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1.
Gulab D. Khedkar A. Chandra Shekar Reddy Persis Mann Kondadhasula Ravinder Kshitish Muzumdar 《Molecular biology reports》2010,37(3):1355-1362
Genetic similarity and diversity of catfish Clarias batrachus (Linn.1758) populations collected from three regions of Indian riverine system were examined using randomly amplified polymorphic
DNA-polymerase chain reaction (RAPD-PCR). Out of 22 random primers tested, six primers produced 462 RAPD bands ranging from
105 to 128 polymorphic bands per primer in size between 100 and 1,200 bp. The polymorphic bands in these populations ranged
from 26.5 to 30.5. Polymorphic bands within populations ranged from 25 to 35.7%. The degree of similarity within Hussainabad
population varied from 0.125 to 0.842 based on average level of band sharing (BS) values. The level of band sharing values
within the catfish populations were 0.26 ± 0.021 for Banaras, 0.60 ± 0.033 for Bhubaneshwar and 0.377 ± 0.058 for Hussainabad
respectively. The results from the present study indicate that there is great degree of genetic similarity between Bhubaneshwar
and Hussainabad populations where as Banaras catfish population is distinct. It may appear that Bhubaneshwar and Hussainabad
are geographically connected by rivers and most of the major catfish hatcheries are located in this region, therefore the
individuals from these populations are get reared in the same environmental conditions, migration or by inbreeding during
several generations may be possible. This may be the reason that catfish population is lacking genetic diversity in major
riverine system of India. In nearer future, the lack in genetic diversity can lead to inbreeding which can be resulted in
poor growth and disease susceptibility, Bhubaneshwar and Hussainabad catfish population may have this problem. 相似文献
2.
Winnie Ip Juliana M.F. Silva Hubert Gaspar Arindam Mitra Shreenal Patel Kanchan Rao Robert Chiesa Persis Amrolia Kimberly Gilmour Gul Ahsan Mary Slatter Andrew R. Gennery Robert F. Wynn Paul Veys Waseem Qasim 《Cytotherapy》2018,20(6):830-838
Background
Adenovirus (ADV) reactivation can cause significant morbidity and mortality in children after allogeneic stem cell transplantation. Antiviral drugs can control viremia, but viral clearance requires recovery of cell-mediated immunity.Method
This study was an open-label phase 1/2 study to investigate the feasibility of generating donor-derived ADV-specific T cells (Cytovir ADV, Cell Medica) and to assess the safety of pre-emptive administration of ADV-specific T cells in high-risk pediatric patients after allogeneic hematopoietic stem cell transplantation (HSCT) to treat adenoviremia. Primary safety endpoints included graft-versus-host disease (GvHD), and secondary endpoints determined antiviral responses and use of antiviral drugs.Results
Between January 2013 and May 2016, 92 donors were enrolled for the production of ADV T cells at three centers in the United Kingdom (UK), and 83 products were generated from 72 mobilized peripheral blood harvests and 20 steady-state whole blood donations. Eight children received Cytovir ADV T cells after standard therapy and all resolved ADV viremia between 15 and 127 days later. ADV-specific T cells were detectable using enzyme-linked immunospot assay (ELISpot) in the peripheral blood of all patients analyzed. Serious adverse events included Grade II GvHD, Astrovirus encephalitis and pancreatitis.Conclusion
The study demonstrates the safety and feasibility of pre-emptively manufacturing peptide pulsed ADV-specific cells for high-risk pediatric patients after transplantation and provides early evidence of clinical efficacy. 相似文献3.
Persis M Chandra Sekhar Reddy A Rao LM Khedkar GD Ravinder K Nasruddin K 《Molecular biology reports》2009,36(7):1733-1740
Mitochondrial DNA, cytochrome oxidase-1 gene sequences were analyzed for species identification and phylogenetic relationship
among the very high food value and commercially important Indian carangid fish species. Sequence analysis of COI gene very
clearly indicated that all the 28 fish species fell into five distinct groups, which are genetically distant from each other
and exhibited identical phylogenetic reservation. All the COI gene sequences from 28 fishes provide sufficient phylogenetic
information and evolutionary relationship to distinguish the carangid species unambiguously. This study proves the utility
of mtDNA COI gene sequence based approach in identifying fish species at a faster pace. 相似文献
4.
Hematopoietic growth factor inducible neurokinin-1 type: a transmembrane protein that is similar to neurokinin 1 interacts with substance P 总被引:4,自引:0,他引:4
Bandari PS Qian J Yehia G Joshi DD Maloof PB Potian J Oh HS Gascon P Harrison JS Rameshwar P 《Regulatory peptides》2003,111(1-3):169-178
Neurokinin 1 (NK-1) is a member of seven transmembrane G protein-coupled receptors. NK-1 interacts with peptides belonging to the tachykinin family and showed preference for substance P (SP). NK-1 is induced in bone marrow (BM) stroma. NK-1-SP interactions could lead to changes in the functions of lymphohematopoietic stem cell (LHSC). This report describes the cloning and characterization of a cDNA clone isolated after screening of three cDNA libraries with an NK-1-specific probe. Based on its expression, the cDNA clone was designated hematopoietic growth factor inducible neurokinin-1 type (HGFIN). Computational analyses predicted that HGFIN is transmembrane with the carboxyl terminal extracellular. Proteomic studies with purified HGFIN and SP showed noncovalent interactions. HGFIN-SP interactions were supported by transient expression of HGFIN in CHO cells. Transient expression of HGFIN in unstimulated BM fibroblasts led to the induction of endogenous NK-1. Since NK-1 expression in BM fibroblasts requires cell stimulation, these studies suggest that there might be intracellular crosstalk between NK-1 and HGFIN. Northern analyses with total RNA from different BM cell subsets showed that HGFIN was preferentially expressed in differentiated cells. This suggests that HGFIN might be involved in the maturation of LHSC. HGFIN was detected in several other tissues, but not in brain where NK-1 is constitutively expressed. 相似文献
5.
Butte AJ Sigdel TK Wadia PP Miklos DB Sarwal MM 《Molecular & cellular proteomics : MCP》2011,10(3):M110.000497
Biomarkers for early detection of chronic kidney disease are needed, as millions of patients suffer from chronic diseases predisposing them to kidney failure. Protein microarrays may also hold utility in the discovery of auto-antibodies in other conditions not commonly considered auto-immune diseases. We hypothesized that proteins are released as a consequence of damage at a cellular level during end-organ damage from renal injury, not otherwise recognized as self-antigens, and an adaptive humoral immune response to these proteins might be detected in the blood, as a noninvasive tracker of this injury. The resultant antibodies (Ab) detected in the blood would serve as effective biomarkers for occult renal injury, enabling earlier clinical detection of chronic kidney disease than currently possible, because of the redundancy of the serum creatinine as a biomarker for early kidney injury. To screen for novel autoantibodies in chronic kidney disease, 24 protein microarrays were used to compare serum Ab from patients with chronic kidney disease against matched controls. From a panel of 38 antigens with increased Ab binding, four were validated in 71 individuals, with (n=50) and without (n=21) renal insufficiency. Significant elevations in the titer of novel auto-Ab were noted against angiotensinogen and PRKRIP1 in renal insufficiency. Current validation is underway to evaluate if these auto-Ab can provide means to follow the evolution of chronic kidney disease in patients with early stages of renal insufficiency, and if these rising titers of these auto-Ab correlate with the rate of progression of chronic kidney disease. 相似文献
6.
Add-back of allodepleted donor T cells to improve immune reconstitution after haplo-identical stem cell transplantation 总被引:1,自引:0,他引:1
Amrolia PJ Mucioli-Casadei G Huls H Heslop HE Schindler J Veys P Vitetta ES Brenner MK 《Cytotherapy》2005,7(2):116-125
Poor immune reconstitution after haplo-identical stem cell transplantation results in high mortality from viral infections and relapse. One approach to overcome this problem is to deplete alloreactive cells selectively by deleting T cells activated by recipient stimulators, using an immunotoxin directed against the activation marker CD25. However, the degree of depletion of alloreactive cells is variable following stimulation with recipient PBMC, and this can result in GvHD. We have shown that using recipient EBV-transformed LCL as stimulators to activate donor alloreactive T cells results in more consistent depletion of in vitro alloreactivity while preserving T-cell responses to viral and potential myeloid tumor Ag. Based on these data, we have embarked on a phase I clinical dose escalation study of add-back of allo-LCL-depleted donor T cells in the haplo-identical setting, to determine if the allodepletion we achieve to allow infusion of sufficient T cells to restore useful antiviral/anti-leukemic responses without causing GvHD. Fifteen patients have so far been treated. The incidence of significant acute or chronic GvHD has been low (2/15), as has mortality from infection (1/15). Preliminary data show accelerated immune reconstitution in dose level 2 patients. Infused allodepleted donor T cells appear able to expand significantly in the face of viral reactivations, and doses as low as 3 x 10(5)/kg may be sufficient to confer useful antiviral immunity in this setting. At a median follow-up of 19.5 months, nine of 15 patients are alive and disease-free. Five patients have relapsed, all of whom have died. 相似文献
7.
Sarah J. Albon Christoph Mancao Kimberly Gilmour Geoffrey White Ida Ricciardelli Jennifer Brewin Gertjan Lugthart Rebecca Wallace Persis J. Amrolia 《Cytotherapy》2013,15(1):109-121
Background aimsImmunotherapy with allodepleted donor T cells improves immunity after T cell-depleted hematopoietic stem cell transplantation. We developed a methodology for selective depletion of alloreactive T cells after activation with host antigen-presenting cells by targeting T cells up-regulating CD25 and CD71. Combined depletion of these cells yields a pool of allodepleted donor T cells with antiviral properties with minimal capacity to cause graft-versus-host disease.MethodsMature dendritic cells were irradiated and used to stimulate donor peripheral blood mononuclear cells for 4 days. The co-culture was stained with anti-CD71-biotin followed by CliniMACS CD25 and Anti-Biotin Reagents (Miltenyi Biotec GmbH; Bergisch Gladbach, Germany) before depletion on the CliniMACS Plus (Miltenyi Biotec GmbH). Residual alloreactivity was tested by flow cytometry, a secondary mixed lymphocyte reaction and limiting dilution analysis, and specific anti-viral immunity with pentamer staining. The large-scale protocol was tested under current good manufacturing practice conditions in five donor-recipient pairs of human leukocyte antigen-matched volunteer donors.ResultsWe developed a closed-system methodology using cell differentiation bags for cell culture and the COBE2991 Cell Processor (CaridianBCT, Lakewood, CO, USA). We also validated an anti-CD71-biotin generated for ex vivo clinical use. In five large-scale runs, the depleted fraction demonstrated excellent viability (99.9%), minimal residual expression of CD3/CD25 and CD3/CD71 (<0.2%) and passed tests for Mycoplasma, endotoxin, bacterial and fungal sterility. In secondary mixed lymphocyte reaction assays, the median response to host after allodepletion was 0%, whereas responses to third-party peripheral blood mononuclear cells were preserved (median, 105%; range 37%–350%). Limiting dilution analysis assays also demonstrated a reduction in response to host (median, ?1.11 log) with preservation of third-party responses, and testing with human leukocyte antigen-restricted pentamers showed that populations of Epstein-Barr virus-specific and cytomegalovirus-specific CD8+ T cells were retained after depletion.ConclusionsWe optimized a protocol for the combined immunomagnetic depletion of alloreactive CD25/CD71 T cells under current good manufacturing practice conditions and tested the efficacy in five donor-recipient pairs. 相似文献
8.
B cells promote insulin resistance through modulation of T cells and production of pathogenic IgG antibodies 总被引:2,自引:0,他引:2
Winer DA Winer S Shen L Wadia PP Yantha J Paltser G Tsui H Wu P Davidson MG Alonso MN Leong HX Glassford A Caimol M Kenkel JA Tedder TF McLaughlin T Miklos DB Dosch HM Engleman EG 《Nature medicine》2011,17(5):610-617
Chronic inflammation characterized by T cell and macrophage infiltration of visceral adipose tissue (VAT) is a hallmark of obesity-associated insulin resistance and glucose intolerance. Here we show a fundamental pathogenic role for B cells in the development of these metabolic abnormalities. B cells accumulate in VAT in diet-induced obese (DIO) mice, and DIO mice lacking B cells are protected from disease despite weight gain. B cell effects on glucose metabolism are mechanistically linked to the activation of proinflammatory macrophages and T cells and to the production of pathogenic IgG antibodies. Treatment with a B cell-depleting CD20 antibody attenuates disease, whereas transfer of IgG from DIO mice rapidly induces insulin resistance and glucose intolerance. Moreover, insulin resistance in obese humans is associated with a unique profile of IgG autoantibodies. These results establish the importance of B cells and adaptive immunity in insulin resistance and suggest new diagnostic and therapeutic modalities for managing the disease. 相似文献
9.
Rameshwar P Gascon P Bandari PS Joshi DD Fernandes A Dang A 《Canadian journal of physiology and pharmacology》2002,80(5):475-481
In the adult bone marrow (BM), immune cells are replenished through the process of definitive hematopoiesis, which is regulated by a complex process of cellular and humoral interactions. The latter include substance P (SP), a neurotransmitter that is produced by neural and nonneural cells. Neurokinin-1 (NK-1), the high-affinity SP receptor, shares structural similarity with fibronectin, a component of the BM extracellular matrix proteins. This study examines how such similarity could alter the effects of SP on the proliferation of the immature BM progenitors. In vitro studies show that 1 ng fibronectin/mL enhanced the stimulatory effect of SP on the proliferation of primitive BM progenitors. This finding was studied by computational studies: proteomics and three-dimensional molecular modeling. Use of surface-enhanced laser desorption/ionization ProteinChip technology showed that despite the induction of neutral endopeptidase, exogenous fibronectin hindered the degradation of SP to SP(1-4). These findings support a protective role for fibronectin in the digestion of SP. Since SP(1-4) is a negative regulator of hematopoiesis, this report indicates that the structural similarity between fibronectin and NK-1 could be important for maintaining hematopoietic stimulation. These studies could be extrapolated to hematological disorders that are associated with SP-fibronectin complexes. 相似文献
10.