on the local hemodynamic forces. Cells are polygonal and randomly oriented in areas of low shear stress, but they are elongated and aligned in the direction of fluid flow in regions of high shear stress. Endothelial cells in vitro also have a polygonal shape, but the application of shear stress orients and elongates the cells in the direction of fluid flow. The corresponding spatial reorganization of the cytoskeleton in response to the applied hemodynamic forces is unknown. In this study, we determined the spatial reorganization of the cytoskeleton throughout the volume of cultured bovine aortic endothelial cells after the cells had been exposed to a physiological level of shear stress for 0, 1.5, 3, 6, 12, or 24 h. The response of the monolayer to shear stress was not monotonic; it had three distinct phases. The first phase occurred within 3 h. The cells elongated and had more stress fibers, thicker intercellular junctions, and more apical microfilaments. After 6 h of exposure, the monolayer entered the second phase, where the cells exhibited characteristics of motility. The cells lost their dense peripheral bands and had more of their microtubule organizing centers and nuclei located in the upstream region of the cell. The third phase began after 12 h of exposure and was characterized by elongated cells oriented in the direction of fluid flow. The stress fibers in these cells were thicker and longer, and the heights of the intercellular junctions and microfilaments were increased. These results suggest that endothelial cells initially respond to shear stress by enhancing their attachments to the substrate and neighboring cells. The cells then demonstrate characteristics of motility as they realign. The cells eventually thicken their intercellular junctions and increase the amount of apical microfilaments. The time course of rearrangement can be described as a constrained motility that produces a new cytoskeletal organization that alters how the forces produced by fluid flow act on the cell and how the forces are transmitted to the cell interior and substrate.