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Biomedical subjects

N Watanabe

Publications and source records attributed to N Watanabe.

At least 973 records · Page 54Linked to original sources
PubMed1988

Self-induction of defense against tumor necrosis factor cytotoxicity in tumor cells and normal cells.

Investigation on the effect of TNF on RNA and protein synthesis by tumorigenic and normal cell lines showed their synthesis in tumor cells to be increased at 12 h and to peak at 24 h of incubation with TNF, while that in normal diploid fibroblast (HEL) cells was apparently unaffected by the presence of TNF. The increase correlated with cell susceptibility to cytotoxic effect by TNF. Artificial inhibition of either RNA or protein synthesis by L-M cells, by addition of actinomycin D or cycloheximide, increased the cytotoxic effect of TNF and thus suggested that the elevated RNA and protein synthesis is related not to the cytotoxic reaction itself but rather to a defense mechanism. Similar incubation of HEL cells with TNF in the presence of either inhibitor resulted in the occurrence of cytotoxicity not observed with TNF alone, thus suggesting the existence of a defense mechanism in normal, TNF-resistant cells which is absent or greatly weakened in tumor cells.

Animals↗
PubMed1988

Therapeutic effect of OK-432 induced endogenous TNF on tumor bearing mice and cancer patients.

The therapeutic effect of OK-432 induced endogenous TNF on tumor bearing mice and cancer patients was investigated. OK-432 (10 KE/mouse) was administered intraperitoneally to Balb/c mice 7 days prior to the transplantation of Meth A cells (1 x 10(6)/mouse) into the abdominal cavity. And at day 1 of tumor inoculation, 1 KE/mouse of OK-432 was administered intraperitoneally. The significant prolongation of life span was observed in these mice. On the basis of these observation, therapeutic effect of endogenous TNF on cancer patients was clinically evaluated. OK-432 was administered intraperitoneally or intrapleurally to cancer patients with peritonitis carcinomatosa or pleuritis carcinomatosa 4 times (10KE each) every other day and 50KE of OK-432 was readministered with the interval of 7 days. An appreciable activity of TNF was detected in peritoneal fluids or pleural effusion, and the significant decreasing of these fluids was observed. It is therefore concluded that these therapeutic approach may well be taken into account in treatment of cancer.

Aged↗
PubMed1988

Growth promoting activity of PDGF, EGF and TGF-beta on highly metastatic subline of Meth A cells.

The response of a highly metastatic cell line of methylcholanthrene induced A fibrosarcoma (Meth A) to growth factors from platelets was examined. The highly metastatic cell subline (MH) proliferated more rapidly than its parental counterpart cell subline (ML) in a medium containing platelet lysate. However, when the three major growth factors from platelets, ie, platelet-derived growth factor, epidermal growth factor, and transforming growth factor-beta (PDGF, EGF, TGF-beta), were independently examined for their growth promoting activity, the former 2 growth factors preferentially stimulated the proliferation of ML and the latter growth factor rather suppressed the growth of both cells. On the other hand, the combined effects of these factors were more marked on MH. This combination effect was supported by the evidence that the number of receptors for EGF (which is probably an essential growth factor for the Meth A cell) was increased by pretreatment with PDGF or TGF-beta. Thus, the highly metastatic cells of MH were considered to be the most susceptible to growth factors released from platelets. This conclusion is consistent with the concept that platelets may play an important role in the formation of blood-borne metastasis by releasing growth factors to promote the proliferation of tumor cells, following aggregation with tumor cells.

Animals↗
PubMed1988

Cytocidal mechanism of TNF: effects of lysosomal enzyme and hydroxyl radical inhibitors on cytotoxicity.

The participation of lysosomal enzymes, hydroxyl radicals, and mitochondrial respiration in the cytocidal effect of TNF on tumor cells was investigated. The cytotoxicity of TNF on L-M cells was clearly reduced by lysosomotropic agents, DMSO (hydroxyl radical scavenger), NDGA (lipoxygenase inhibitor), and sodium azide (mitochondrial respiration inhibitor). The results suggest that lysosomal enzyme and hydroxyl radicals play an important triggering role in the destruction of tumor cells by TNF, and that the process of destruction might require ATP.

Ammonium Chloride↗
PubMed1988

Synergistic cytotoxicity of recombinant human TNF and various anti-cancer drugs.

A synergistic increase in the cytotoxic effects of recombinant human tumor necrosis factor (rH-TNF) and anti-cancer drugs was demonstrated in vitro. The cytotoxicity of rH-TNF against L-M cells in combination with Mitomycin C (MMC), Adriamycin (ADM), Cytosine arabinoside (Ara-C), Actinomycin D (ACD), Daunomycin (DM), Cisplatin (CDDP), Vincristine (VCR), and 5-Fluorouracil (5FU), based on the concentration necessary for 50% inhibition of cell growth (IC50), was 4 to 347 times as high as that of rH-TNF alone. The results suggest that combination therapy including rH-TNF and anti-cancer drugs may be of value in the treatment of malignancy in human patients.

Antineoplastic Agents↗
PubMed1988

IgE antibody production and cutaneous anaphylactic reactions in rats infected with Clonorchis sinensis.

Rats were infected orally with 50 or 100 metacercariae of Clonorchis sinensis. Anti-Clonorchis IgE antibody, determined by passive cutaneous anaphylaxis, in the serum of infected rats appeared 30-40 days after infection and persisted for at least 120 days. Total amount of IgE fixed on the mast cells, detected by reverse passive cutaneous anaphylaxis with anti-rat IgE, was significantly more in the infected rats than in uninfected rats. Worm burden at 290 days post-infection did not correlate to anti-Clonorchis IgE antibody titers, reverse passive cutaneous anaphylaxis titers, or anti-Clonorchis anaphylactic antibody on the mast cells, determined by active cutaneous anaphylaxis. Active cutaneous anaphylaxis titers interrelated to reverse passive cutaneous anaphylaxis titers, suggesting a correlation between the amount of anti-Clonorchis anaphylactic antibodies and total IgE on the mast cells. Sensitivity of passive cutaneous anaphylaxis with anti-BSA IgE antibody was significantly suppressed in Clonorchis infected rats. Moreover, anti-BSA IgE titers in the infected rats were inversely related to reverse passive cutaneous anaphylaxis titers, indicating that increase of IgE antibody on the mast cells by Clonorchis infection interfered with sensitization of anti-BSA IgE antibody.

Animals↗
PubMed1988

Antitumor synergism between recombinant human tumor necrosis factor and recombinant human interferon-r.

We studied the antitumor synergy of human recombinant tumor necrosis factor (TNF) in combination with recombinant interferon-r (IFN-r) both in vitro and in vivo. Synergistic cytotoxic effects were observed in all three of the human tumor cells lines examined. Binding assays of KB human nasopharynx carcinoma cell surface receptors for TNF revealed that IFN-r increased the number of receptors and suggest that this increase may play a key role in the synergism. Furthermore, a remarkable antitumor effect by TNF in combination with IFN-r was observed in nude mice implanted with KB cells. The results thus suggest that TNF and IFN-r in combination may provide the basis for a useful antitumor therapeutic regimen.

Animals↗
PubMed1988

[Continuous internalization of TNF receptors in a human myosarcoma cell line].

The cell dynamics of the receptor on tumor necrosis factor (TNF) were studied with the use of TNF-sensitive KYM cells derived from human myosarcoma. With receptor synthesis inhibited by cycloheximide, the half-life of the surface TNF receptor was 2h in the absence of TNF and 30min in its presence, suggesting that the TNF receptor was non-recycling and that its internalization was accelerated by TNF. During cell incubation with suppression of TNF receptor degradation by chloroquine, the number of surface TNF receptors remained approximately constants, but the total number of surface and internal TNF receptors increased gradually, at 3h reaching 1.5 times of the initial number, thus suggesting continuous synthesis, externalization, internalization, and degradation of the TNF receptor in the absence of cycloheximide. When the cells were incubated with 125I-TNF, the intracellular quantity of the pulse-labeled TNF-receptor complex promptly increased, reaching a maximum at 20 min, and then declining gradually. Thus, it was confirmed that the TNF receptor is internalized as a TNF-receptor complex in the presence of TNF. In incubation with suppression of protein synthesis by cycloheximide following surface TNF receptor digestion by trypsin, TNF receptors reappeared on the cell surface, increasing in the number to a peak level at 60 min and gradually decreasing. The cells previously exposed to cycloheximide with or without TNF showed no recurrence of surface TNF receptors, suggesting that the TNF receptor is non-recycling. The results thus suggest that the TNF receptor is continuously internalized and degraded intracellularly by lysosomes without being recycled regardless of the presence or absence of TNF, and further that its internalization is accelerated when it is part of the TNF-receptor complex.

Cell Line↗
PubMed1988

Analysis of the TNF receptor on KYM cells by binding assay and affinity cross-linking.

The existence of a tumor necrosis factor (TNF) receptor on KYM human myosarcoma cells was elucidated by Scatchard plot and cross-linking analysis. The average number of specific binding sites per cell was 15,300 and the apparent dissociation constant Kd was 4.0 X 10(-10) M. The estimated relative molecular mass of a TNF receptor on KYM cell was approximately 95,000.

Cell Line↗
PubMed1988

[Implication of hydroxyl radical production in the killing of tumor cells by recombinant human tumor necrosis factor].

We investigated the effect of recombinant human tumor necrosis factor (rhTNF) on hydroxyl radical production by established cell lines in vitro, and its implication in the killing of tumor cells by rhTNF. During incubation of TNF sensitive mouse tumorigenic fibroblast L-M cells in the presence of rhTNF, hydroxyl radical production detected by the evolution of methane gas from dimethyl sulfoxide increased gradually, at 18 hours reached 1.8 times of that in the absence of rhTNF. This increase of hydroxyl radical production was dependent on the concentration of rhTNF. The addition of iron chelator 2,2'-bipyridine which inhibits iron catalized Fenton reaction and inhibits hydroxyl radical generation, suppressed both the increase of hydroxyl radical production and the cytotoxicity induced by rhTNF. The increase of hydroxyl radical production stimulated by rhTNF was also detected in TNF sensitive human myosarcoma derived KYM cells as well as in L-M cells, but no change was detected in TNF insensitive human embryonic lung fibroblast HEL cells. These results suggest that rhTNF induced increase of hydroxyl radical production may play a significant role in the mechanism of tumor cell killing by rhTNF.

Cell Line↗
PubMed1988

T lymphocyte subpopulations and immunoglobulin-containing cells in the colonic mucosa of ulcerative colitis; a morphometric and immunohistochemical study.

T lymphocyte subpopulations and immunoglobulin containing cells in the colonic mucosa of 25 patients with ulcerative colitis have been studied using an indirect immunoperoxidase technique. In ulcerative colitis a marked increase in the population of Leu 3a positive cells (helper/inducer T cells) and IgG containing cells was observed in the mucosal lamina propria. In the intraepithelial spaces, a remarkable decrease in the population of Leu 2a positive cells (suppressor/cytotoxic T cells) and a marked increase in the number of Leu 3a positive cells were revealed. There was a very significant correlation between the population of IgG containing cells and the ratio of Leu 3a positive cells to Leu 2a positive cells in the lamina propria of patients with ulcerative colitis. These results suggest that an imbalance of mucosal immunoregulatory T cells and an increased production of IgG occurred in correlation with inflammatory activities of ulcerative colitis.

Adolescent↗
PubMed1988

[The course of pregnancy in patients with cardiac disease].

The outcome of 240 pregnancies in 202 patients with cardiac disease, who delivered between Jan. 1982 and Dec. 1987 at the National Cardiovascular Center was analyzed. Ninety-six patients had congenital heart disease. Forty-two had acquired valvular heart disease, 83 had cardiac arrhythmia, 7 had aortitis syndrome, 7 had cardiomyopathy and 2 had secondary angina pectoris. There was one case of each of the following cardiac diseases: Primary pulmonary hypertension, Marfan's syndrome and pericarditis. Nineteen of the above lapsed into congestive heart failure and there were two cases of maternal death. One was a case of primary pulmonary hypertension and the other had had an aortic valve replaced with a Bjork-Shiley prosthesis because of rheumatic valve disease. Another 16 mothers had artificial preterm delivery at a gestational age of 30 weeks to 36 weeks to reduce the risk of congestive heart failure. There were 5 cases of IUFD, three of which were attributed to maternal cardiac disease and another to fetal failure. Neonatal congenital heart disease was found in 8 cases. The percentage of IUGR, excepting twin pregnancies, was 14.8%.

Female↗
PubMed1988

[A case of acute adult T-cell leukemia with long-term remission by cisplatin therapy].

A 37-year-old man was admitted because of general malaise, slight fever, pain in the knee joint and lower extremities, polydypsia, polyuria and skin lesion in September, 1985. The white blood cell count was 16,920/cmm with 41% of abnormal lymphoid cells with convoluted nuclei, which were compatible with adult T-cell leukemia (ATL). The serum calcium level was 15.1 mg/dl, serum LDH 307 IU/l, and the titer of anti-ATLA antibody in serum x 160. The cell surface phenotype of abnormal lymphocyte was OKT-3+, OKT-4+ and OKT-8-. Therefore the diagnosis of acute ATL was made. He was treated with cisplatin because VEPA therapy was not effective. About five months after the start of chemotherapy, he entered remission with almost complete disappearance of abnormal lymphocyte. The remission continued over twenty-nine months with maintenance therapy by cisplatin alone. The clinical course of this patient suggests that cisplatin could be applied to a case of ATL which is refractory to the conventional treatment.

Adult↗
PubMed1988

Changes of portal systemic shunting after sclerotherapy and/or partial splenic embolization observed by thallium-201 per rectal administration.

Tl-201 per-rectal scintigraphy was performed before and after injection sclerotherapy of esophageal varices and/or partial splenic embolization in patients with esophageal varices to observe the changes of portal systemic shunting by these treatments. The changes in the heart-to-liver uptake ratio of Tl-201 after injection sclerotherapy ranged widely from a decrease to an increase with a mean change rate (mean of the absolute value of change rate) and one standard deviation of 19.0 +/- 19.9%. By partial splenic embolization the heart-to-liver uptake ratio was decreased significantly with the mean change rate and one standard deviation of 26.2 +/- 17.4% (P less than .05). This noninvasive and simple method seems to be useful in evaluating pathophysiological changes of portal systemic shunting observed from inferior mesenteric vein blood flow after treatments of portal circulation system.

Administration, Rectal↗