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S C Gulati

Publications and source records attributed to S C Gulati.

At least 91 records · Page 5Linked to original sources
PubMed1987

Photoradiation models for the clinical ex vivo treatment of autologous bone marrow grafts.

To assess the potential of photoradiation therapy for the in vitro purging of residual tumor cells from autologous bone marrow (BM) transplants, we studied normal marrow and tumor cell clonogenicity in response to different light-activated compounds by using the fluorescent dyes dihematoporphyrin ether (DHE) and merocyanine-540 (MC-540). After photoradiation of cells with white light, both DHE and MC-540 showed high cytocidal activity toward lymphoid and myeloid neoplastic cells but had a significantly lesser effect on normal granulocyte-macrophage (CFU-GM), erythroid (BFU-E), and mixed colony-forming (CFU-GEMM) progenitor cells. Acute promyelocytic leukemia (HL-60), non-B, non-T, CALLA-positive acute lymphoblastic leukemia (Reh), and diffuse histocytic B cell lymphoma (SK-DHL-2) cell lines were exposed to different drug concentrations in combination with white light at a constant illumination rate of 50,000 lux. With DHE doses varying from 2.0 to 2.5 micrograms/mL and MC-540 concentrations of 15 to 20 micrograms/mL, clonogenic tumor cells could be reduced by more than 4 logs when treated alone or in mixtures with normal irradiated human marrow cells. However, preferential cytotoxicity towards neoplastic cells was highly dependent on the mode of light activation. MC-540 had no substantial effect on malignant lymphoid (SK-DHL-2) and myeloid (HL-60) cells and on normal marrow myeloid (CFU-GM) precursors when drug incubation was performed in the dark and followed by light exposure of washed cells. Equal doses of MC-540 (15 to 20 micrograms/mL) could preferentially eliminate tumor cells under conditions of simultaneous light and drug treatment (30 minutes at 37 degrees C). When using DHE (2.5 micrograms/mL), 29.3%, 46.8%, and 27.5% of normal marrow CFU-GM, BFU-E, and CFU-GEMM, respectively, were spared after sequential drug and light exposure of cells, whereas simultaneous treatment reduced both normal (CFU-GM) and neoplastic cells below the limits of detection. In summary, our results indicate the usefulness of various photoradiation models for the ex vivo treatment of leukemic and lymphomatous bone marrow autografts.

Bone Marrow↗
PubMed1987

Preclinical assessment of purging with VP-16-213: key role for long-term marrow cultures.

An evaluation of the effects of VP-16 on normal human marrow cells and representative lymphoma-leukemia cell lines was performed to assess this agent's applicability to ex vivo marrow purging. Tumoricidal dose curves were defined using malignant lymphoid (SK-DHL2 and Reh) and myeloid (HL-60) cells admixed with a 20-fold excess of irradiated marrow cells to simulate a borderline remission marrow. One-hour treatments yielded ID50 of less than 5 mumol/L of VP-16 for clonogenic units from each cell line; rare-to-zero clonogenic units survived exposure to 50 to 100 mumol/L. CFU-Mix, BFU-E, and CFU-GM were equal in their sensitivity to VP-16 (ID50s25 to 30 mumol/L). Marrows treated with 75 mumol/L were completely depleted of these colony-forming cells but produced CFU-GM in one-stage long-term marrow cultures (LTMCs). This dose had little adverse effect on the proliferative capacity of marrow stromal progenitors, as measured by CFU-F (ID50 271 mumol/L) and by the unperturbed development of adherent layers in LTMCs. Furthermore, these stromal layers were able to support hematopoiesis as well as controls in co-culture experiments with autologous marrow cells (two-stage LTMCs). In conclusion, doses of VP-16 that cleanse marrow of lymphoma-leukemia cells spare hematopoietic and stromal progenitors as demonstrated by LTMCs. These data favor the use of VP-16 in the clinical autotransplant setting.

Bone Marrow↗
PubMed1986

Growth and development of children born to patients after cancer therapy.

Eighteen children born to parents who had previously received chemotherapy or radiotherapy were examined for physical health, growth, and development. The immunologic and the hematologic status of these children was also evaluated. Their ages ranged from birth to 15 years. The children had a careful history and physical examination to detect any abnormal symptoms or signs, and the parent's previous treatment was carefully documented. Four sets of parents had children while one of the parents was on active treatment (2 male and 2 female). Of the male patients, one patient's wife had a baby that was "small for gestational age" at birth and had transient failure to thrive; the other child was normal. Of the female patients, one offspring was small for gestational age at birth and the other was normal, but both continued to have failure to thrive for up to 17 months and 26 months, respectively. Ten parents procreated after being treated with chemotherapy and/or radiotherapy, to whom 14 children were born. One child was a stillbirth with multiple congenital abnormalities, and another child had trisomy 13-15 and died 6 months later. The other 12 children were normal at birth, but one child is under the 5th percentile for growth at twelve months of age. In all children studied, immune function test, complete blood count, and viral titers were considered normal for age. In our study, we found that three out of four children born to parents who were on chemotherapy had failure to thrive. Of the 14 children born to parents who conceived after being off chemotherapy, 11 were found to be normal in growth and development. These results imply that there is a high risk of complications in children born to parents who procreated while receiving chemotherapy. Further studies are needed to develop better guidelines for counseling cancer patients who want to have children.

Abnormalities, Multiple↗
PubMed1986

Comparison of the cytotoxic effects of merocyanine-540 on leukemic cells and normal human bone marrow.

Various chemical compounds have been described to induce photosensitization of tumor cells resulting in cell death. We studied the effect of merocyanine-540 (MC-540) on both leukemic and normal bone marrow (BM) cells. Acute promyelocytic leukemia (HL-60) and common acute lymphoblastic leukemia antigen-positive non-T, non-B acute lymphoblastic leukemia (Reh) cell lines were incubated with MC-540 and simultaneously exposed to white light. Normal human BM and mixtures of leukemic cells with BM cells were treated under similar conditions. At constant illumination rates of 50,000 lx, significant (at least 4 to 5 logs) tumor cell destruction was obtained with MC-540 concentrations of 20 micrograms/ml or more for HL-60, and 10 micrograms/ml or more for Reh cells. Incubation of BM under equivalent conditions preserved 18.0% of granulocyte-macrophage colony-forming units and 14.2% of erythroid burst-forming units. Similar results were obtained when tumor cells were mixed with irradiated BM and then treated with MC-540. In summary, cell photosensitization with MC-540 has a selective cytotoxic effect towards leukemic cells and therefore may be useful for purging tumor cells from autologous BM.

Bone Marrow↗
PubMed1985

Identification of the G-genome donor to Triticum timopheevii by DNA:DNA hybridizations.

In vitro DNA:DNA hybridizations and hydroxyapatite thermal-elution chromatography were employed to identify the diploid Triticum species ancestral to the G genome of Triticum timopheevii. Total genomic, unique-sequence, and repeated-sequence fractions of 3H-T. timopheevii DNA were hybridized to the corresponding fractions of unlabeled DNAs of T. searsii, T. speltoides, T. sharonensis, T. longissimum, and T. bicorne. The heteroduplex thermal stabilities indicated that, of the five species examined, T. speltoides was the most closely related to the G genome of T. timopheevii. Thus, T. speltoides appears to be the G-genome donor to T. timopheevii. The thermal stability profiles further indicated that the repeated DNA fractions from the five diploid species and the tetraploid T. timopheevii are more similar than the unique DNA fractions. This indicates that all of these species are closely related and that the sequences which comprise the current repeated fractions in the various species have not undergone any significant change since the formation of various species.

Base Sequence↗
PubMed1985

Growth of human bone marrow in vitro.

Attempts were made to establish human bone marrow (HBM) culture. Cell proliferation was triggered by medium conditioned by acute myelocytic leukemic (AML) cells exposed to 12-0-tetradecanoyl-phorbol-13-acetate (TPA). A 6-15 fold multiplication of myelomonocytic cells was obtained in tissue culture from HBM cells. Proliferation of granulocyte-macrophage colony forming cells (CFC-GM) occurred up to 30-fold. The morphology of the cells and cytochemical markers were investigated at all stages of the culture.

Bone Marrow Cells↗
PubMed1985

Synergistic effect of 4-hydroperoxycyclophosphamide and etoposide on a human promyelocytic leukemia cell line (HL-60) demonstrated by computer analysis.

Autologous stem cell transplantation using cryopreserved bone marrow offers the opportunity to rescue patients from hematopoietic toxicity caused by intensive chemotherapy. This approach is potentially useful for high-risk leukemias as well as for other cancers. The development of suitable methods for purging malignant cells from the bone marrow will offer a better chance of success for autologous stem cell transplantation. In this paper, we describe our efforts at purging myeloid cells. HL-60, a promyelocytic leukemia cell line, was used as a model. 4-Hydroperoxycyclophosphamide (4-HC) and VP-16-213 (VP-16) (either alone or in combination) were used to treat HL-60 cells and normal bone marrow. The cytotoxic effect of 4-HC (29.2 micrograms/ml; 100 microM) upon the HL-60 cell line was 99.8 +/- 0.12% (SE), and the colony-forming units-granulocyte, macrophage (CFU-cs) of normal bone marrow was inhibited by 82.5%. VP-16, at a concentration of 25 micrograms/ml (42.5 microM), can kill 99% of HL-60 cells and inhibit 72.7% of the CFU-cs. A drug mixture containing 4-HC (29.2 micrograms/ml) and VP-16 (10 micrograms/ml) (combination ratio, 1:0.342) reduces HL-60 cells to an undetectable number, and the CFU-cs were inhibited by 87.2%. The laboratory data were further analyzed for the synergistic effect of these two drugs by quantitative determination of the median effect plot and the multiple drug equation recently described by Chou and Talalay (Adv. Enz. Regul., 22: 27-55, 1984). Interactions of two drugs at different effect levels and at different combination ratios were then determined by computer simulation. At high effect levels, 4-HC and VP-16 in combination gave a synergistic cytocidal effect on HL-60 leukemic cells and gave an antagonistic inhibitory effect on normal bone marrow CFU-cs. This combination greatly increases the safety margin. Computer simulation of a dose effect relationship has also shown that the 4-HC:VP-16 combination ratio of 1:0.342 yields a better selective effect than a ratio of 1:0.856. This quantitative analysis suggests that the combination of these two drugs at the selected dose level offers a good method for purging nonlymphoblastic leukemia cells.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Effects of in vitro purging with 4-hydroperoxycyclophosphamide on the hematopoietic and microenvironmental elements of human bone marrow.

UNLABELLED: We describe the effects of 4-hydroperoxycyclophosphamide (4-HC) on the hematopoietic and stromal elements of human bone marrow. Marrow cells were exposed to 4-HC and then assayed for mixed (CFU-Mix), erythroid (BFU-E), granulomonocytic (CFU-GM), and marrow fibroblast (CFU-F) colony-forming cells and studied in the long-term marrow culture (LTMC) system. The inhibition of colony formation by 4-HC was dose and cell-concentration dependent. The cell most sensitive to 4-HC was CFU-Mix (ID50 31 mumol/L) followed by BFU-E (ID50 41 mumol/L), CFU-GM (ID50 89 mumol/L), and CFU-F (ID50 235 mumol/L). In LTMC, a dose-related inhibition of CFU-GM production was noted. Marrows treated with 300 mumol/L 4-HC were completely depleted of CFU-GM but were able to generate these progenitors in LTMC. Marrow stromal progenitors giving rise to stromal layers in LTMC, although less sensitive to 4-HC cytotoxicity, were damaged by 4-HC also in a dose-related manner. Marrows treated with 4-HC up to 300 mumol/L, gave rise to stromal layers composed of fibroblasts, endothelial cells, adipocytes, and macrophages. Cocultivation experiments with freshly isolated autologous hematopoietic cells showed that stromal layers derived from 4-HC-treated marrows were capable of sustaining the long-term production of CFU-GM as well as controls. IN CONCLUSION: (1) Hematopoietic progenitors cells, CFU-Mix, BFU-E, and CFU-GM, are highly sensitive to 4-HC, whereas marrow stromal progenitor cells are relatively resistant. (2) Marrows treated with 300 mumol/L 4-HC that are depleted of CFU-Mix, BFU-E, and CFU-GM can generate CFU-GM in LTMC, suggesting that most primitive hematopoietic stem cells (not represented by CFU-Mix) are spared by 4-HC up to this dose. (3) Consequently, the above colony assays are not suitable tools for predicting pluripotent stem cell survival after 4-HC treatment in vitro.

Bone Marrow↗
PubMed1983

Implication of Triticum searsii as the B-genome donor to wheat using DNA hybridizations.

In vitro DNA:DNA hybridizations and hydroxyapatite thermal chromatography were employed to help identify the species ancestral to the B genome of the polyploid wheats. We hybridized 3H-Triticum aestivum DNA to the unlabeled DNAs of T. urartu, T. speltoides, T. sharonensis, T. bicorne, T. longissimum, and T. searsii, 3H-Labeled DNA of T. urartu was hybridized with the DNA of a synthetic tetraploid. AADD. The heteroduplex thermal stabilities indicated that T. searsii was most closely related to T. aestivum (ABD) and that the genome of T. urartu was more closely related to the A genome than the B genome. The degree of reassociation which may have occurred between the six diploid species and the D genome of T. aestivum was evaluated by hybridizing 3H-T. tauschii DNA with the DNAs of the diploids. The results indicated that T. urartu had the least sequence homology to T. tauschii, the D-genome donor lending additional support to the conclusion that T. urartu is related to the A genome. Thus, it is highly probable that T. searsii is the B-genome donor to the polyploid wheats or a major chromosome donor if the B genome is, in fact, polyphyletic in origin.

DNA↗
PubMed1980

Analysis of multiple cell markers in acute leukemia complicating Hodgkin's disease.

A multidisciplinary methodology was applied to study 6 patients with acute leukemia (AL) following treatment for Hodgkin's disease. All 6 patients developed acute monocytic leukemia according to cytochemical criteria; morphologically, 3 cases were undifferentiated monoblastic leukemia; 3 cases were partially differentiated monocytic leukemia. In 3 of the 6 cases, cell suspensions from peripheral blood and/or bone marrow bore predominantly surface receptors for the Fc fragment of IgG and/or C-3 fraction of complement and exhibited variable degrees of phagocytosis. Two cases lacked any recognizable membrane markers or phagocytic activity. Terminal transferase enzymatic activity was not diagnostically elevated. Soft agar bone marrow culture studies revealed no growth or a characteristic leukemic cluster pattern. Chromosome analysis done in 1 of the 2 patients studied revealed hypodiploidy and structural rearrangement. Prospective studies, done serially, will help determine whether development of AL in patients with Hodgkin's disease results from the influence of intensive and potentially oncogenic therapy or represents progression from a preleukemic stage inherent to the original tumor.

Adult↗
PubMed1980

Microangiopathic anemia observed after treatment of epidermoid carcinoma with mitomycin C and 5-fluorouracil.

Two patients with epidermoid carcinoma treated with mitomycin-C (Mit-C) and 5-fluorouracil (5-FU) developed microangiopathic hemolytic anemia (MAHA), renal failure, and altered mental status. Patient 1 was free of metastatic disease, on maintenance Mit-C and 5-FU when MAHA changes appeared. Patient 2 had recurrent carcinoma in the pelvic area when MAHA changes appeared. In both patients, MAHA changes and neurologic function improved after exchange plasmapheresis. This is the first report of epidermoid carcinoma manifesting MAHA changes after chemotherapy. Speculation as to pathogenesis and appropriate therapy are discussed.

Anemia, Hemolytic↗
PubMed1980

Cerebral metabolism following brain injury. I. Acid-base and pO2 changes.

Acid-base parameters and oxygen tension were studied in arterial blood and lumbar CSF of 45 subjects in three groups of controls, head injuries, and postoperative cases. CSF in both groups of head injury and postoperative cases showed changes of metabolic acidosis with the arterial blood changes of respiratory alkalosis. Both groups had significant hypoxaemia. CSF acidosis is an indication of cerebral metabolic disturbance. It is proportional to the severity of brain damage, and permits a prognosis for further clinical progress. It is recommended that patients with severe brain lesions should be put on controlled ventilation to relieve them of respiratory overwork and to combat cerebral oedema.

Acid-Base Equilibrium↗
PubMed1980

Cerebral metabolism following brain injury. II. Lactic acid changes.

Lactic acid levels were estimated in cerebrospinal fluid and blood of 25 normal individuals and 50 patients with varying grades of head injury. CSF lactic acid levels showed significant elevation proportionate to the degree of brain injury. Elevation of blood lactic acid was less pronounced. CSF lactic acid levels closely correlated with the prognosis of the case, and an increase above 50 mgm% was not compatible with life.

Brain Injuries↗
PubMed1980

Cerebral metabolism following brain injury, III. Transaminase changes.

Glutamic oxalacetic and glutamic pyruvic transaminase levels in CSF and blood were estimated in 25 normal individuals and 50 patients with varying grades of head injury. CSF GOT, and to a lesser extent GPT, showed significant elevation proportionate to the degree of brain injury. Serum GOT was raised in more severe injuries. CSF GOT and GPT levels showed a significant correlation with the prognosis of the case.

Alanine Transaminase↗
PubMed1977

An improved procedure for purifying RNA tumor viruses from malignant tissue.

A convenient method for purifying RNA tumor viruses is described. Viruses banded in isopycnic gradients are contaminated with membranes that can be removed by velocity sedimentation in glycerol gradients. On sodium dodecyl sulfate (SDS) gel electrophoresis, the particles purified by these procedures from mouse mammary tumor tissue show protein profiles typical of those observed with virus purified from milk.

Animals↗
PubMed1974

Os penis.

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Adult↗