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Biomedical subjects

T Yoshioka

Publications and source records attributed to T Yoshioka.

At least 199 records · Page 11Linked to original sources
PubMed1999

A new combination chemotherapy with cis-diammine-glycolatoplatinum (Nedaplatin) and 5-fluorouracil for advanced esophageal cancers.

OBJECTIVE: The efficacy of a new chemotherapeutic combination consisting of Cis-diammineglycolatoplatinum (Nedaplatin), a derivative of cisplatin (CDDP), and 5-fluorouracil (5FU) was evaluated in patients with advanced esophageal carcinomas. METHODS: Nedaplatin was administered at a dose of 80 or 100 mg/m2 with 500 ml of saline by slow drip infusion for 120 minutes on day 1. 5FU at a dose of 350 or 500 mg/m2 was mixed with 1,000 ml of saline and administered by continuous infusion for 24 hours on days 1 to 5. PATIENTS OR MATERIALS: This combination chemotherapy was tried in 17 patients with metastatic, recurrent, or bulky unresectable esophageal cancers. Of these, 15 evaluable patients received at least two courses of chemotherapy. RESULTS: The response rates in assessable and all patients were 60% and 52.9%, respectively. Cases with lymph node and liver metastases, as well as primary lesions, showed excellent response to the therapy with positive response rates of 54.5% (6/11), 100% (5/5) and 58.4% (7/12), respectively. The median response duration was 7 (range 3 to 37+) months for patients who achieved a partial response. Adverse drug reactions were limited to three cases of grade 3 toxicity, including allergy, and decreased hemoglobin and platelets, which were well tolerated by the patients. CONCLUSION: The present study thus indicated the combination chemotherapy of Nedaplatin and 5FU to be safe and efficacious for advanced esophageal cancer. Further investigations are clearly warranted.

Aged↗
PubMed1999

Involvement of agouti-related protein, an endogenous antagonist of hypothalamic melanocortin receptor, in leptin action.

To understand the role of agouti-related protein (AGRP), an endogenous antagonist of hypothalamic melanocortin receptor, in leptin action, we produced a full-length recombinant AGRP and examined its effect on the satiety effect of leptin. We also studied leptin's regulation of hypothalamic AGRP mRNA expression. A single intracerebroventricular (i.c.v.) injection of AGRP significantly increased cumulative food intake and body weight in a dose-dependent manner in rats. The leptin-induced inhibition of food intake and body weight was reversed by co-injection of AGRP in a dose-dependent manner. Hypothalamic AGRP mRNA expression was upregulated in leptin-deficient ob/ob mice and leptin receptor-deficient db/db mice and downregulated in lethal yellow agouti mice (KKAy mice) with hyperleptinemia. A single i.c.v. injection of leptin reversed the increased AGRP mRNA levels in ob/ob mice but not in db/db mice. In control mice and KKAy mice, AGRP mRNA expression was upregulated during fasting, when plasma leptin concentrations were decreased. No significant increase in AGRP mRNA expression was noted during fasting in control mice and KKAy mice treated with leptin. This study provides the first direct evidence that AGRP is a negative regulator of leptin action, and leptin downregulates hypothalamic AGRP production. Because leptin is shown to increase hypothalamic alpha-melanocyte stimulating hormone (alpha-MSH) production, our data suggest that its action via the hypothalamic melanocortin system is determined by the balance between the levels of its agonist and antagonist, alpha-MSH and AGRP.

Agouti-Related Protein↗
PubMed1999

Rhodopeptins (Mer-N1033), novel cyclic tetrapeptides with antifungal activity from Rhodococcus sp. I. Taxonomy, fermentation, isolation, physico-chemical properties and biological activities.

Five novel cyclic tetrapeptides, named rhodopeptin C1, C2, C3, C4 and B5, were isolated from a strain named Rhodococcus sp. Mer-N1033. They are a novel type of cyclic tetrapeptide composed of a beta-amino acid and three usual alpha-amino acids. Rhodopeptins show high in vitro antifungal activity against Candida albicans and Cryptococcus neoformans, whereas they show no activity against bacteria.

Animals↗
PubMed1999

Rhodopeptins, novel cyclic tetrapeptides with antifungal activities from Rhodococcus sp. II. Structure elucidation.

The structures of rhodopeptins, novel antifungal peptides, were determined on the basis of physico-chemical analyses of the intact molecules and their acid hydrolysates. The structures of rhodopeptins C1, C2, C3, C4 and B5 were determined to be cyclo (-Gly-L-Orn-L-Val-3-amino-10-methyldodecanoyl-), cyclo (-Gly-L-Orn-L-Ile-3-amino-10-methyldodecanoyl-), cyclo (-Gly-L-Orn-L-Val-3-amino-12-methyltridecanoyl-), cyclo (-Gly-L-Orn-L-Val-3-amino- 12-methyltetradecanoyl-) and cyclo (-Gly-L-Lys-L-Val-3-amino-13-methyltetradecanoyl-), respectively. They are novel cyclic tetrapeptides containing a lipophilic beta-amino acid.

Amino Acid Sequence↗
PubMed1999

Rhodopeptins, novel cyclic tetrapeptides with antifungal activities from Rhodococcus sp. III. Synthetic study of rhodopeptins.

Total syntheses of cyclo (-Gly-L-Lys-L-Val-(R)-3-aminododecanoyl-); LV9nA and its diastereomer cyclo (-Gly-L-Lys-L-Val-(S)-3-aminododecanoyl-); LV9nB, congeners of rhodopeptin B5 on beta-amino acid moiety, were achieved. The beta-amino acid moiety was prepared as a racemate by the thermal Michael addition of an amine to alpha,beta-unsaturated ester. The racemic beta-amino acids were converted to their L-Valylamide derivatives and the obtained diastereomers were separated. Coupling of both diastereomers, L-Val-beta-amino acids with Gly-L-Lys gave linear tetrapeptides, and tetrapeptides were cyclized by diphenylphosphoryl azide (DPPA) method between C-terminus of beta-amino acid and N-terminus of Gly to give cyclic tetrapeptides. The deprotected cyclic tetrapeptides, LV9nA and LV9nB, both exhibited almost the same antifungal activity as the naturally obtained rhodopeptins. Furthermore, comparison of the 1H NMR spectra of two congeners and rhodopeptin B5 suggested that the stereochemistry of beta-amino acid moiety in natural rhodopeptin B5 has (R)-configuration.

Antifungal Agents↗
PubMed1999

Stresgenin B, an inhibitor of heat-induced heat shock protein gene expression, produced by Streptomyces sp. AS-9.

Stresgenin B was isolated as an inhibitor of heat-induced heat shock protein (HSP) gene expression from a culture broth of Streptomyces sp. AS-9 by silica gel chromatography and HPLC. The molecular formula of the novel compound was determined as C11H13NO5 by high resolution FAB-MS analysis, and the structure was determined by UV, 1H NMR, 13C NMR, HMQC, HMBC, and NOESY spectra. Stresgenin B inhibited heat-induced luciferase reporter-gene expression directed by the human hsp70B promoter in Chinese hamster ovary (CHO) cells at concentrations lower than the concentrations for inhibition of dexamethasone-induced luciferase reporter-gene expression directed by the mouse mammary tumor virus (MMTV)-LTR promoter. The inhibition of heat-induced reporter gene expression was evident even when cells were exposed to stresgenin B only during heat stress treatment. Moreover, the compound inhibited heat-induced syntheses of hsp72/73, hsp90, and hsp110 and thereby suppressed the induction of thermotolerance. Stresgenin B showed moderate cytotoxic activities against several neoplastic cell lines and also showed antibacterial activities against Micrococcus luteus, Bacillus subtilis and Staphylococcus aureus strains.

Animals↗
PubMed1999

[Spontaneous peripelvic urine extravasation associated with ileocecal cancer: a case report].

A case of spontaneous peripelvic extravasation with ileocecal cancer is reported. A 60-year-old man with right flank pain was referred to our department. Dripinfusion pyelography showed right peripelvic extravasation. Neither computed tomography (CT) nor retrograde pyelography revealed any ureteral stones or tumors. Urinary cytology was negative. One month later, right retrograde pyelography demonstrated the filling defect in the right ureter, but no stones, ureteral tumors or other tumors related to the ureter were detected by CT. An exploratory laparotomy was done. We found an ileocecal tumor invading to the right ureter and disseminated to the peritoneum. Histological diagnosis was mucinous carcinoma.

Adenocarcinoma, Mucinous↗
PubMed1999

[Valve replacement in children].

Between May 1979 and September 1998, 202 children underwent surgical treatment for valvular heart disease. Of these 23, who ranged in age from 25 days to 15 years, underwent valve replacement, including 1 reoperation. The valve replacement consisted of the aortic valve in 5 patients, the mitral valve in 3, the tricuspid valves in 9, including 5 systemic atrioventricular valves for atrioventricular discordance, the pulmonary valve in 6, 5 bioprostheses and 18 mechanical prostheses. There were 4 operative deaths, 1 hospital death and 3 late deaths. At the 10-years follow-up, the actual survival rate was 67.8%, the event free rate was 76.1% and the freedom from reoperation rate was 86.2%. Valve re-replacement was performed in only 1 patient due to a thrombosed tricuspid valve. These results suggest that there is a small risk of major complications and reoperation in children who undergo valve replacement, whether a bioprosthetic valve or a mechanical valve. The long-term results of younger patients should be followed more closely according to their growth.

Adolescent↗
PubMed1999

[Interventional radiology for recurrent cancer].

The indications for the reoperative treatment for postoperative recurrence of cancer in the field of gastroenterology are usually limited. Interventional radiology (IVR), which is less invasive and effectively enhances the quality of life, will play an important role in the treatment of patients with postoperative recurrent cancer. This paper evaluate IVR as a therapeutic strategy for postoperative recurrent cancer in gastroenterology based on our experience. Metallic stents have proven useful for stenosis of the alimentary tract due to recurrence after surgery for esophageal or gastric cancer and for jejuno-biliary anastomotic stenosis caused by postoperative recurrent bile duct cancer. Segmental Lipiodol TAE is more effective and result in better cumulative survival rates than conventional TAE in the treatment of postoperative recurrence of hepatoma.

Bile Duct Neoplasms↗
PubMed1999

[Vitamins in pregnancy].

Vitamins are essential for the growth and normal function of human body. There are very few reports on vitamin A deficiency in pregnant women and newborn. Vitamin B complex includes various fractions essential to proper nutrition. The absence of vitamin C results Barlow disease in newborn. Vitamin D, the antirachitic Vitamin, is of great importance in safeguarding the mother and fetus from its relation to calcium and phosphorus metabolism. Vitamin E is also useful for the treatment of toxemia of pregnancy, intra-uterine growth retardation (IUGR), and neonatal jaundice. Vitamin K is well known for the protection of neonatal hemorrhage. The 6th recommended dietary allowances for Japanese in 1999 is shown in the table.

Female↗
PubMed1999

[Antiangiogenic and antitumor effect of BPHA, an orally-active matrix metalloproteinase inhibitor, in in vivo murine and human tumor model].

We examined the antiangiogenic and antitumor efficacy of a newly-developed matrix metalloproteinase (MMP) inhibitor, BPHA (N-biphenyl sulfonyl-phenylalanine hydroxiamic acid). BPHA potently inhibits MMP-2, 9 and 14 but not MMP-1, 3 or 7. In contrast, (-)BPHA, an enantiomer of BPHA, was inactive against all MMP tested. Daily oral administration of BPHA in mice resulted in potent inhibition of tumor-induced angiogenesis, primary tumor growth and liver metastasis, whereas (-)BPHA did not. These results demonstrate that selective MMP inhibition is correlated with antiangiogenic and antitumor efficacy and that the selective MMP inhibitor BPHA has therapeutic potential without hematotoxic effect or loss of body weight.

Animals↗
PubMed1999

Role of nuclear lamins in nuclear segmentation of human neutrophils.

Nuclear breakdown leading to the formation of apoptotic bodies has been postulated to involve degradation of nuclear structural proteins, such as lamins A/C and B. Although nuclear segmentation occurs during the maturation of polymorphonuclear leukocytes (neutrophils), its mechanism is not known. We found that human neutrophils have lamin B but lack lamins A/C while mononuclear cells possess all three types of lamin as assessed by immunoblotting. Differentiation of human promyelocytic HL-60 cells into neutrophil-like cells was also accompanied by the down-regulation of lamins A/C but not of lamin B. Moreover, when compared with normal cells, neutrophils with the Pelger-Huët anomaly of nuclear hyposegmentation exhibited significantly lower activity of caspase-6, a lamin A/C-cleaving enzyme. Differentiated HL-60 cells showed higher activity of caspase-6 than that of untreated cells. These observations allow us to speculate that remodeling of nuclear lamins might underlie the mechanism for nuclear segmentation of neutrophils.

Apoptosis↗
PubMed1998

Phospholipase C-independent group I metabotropic glutamate receptor-mediated inward current in mouse purkinje cells.

The mGluR agonist 1S,3R-ACPD induces a potent excitatory inward current in various central neurons, but the underlying mechanism is not fully understood. Thus, we explored the signal transduction mechanism underlying the 1S,3R-ACPD-induced inward current in mouse cerebellar Purkinje cells. Iontophoretic application of 1S,3R-ACPD produced a group I mGluR antagonist-sensitive inward current. This current closely resembled a slow synaptic inward current evoked by repetitive stimulation of parallel fibers. Although phosphoinositide hydrolysis is shown to be coupled with group I mGluRs, we found that intracellular injections of various PLC inhibitors and an IP3 receptor antagonist heparin only partially inhibited the 1S, 3R-ACPD-induced current. Moreover, intracellular injection of the Ca2+ chelator BAPTA or a selective Na+/Ca2+ exchange inhibitor KB-R7943 affected slightly the inward current. In contrast, infusion of GDPbetaS and GTPgammaS markedly suppressed the 1S,3R-ACPD-induced current. These results suggest that activation of mGluR1 in mouse cerebellar Purkinje cells by 1S,3R-ACPD application or by repetitive stimulation of parallel fibres induces an inward current with a minor contribution from intracellular Ca2+ or Na+/Ca2+ exchange.

Animals↗