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Biomedical subjects

K Sakata

Publications and source records attributed to K Sakata.

At least 415 records · Page 23Linked to original sources

Immunohistochemical localization of human lung adenocarcinoma-associated antigen with a monoclonal antibody.

The monoclonal antibody, 5C7, reacted immunohistochemically with 62 out of bronchial cells of normal lung tissue, adjacent to neoplastic lesions, were negative for lung adenocarcinoma-associated antigen. Reactions with the antibody were observed in half the cases of squamous cell lung cancer, but were only sporadic. The antibody appears to react with an antigen which is either restricted to malignant cells or is at least greatly amplified in expression by malignant cells compared to normal human tissues. The major value of this monoclonal antibody at present is in classifying lung cancers as either adenocarcinoma or non-adenocarcinoma.

Adenocarcinoma↗

[Facilitation of tumor metastasis to the lung by operative stress in the rat--influence of adrenocortical hormones and preoperative administration of OK-432].

Experimental studies were performed to clarify the mechanism of facilitation of tumor metastasis to the lung by operative stress, using an experimental model in which 5-week old female Sprague-Dawley (SD) rats were inoculated with a low antigenic and easily metastasizable tumor, MRMT-1. In particular, relevance of adrenocortical hormones to the facilitation of tumor metastasis was examined. Furthermore preventive effects of preoperative administration of a nonspecific immunopotentiator, OK-432, were examined. Number of metastatic nodules was increased significantly by operative stress and the increase was proportionate to severity of the stress. The facilitation of metastasis by operative stress was significantly inhibited by preoperative OK-432 administration. In adrenalectomized rats, no such facilitation of metastasis by operative stress was observed. After administration of 2.5 to 20mg of hydrocortisone, number of metastatic nodules increased dose-dependently. The increase in metastatic nodules by administration of 5mg of hydrocortisone was inhibited by preoperative OK-432 administration. Thus it was concluded that facilitation of tumor metastasis by operative stress was proportionate to severity of the stress, and one of its essential causative factors was the stress-induced adrenocortical hypersecretion, which suppressed immunity of the host. Administration of OK-432 was effective for counteracting the stress-induced facilitation of metastasis.

Adrenal Cortex Hormones↗

[Effects of serum immunosuppressive factors on the cytotoxicity of lymphokine-activated killer (LAK) cells induced by recombinant interleukin 2(R-IL2)].

Fundamental studies were performed on adoptive immunotherapy, especially on effects on lymphocytic cytotoxic activity, of nonspecific immunosuppressive factors (ferritin, IAP, AFP) and of serum factors obtained from gastric cancer patients, and possible intervention of suppressor T cells in serum immunosuppressive activity on the cytotoxicity was also examined. The following results were obtained. 1) Cytotoxicity of LAK cells induced by culturing normal peripheral blood lymphocytes (PBL) with R-IL2 in the medium containing normal AB-type sera, was higher than that of PBL. 2) Effect of nonspecific immunosuppressive factors on cytotoxicity of LAK cells was lower than that on cytotoxicity of PBL. 3) Cytotoxicity of PBL was inhibited in a relatively specific fashion by sera from patients of the cancers which were of identical histological types with the target tumor cells, while that of LAK cells was hardly inhibited by patients' sera. 4) Cytotoxicity of Leu 15-PBL was inhibited by nonspecific immunosuppressive factors and also by cancer patients' sera in a relatively specific fashion in relation to histology. 5) Cytotoxicity of Leu 15-LAK cells was hardly inhibited by serum nonspecific and specific immunosuppressive factors. The above results showed that serum immunosuppressive factors might act on PBL cytotoxicity without intervention of suppressor T cells, and that LAK cells were hardly inhibited by such immunosuppressive factors. All these results suggested usefulness of adoptive immunotherapy with LAK.

Adult↗

[Malignant melanoma in the anorectal region--a report of two cases].

Case 1. A 61-year-old male, suffering from an anorectal tumor with anal bleeding, underwent an abdominoperineal rectal amputation with an R3 lymphadenectomy. The tumor was a Stage I (H0, P0, N0, S0) malignant melanoma. Despite DAV (DTIC, ACNU, and VCR) therapy, liver metastasis was detected 1 year later and the patient died 1.5 years after the operation. Case 2. A 80-year-old female, complaining of bloody stool, was diagnosed to have an anorectal malignant melanoma. She was at Stage IV and underwent an abdominoperineal rectal amputation with an R3 lymphadenectomy. The tumor 4.5 X 2.7 X 1.2 cm in size, was diagnosed to be at Stage IV (pm, n2+). She is still alive 4 years later without having received sufficient chemotherapy.

Aged↗

[Experimental studies on induction of various lymphokine-activated killer cells using recombinant interleukin 2].

Fundamental studies were performed on adoptive immunotherapy, especially on promotion of cell proliferation and on augmentation of cytotoxicity of various lymphokine-activated killer cells, induced by recombinant interleukin 2(R-IL2) with (P-LAK) or without (LAK) PHA, from peripheral blood lymphocytes (PBL) of healthy volunteers. The following results were obtained. 1) In LAK induced by culturing normal PBL with R-IL2, a cell proliferation was observed in 14 days. Their cytotoxic activity against all the strain cells examined, was higher than PBL already on the third day of culture. 2) Culturing normal PBL with PHA (with or without R-IL2) for 3 days, followed by culturing with R-IL2 for 11 days, caused a marked increase in cell number by about 65 times in 14 days. Cytotoxicity of these cells against MKN-28, MKN-45 and KATO III was found to increase with lapse of culture time. 3) On the 14th day of culture, cytotoxicity of LAK was higher than that of P-LAK. 4) Surface phenotype analysis of LAK revealed that OKT3+ (cell ratio) tended to increase, OKT8+ increased significantly, OKT4+ and Leu7+ tended to decrease, and OKT4+/OKT8+ ratio decreased significantly. Analysis of P-LAK revealed that OKT3+ and OKT8+ increased significantly and OKT4+, Leu7+, and OKT4+/OKT8+ ratio decreased significantly. 5) The rate of total increase in cytotoxicity, calculated in multiplying the rate of cell number increase by the rate of increase in cytotoxicity, was higher in P-LAK than in LAK. The above results showed that P-LAK induced by addition of PHA for the first few days, could cause marked increase both in cell number and in total cytotoxicity.

Adult↗

Enhanced expression of a glyceraldehyde-3-phosphate dehydrogenase gene in human lung cancers.

We have shown that a Mr 37,000 protein whose expression is strongly enhanced in human lung cancer tissues is the subunit of glyceraldehyde-3-phosphate (GAPDH, EC 1.2.1.12). We have isolated a GAPDH complementary DNA from human lung cancer cells and deduced the complete amino acid sequence of the encoded protein. The structure of the lung cancer GAPDH is identical to that of liver GAPDH. In addition, we have found that GAPDH mRNA expression is markedly increased in human lung cancer tissues. These results disclose a molecular basis of increased glycolysis in cancer cells and reveal an important role of energy creating reaction in cancer cell growth.

DNA↗

Effect of actinomycin D on DNA replication and c-myc expression during rat liver regeneration.

In an attempt to elucidate the mechanisms that control the hepatic DNA replication, effect of low doses of actinomycin D on DNA synthesis and c-myc expression during the early stage of liver regeneration was investigated. Small amounts of actinomycin D, in amounts that had no effect on the rate of RNA synthesis in normal rats, were multiple injected at 0, 2 and 4 hours after partial hepatectomy. DNA synthesis and c-myc expression in these rats were compared with those in untreated rats. Hepatic DNA synthesis in the treated rats was delayed about 4 to 6 hours in comparison with control rats. In contrast, time course of c-myc expression in inhibitor treated rats was very similar to that in control rats.

Animals↗

Effects of serum immunosuppressive factors on antitumor cytotoxicity of interleukin 2-induced lymphocytes.

The cytotoxic ability of interleukin 2 (IL2)-induced T cells and the effect on their cytotoxicity of serum suppressive factors obtained from cancer patients were examined. Peripheral blood mononuclear cells (PBL) of healthy adults were IL2-cultured for 72 h either together with a gastric carcinoma cell line MKN-28 or with phytohemagglutinin, then IL2-cultured for another 11 days. Cytotoxicity of the MKN-28 precultured lymphocytes against MKN-28 was particularly increased. Presence during preculture or during cytotoxicity assay of sera from gastric cancer patients having the same histological type as MKN-28 suppressed the cytotoxicity. However, the serum suppressive effect on cytotoxicity of the IL2-cultured lymphocytes was far milder than that on PBL cytotoxicity.

Adenocarcinoma↗

Advanced gastric cancer successfully resected following cisplatin therapy: report of a case.

A case of unresectable advanced gastric cancer was treated with cis-dichlorodiammine platinum (CDDP) at a dosage of 30 mg/day for 5 days every month after operation. After three courses of administration, examinations revealed that the tumor had disappeared, and an evaluation of complete response was made. Four months later, a second-look operation was performed; and it was found that the cancer was smaller than a thumb and could be resected radically. No significant side effects were observed during CDDP therapy.

Adenocarcinoma↗

Significance of intimal tears in the mechanism of luminal enlargement in percutaneous transluminal coronary angioplasty: correlation of histologic and angiographic findings in postmortem human hearts.

Transluminal coronary angioplasty was performed in 17 coronary arteries with stenotic lesions of 15 postmortem human hearts. Morphologic changes of dilated vessels were examined angiographically and histologically. Angiographic evidence of coronary dissection was present in 8 (47%) of the 17 vessels. Histologic examination showed that intimal, medial, and adventitial tears were present in 17 (100%), 11 (65%), and one (6%) of the 17 vessels, respectively. In vessels with angiographic evidence of coronary dissection, the tear extended to more than one fourth of the circumference of the vessel. The tear was histologically demonstrated also in vessels which had no angiographic evidence of coronary dissection. Circumferential extension of the tear was greater in women than in men. There were no significant relationships between severity of the tear and histologic or angiographic characteristics of the target lesions. These results suggest that intimal or medial tears may frequently occur also in clinical cases treated with percutaneous transluminal coronary angioplasty and may be necessary for the success of the procedure.

Aged↗

The regulation of tissue eosinophilia. V. Induction of lymphocyte-derived eosinophil chemotactic inhibitory factor production by a macrophage product from complete Freund's adjuvant-treated guinea pigs.

Splenic T lymphocytes of complete Freund's adjuvant (CFA)-treated guinea pigs spontaneously produce a lymphokine, eosinophil-directed chemotactic inhibitory factor (ECIF), which selectively inhibits the chemotactic response of the treated eosinophils to a certain chemotactic lymphokine for eosinophils. In the present paper, induction of spontaneous ECIF production was examined in CFA-treated guinea pigs. Although short-time (3-hr) cultured supernatants of CFA-treated spleen cells exhibited little or no ECIF activity, the supernatants could stimulate normal T lymphocytes to produce and release distinct ECIF activity. The factor with ECIF-releasing activity (ECIF-RF) was produced by splenic adherent cells of CFA-treated animals. ECIF-RF activity was absorbed only by T lymphocytes, suggesting that target cells of ECIF are T lymphocytes. ECIF-RF activity was eluted near cytochrome c (MW 12,500) on a Sephadex G-100 column. It was further found that ECIF-RF was sensitive to heating at 56 degrees C, to enzyme treatment with trypsin and neuraminidase, and to acid and alkaline condition. We thus concluded that ECIF-RF derived from adherent cells of CFA-treated animals may be involved in the suppression of cell-mediated tissue eosinophilia by stimulation of T lymphocytes to produce and release ECIF activity.

Animals↗

Experimental study on mechanism of absorption of cryonecrotized tumor antigens.

On Day 7 of subcutaneous MRMT-1 tumor inoculation in the thigh of Sprague-Dawley rats, the tumor was treated cryosurgically by contact method. Postoperative changes in local blood circulation were observed by colloidal carbon perfusion and hydrogen-clearance methods, and the pathway and time course of tumor antigen absorption were observed by measuring uptake in serum and lymph nodes of [3H]thymidine injected intratumorally. Results were: At 0.5 to 1 hr after cryosurgery, vascular stasis, dilatation, and tortuosity were observed. There was no inflow of carbon and almost no uptake of [3H]thymidine. At 6 hr, vascular stasis and sludging become more marked. There was no inflow of carbon, while uptake of [3H]thymidine markedly increased. At 24 hr, some carbon inflow in fin vessels and partial recovery of blood circulation in the peritumoral region were observed. Rate of [3H]thymidine uptake was further increased. At 72 hr, carbon inflow and blood circulation increased further, while the cryonecrotized tumor showed hyaline degeneration. At 168 hr, increase of newly formed vessels and recovery of blood circulation were remarkable, but uptake of [3H]thymidine was decreased in parallel with increased demarcation of the cryonecrotized tumor. From these results, it was suggested that the absorption of cryonecrotized tumor antigens started through lymphatic channels in the early period and then took place also through newly formed capillaries surrounding the tumor at 24 hr after cryosurgery and continued until 72 hr after cryosurgery.

Absorption↗

Clinical effects of intravenous diltiazem hydrochloride on renal hemodynamics.

We administered diltiazem HCl i.v. (0.05 mg/kg in bolus followed by 0.01 mg/kg/min for 45 min), and determined the changes in blood pressure (BP), glomerular filtration rate (GFR), renal blood flow (RBF), total renal resistance, urinary volume (UV), urinary sodium (UNa) and potassium excretion, urea and osmolar clearance, and tubular reabsorption ratio of sodium (TRNa%). The serum concentration of diltiazem achieved was similar to the maximum level after a single oral dose of 120 mg. GFR and RBF were measured by i.v. infusion of sodium thiosulfate and sodium rho-amino-hippurate, respectively, as indicators. The subjects included 12 cases of essential hypertension (EH), 10 of chronic glomerular nephritis (CGN) with hypertension, 12 of CGN without hypertension, 12 of ischemic heart disease (IHD), and 10 of normotensive controls. BP decreased in hypertensives but not in normotensives. In patients with EH, GFR and RBF increased markedly (by 25.3 +/- 33.8% and 30.7 +/- 39.5%, respectively). In patients with IHD, GFR increased slightly by 9.8 +/- 17.6%, whereas in patients with CGN with hypertension, GFR decreased by -4.3 +/- 14.3%. No significant change of these indices was observed in normal subjects and in patients with CGN without hypertension. UV and UNa increased and TRNa% decreased in all groups. Urea and osmolar clearance increased in almost every group.

Adult↗

Toxicity of D, L-mandelonitrile-beta-D-glucoside, "prulaurasin" in rat.

Toxicity of cyanogenetic glucoside was studied with rats using synthesized D, L-mandelonitrile-beta-D-glucoside. Considering from blood cyanide level, the cause of death was presumed to be cyanide intoxication. Hydrolysis of cyanogenetic glucoside occurred mainly in small and large intestines. Cyanide level in the intestine seemed to be independent of the amount of glucoside present. LD50 value was calculated to 560 mg/kg but good dose dependent result was not obtained. Relatively rapid absorption of the glucoside from the gastrointestinal tract was observed with the highest absorption rate of 53.4% within 165 min. About 30-45% of the administered glucoside was excreted within 24 hr without alteration and dose dependence appeared in an excreted ratio. The ratio of D-mandelonitrile-beta-D-glucoside to L-form excreted in the urine or remained in the gastrointestinal tract was almost in the same as at administration, and hence biological behaviors, such as absorption, excretion and hydrolysis, of both D- and L-forms of glucoside were almost the same.

Animals↗