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Biomedical subjects

S Taniguchi

Publications and source records attributed to S Taniguchi.

At least 487 records · Page 27Linked to original sources

Systemic chemotherapy in tumor-bearing rats using high-dose cis-diamminedichloroplatinum(II) with low nephrotoxicity in combination with angiotensin II and sodium thiosulfate.

Systemic chemotherapy using high-dose DDP and its antidote, STS, was combined with the AT-II-induced hypertension method and evaluated for efficacy against s.c. tumors in rats. After i.v. infusion of DDP plus AT-II for 5 min, STS was administered i.v. over a further 5 min. The rats treated with this combination chemotherapy showed normal levels of BUN and serum creatinine 4 days after the treatment, although most rats given i.v. STS after DDP without AT-II showed severe nephrotoxicity. The absence of obvious nephrotoxicity in AT-II-combined chemotherapy using i.v. DDP plus post-administered STS can be explained by a transient inhibition of DDP-delivery to the kidney during the AT-II-induced hypertension. The anti-tumor effect of this modified therapy, evaluated by inhibition of tumor growth, was superior to other treatments, as follows: concomitant i.v. administrations of DDP and STS; i.v. DDP, with or without AT-II. The improvement in anti-tumor effect of this combination therapy is explained by the delayed neutralization of active DDP by STS at the tumor site and the selective enhancement of DDP delivery to the tumor tissue, as produced by AT-II. Thus, systemic chemotherapy using high-dose DDP induced no obvious nephrotoxicity and improved the anti-cancer effect in the case of concomitant administration of DDP plus AT-II and the time-delayed injection of STS.

Angiotensin II↗

Expression of retinoic acid receptor genes in neural crest-derived cells during mouse facial development.

Retinoic acid (RA) is known as a teratogen that induces abnormalities in facial structures which are made up mainly of neural crest-derived mesenchyme. We investigated expression patterns of RA receptor (RAR) genes (subtypes alpha, beta, gamma) during mouse facial development. The expression of the RAR beta gene is specific for the mesenchyme around developing eyes and nose, whereas the RAR gamma gene is expressed in the mesenchyme differentiating to facial cartilages and bones. In contrast, the RAR alpha gene is expressed weakly and uniformly over the facial region. These results suggest that crucial roles of endogenous RA in facial development depend on differential functions of the RAR subtypes.

Animals↗

Augmented excretion of procathepsin L of a fos-transferred highly metastatic rat cell line.

We previously reported that v-fos transfer to a src-transformed rat 3Y1 cell line (SR-3Y1-2) enhanced lung metastasis accompanied with an increase in invasiveness. When analyzing factors relating to the high invasiveness, with special reference to typical lysosomal proteases (cathepsins), involving degradation of stroma, we found that the excretion of procathepsin L was significantly larger in the fos-transferred highly metastatic cell line (fos-SR-3Y1-202) than that in the recipient cell lines. The cathepsin D-induced enzyme activity of the excreted procathepsin L in fos-SR-3Y1-202 was about 4 and 13 fold that of SR-3Y1-2 and 3Y1, respectively. The increase in the excretion of procathepsin L from fos-SR-3Y1-202 may play a role in the high invasiveness induced by transfer with the v-fos oncogene.

Animals↗

Expression pattern of acidic and basic fibroblast growth factor genes in adult rat eyes.

Although the retinal angiogenic and mitogenic factors have been identified to be acidic and basic fibroblast growth factors (aFGF and bFGF), little information has so far been available about the cells producing them and their function in retinal tissues. We found, by in situ hybridization, that the expression pattern of the aFGF gene differed remarkably from that of the bFGF gene in adult rat eyes. Our results demonstrated that the aFGF gene was produced by photoreceptor visual cells, neuronal cells in the inner nuclear layer and ganglion cells of the retina, in addition to pigment epithelial cells of the choroid, iris and ciliary body, and epithelial cells of the cornea, conjunctiva and lens, while bFGF was synthesized solely by the photoreceptor visual cells.

Animals↗

Human gamma delta T-cell receptor-positive cell-mediated inhibition of erythropoiesis in vitro in a patient with type I autoimmune polyglandular syndrome and pure red blood cell aplasia.

The gamma delta T-cell receptor-positive (gamma delta TCR+) lymphocytes were markedly expanded up to 68% of peripheral blood lymphocytes in a case with type I autoimmune polyglandular syndrome and pure red blood cell aplasia (PRCA). The gamma delta TCR+ cells showed CD4 negative, 16% dim-CD8 positive and 10% to 46% human leukocyte antigen-D-related (HLA-DR) positive, and exhibited no monoclonality as assessed by the patterns of TCR gene rearrangements. Functional studies revealed that the proliferative responses of the patient's peripheral blood mononuclear cells (PBMC) were severely depressed to candida antigen, alloantigens, and autoantigens (non-T cells). The gamma delta TCR+ cells had no suppressive effect on the proliferative response of the alpha beta TCR+ cells to candida. The patient's PBMC, isolated gamma delta TCR+ cells but not alpha beta TCR+ cells, exhibited non-major histocompatibility complex (MHC)-restricted cytotoxicity. Furthermore, the patient's PBMC and isolated gamma delta TCR+ cells inhibited burst-forming units-erythroid (BFU-E), but not colony-forming units/granulocyte-macrophage (CFU-GM). Supernatants derived from the patient's T cells similarly inhibited BFU-E but not CFU-GM. The clinical course of the patient also showed a close correlation between the decreased number of total lymphocyte counts, especially HLA-DR + gamma delta TCR+ cell counts, and recovery from PRCA. These observations suggest that the gamma delta TCR+ cells might be functional in vivo and involved in the pathogenesis of PRCA in this patient.

Adult↗

Functional modes of retinoic acid in mouse osteoblastic clone MC3T3-E1, proved as a target cell for retinoic acid.

Mouse osteoblastic clone MC3T3-E1 was proved as a target cell for retinoic acid (RA) in bone tissues through the demonstration of RA-receptor gene expression by the northern blot analysis. The effect of RA on the cell growth of MC3T3-E1 was repressive for both subconfluent and confluent growth, whereas RA enhancement of alkaline phosphatase expression was observed at the confluent stage. This implies that RA is a regulatory factor leading osteogenesis of the cells after the confluent stage. RA exhibited simultaneously the stage-dependent effects on EGF-dependent mitogenesis: promotive at the subconfluent, but repressive at the confluent stage.

Alkaline Phosphatase↗

Central nervous system involvement in adult T-cell leukemia/lymphoma.

Central nervous system (CNS) involvement was reviewed in 99 patients with adult T-cell leukemia/lymphoma (ATLL). Fifteen episodes of CNS involvement developed in ten of 99 patients (10.1%); nine had leptomeningeal involvement, whereas two developed intracerebral invasion, one developed cord involvement, and one developed both. CNS involvement was more frequent in the lymphoma type than in the other types of ATLL. Nuchal rigidity was not common (33%) and a syndrome of inappropriate secretion of antidiuretic hormone (ADH) occurred in association with CNS involvement (40%). Three episodes of marked hypoglycorrhachia also were noticed. The systemic progression of ATLL was the most common setting of CNS involvement (80%) and the major cause of death (80%). As for the acute and lymphoma types of ATLL, no significant difference was observed in survival between patients with and those without CNS involvement. These results indicate that CNS involvement is not an essential prognostic factor of ATLL and that it should be treated with systemic chemotherapy coupled with intrathecal chemotherapy. The control of systemic ATLL is important for the prophylaxis of CNS involvement.

Adult↗

Hepatic subsegmentectomy with segmental hepatic vein sacrifice.

There is no clinical disorder in partial Budd-Chiari syndrome or in a major hepatic vein ligation in hepatic trauma. When considering these findings, it is significant to investigate hepatic subsegmentectomies in which a major hepatic vein is sacrificed. We performed such hepatic subsegmentectomies in nine cases of hepatocellular carcinoma. With the sacrifice of the right hepatic vein, S7, S8 resection was done in three patients, S7 resection in two patients, S8 resection in one patient, and S5 resection in one patient. With the sacrifice of the middle hepatic vein, S8 resection was done in two patients. These resections were successfully performed with no postoperative problem. Further, there were no significant differences in postoperative liver function tests of the patients from those of a control group of the commonly performed systematic segmentectomy and subsegmentectomy. By performing such resections, resection was made possible in three cases and curative resection was made feasible in six cases.

Aged↗

Purification of a granulocyte colony-stimulating factor from the conditioned medium of a subclone of human bladder carcinoma cell line 5637, HTB9.

A colony-stimulating factor (CSF) has been purified to homogeneity from the conditioned medium (CM) of a subclone, designated HTB9, of human bladder carcinoma cell line 5637. HTB9 cells were successfully cultured on micro-carrier beads at low-serum concentration, and the resulting CM (HTB9-CM) was concentrated by ultrafiltration. Purification procedures consisted of anion-exchange column chromatography, gel-filtration column chromatography, and reverse-phase column chromatography. The finally purified protein possessed a specific activity more than 10(8) U/mg protein for day-7 CFU-GM colony formation and exhibited a single band representing a molecular weight of 17,000 upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Biological activity was apparently specific for a neutrophilic granulocyte lineage of human non-phagocytic bone-marrow cells in vitro, and antiserum raised against this purified protein completely inhibited the activity of recombinant granulocyte colony-stimulating factor.

Chromatography, Gel↗

Histamine metabolism in delayed type hypersensitivity--comparative analysis with cellular infiltrates.

We examined the dynamic changes of histamine metabolism and infiltrating cell populations in lesional sites of representative cutaneous delayed type hypersensitivity (DTH), including dinitrochlorobenzene (DNCB) allergic dermatitis, purified protein derivative of tuberculin (PPD) reaction, and keyhole limpet homocyanin (KLH)-induced cutaneous basophil hypersensitivity. The concentration of histamine increased with time in all DTH reactions examined, though the time course varied among these reactions. In DNCB allergic dermatitis, the maximum content of the amine at 3 days after the initiation was about three times that of the control baseline. In PPD reaction, the maximum content and the time course were almost similar to that in DNCB allergic dermatitis. However, in KLH-induced cutaneous basophil hypersensitivity the maximum content was about ten times that in DNCB allergic dermatitis or PPD reaction, and was observed earlier, on the 2nd day. There was no remarkable change in the activities of histamine-degrading enzymes in these reactions. There was little infiltration of mast cells, while time-dependent changes of the basophil infiltration were almost parallel those of the histamine concentration in all these reactions. Basophils in DNCB allergic dermatitis showed a piecemeal degranulation, while those in either the PPD reaction or KLH-induced cutaneous basophil hypersensitivity remained intact. These results clearly suggest that the increase of histamine concentration in cutaneous DTH depends on the number of basophils infiltrating the lesional sites, even if the regulatory mechanisms of the activation of the cells differ among the DTH reactions.

Animals↗

Enhanced melanogenesis of murine melanoma cells cultured on or in collagen gel.

To elucidate the interaction between melanoma and its matrix, we cultured B16 murine melanoma cells on and in type I collagen gel and evaluated specified functions of melanoma cells; tyrosinase activity and melanin-synthesizing capacity. Proliferation of cells cultured in these environments was markedly suppressed compared with that of cells cultured conventionally on plastic. On the other hand, the tyrosinase activity of cells cultured in or on collagen gel was two to three times higher than that of cells cultured on the plastics, while their melanin production was approximately double that achieved during conventional culture of cells. In conclusion, collagen gel influenced the growth and cell-specific functions of the melanoma cell. The culture system using collagen gel as substrate may be useful for the investigation of the interaction between melanoma and its matrix.

Animals↗

Cholinergic agonists increase cell calcium in rat medullary collecting tubules. A fura-2 study.

The intracellular free calcium concentration [Ca2+]i of rat medullary collecting tubules was calculated from microscope fluorescence measurements in single pieces of fura-2-loaded tubules superfused at 37 degrees C. When carbachol (10(-4)-10(-3) M) was added in the superfusate, a biphasic increase in [Ca2+]i was generally obtained, which included an early peak phase and a sustained plateau thereafter; sometimes, the peak phase was not apparent; the plateau was maintained as long as the agonist was applied. Several responses could be induced successively without a fall in responsiveness. From dose/response curves, K1/2 values of about 10(-5) M for carbachol and 10(-6) M for acetylcholine were obtained. The effects of the agonists were suppressed with 10(-4) M of atropine or pirenzepine, indicating the presence of muscarinic receptors of the M1 type. In the absence of external calcium, the peak phase of the response was preserved while the plateau phase was suppressed; thus, the peak involves the release of calcium stored in organelles, whereas the plateau involves the entry of external calcium through calcium channels which were voltage independent and insensitive to the usual calcium blockers.

Acetylcholine↗

Surgical treatment of renal cell carcinoma with a tumor thrombus extending into the right atrium.

We experienced surgical treatment on two patients having renal cell carcinoma with a tumor thrombus extending into the right atrium. In these patients, we performed nephrectomy, dissection of lymph nodes and removal of a tumor thrombus using cardiopulmonary bypass. One died of multiple organ failure 42 days postoperatively; the other was discharged from the hospital and is currently doing well 12 months after the operation. Cardiopulmonary bypass combined with hypothermia and low blood flow significantly facilitated removal of the tumor thrombus extending into the right atrium without the risk of pulmonary embolism or brisk hemorrhage.

Aged↗

Increased therapeutic effect on metastatic liver tumors in rats of two-route chemotherapy using cis-diamminedichloroplatinum (II) and its antidote, sodium thiosulfate, with temporary clamping of the abdominal aorta.

To improve the therapeutic effects of conventional "two-route chemotherapy" (TRC) comprising cis-diamminedichloroplatinum(II) (CDDP) given via the hepatic artery plus simultaneous i.v. sodium thiosulfate (STS) on metastatic liver tumors in rats, we combined TRC with aortic clamping at the supraceliac level. Treatments were evaluated in Wistar-King-Aptekman (WKA) rats bearing metastatic liver tumors 7 days after the inoculation of 10(6) syngenic RBT-1 (transitional-cell carcinoma) cells via the mesenteric vein. When 15 mg/kg CDDP was injected i.a. over 5 min, immediately followed by STS 1,580 mg/kg (200-fold the molar equivalent of 15 mg/kg CDDP) given i.v. over a further 5 min, the antitumor activity, evaluated by the number of tumor nodules present 12 days after treatment, was superior to that of conventional TRC (15 mg/kg i.a. CDDP plus simultaneous administration of 1,580 mg/kg i.v. STS), but the blood urea nitrogen (BUN) level was highly elevated (63.6 mg/dl). With aortic clamping for 7.5 min during CDDP administration and the first half of STS treatment, the TRC consisting of CDDP plus delayed STS (modified TRC) exhibited a further improvement in antitumor activity, with no nephrotoxicity (BUN, 17.1 mg/dl). Although the antitumor activity of 3 or 5 mg/kg i.a. CDDP was also increased by aortic clamping, in animals with normal BUN levels the survival of those treated with modified TRC was greater than that of rodents given 3 mg/kg i.a. CDDP with aortic clamping; however, the former was the same as that of animals given 5 mg/kg i.a. CDDP with aortic clamping whose BUN levels were elevated (31.2 mg/dl). Loss of body weight, the decrease in WBC counts, and changes in the serum transaminase levels in rats given modified TRC were tolerable. The improved therapeutic effect of modified TRC can be explained as follows: during aortic clamping, (a) CDDP delivery to the kidney decreased by 96% and made feasible the delay in STS administration after CDDP without nephrotoxicity, and (b) CDDP retention in the liver was increased by 366%, as aortic clamping decreased the portal blood flow, thereby inhibiting the washout of CDDP from the liver.

Animals↗

Disappearance of thyroid-stimulation blocking antibody by glucocorticoid therapy in a patient with primary myxedema who developed aortitis syndrome during L-thyroxine supplementation.

A 39-year-old woman with primary myxedema, who had the potent activities of thyrotropin-binding inhibitory immunoglobulins (TBII) and thyroid-stimulation blocking antibodies (TSBAb), developed aortitis syndrome about 6 months after the initiation of L-thyroxine (L-T4) supplementation. A 35 mg daily dose of prednisolone for aortitis syndrome was initiated, and the dose was gradually reduced. TBII and TSBAb activities were gradually decreased, and both reached normal levels (7.7% and 10.1%, respectively) 3 months after the initiation of prednisolone. Therefore, dose of L-T4 was gradually reduced, and L-T4 supplementation was stopped. Subsequently, however, recurrence of hypothyroidism was not observed. These observations indicate the possibility that hypothyroidism remits with disappearance of TBII and TSBAb activities in not only neonatal cases but also adult cases.

Adult↗

Clinical characteristics of hybrid leukemia: report of five cases.

We studied clinical and biological features of five cases of hybrid leukemia. Three of the five patients were classified as biphenotypic leukemia because of the coexpression of myeloid/B lymphoid markers in patients 1 (FAB M2) and 2 (FAB CMMoL) and myeloid/T lymphoid markers in patient 3 (FAB M4). Patient 4 was identified as bilineal-biphenotypic leukemia because acute myelogenous leukemia (AML) (FAB M4) and acute lymphoblastic leukemia (ALL) (FAB L1) coexisted and each population coexpressed myeloid and T lymphoid markers. Patient 5 was identified as bilineal leukemia due to the conversion from AML (FAB M1) to ALL (FAB L1) at an interval of 3 months. The Philadelphia (Ph1) chromosome was negative in all cases. A leukemic blast colony formation using cell line 5637 conditioned medium as a stimulator was obtained in all four patients examined. Three of the five patients had been suffering from so-called stem cell disorders such as aplastic anemia in patient 2, trilineage myelodysplasia in patient 4 and refractory anemia with excess of blasts in transformation in patient 5. The pre-existing impairment of pluripotent stem cell was probably the background of these hybrid leukemia. Hybrid leukemia appears to have an inferior prognosis: an AML-directed chemotherapy resulted in a low remission rate (2/5) with a short duration of relapse free survival (1/2) and an ALL-directed chemotherapy produced no remission (0/3). Chronological phenotypic analysis revealed that hybrid features of leukemic blasts disappeared at the time of relapse in patient 1 and progression to AML in patient 2. Monitoring of lineage-associated markers should be required for the management of hybrid leukemia.

Adult↗