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Biomedical subjects

S S Joshi

Publications and source records attributed to S S Joshi.

70 records · Page 4Linked to original sources
PubMed1987

Detection of malignant cells in histologically normal bone marrow using culture techniques.

Cellular material retained on screens used to filter aspirated bone marrow for future autologous marrow transplantation was studied using long-term culture techniques in 20 consecutive patients. All patients had marrow aspirate and biopsy specimens that were normal histologically. Cultures from five patients grew malignant cells similar to those of the known underlying malignancy. Two types of culture methods were used in these studies. Method I consisted of a long-term bone marrow culture system which predominantly favors adherent cells, and Method II consisted of a suspension type culture system favoring expansion of mononuclear cell types. These findings suggest that tumor cells are reinfused more often at the time of autologous bone marrow transplantation than has been previously suspected. Although the clinical significance of these findings is not known, it is clear that culture techniques combined with special stains and molecular probing will allow the improved detection of occult tumor cells in bone marrow from patients undergoing autologous marrow transplantation. These observations emphasize the need for a comprehensive study of histologically normal autologous marrow using culture techniques to determine the frequency of occult involvement by viable malignant cells and the clinical implications of these findings.

Adult↗
PubMed1985

Differentiation inducing effects of butyrate and DMSO on human intestinal tumor cell lines in culture.

In the present report, we have studied the effects of butyrate and dimethyl sulfoxide (DMSO) on the characteristics of four human intestinal tumor cell lines in vitro; namely a duodenal adenocarcinoma HTB-40 and three adenocarcinomas of colon: HT-29, CCL-218, and CCL-222. In the presence of concentrations of 2 mM butyrate and 2% DMSO the growth of all these four cell lines was significantly inhibited. Both these agents lengthened the doubling time of these cell lines by about twofold. In addition, the morphology of the treated cells was altered. All four cell lines grow in semisolid agar and form characteristic colonies. Butyrate and DMSO inhibited the colony forming efficiency of these cell lines by 40-60%. Using flow cytometric analysis, the cells that were grown in the presence of butyrate and DMSO were analyzed for their lectin-binding properties. For this purpose the lectins used were concanavalin-A (Con-A), peanut agglutinin (PNA), wheat germ agglutinin (WGA), and succinylated wheat germ agglutinin (SWGA). All four cell lines showed an increase in lectin-binding cells. CCL-218, which showed no PNA binding when grown without these agents, acquired about 25% reactivity when grown in the presence of butyrate or DMSO. All these cell lines showed an increase in the percentage of positive cells for the lectin SWGA that unlike WGA does not bind to sialic acid on the cell surface, suggesting an increase in nonsialated residues on all the treated cells. These results indicate a differentiation inducing effect of butyrate and DMSO on these cell lines.(ABSTRACT TRUNCATED AT 250 WORDS)

Butyrates↗
PubMed1983

Modified combination chemotherapy of leukemia. An attempt to overcome drug resistance.

Vincristine and prednisolone are important drugs for induction therapy in acute lymphoblastic leukemia. In our experience quite a number of patients relapse during maintenance therapy after induction. At this stage some of the patients are resistant to vincristine and prednisolone. In the present study we attempted to explore whether vincristine could be used together with cytosine arabinoside. Vincristine being a phase-specific agent is known to synchronize the leukemic cells in vitro and a drug like cytosine arabinoside added after vincristine at the appropriate time is expected to have added cell kill. In vitro studies with leukemic cells confirmed the expected increase in cell kill with the addition of cytosine arabinoside 6 h after vincristine treatment. Simultaneously, the same approach was explored in the clinic. Acute lymphoblastic leukemia patients who were resistant to vincristine and prednisolone for reinduction, remitted with this strategy, i.e. with the addition of cytosine arabinoside 6 h after the vincristine treatment.

Adolescent↗
PubMed1976

Badenoch's pull-through operation for urethral stricture.

14 patients with strictures in the region of the membranous urethra were treated by Badenoch's urethral pull-through operation or a slight modification of this. The results were good in 10 of the cases. This procedure has advantages over those using scrotal flaps in hot climates.

Adolescent↗
PubMedDate not supplied

Characterization of metastasis-associated antigens on RAW117 lymphosarcoma cell lines.

A syngeneic murine model system was used to study the immunobiology of metastasis. The highly malignant RAW117-H10 cell line was compared to the less malignant parental RAW117-P cell line from which it was derived, for expression of cell surface antigens. Using rabbit antisera, two major glycoprotein antigens were detected on the tumor cell surfaces. Antigen-I was uniformly distributed over the surface of these cells whereas antigen-II had a patchy, punctate distribution. Antigen-I was displayed less on RAW117-H10 cells than on RAW117-P cells, while the expression of the other serologically distinct antigen (antigen-II) was increased on RAW117-H10 cells compared to the less malignant parental (RAW117-P) cells. This differential antigen expression was assessed by immunodiffusion, a 125I-labeled protein-A binding assay, flow cytometry and rocket immunoelectrophoresis. Both these antigens had a molecular weight of 70,000 daltons. Antigen-I bound the lectin concanavalin-A whereas antigen-II did not, suggesting that antigen-I might be the viral envelope glycoprotein gp70. The identity of antigen-II is presently unknown. Syngeneic Balb/c mice injected with highly malignant and metastatic RAW117-H10 cells coated with antiserum to antigen-I were protected from early death; this effect was not seen with RAW117-H10 cells coated with antiserum to antigen-II. The opsonizing qualities of these antisera may be different due to antibody to antigen-II being shed more rapidly than antibody to antigen-I.

Animals↗
PubMedDate not supplied

Enhanced antiproliferative activity by metastatic RAW117 lymphoma cells.

The highly malignant/metastatic murine large cell lymphoma cell line RAW117-H10 forms 100-200 times more liver metastatic tumors than its parental counterpart cell line RAW117-P. RAW117-H10 cells, but not the less malignant/metastatic parental cells, significantly inhibited the mitogen-induced proliferation of normal syngeneic Balb/c and allogeneic ICRC mouse spleen cells. Such an inhibition also occurred when mitomycin-C treated metastatic lymphoma cells were added 24 h after initiation of culture, indicating that no competition with mitogen binding sites on the lymphocytes was necessary for inhibition of proliferation. 'Antiproliferative' cell surface molecules were extracted non-cytolytically from the RAW117-H10 cells using butanol. The butanol extracts from the metastatic RAW117-H10 cells also inhibited the mitogen-induced proliferation and natural killer (NK) cell-mediated cytotoxicity of normal spleen cells. Our results indicate that these 'antiproliferative' cell surface molecules of metastatic murine RAW117-H10 lymphoma cells may have important role(s) in tumor-mediated host immunosuppression.

Animals↗
PubMedDate not supplied

Macrophage-like-cell-induced growth regulation of lymphoma cells.

Since hematopoietic stromal cells play a major role in regulating the growth and differentiation of hematopoietic cells, we have studied the effects of stromal cells on the in vitro growth of highly malignant murine RAW117-H10 lymphoma cells. These cells, when grown on a preformed layer of syngeneic Balb/c macrophage/monocyte cell line, J774A.1, stop proliferating 48 h after coculture. This stromal-cell-mediated growth regulation appears to require cell-to-cell contact between stromal cells and RAW117-H10 cells, since the J774A.1 cell supernatant did not significantly inhibit the in vitro growth of RAW117-H10 cells. Because one of the cytokines produced by the macrophages is tumor necrosis factor (TNF)-alpha, which is known to inhibit certain tumor cells, we also studied the effects of various concentrations of TNF-alpha on the in vitro growth of RAW117-H10 lymphoma cells. TNF-alpha did not significantly affect the growth of these cells in vitro. However, TNF-alpha induced significant morphologic changes in these cells similar to those seen in plasma cytoid differentiation. Thus, our results indicate that the macrophage-like stromal cells regulate the in vitro growth of malignant lymphoma cells, and that direct cell surface contact between stromal and lymphoma cells is necessary for the growth regulation, and the growth inhibition is not due to TNF-alpha secreted by the macrophages. TNF-alpha is associated with differentiation of these lymphoma cells.

Animals↗
PubMedDate not supplied

Extent and role of urogastrone in the adaptive response of rat intestine to patching of a surgical defect in the ileum.

Crypt cell production rate, morphometric changes and uptake of radiolabeled human urogastrone (125I rhUG) were evaluated in intestinal tissues of the rat at 2, 4, 8, and 12 days following patching of a surgical defect in the ileum with adjacent cecum. The terminal ileum was incised along its antimesenteric border and the margin of the opened ileum was sutured onto the serosal surface of the cecum. At autopsy, the animals were injected intraperitoneally with 1 microgram/g body weight of the metaphase arrest agent, vincristine sulfate, and 50 microCI of 125I-rhUG (specific activity 1.7 microCi/micrograms) to quantify the crypt cell production rate and uptake of radiolabeled urogastrone, respectively. The results indicated that the crypt cell production rate was increased significantly throughout the small intestine of operated animals till the 12th postoperative day as compared to unoperated rats. The colon showed significantly increased crypt cell production rate only on the 4th day after surgery compared to unoperated rats. The stomach showed no changes. The uptake of 125I-rhUG increased significantly on the 2nd and 4th postoperative days in the small intestine and on the 2nd postoperative day in the colon as compared to unoperated rats and gradually decreased with increasing time after surgery. These results suggest that patching of an ileal defect resulted in a strong compensatory response in the small intestine. These results also demonstrated a close association between epithelial cell proliferation and uptake of 125I-rhUG, particularly in the early part of intestinal adaptation following the surgical stimulus to ileum.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMedDate not supplied

The immunomodulatory beta-galactoside-specific lectin from mistletoe: partial sequence analysis, cell and tissue binding, and impact on intracellular biosignalling of monocytic leukemia cells.

Nanogram quantities of the beta-galactoside-specific lectin from mistletoe (ML-I) that is composed of two different types of subunits exhibit immunomodulatory potency and enhance cytokine secretion in vitro and in vivo. Partial sequence analysis of the carbohydrate-binding B chain revealed a ragged N-terminus and overall homologies to the B subunit of Ricin D and Ricin E. Two evolutionarily neutral substitutions were apparent in the otherwise identical N-terminal sequences of the two toxic chains within the lectin preparation. On the basis of the influence of chemical modification by group-specific reagents on ligand binding, the lectin was biotinylated with biotinyl-N-hydroxysuccinimide ester to allow monitoring of cell binding. Monocytic leukemia cells (THP-1) specifically bound the lectin with positive cooperativity at low lectin concentrations. Radiolabelled lectin could be found in several organs and in an experimental solid tumor in biodistribution in mice. Its presence in a notable amount in spleens is especially noteworthy with respect to the already reported immunomodulation. To determine intracellular responses that precede the lectin-dependent augmentation of cytokine secretion, phosphorylation of proteins and phospholipids as well as Ca(2+)-mobilization were assessed in THP-1 cells. Quantitative increases of [32P]-phosphate incorporation were determined for a 28 kDa protein and for phosphatidylinositol-4,5-biphosphate. Similarly, the fluorescence activity of the intracellular Ca(2+)-indicator fluo-3 is elevated by approximately 25% after lectin treatment. Apparently, cell binding of the lectin is followed by modulation of biosignalling processes.

Amino Acid Sequence↗
PubMedDate not supplied

Establishment, characterization and determination of cell surface sugar receptor (lectin) expression by neoglycoenzymes of a human myeloid marker-expressing B lymphoblastoid cell line.

Mediation of cellular interactions by protein (lectin)-carbohydrate recognition presupposes the expression of respective surface determinants. Due to the importance of cellular contacts between bone marrow stromal cells, recently shown to express cell surface lectins, and tumor or normal progenitor cells for biosignaling and marrow egress, quantitation of cell surface sugar receptor expression by a panel of chemically glycosylated enzymes (tetrameric E. coli beta-galactosidase) for human leukemia/lymphoma cells was initiated. Cells of the new B lymphoblastoid line Croco II that are partially positive for the CD15-specific epitope expressed receptors for various sugar specificities on their surface, fulfilling an indispensable prerequisite for establishment of glycobiological interactions. Binding studies with increasing neoglycoenzyme concentrations up to saturation in four cases disclosed values for apparent affinity constants in the range of 25-200 nM with 0.25-3 x 10(5) bound probes per cell. The presence of receptors for constituents of carbohydrate chains of cellular glycoconjugates was also ascertained biochemically, namely for beta-galactosides, alpha-mannosides, alpha-fucosides and N-acetylgalactosaminides. Expression of this property was modulated by changes in the culture conditions, as revealed by binding studies with cells, derived from growth in medium containing different serum concentrations. These findings indicate that cell surface sugar receptors of tumor cells warrant further attention with respect to recognitive interactions.

Antigens, CD↗
PubMedDate not supplied

Are matrix-immobilized neoglycoproteins, plant and human lectins and carbohydrate--binding antibodies from human serum mediators of adhesion in vitro for carcinoma and lymphosarcoma cells?

Mediation of cell adhesion by defined molecules can be studied by their immobilization onto a nitrocellulose matrix and incubation with cells. In order to infer the capacity of deliberately selected protein-carbohydrate interactions to establish sugar-inhibitable cell adhesion, a panel of immobilized neoglycoproteins was employed for the murine lymphosarcoma lines RAW-117 with low (P) and high (H10) metastatic capacity, a human mammary carcinoma line (DU4475) and three human colon carcinoma lines (C205, SW480, SW620). Exhibiting an otherwise rather similar behavior relative to the line with low metastatic potential, the murine line RAW117-H10 bound strongly to the matrix with carboxyl group-bearing N-acetylneuraminic acid and glucuronic acid as well as rhamnose. Whereas the analysis of carbohydrate-mediated adhesion yielded comparable results for the three colon carcinoma lines, a markedly reduced number of adherent cells was counted for matrix-attached alpha- and beta-galactosyl, alpha-mannosyl and alpha-glucosyl moieties in the case of the mammary carcinoma line, raising evidence for cell lineage-dependent alterations of this property. From the carbohydrate-binding proteins, the plant lectin, concanavalin A and Viscum album agglutinin almost invariably served well as cell adhesion molecules. Appropriate cell surface sugar receptors, probed with neoglycoproteins, and glycoconjugates, probed with lectins, thus can contribute to adhesion in this model system. The immobilized human beta-galactoside-binding lectin (Mr 14kDa) caused adhesion of the murine lines and one colon carcinoma line (SW480). Neither C-reactive protein under conditions that induce its activity as lectin nor serum amyloid P component nor a lactose-binding immunoglobulin G fraction from human serum were reactive. However, cell adhesion to the alpha-galactoside-binding immunoglobulin G fraction of human serum was seen with the murine line of low metastatic capacity and the mammary carcinoma line. Cells of this line adhered also to the mannan-binding protein from human serum, supporting the view for its potential role in host defence against aberrantly glycosylated tumor cells.

Adenocarcinoma↗