Biomedical subjects

Vipin Kumar

Publications and source records attributed to Vipin Kumar.

26 records · Page 2Linked to original sources

PubMed2004

Generation of porous microcellular 85/15 poly (DL-lactide-co-glycolide) foams for biomedical applications.

Porous 85/15 poly (DL-lactide-co-glycolide) or PLGA foams were produced by the pressure quench method using supercritical CO2 as the blowing agent. The rate of CO2 uptake and CO2 equilibrium concentration in PLGA at different processing conditions were studied by performing sorption experiments. The effects of saturation pressure and temperature on average cell size and relative density of the resulting foams were also studied. The time required to approach equilibrium exhibited a minimum with increasing saturation pressure. The diffusion coefficient and equilibrium concentration of CO2 in PLGA increased with an increasing pressure in an approximately linear relationship. Porous PLGA foams were generated with relative densities ranging from 0.107 to 0.232. Foams showed evidence of interconnected cells with porosities as high as 89%. The pore size ranged from 30 to 100 microm.

Biocompatible Materials↗

PubMed2004

Investigation in tea on fate of fenazaquin residue and its transfer in brew.

Fenazaquin is a non-systemic acaricide/insecticide used widely in controlling mites and other related pests in fruits, vegetables and tea. The objective of this research was to investigate the disappearance trend in tea of fenazaquin residue level and its transfer in brew. Fenazaquin was applied on a tea crop at two rates, 125 and 250 g A.I./ha in wet and dry seasons under field conditions. Samples (green shoots, made tea and its brew) were analyzed for fenazaquin and quantification was by high performance liquid chromatography using a UV detector. The residue dissipated faster in the wet season than in the dry season. Seven days after the treatment (normal round of plucking) the residues observed in green shoots at the two rates were 0.32, 0.50 mg/kg and 2.04, 2.84 mg/kg in the wet and dry seasons, respectively. However, the degradation rate in both seasons followed first order kinetics. Half lives in green shoots were in the range 1.20-1.32 and 2.10-2.21 days and in made tea 1.03-1.06 and 1.87-1.94 days for wet and dry seasons, respectively. During processing of green shoots to made tea considerable loss (42-70%) of residue was observed. The transfer of residue from made tea to brew was in the range 3-17%. In brew residues were below 0.003 mg/l after 5 days of application at both the rates in either of the seasons. The estimated intake with brew (normal consumption of 10 cup/day/adult) thus would be below the acceptable daily intake for fenazaquin (0.005 mg/kg-body weight). To avoid health hazards due to the toxic effect of residues in brew, a waiting period for plucking the tea shoots after fenazaquin application of more than 3 days for wet season and 5 days for dry season at recommended rate (125 g A.I./ha) may be suggested and considered quite safe.

Chromatography, High Pressure Liquid↗

PubMed2004

Homeostatic control of immunity by TCR peptide-specific Tregs.

Regulation of the immune response is a multifaceted process involving lymphocytes that function to maintain both self tolerance as well as homeostasis following productive immunity against microbes. There are 2 broad categories of Tregs that function in different immunological settings depending upon the context of antigen exposure and the nature of the inflammatory response. During massive inflammatory conditions such as microbial exposure in the gut or tissue transplantation, regulatory CD4+CD25+ Tregs broadly suppress priming and/or expansion of polyclonal autoreactive responses nonspecifically. In other immune settings where initially a limited repertoire of antigen-reactive T cells is activated and expanded, TCR-specific negative feedback mechanisms are able to achieve a fine homeostatic balance. Here I will describe experimental evidence for the existence of a Treg population specific for determinants that are derived from the TCR and are expressed by expanding myelin basic protein-reactive T cells mediating experimental autoimmune encephalomyelitis, an animal prototype for multiple sclerosis. These mechanisms ensure induction of effective but appropriately limited responses against foreign antigens while preventing autoreactivity from inflicting escalating damage. In contrast to CD25+ Tregs, which are most efficient at suppressing priming or activation, these specific Tregs are most efficient in controlling T cells following their activation.

Animals↗

PubMed2003

Regulatory T cells control autoimmunity in vivo by inducing apoptotic depletion of activated pathogenic lymphocytes.

Clinical autoimmunity requires both activation of self-reactive T cells as well as a failure of peripheral tolerance mechanisms. We previously identified one such mechanism that involves regulatory T cells recognizing TCR V beta 8.2 chain-derived peptides in the context of MHC. How this regulation affects the fate of target V beta 8.2(+) T lymphocytes in vivo that mediate experimental autoimmune encephalomyelitis has remained unknown. The present study using immunoscope and CFSE-labeling analysis demonstrates that the expansion of regulatory CD4 and CD8 T cells in vivo results in apoptotic depletion of the dominant, myelin basic protein-reactive V beta 8.2(+) T cells, but not subdominant V beta 13(+) T cells. The elimination of only activated T cells by this negative feedback mechanism preserves the remainder of the naive V beta 8.2(+) T cell repertoire and at the same time results in protection from disease. These studies are the first in clearly elucidating the fate of myelin basic protein-specific encephalitogenic T cells in vivo following regulation.

Amino Acid Sequence↗

PubMed2003

Protection against experimental autoimmune encephalomyelitis generated by a recombinant adenovirus vector expressing the V beta 8.2 TCR is disrupted by coadministration with vectors expressing either IL-4 or -10.

Adenovirus vectors are increasingly being used for genetic vaccination and may prove highly suitable for intervention in different pathological conditions due to their capacity to generate high level, transient gene expression. In this study, we report the use of a recombinant adenovirus vector to induce regulatory responses for the prevention of autoimmune diseases through transient expression of a TCR beta-chain. Immunization of B10.PL mice with a recombinant adenovirus expressing the TCR Vbeta8.2 chain (Ad5E1 mVbeta8.2), resulted in induction of regulatory type 1 CD4 T cells, directed against the framework region 3 determinant within the B5 peptide (aa 76-101) of the Vbeta8.2 chain. This determinant is readily processed and displayed in an I-A(u) context, on ambient APC. Transient genetic delivery of the TCR Vbeta8.2 chain protected mice from Ag-induced experimental autoimmune encephalomyelitis. However, when the Ad5E1 mVbeta8.2 vector was coadministered with either an IL-4- or IL-10-expressing vector, regulation was disrupted and disease was exacerbated. These results highlight the importance of the Th1-like cytokine requirement necessary for the generation and activity of effective regulatory T cells in this model of experimental autoimmune encephalomyelitis.

Adenoviruses, Human↗

PubMed2003

Seven surprises in the TCR-centred regulation of immune responsiveness in an autoimmune system.

Self-reactivity is potentially so devastating to the organism that a variety of regulatory devices have evolved to control it. One broadly used strategy is that employing the processed T cell receptor (TCR) as a target for TCR-specific regulatory cells. In several autoimmune models, feedback regulation employing both CD4+ and CD8+ T cells of TCR specificity can be shown to occur and to account for remission from the transient disease state, or for its prevention. We will focus here on the experimental autoimmune encephalomyelitis (EAE) model in the B10.PL (H-2u) mouse. In this model, the acetylated 1-9 N-terminal antigenic determinant from myelin basic protein (MBP) induces a transient paralytic disease owing to the activation of self-directed, high-affinity, CD4+ T cells. Although the response is multiclonal, a particularly aggressive member of this repertoire, bearing a Vbeta8.2,Jbeta2.7 receptor, which we have termed a 'driver clone', appears to be largely responsible for the disease process. A CD4+ T cell directed against a TCR determinant in the framework region of the Vbeta chain, and a CD8+ T cell directed against an upstream, distinct framework determinant, both of which are necessary for regulation, bring about a reversal of the disease process. To accomplish this, there must be a Th1 milieu during the induction of regulation, which is provided in part by the CD4+ regulatory cells themselves. To act as a target, the Vbeta8.2 MBP-reactive T cell must be activated, and the Th1 driver clone(s) is down-regulated via apoptotic killing, leaving a group of Th2, MBP-specific clones of weak affinity, which themselves may help in perpetuating long-term regulation. Similar results are also found in the collagen arthritis and NOD diabetes models.

Animals↗

PubMed2002

Induction of autoantibody production is limited in nonautoimmune mice.

Many individuals develop a single or a few brief episodes of autoimmunity from which they recover. Mechanisms that quell pathologic autoimmunity following such a breakdown of self-tolerance are not clearly understood. In this study, we show that in nonautoimmune mice, dsDNA-specific autoreactive B cells exist but remain inactive. This state of inactivation in dsDNA-specific B cells could be disrupted by autoreactive Th cells; in this case T cells that react with peptides from the V(H) region of anti-DNA Abs (hereafter called anti-V(H) T cells). Immunization with anti-DNA mAb, its gamma-chain or peptides derived from its V(H) region induced anti-V(H) Th cells, IgG anti-dsDNA Ab, and proteinuria. The breakdown of B cell tolerance in nonautoimmune mice, however, was short-lived: anti-DNA Ab and nephritis subsided despite subsequent immunizations. The recovery from autoimmunity temporally correlated with the appearance of T cells that inhibited anti-DNA Ab production. Such inhibitory T cells secreted TGFbeta; the inhibition of anti-DNA Ab production by these cells was partly abolished by anti-TGFbeta Ab. Even without immunization, nonautoimmune mice possess T cells that can inhibit autoantibody production. Thus, inhibitory T cells in nonautoimmune mice may normally inhibit T-dependent activation of autoreactive B cells and/or reverse such activation following stimulation by Th cells. The induction of such inhibitory T cells may play a role in protecting nonautoimmune mice from developing chronic autoimmunity.

Amino Acid Sequence↗

PubMedDate not supplied

Feedback regulation of autoimmunity via TCR-centered regulation.

The complexity of a self-regulatory system demands a balance between effectors and regulators; that is, it is necessary for both cell types to exist. Regulation of self-reactive T cells can occur at several complementary but different levels: (1) at the level of priming itself: for example, inhibition of expansion of antigen-reactive T cells by regulatory CD4+ CD25+ T cells; (2) after the priming of self-reactive T cells, regulatory T-cell populations with reactivity to distinct self-determinants derived from the T-cell receptor (TCR) can be engaged via a negative feedback mechanism. Thus, these mechanisms ensure induction of effective and appropriately limited responses against foreign antigens while preventing autoreactivity from inflicting self-damage.

Animals↗