Multicenter evaluation of parametric response mapping as an indicator of bronchiolitis obliterans syndrome after hematopoietic stem cell transplantation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156134/2/ajt15814_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156134/1/ajt15814.pd

Myocardial production and release of MCP-1 and SDF-1 following myocardial infarction: differences between mice and man

<p>Abstract</p> <p>Background</p> <p>Stem cell homing to the heart is mediated by the release of chemo-attractant cytokines. Stromal derived factor -1 alpha (SDF-1a) and monocyte chemotactic factor 1(MCP-1) are detectable in peripheral blood after myocardial infarction (MI). It remains unknown if they are produced by, and released from, the heart in order to attract stem cells to repair the damaged myocardium.</p> <p>Methods</p> <p>Murine hearts were studied for expression of MCP-1 and SDF-1a at day 3 and day 28 following myocardial infarction to determine whether production is increased following MI. In addition, we studied the coronary artery and coronary sinus (venous) blood from patients with normal coronary arteries, stable coronary artery disease (CAD), unstable angina and MI to determine whether these cytokines are released from the heart into the systemic circulation following MI.</p> <p>Results</p> <p>Both MCP-1 and SDF-1a are constitutively produced and released by the heart. MCP-1 mRNA is upregulated following murine experimental MI, but SDF-1a is suppressed. There is less release of SDF-1a into the systemic circulation in patients with all stages of CAD including MI, mimicking the animal model. However MCP-1 release from the human heart following MI is also suppressed, which is the exact opposite of the animal model.</p> <p>Conclusions</p> <p>SDF-1a and MCP-1 release from the human heart are suppressed following MI. In the case of SDF-1a, the animal model appropriately reflects the human situation. However, for MCP-1 the animal model is the exact opposite of the human condition. Human observational studies like this one are paramount in guiding translation from experimental studies to clinical trials.</p

HLA Class I and Class II Associations in Dengue Viral Infections in a Sri Lankan Population

BACKGROUND: HLA class I and class II alleles have been shown to be associated with the development of dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS) in different populations. However, the majority of studies have been based on limited numbers of patients. In this study we aimed to investigate the HLA-class I and class II alleles that are positively and negatively associated with the development of DSS in a cohort of patients with DHF and also the alleles associated with development of DHF during primary dengue infections in a Sri Lankan population. METHODOLOGY/PRINCIPAL FINDINGS: The allele frequencies of HLA class I and class II alleles were compared in 110 patients with DHF and 119 individuals from the population who had never reported a symptomatic dengue infection at the time of recruitment. We found that HLA-A*31 (corrected P = 0.01) and DRB1*08 (corrected P = 0.009) were associated with susceptibility to DSS when infected with the dengue virus, during secondary dengue infection. The frequency of DRB1*08 allele was 28.7 times higher than in the normal population in patients with DSS. HLA-A*31 allele was increased 16.6 fold in DHF who developed shock when compared to those who did not develop shock. A*24 (corrected P = 0.03) and DRB1*12 (corrected P = 0.041) were strongly associated with the development of DHF during primary dengue infection. CONCLUSIONS/SIGNIFICANCE: These data suggest that certain HLA alleles confer susceptibility/protection to severe dengue infections. As T cell epitope recognition depend on the HLA type of an individual, it would be now important to investigate how epitope specific T cells associate with primary and secondary dengue infections and in severe dengue infections

Synthesis, Antibacterial and Antioxidant Evaluation of Novel 1-(5,7-Dichloro-1,3-benzoxazol-2-yl)-1H-pyrazolo[3,4-b]quinoline Derivatives

Some novel 1-(5,7-dichloro-1,3-benzoxazol-2-yl)-1H-pyrazolo[3,4-b]quinoline derivatives 8(a–f) were synthesized by reacting 5,7-dichloro-2-hydrazino-1,3-benzoxazole 4 and substituted-2-chloro-3-quinoline carbaldehydes using p-toluenesulfonic acid (PTSA) as a catalyst for the cyclisation. The target molecules have been characterized by IR, 1H NMR, 13C NMR, and mass spectral studies. The synthesized compounds were screened for biological activities, and some of the compounds have exhibited encouraging antibacterial and antioxidant activities. The compounds 8a and 8e showed potent antibacterial activity, whereas the compounds 8e and 8f act as antioxidants

Synthesis and Biological Evaluation of Novel 5,7-Dichloro-1,3-benzoxazole Derivatives

A new class of 5,7-dichloro-1,3-benzoxazole derivatives 4–11 were synthesized by fusing 5,7-dichloro-2-hydrazino-1,3-benzoxazole 3 nucleus with aliphatic acids, active methylene compounds, and with selected esters to form heterocyclic ring systems like 1,2,4-triazoles, pyrazoles, and triazine moieties. The compound 3 on diazotization reaction affords the tetrazole compound. The synthesized compounds were characterized by 1H NMR, IR, Mass, and 13C NMR spectral data and screened for cytotoxic, antimicrobial, antioxidant, and antilipase activities. The compounds 4, 5, and 8 have shown significant antimicrobial activities, whereas compounds 6 and 8 have been emerged as leading cytotoxic agents. The compounds 9, 10, and 11 were found to be strong enzyme inhibitors

New Dengue Virus Type 1 Genotype in Colombo, Sri Lanka

The number of cases and severity of disease associated with dengue infection in Sri Lanka has been increasing since 1989, when the first epidemic of dengue hemorrhagic fever was recorded. We identified a new dengue virus 1 strain circulating in Sri Lanka that coincided with the 2009 dengue epidemic

A Comparative Oncology Drug Discovery Pipeline to Identify and Validate New Treatments for Osteosarcoma

Background: Osteosarcoma is a rare but aggressive bone cancer that occurs primarily in children. Like other rare cancers, treatment advances for osteosarcoma have stagnated, with little improvement in survival for the past several decades. Developing new treatments has been hampered by extensive genomic heterogeneity and limited access to patient samples to study the biology of this complex disease. Methods: To overcome these barriers, we combined the power of comparative oncology with patient-derived models of cancer and high-throughput chemical screens in a cross-species drug discovery pipeline. Results: Coupling in vitro high-throughput drug screens on low-passage and established cell lines with in vivo validation in patient-derived xenografts we identify the proteasome and CRM1 nuclear export pathways as therapeutic sensitivities in osteosarcoma, with dual inhibition of these pathways inducing synergistic cytotoxicity. Conclusions: These collective efforts provide an experimental framework and set of new tools for osteosarcoma and other rare cancers to identify and study new therapeutic vulnerabilities