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Biomedical subjects

Y Takano

Publications and source records attributed to Y Takano.

At least 361 records · Page 20Linked to original sources
PubMed1992

[PMUE therapy (CDDP, MMC, UFT, etoposide) for advanced gastric cancer--a case report].

CDDP, MMC, UFT and Etoposide (PMUE)-combined therapy was given to a 62-year-old man with advanced gastric carcinoma. PMUE therapy consists of i.v. injection of CDDP 75 mg/m2 and MMC 10 mg/body on day 1, i.v. injection of Etoposide 50 mg/body on days 3, 4 and 5 and consecutive daily administration of UFT 400 mg/body, with 3 weeks as one course. He was admitted for Borrmann type 3 gastric carcinoma with multiple liver metastasis, lymph node metastases and peritoneal dissemination, the underwent total gastrectomy with R2 lymph node dissection. He was treated four times with this therapy after sensitivity test for carcinostatic agents (SDI test), which resulted in complete remission, as confirmed by CT scan and second-look operation. The patient has currently been free of disease, and we conclude that this PMUE therapy is extremely effective for advanced gastric carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Synthesis and antitumor activity of poly(ethylene glycol)s linked to 5-fluorouracil via a urethane or urea bond.

In order to provide a macromolecular prodrug of 5-fluorouracil (5FU) with reduced side-effects and exhibiting strong antitumor activity, 5FU was covalently linked to poly(ethylene glycol) (PEG) via a urethane or urea bond. For the purpose of evaluating the release behavior of 5FU, the hydrolysis of the urethane or urea bond in the obtained conjugate of PEG-end capped with 5FU was investigated in vitro at 37 degrees C in aqueous solution media. The survival effect for the conjugate was assessed in vivo against p388 lymphocytic leukemia in female CDF1 mice by intraperitoneal (i.p.) transplantation/i.p. injection. The effects of a hydrophobic hexamethylene spacer group, the end group and the number n of ethylene oxide (EO) units in PEG on the release behavior of 5FU and the survival effect were investigated. The release rate of 5FU from the 5FU-terminated PEG conjugates via urethane or urea bond was very fast. However, it became slow with increasing n of EO units in PEG and was depressed by the introduction of hydrophobic spacer group. The 5FU-terminated PEG conjugates obtained exhibited significant survival effects against p388 leukemia mice i.p./i.p. Especially, the methoxy PEG (n = 113)/urethane/hexamethylene/urea/5FU conjugate showed the strongest survival effect among the synthesized 5FU-capped PEG conjugates via urethane or urea bond compared to free 5FU against p388 leukemia mice. These conjugates obtained did not display an acute toxicity even in high dose ranges.

Animals↗
PubMed1992

Contrasting effects of interferon-gamma and interleukin-4 on neopterin generation from human adherent monocytes.

The production of neopterin is closely correlated with activation of cell-mediated immunity. Neopterin appears to be produced by human macrophages specifically stimulated with interferon-gamma (IFN-gamma). Interleukin-4 (IL-4), a B and T stimulatory factor, has recently been shown to inhibit monocyte/macrophage functions, including the ability to suppress monocyte-generated cytokines. In this report we confirmed previous studies that identified the monocyte/macrophage as the main producing cell among human blood cells and that secretion is stimulated by IFN-gamma and lipopolysaccharides (LPS). IL-4 inhibits the generation of neopterin from unstimulated monocytes. This inhibitory effect was dose dependent and occurred at concentrations lower than 0.01 ng/ml. However, IL-4 had only a minimal inhibitory effect on LPS-induced generation of neopterin and could not reverse IFN-gamma-induced neopterin secretion from adherent monocytes. Furthermore, we report that LPS induced IFN-gamma production in monocyte culture. This production is strongly inhibited by IL-4 treatment. These findings indicate that IL-4 can regulate the synthesis of neopterin by adherent blood mononuclear cells and provide further evidence that LPS-induced neopterin in macrophages may act by IFN-gamma-independent mechanisms.

Biopterins↗
PubMed1992

[Infiltration into the aqueous humor (uveitis) in a patient with malignant lymphoma].

An 80-year-old male was admitted to our hospital because of multiple tumors in October 1989. A pathological diagnosis of non-Hodgkin's lymphoma (diffuse, medium-sized cell type) was made with the histological examination of his biopsied tumors. His clinical stage was stage IV A. Chemotherapy (CHOP) brought him to complete remission. In May 1990, relapse of non-Hodgkin's lymphoma was observed in the neck and both eyes. The diagnosis of uveitis due to involvement of lymphoma cells was confirmed by an aspiration biopsy of left aqueous humor. Complete recovery of his visual acuity was possible with additional chemotherapy, and lymphoma cells in his right aqueous humor were expelled completely, while his cervical tumor remained 1/3 of the original size. He eventually died of pneumonia on December 9th, 1990. Intraocular involvement of malignant lymphoma is rare in comparison with extraocular involvement. Especially, the patient who has only turbid aqueous humor as an ophthalmic sign is very rare. In this paper, we reported a case of lymphoma with intraocular involvement and discussed the mechanisms of infiltration of lymphoma cells into the aqueous humor and the therapy.

Aged↗
PubMed1992

[A population based survey of attendance at screenings in urban areas].

To clarify the present situation of screenings in urban areas, a population based survey on attendance at screenings was conducted in Kitakyushu City. Self-administered mailed questionnaires were sent to three thousand randomly selected subjects 40 years of age or over living in Kitakyushu City. The results are summarized as follows: 1. Considerable differences were observed in the number of people who were offered screenings at work sites for those between the ages of 40-59 compared to those 60 years of age or over, and between full-time employees and part-time or self-employed workers. 2. Among people who obtained stomach examinations, middle age men mainly received cancer screenings at work sites, while women or older men were mainly examined when they went to clinics or hospitals when abdominal discomforts occurred. Among women who received uterine examinations, all age groups mainly received cancer screenings at city administered screenings at clinics or hospitals, and rates decreased as age increased. 3. Among people who did not obtain stomach examinations, many middle age people wanted to be examined for stomach cancer but were unable to, while older people did not think it necessary. In the case of uterine cancer screening, middle age women did not want to receive it, while older women did not think it necessary. 4. For those people who are not offered cancer screenings at workplaces, it is assumed that those who have a positive attitude toward screening will obtain it, if offered, at sites conducted by the local government.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Establishment from a human chondrosarcoma of a new immortal cell line with high tumorigenicity in vivo, which is able to form proteoglycan-rich cartilage-like nodules and to respond to insulin in vitro.

The human chondrosarcoma cell line (HCS-2/8) established by our group expresses cartilage phenotypes such as production of cartilage-type proteoglycans and collagen type II, but its tumorigenicity is low. To develop an in vitro experimental system for studies of human chondrosarcomas, a new immortal cell line of human chondrosarcoma, named HCS-2/A, was established from the same tumor. HCS-2/A cells proliferated with a doubling time of 3 1/2 days in a medium containing 20% fetal bovine serum (FBS). This growth rate was comparable to that of HCS-2/8 cells. However, HCS-2/A cells proliferated more rapidly than HCS-2/8 cells in the presence of 2-10% FBS. Like HCS-2/8 cells, HCS-2/A cells had a polygonal shape in sparse cultures and became spherical as they reached confluence, after which they formed nodules composed of multilayered cells and a large quantity of extracellular matrix showing strong metachromasia. The nodules formed by HCS-2/A cells were thicker and also larger in diameter than those formed by HCS-2/8 cells. Electron microscopically, the cells in the nodules resembled chondrocytes in vivo, but each cell had an irregular-shaped nucleus which is a characteristics of tumor cells. The cells actively synthesized "cartilage-specific" large proteoglycans and their level of proteoglycan synthesis was comparable to that of HCS-2/8 cells. Insulin, which stimulates proteoglycan and DNA syntheses in cultured chondrocytes, markedly increased proteoglycan synthesis in HCS-2/A cells. On the other hand, the hormone only slightly increased proteoglycan synthesis in HCS-2/8 cells. Insulin also stimulated DNA synthesis in cultured HCS-2/A cells, but not in HCS-2/8 cells. Immunostaining revealed that HCS-2/A cells produced type-II collagen but not type-I collagen. However, the level of collagen synthesis of HCS-2/A cells was lower than that of HCS-2/8 cells. Inoculation of HCS-2/A cells into athymic mice resulted in the formation of chondrosarcomas that grew faster than those arising from HCS-2/8 cells.

Aged↗
PubMed1991

The central pressor actions of a novel tachykinin peptide, gamma-preprotachykinin-(72-92)-peptide amide.

Intracerebroventricular (i.c.v.) injections of a novel tachykinin peptide, gamma-preprotachykinin-(72-92)-peptide amide (neuropeptide gamma, NP gamma), caused dose-dependent increases in blood pressure. The NP gamma-induced pressor responses (1 microgram i.c.v.) were blocked by peripheral administration of pentolinium (10 mg/kg i.v.) and phentolamine (10 mg/kg i.v.), but were not inhibited by a vasopressin antagonist. These results suggest that central NP gamma increases the blood pressure via sympathetic nerve activity.

Animals↗
PubMed1991

Characterization of a novel aldose reductase inhibitor, FR74366, and its effects on diabetic cataract and neuropathy in the rat.

FR74366 (FK366) ([3-(4-bromo-2-fluorobenzyl)-7-chloro-2,4-dioxo-1,2,3,4- tetrahydroquinazolin-1-yl] acetic acid) is a chemically novel aldose reductase (AR) inhibitor. It exhibited a highly potent, reversible, and mixed type inhibition of partially purified AR from the rat sciatic nerve (IC50 = 3.6 nmol/L) and rat lens (IC50 = 4.4 nmol/L). FR74366 inhibited sorbitol accumulation in the isolated human erythrocyte (IC50 = 1.6 mumol/L), rat lens (IC50 = 39 mumol/L), and rat sciatic nerve (IC50 = 17 mumol/L) incubated with high glucose concentrations. The oral administration of FR74366 to streptozotocin (STZ)-induced diabetic rats for 2 weeks decreased sorbitol levels (ED50 = 3.7 mg/kg for sciatic nerve, 23 mg/kg for lens, 52 mg/kg for retina, and 62 mg/kg for renal cortex). Administration of FR74366 to diabetic rats for 17 weeks delayed cataract formation and admixture of 0.028% FR74366 in the diet completely inhibited the cataract formation. Moreover, the recovery of reduced motor nerve conduction velocity by FR74366 in diabetic rats was demonstrated in prevention and reversal experiments. This recovery effect correlated well with reduction of accumulated sorbitol and fructose levels and normalization of decreased myoinositol levels. The duration and tissue specificity of inhibitory effects of FR74366 on sorbitol accumulation also correlated well with the levels of FR74366 in various tissues of diabetic rats. These data indicate that both decreases in tissue sorbitol levels and improvement of functional defects reflect FR74366 levels in tissue rather than plasma in diabetic rats. These results, taken together, suggest that FR74366, which is currently undergoing clinical trials in Japan and the United States, will be a useful therapeutic agent for diabetic complications.

Aldehyde Reductase↗