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Biomedical subjects

T Ghose

Publications and source records attributed to T Ghose.

At least 73 records · Page 4Linked to original sources
PubMed1982

Imaging of human melanoma xenografts in nude mice with a radiolabeled monoclonal antibody.

External photoscanning with display of radioactivity data as a color-scaled image detected xenografts of human melanoma in male nude inbred mice of BALB/c background 48 hours after injection of 131I-labeled monoclonal IgG 225.28S that is specific for human melanoma. A 131I-labeled polyclonal goat IgG against human melanoma-associated antigens could also image the tumor, but with this preparation there was considerable localization of radioactivity in normal tissues, resulting in less satisfactory tumor definition. Labeled normal mouse IgG did not image the melanoma grafts. Assay of radioactivity in tissues of melanoma-grafted mice confirmed tumor-specific localization of the antimelanoma antibodies. The tumor:blood ratio of radioactivity was 6.55 with the monoclonal antimelanoma IgG and 0.45 with the polyclonal IgG.

Animals↗
PubMed1981

A light and electron microscopic study of liver and lung tumors induced by a single low dose of diethylnitrosamine (DEN) in C57BLXC3H F1 mice.

The effect of a single intragastric dose of DEN was studied in 15-day-old male C57BLXC3H F1 mice. Group 1 was given 0.315, group 2, 0.625 micrograms/g, and group 3 served as a vehicle control. Animals were sacrificed at regular intervals up to 75 weeks. Liver and lung tissue were examined by light and electron microscopy. Mice of group 1 and 2 developed liver lesions ranging from hyperplastic nodules to hepatocellular adenomas and carcinomas. The incidence of these lesions varied with the length of observation period. Electron-dense crystalline inclusions of alpha 1 antitrypsin were found in the dilated cisternae of the rough endoplasmic reticulum of the hyperplastic and adenomatous nodules. The incidence of lung adenomas was significantly higher in group 3 than groups 1 and 2; ultrastructurally these tumors contained both Clara cells and type II pneumocytes. The results indicate that DEN is effective even in a low single dose in inducing liver and lung tumors in mice.

Animals↗
PubMed1980

Alpha-1-antitrypsin in intracellular inclusions of diethylnitrosamine induced hepatomas of C57BLxC3H F1 mice.

Six large hepatic nodules obtained 46 to 74 weeks after a single dose of diethylnitrosamine (0.625 or 1.25 micrograms/gm) in infant C57BLxC3H F1 male mice were studied to elucidate the nature of intracytoplasmic inclusions in the hepatic cells of these nodules. By light microscopy, the nodules constituted a spectrum of lesions ranging from some which were well differentiated adenomas to others which were frank carcinomas. Round or oval eosinophilic intracytoplasmic inclusions were consistently seen in the well differentiated adenomatous lesions. Some of these inclusions were PAS positive and resisted diastase digestion while others were either negative or only weakly PAS positive. By electron microscopy, they were most commonly crystalline, contained a reticulated electron dense material and were located in the distended rough endoplasmic reticulum. On immunofluorescence the inclusions showed marked specific reactivity with antisera against human alpha-1-antitrypsin. The presence of alpha-1-antitrypsin in these inclusions was further supported by the resistance of these inclusions to digestion by trypsin or papain but not by the pepsin or pronase.

Animals↗
PubMed1979

Production and characterization of xenogeneic antisera to a human renal cell carcinoma-associated antigen.

Antisera to human renal cell carcinomas were produced by the immunization of goats and rabbits with dissociated tumor cells and/or tumor homogenates from single donors. After absorptions with human red blood cells and homogenates of human liver, lung, spleen, and heart, all the immune sera reacted on immunofluorescence with the brush border of the proximal convoluted tubules of adult and fetal human kidneys and with the proximal convoluted tubular epithelia of rabbits, guinea pigs, rats, and mice. After further absorption with pooled normal human kidney homogenates, the immune sera on immunofluorescence showed cytoplasmic staining of smears and sections of 21 of the 22 human renal cell carcinomas tested. These sera did not show any staining of normal adult human tissues including normal kidney adjacent to the carcinomas, perirenal fibroblasts and peripheral blood leukocytes from the patients, human fetal kidneys, transplanted renal adenocarcinoma of BALB/c mice, and several human tumors tested, i.e., transitional cell carcinoma of the bladder, adenocarcinomas of the breast and colon, squamous cell carcinoma of the lungs, malignant lymphoma, and melanoma. Autoradiography of tissue sections with 131I-labeled antitumor globulins revealed greater localization of radioactivity in tumors than in adjacent normal kidney. Membrane immunofluorescence with the immune sera rendered tumor-specific after appropriate absorptions revealed tumor-associated antigens on the surfaces of all 5 human renal carcinoma cell lines tested.

Adenocarcinoma↗
PubMed1978

Radionuclide imaging of metastases from renal-cell carcinoma by 131I-labeled antitumor antibody.

On immunofluorescence assay, goat antisera reacted with renal-cell carcinomas from 20 patients, but not with adult normal human tissues (including patient's normal kidney). After in travenous injection, the 131I-labeled antibody localized preferentially in metastatic renal carcinoma in 6 consecutive patients. Labeled antitumor antibodies may have the specificity for tumor imagining which current radiopharmaceuticals lack.

Adenocarcinoma↗
PubMed1978

An experimental model of acute immune-complex uveitis.

We developed an experimental model of anterior uveitis by injecting ovalbumin or bovine serum albumin into the anterior chamber of sensitized rabbits. All the eyes showed leakage of serum proteins into the aqueous humor within 30 min. and developed uveitis within 24 hrs. which lasted at least a week. On histological examination, large numbers of polymorphonuclear (PMN) leucocytes and only occasional mononuclear cells were seen in the iris, the ciliary body and the irido-corneal angle. Immunohistological examination revealed 7s gamma globulin in the walls of blood vessels, in the interstitium and inside the PMN leucocytes. Contact radiographs of eyes challenged repeatedly showed extensive neovascularization of the iris and ciliary body.

Animals↗
PubMed1978

Radionuclide imaging of primary renal-cell carcinoma by I-131-labeled antitumor antibody.

A goat antibody against human renal-cell carcinoma reacted on immunofluorescence with renal-cell carcinomas from 20 patients, but not with normal adult human tissues, including kidney. After i.v. administration the I-131-linked antibody showed preferential tumor localization in six of seven patients with primary renal carcinoma. Labeled antitumor antibodies may have the specificity for tumor imaging that current radiopharmaceuticals lack.

Adenocarcinoma↗
PubMed1978

Antibody-linked cytotoxic agents in the treatment of cancer: current status and future prospects.

Antibodies against tumor cell surface antigens have been used as selective carriers of anticancer drugs, which themselves lack selectivity. Although such antibodies have been demonstrated in tumor hosts, xenogeneic antitumor sera should provide larger yields of better-defined antitumor antibodies for therapeutic purposes. This review examined factors that influence the immune response to tumor-associated transplantation antigens (TATA) and the methods for rendering tumor cells more immunogenic. Consideration was also given to techniques for elimination of irrelevant immunoglobulin molecules. These could involve purification of both antitumor sera and TATA fractions for immunization, as well as tailoring of the immunization protocol. Various toxic agents that have been linked to antitumor globulins with retention of agent and antibody activity were tabulated: alkylating drugs, antibiotics, antimetabolites, cell surface agents, protein synthesis inhibitors, and unconventional anticancer agents that selectively convert nontoxic arsenicals or halides into cytocidal derivatives. The methods by which effective conjugates can be produced and their possible mode of action were described for the different types of agents. Several problems inherent in this modality of tumor therapy include: 1) the necessity of binding therapeutically effective amounts of antitumor agent, 2) ensuring of delivery of drug in active form to target sites, 3) avoidance of host reactions to foreign proteins, and 4) possible emergence of resistant tumor cell populations. Antibody-linked cytotoxic agents may find their greatest use in the eradication of small numbers of circulating tumor cells and micrometastases remaining after removal of primary tumors.

Alkylating Agents↗
PubMed1977

In vivo suppression of EL 4 lymphomas by rabbit antitumor sera.

Three of more than 50 batches of rabbit antisera raised against the mouse EL 4 lymphoma could inhibit the growth of the tumor in the syngeneic C57BL/6J mice either after exposure of the tumor cells to the antitumor globulin (ATG) in vitro or after the administration of ATG in mice preinoculated with various numbers of EL 4 cells, even though the ATG was not cytotoxic to the tumor cells in the presence of complement. The outcome of immunotherapy with ATG in tumor-bearing C57BL/6J mice depended on the tumor load, the interval between tumor inoculation and the institution of therapy, the total dose, and the schedule of administration of ATG. Complete tumor suppression could be obtained in a proportion of mice preinoculated with 10(5) EL 4 cells, i.e., 10(4) times more than the minimum number of EL 4 cells necessary for 100% tumor takes. Whole-body irradiation (400 rads) or complement depletion of tumor host by cobra venom factor had no effect on tumor suppression by ATG. No evidence of immunity against the EL 4 lymphoma could be detected in EL 4-bearing mice that survived after serotherapy. Anti-EL 4 sera raised in goats and goat and rabbit antisera raised against a lymphoma in the AKR mice have, so far, failed to show any tumor inhibition.

Animals↗
PubMed1977

Immunochemotherapy of malignant melanoma with chlorambucil-bound antimelanoma globulins: preliminary results in patients with disseminated disease.

Thirteen consecutive patients with inoperable recurrent malignant melanoma were treated by immunochemotherapy with the use of chlorambucil noncovalently bound to goat or rabbit antihuman melanoma globulins. The next consecutive 11 patients fulfilling the criteria for admission into this study were treated with chemotherapy only, i.e., dimethyltriazenoimidazole carboxamide (DTIC). Follow-up was for a minimum of 29 months or until death. Two patients showing an objective response to immunochemotherapy had disease confined to lymph nodes and cutaneous sites; 5 others showed stabilization of cutaneous, nodal, and visceral disease, and 6 patients showed progression of their disease. The median survival of the responders and stabilizers was 20 months, but only 3.5 months for patients with disease progression. None of the 11 patients treated with DTIC had objective tumor regression, and all died within 11 months of the start of treatment with a median survival of 3 months. Immunochemotherapy significantly prolonged the survival compared to that in the DTIC-treated group (P less than 0.05). No hematologic or renal toxicity was detected after immunochemotherapy, but 2 patients in this group developed anaphylactic reactions. Skin reactivity tests to dinitrochlorobenzene and purified protein derivative were of no prognostic value

Adolescent↗
PubMed1977

A study of the effects of systemic administration of adrenal glucocorticoids in an experimental model of hypersensitivity pneumonitis.

To study the effects of steroids on the pulmonary lesions in experimental hypersensitivity pneumonitis, rabbits were sensitized to ovalbumin (OA) by injections of OA into footpads and 3 weeks later they were subjected to two successive aerosol challenges with OA at an interval of 48 hr. Injections of hydrocortisone sodium succinate 10 mg twice daily (but not at the reduced dosage of 5 mg twice daily) or methyprenisolone acetate 5 mg twice daily beginning 30 min before the first challenge and continued to the time of killing reduced the extent and intensity of vasculitis in both the treated groups and showed less alveolar septal thickening in the hydrocortisone treated group and less alveolar consolidation in the methylprednisolone treated group compared to the pulmonary lesions in the rabbits which were sensitized and then subjected to OA aerosol challenges, but received no treatment. In view of the observation that even in a steroid sensitive species like the rabbit, extensive pulmonary changes like alveolar consolidation, septal thickening and vasculitis persisted in spite of treatment with relatively large doses of these steroids, it was felt that in human hypersensitivity pneumonitis steroids might only suppress the warning symptoms without substantially affecting the progress of the pulmonary lesions.

Alveolitis, Extrinsic Allergic↗
PubMed1977

Interaction in vitro between myocardial cells and autologous lymphocytes and sera from patients with rheumatic carditis.

The cytotoxicity of antimyocardial antibodies and peripheral blood lymphocytes from patients with rheumatic carditis on autologous myocardial cells was investigated. Although sera obtained after open-heart surgery from seven out of eight patients with rheumatic carditis were bound to cultures of autologous myocardial cells, they were not cytotoxic. Peripheral blood leukocytes obtained both before and after surgery from one of these eight patients aggregated around and underwent blast transformation when exposed to autologous myocardial cells in vitro, but not after exposure to autologous skin fibroblasts. Only the postoperative leukocytes from another of these eight patients aggregated around autologous myocardial cells in vitro; however, these lymphocytes were also not cytotoxic to autologous myocardium. To investigate the effect of antimyocardial antibodies on myocardial function, antimyocardial antibodies were added to the culture medium of pulsating cultures of mouse myocardial explants. Although antimyocardial antibody from 27 patients with chronic rheumatic carditis and seven postcardiotomy patients had no effect on the pulsation of the mouse myocardial cultures, serum gamma-globulin from a patient suffering from acute rheumatic fever with myocardial involvement first accelerated and then gradually stopped the pulsation of mouse myocardial explants.

Antibodies↗