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Biomedical subjects

M Ohtani

Publications and source records attributed to M Ohtani.

At least 109 records · Page 6Linked to original sources
PubMed1997

[Evaluation of urinary NMP22 (nuclear matrix protein 22) as a diagnostic marker for urothelial cancer--screening for urothelial cancer in patients with microscopic hematuria. NMP Study Group].

This study was undertaken to determine the clinical usefulness of NMP22 (Nuclear Matrix Protein 22) as a urinary marker for the screening of urothelial cancer in patients with microscopic hematuria, especially in comparison with that of voided urine cytology. Urinary NMP22 values were determined for 183 patients with microscopic hematuria by use of a UNMP22 Test kit, which is based on an enzyme-linked immunosorbent assay. All patients were entered in this study before cystoscopy was performed, and were evaluated for NMP22 values and voided urine cytology simultaneously from the same urine samples. Of the 183 patients with microscopic hematuria, 14 cases of urothelial cancer were detected. For the other cases, 65 were of benign diseases and 104 were designated NED (No Evidence of Disease). The median NMP22 values for urothelial cancer, benign diseases, and NED were 26.5 U/ml (95% CI: 18.5-228.2; 4.9 U/ml (95% CI: 3.6-8.3), and 5.9 U/ml (95% CI: 4.8-6.5), respectively. The urinary NMP22 value for urothelial cancer was significantly higher than for benign diseases and NED. When the cut-off value of urinary NMP22 was set at 12 U/ml, the positive rate of NMP22 for urothelial cancer was 85.7%, significantly higher than the 50% positive rate by voided urine cytology. This study indicates that urinary NMP22 is a useful tool for the screening of urothelial cancer in patients with microscopic hematuria.

Adult↗
PubMed1997

[Chronic myelogenous leukemia received unrelated bone marrow transplantation following surgical resection of cerebral arteriovenous malformation--first case report].

We report a 15-year-old boy with chronic myelogenous leukemia who received unrelated bone marrow transplantation (uBMT) after surgical resection of cerebral arteriovenous malformation (AVM). The incidence of cerebral hemorrhage caused by rupture of cerebral ABM in cases of BMT is uncertain. However, since the risk of rupture of AVM was supposed to increase due to both severe thrombocytopenia after intensive chemotherapy and increased intracranical pressure because of total body irradiation (TBI) as preconditioning therapy for BMT, we have first carried out surgical resection of the cerebral AVM, and subsequently performed uBMT. This resulted in a favorable clinical course without serious complications.

Adolescent↗
PubMed1996

Synthesis and phospholipase A2 inhibitory activity of thielocin B3 derivatives.

We prepared several types of derivatives of thielocin B3, a very potent naturally occurring inhibitor for human nonpancreatic secretory PLA2 (sPLA2-II), and conducted a structure-activity relationship study to identify potent sPLA2-II inhibitors with the aim of developing antiinflammatory drugs. The total number of aromatic rings is critical for sPLA2-II inhibition, and the best result was obtained in the case of six rings. The structure of the central part of the inhibitors was not specific, and potent inhibitors were found among the sulfide, sulfone, ether, methylene, and amino derivatives. Although a diester of the terminal carboxylic acid lost its inhibitory activity, having both of the carboxylic acids was not necessary for expression of activity, as illustrated by a glycine derivative with the benzyl ester group 36. Among the newly synthesized derivatives, 18, 20, 29, and 36 showed very potent human sPLA2-II inhibitory activity comparable to that of natural thielocin B3. Their IC50 values are in the range 0.069-0.14 microM, and they are a class of compounds showing the most potent sPLA2-II inhibition to date.

Benzhydryl Compounds↗
PubMed1996

Potent inhibitors of secretory phospholipase A2: synthesis and inhibitory activities of indolizine and indene derivatives.

Phospholipase A2 is an enzyme which hydrolyzes the sn-2 position of certain cellular phospholipids. The liberated lysophospholipid and arachidonic acid are precursors in the biosynthesis of various biologically active products. As human nonpancreatic sPLA2 is present in high levels in the blood of patients in several pathological conditions, the potent sPLA2 inhibitors have been suggested to be useful drugs. Here we describe the synthesis, structure-activity relationship, and inhibitory activities of indolizine and indene derivatives. 1-(Carbamoylmethyl)indolizine derivatives and 1-oxamoylindolizine derivatives exhibited very potent inhibitory activity. The former was unstable to air oxidation, but the latter exhibited an improvement both in stability and in potency. Some compounds approached the stoichiometric limit of the chromogenic assay.

Alkylation↗
PubMed1996

Oxamflatin: a novel compound which reverses malignant phenotype to normal one via induction of JunD.

In the course of screening for inhibitors of tumorigenic phenotype of K-ras-transformed NIH3T3 cells (DT cells), we found a novel compound, oxamflatin, an aromatic sulfonamide hydroxamate derivative, which induces flat phenotype in these cells and suppresses their anchorage-independent growth. In contrast to DT cells, in v-raf-transformed NIH3T3 cells, no change in their morphology and no specific inhibition of their anchorage-independent growth was observed. Interestingly, oxamflatin was effective to NIH3T3 cells transformed by constitutively activated mutant of MEK, indicating the possibility that oncogene-induced morphological change is not necessarily induced by common signaling pathway such as MAP kinase cascade. In oxamflatin-treated DT cells, the expression of transcription factor junD was highly augmented, resulting in trans-activation of fibronectin gene by junD via cyclic AMP responsive element in its promoter. This behavior of junD was confirmed to correlate well with partial blocking of malignant phenotype in DT cells. Thus, oxamflatin can be categorized as the first reagent which induces genes whose products can interfere with oncogene-dependent transformation.

3T3 Cells↗
PubMed1996

Immunohistochemically-determined changes in the distribution of insulin-like growth factor-I (IGF-I) and epidermal growth factor (EGF) in the bovine endometrium during the estrous cycle.

The aims of this study were to investigate whether there are cell-specific distributions of insulin-like growth factor I (IGF-I) and epidermal growth factor (EGF) in the endometrium, and to determine whether or not the expression of these factors varies with the stage of the estrous cycle. Fifty-four endometrial biopsy specimens were collected from normal cycle Holstein-Friesian heifers. The endometrial specimens were divided into nine groups (at least five different animals per group) corresponding to the following days of the cycle: days 20-0, 1-3, 4-5, 6-7, 8-10, 11-13, 14-15, 16-17, and 18-19 (day 0 = estrus). IGF-I and EGF were localized by immunohistochemistry in the intact heifer endometrium throughout the estrous cycle. Throughout the estrous cycle, IGF-I was localized in the luminal epithelium and stroma with a little staining in the glandular epithelium (P < 0.01). In the luminal epithelium, the number of IGF-I-positive cells increased on days 1-3, 6-7, 11-13, and 16-17. In the stroma, the number of IGF-I-positive cells increased on days 8-10 and 20-3. The number of positively stained cells in the glandular epithelium increased around the estrous period. EGF stained intensely in the stroma but very little in the luminal and glandular epithelia (P < 0.01). In the stroma, three peaks in the number of EGF-positive cells were observed: on days 1-3, 6-7, and 11-13. These results demonstrate cyclical changes in the endometrial cell types localization of IGF-I and EGF.

Animals↗
PubMed1996

Chemical modification of PA-48153C, a novel immunosuppressant isolated from Streptomyces prunicolor PA-48153.

5beta-Methoxy (20), 14-methyl (24), 14,14-dibromo-15-nor (25), 8-O-acyl (26-45), 8-O-alkyl (46), 8-O-alkoxycarbonyl (47, 48), and 8-O-carbamoyl (49) derivatives of PA-48153C, a novel immunosuppressant isolated from fermentation products of Streptomyces prunicolor PA-48153, were prepared. These compounds were found to retain the inhibitory activity on the responses of both T and B cells to mitogens. Among them, the C-8 hexanoate 28 showed potent suppressive effects on mitogen responses with less cytotoxicity to EL4 cells and was selected for in vivo evaluation.

Animals↗
PubMed1996

[Perioperative fractionated high dose rate brachytherapy in bone and soft-tissue tumors].

The 13 lesions of 11 patients with bone and soft-tissue tumors (four primary and nine recurrent lesions) were treated with surgery and postoperative fractionated high dose rate (HDR) brachytherapy started on the 6-7th day after surgery. The total dose was 40-50 Gy/7-10 fr/6-7d(bid) at 5 mm from the source. Local control was achieved in eight of 13 lesions (62%). Four of the five uncontrolled lesions had macroscopic residual tumor after the surgery. There was one peripheral nerve damage as a side effect. This study indicates that the use of perioperative fractionated HDR brachytherapy is feasible and well tolerated.

Adolescent↗
PubMed1996

[Usefulness of contrast-enhanced CT of the peritoneum to evaluate efficacy of neoadjuvant chemotherapy for peritoneal dissemination in an advanced gastric cancer case].

We performed contrast-enhanced CT before and after chemotherapy in a patient with advanced gastric cancer to assess the efficacy of neoadjuvant chemotherapy for peritoneal dissemination. The patient was preoperatively given combined chemotherapy with UFT and CDDP. Hepatic metastatic and peritoneal disseminated foci were markedly reduced on CT. Thus CT proved to be useful for assessing peritoneal dissemination and the efficacy of neoadjuvant chemotherapy.

Aged↗
PubMed1995

A case of secondary syphilis with mucous patches on the hard palate.

A rare case of secondary syphilis showing mucous patches on the hard palate is reported. A 31-year-old male had two erosive patches which were slightly raised on his hard palate. A linear lesion was also present on the inside of his right alveolar process. Many red-brown macules on his abdomen and bilateral inguinal lymphadenopathy accompanied these symptoms. The serological tests for syphilis were positive: VDRL test 1:512, TPHA test 1:20,480, and IgM-FTA-ABS test 1:40. Immunohistochemical staining with rabbit monoclonal antibody to Treponema pallidum by the biotin-streptoavidin system detected treponemal organisms in the paraffin-embedded specimen from his mucous patch. A diagnosis of secondary syphilis was made, and he was given amoxicillin (AMPC) at 750 mg per day for 4 weeks. His eruptions, including the mucous patch, healed in a week.

Adult↗
PubMed1995

Radiographic changes following radiotherapy in the patients with lung cancer. Is the irradiated area of the mediastinum in the simulation film a significant factor?

BACKGROUND: Radiation induced lung injury is an ominous adverse reaction in the management of thoracic disease by radiation therapy. Although the importance of the area of irradiated lung is well known, the irradiated area of mediastinum is little to be considered in the routine treatment. PURPOSE: To evaluate the significance of the irradiated area of the mediastinum in the simulation film for radiation induced lung injury. PATIENTS AND METHODS: A total of 208 patients with primary lung cancer treated with radiation therapy were analyzed for incidence of radiation induced lung injury. Lung injury was defined as the appearance of an abnormal shadow on the chest radiograph. CT images were used to differentiate recurrence or other conditions. Age, sex, irradiation dose, irradiated lung area, T and N factors of the tumor, irradiated mediastinum area, performance status of patients, location of irradiated fields and use of chemotherapy were analyzed with Cox's multivariate regression model. RESULTS: The cumulative rate of radiation induced lung injury at 12 months was 85%. Significant factor of radiation induced lung injury was irradiated area of the mediastinum (p = 0.03). Irradiated area of the lung (p = 0.18, n.s.), total tumor dose (p = 0.1, n.s.), use of chemotherapy (p = 0.08, n.s.) and location of irradiated field (p = 0.08, n.s.) may also have an effect on radiation induced lung injury. CONCLUSION: The irradiated area of the mediastinum is one of the significant factors in radiation induced lung injury.

Adult↗
PubMed1995

[Local chemotherapy by a sustained-release preparation with fibrin seal against the operative wound in head and neck cancer].

Fibrin seal has been used for hemostasis and sealing in operative field of tumors in the head and neck. The authors applied it for drug preparation and tried a local chemotherapy to treat residual and disseminated tumors of cellular level in the operative wound using 5-FU. The drug release rate in this therapy in vitro study was 50% after 24 hrs. When injected to rats bearing Yoshida sarcoma, it exhibited a marked antitumor effect compared to the control group given 5-FU alone. This therapy is easy to make the dosage adjustment and can apply drugs directly to the tumor residue at the high concentration. It will be clinically a useful adjuvant therapy for radiotherapy, surgery or chemotherapy.

Animals↗
PubMed1995

Comparative analysis of buprenorphine- and norbuprenorphine-induced analgesic effects based on pharmacokinetic-pharmacodynamic modeling.

The relationships between plasma or brain concentrations and analgesic effects of both buprenorphine (BN) and an active metabolite, norbuprenorphine (NBN), were investigated in rats. Maximal analgesic effects measured by a tail flick test were obtained at 10 and 30 min after intravenous (i.v.) administration of BN (8 micrograms/kg dose) and NBN (100 micrograms/kg dose), respectively. No correlation was observed between analgesic effect and the early plasma BN or NBN concentrations. However, at latency times, the concentration of BN in the plasma, cerebellum and the rest of the brain (including the brainstem, midbrain and cerebrum) was related in a counterclockwise hysteresis fashion to analgesia. There was no relationship between the estimated specific binding concentration of BN in the brain and the analgesic effects. After i.v. administration of BN or NBN, the analgesic effect of NBN was approximately one-fiftieth that of BN. The n-octanol/water partition coefficient of NBN was one-tenth that of BN. Further, the results of intraventricular administration of each drug suggested that the intrinsic analgesic activity of NBN was one-fourth that of BN. From these findings, we conclude that the remarkably weak pharmacological effect of NBN after i.v. administration may be due not only to the low permeability of NBN into the brain but also to its small intrinsic pharmacological effect.

Analgesia↗
PubMed1995

Structure and action of MIP (Mytilus inhibitory peptide)-related tetrapeptides synthesized with a multipeptide synthesizer.

Using a multipeptide synthesizer we synthesized 19 peptide libraries, each of which consisted of 19 MIP-related tetrapeptides, and isolated a number of peptides, which have an inhibitory effect on phasic contraction of the ABRM of Mytilus, from the libraries. To the present, the structures of about 30 species of the peptides were determined, and the peptides with the determined structures were synthesized. The structure and action of each synthetic peptide was compared with those of others to explain structure-activity relationship of MIPs.

Amino Acid Sequence↗
PubMed1994

The effect of dose intensity on M-VAC therapy for advanced urothelial cancer.

M-VAC therapy (methotrexate, vinblastine, Adriamycin, and cisplatin) has improved the treatment results of urothelial cancer patients. However, it is sometimes complicated by drug toxicities, including bone marrow suppression. We analyzed the relative dose intensity in each patient undergoing M-VAC chemotherapy in relation to the chemotherapeutic effect and survival. In addition, the role of granulocyte colony-stimulating factor (G-CSF) in the dose intensity of M-VAC therapy was analyzed. Between June 1988 and March 1993, 29 patients with advanced urothelial cancer were treated with M-VAC therapy in our institution. Of 18 patients with evaluable lesions, 2 (11.1%) showed a complete response (CR) and 7 (38.9%) showed a partial response (PR), and the overall response rate was 50.0%. The median follow-up period for these 18 patients was 14.6 months and the median survival was 8.7 months, with 12 of the 18 patients being alive at the time of analysis. The relative dose intensity (RDI) for these 18 patients was 0.81 for methotrexate, 0.80 for vinblastine, 0.92 for Adriamycin, and 0.91 for cisplatin, for a mean RDI of 0.87. There was no correlation between the chemotherapeutic effect and the RDI. When we calculated the RDI for all 29 patients who underwent M-VAC therapy, G-CSF increased the RDI of Adriamycin significantly. The results of this retrospective study indicate that a dose intensity for M-VAC therapy in the range of 0.61-1.00 is unlikely to correlate with the chemotherapeutic effect, although G-CSF contributes to increasing the RDI of Adriamycin.

Adenocarcinoma↗