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Biomedical subjects

S K Datta

Publications and source records attributed to S K Datta.

At least 19 recordsLinked to original sources

Pyramiding transgenes for multiple resistance in rice against bacterial blight, yellow stem borer and sheath blight.

Here we describe the development of transgene-pyramided stable elite rice lines resistant to disease and insect pests by conventional crossing of two transgenic parental lines transformed independently with different genes. The Xa21 gene (resistance to bacterial blight), the Bt fusion gene (for insect resistance) and the chitinase gene (for tolerance of sheath blight) were combined in a single rice line by reciprocal crossing of two transgenic homozygous IR72 lines. F4 plant lines carrying all the genes of interest stably were identified using molecular methods. The identified lines, when exposed to infection caused by Xanthomonas oryzae pv oryzae, showed resistance to bacterial blight. Neonate larval mortality rates of yellow stem borer ( Scirpophaga incertulas) in an insect bioassay of the same identified lines were 100%. The identified line pyramided with different genes to protect against yield loss showed high tolerance of sheath blight disease caused by Rhizoctonia solani.

Animals↗

Dominant NZB contributions to lupus in the (SWR x NZB)F1 model.

(SWR x NZB)F1 (or SNF1) mice succumb to lupus nephritis. Analysis of NZB x SNF1 backcross mice has recently revealed the existence of four dominant SWR loci (H2 on Chr 17, Swrl-1 on Chr 1, Swrl-2 on Chr 14 and Swrl-3 on Chr 18), and two NZB loci (Nba1 and Lbw2/Sbw2, both on Chr 4) conferring lupus susceptibility. The present study focusing on a panel of 88 SWR x SNF1 backcross mice reveals the existence of five suggestive loci for antinuclear antibody formation, consisting of three dominant NZB contributions (Nba4 on Chr 5, Lbw4 on Chr 6, and Nba5 on Chr 7), and two recessive SWR contributions (Swrl-1 on Chr 1, and Swrl-4 on Chr 10). In addition, this study reveals a dominant NZB locus for GN (Nba3 on Chr 7, peak at 31 cM), and a dominant NZB locus linked to early mortality, on Chr 10 (peak at 4 cM). Collectively, these studies suggest that lupus in the SNF1 strain is the epistatic end-product of four dominant SWR loci and four dominant NZB loci. The immunological functions and molecular identities of these loci await elucidation.

Animals↗

Elastic guided waves in a layered plate with rectangular cross section.

Guided waves in a layered elastic plate of rectangular cross section (finite width and thickness) has been studied in this paper. A semianalytical finite element method in which the deformation of the cross section is modeled by two-dimensional finite elements and analytical representation of propagating waves along the length of the plate has been used. The method is applicable to arbitrary number of layers and general anisotropic material properties of each layer, and is similar to the stiffness method used earlier to study guided waves in a laminated composite plate of infinite width. Numerical results showing the effect of varying the width of the plate on the dispersion of guided waves are presented and are compared with those for an infinite plate. In addition, effect of thin anisotropic coating or interface layers on the guided waves is investigated.

Elasticity↗

Angioplasty for chronic total coronary occlusions: safety and efficacy.

OBJECTIVE: To determine the short term results and safety of angioplasty in chronic coronary occlusions. METHODS: Eighty consecutive patients undergoing percutaneous transluminal coronary angioplasty (PTCA) for chronic coronary occlusions were prospectively analyzed for acute success rate and safety of the procedure. RESULTS: The mean age was 46.7 years (range 30-78 years). There were 72 males and eight females. Clinical presentation was recent myocardial infarction (MI) in four cases (5%), unstable angina in 20 (25%), chronic stable angina in 24 (30%) and past history of MI in 32 (40%) cases. Vessel distribution was left anterior descending artery (LAD) in 40 (50%), left circumflex artery (LCx) in 12 (15%) and right coronary artery (RCA) in 28 (35%) cases. Lesion length varied from 8 mm to 37 mm with a mean of 16.7 mm. Acute success rate was 70% (56/80). Twenty four cases (30%) had unsuccessful result due to failure to cross with wire (18 cases) or inability to cross with the balloon (six cases). One major complication in the form of type III coronary perforation was encountered which was successfully managed surgically. CONCLUSION: Percutaneous transluminal coronary angioplasty (PTCA) in chronic total occlusion has a reasonable success rate and very low complication rate.

Adult↗

Genetic contributions of nonautoimmune SWR mice toward lupus nephritis.

(SWR x New Zealand Black (NZB))F(1) (or SNF(1)) mice succumb to lupus nephritis. Although several NZB lupus susceptibility loci have been identified in other crosses, the potential genetic contributions of SWR to lupus remain unknown. To ascertain this, a panel of 86 NZB x F(1) backcross mice was immunophenotyped and genome scanned. Linkage analysis revealed four dominant SWR susceptibility loci (H2, Swrl-1, Swrl-2, and Swrl-3) and a recessive NZB locus, Nba1. Early mortality was most strongly linked to the H2 locus on chromosome (Chr) 17 (log likelihood of the odds (LOD) = 4.59 - 5.38). Susceptibility to glomerulonephritis was linked to H2 (Chr 17, LOD = 2.37 - 2.70), Swrl-2 (Chr 14, 36 cM, LOD = 2.48 - 2.71), and Nba1 (Chr 4, 75 cM, LOD = 2.15 - 2.23). IgG antinuclear autoantibody development was linked to H2 (Chr 17, LOD = 4.92 - 5.48), Swrl-1 (Chr 1, 86 cM, colocalizing with Sle1 and Nba2, LOD = 2.89 - 2.91), and Swrl-3 (Chr 18, 14 cM, LOD = 2.07 - 2.13). For each phenotype, epistatic interaction of two to three susceptibility loci was required to attain the high penetrance levels seen in the SNF(1) strain. Although the SWR contributions H2, Swrl-1, and Swrl-2 map to loci previously mapped in other strains, often linked to very similar phenotypes, Swrl-3 appears to be a novel locus. In conclusion, lupus in the SNF(1) strain is truly polygenic, with at least four dominant contributions from the SWR strain. The immunological functions and molecular identities of these loci await elucidation.

Animals↗

Immunostimulatory DNA-based vaccines elicit multifaceted immune responses against HIV at systemic and mucosal sites.

Immunostimulatory DNA sequences (ISS, also known as CpG motifs) are pathogen-associated molecular patterns that are potent stimulators of innate immunity. We tested the ability of ISS to act as an immunostimulatory pathogen-associated molecular pattern in a model HIV vaccine using gp120 envelope protein as the Ag. Mice immunized with gp120 and ISS, or a gp120:ISS conjugate, developed gp120-specific immune responses which included: 1) Ab production; 2) a Th1-biased cytokine response; 3) the secretion of beta-chemokines, which are known to inhibit the use of the CCR5 coreceptor by HIV; 4) CTL activity; 5) mucosal immune responses; and 6) CD8 T cell responses that were independent of CD4 T cell help. Based on these results, ISS-based immunization holds promise for the development of an effective preventive and therapeutic HIV vaccine.

AIDS Vaccines↗

Off-axis propagation of ultrasonic guided waves in thin orthotropic layers: theoretical analysis and dynamic holographic imaging measurement.

The elastic properties of many materials in sheet or plate form can be approximated with orthotropic symmetry. In many sheet material manufacturing industries (e.g., the paper industry), manufacturers desire knowledge of certain anisotropic elastic properties in the sheet for handling and quality issues. Ultrasonic wave propagation in plate materials forms a method to determine the anisotropic elastic properties in a nondestructive manner. This work explores exact and approximate analysis methods of ultrasonic guided wave propagation in thin layers, explicitly dealing with orthotropic symmetry and propagation off-axis with respect to the manufacturing direction. Recent advances in full-field ultrasonic imaging methods, based on dynamic holography, allow simultaneous measurement of the plate wave motion in all planar directions within a single image. Results from this laser ultrasonic imaging approach are presented that record the lowest anti-symmetric (flexural) mode wavefront in a single image without scanning. Specific numerical predictions for flexural wave propagation in two distinctly different types of paper are presented and compared with direct imaging measurements. Very good agreement is obtained for the lowest anti-symmetric plate mode using paper properties independently determined by a third party. Complete determination of the elastic modulus tensor for orthotropic layers requires measurement of other modes in addition to the lowest anti-symmetric. Theoretical predictions are presented for other guided wave modes [extensional (S), flexural (A), and shear-horizontal (SH)] in orthotropic plates with emphasis on propagation in all planar directions. It is shown that there are significant changes in the dispersion characterization of these modes at certain frequencies (including off-axis mode coupling) that can be exploited to measure additional in-plane elastic moduli of thin layers. At present, the sensitivity of the imaging measurement approach limits experimental investigation to relatively large amplitudes easily produced by flexural wave motion (> 0.1 nm). Extension of the measurement range and application to other plate wave modes are in progress and shall be reported in future work.

Journal Article↗

Regulatory defects in Cbl and mitogen-activated protein kinase (extracellular signal-related kinase) pathways cause persistent hyperexpression of CD40 ligand in human lupus T cells.

To identify intrinsic defects in lupus, we studied short-term, CD4(+) T cell lines that were established from 16 lupus patients (active or inactive) and 15 normal subjects by stimulating once with anti-CD3, anti-CD28, and IL-2. After resting, the pure CD4(+) T cells were exposed to anergy-inducing stimulation with plate-bound anti-CD3 mAb in the absence of APC. Lupus T cells showed prolonged high level expression of CD40 ligand (CD40L, CD154) even in the face of anergy protocol, which shut down CD40L expression in normal T cells. The sustained CD40L expression in lupus T cells did not correlate with memory status or Th deviation, and was relatively independent of IL-2 or other autocrine or paracrine signals via CD28 or CTLA-4. Cyclosporin A could block CD40L expression by lupus T cells when added early during the anti-CD3 stimulation period, but only partially when added later, indicating that another mechanism regulates the prolonged hyperexpression of CD40L besides the Ca(2+) --> calcineurin-dependent NF-AT pathway. When exposed to the anergy protocol, lupus T cells, in marked contrast to normal T cells, did not phosphorylate Cbl/Cbl-b but continued to express strongly phosphorylated extracellular signal-regulated kinase (ERK); U0126, a specific inhibitor of mitogen-activated protein kinase kinase --> ERK, could block both the early and the prolonged hyperexpression of CD40L. Thus, pathways regulating the activities of Cbl and one particular mitogen-activated protein kinase, ERK, are involved in the prolonged hyperexpression of CD40L in lupus T cells.

Abatacept↗

The use of enzyme therapy to regulate the metabolic and phenotypic consequences of adenosine deaminase deficiency in mice. Differential impact on pulmonary and immunologic abnormalities.

Adenosine deaminase (ADA) deficiency results in a combined immunodeficiency brought about by the immunotoxic properties of elevated ADA substrates. Additional non-lymphoid abnormalities are associated with ADA deficiency, however, little is known about how these relate to the metabolic consequences of ADA deficiency. ADA-deficient mice develop a combined immunodeficiency as well as severe pulmonary insufficiency. ADA enzyme therapy was used to examine the relative impact of ADA substrate elevations on these phenotypes. A "low-dose" enzyme therapy protocol prevented the pulmonary phenotype seen in ADA-deficient mice, but did little to improve their immune status. This treatment protocol reduced metabolic disturbances in the circulation and lung, but not in the thymus and spleen. A "high-dose" enzyme therapy protocol resulted in decreased metabolic disturbances in the thymus and spleen and was associated with improvement in immune status. These findings suggest that the pulmonary and immune phenotypes are separable and are related to the severity of metabolic disturbances in these tissues. This model will be useful in examining the efficacy of ADA enzyme therapy and studying the mechanisms underlying the immunodeficiency and pulmonary phenotypes associated with ADA deficiency.

Adenosine↗

A sesquiterpene acid and flavonoids from Polygonum viscosum.

4-Isobutyl-6-methyl-5-oxo-3a,4,5,7a-tetrahydro-1H-inden-13-oic acid (named viscosumic acid) and quercetin 3-O-(6"-feruloyl)-beta-D-galactopyranoside, and the known 3',5-dihydroxy-3,4',5',7-tetramethoxyflavone have been isolated from Polygonum viscosum. The structures of these isolates were determined primarily on the basis of extensive 1D and 2D NMR spectral analyses, notably, 13C PENDANT, COSY45, TOCSY, GOESY, NOESY, HMQC and HMBC.

Flavonoids↗

Quercetin 3-O-(6"-caffeoyl)-beta-D-galactopyranoside from Polygonum viscosum.

The methanol extract of the whole plant parts of Polygonum viscosum has yielded a flavonol glycoside, 3-O-(6"-caffeoyl)-beta-D-galactopyranoside (1), the structure of which has been determined unambiguously by UV and a series of one- and two-dimensional NMR experiments, notably, (1)H, (13)C, DEPT, COSY45, HMBC and HMQC.

Caffeic Acids↗

Field performance of transgenic elite commercial hybrid rice expressing bacillus thuringiensis delta-endotoxin.

Here we describe development of transgenic elite rice lines expressing a Bt fusion gene derived from cryIA(b) and cryIA(c) under the control of rice actinI promoter. The lines used in the study were indica CMS restorer line of Minghui 63 and its derived hybrid rice Shanyou 63. The level of Bt fusion protein CryIA(b)/CryIA(c) detected in Minghui 63 (T51-1) plants was 20 ng/mg soluble protein. The Bt Shanyou 63 was field-tested in natural and repeated heavy manual infestation of two lepidopteran insects, leaffolder and yellow stem borer. The transgenic hybrid plants showed high protection against both insect pests without reduced yield.

Actins↗

Antigen-specific therapy of murine lupus nephritis using nucleosomal peptides: tolerance spreading impairs pathogenic function of autoimmune T and B cells.

In the (SWR x NZB)F1 mouse model of lupus, we previously localized the critical autoepitopes for nephritogenic autoantibody-inducing Th cells in the core histones of nucleosomes at aa positions 10-33 of H2B and 16-39 and 71-94 of H4. A brief therapy with the peptides administered i.v. to 3-mo-old prenephritic (SWR x NZB)F1 mice that were already producing pathogenic autoantibodies markedly delayed the onset of severe lupus nephritis. Strikingly, chronic therapy with the peptides injected into 18-mo-old (SWR x NZB)F1 mice with established glomerulonephritis prolonged survival and even halted the progression of renal disease. Remarkably, tolerization with any one of the nucleosomal peptides impaired autoimmune T cell help, inhibiting the production of multiple pathogenic autoantibodies. However, cytokine production or proliferative responses to the peptides were not grossly changed by the therapy. Moreover, suppressor T cells were not detected in the treated mice. Most interestingly, the best therapeutic effect was obtained with nucleosomal peptide H416-39, which had a tolerogenic effect not only on autoimmune Th cells, but autoimmune B cells as well, because this peptide contained both T and B cell autoepitopes. These studies show that the pathogenic T and B cells of lupus, despite intrinsic defects in activation thresholds, are still susceptible to autoantigen-specific tolerogens.

Animals↗

Combinatorial interactions regulate cardiac expression of the murine adenylosuccinate synthetase 1 gene.

The mammalian heart begins contracting at the linear tube stage during embryogenesis and continuously pumps, nonstop, throughout the entire lifetime of the animal. Therefore, the cardiac energy metabolizing pathways must be properly established and efficiently functioning. While the biochemistry of these pathways is well defined, limited information regarding the regulation of cardiac metabolic genes is available. Previously, we reported that 1.9 kilobase pairs of murine adenylosuccinate synthetase 1 gene (Adss1) 5'-flanking DNA directs high levels of reporter expression to the adult transgenic heart. In this report, we define the 1.9-kilobase pair fragment as a cardiac-specific enhancer that controls correct spatiotemporal expression of a reporter similar to the endogenous Adss1 gene. A 700-base pair fragment within this region activates a heterologous promoter specifically in adult transgenic hearts. Proteins present in a cardiac nuclear extract interact with potential transcription factor binding sites of this region and these cis-acting sites play important regulatory roles in the cardiac expression of this reporter. Finally, we report that several different cardiac transcription factors trans-activate the 1.9HSCAT construct through these sites and that combinations result in enhanced reporter expression. Adss1 appears to be one of the first target genes identified for the bHLH factors Hand1 and Hand2.

Adenylosuccinate Synthase↗

Regulation of forestomach-specific expression of the murine adenosine deaminase gene.

The maturation of stratified squamous epithelium of the upper gastrointestinal tract is a highly ordered process of development and differentiation. Information on the molecular basis of this process is, however, limited. Here we report the identification of the first murine forestomach regulatory element using the murine adenosine deaminase (Ada) gene as a model. In the adult mouse, Ada is highly expressed in the terminally differentiated epithelial layer of upper gastrointestinal tract tissues. The data reported here represent the identification and detailed analysis of a 1. 1-kilobase (kb) sequence located 3.4-kb upstream of the transcription initiation site of the murine Ada gene, which is sufficient to target cat reporter gene expression to the forestomach in transgenic mice. This 1.1-kb fragment is capable of directing cat reporter gene expression mainly to the forestomach of transgenic mice, with a level comparable to the endogenous Ada gene. This expression is localized to the appropriate cell types, confers copy number dependence, and shows the same developmental regulation. Mutational analysis revealed the functional importance of multiple transcription factor-binding sites.

Adenosine Deaminase↗