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Biomedical subjects

Y Ohi

Publications and source records attributed to Y Ohi.

At least 37 records · Page 2Linked to original sources
PubMed1999

Goserelin acetate with or without antiandrogen or estrogen in the treatment of patients with advanced prostate cancer: a multicenter, randomized, controlled trial in Japan. Zoladex Study Group.

OBJECTIVE: The aims of this randomized, controlled study were to investigate the efficacy and safety of long-term monotherapy with the luteinizing hormone-releasing hormone agonist goserelin acetate compared with both short- and long-term combined androgen blockade. METHODS: Patients with advanced prostate cancer (n = 371) were randomized to treatment with goserelin acetate alone or a combination of goserelin acetate plus either long-term or short-term antiandrogen (chlormadinone acetate) or short-term estrogen (diethylstilbestrol diphosphate). RESULTS: There were no significant differences between the treatment groups with respect to objective progression, overall survival or disease-specific survival. Nevertheless, subgroup analysis suggested that patients with minimal disease or a good prognosis might benefit more from combined androgen blockade than other patients. Combined androgen blockade significantly reduced the incidence of disease flare compared with goserelin acetate treatment alone. CONCLUSIONS: Neither short- nor long-term combined androgen blockade had a survival advantage over goserelin acetate alone.

Aged↗
PubMed1999

Ca2+ spark as a regulator of ion channel activity.

Ca2+ spark is a local and transient Ca2+ release from sarcoplasmic reticulum (SR) through the ryanodine receptor Ca2+-releasing channel (RyR). In cardiac myocytes, Ca2+ spark is an elementary unit of Ca2+-induced Ca2+ release (CICR) by opening of RyR(s) in junctional SR (jSR), which is triggered by Ca2+-influx through L-type Ca2+ channels to the narrow space between a transverse tubule and jSR. Ca2+ spark has, therefore, been described as the evidence for "the local control of excitation-contraction coupling". In contrast, Ca2+ sparks in smooth muscle have been reported in relation to Ca2+-dependent K+ (K(Ca)) channel activation and muscle relaxation. A spontaneous Ca2+ spark in a superficial area activates 10-100 K(Ca) channels nearby and induces membrane hyperpolarization, which reduces Ca2+ channel activity. In several types of smooth muscle cells, which have relatively high membrane excitability, an action potential (AP) elicits 5-20 Ca2+ hot spots (evoked sparks with long life) in the early stage via CICR in discrete superficial SR elements and activates K(Ca)-channel current highly responsible for AP repolarization and afterhyperpolarization. CICR available for contraction may occur more slowly by the propagation of CICR from superficial SR to deeper ones. The regulatory mechanism of ion channel activity on plasma membrane by superficial SR via Ca2+ spark generation in smooth muscle cells may be analogously common in several types of cells including neurons.

Action Potentials↗
PubMed1999

Activation and the interaction of proapoptotic genes in modulating sensitivity to anticancer drugs in gastric cancer cells.

Taxotere (Docetaxel) is a novel microtubulin inhibitor which is currently in phase II/III clinical trial. We found that the sensitivity to taxotere was correlated with apoptotic cell death determined by the internucleosomal DNA ladders in gastric cancer cell lines. The treatment of taxotere activated proapoptotic genes such as bcl-Xs and bax genes. The relationship between the mRNA induction of bcl-Xs and bax genes and the internucleosomal DNA ladders by taxotere was significant, respectively (p<0.05). The introduction of bcl-Xs gene into MKN45 gastric cancer cells increased the sensitivity to VP-16 and taxotere 2-3-fold in the IC50 values, whereas the introduction of bax gene increased the sensitivity to CDDP, VP-16 and taxotere 2-5-fold in the IC50 values, as compared to that of the Neo-transfected MKN45 cells. The mRNA overexpression of bax gene was found in the bcl-Xs-transfected cells. Likewise, the mRNA overexpression of bcl-Xs gene was also found in the bax-transfected cells. These results indicate that the activation of bcl-2 family genes such as bcl-Xs and bax plays a crucial role in modulating apoptotic cell death in the sensitivity to anticancer drugs, and suggest that these proapoptotic genes might interact in the up-regulation for activating downstream signals leading to apoptosis in gastric cancer cells.

Antineoplastic Agents↗
PubMed1999

Comparative study of single-dose and three-day therapy for acute uncomplicated cystitis.

To assess the efficacy and safety of a single-dose therapy for acute uncomplicated cystitis (AUC), we compared 4 treatment regimens in 120 women. Patients eligible for the study were randomly assigned to one of four treatment groups: Ciprofloxacin (CPFX) 200 mg in a single oral dose (group A); 200 mg once daily for 3 days (group B); 200 mg twice daily for 3 day (group C); and cefpodoxime-proxcetil (CPDX-PR) 200 mg once daily for 3 days (group D). The efficacy was evaluated 3 days after the single-dose therapy or at the end of a three-day therapy according to the criteria proposed by the Japanese UTI Committee. The overall clinical efficacy in a total of 107 patients was evaluated to be excellent, moderate, and poor in 72 (67.3%), 35 (31.8%), and 1 (0.9%), respectively. The causative organisms were eradicated in 88.0, 85.2, 85.2, and 82.1% of the patients in groups A, B, C, and D, respectively. Recurrence was identified in 3 (2 in group A and one in group D) of 16 patients who were followed at 2 to 3 weeks after the treatment. No adverse reactions related to the antibiotics were recognized in the study. There were no significant differences in the clinical efficacy or recurrence rate among these four treatment regimens. These results indicate that the single-dose therapy of CPFX is the treatment of choice in women with AUC.

Acute Disease↗
PubMed1999

[Spontaneous rupture of renal cell carcinoma: a case report].

A 74-year-old man with severe right flank pain and hypochondralgia, was admitted to a hospital where he was found to have an abnormality of the right kidney on computed tomographic (CT) scan. He was referred to our department for further examination and treatment on the next day. Spontaneous rupture of the right renal cell carcinoma was mostly suspected from preoperative clinical findings obtained by ultrasonography. CT scan and angiography. Extravasation was not recognized on angiography. We chose emergent transcatheter arterial embolization prior to radical nephrectomy. The surgical specimen contained a solid and yellowish mass invading into the renal pelvis. Subcapsular rupture was identified. Histopathological diagnosis was renal cell carcinoma consisting of invasive growth of highly atypical epithelial cells with a sarcomatous pattern, and the tumor cells were present in the renal pelvis. He died of lung cancer 26 months after the operation.

Aged↗
PubMed1999

A phase II trial of low dose administration of 5-fluorouracil and cisplatin in patients with advanced and recurrent gastric cancer.

The clinical efficacy of chemotherapy for patients with advanced gastric cancer has not been established. We investigated in a phase II study the combination chemotherapy of low dose 5-fluorouracil (5-FU) and cisplatin (low dose FP) to evaluate its clinical efficacy in terms of response, quality of life and survival in 43 gastric cancer patients including 29 advanced and 14 recurrent cases. The administration of 5-FU was done by continuous intravenous infusion for 28 consecutive days with a dose of 250 mg/m2, while the administration of cisplatin was done by 1-h intravenous drip-infusion for 5 consecutive days and 2-day intervals per week with a dose of 3.5 mg/m2, that was repeated for 4 weeks in one cycle. The response rate in advanced cases was 48.3%, evaluated in 14 cases of partial response (PR), whereas its response rate in recurrent cases was 35.7%, evaluated in 5 cases of PR. The most effective lesions for low dose FP chemotherapy were primary lesion and lymph node metastasis. The quality of life assessed by performance status and oral intake was improved in 13.8% and 37.9% of advanced cases, and 21.4% and 28.6% of recurrent cases, respectively, as compared to those of pretreatment. The median survival time and 1-year survival rate were 6 months, 21.6% in advanced cases and 10 months, 28.8% in recurrent cases, respectively. The major adverse effect was observed in gastrointestinal toxicity and leukopenia, and the all toxicities were less than grade 2, that were controllable during the treatment. These results indicated that the combination chemotherapy of low dose administration of 5-FU and cisplatin might have therapeutic efficacy in tumor response and offer improvement in quality of life in patients with advanced and recurrent gastric cancer.

Adult↗
PubMed1998

Ca2+ images and K+ current during depolarization in smooth muscle cells of the guinea-pig vas deferens and urinary bladder.

1. Electrical events and intracellular calcium concentration ([Ca2+]) imaged using fluo-3 and laser scanning confocal microscopy were simultaneously monitored in single smooth muscle cells freshly isolated from guinea-pig vas deferens or urinary bladder. 2. Images obtained every 8 ms, during stepping from -60 to 0 or +10 mV for 50 ms under voltage clamp, showed that a rise in [Ca2+] could be detected within 20 ms of depolarization in five to twenty small (< 2 micrometer diameter) 'hot spots', over 95 % of which were located within 1.5 micrometer of the cell membrane. Depolarization at 30 s intervals activated hot spots at the same places. 3. Cd2+ or verapamil abolished both hot spots and Ca2+-activated K+ current (IK,Ca). Caffeine almost abolished hot spots and markedly reduced IK,Ca. Cyclopiazonic acid, which raised basal global [Ca2+], decreased the rise in hot spot [Ca2+] and IK,Ca amplitude during depolarization. These results suggest that Ca2+ entry caused Ca2+-induced Ca2+ release (CICR). 4. Under voltage clamp, hot spot [Ca2+] closely paralleled the rise in IK,Ca and reached a peak within 20 ms of the start of depolarization, but the rise in global [Ca2+] over the whole cell area was much slower. Step depolarization to potentials positive to -20 mV caused hot spots to grow in size and coalesce, leading to a rise in global [Ca2+] and contraction. Ca2+ hot spots also occurred during the up-stroke of an evoked action potential under current clamp. 5. It is concluded that the entry of Ca2+ in the early stages of an action potential evokes CICR from discrete subplasmalemma Ca2+ storage sites and generates hot spots that spread to initiate a contraction. The activation of Ca2+-dependent K+ channels in the plasmalemma over hot spots initiates IK,Ca and action potential repolarization.

Action Potentials↗
PubMed1998

A long-term surviving patient with cancer of papilla of Vater after local resection.

We report successful local resection for cancer of papilla of Vater in an 86-year-old woman. She was referred to our hospital because of right hypochondralgia. Abdominal ultrasonography and computed tomography showed marked dilatation of the common bile duct (CBD). Endoscopic retrograde cholangiography disclosed a small shadow defect in the terminal of the dilated CBD. Biopsy of the papilla revealed well-to-moderately differentiated adenocarcinoma. Considering her extreme old age and keeping in mind her quality of life after the operation, and the finding that the tumor was localized within the papilla and highly differentiated, we performed local resection. In addition, the intrapancreatic portion of the CBD and part of the main pancreatic duct (MPD) were further resected to secure a negative margin, confirmed by frozen section. The MPD was reapproximated to the duodenal mucosa and a choledocho-duodenostomy was performed for CBD reconstruction. Histopathological examination showed the tumor was papillary adenocarcinoma, 10 x 15 mm in size; there was no invasion beyond the sphincter of Oddi, it had partly infiltrated the CBD, but had not invaded to the pancreas or duodenum. The patient's postoperative course was not eventful and she has had good quality of life for the past 6 years since the operation, without any evidence of recurrence. Although radical pancreaticoduodenectomy is now the standard procedure in patients with malignant tumor of the papilla of Vater, local resection is a reasonable alternative for high-risk patients with highly differentiated, apparently localized carcinomas.

Adenocarcinoma↗
PubMed1998

A new treatment for penile conservation in penile carcinoma: a preliminary study of combined laser hyperthermia, radiation and chemotherapy.

OBJECTIVE: To investigate the role of laser hyperthermia in penis-conserving therapy for penile carcinoma. PATIENTS, MATERIALS AND METHODS: Penile carcinoma KPK-1 cells were transplanted into nude mice to induce tumour; the effects of laser hyperthermia, the chemotherapeutic agent peplomycin, or their combination on the inhibition of KPK-1 tumour growth were assessed. In a clinical study, two patients with well-differentiated, stage T2 penile tumours with corporeal involvement were treated to conserve the penis using concurrent radiation, laser hyperthermia and peplomycin. They had no pathologically identified regional lymph node metastasis. Radiation was given for 5 days a week for 3 weeks at a total dose of 30 Gy. Nd:YAG laser hyperthermia was administered at 42-43 degrees C for 15 min twice a week for 3 weeks immediately after radiation. Peplomycin (10 mg per day) was administered intravenously over 24 h together with the laser hyperthermia. RESULTS: The combined treatment with laser hyperthermia and peplomycin completely inhibited KPK-1 tumour growth, but the treatment with either laser hyperthermia or peplomycin alone had little effect. The results were also corroborated by the histopathological findings; the necrotic area in mice treated with combined therapy was much larger than that in those treated with laser hyperthermia alone. Both patients given combined laser hyperthermia, radiation and peplomycin were treated successfully, with the penis and sexual function conserved, and both survived for > 7 years with no evidence of any local or regional recurrence. There were no major complications related to the combined treatment. CONCLUSIONS: This preliminary study showed that combined treatment with laser hyperthermia, radiation and peplomycin might be a promising therapy for conserving the penis in some patients with stage T2 penile tumours.

Animals↗
PubMed1998

Endoscopic treatment of refractory filarial chyluria: a preliminary report.

PURPOSE: We report our experiences treating 5 patients who had filarial chyluria using an endoscopic approach. MATERIALS AND METHODS: Two men and 3 women 47 to 83 years old with chyluria were treated with endoscopic coagulation using guide tube methods. Intrarenal pelvic instillation of silver nitrate was not effective in 4 patients and catheterization was impossible in 1. RESULTS: The responsible lesion was successfully coagulated in all 5 patients. Because the lesion was in the ruptured portion of the caliceal fornix, we thought that chyluria had arisen in the fragile portion of the fornix (fistulization). After endoscopic treatment there was no recurrence in any patient. CONCLUSIONS: Endoscopy is effective and minimally invasive therapy for filarial chyluria.

Aged↗
PubMed1998

The expression of thymidine phosphorylase/platelet-derived endothelial cell growth factor is correlated to angiogenesis in breast cancer.

It has been shown that human thymidine phosphorylase (TP) is identical to platelet-derived endothelial cell growth factor and has angiogenic activity. In the present study, the expression of TP was examined in 139 mammary carcinomas and 35 benign mammary disorders using biochemical and immunohistochemical methods. Moreover, in order to evaluate the significance of TP expression in mammary carcinomas, the relationship between vascular density and various clinicopathological factors, including age and menopausal status of patients with a mammary carcinoma, were compared with the size, nodal status, expression of estrogen receptor (ER), progesterone receptor (PgR), c-erbB-2, p53 and TP of a mammary carcinoma. Thymidine phosphorylase expression increased in both the nuclei and cytoplasm of mammary carcinoma cells in comparison to mammary benign disorder cells. The number of microvessels in mammary carcinomas was generally correlated to the number of tumor cells with TP expression in cytoplasm. The number of cells with TP expression in cytoplasm was significantly large in tumors that measured 3-4 cm in diameter, compared with tumors measuring 1-2 and 5-6 cm in diameter. In mammary tumors of 1-4 cm diameter, TP expression and vessel density were significantly high in tumors negative for ER or positive for c-erbB2 and in tumors positive for TP or c-erbB2, respectively; whereas tumors of 5-6 cm in diameter were not modified by any clinicopathological factors. The results indicated that TP plays an important angiogenetic role in mammary carcinomas, especially tumors with a certain progression.

Adult↗
PubMed1998

Diffusion of piperacillin, cefotiam, minocycline, amikacin and ofloxacin into the prostate.

BACKGROUND: The successful treatment of bacterial prostatitis depends on an effective antimicrobial concentration in prostatic tissue against the infecting organism. In this study we compared the diffusion of 5 types of antimicrobials into the prostate. METHODS: The concentrations of piperacillin, cefotiam, minocycline, amikacin, and ofloxacin were determined in prostatic fluid, prostatic tissue, and serum 2.5 to 3 hours after a single administration from 55 patients with benign prostatic hypertrophy. RESULTS: Although amikacin showed the highest mean concentration both in prostatic tissue and prostatic fluid, the prostatic tissue/serum ratio was significantly higher (P < 0.01) for ofloxacin (1.49 +/- 0.80) and minocycline (0.94 +/- 0.39) compared with those for amikacin (0.49 +/- 0.21) and piperacillin (0.21 +/- 0.15). Also, the prostatic fluid/serum ratio was lower than the prostatic tissue/serum ratio for each drug, however, the prostatic fluid/serum ratio of ofloxacin was significantly higher than that of other antimicrobials tested (P < 0.01). CONCLUSION: These results support earlier studies demonstrating that fluoroquinolones are a useful class of antimicrobials for the treatment of chronic bacterial prostatitis. They also suggest that in view of the pharmacokinetic properties and antimicrobial activities, amikacin and minocycline may be alternate antimicrobial options for selected patients with bacterial infections of the prostate.

Aged↗
PubMed1997

Sphingosine induces apoptosis in androgen-independent human prostatic carcinoma DU-145 cells by suppression of bcl-X(L) gene expression.

Our recent studies have suggested that sphingosine, an endogenous protein kinase C (PKC) inhibitor, may mediate apoptosis induced by a phorbol ester (PMA) in human promyelocytic leukemia HL-60 cells [Ohta et al. Cancer Res. 1995;55:691-697], and that the apoptotic induction by both PMA and sphingosine is accompanied by down-regulation of bcl-2, a gene which acts to prevent apoptotic cell death [Sakakura et al. FEBS Lett. 1996;397:177-180]. In this study, we examined the sphingosine-induced apoptosis of the androgen-independent human prostatic carcinoma cell line DU-145, which expresses bcl-X(L) and Bax but not bcl-2, and found that treatment of DU-145 cells with sphingosine suppressed bcl-X(L) in both mRNA and protein levels but did not change bax expression at all. In contrast, in apoptotic cells treated with a PKC inhibitor, staurosporine, no effect on bcl-X(L) or bax expression was observed. The initial metabolites of sphingosine in the cells, ceramide and sphingosine 1-phosphate, failed to induce apoptosis. These results indicate that, in DU-145 cells, sphingosine, but not its metabolites, induces apoptosis through down-regulation of bcl-X(L), independently of PKC inhibition. Our present results, together with previous observations, strongly suggest that apoptosis regulatory genes differ according to cell type and apoptosis induction through sphingosine is accompanied by inhibition of either bcl-2 or bcl-X(L) activity in these cells.

Androgens↗
PubMed1997

Identification of the replication region of the Lactobacillus acidophilus plasmid pLA106.

The complete nucleotide sequence of plasmid pLA106 (2862 bp) from Lactobacillus acidophilus TK8912 was determined. Based on this sequence, the location of the genes for mobilization-plasmid recombination protein (mob), replication origin (ori), transcriptional repressor protein (repA) and replication initiation protein (repB) were predicted. Deletion analysis showed that the 1.4-kb PstI-EcoRV fragment carrying the ori, repA and repB genes is able to replicate in Lactobacillus and Escherichia coli cells. The plasmid pLA106 appears to have most features of the pLS1/pE194 plasmid family.

Amino Acid Sequence↗
PubMed1997

Metanestin, a glycoprotein with metastasis-associated expression in transitional cell carcinoma of the urinary bladder.

A 60-kDa glycoprotein named metanestin was identified by molecular cloning. The glycoprotein had a twice-repeated motif of Pro-Gly-Pro-Gly and carried metastasis-associated carbohydrate epitopes. The antibody to the protein portion of metanestin strongly reacted with lymph-node metastasis of transitional-cell carcinoma of the urinary bladder, but the reactivity to the primary tumor was generally weaker and the normal urothelium was scarcely reactive. Thus both metanestin and the carbohydrate on it showed metastasis-associated expression. In addition, we identified a 100-kDa glycoprotein with a 4-times-repeated motif of Pro-Ala-Pro-Ala. The antibody to the 100-kDa glycoprotein showed reactivity similar to that to metanestin.

Amino Acid Sequence↗