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R Chavan

Publications and source records attributed to R Chavan.

5 recordsLinked to original sources

Expression of CCL20 and granulocyte-macrophage colony-stimulating factor, but not Flt3-L, from modified vaccinia virus ankara enhances antiviral cellular and humoral immune responses.

While modified vaccinia virus Ankara (MVA) is currently in clinical development as a safe vaccine against smallpox and heterologous infectious diseases, its immunogenicity is likely limited due to the inability of the virus to replicate productively in mammalian hosts. In light of recent data demonstrating that vaccinia viruses, including MVA, preferentially infect antigen-presenting cells (APCs) that play crucial roles in generating antiviral immunity, we hypothesized that expression of specific cytokines and chemokines that mediate APC recruitment and activation from recombinant MVA (rMVA) vectors would enhance the immunogenicity of these vectors. To test this hypothesis, we generated rMVAs that express murine granulocyte-macrophage colony-stimulating factor (mGM-CSF), human CCL20/human macrophage inflammatory protein 3alpha (hCCL20/hMIP-3alpha), or human fms-like tyrosine kinase 3 ligand (hFlt3-L), factors predicted to increase levels of dendritic cells (DCs), to recruit DCs to sites of immunization, or to promote maturation of DCs in vivo, respectively. These rMVAs also coexpress the well-characterized, immunodominant lymphocytic choriomeningitis virus nucleoprotein (NP) antigen that enabled sensitive and quantitative assessment of antigen-specific CD8(+) T-cell responses following immunization of BALB/c mice. Our results demonstrate that immunization of mice with rMVAs expressing mGM-CSF or hCCL20, but not hFlt3-L, results in two- to fourfold increases of cellular immune responses directed against vector-encoded antigens and 6- to 17-fold enhancements of MVA-specific antibody titers, compared to those responses elicited by nonadjuvanted rMVA. Of note, cytokine augmentation of cellular immune responses occurs when rMVAs are given as primary immunizations but not when they are used as booster immunizations, suggesting that these APC-modulating proteins, when used as poxvirus-encoded adjuvants, are more effective at stimulating naïve T-cell responses than in promoting recall of preexisting memory T-cell responses. Our results demonstrate that a strategy to express specific genetic adjuvants from rMVA vectors can be successfully applied to enhance the immunogenicity of MVA-based vaccines.

Animals↗

Does salvage and tranexamic acid reduce the need for blood transfusion in revision hip surgery?

We carried out a retrospective case-control study in 80 patients who underwent a revision total hip replacement. Group A (40 patients) received tranexamic acid and intra-operative cell salvage. Group B (40 patients) was a matched control group and did not receive this management. Each group was divided into four subgroups: revision of both components, revision of both components with bone grafting, revision of the acetabular component with or without bone graft, and revision of the femoral component with or without bone graft. In group A the total number of units transfused was 52, compared with 139 in group B, representing a reduction in blood usage of 62.5%. The mean amount of blood transfused from cell salvage in each group was 858 ml (113 to 2100), 477 ml (0 to 2680), 228 ml (75 to 315) and 464 ml (120 to 1125), respectively. There was a significant difference in the amount of blood returned between the groups (p < 0.0001). In group A, 22 patients needed transfusion and in group B, 37 (p < 0.0001). A cost analysis calculation showed a total revenue saving of pounds sterling 70 000 and a potential saving throughout our facility of pounds sterling 318 288 per year. Our results show that a significant reduction in blood transfusion can be made using combined cell salvage and tranexamic acid in revision surgery of the hip.

Analysis of Variance↗

Comparison of cough of 2 and 3 weeks to improve detection of smear-positive tuberculosis cases among out-patients in India.

SETTING: Governmental health facilities in six districts of India. OBJECTIVE: To estimate the prevalence of cough and to compare the detection of smear-positive tuberculosis (TB) among out-patients with cough of > or =2 or > or =3 weeks. DESIGN: Trained health workers questioned each out-patient for presence of cough. Those with cough > or =2 weeks underwent sputum microscopy. RESULTS: Of 55561 out-patients interviewed, 2210 (4%) had cough > or =2 weeks, of whom 267 had sputum-positive TB, compared to 182/1370 with cough > or =3 weeks. The 31% who did not spontaneously complain of cough were less likely to be sputum-positive than those who did (45/680 [7%] vs. 222/1530 [15%], P < 0.001), but they accounted for 45/267 smear-positive cases. Using cough > or =2 weeks as the screening criterion, the estimated number of smears performed per day at each primary and secondary health care facility was respectively 8 and 19, compared to 5 and 12 using cough > or =3 weeks. CONCLUSION: The detection of smear-positive TB cases can be substantially improved by actively eliciting history of cough from all out-patients, and by changing the screening criterion for performing sputum microscopy among out-patients from cough > or =3 weeks to > or =2 weeks. Before implementing this change nationally, its programmatic feasibility should be assessed.

Adolescent↗

Steady-state fully noninductive current driven by electron cyclotron waves in a magnetically confined plasma

A steady-state, fully noninductive plasma current has been sustained for the first time in a tokamak using electron cyclotron current drive only. In this discharge, 123 kA of current have been sustained for the entire gyrotron pulse duration of 2 s. Careful distribution across the plasma minor radius of the power deposited from three 0. 5-MW gyrotrons was essential for reaching steady-state conditions. With central current drive, up to 153 kA of current have been fully replaced transiently for 100 ms. The noninductive scenario is confirmed by the ability to recharge the Ohmic transformer. The dependence of the current drive efficiency on the minor radius is also demonstrated.

Journal Article↗