PubMed Health⌕ Search

Biomedical subjects

S S Kulkarni

Publications and source records attributed to S S Kulkarni.

At least 37 records · Page 2Linked to original sources
PubMed1989

Elimination of drug-resistant myeloma tumor cell lines by monoclonal anti-P-glycoprotein antibody and rabbit complement.

The effectiveness of ex vivo chemotherapy with drugs, such as vincristine, etoposide, and Adriamycin (doxorubicin, Adria Labs, Columbus, OH) for elimination of residual tumor cells from human bone marrow grafts could be undermined by the presence of multidrug-resistant tumor cells in the bone marrow. Therefore, to supplement chemoseparation, we investigated whether MRK-16, a monoclonal antibody (MoAb) to the surface moiety of multidrug resistance-associated P-glycoprotein antigen, can eliminate drug-resistant tumor cells in the presence of rabbit complement (RC). Two doxorubicin (DOX)-resistant human myeloma tumor cell line, 8226/DOX40 (resistant to 4 x 10(-7) mol/L DOX) and 8226/DOX6 (6 x 10(-8) mol/L DOX) with high and low amounts of cell surface P-glycoprotein, respectively, and the drug-sensitive parent cell line 8226/S were used as tumor models in this study. Using the limiting dilution assay, we have shown that three cycles of treatment with 25 micrograms/mL of MRK-16 MoAb and a 1:4 final dilution of RC eliminated 2.90 +/- 0.10 logs of 8226/DOX40 cells and 1.94 +/- 0.18 logs of 8226/DOX6 cells. One and two cycles of treatment were less effective, eliminating 0.47 +/- 0.40 and 1.94 +/- 0.36 logs of 8226/DOX40 and 0.12 +/- 0.20 and 1.63 +/- 0.58 logs of 8226/DOX6 cells, respectively. The 8226/S cell growth was unaffected by one to three cycles of treatment. The cell kill was not impaired when the antibody plus complement treatment was carried out on a mixture of 8226/DOX40 or 8226/DOX6 cells with a ninefold excess of irradiated bone marrow mononuclear cells (MNCs). The three cycles of treatment with antibody plus complement did not adversely affect granulocyte-macrophage colony-forming unit (GM-CFU) survival in hematologically normal marrows (92.5% to 104% survival) or in myeloma patient marrows (85% to 100%). These results show that it is possible to eliminate drug-resistant myeloma tumor cell lines from the admixed human bone marrow by treatment with MRK-16 MoAb plus RC. This method could prove to be effective for elimination of other drug-resistant tumor cell lines including those of leukemia and solid tumors, and will be further useful for supplementing chemopurging, and immunopurging of bone marrow with other antitumor cell antibodies.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1986

Regeneration of T lymphocytes from human bone marrow cells after depletion with methylprednisolone.

This study evaluates the propagation of T lymphocytes in bone marrow cells after in vitro methylprednisolone treatment. Previous studies from this laboratory showed that immunocompetent T lymphocytes could be eliminated from the bone marrow cells by incubation with 15 mg/ml (0.04 M) of methylprednisolone for 1 hr. The effectiveness of the chemoseparation was assessed by E-rosette forming cell assay, mitogen-induced lymphoblastogenic responses, and lymphocyte surface markers. In this study, bone marrow cells treated with different concentrations of methylprednisolone were cultured in the presence of PHA and Interleukin-2. The mitogen-induced lymphoblastogenesis was restored in the 15 mg/ml MP-treated bone marrow cells by the 8th day of culture in the presence of Interleukin-2. The cells in the culture were analyzed by E-rosette forming cell assay. It was shown that the predominant cells in the cultures were E-rosette forming cells. This study demonstrates that immunocompetent T lymphocytes can be regenerated in the presence of mitogen and Interleukin-2 from bone marrow cells treated with 15 mg/ml of methylprednisolone.

Bone Marrow↗
PubMed1986

Enhanced recovery of gut-associated lymphoid tissue by infusion of buffy coat cells and gut leukocytes in the murine syngeneic bone marrow transplantation model.

Ways of accelerating recovery of the mucous membrane immune system in lethally irradiated mice following syngeneic bone marrow transplantation were studied over a 35-day period by quantification of jejunal intraepithelial lymphocytes (IELs) and lamina propria plasma cells. Recovery after a low bone marrow dose allowing 100% animal survival (LBM) was compared with a high (five times minimal) dose (HBM), or a minimal dose augmented with equal numbers of buffy coat cells (LBM + BC) or small gut mucosal lymphocytes (LBM + GL). The maximal decline and subsequent peak repopulation of IELs were: LBM, days 7 through 14, peaking suboptimally by day 28; HBM, day 14, peaking suboptimally but higher than LBM by day 35; LBM + BC, days 11 through 14, peaking at control levels by day 35; and LBM + GL, day 7, peaking at control levels by day 28. The IEL decline was most severe with LBM and HBM treatment and least with LBM + GL. All transplant groups experienced maximal plasma cell decline by day 7. LBM had the most severe depletion, and LBM + GL had the least. Recovery to control levels for the LBM, HBM, LBM + BC and LBM + GL groups occurred by days 28, 21, 21, and 14, respectively. In all instances, greater than 95% of the plasma cells were IgA positive.

Animals↗
PubMed1985

Effect of pretreatment with cyclophosphamide on high-dose toxicity of melphalan in mice.

This study was undertaken to evaluate the effect of pretreatment (or priming) with cyclophosphamide (CY) on lethal toxicity of high-dose melphalan (MELPH) in mice. In C57BL/6 X DBA/2 F1 (hereafter called B6D2F1) mice given an injection of a single dose of CY, 50 mg/kg, 1-5 days before MELPH, 20 mg/kg, improved survival was noted in only one of five experiments. Reducing the challenge dose of MELPH to 17 mg/kg did not improve survival consistently. Priming with CY, 50 mg/kg, 3 days before a dose of MELPH, 20 mg/kg, did not improve survival in CBA/J or C57BL/6 mice. These results indicate that CY is an inconsistent priming agent for abrogating high-dose MELPH toxicity in mice. A slightly earlier recovery of regenerating hemopoietic and of jejunal crypt cells was noted in CY-primed B6D2F1 mice given injections of a low dose of MELPH, 15 mg/kg. The occasional improved animal survival noted in CY-primed B6D2F1 mice might be related to this earlier cell recovery.

Animals↗
PubMed1984

Functional impairment of T-lymphocytes in mouse radiation chimeras by a nucleotide-free diet.

We examined the effect of a nucleotide-free diet on the immune function of mouse syngeneic bone marrow radiation chimeras. The graft-versus-host disease mortality assay revealed that GVH activity of spleen cells from radiation chimeras fed NFD (RCNFD) was reduced at 6-18 weeks after transplantation as compared with the radiation chimeras fed a control diet (RCCD). When tested 11-18 weeks after transplantation, the proliferative response of RCNFD spleen cells to phytohemagglutinin was significantly reduced at 11 and 13 weeks, the response to pokeweed mitogen (PWM) was significantly reduced at 11, 13, and 15 weeks, and the response to bacterial lipopolysaccharide remained virtually unaffected. At both six and eight weeks after transplantation, RCNFD and RCCD showed comparable numbers of CFUc/femur. RCNFD and RCCD did not differ significantly from each other in body weights or in spleen and bone marrow cellularity at 6-18 weeks after transplantation. These results suggest that dietary nucleotides are important for the normal function of mouse T-lymphocytes.

Animals↗
PubMed1983

Isolation of murine small bowel intraepithelial lymphocytes.

A method for the preparation of cellular suspensions of the epithelium of murine small bowel for the purpose of isolation and recovery of intraepithelial lymphocytes employing intraluminal hyaluronidase digestion is described. Discontinuous Percoll centrifugation of these suspensions yielded a 76-82% pure population of intraepithelial lymphocytes. Between 1.6 and 4.0 X 10(7) viable intraepithelial lymphocytes were obtained per gram of gut. The isolate contained approximately equal numbers of T, B and null lymphocytes.

Animals↗
PubMed1981

Amelioration of graft-versus-host disease by pretreatment of allogeneic cells with Fab fragments.

We have previously reported the protective effect of pretreatment of semiallogeneic marrow and spleen cells with Fab fragments of horse anti-mouse thymocyte globulin against otherwise 100% fatal acute graft-versus-host disease (GVHD). We have now examined the effect of this pretreatment in three allogeneic strain combinations of mice, namely, A leads to C57, CBA leads to CAF1, and CBA leads to BALB/c. Acute GVHD mortality at 15 days postirradiation and transplantation of untreated marrow and spleen cells was 100% in all the strain combinations. However, pretreatment of cells with Fab reduced acute GVHD mortality to 6, 13, and 33% for the CBA leads to CAF1, CBA leads to BALB/c, and A leads to C57 strain combinations, respectively. The combined mortality from both acute and secondary GVHD and all other causes at 60 and 200 days postirradiation was 6 and 11%, 20 and 39%, 50 and 66% for each of these strain combinations, respectively. These results provide additional evidence for the effectiveness of Fab in ameliorating acute GVHD and establish its applicability to allogeneic strain combinations.

Animals↗