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341.
Kohli E Raj HG Kumari R Rohil V Kaushik NK Prasad AK Parmar VS 《Bioorganic & medicinal chemistry letters》2002,12(18):2579-2582
Earlier work carried out in our laboratory highlighted the mode of action of acetoxy 4-methylcoumarins in preventing the genotoxicity of aflatoxin B(1) (AFB(1)). We have in this report extended the observations to quercetin pentaacetate (QPA), which unlike quercetin (Q) has demonstrated time-dependent inhibition of liver microsome catalysed AFB(1) epoxidation as measured by AFB(1) binding to DNA. The action of QPA is similar to that of the acetoxy 4-methylcoumarins in that they are acted upon by microsomal transacetylase leading to modulation of catalytic activities of certain enzymes (such as P-450 enzymes, NADPH cytochrome C reductase and glutathione S-transferase) possibly by way of protein acetylation. In the present work, we have documented the transacetylase-mediated action of QPA in preventing genotoxicity due to AFB(1). 相似文献
342.
Knox KS Day RB Wood KL Kohli LL Hage CA Foresman BH Schnizlein-Bick CT Twigg HL 《Cellular immunology》2004,229(2):130-138
Macrophages are accessory cells that are vulnerable to infection by HIV-1. HTLV-IIIB, a lymphotropic strain of HIV, infects macrophages poorly resulting in either no or low levels of virus expression compared to high levels of productive infection after exposure of macrophages to the monocytotropic HIV strain Ada-M. Whether this results in an impaired ability of HTLV-IIIB-exposed macrophages to initiate protective cytotoxic T lymphocyte (CTL) immune responses against these strains is not well defined. We investigated the ability of monocyte-derived macrophages (MDM) exposed to lymphotropic and monocytotropic HIV strains to initiate primary CTL responses in vitro. MDM exposed to HTLV-IIIB induced a specific primary CTL response that was comparable to MDM exposed to the monocytotropic strain Ada-M despite marked differences in productive HIV infection in MDM between the two strains. CTL generated in this model were MHC-restricted, strain-specific, and CD8+. These data demonstrate that high levels of productive HIV infection in accessory cells are not a prerequisite for the generation of a primary CTL response, suggesting a novel immunologic interaction between MDM and lymphotropic HIV strains. 相似文献
343.
Rotavirus 2/6 virus-like particles administered intranasally in mice, with or without the mucosal adjuvants cholera toxin and Escherichia coli heat-labile toxin, induce a Th1/Th2-like immune response 总被引:2,自引:0,他引:2 下载免费PDF全文
We investigated the rotavirus-specific lymphocyte responses induced by intranasal immunization of adult BALB/c mice with rotavirus 2/6 virus-like particles (2/6-VLPs) of the bovine RF strain, by assessing the profile of cytokines produced after in vitro restimulation and serum and fecal antibody responses. The cytokines produced by splenic cells were first evaluated. Intranasal immunization with 50 microg of 2/6-VLPs induced a high serum antibody response, including immunoglobulin G1 (IgG1) and IgG2a, a weak fecal antibody response, and a mixed Th1/Th2-like profile of cytokines characterized by gamma interferon and interleukin 10 (IL-10) production and very low levels of IL-2, IL-4, and IL-5. Intranasal immunization with 10 microg of 2/6-VLPs coadministered with the mucosal adjuvants cholera toxin and Escherichia coli heat-labile toxin (LT) considerably enhanced the Th1/Th2-like response; notably, significant levels of IL-2, IL-4, and IL-5 were observed. Since rotavirus is an enteric pathogen, we next investigated the production of IL-2 and IL-5, as being representative of Th1 and Th2 responses, by Peyer's patch and mesenteric lymph node cells from mice immunized intranasally with 2/6-VLPs and LT. The results were compared to those obtained from splenic and cervical lymph node cells. We found that both cytokines were produced by cells from each of these lymphoid tissues. These results confirm the Th1/Th2-like response observed at the systemic level and show, on the assumption that T cells are the primary cells producing the cytokines after in vitro restimulation, that rotavirus-specific T lymphocytes are present in the intestine after intranasal immunization with 2/6-VLPs and LT. 相似文献
344.
Transposon insertional mutagenesis in rice 总被引:4,自引:0,他引:4
Greco R Ouwerkerk PB Sallaud C Kohli A Colombo L Puigdomènech P Guiderdoni E Christou P Hoge JH Pereira A 《Plant physiology》2001,125(3):1175-1177
345.
Dipesh Debnath Sona Yengkokpam B. K. Bhattacharjya Pradyut Biswas C. Prakash M. P. S. Kohli A. P. Sharma 《Proceedings of the Zoological Society》2018,71(1):74-82
Keeping the importance and search for unconventional feed resources and/or standardizing their level of incorporation in mind, we incorporated dry-powdered water hyacinth (Eichhornia crassipes) meal in feeds and studied its effect on growth and digestibility in Labeo rohita fingerlings. Five feeds with 30 % crude protein level were formulated using Eichhornia meal (EM) at 0 (control), 5 (EMF1), 10 (EMF2), 15 (EMF3) or 20 % (EMF4) of the diet replacing rice bran by equal proportions. Three hundred fingerlings (7.40 ± 0.05 cm; 5.27 ± 0.12 g) were distributed into fifteen tanks (200 l capacity) and fed the experimental diets for 60 days. In the last 30 days, digestibility studies were conducted using 0.5 % chromic oxide as an external marker in feed. At 10 % inclusion of EM, the experimental fish showed the highest weight gain percent (WG%), specific growth rate (SGR), protein efficiency ratio and apparent net protein utilization with lowest feed conversion ratio. Whereas the growth performance at 15 % inclusion level was comparable with the control and further increase to 20 % level of EM showed reduced growth responses but the feed was fairly palatable to the fish. Lower digestibility was also observed in EMF4 group. It is concluded that EM can be included at 15 % level in the feed of L. rohita fingerlings without adversely affecting the growth, dry matter and nutrient digestibility. However, economic feasibility of this feedstuff needs to be analyzed to see whether the reduced cost of diets would compensate for the reduced performance of fish at higher inclusion levels. 相似文献
346.
Viral N. Shah Balneek Singh Cheema Rajni Sharma Madhu Khullar Harbir Singh Kohli Tarunveer Singh Ahluwalia Viswanathan Mohan Anil Bhansali 《Molecular and cellular biochemistry》2013,372(1-2):191-198
Patients with type 2 diabetes (T2DM) are usually obese and concurrent obesity results into activation of the renin–angiotensin-system (RAS) which is a risk factor for diabetic nephropathy (DN). Gene–gene interaction between acetyl-coenzymeA carboxylase beta (ACACβ) gene, which is involved in fatty acid metabolism and angiotensin II receptors (AGTR1) gene, which mediates RAS proteins actions on renal tissue, polymorphism with DN have not been studied earlier. The present study was designed with the aim to examine the association of an ACACβ (rs2268388) and AGTR1 (rs5186) gene polymorphism with the risk of DN in Asian Indians. 1,158 patients with T2DM belonging to two independently ascertained North Indian and one South Indian cohorts were genotyped for ACACβ (rs2268388) and AGTR1 (rs5186) polymorphism using real time PCR-based Taq-man assay and PCR–RFLP assays. In all the three cohorts, a significantly higher frequency of T allele and TT genotypes of ACACβ and C allele and CC genotypes of AGTR1 were found in patients with DN as compared to patients without nephropathy. Further, T allele of ACACβ and C allele of AGTR1 were found to be significantly associated with proteinuria, a hallmark of DN. We also found significant epistatic interactions between these two genes. TT genotypes of ACACβ gene and CC genotype of AGTR1 gene confers the risk of DN and both genes had significant epistatic interaction in Asian Indian patients with T2DM. 相似文献
347.
Therapy-induced autophagy is recognized as a critical determinant of treatment outcome in cancer patients, primarily as a factor underlying drug resistance. However, recent investigations point toward a context-dependent, death-inducing role for autophagy, the mechanism of which remains largely unknown. Our recent study provides evidence that autophagy can directly mediate cell killing in multiple tumor cell types by facilitating degradation of KRAS/K-Ras, a key survival protein. These findings have broad implications for strategies employing autophagy modulation to target tumor cells. 相似文献
348.
Nikhil Kothari Jaishri Bogra Haider Abbas Monica Kohli Anita Malik Divya Kothari Shivani Srivastava Prithvi K. Singh 《Cytokine》2013,61(2):676-681
IntroductionSystemic sepsis releases several cytokines among which tumor necrosis factor alfa (TNFα) has emerged as key cytokine causing septic shock. Single Nucleotide Polymorphisms (SNPs) at positions ?238, ?308, ?376 and +489 in the promoter region of TNF gene exhibit differential association to inflammation and increased TNF production in sepsis.Materials and MethodsThis research work was carried out in 278 critically ill patients and 115 controls. The patients were divided into four groups: Healthy controls, SIRS, Sepsis and Septic shock. Plasma cytokine level was evaluated by ELISA. Specific sequences of TNF gene (?238, ?308, ?376, +489) were amplified using polychromase chain reaction (PCR). SNP detected by BamHiI, NcoI, FokI, TaiI restriction enzymes.ResultsMean plasma TNFα level in healthy Control group was 8.37 ± 2.23 pg/ml, in SIRS group, the mean plasma TNFα level was 77.99 ± 5.51 pg/ml, in Sepsis patients 187.1 ± 14.33 pg/ml and in septic shock 202.2 ± 14.85 pg/ml; range 56.17–417.1 pg/ml. SNP was studied among different patient groups, which showed a higher frequency of mutants among sepsis and shock patients as compared to control.ConclusionPlasma TNF alpha level was significantly high in patients with sepsis and septic shock. SNP of TNF gene showed significant association between polymorphism and development of severe sepsis and septic shock, this would help us in evaluating patients at high risk for septic shock and such patients needed to obtain a rational basis for therapy. 相似文献
349.
Lihui Xu Neeraj Kohli Rachel Rennard Yang Jiao Maja Razlog Kathy Zhang Jason Baum Bryan Johnson Jian Tang Birgit Schoeberl Jonathan Fitzgerald Ulrik Nielsen Alexey A. Lugovskoy 《MABS-AUSTIN》2013,5(2):237-254
Multispecific antibody-like molecules have the potential to advance the standard-of-care in many human diseases. The design of therapeutic molecules in this class, however, has proven to be difficult and, despite significant successes in preclinical research, only one trivalent antibody, catumaxomab, has demonstrated clinical utility. The challenge originates from the complexity of the design space where multiple parameters such as affinity, avidity, effector functions, and pharmaceutical properties need to be engineered in concurrent fashion to achieve the desired therapeutic efficacy. Here, we present a rapid prototyping approach that allows us to successfully optimize these parameters within one campaign cycle that includes modular design, yeast display of structure focused antibody libraries and high throughput biophysical profiling. We delineate this approach by presenting a design case study of MM-141, a tetravalent bispecific antibody targeting two compensatory signaling growth factor receptors: insulin-like growth factor 1 receptor (IGF-1R) and v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (ErbB3). A MM-141 proof-of-concept (POC) parent molecule did not meet initial design criteria due to modest bioactivity and poor stability properties. Using a combination of yeast display, structured-guided antibody design and library-scale thermal challenge assay, we discovered a diverse set of stable and active anti-IGF-1R and anti-ErbB3 single-chain variable fragments (scFvs). These optimized modules were reformatted to create a diverse set of full-length tetravalent bispecific antibodies. These re-engineered molecules achieved complete blockade of growth factor induced pro-survival signaling, were stable in serum, and had adequate activity and pharmaceutical properties for clinical development. We believe this approach can be readily applied to the optimization of other classes of bispecific or even multispecific antibody-like molecules. 相似文献
350.
Johannes M. Hennings Martin A. Kohli Darina Czamara Maria Giese Anne Eckert Christiane Wolf Angela Heck Katharina Domschke Volker Arolt Bernhard T. Baune Sonja Horstmann Tanja Brückl Torsten Klengel Andreas Menke Bertram Müller-Myhsok Marcus Ising Manfred Uhr Susanne Lucae 《PloS one》2013,8(6)