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S Raychaudhuri

Publications and source records attributed to S Raychaudhuri.

At least 37 records · Page 2Linked to original sources
PubMed1997

A simple mass balance model of nitrogen flow in a bioregenerative life support system.

A mathematical model of the nitrogen cycle in a bioregenerative life support system (BLSS) was developed to help conceptualize and quantify nitrogen flux and storage in BLSS processes and subsystems. The mathematical model was initially designed as a simple mass balance, donor-controlled system that quantified the amount of nitrogen in moles per person. Dynamic equations were then applied to describe certain relationships more accurately. Comparison of nitrogen fluxes suggests that even at very low atmospheric leakage rates, loss of nitrogen gas would account for the largest nitrogen movement in the "closed" system. This observation decreases the relative importance of denitrification and nitrification in closed system nitrogen balances. Sensitivity analysis was used to determine the relative stability of various model subsystems, and demonstrated the importance of plant nitrogen uptake on overall system dynamics of nitrogen.

Animals↗
PubMed1996

Insights into the local residual entropy of proteins provided by NMR relaxation.

A simple model is used to illustrate the relationship between the dynamics measured by NMR relaxation methods and the local residual entropy of proteins. The expected local dynamic behavior of well-packed extended amino acid side chains are described by employing a one-dimensional vibrator that encapsulates both the spatial and temporal character of the motion. This model is then related to entropy and to the generalized order parameter of the popular "model-free" treatment often used in the analysis of NMR relaxation data. Simulations indicate that order parameters observed for the methyl symmetry axes in, for example, human ubiquitin correspond to significant local entropies. These observations have obvious significance for the issue of the physical basis of protein structure, dynamics, and stability.

Entropy↗
PubMed1995

The induction of cytotoxic T cells and tumor regression by soluble antigen formulation.

CTLs specific for tumor antigens play a major role in the immunity against cancer. We have shown that class I-restricted CTLs can be induced by injecting soluble antigens mixed in an antigen formulation (AF) that consists of squalane, Tween 80, and Pluronic L121 (S. Raychaudhuri et al., Proc. Natl. Acad. Sci. USA, 89: 8308-8312, 1992). In this study, using ovalbumin and the ovalbumin-expressing transfectoma (EG7) as a tumor model system, we examined the in vivo antitumor effect of antigen-AF mixture. Vaccination of mice with ovalbumin in AF 2 or 3 days after EG7 tumor challenge showed significant inhibition of tumor growth compared to mice vaccinated with ovalbumin in alum or in saline. Depletion of CD8+ cells at the time of immunization completely abrogated the AF-induced tumor protection, indicating that CD8+ T cells are the major effectors in tumor protection in vivo. Depletion of CD4+ cells led to a marginal loss of tumor protection, which may be the result of inhibition of ovalbumin-specific CTL response due to the lack of T-helper activity. Our results demonstrate that AF can be used in subunit vaccines to stimulate CTLs and tumor regression in vivo.

Animals↗
PubMed1993

Can soluble antigens induce CD8+ cytotoxic T-cell responses? A paradox revisited.

Cytotoxic T lymphocyte (CTL) induction usually follows processing of antigens via endogenous pathways before presentation on the cell surface in association with MHC class I molecules. Soluble antigens do not, in general, induce specific CTL responses. Here, Syamal Raychaudhuri and John Morrow suggest that a novel adjuvant formulation can elicit CTL responses to soluble antigens and discuss the implications for vaccine development.

Adjuvants, Immunologic↗
PubMed1992

Induction of antigen-specific class I-restricted cytotoxic T cells by soluble proteins in vivo.

Cytotoxic T lymphocytes (CTL) are induced specifically against viral and tumor antigens presented by major histocompatibility complex class I molecules on the surface of infected or transformed cells. Intracellular synthesized antigens are processed and associated with class I antigens within cells before presentation on the cell surface. Because of this special requirement for CTL induction, exogenous soluble antigens do not, in general, induce specific CTL responses. To overcome this problem, various laboratories have resorted to the use of vaccinia virus and other replicating expression vectors for intracellular antigen delivery leading to the stimulation of humoral and cell-mediated immunity to specific proteins. However, for human use it is safer to use purified and defined antigens for inducing immune responses. Using soluble ovalbumin and human immunodeficiency virus glycoprotein gp120, we have explored the possibility of using an antigen formulation consisting of squalane and Tween 80 to elicit antigen-specific CTL responses in mice. We have demonstrated that this antigen formulation is a potent inducer of CD8+, class I-restricted, antigen-specific CTLs. The CTL priming induced by soluble antigen in squalane/Tween 80 resembles the reported response to the vaccinia recombinant containing human immunodeficiency virus envelope protein and by splenocytes cytoplasmically loaded with soluble ovalbumin. The ramifications of these findings for vaccine development are discussed.

Adjuvants, Immunologic↗
PubMed1992

Murine monoclonal anti-idiotope antibody breaks unresponsiveness and induces a specific antibody response to human melanoma-associated proteoglycan antigen in cynomolgus monkeys.

The mouse monoclonal antibody MEM136 (mAb1) is directed against an epitope on human melanoma-associated proteoglycan antigen (MPG). This epitope is also present on various normal human and subhuman tissues. A monoclonal murine anti-idiotope (anti-Id) antibody (mAb2), designated I-Mel-2, was generated against MEM136 and used as a surrogate antigen for the MPG molecule. I-Mel-2 was tested in cynomolgus monkeys (Macaca fascicularis) for its ability to induce anti-MPG humoral responses. All monkeys immunized with Ab2 developed specific anti-anti-idiotype (Ab3) responses that were capable of inhibiting binding of Ab2 to Ab1. Furthermore, I-Mel-2 immune monkey serum contained anti-MPG antibodies (Ab1') that bound to MPG-positive but not to MPG-negative melanoma cell lines. Monkeys immunized with Colo38 melanoma cells (membrane-bound MPG antigen) did not contain anti-MPG antibodies that inhibited the binding of two distinct anti-MPG mAb 125I-labeled MEM136 or 125I-labeled 225.28 to Colo38 cells. The induction of anti-MPG responses in monkeys did not cause any apparent side effects in animals, despite the fact that the MPG antigen is expressed by many normal tissues. The affinity-purified, I-Mel-2 idiotype-specific, Ab3 immunoprecipitated MPG antigen from melanoma cells. Furthermore, the I-Mel-2-induced Ab3 inhibited melanoma cell invasion in an in vitro assay, implying that these antibodies have biological significance.

Animals↗
PubMed1991

Human high molecular weight-melanoma associated antigen mimicry by an anti-idiotypic antibody: characterization of the immunogenicity and the immune response to the mouse monoclonal antibody IMel-1.

The mouse anti-idiotype (anti-id) monoclonal antibody (mAb) IMel-1 recognizes an idiotope in the antigen combining site of the immunizing anti-human high molecular weight melanoma-associated antigen (HMW-MAA) mAb 225.28. The mAb IMel-1 is able to induce an immune response against self cross-reacting HMW-MAA in rabbits that express HMW-MAA in normal tissues. Most of the rabbit anti-anti-id antibodies recognize a spatially distant determinant(s) from that defined by anti-HMW-MAA mAb 225.28. The immunogenicity of mAb IMel-1 is enhanced by its administration with the muramyl dipeptide-derived adjuvant. Anti-HMW-MAA antibodies were not detected in sera from rabbits immunized with HMW-MAA bearing cultured human melanoma cells. The differential immunogenicity of mAb IMel-1 and cell membrane bound HMW-MAA may account for the ability of anti-id mAb to induce anti-HMW-MAA immunity in patients who have not mounted such a response to HMW-MAA present in their lesions. Rabbit anti-HMW-MAA antibodies induced by anti-id mAb IMel-1 inhibited interactions of melanoma cells with elements of extracellular matrix. This may represent an additional mechanism by which anti-HMW-MAA immunity may affect the biology of melanoma cells in patients with melanoma immunized with anti-id mAb IMel-1.

Animals↗
PubMed1991

Analysis of anti-tumor antibodies in mice and rabbits induced by monoclonal anti-idiotope antibodies.

Eight different mouse monoclonal anti-idiotope antibodies (mAb2) generated against a mouse monoclonal anti-human melanoma proteoglycan Ag (MPG) antibody (mAb1), MEM136, were tested for their ability to induce anti-MPG responses in mice and rabbits. All Ab2 were idiotypically cross-reactive and combining site-specific as demonstrated by competitive cross-inhibition studies and their ability to inhibit the binding of MEM136 to the melanoma cells, Colo38. However, only two Ab2, IM32 and IM06, were able to induce specific anti-TAA-specific (Ab1') responses in rabbits. When IM32 and IM06 were tested in allogeneic stains of mice for the induction of anti-MPG responses, only IM32 produced an Ab1' response. In mice, the Ab3 response induced by IM32 is idiotypically cross-reactive with its Ab1. Furthermore, the IM32-induced murine Ab3 and MEM136 recognized a similar MPG epitope on the melanoma cells because the Ab3 inhibited the binding of MEM136 to melanoma cells. The Ab3 induced by IM32 and IM06 in rabbits also recognized a similar epitope as the Ab1. In rabbits, the Ab3 response induced by IM32 and IM06 were idiotypically cross-reactive with each other. However, additional studies indicated that the majority of Ab3 induced by IM32 were IM32 Id-specific and lacked IM06 idiotopes. Further experimentation indicated that IM32-induced rabbit Ab3 were biologically active as demonstrated by the ability of the Ab3 to inhibit melanoma cell invasion in a Matrigel assay.

Animals↗
PubMed1991

Monoclonal anti-idiotypic antibodies to human melanoma-associated proteoglycan antigen: generation and characterization of anti-idiotype antibodies.

We have characterized a number of monoclonal anti-idiotype antibodies (mAb2s) made against a monoclonal antitumor antibody, MEM136. The monoclonal antibody 1 (mAb1) MEM136 recognizes an epitope on human melanoma-associated proteoglycan and blocks melanoma cell interaction with basement membrane components in vitro. The anti-idiotype antibodies (Ab2s) made against MEM136 each cross-inhibited, to varying degrees, their binding to MEM136. Thus, the mAb2s recognized overlapping idiotopes on MEM136. In an attempt to identify potential internal image candidates we set up a cell migration inhibition assay. In this assay, migration of melanoma-associated proteoglycan-positive Colo38 cells was determined through a membrane barrier impregnated with Matrigel, which is composed of extracellular matrix components, i.e., collagen type IV, heparan sulfate, and laminin. Interestingly, only Ab2s IM06 and IM32 inhibited melanoma cell migration. Additional studies indicate that of eight mAb2s tested, only IM32 and IM06 induced anti-MPG responses in rabbits. The possibility that IM32 and IM06 bear images of melanoma cell surface-associated proteoglycan epitopes is discussed.

Antibodies, Anti-Idiotypic↗
PubMed1990

Tumor idiotype vaccines. VII. Analysis and correlation of structural, idiotypic, and biologic properties of protective and nonprotective Ab2.

We have previously generated and used anti-Id mAb (Ab2) to induce protective immunity against the L1210 DBA/2 tumor and for immunotherapy of established tumors. Among various anti-Id that were typed serologically as internal image Ab2 of the mouse mammary tumor virus tumor-associated Ag gp52, only one induced protective immunity and was effective in immunotherapy. In this study we compared the structural, idiotypic, and network properties of the protective and nonprotective antiidiotypic antibodies. The DNA sequence of the variable regions of six anti-Id was determined. The VH sequence of four Ab2, including the protective Ab2, are highly homologous, whereas the VL sequences differ and were assigned to different Vk families. In addition, the DH sequence region of the same four Ab2 are identical, whereas one is highly homologous and another one without homology. Search for amino acid sequence homologies between the Ab2 and gp52 showed the strongest similarities in the CDR2 of the L chain from the protective Ab2. In addition, the CDR2 region also had homology with a T cell epitope on gp52. The biologic basis of effective idiotypic mimicry was studied at the level of Ab3 induced by the Ab2. Id inhibition analysis using Ab3 induced by either protective or nonprotective Ab2, revealed differences. Thus, there is evidence for differences among the Ab1-Ab2-Ab3 cascade induced by protective and nonprotective anti-Id.

Amino Acid Sequence↗