348 research outputs found

    Disparate Osteogenic Response of Mandible and Iliac Crest Bone Marrow Stromal Cells to Pamidronate

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    OBJECTIVE Long-term administration of intravenous bisphosphonates like pamidronate is associated with jaw osteonecrosis but axial and appendicular bones are unaffected. Pathogenesis of bisphosphonate-associated jaw osteonecrosis may relate to skeletal-site specific effects of bisphosphonates on osteogenic differentiation of bone marrow stromal cells (BMSCs) of orofacial and axial/appendicular bones. This study evaluated and compared skeletal site-specific osteogenic response of mandible (orofacial bone) and iliac crest (axial bone) human BMSCs to pamidronate. MATERIALS AND METHODS Mandible and iliac crest BMSCs from six normal healthy volunteers were established in culture and tested with pamidronate to evaluate and compare cell survival, osteogenic marker alkaline phosphatase, osteoclast differentiation in co-cultures with CD34+ hematopoietic stem cells, gene expression of receptor activator of NFκB ligand (RANKL) and osteoprotegerin, and in vivo bone regeneration. BRESULTS Mandible BMSCs were more susceptible to pamidronate than iliac crest BMSCs based on decreased cell survival, lower alkaline phosphatase production and structurally less organized in vivo bone regeneration. Pamidronate promoted higher RANKL gene expression and osteoclast recruitment by mandible BMSCs. CONCLUSION Mandible and iliac crest BMSC survival and osteogenic differentiation are disparately affected by pamidronate to favor dysregulated mandible bone homeostasis

    Aldose Reductase Genotypes and Cardiorenal Complications: An 8-year prospective analysis of 1,074 type 2 diabetic patients

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    OBJECTIVE—We report the independent risk association of type 2 diabetic nephropathy with the z−2 allele of the 5′-(CA)n microsatellite and C-106T promoter polymorphisms of the aldose reductase gene (ALR2) using a case-control design. In this expanded cohort, we examined their predictive roles on new onset of cardiorenal complications using a prospective design

    Additive Interaction of Hyperglycemia and Albuminuria on Risk of Ischemic Stroke in Type 2 Diabetes: Hong Kong Diabetes Registry

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    OBJECTIVE—The study aims to test whether biological interaction between hyperglycemia and albuminuria can explain the inconsistent findings from epidemiological studies and clinical trials about effects of hyperglycemia on stroke in type 2 diabetes

    Measurement of the branching fraction for Υ(1S)τ+τ\Upsilon (1S) \to \tau^+ \tau^-

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    We have studied the leptonic decay of the Υ(1S)\Upsilon (1S) resonance into tau pairs using the CLEO II detector. A clean sample of tau pair events is identified via events containing two charged particles where exactly one of the particles is an identified electron. We find B(Υ(1S)τ+τ)=(2.61 ± 0.12 +0.090.13)B(\Upsilon(1S) \to \tau^+ \tau^-) = (2.61~\pm~0.12~{+0.09\atop{-0.13}})%. The result is consistent with expectations from lepton universality.Comment: 9 pages, RevTeX, two Postscript figures available upon request, CLNS 94/1297, CLEO 94-20 (submitted to Physics Letters B

    Programmable antivirals targeting critical conserved viral RNA secondary structures from influenza A virus and SARS-CoV-2

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    Influenza A virus’s (IAV’s) frequent genetic changes challenge vaccine strategies and engender resistance to current drugs. We sought to identify conserved and essential RNA secondary structures within IAV’s genome that are predicted to have greater constraints on mutation in response to therapeutic targeting. We identified and genetically validated an RNA structure (packaging stem–loop 2 (PSL2)) that mediates in vitro packaging and in vivo disease and is conserved across all known IAV isolates. A PSL2-targeting locked nucleic acid (LNA), administered 3 d after, or 14 d before, a lethal IAV inoculum provided 100% survival in mice, led to the development of strong immunity to rechallenge with a tenfold lethal inoculum, evaded attempts to select for resistance and retained full potency against neuraminidase inhibitor-resistant virus. Use of an analogous approach to target SARS-CoV-2, prophylactic administration of LNAs specific for highly conserved RNA structures in the viral genome, protected hamsters from efficient transmission of the SARS-CoV-2 USA_WA1/2020 variant. These findings highlight the potential applicability of this approach to any virus of interest via a process we term ‘programmable antivirals’, with implications for antiviral prophylaxis and post-exposure therapy

    Production and Decay of D_1(2420)^0 and D_2^*(2460)^0

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    We have investigated D+πD^{+}\pi^{-} and D+πD^{*+}\pi^{-} final states and observed the two established L=1L=1 charmed mesons, the D1(2420)0D_1(2420)^0 with mass 242122+1+22421^{+1+2}_{-2-2} MeV/c2^{2} and width 2053+6+320^{+6+3}_{-5-3} MeV/c2^{2} and the D2(2460)0D_2^*(2460)^0 with mass 2465±3±32465 \pm 3 \pm 3 MeV/c2^{2} and width 2876+8+628^{+8+6}_{-7-6} MeV/c2^{2}. Properties of these final states, including their decay angular distributions and spin-parity assignments, have been studied. We identify these two mesons as the jlight=3/2j_{light}=3/2 doublet predicted by HQET. We also obtain constraints on {\footnotesize ΓS/(ΓS+ΓD)\Gamma_S/(\Gamma_S + \Gamma_D)} as a function of the cosine of the relative phase of the two amplitudes in the D1(2420)0D_1(2420)^0 decay.Comment: 15 pages in REVTEX format. hardcopies with figures can be obtained by sending mail to: [email protected]

    Measurement of the Decay Asymmetry Parameters in Λc+Λπ+\Lambda_c^+ \to \Lambda\pi^+ and Λc+Σ+π0\Lambda_c^+ \to \Sigma^+\pi^0

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    We have measured the weak decay asymmetry parameters (\aLC ) for two \LC\ decay modes. Our measurements are \aLC = -0.94^{+0.21+0.12}_{-0.06-0.06} for the decay mode Λc+Λπ+\Lambda_c^+ \to \Lambda\pi^+ and \aLC = -0.45\pm 0.31 \pm 0.06 for the decay mode ΛcΣ+π0\Lambda_c \to \Sigma^+\pi^0 . By combining these measurements with the previously measured decay rates, we have extracted the parity-violating and parity-conserving amplitudes. These amplitudes are used to test models of nonleptonic charmed baryon decay.Comment: 11 pages including the figures. Uses REVTEX and psfig macros. Figures as uuencoded postscript. Also available as http://w4.lns.cornell.edu/public/CLNS/1995/CLNS95-1319.p
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