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Biomedical subjects

Y Takano

Publications and source records attributed to Y Takano.

At least 325 records · Page 18Linked to original sources
PubMed1993

[Intraarterial infusion chemotherapy for recurrent or unresectable gastric cancer].

Sixteen patients with recurrent or unresectable gastric cancer were treated by intraarterial infusion chemotherapy. The tip of the catheter was located at the 9-10th Th level in the aorta of 14 patients and in the common hepatic artery of two. The drug combination was methotrexate + 5-fluorouracil (5-FU), cisplatin, mitomycin C (MMC) + etoposide and MMC + 5-FU. Side effects such as bone marrow suppression, diarrhea and appetite loss were seen in 63% (10/16). The response rate was 36% (4/11) in those who were evaluated, and another three showed relief from symptoms. Median survival time was 11 months, and the one year survival rate was 41%, while two patients showing PR have been alive for more than one year.

Adult↗
PubMed1993

[A case of gastric cancer with multiple liver metastases showing marked efficacy of preoperative and postoperative chemotherapy with CDDP, MMC and UFT(PMU), or CDDP, MMC, UFT and etoposide (PMUE)].

The patient, a 65-year-old male with far advanced gastric cancer of H3N4 (Stage 4), was assumed inoperable on admission and chemotherapy using CDDP, MMC and UFT(PMU) was carried out. As a result, the levels of AFP and CEA were reduced notably, and PR effects were recognized in liver and lymphnode metastatic lesion. Thus, 2 months later, reduction surgery was performed, during which primary lesion was resected and a reservoir tube for chemotherapy was placed in the common hepatic artery. Subsequently, the chemotherapy with Etoposide added to PMU(PMUE) was continued by utilization of a reservoir, so that liver metastasis decreased more than 90% from the maximum. However, metastasis lesions of left lobe of the liver had enlarged with reincrease of AFP and CEA since 6 months after the operation. A month later left lobectomy of the liver was performed. Residual metastases of the liver were then enlarged. PMUE with Ca antagonist was used with little effect then. The patient died of liver failure 15 months after initial admission.

Adenocarcinoma, Papillary↗
PubMed1992

Central pressor actions of tachykinin NK-3 receptor in the paraventricular nucleus of the rat hypothalamus.

The central pressor actions of the tachykinin NK-3 receptor in the paraventricular nucleus (PVN) of the hypothalamus were examined in anesthetized rats. In forebrain-restricted animals, the selective tachykinin NK-3 receptor agonist senktide (10 micrograms, i.c.v.) increased the blood pressure, and this pressor response was more potent than in control animals. Injection of senktide into the PVN also increased the blood pressure, and this pressor response was inhibited by pretreatment with the vasopressin V1 receptor antagonist (10 micrograms/kg, i.v.). These results suggest that central injection of senktide stimulated the NK-3 receptor in the PVN of the hypothalamus, and increased blood pressure by inducing release of vasopressin from the pituitary gland.

Animals↗
PubMed1992

The effect of intrathecally administered imiloxan and WB4101: possible role of alpha 2-adrenoceptor subtypes in the spinal cord.

To define the antagonist pharmacology of spinal antinociceptive effects of alpha 2-adrenoceptor agonists, the ability of WB4101 (2-(2,6-dimethoxyphenoxyethyl)-aminomethyl-1,4-benzodioxane) and imiloxan to antagonize the effect of spinal ST-91 (2-[2,6-diethylphenylamino]-2-imidazoline), clonidine and dexmedetomidine was examined. Antinociceptive effects of ST-91 were antagonized by WB4101 and imiloxan; clonidine only by WB4101; and, dexmedetomidine was not antagonized by either antagonist. It is hypothesized that the alpha 2 adrenoceptor subtype alpha 2A is involved in the antinociception of spinal clonidine and dexmedetomidine, and alpha 2B is involved in that of ST-91.

Adrenergic alpha-Agonists↗
PubMed1992

Role of NK-1 receptor in central cardiovascular regulation in rats: studies on a novel non-peptide antagonist, CP-96,345, of substance P NK-1 receptor.

CP-96,345[(2S,3S)-cis-2-(diphenylmethyl)-N-[(2-methoxyphenyl)- methyl]-1-azabicyclo [2.2.2] octan-3-amine] was recently discovered to be a nonpeptide substance P (SP) antagonist. We examined the effects of CP-96,345 on the central cardiovascular responses to tachykinin peptides in anesthetized rats. CP-96,345 (200 nmol, i.c.v.) inhibited the pressor responses of the NK-1 receptor-selective agonist GR 73632 (0.5 nmol, i.c.v.) and SP (7 nmol, i.c.v.). It also inhibited the increase in blood pressure elicited by neurokinin A (7 nmol, i.c.v.). However, it had no effect on the earlier pressor response induced by neuropeptide gamma (l nmol, i.c.v.) or by a selective NK-3 agonist senktide (1 nmol, i.c.v.). These findings suggest that SP (i.c.v.) induces pressor responses via the NK-1 receptor, and that the pressor response to neurokinin A may also be mediated by the NK-1 receptor in the brain.

Animals↗
PubMed1992

Cellular mechanisms: induction of heart allograft survival in rats by 15-deoxyspergualin.

Survival of ACI rat heart grafts in Lewis rat (LEW) recipients treated with a short course of 15-deoxyspergualin (DSG), in a dose of 5 mg/kg daily beginning from day 4 of grafting, was markedly prolonged, with a mean survival time of 29.8 +/- 3.0 days. On day 20 after grafting, the cellular mechanism of inducing allograft survival after DSG treatment was analyzed by testing the activation of spleen cells in several assay systems. The results indicate that spleen cells from DSG-treated rats with surviving heart allografts show almost no proliferative response against donor strain stimulator cells in the mixed lymphocyte reaction (MLR) as compared with controls. Their cytotoxic activity was lower than that of spleen cells from rats with heart allograft rejection towards donor strain target cells. Adding various concentrations of spleen cells from DSG-treated LEW rats with surviving ACI heart allografts to the MLR when the responder cells from normal LEW rats were exposed to irradiated ACI or Wistar (third party) stimulator cells revealed a strong suppression, in a cell-dose-dependent manner. Moreover, the transfer of 2.0 x 10(8) spleen cells from DSG-treated LEW rats with surviving ACI heart allografts to an irradiated grafted host did not prolong the survival either of the ACI heart grafts or of the third party Wistar heart grafts. These results suggest that the proliferative response and cytotoxic activity are lowered and suppressor cells are induced by treatment with DSG, in rats with surviving allografts.

Animals↗
PubMed1992

Control of humoral and cellular immunity-mediated accelerated heart allograft rejection in sensitized rats by low dose FK 506 and splenectomy.

UNLABELLED: ACI heart grafts are rejected, at an accelerated pace, in Lewis (LEW) rats sensitized by donor-type blood admixed with immunoadjuvant (adjuvant complete Freund, ACF) 7 days earlier. In an in vitro study, the anti-ACI cytotoxic antibody titers in the serum increased from 1:4 in nonsensitized rats to 1:128 in sensitized rats; the spontaneous blastogenesis in spleen cells was higher in sensitized rats than in nonsensitized rats; spleen cells from sensitized rats showed a strong proliferative response against donor strain stimulator cells compared with the control; the cytotoxic T cell activity of spleen cells from sensitized rats was higher than that of spleen cells from nonsensitized rats. Treatment with low dose FK 506 in combination with splenectomy (Spx) synergistically prolonged the heart allograft survival in this sensitized rat model. IN CONCLUSION: (1) Both humoral and cellular responses against the donor antigen appear in the serum and in the spleen of rats sensitized by donor-type blood admixed with immunoadjuvant ACF. (2) A low dose of FK 506 together with Spx appears to control this sensitization through different mechanisms, resulting in a prolongation of heart allograft survival.

Animals↗
PubMed1992

In vitro FK506 kidney tubular cell toxicity.

Nephrotoxicity is the most prominent side effect of the new immunosuppressive drug FK506. Some of the histopathological changes associated with cyclosporine (CyA) nephrotoxicity such as tubular vacuolization and glomerular thrombosis have also been reported with FK506 therapy. In this study we used kidney tubular cells in culture to address the issue of FK506- and CyA-induced tubular damage. Exposure of tubular cells to high concentrations of FK506 or CyA (10, 50 and 100 microM) induced a time- and dose-dependent cell injury in vitro characterized by a direct cytotoxic effect on tubular cells as expressed by release of 3H-thymidine from prelabelled cells, N-acetyl-beta-D-glucosaminidase (NAG) release and cell detachment. Ultrastructural changes (vacuolization, swelling and mitochondrial enlargement) and inhibition of the growth (DNA and RNA synthesis) of cultured tubular cells were also observed at high concentrations of FK506 and CyA. These concentrations are higher than those reached in clinical situations, but close to the concentrations that may be reached by FK506 or CyA in tissues. Low concentrations of FK506 and CyA (1, 0.1 and 0.01 microM) were not cytotoxic and induced only a minimal inhibitory effect on the growth of tubular cells in vitro. At the same concentration CyA induced more cell detachment, more NAG release and a stronger inhibitory effect on cell growth than FK506 (P < 0.01). Since an evident cytotoxic effect was observed only at high concentrations, we can speculate that tubular toxicity is due to the accumulation of drug in the cells inducing cell disruption and death.

Animals↗
PubMed1992

FK506 mechanism of nephrotoxicity: stimulatory effect on endothelin secretion by cultured kidney cells.

The administration of FK506 or cyclosporin A (CyA) to animals and humans induces a decrease in glomerular filtration rate and renal plasma flow and an increase in renal vascular resistance. Endothelins (ET-1), very powerful renal vasoconstrictors, are involved in CyA-related alteration in renal haemodynamics. In this study we sought to determine whether FK506 and CyA had a stimulatory effect on endothelin secretion by cultured kidney cells (tubular and mesangial cells) and whether this stimulatory effect coincided with an increase in ET-1 serum level in FK506- and CyA-treated rats. FK506 concentrations of 1, 0.1, 0.01 and 0.001 microM significantly stimulated ET-1 secretion by cultured tubular and mesangial cells. CyA at 10, 1, 0.1 and 0.01 microM also exerted an enhancing effect on ET-1 secretion in cultured tubular cells whereas CyA only at 10 and 1 microM had a stimulatory effect on ET-1 secretion by human mesangial cells. We observed that the concentrations of CyA that induced the most substantial enhancing effect were 10 or 100 times higher than those required for FK506 to produce the same effect. The concentrations of FK506 or CyA which induced ET-1 secretion by tubular cells and kidney cells were not cytolytic as assessed by N-acetyl-beta-D-glucosaminidase (NAG) release and lactic dehydrogenase (LDH) release. FK506 or CyA treatment at toxic doses induced an increase in serum level of ET-1 in treated rats. We conclude that FK506 and CyA induced an increase in the synthesis of endothelin in the kidney which may explain the increase in circulating ET-1. This stimulatory effect may contribute to the genesis of haemodynamic preturbations associated with FK506 and CyA.

Acetylglucosaminidase↗
PubMed1992

Nonspecific hemolytic effector of activated macrophages as activation marker of allograft rejection.

The aim was to assess a nonspecific hemolytic effector of activated monocytes/macrophages, designated spontaneous plaque-forming cell (SPFC), as an activation marker in allograft rejection. An in vitro study on the immunologic characteristics of SPFC monocytes in man and an in vivo study in Lewis rats as to the monitoring of SPFC generation of allograft infiltrating cells with or without immunosuppression were conducted. Hemolysis of SPFC was mediated by CR3 adhesion molecules, detected by Mo-1 and OKM10 monoclonal antibodies. Hemolysis of SPFC was nonspecific, and nonrosette-forming T cells with autologous erythrocytes (non-ARFC-T) acted as suppressor T cells inhibiting SPFC-hemolysis against autologous erythrocytes. A 6-day course of immunosuppression with a daily dose of cyclosporin A (CyA) 10 mg/kg and of FK506 1 mg/kg suppressed the SPFC generation to the level of syngeneic control. In contrast, peak SPFC generation coincided with rejection, and the degree of SPFC generation reflected the grade of histoincompatibility. The present findings suggested that SPFC-activated monocytes/macrophages may be one of the activation markers in allograft rejection and lead to a new concept of graft rejection and self or nonself discrimination mediated by nonspecific, hemolytic SPFC effectors and suppressor T cells inhibiting autoreactivity.

Animals↗
PubMed1992

In vivo and in vitro mechanisms of cardiac allograft acceptance in the rat after short treatment with 15-deoxyspergualin.

15-Deoxyspergualin (DSG) has been reported to be a useful immunosuppressive agent already used to inhibit acute rejection in clinical transplantation. In the present study, the survival of heart allograft in rats after a short course of DSG treatment and the mechanisms underlying DSG-induced heart allograft acceptance were studied. Male LEW rats were used as recipients. Male ACI and Wistar rats were used as donors and third-party donors, respectively. Survival of ACI heart grafts in LEW recipients treated with a short course of DSG starting on day 4 after grafting was markedly prolonged, with a mean survival time of 16.6 +/- 5.8 days and 29.8 +/- 3.0 days at doses of 2.5 mg/kg per day and 5 mg/kg per day, respectively. On day 20 after grafting, the mechanism of inducing allograft survival after DSG treatment at a dose of 5 mg/kg per day was analyzed by testing the activation of spleen cells or serum in several assay systems. Spleen cells from DSG-treated rats with surviving heart allografts showed almost no proliferative response against donor strain stimulator cells compared with controls. The cytotoxic activity towards donor strain target cells of spleen cells from DSG-treated rats with surviving heart allografts was lower than that of spleen cells from rats with rejected heart allografts.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Argyrophilic nucleolar organizer regions in human adrenocortical neoplasms.

Argyrophilic nucleolar organizer regions (AgNOR) in human adrenocortical neoplasms, including five carcinomas and ten adenomas, were studied using a semi-automatic image analyzer. Both the number and total area of AgNOR per nucleus in the carcinomas were found to be statistically greater than in adenomas and control tissues. However, there were no statistically significant differences in total AgNOR area per nuclear area or in the mean area of individual AgNOR dots. The AgNOR of neoplastic and normal cells were of four morphological types: type 1 had a few dots at the periphery of the nucleus, type 2 a few dots at the center, type 3 a large round dot along with several small ones at the center, and type 4 numerous diffusely distributed polymorphic dots. Most type 3 and 4 cells were found in carcinoma cases. Type 1 cells decreased in proportion to the severity of biological malignancy. It follows from these findings that careful observation of AgNOR should facilitate the distinction of malignant from benign adrenocortical neoplasms.

Adenoma↗
PubMed1992

Molecular-genetic analysis of ocular adnexal benign lymphoid hyperplasias by a two-step polymerase-chain-reaction.

Twelve biopsied ocular adnexal benign lymphoid hyperplasias (OABLH) satisfying benign histological criteria were investigated for clonal immunoglobulin (Ig) heavy-chain gene rearrangement by means of a two-step polymerase chain reaction (PCR) method using formalin-fixed and paraffin-embedded tissue. Of the 12, 4 (33%) demonstrated clear single bands of the rearranged gene for the Ig heavy-chain, of between 100 and 150 base pairs. The selected cases were all free of malignant lymphoma and all of the lesions were small (2 x 2-22 x 6 mm; median 4.5 x 3 mm). Histopathological and cytological features were not essentially different between monoclonal and non-monoclonal examples. Immunohistochemistry was of little benefit in separating the two. It is concluded that OABLH demonstrating a benign clinical course frequently contain monoclonal B cell populations suggesting a continuous progressive spectrum of lesions in B cell neoplasia. In addition, the significance of molecular-genetic analysis for OABLH and the utility of the two-step PCR method should be emphasized.

Adolescent↗