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Biomedical subjects

S Todo

Publications and source records attributed to S Todo.

At least 595 records · Page 33Linked to original sources
PubMed1986

Cell kinetic studies of PGD2 cytotoxicity on the in vitro growth of human neuroblastoma.

To determine the mechanism of the antineoplastic effect of PGD2, we studied the intracellular adenosine 3',5'-cyclic monophosphate (cAMP), cell growth and the kinetics of a human neuroblastoma (NCG line) in culture. Cells were maintained in RPMI 1640 with 10% FCS. cAMP level was determined for the cells, which were incubated for 10 min. with and without PGD2 (1 microgram/ml) in the presence of 100 microM papaverine. Growth inhibition was examined by counting viable cells after treatment with PGD2 (0-100 micrograms/ml) for 4 consecutive days starting at Day 4 after subculture. Effects on cell kinetics were examined for similarly treated cells by DNA cytofluorometry combined with 3H-thymidine autoradiography. In response to PGD2, the NCG line failed to increase its cAMP; however, cell growth was inhibited (IC50 13 micrograms/ml), accompanied by the marked decrease of S phase cells. The results indicate that PGD2 exerts its cytotoxic effect by a probable G1 block of the cell cycle and not through cAMP action.

Antineoplastic Agents↗
PubMed1986

Antitumor effect of gamma-linolenic acid on cultured human neuroblastoma cells.

gamma-linolenic acid (GLA) was found to suppress the cell growth of 4 human neuroblastoma cell lines. GOTO was the most sensitive, followed by SK-N-DZ and NKP, while NCG was much less sensitive to GLA. In terms of GLA cytotoxicity, neither cyclo-oxygenase inhibitors nor a lipoxygenase inhibitor showed any effect. On the other hand, 4 antioxidants (Coenzyme Q, (D) alpha-tocopherol, (DL) alpha-tocopherol, butylated hydroxytoluene) reduced the growth inhibitory effect of GLA, but not in proportion to the decrease of GLA-stimulated lipid peroxidation. Accordingly, prostaglandins and leukotrienes probably do not play a role, and lipid peroxide may only be partly involved in the GLA effect.

Antineoplastic Agents↗
PubMed1986

Canine liver transplantation under Nva2-cyclosporine versus cyclosporine.

The immunosuppressive qualities and other features of a new cyclosporine (CsA) analogue, Nva2-cyclosporine (Nva2-CsA) were examined using canine orthotopic liver allografts. The mean survival time was 11.8 +/- 9.6 (SD) days in dogs without treatment, 60.8 +/- 4.4 days with Nva2-CsA and 65.1 +/- 33.0 days with CsA. Functional abnormalities indicating toxic side effects were not noted either with Nva2-CsA or with CsA. Using the same oral dose, the rate of blood level rise and the amount of the rise were greater with Nva2-CsA. Histopathologically, Nva2-CsA treatment was associated with the same degree of hydropic vocuolation in the pars recta of the proximal tubules as CsA treatment. Thus, in the dog, Nva2-CsA had identical immunosuppressive properties as CsA, with no functionally detectable toxicity affecting the liver and kidney.

Animals↗
PubMed1986

Etoposide and cytosine arabinoside combination chemotherapy for refractory acute lymphocytic leukemia in childhood.

Eighteen children with refractory acute lymphocytic leukemia (ALL) who had been heavily pretreated, were treated with combination etoposide and cytosine arabinoside (ara-C) chemotherapy. Seventeen of these 18 patients were in their first to third relapses; the remaining patient had never responded to induction therapy. The drug combination of etoposide followed by ara-C was administered as an intravenous (IV) infusion twice a week for two consecutive weeks, a total of four doses. The dosage was 150 mg/m2/dose for each drug. Seven (39%) of the 18 patients attained a complete remission (CR) and three (17%) attained a partial remission (PR). Complete response was obtained in two of eight patients in first marrow relapse, and in five of nine patients in second and third relapse. Five patients achieved a CR after one course of therapy and two achieved a CR after two courses of therapy. Of three patients who had previously received teniposide, two attained a CR with this combination. The duration of these responses was brief with a median of 1 month, ranging from 0.5 to 3 months, with the exception of one case, which has been in remission for 2.5 + months. Although myelosuppression was observed, none of the patients died from infection or bleeding. Allergic reaction with fever and rash was observed in two patients. The efficacy of the etoposide and ara-C combination for refractory childhood ALL is encouraging in several current reinduction regimens.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Distinct isozyme patterns of cyclic nucleotide phosphodiesterase in human neuroblastoma and ganglioneuroma; a possible marker of differentiation of neural crest-derived tumors and Schwann cells.

By DEAE-cellulose chromatography, the 30,000g supernatants of human neuroblastoma (n = 7), ganglioneuroma (n = 5), sympathetic ganglia (n = 3), and Schwannoma (n = 2) were found to contain three major peaks of adenosine 3',5'-cyclic monophosphate (cAMP) phosphodiesterase (PDE) activity, which were termed peaks I, II, and III in the order of their elution from the column. Peak I isozyme was calmodulin-dependent, and had two different Km values for cAMP (32 and 2.3 microM) and a low Km for guanosine 3',5'-cyclic monophosphate (cGMP) (2.9 microM). Peak II isozyme had a high Km for both cAMP, 76 microM, and cGMP, 32 microM, and peak III isozyme was a cAMP-PDE with Km of 1.8 microM. The peak II and III isozymes were calmodulin-independent. The activity ratio of peak I isozyme to peak III isozyme (I/III isozyme ratio) was significantly different (P less than 0.001) in neuroblastoma and in ganglioneuroma/sympathetic ganglia, i.e., 0.23 +/- 0.11 for neuroblastoma vs. 0.79 +/- 0.20 for ganglioneuroma and 0.51 +/- 0.08 for sympathetic ganglia. Schwannoma showed the highest value of 1.05 (P less than 0.05). These results suggest that the I/III isozyme ratio of cAMP-PDE could be a useful marker in studies on the differentiation of neural crest-derived tumors and Schwann cells.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1986

Liver transplantation across ABO blood groups.

Six hundred seventy-one first, second, and third orthotopic liver allografts in 520 patients were reviewed to determine the effect of donor-recipient mismatches or incompatibilities for the ABO blood groups on graft survival. A significant advantage for ABO donor-recipient identity was found, especially in adults and for first grafts. However, a surprisingly large number of ABO incompatible grafts were successful. We recommend that nonidentical or incompatible grafts be limited to patients such as small children for whom the supply of available donors is severely limited or for patients in urgent need of transplantation or retransplantation.

ABO Blood-Group System↗
PubMed1986

The antibody crossmatch in liver transplantation.

Six hundred sixty-seven first, second, and third orthotopic liver allografts in 520 patients were reviewed to determine the effect of recipient panel-reactive antibody (PRA) and donor-recipient antibody crossmatch on 2-year patient and liver allograft survival rates. Neither a high panel-reactive antibody nor a positive crossmatch for donor-specific preformed antibody was associated with decreased patient or liver allograft survival for primary grafts or retransplants. Two patients have been given kidney transplants immediately after a liver allograft from a donor with whom each patient had an initial strongly positive donor-specific antibody crossmatch. The liver apparently removed or neutralized circulating anti-donor antibody, since the renal allografts functioned promptly and did not experience hyperacute rejection.

Actuarial Analysis↗
PubMed1986

[Improved results of treatment in 30 cases of acute nonlymphocytic leukemia in childhood].

Thirty cases of childhood acute nonlymphocytic leukemia (ANLL) have been treated with intermittent, intensive multi-drug combinations during the past 5 years. Three patients never attained complete remission (CR) and 3 died of complications after less than one month of treatment. Twenty-four (86.7 %) attained CR with a median CCR of 26 months. The median for disease-free survival (DFS) among the total 30 cases was 15 months. Twelve out of the 24 CR patients have been disease-free for longer than 16 months, indicating significantly improved therapeutic results. Among the factors affecting prognosis, we found that patients with certain clonal abnormalities of leukemic cells and initial leukocytosis (greater than 40,000/microliter) had poor prognosis. Further revision of treatment should be considered for patients with high-risk ANLL.

Acute Disease↗
PubMed1986

[Etoposide (VP 16/NK 171) and cytosine arabinoside combination chemotherapy in refractory childhood leukemia].

Combination chemotherapy consisting of etoposide and cytosine arabinoside (Ara-C) was given to 38 children with hematological malignancy. They included 18 patients with acute lymphocytic leukemia (ALL), two with non-Hodgkin's lymphoma (NHL), one with myeloproliferative disorder (MPD), and one with histiocytic medullary reticulosis (HMR), all of whom had relapsed or not responded to initial treatment. Sixteen patients with nonlymphocytic leukemia (ANLL), 13 in remission, two in relapse, and one in induction failure, were also studied. The drug combination was administered by intravenous infusion twice a week for two consecutive weeks at a dosage of 150 mg/m2 for each drug. Among the 18 patients with ALL, seven complete responses and three partial responses were achieved. Six of the seven complete responders relapsed at 0.5-3 months, and the remainder has been in remission for 2.5+ months. None of the patients with refractory ANLL, NHL, MPD or HMR achieved complete remission; however, two of three ANLL patients and one HMR patient demonstrated partial response. Among the 13 ANLL patients in remission, 9 patients have continued remission for more than 4 months with a median of 26+ months, ranging from 6+ months to 40+ months, while 4 relapsed within 4 months after the administration of this regimen. The toxic effects were tolerable. Results indicate that an etoposide and Ara-C combination is effective especially in refractory ALL in childhood.

Acute Disease↗
PubMed1984

[Differentiation induction and potentiation of chemotherapy by PGE1 infusion in patients with neuroblastoma--effect of PGE1 on metastatic potential of neuroblastoma].

Combination of dibutyryl adenosine 3', 5'-cyclic monophosphate or prostaglandin E1 (PGE1) and papaverine effectively induced differentiation of neuroblastoma in mice. Two cases of human neuroblastoma with stage III and IV were administered intraaortic PGE1 infusion combined with oral papaverine and conventional chemotherapy. There were no noticeable side effects and the treatment was effective in decreasing tumor size and promoting tumor maturation in the infused area. However, distant osseous metastases were developed in both cases, during and after the PGE1 administration. They survived 30 and 17 months, respectively, from the initiation of therapy. (Jpn J Cancer Chemother 10(9): 1936-1943, 1983) These results prompted us to study the metastatic potentials of neuroblastoma. In vitro studies demonstrated that cultured human neuroblastoma cells (NB-1, GOTO, SK-N-DZ, SJ-N-KP, SJ-N-CG and SK-N-FI) aggregate human platelets with maximum aggregation ranging from 28% to 51%. Addition of PGE1 or PGD2 to PRP effectively inhibited the tumor-cell-platelet interaction, with IC50 approximately 100 nM for PGE1 and 10 nM for PGD2, respectively. In addition, 50 microM PGE1 or PGD2, 5 microM PGI2 reversed neuroblastoma-induced platelet aggregation in 4 out of 5 cell lines were studied. These findings indicate a the possible role of PGs in effective inhibition of neuroblastoma metastases in vivo. However, two cell lines (SK-N-DZ and SJ-N-CG), which had been exposed to 8.5 microM PGE1 or PGD2 for 90 min and 72 hr, respectively, retained the platelet aggregating activity which was not significantly different from that of untreated cells. We conclude that clinical application of intraaortic PGE1 in the treatment of advanced neuroblastoma has advantage in potentiation of tumor cell kill and in inducing maturation. Administered PGE1 may exert its action in two ways: in preventing tumor metastasis or possibly in enhancing the metastatic potential of neuroblastoma cells. Further refinement of these modalities including other PGs such as PGD2 or PGI2 and more detailed studies on optimal PG administration to prevent metastasis should be evaluated in future.

Alprostadil↗
PubMed1983

Management of massive hemobilia with angiographic embolization.

Two cases of angiographic embolization for the management of massive hemobilia due to hepatico-jejunostomy and percutaneous transhepatic biliary drainage are presented. The clinical features are described together with a short review of the literature. In addition to defining the bleeding source, angiography provides an effective and safe alternative to surgery for the control of hemobilia.

Aged↗