Radiosensitization of EL4 lymphoma cells by a commonly used food additives-butylated hydroxytoluene (BHT).
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Biomedical subjects
Publications and source records attributed to T Ghose.
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Cell-surface localizing heterologous antibodies against the mouse EL4 lymphoma and a human malignant melanoma could be bound to chlorambucil without causing the loss of the alkylating activity of chlorambucil or interfering with the reactivity of the antibodies with their respective tumour cells. When given to mice preinoculated with tumour cells 2, 24, 72, and 120 hours before the beginning of treatment the chlorambucil-bound antibody was a much more effective tumour inhibitor than chlorambucil or the antibody alone. In a patient with disseminated malignant melanoma injection of the chlorambucil-bound anti-melanoma antibody first locally into a few metastatic nodules and then by the intravenous route was followed by the regression of all the metastatic nodules.
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Efficacy of antibody mediated targeting depends on retention of immunoreactivity in conjugates. Retention can be improved by site-specific linkage of drugs or drug-loaded carriers to residues that are located well away from the antigen-binding sites. In this study we describe the site-specific linkage of a potential drug carrier, human serum albumin (HSA), to the carbohydrate residues in Dal K20, a murine IgG1 monoclonal antibody (mAb) against human renal cell carcinoma, using disulfide exchange between 3-(2-pyridyldithio)propionic acid succinimidyl ester (SPDP)-derivatized HSA and 11-[[3-(2-pyridyldithio)propionyl]amino]undecanoic acid hydrazide (AUPDP)-derivatized mAb Dal K20. AUPDP gave a higher yield of the conjugate than a functionally analogous 3-(2-pyridyldithio)propionic acid hydrazide (HPDP), suggesting that the extra length of the former facilitated the linkage. The conjugates were found to be unstable without reduction of the hydrazone linkage using sodium cyanoborohydride. Stabilized 1:1 HSA:K20 carbohydrate-linked conjugates were isolated and compared with non-site-specific 1:1 conjugates in which HSA was conjugated to amino groups in mAb Dal K20. The yield and stability of the two conjugates were comparable, but the site-specific conjugate was found to retain three times more antibody activity than the non-site-specific conjugate.
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BACKGROUND: Until recently, conventional intracoronary stent deployment required predilatation of the lesion with a balloon. However, "direct stenting" of the lesion without predilatation offers certain theoretical and practical advantages. We assessed the safety and feasibility of direct stenting in a select group of patients who were likely to benefit most from these advantages, namely, those with acute coronary syndromes. saphenous vein graft lesions, associated renal or left ventricular dysfunction and those requiring multivessel intervention. METHODS AND RESULTS: After direct stenting, intravascular ultrasound was used to assess the adequacy of stent expansion in 51 patients. One hundred and twenty patients with a total of 125 lesions (83.3% males, average age 54.6+/-12.4 years) were enrolled for direct stenting. Of these, 90% of patients had presented with acute coronary syndromes, 21.6% of patients had associated moderate-to-severe left ventricular systolic dysfunction, 6.7% of patients had associated renal dysfunction and 30.8% of patients required multivessel intervention. Angiographically visible thrombus was present in 35.2% of patients. The mean reference diameter of the lesion was 3.18+/-0.32 mm and mean percentage diameter stenosis was 76.4+/-11.2%. Almost all varieties of stents were used (8.8% bare and 91.2% mounted). Procedural success was achieved in 98.3% of patients (98.4% of lesions). In two cases, the lesion had to be predilated prior to stenting. On angiography, the need for postdilatation of the stent was apparent in 29 (23.6%) lesions. In contrast, on intravascular ultrasound evaluation done in 51 lesions after stent deployment, the need for postdilatation to optimize stent expansion was seen in 43 (84.3%) lesions. There was one instance of acute stent thrombosis and two instances of slow-flow phenomenon. There were no deaths, myocardial infarction or need for urgent bypass surgery. CONCLUSIONS: We conclude that direct stenting is feasible and safe in selected groups of patients. Optimization of stent expansion after direct stenting may often require aggressive postdilatation.