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Biomedical subjects

B Mukherji

Publications and source records attributed to B Mukherji.

At least 73 records · Page 4Linked to original sources

Prolonged retention in the circulation of emulsified lipid-coated perfluorochemicals.

A new emulsion of perfluorochemical, in which the emulsified particles are coated with lecithin, has been infused in rats. The retention of the emulsified perfluorochemical in the circulation has been prolonged more than 300% by injections of lecithin, which maintain a high concentration of lecithin in the plasma. This prolonged retention in the circulation resulted in a marked decrease in the amount of perfluorochemical retained in the liver and spleen.

Animals↗

Is prolactin secreted ectopically?

The ectopic secretion of prolactin by neoplasms has been reported only rarely although in one preliminary report it has been found to be present commonly in tumor extracts. To ascertain whether this is due to a true rarity of prolactin-secreting tumors or to the fact that prolactin hypersecretion causes few notable clinical symptoms in patients with cancer, we measured prolactin levels by radioimmunoassay in the serums of 215 patients who had a variety of malignancies. Prolactin levels were elevated (greater than 25 ng/ml) in 15 patients. In 12 of these 15 patients, the elevations could be explained by the use of phenothiazine or opiates, or prior irradiation to the chest wall or head. Additional serum samples showed clearly normal prolactin levels in one of the patients. Of the entire series of 215 patients, therefore, only two patients (1 percent) had modestly elevated prolactin levels without having known causes for hyperprolactinemia: one patient with squamous cell carcinoma of the lung (prolactin 34.1 ng/ml) and one patient with breast cancer (prolactin 45.4 ng/ml). Even in these two patients the hyperprolactinemia could as likely be due to stimulation of afferent nerves in the chest wall as to ectopic secretion by the tumors. There is no clear evidence in our study or in the literature that prolactin is secreted ectopically; this is in sharp contrast to many studies showing the high frequencies of the ectopic secretion of a number of other hormones. Why this is so is unknown.

Humans↗

Granulomatous hepatitis as a late complication of BCG immunotherapy.

A case of BCG-induced granulomatous hepatitis, which developed 1 1/2 years after BCG immunotherapy for recurrent malignant melanoma, is described to document the development of this disease entity as a potential late complication of BCG immunotherapy. The clinical implications of the late development of BCG-induced granulomatous hepatitis, use of immunosuppressive chemotherapy, and possible alternatives for BCG in intratumor immunotherapy are discussed.

Aged↗

Lymphocyte cytotoxicity of patients developing multiple primary melanomas.

A study of cellular immunity was conducted, with particular attention to natural killer cell mediated in vitro cytotoxicity in 6 patients who had two or three primary melanomas (2 patients presenting synchronously with multiple primaries and additional melanomas subsequently developing in 4). All 6 patients were reactive to one or other recall skin test antigens (PPD, streptokinase streptodornase (SK-SD), monilia, mumps) and DNCB skin testing. All exhibited natural killing against melanoma and nomelanoma tumor target cells when examined in the 3H proline microcytotoxicity test with unfractionated as well as natural killer cell enriched (Fc receptor positive cells recovered as Fc receptor rosettes) lymphocyte fractions. None of the 4 patients who subsequently had additional primary tumors was found to lack in mature T or natural killer cell mediated cytotoxicity at the time of the development of additional primaries. Two melanoma cell lines were established from two separate primary tumors in 1 patient and in vitro cytotoxicity assays were performed with that patient's lymphocytes (unfractionated, T enriched, and natural killer cell enriched fractions) against these two lines. While the first melanoma cell line was consistently sensitive to lysis by all three lymphocyte fractions, the other cell line showed no sensitivity either for natural killing or for T enriched lymphocyte mediated lysis at any effector to target ratio. These results suggested that in vitro natural cytotoxicity was not translated into any substantive immunoprotective role in the development of multiple primary tumors and that the two separate melanoma cell lines from the same patient were antigenically hererogenous. Antigenic heterogeneity between different primary tumors may explain the lack of immunity against such development of multiple tumors of the same histology.

Antibody-Dependent Cell Cytotoxicity↗

In vitro assay of spontaneous cytotoxicity by human monocytes and macrophages against tumor cells.

The [3H]proline microcytotoxicity technique has been adopted to examine the spontaneous cytotoxic property of human circulating monocytes (M) derived from the peripheral blood and resident monocytes/macrophages (M0) derived from effusion fluids. A leukocyte fraction is obtained by centrifugation in Ficoll-Hypaque (F-H) gradient. M are then isolated as adherent cells following incubation of the leukocyte fraction in plastic flasks containing 50% fetal calf serum (FCS) in culture medium. M0 are isolated from effusion fluids after first separating the Fc receptor bearing cells (as Fc receptor-7S EA resettes) in F-H gradient and then enriching them as adherent cells. The above techniques yield a M/M0 population of some 90-98% purity. The M/M0 non-selectively lyse tumor cells and allogeneic normal fibroblasts in the 48 h [3H]proline assay. The fibroblasts, however, exhibit considerable resistance to lysis, particularly at lower effector to target ratios. While appreciable levels of cytotoxicity are observed with resident M0 at 6 h, followed by a further increase in the level of cytotoxicity at 24-48 h, circulating M exhibit a consistent level of cytotoxicity only at 24-48 h. When circulating M and resident M0 from the same donor are examined concurrently for cytotoxicity, resident M0 are consistently found to show significantly higher levels of cytotoxicity when compared to circulating M. This may reflect a true functional heterogeneity within this lineage of effector cells or some degree of in vivo activation of resident M0 in malignant and non-malignant effusion fluids. Further studies of spontaneous cytotoxicity by M/M0 through CMC assay techniques, such as the [3H]proline microtoxicity technique, will be useful in the examination of the role of M/M0 in cell mediated immunity and immunosurveillance against cancer.

Cell Line↗

High dose methotrexate with and without BCG therapy in advanced head and neck malignancy.

Twenty-three patients with advanced recurrent head and neck carcinoma were randomized to receive either high dose methotrexate with calcium leucovorin rescue (HDMTX) or HDMTX in combination with bacilli Calmette Guerin (HDMTX/BCG). An additional eight patients were treated with escalating doses of HDMTX ranging from 1 to 7 g of methotrexate. Of 12 patients receiving HDMTX, one complete response and two partial responses were noted. Of 11 patients in the HDMTX/BCG group, one complete response and two partial responses were observed. Only one partial response was noted in eight patients receiving escalating doses of the drug. Responses were brief and no significant difference in response duration was seen in any particular group. Toxicities in all groups were tolerable. BCG did not improve response rate, median duration of response, or median survival in these patients. Reported experiences with high dose methotrexate have been reviewed and again, responses to "high dose methotrexate" were found to be of brief duration. Despite acceptable toxicity, the brief duration of response and cost of such therapy raises serious question on the usefulness of chemoimmunotherapy utilizing high dose methotrexate with leucovorin rescue and BCG in the management of advanced recurrent carcinomas of the head and neck region.

Adult↗

Selective and non-selective lymphocytotoxicity in human melanoma: observation on the effect of long-term culture and fetal bovine serum on target-cell sensitivity to lymphocytes.

In vitro cell mediated cytotoxicity (CMC) assays have been conducted in a human melanoma system with a 3H-proline retention technique. Melanoma target cells from long-term cultures ("cell lines") are found to exhibit increased susceptibility for lymphocyte cytotoxicity in comparison to the same target cells from short-term culture. The higher sensitivity of the "cell line" derived target cells is seen with lymphocytes, irrespective of diagnosis of the donor. In parallel experiments with the target cells grown in medium supplemented with fetal calf serum (FCS) and AB+ human serum (from a normal male doner), the melanoma target cells grown with FCS do not show any enhanced cytotoxicity, suggesting no causal relationship of such enhanced sensitivity of "cell line"-derived target cells to "heterologous melanoma antigens" that might have been acquired by the target cells following the use of FCS in tissue culture. In controlled assays of in vitro CMC, lymphocytes from melanoma patients (14/44) exhibited selective cytotoxicity (destruction of only one target-cell type) against the melanoma target cells, whereas only 3/97 control lymphocytes (other malignancies and normal donors) showed such melanoma-selective cytotoxicity. This difference is statistically significant at p less than 0.001. Non-selective cytotoxicity (destruction of two or more unrelated target cell types) was seen with lymphocytes from 9/44 melanoma patients, 13/51 patients with other malignancies and 8/46 normal donors. No correlation of selective cytotoxicity could be established with donors' age, sex, stage of disease, therapy or history of blood transfusion. Such a correlation may emerge as our series becomes larger. Despite the lack of any correlation between selective cytotoxicity and disease status, our study reaffirms the existence of selective cytotoxicity by melanoma patients' lymphocytes against melanoma target cells.

Animals↗

Variables and specificity of in vitro lymphocyte-mediated cytotoxicity in human melanoma.

In vitro cell-mediated cytotoxicity (CMC) assays have been carried out in human melanoma system with blood effector lymphocytes on [3H]proline-labeled target cells in a 48-hr microcytotoxicity technique. Three lymphocyte purification procedures (Ficoll:Hypaque gradient, plasma gel sedimentation followed by nylon column incubation, and plasma gel sedimentation followed by separation with nylon powder and glass beads) are compared in parallel experiments for characteristic effector cell composition and cytotoxic potential against target cells of dissimilar histology. The cytotoxicity is defined by the loss of target cell 3H cpm as measured by residual target cell 3H cpm in individual microwell following incubation with lymphocytes. Target cell 3H cpm loss by test lymphocytes is compared with target cell 3H cpm loss by several age and sex matched control lymphocytes (from normal donors and unrelated cancer patients); further comparison between the various control lymphocytes is also made in each assay. As control for target cells, autologous fibroblasts and homologous tumor cells of dissimilar histology are always included in each assay. Specific cytotoxicity is defined as statistically significant and selective destruction of only melanoma cells by the test lymphocytes as compared to the control lymphocytes. Significant but nonselective destruction of 2 or more target cells of unrelated histology is regarded as nonspecific cytotoxicity, while no destruction of any target cells signifies no cytotoxicity. The Ficoll:Hypaque preparations consistently exhibit the highest nonlymphocytic cell contamination (8 to 16%); the nonlymphocytic cells are, almost exclusively, monocytes. They also produce relatively high percentage of thymus independent (B) cells (8 to 15%). The ultimate cell composition of the 2 plasma gel-nylon preparations is essentially identical. In either plasma gel-nylon preparations, the nonlymphocytic contamination is minimal (0 to 4%) and thymus-dependent (T) cell percentage is considerably higher (92 to 99%) with none or few B cells.

Cell Separation↗