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Biomedical subjects

S K Chatterjee

Publications and source records attributed to S K Chatterjee.

At least 19 recordsLinked to original sources
PubMed2002

New modified single chained glycolipids. Part 1: synthesis of deoxy and partially O-methylated glycolipids with or without a sulfur containing spacer.

A way to synthesize neoglycolipids with high yields and anomeric purity is described. Starting point of the synthesis strategy is the glycosylation of allyl alcohol with definite steric orientation. Introduction of the hydrophobic moiety was achieved by photoaddition of n-hexadecanethiol and 3-mercaptopropionic acid followed by amidation with n-hexadecylamine, respectively. In order to investigate the influence of different carbohydrate headgroups in the physicochemical behavior of the general glycolipid, especially the orientation of the alkyl chain, a range of neoglycolipids was synthesized. Beside the differences in the configuration between unfunctionalized glycopyranoses like D-glucose, D-galactose and D-mannose, a number of deoxy and partially O-methylated sugar derivatives was prepared. The divergences concerning the different carbohydrate headgroups and the hydrophobic moiety, respectively, can be compared to relatively simple structured glycolipids with hexadecyl residue and without spacer function.

Glycolipids↗
PubMed2002

Is squatting a triggering factor for stroke in Indians?

BACKGROUND: Undocumented observations of ours suggested increased occurrence of strokes in the early hours of the morning and in the toilets where most Indians still squat. The present study has been designed to assess the validity of this observation and to identify the likely triggering factor in stroke onset in such situations. MATERIAL AND METHODS: Part A of the study looked into stroke onset data of 100 consecutive CT-confirmed stroke patients specially in relation to time of day, place, posture and activity of the individual. Part B of the study included 67 healthy volunteers (age 24-49 years) whose supine and squatting blood pressure (BP) were measured and the differences noted. Part C of the study consisted of repeating the same procedure in 104 known hypertensives on treatment (age 28-60 years). RESULTS: Part A of the study revealed that most strokes (52%) occurred in the morning and at home (86%) and over a third (36%) while in toilets. Thirty-six per cent of the strokes occurred while the subjects squatted, mostly during the act of defecation. More than half of the haemorrhagic strokes occurred while the subjects were in squatting position. In normal healthy volunteers squatting produced a small (8.09 +/- 7.04 mmHg) but significant rise in systolic blood pressure (SBP) but not in diastolic blood pressure (DBP) (0.9 +/- 7.38 mmHg). In contrast, in treated hypertensives squatting produced a significantly higher rise in both SBP (14.49 +/- 11.63 mmHg) and DBP(9.10 +/- 9.19 mmHg). CONCLUSION: The relationship of the clinical observations regarding stroke onset with the BP changes noted on squatting in healthy as well as hypertensive subjects appears to be more than fortuitous. Squatting induced rise in BP appears to be an important triggering factor for stroke onset in subjects at risk in India.

Adult↗
PubMed2002

Squatting, blood pressure and stroke.

Most Indians still adopt squatting posture in toilets. In a group of 67 healthy volunteers, squatting produced a small (8.09 +/- 7.04 mm Hg) but significant rise in systolic blood pressure (SBP) but not in diastolic (DBP). However, in a group of randomly selected treated hypertensives (N=104) squatting produced a much greater and significant rise in both SBP (14.46 +/- 11.63 mm Hg) and DBP (9.10 +/- 9.19 mm Hg). The possible clinical significance of this rise of BP in squatting has been evaluated in 100 consecutive CT proved patients with stroke by analysing their stroke onset data in relation to time, place, posture and activity. Most strokes (52%) occurred in the morning hours (5 am-9 am) and at home (86%) and over a third (36%) while in toilets. Thirty six percent of strokes occurred when the subjects squatted, mostly during defecation. More than half of hemorrhagic strokes occurred in the squatting position. The relationship of these clinical observations with the BP changes noted above on squatting appears to be more than fortuitous. We would suggest that hypertensive subjects and those at risk of stroke should avoid squatting and urge physicians to check squatting BP while monitoring anti-hypertensive therapy.

Adult↗
PubMed2001

Synthesis and microtubule binding of fluorescent paclitaxel derivatives.

The preparation of two new fluorescent derivatives of paclitaxel in which the fluorophore is bonded to paclitaxel at the C-10 position is reported. Both analogues, 10-deacetyl-10-(m-aminobenzoyl)paclitaxel (1, BTax) and 10-deacetyl-10-[7-(diethylamino) coumarin-3-carbonyl]paclitaxel (2, CTax) retain good activity as promoters of in vitro tubulin assembly. Microtubule binding enhances the emission intensity of both probes.

Fluorescent Dyes↗
PubMed2001

Synthesis and biological evaluation of novel macrocyclic paclitaxel analogues.

[reaction: see text] This work describes the synthesis of two novel macrocyclic taxoid constructs by ring-closing olefin metathesis (RCM) and their biological evaluation. Computational studies examine conformational profiles of 1 and 2 for their fit to the beta-tubulin binding site determined by electron crystallography. The results support the hypothesis that paclitaxel binds to microtubules in a "T" conformation.

Antineoplastic Agents, Phytogenic↗
PubMed2001

Baccatin III induces assembly of purified tubulin into long microtubules.

Baccatin III is widely considered to be an inactive derivative of Taxol. We have reexamined its effect on in vitro assembly of tubulin under a variety of conditions. We found baccatin III to be active in all circumstances in which Taxol is active: it assembled GTP-tubulin, GDP-tubulin, and microtubule protein into normal microtubules and stabilized these polymers against cold-induced disassembly. The effect of baccatin III on in vitro microtubule assembly was quantitatively assessed through determination of critical concentrations, which can be used to obtain the apparent equilibrium constants for the addition of tubulin subunits to growing microtubules. The apparent equilibrium constants for the growth reaction for baccatin III-induced GTP-tubulin and GDP-tubulin assembly measured at 37 degrees C were 4.2-4.6-fold less than those measured for Taxol-induced GTP-tubulin and GDP-tubulin assembly. These data indicate that the entire Taxol side chain contributes only about -1 kcal/mol to the apparent standard free energy of microtubule growth at 37 degrees C regardless of the nature of the E site nucleotide. These data also support the idea that the majority of the interactions between Taxol and tubulin that affect this equilibrium occur between the baccatin portion of the molecule and the binding site. We have also observed a structural difference in microtubules formed using baccatin III and Taxol. Baccatin III-induced microtubules were routinely much longer than those assembled by Taxol, even when very high concentrations of baccatin III were employed. One interpretation of these data is that baccatin III and Taxol differ in their abilities to nucleate GTP-tubulin. This difference in activity may have bearing on the large disparity in cytotoxicity of the two molecules.

Alkaloids↗
PubMed2001

Gene therapy for head and neck cancer using vaccinia virus expressing IL-2 in a murine model, with evidence of immune suppression.

We evaluated the efficiency of recombinant vaccinia virus expressing interleukin-2 (rvv-IL-2) as a tumor vaccine in an immunocompetent mouse model of head and neck squamous cell carcinoma (SCC VII/SF). Mice with five-day-old tumors in the floor of the mouth were treated with rvv-IL-2 by intratumoral injections. These treated mice survived longer (P <.03) than mice treated with control vaccines. Splenocytes, bone marrow, and lymph node cells from tumor-bearing mice responded poorly to concanavalin A stimulation, suggesting induction of immunosuppression. The rvv-IL-2 virus grew for 7 days in the tumor following intratumoral injection. We did not detect any virus particles in several normal organs following rvv-IL-2 injection. Comparison of expression levels of several potential immune inhibitory mediators between the tumors growing in mice and cultured tumor cells demonstrated higher expression of IL-10, GM-CSF, TGF-beta, and NO synthetase in tumors. These results suggested possible roles for these molecules in immunosuppression. We conclude that rvv-IL-2 has potential as a therapeutic vaccine for head and neck cancer and that it can be more effective provided the immunosuppression is reversed.

Animals↗
PubMed2001

Posterior urethral valves: the scenario in a developing center.

We have reviewed 233 patients with posterior urethral valves treated in a single center in Calcutta, India, over the last 20 years: 37 were neonates, 75 were between 1 and 12 months, 88 were between 1 and 5 years, and 33 were more than 5 years old when first seen. The clinical presentation and methods employed in diagnosis and assessment are described. Primary endoscopic valve ablation was performed in 140 patients (60%). One or other form of diversion was done in 100 (43%), 93 before and 7 either during or after valve ablation. The short- and long-term results have been studied. Eleven patients died during the initial hospitalization, 3 died subsequently, 15 are in end-stage renal disease, 17 are in poor health, and 18 have been totally lost to follow-up. The remaining 169 have been in good health for periods between 1 and 20 years. While our results of primary valve ablation in low-risk patients with responsible parents are as good as anywhere else in the world, we are concerned at our relatively high diversion rate and relatively poor long-term follow up; the methods being adopted to reduce these problems are discussed.

Child, Preschool↗
PubMed2001

Rectourinary fistula with a narrow urethra.

A rectourinary fistula is a common accompaniment of anorectal malformations (ARM) in boys. Most boys pass urine normally after reconstruction and closure of the fistula, but a few have serious problems because of a narrow urethra. In our series, a narrow urethra was encountered in three types of male ARM: 3 rectourethral fistulae, 4 rectovesical fistulae, and 6 H-fistulae. We have studied the diagnostic and therapeutic problems that a narrow urethra produces in patients afflicted with each of these malformations.

Abnormalities, Multiple↗
PubMed2001

Intraocular pressure changes and mountaineering--preliminary observations and possible application.

Measurement of intraocular pressure (IOP) has been suggested as an indirect way of assessing the intra cranial pressure (ICP) because of the anatomical relationship between the brain and the eyeball. Mountain-sickness during high altitude climbing results from acute rise in ICP. In this preliminary study, we have observed gradual increase in IOP with gain in altitude in a group of healthy mountain trekkers. Although the rise in IOP had not been steep in most climbers who did not experience any significant symptoms, the rise had been steep into two subjects who experienced symptoms of acute mountain sickness with raised IOP. While clearly further work is needed in this field with larger number of subjects, measurement of IOP appears to be a useful non-invasive screening test in high altitude climbers to avert the risk of acute mountain sickness.

Adult↗
PubMed2001

The anti-idiotype vaccines for immunotherapy.

Certain anti-idiotypic antibodies that bind to the antigen-combining sites of antibodies can effectively mimic the three-dimensional structures and functions of the external antigens and can be used as surrogate antigens for active specific immunotherapy. Extensive studies in animal models have demonstrated the efficacy of these vaccines for triggering the immune system to induce specific and protective immunity against bacterial, viral and parasitic infections as well as tumors. Several monoclonal anti-idiotype antibodies that mimic distinct human tumor-associated antigens have been developed and characterized. Encouraging results have been obtained in recent clinical trials using these anti-idiotype antibodies as vaccines. In this article, we will review the current literature and discuss the potential of this novel therapeutic approach for various human cancers.

Animals↗
PubMed2000

Anti-idiotype vaccine against cancer.

Immunization with anti-idiotype (Id) antibodies represents a novel new approach to active immunotherapy. Extensive studies in animal tumor models have demonstrated the efficacy of anti-Id vaccines in preventing tumor growth and curing mice with established tumor. We have developed and characterized several murine monoclonal anti-Id antibodies (Ab2) which mimic distinct human tumor-associated antigens (TAA) and can be used as surrogate antigens for triggering active anti-tumor immunity in cancer patients. Encouraging results have been obtained in recent clinical trials. In this article, we will review the existing literature and summarize our own findings showing the potential of this approach for various human cancers. We will also discuss where anti-Id vaccines may perform better than traditional antigen vaccines.

Animals↗
PubMed2000

Counterpoint. Cancer vaccines: single-epitope anti-idiotype vaccine versus multiple-epitope antigen vaccine.

Anti-idiotype (Id) vaccine therapy has been tested and shown to be effective, in several animal models, for triggering the immune system to induce specific and protective immunity against bacterial, viral and parasitic infections. The administration of anti-Id antibodies as surrogate tumor-associated antigens (TAA) also represents another potential application of the concept of the Id network. Limited experience in human trials using anti-Id to stimulate immunity against tumors has shown promising results. In this "counter-point" article, we discuss our own findings showing the potential of anti-Id antibody vaccines to be novel therapeutic approaches to various human cancers and also discuss where anti-Id vaccines may perform better than traditional multiple-epitope antigen vaccines.

Adjuvants, Immunologic↗
PubMed2000

Construction and characterization of DNA vaccines encoding the single-chain variable fragment of the anti-idiotype antibody 1A7 mimicking the tumor-associated antigen disialoganglioside GD2.

Anti-idiotype antibody, 1A7, functionally mimics the tumor-associated antigen disialoganglioside GD2, which is overexpressed on the surface of a number of neuroectodermal tumors such as melanoma, neuroblastoma, soft tissue sarcoma, and small cell carcinoma of the lung. Immunization of mice with 1A7 generated the production of anti-GD2 antibodies. In a phase I clinical trial, immunization of patients with 1A7, mixed with the adjuvant QS21, demonstrated that 1A7 could act as a surrogate antigen for GD2 and induce strong humoral immune responses in advanced stage melanoma patients. DNA vaccines have recently been shown to invoke humoral as well as cellular responses in injected hosts against the transgene product. To evaluate the efficiency of DNA vaccines encoding anti-idiotype antibodies, we constructed expression plasmids encoding the variable heavy (VH) and variable light (VL) chains of 1A7. The plasmids were made in two configurations, expressing either the VH (pc1A7VHLnVL) or the VL (pc1A7VLLnVH) chain of 1A7 at the amino terminus, linked together by a 15-amino acid linker (Ln). In vitro transcription/translation assays and transfection of CHO-K1 cells with the plasmids demonstrated that a approximately 30-kDa protein was expressed by both configurations of the single-chain variable fragment. This protein can be specifically precipitated by monoclonal anti-GD2 antibody, 14G2a. Following intramuscular injection in mice, the plasmids were detectable in the injected tissues for at least 3 months and the injected plasmids actively transcribed the single-chain variable fragment 1A7 gene at the injected site. A single, intramuscular immunization of a group of C57BL/6 mice with pc1A7VLLnVH in phosphate-buffered saline induced humoral immune responses against 1A7 as well as GD2, the nominal antigen. Multiple immunizations, however, were required to elicit stronger immune responses.

Amino Acid Sequence↗
PubMed1999

Construction and characterization of a chimeric fusion protein consisting of an anti-idiotype antibody mimicking a breast cancer-associated antigen and the cytokine GM-CSF.

Anti-idiotype antibody, 11D10 mimics biologically and antigenically a distinct and specific epitope of the high molecular weight human milk fat globule (HMFG), a cancer-associated antigen present in over 90% of breast tumor samples. To augment the immunogenicity of 11D10 without the aid of a carrier protein or adjuvant, we made a chimeric 11D10-GM-CSF fusion protein for use as a vaccine. An expression plasmid for 11D10 was made by ligation of the DNA sequences of the 11D10 light-chain variable region upstream of the human kappa constant region. The heavy-chain plasmid carrying GM-CSF was made by ligation of the heavy-chain variable region sequences upstream of the human gamma1 constant region CH1 fused to the DNA fragment encoding the mature GM-CSF peptide 3' to the CH3 exon. NS1 plasmacytoma cells were transfected with the light and heavy-chain vectors by electroporation. Fusion protein secreted in the culture medium was purified and was characterized by gel electrophoresis as well as by determination of the biological activity of the fused GM-CSF. In nonreducing SDS-polyacrylamide gels, a single band approximately 200 Kd reacted with anti-human kappa, anti-human lambda1 and anti-GM-CSF antibodies. In reducing polyacrylamide gels, a approximately 74 kd protein reacted with anti-human lambda1 and anti-GM-CSF antibodies. The fusion protein induced proliferation of GM-CSF dependent NFS-60 cells. These results suggest that the protein is a chimeric anti-idiotype antibody consisting of 11D10 variable domains, human kappa and lambda1 constant domains and that the GM-CSF moiety fused to the constant region lambda1 is biologically active.

Adjuvants, Immunologic↗
PubMed1999

Clinical and immune responses in resected colon cancer patients treated with anti-idiotype monoclonal antibody vaccine that mimics the carcinoembryonic antigen.

PURPOSE: We generated an anti-idiotype antibody, designated CeaVac, that is an internal image of the carcinoembryonic antigen (CEA). We previously demonstrated that the majority of patients with advanced colorectal cancer generate specific anti-CEA responses. The purpose of the current study was to treat patients with surgically resected colon cancer with CeaVac to determine the immune response and clinical outcome to treatment with vaccine. We also compared the immune responses between patients treated with fluorouracil (5-FU) chemotherapy regimens plus vaccine versus vaccine alone. PATIENTS AND METHODS: Thirty-two patients with resected Dukes' B, C, and D, and incompletely resected Dukes' D disease were treated with 2 mg of CeaVac every other week for four injections and then monthly until tumor recurrence or progression. Fourteen patients were treated concurrently with 5-FU chemotherapy regimens. RESULTS: All 32 patients entered onto this trial generated high-titer immunoglobulin G and T-cell proliferative immune responses against CEA. The 5-FU regimens did not have a qualitative or quantitative effect on the immune response. Three of 15 patients with Dukes' B and C disease progressed at 19, 24, and 35 months. Seven of eight patients with completely resected Dukes' D disease remained on study from 12 to 33 months; one patient with resected Dukes' D disease relapsed at 9 months. One patient with incompletely resected Dukes' D disease remained on study at 14 months without evidence of progression; eight experienced disease progression at 6 to 31 months. CONCLUSION: CeaVac consistently generated a potent anti-CEA humoral and cellular immune response in all 32 patients entered onto this trial. A number of very high-risk patients continue on study. 5-FU regimens, which are the standard of care for patients with Dukes' C disease, did not affect the immune response. These data warrant a phase III trial for patients with resected colon cancer.

Adjuvants, Immunologic↗