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Biomedical subjects

Y Niitsu

Publications and source records attributed to Y Niitsu.

At least 253 records · Page 14Linked to original sources
PubMed1989

[A case of chronic myelogenous leukemia complicated with nephrotic syndrome].

An 81-year-old woman was admitted, complained general malaise, and edema on face and lower extremities. In the peripheral blood, leucocytosis (17,220/mm3), microcytic hypochromic anemia (RBC 348 x 10(4)/mm3, Hb 9.6 g/dl, Ht 29.2%), and thrombocytosis (130 x 10(4)/mm3) were present, and many myeloid cells containing of myeloblasts, promyelocytes and so on were observed. Bone marrow aspiration revealed increment of the myeloid series without hiatus leukemia . The Neutrophil Alkaline Phosphatase score and rate was low, and on bone marrow scintigram using indium chloride, liver and extremities were shown. On admission, proteinuria (21.5 g/dl) and hypoalbuminemia (2.5 g/day) were pointed out, and the renal biopsy specimen showed membraneous proliferative glomerulonephritis (MPGN), so we diagnosed this case that chronic myelogenous leukemia (CML) complicated with nephrotic syndrome. At first, she was treated with prednisolone, but proteinuria was not entirely improved, then busulfan was given, myeloid cells in peripheral blood were disappeared and proteinuria was gradually decreased. From this coarse, the causality between CML and nephrotic syndrome was verified.

Aged↗
PubMed1989

[A case of cutaneous T cell lymphoma improved with local administration of tumor necrosis factor].

A 63-aged woman with cutaneous T cell lymphoma successfully treated with local administration of tumor necrosis factor (TNF) was reported. She was admitted to our hospital because of tumors and subcutaneous nodules on her bilateral inner thigh. A pathological study of her skin of right inner thigh showed mononuclear atypical cells with hyperlobulated nuclei. In peripheral blood the same lymphoid cells were found. Immunohistochemical staining of these cells was positive for OKT-3 and OKT-4, but negative for OKT-8. No lymph node swelling and no visceral involvement were detected by a CT scan and a Echography of the chest and the abdomen. A diagnosis of cutaneous T cell lymphoma was made (stage IIb TNM classification). Although the chemotherapy of VEPA and CHOP was done, about 70% (PR) of the bilateral inner thigh tumors were retracted. Owing to the interstitial pneumonia aroused in the period of bone marrow suppression and cardiomyopathy after chemotherapy, we gave up further systemic chemotherapy. And then the local administration of TNF was done and the disappearance of the bilateral inner thigh tumors was obtained. Our therapy with local administration of TNF for CTCL in the first report.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

[Blood coagulation and metastasis].

To elucidate the correlation of platelet aggregating activity of tumor cells and their metastatic potentials, we established a highly and a low metastatic clone with a different platelet aggregating activity from murine fibrosarcoma (Meth A). The parental Meth A cell and its low metastatic clone (ML-01) showed a typical platelet aggregation pattern with a certain lag time, while a highly metastatic clone (MH-02) showed a biphasic aggregation with no lag time in which the first reversible aggregation was caused by ADP released from MH-02, since it was eliminated by apyrase treatment. The highly metastatic potential, however, was not solely due to the platelet aggregating activity because the administration of PGI2-analogue TEI-8153A did not completely inhibit their pulmonary metastasis. In fact, MH-02 attached more preferentially to type IV collagen or endothelial cell than ML-01 in vitro. These results suggest that MH-02 exerts its high metastatic property through the mechanisms involving multiple factors such as the increased platelet aggregating potential or enhanced adhesiveness.

Animals↗
PubMed1988

Induction of synthesis of tumor necrosis factor in human and murine cell lines by exogenous recombinant human tumor necrosis factor.

Treatment of sensitive human myosarcoma cells (KYM-S) with exogenous tumor necrosis factor (r-TNF) resulted in the production of TNF by the cells. The newly synthesized cellular TNF was identified immunologically on Western blots and as a single 1.8-kilobase band on Northern blots. TNF synthesis began within 2 h of administration of the exogenous TNF in a dose-dependent manner. r-TNF also induced TNF synthesis in mouse tumorigenic fibroblasts (L-M). Resistant sublines of these cells as well as TNF nonsensitive human diploid fibroblasts possessed TNF mRNA without pretreatment, indicating an inverse correlation between levels of TNF expressed and sensitivity to the cytotoxic effects of exogenous TNF. It is conceivable that the newly synthesized cellular TNF functions in some protective manner to block cytolytic effects of exogenous TNF.

Animals↗
PubMed1988

Continuous internalization of tumor necrosis factor receptors in a human myosarcoma cell line.

The cell dynamics of the receptor for tumor necrosis factor (TNF) were examined in TNF-sensitive KYM cells derived from human myosarcoma. With receptor synthesis inhibited by cycloheximide, the half-life of the surface TNF receptor was 2 h in the absence of TNF and 30 min in its presence, suggesting that the TNF receptor is non-recycling and that its internalization is accelerated by TNF. During cell incubation with TNF receptor degradation suppressed by chloroquine, the number of surface TNF receptors remained approximately constant, but the total number of surface and internal TNF receptors increased gradually, at 3 h reaching 1.5 times the initial number, thus suggesting continuous synthesis, externalization, internalization, and degradation of the TNF receptor in the absence of cycloheximide. On cell incubation with 125I-TNF, the intracellular quantity of the pulse-labeled TNF-receptor complex promptly increased, reaching a maximum at 20 min, and then gradually declined, thus confirming that the TNF receptor is internalized as a TNF-receptor complex in the presence of TNF. During incubations with protein synthesis suppressed by cycloheximide following surface TNF receptor digestion by trypsin, TNF receptors reappeared on the cell surface, increasing in number to a peak at 60 min and gradually decreasing, and 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 of the study 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

Toxic effect of tumor necrosis factor on tumor vasculature in mice.

Stereoscopic observation via an implanted sight glass in mice bearing transplanted methylcholanthrene-induced A-cells showed tumorivascular hemorrhage at 1-2 h after tumor necrosis factor (TNF) administration, congestion at 4-6 h, and hemorrhage, congestion, and blood circulation blockage at 24 h. Histological examination after TNF administration to mice bearing similar methylcholanthrene-induced A-cell transplants showed thrombus formation in the tumor vasculature at 4 h and thereafter. Suppression of this thrombus formation with heparin had no apparent influence on the necrotic response, tumor growth inhibition or complete cure rate following TNF administration to mice bearing the methylcholanthrene-induced A-cell tumors. The results suggest that direct toxicity of TNF on tumor vasculature is a factor in the overall antitumor mechanism of TNF.

Animals↗
PubMed1988

Synergistic effects of recombinant human tumor necrosis factor and hyperthermia on in vitro cytotoxicity and artificial metastasis.

Synergy in cytotoxic effect between recombinant human tumor necrosis factor and hyperthermia (incubation at 38.5 degrees C or 40 degrees C) was observed to occur against L-M (mouse tumorigenic fibroblast) cells and shown to be related to an accelerated turnover rate of recombinant human tumor necrosis factor-receptor complex under elevated temperatures rather than to changes in number of cell receptors or binding strength. However, no synergy in cytotoxic effect was observed to occur against human embryonic lung (HEL) cells. A clearly synergistic inhibition of metastatic tumor growth by combined administration of recombinant human tumor necrosis factor (300 units) and whole-body hyperthermia (40 degrees C, 30 min) was also observed in BALB/c mice previously given injections of 1 x 10(6) Meth-A (MH) cells/mouse via tail vein, neither of which alone resulted in significant inhibition.

Animals↗
PubMed1988

Synergistic cytotoxic and antitumor effects of recombinant human tumor necrosis factor and hyperthermia.

A synergistic increase in the cytotoxic effects of recombinant human tumor necrosis factor (rH-TNF) and hyperthermia was demonstrated both in vitro and in vivo. The cytotoxicity of rH-TNF against L-M cells in incubation for 12 h at 38.5 and 40 degrees C based on the concentration necessary for 50% cytotoxicity was, respectively, 125 and more than 500 times as high as in similar incubation at 37 degrees C. As observed 18 days after implantation of Meth-A fibrosarcoma cells in mice, single i.v. administration of rH-TNF at 1000 units/mouse resulted in complete cures in five mice when performed in combination with hyperthermia (40 degrees C), whereas rH-TNF alone in the same dose resulted in 27.1% inhibition of tumor growth and hyperthermia alone had no appreciable effect on tumor growth. The i.v. administration of rH-TNF three times at 100 or 300 units/mouse together with hyperthermia (40 degrees C) resulted in 41.2 and 89.0% tumor growth inhibition, respectively; similar administration without hyperthermia appeared to have little or no appreciable effect on tumor growth. The results suggest that combination therapy including rH-TNF and hyperthermia may be of value in the treatment of malignancy in human patients.

Animals↗
PubMed1988

Immunohistochemical identification of type I procollagen in tumour cells of scirrhous adenocarcinoma of the stomach.

Human gastric carcinomas were tested for their immunohistochemical reactivity with anti-type I procollagen antiserum. In all specimens of scirrhous carcinomas, staining of the tumour cells was strongly positive, while in medullary carcinomas staining of the tumour cells was generally poor. These results suggest that the tumour cells in scirrhous carcinomas produce collagen in their stroma.

Adenocarcinoma, Scirrhous↗
PubMed1988

Successful treatment of a VIPoma by continuous subcutaneous infusion of somatostatin analogue (SMS 201-995).

A case with WDHA syndrome due to VIPoma is reported. Injection of somatostatin analogue SMS 201-995 was followed by prompt suppression of vasoactive intestinal polypeptide levels (VIP), decreased stool volume, and restoration of the serum potassium concentration to normal. Long-term treatment with SMS 201-995 for up to 20 weeks produced excellent clinical control and a decrease in tumour size. No adverse effects were noted except for localized pain at the site of injection. This was overcome by using a continuous subcutaneous infusion pump which also enabled the effective daily dosage to be reduced and thereby adverse reactions to be avoided.

Female↗
PubMed1988

Quantitation and characterization of serum transferrin receptor in patients with anemias and polycythemias.

Serum transferrin receptor concentration in patients with anemias and polycythemias was determined. The mean normal value was 258 +/- 82 ng/ml. Comparing with normal values, the higher values were obtained in patients with iron deficiency anemia, autoimmune hemolytic anemia, and polycythemias, while the lower values were obtained in patients with aplsatic anemia. During treatments of patients with iron deficiency anemia and autoimmune hemolytic anemia, serial change of serum receptor was paralleled with that of peripheral reticulocyte counts, suggesting that the circulating receptor values may reflect the activity of bone marrow erythropoiesis. The immunoreactive receptor was migrated at the position of alpha 1-globulin by agarose gel electrophoresis and the isoelectric point(pl) was 3.57 by isoelectric focusing. SDS-polyacrylamide gel electrophorogram of various patients' sera revealed that the autoradiographed band was migrated at the molecular weight of 110,000 daltons in the non-reducing condition and 46,000 and 23,000 daltons in the reducing condition. These bands were also capable of binding to 131I-labelled diferric transferrin. The proposed model of circulating transferrin receptor may be the nicked dimers of 55,000 daltons in which inter- and intra-disulfide bridges were present.

Anemia↗
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↗