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Biomedical subjects

M Takami

Publications and source records attributed to M Takami.

At least 55 records · Page 3Linked to original sources

A possible involvement of thromboxane A2 and peptide leukotrienes in hyperresponsiveness of Sephadex-treated rat lung parenchyma.

An augmented contraction and elevated thromboxane (TX) B2 release were observed, when the isolated parenchyma from Sephadex-treated rats was stimulated by 5-hydroxytryptamine (5-HT). Release of peptide leukotrienes (pLTs) was also increased by the stimuli. In the Sephadex-induced hyperresponsiveness model, DP-1904, a novel TX synthetase inhibitor, at the concentrations of 3 x 10(-7) to approximately 3 x 10(-6) M, reduced the augmented contraction. Also, indomethacin (3 x 10(-6) M), a histamine H1 antagonist and AA-2414 (10(-6) M, a TXA2 antagonist, significantly attenuated the hyperresponsiveness to 5-HT. ICI-198,615 (10(-7) M), a leukotriene receptor antagonist, partially but significantly reduced the augmented contraction. In an ex vivo study, oral DP-1904 significantly inhibited both the augmented contraction and elevated TXB2 release from Sephadex-treated rat parenchyma, but did not affect the blood eosinophilia induced by Sephadex-treatment. These results suggested that the ability to synthesize newly generated lipid mediators such as TXA2 and pLTs to exogenous 5-HT was altered upward by Sephadex injection, and so could lead to augmented contraction of established hyperresponsiveness in rats.

Animals↗

Antioxidants reversibly inhibit the spontaneous resumption of meiosis.

We previously showed that the cell-permeant antioxidant 2(3)-tert-butyl-4-hydroxyanisole (BHA) inhibited germinal vesicle breakdown (GVBD) in oocyte-cumulus complexes (OCC) of the rat. The objective of the present studies was to assess other antioxidants and whether such inhibition was reversible. Spontaneous GVBD in OCC incubated for 2 h was significantly inhibited (P < 0.005) by nordihydroguaiaretic acid (NDGA; GVBD = 19.4%), BHA (GVBD = 25.7%), octyl gallate (OG; GVBD = 52.2%), ethoxyquin (EQ; GVBD = 58.8%), 2, 6-di-tert-butyl-hydroxymethyl phenol (TBHMP; GVBD = 59%), butylated hydroxytoluene (BHT; GVBD = 59.5%), and tert-butyl hydroperoxide (TBHP; GVBD = 60.0%). Other antioxidants that produced lower but significant (P < 0.05) inhibition of oocyte maturation included propyl gallate (PG; GVBD = 70.3%), 2,4,5-trihydroxybutrophenone (THBP; GVBD = 71.4%), and lauryl gallate (LG; GVBD = 71.4%). Antioxidants that had no effect on oocyte maturation at the same concentration (100 microM) included ascorbic acid, vitamin E, and Trolox. Inhibition of GVBD was evident for up to 8 h of incubation of OCC and denuded oocytes (DO) with BHA or NDGA and was reversed by washing. NDGA was less potent than BHA for inhibition of GVBD in DO, unlike that seen with OCC. Oocyte maturation was induced by incubation of follicles for 3 h with human chorionic gonadotropin (hCG), and this response was inhibited by BHA or NDGA. These findings support the conclusion that cell-permeant antioxidants inhibit spontaneous resumption of meiosis, which may implicate a role of oxygen radicals in oocyte maturation.

Animals↗

A simple technique for anatomical slow pathway ablation in atrioventricular nodal reentrant tachycardia.

The slow pathway potential or the slow potential serves as a useful marker in catheter ablation of the slow pathway. However, an anatomical approach without recording of these potentials is also an effective way to cure atrioventricular nodal reentrant tachycardia (AVNRT). Moreover, the origin of these potentials is a matter of controversy. We compared 2 approaches to ascertain whether or not recording of these potentials is necessary in eliminating the slow pathway and to estimate the usefulness of the simple anatomical approach. The study population consisted of 24 patients with a conventional approach (Group P) and 19 patients with an anatomical approach (Group A). In group A, the ablation site was determined by fluoroscopy, which was the lowest one-third of the area between the His bundle electrogram recorded position and the coronary sinus orifice at the right anterior oblique view, and just in front of and above the coronary sinus orifice also posterior to the His catheter at the left anterior oblique view where the His catheter was seen tangentially. The slow pathway was successfully ablated in all patients without any complications, including more than first-degree AV block. Although there were no significant differences in total energy or number of applications between the 2 groups, the procedure time was significantly shorter in group A (p < 0.01). In conclusion, recording of the slow pathway potential or the slow potential is not always necessary for slow pathway ablation in the treatment of AVNRT. Because our anatomical approach was performed simply, effectively and safely, it is recommended for the slow pathway ablation of AVNRT.

Adolescent↗

Percutaneous microwave hepatic tumor coagulation with segmental hepatic blood flow occlusion in seven patients.

OBJECTIVE: We assess the usefulness of microwave hepatic tumor coagulation therapy with balloon occlusion of segmental hepatic blood flow for eight recurrent metastatic hepatic tumors in seven patients. CONCLUSION: Limited early experience with microwave hepatic tumor coagulation therapy and segmental hepatic blood flow occlusion has been positive, suggesting that further clinical evaluation is warranted.

Catheterization↗

[Microwave coagulation therapy under laparotomic ischemia for multiple liver metastases of colorectal cancer].

Microwave coagulation therapy (MCT) under laparotomic ischemia induced by partial obstruction of the hepatic artery and portal vein was conducted on patients with multiple liver metastases of colorectal cancer. The patients were then compared with those who underwent non-ischemic MCT. Among the patients with liver metastasis of colorectal cancer we encountered between August 1990 and October 1998, 14 patients who developed multiple cancer (five or more) in the bilateral liver lobes were enrolled in the study. No clear differences were observed in the sex, age, frequency of simultaneousness, therapy other than MCT, number of foci, and number of MCT between the ischemic MCT and non-ischemic MCT group. Postoperative CT revealed residual foci in one of the seven patients in the ischemic MCT group. A comparison of the cumulative survival rate revealed that the ischemic MCT group had a higher one-year survival rate (50%) than the non-ischemic MCT group (14%). A comparison of patients with a residual lesion and those with no residual lesion showed that all six patients with a residual lesion died less than one year after surgery. Eight patients with no residual lesion had a significantly better prognosis (p < 0.05). It is important to eliminate any residual metastatic lesion during surgery in multiple liver metastases of colorectal cancer If the residual lesion is non-resectable, its elimination by ischemic MCT would contribute to the long-term survival of the patients.

Adult↗

Correlative alteration of thromboxane A2 with antigen-induced bronchoconstriction and the role of platelets as a source of TXA2 synthesis in guinea pigs: effect of DP-1904, an inhibitor of thromboxane synthetase.

A marked and sustained bronchoconstriction after antigen challenge was produced in actively sensitised guinea pigs, and correlated with increments of thromboxane (TX) A2 level in both the plasma and bronchoalveolar lavage fluid. DP-1904 given orally relieved the bronchoconstriction and increase in TXA2 in a dose-dependent manner. In platelet-depleted animals, antigen-induced bronchoconstriction and TXA2 release in the plasma were significantly reduced compared to those of non-platelet-depleted animals, indicating that platelets are a major cell source of TXA2 production, the remainder originating from the other cells excluding platelets. In the platelet-deprived animal, DP-1904 showed further significant inhibition of the constriction and plasma TXA2 level, and therefore likely inhibits TXA2 synthesis of various cells, including platelets, in the bloodstream. The results suggested that TXA2 is an important mediator responsible for producing antigen-induced bronchoconstriction, and endogenously originated from various cells including platelets in guinea pigs.

Animals↗

In vitro effect of DP-1904, a novel anti-asthma agent, against antigen-induced constriction and TXB2 release from the isolated guinea-pig lung parenchymal tissue.

The contractile activity and mobilisation of arachidonic acid metabolites in response to the antigen challenge were studied in isolated lung parenchymal tissue from the actively sensitised guinea pig. The sustained constriction of the lung tissue was evoked by the antigen, associated with significant liberation of TXB2, histamine and p-LTs. Other prostanoids (PGF2 alpha, PGD2, PGE2 and 6-keto-PGF1 alpha) were also released by the antigen challenge. DP-1904, an inhibitor of TX synthetase, significantly suppressed the late phase of the antigen-induced constriction. DP-1904 was potent to inhibit the production of TXB2, while DP-1904 accelerated the formation of PGF2 alpha, PGE2 and 6-keto-PGF1 alpha, presumably indicating the alternative changes of dilatory metabolites to the spasmogenic component. Mepyramine and FPL-77512 augmented the effect of DP-1904. AA-861 inhibited the antigen-induced constriction of the lung parenchymal tissue by inhibiting the release of p-LTs and TXB2. Pretreatment of the lung parenchymes with anti-guinea pig platelet serum, in order to deplete the platelets, did not affect the generation of TXB2 both in resting and also in the antigen-stimulated status, indicating that TXA2 is produced in the topical pulmonary tissue. It is concluded that DP-1904 inhibits the parenchymal contraction through potent inhibition of TXA2 generation, associated with significant elevation in PGE2 and PGI2.

Animals↗

Novel germline mutations of hMSH2 in a patient with hereditary nonpolyposis colorectal cancer (HNPCC) and in a patient with six primary cancers.

We screened for germline mutations of mismatch repair genes, hMLH1 and hMSH2, in five Japanese families carrying hereditary nonpolyposis colorectal cancer (HNPCC) and in a patient with multiple primary cancers. Screening the entire coding regions of both genes using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis, we found two novel germline mutations in hMSH2. One was a 1-bp insertion in exon 12, detected in a patient who had undergone surgery six times for independent tumors (four primary colorectal carcinomas, a small intestinal carcinoma, and an endometrial cancer). The other, in a second patient, was a missense mutation from CTT to TTT at codon 390 in exon 7 that resulted in substitution of phenylalanine for leucine. This conservative alteration was not found in any of 50 normal controls, but we cannot exclude the possibility that it may represent a rare polymorphism rather than a factor in the disease.

Adult↗

Effects of DP-1904, a thromboxane synthetase inhibitor, on the antigen-induced airway hyperresponsiveness and infiltration of inflammatory cells in guinea-pigs.

The effect of DP-1904, a novel thromboxane (TX) synthetase inhibitor, on airway hyperresponsiveness was studied in actively sensitized guinea-pigs. Airway hyperresponsiveness to intravenous ACh was observed at 3 and 7 h after aerosolized antigen challenge. In the model, a significant correlation between increases of respiratory resistance and microvascular leakage was observed, corresponding to the elevation of TXB2 in bronchoalveolar lavage fluid (BALF) in the early phase. DP-1904, at doses of 3 mg/kg or higher given orally one hour prior to the antigen challenge, inhibited the TXB2 production and the development of airway hyperresponsiveness in the early phase. Further, DP-1904 significantly suppressed the accumulation of lymphocytes in BALF and airway hyperresponsiveness in the late phase, although it only slightly decreased the mobilization of eosinophils and neutrophils. The results suggest that TXA2 is possibly involved in the development of airway hyperresponsiveness, and DP-1904 prevented the airway hyperresponsiveness via inhibition of TXA2 production and regulation of inflammatory cells.

Acetylcholine↗

Binding affinity of Cu(II)-VP-16 (etoposide) complex and its analogues to DNA and hydroxyl radical generation during DNA strand breaks.

Conformational effects and affinities of VP-16 (etoposide) and its derivatives to DNA in the presence of Cu(II) ion were examined by circular dichroic (CD) spectra. The Cu(II)/Cu(I) redox kinetics and the hydroxyl radical (.OH) generation from the Cu(II)-complexes were estimated by the stopped-flow kinetics. Based on the results, DNA-cleaving activity of Cu(II)-complexes of VP-16 has been shown to be related with binding affinity of the complex to DNA, Cu(II)/Cu(I) redox and .OH generation, emphasising the mechanism of generated .OH attack to DNA.

Animals↗

Anatomically guided radiofrequency catheter ablation of atrial reentrant tachycardia.

Atrial reentrant tachycardia (ART) was ablated in an anatomically guided approach. Five patients with ART underwent 2 linear incisions without careful pace or activation mapping. One line was from an atrial activation site earlier than P wave onset to the nearest fixed anatomic conduction barrier, i.e., the inferior vena cava or coronary sinus ostium. The other line was made just above or closely crossed the first line vertically. Mean application time was 29 +/- 19 minutes, and the application energy was 14,001 +/- 12,322 joules. Mean follow-up after ablation was 15 +/- 10 months. Three patients underwent electrophysiologic study three months after and sustained ART was not induced. All patients were free of sustained tachycardia events without antiarrhythmic drugs during the postoperative clinical course. Although anatomically guided ablation for ART requires much time and energy, it is easily and effectively done without careful activation or pace mapping, and is indicated if ablation using activation mapping or entrainment technique fails to cure the ART.

Adult↗

[A cooperative study on concomitant with low-dose divided administration of cisplatin (CDDP) and sustained drip infusion of 5-fluorouracil (5-FU) for unresectable advanced gastric cancer. Osaka Cisplatin Gastric Cancer Study Group].

For patients with unresectable gastric cancer registered between July 1994 and September 1995, the following dosage regimen was examined: a drip infusion of cisplatin (CDDP) at 7 mg/m2/day for 5 consecutive days and 2-day withdrawal a week for 3 weeks with concomitant sustained drip infusion of 5-FU at 300 mg/m2/day for 21 days. The whole cycle was repeated again after 2-week withdrawal. The antitumor effect was seen in 39.4% among 33 cases. With respect to histological classification, there was no difference in appearance of the effect between the moderately differentiated type at 62.5% and the low-differentiated type at 42.9%. The cases which became resectable after the administration included those in which the tumor disappeared completely in the resected specimens. As adverse reactions encountered in the cases above Grade 3, anorexia, nausea and vomiting and diarrhea were seen as clinical symptoms in 10, 5.3 and 11.8%, respectively. As laboratory test values, decrease in hemoglobin, leukocytopenia and thrombocytopenia were seen in 16.7, 15.8 and 5%, respectively, while renal or liver dysfunction did not occur. This dosage regimen was considered useful for unresectable advanced gastric cancer, although myelosuppression should be watched carefully.

Adult↗

[Clinical application of ischemic microwave coagulation therapy for malignant liver tumor].

By means of ischemic coagulation of the hepatic artery and portal vein in a microwave coagulation experiment of in vivo swine [correction of bovine] liver, we confirmed approximate doubling of the coagulation diameter compared to the usual coagulation. Based on this fact, for treatment of patients with metastatic liver tumor, we developed an ischemic percutaneous microwave tumor coagulation method using IVR method and applied it in one case, and performed laparotomy microwave tumor coagulation in three cases. We performed the ischemic percutaneous microwave tumor coagulation method on one of the cases. Coagulation was performed for one minute at a dose of 100 W for treatment of metastatic liver tumor of 2 cm in diameter via laparotomy. The postoperative CT showed an extensive coagulation larger than 3 cm. A 2 cm liver tumor was coagulated under balloon ischemia of the hepatic vein and hepatic artery for 13 minutes at a dose of 60 W. The maximum coagulation diameter was 5 cm. Extensive coagulation was possible with percutaneous microwave tumor coagulation through ischemia.

Animals↗

[Good response in case of hepatocellular carcinoma; a case report of interdisciplinary local therapy].

A 47-year-old male patient with chronic hepatitis had a high AFP level during the follow-up period. Abdominal CT revealed at S5, which led to a diagnosis of hepatocellular carcinoma. In August 1992, partial resection of S5 was performed, and ethanol was injected into the tumor at S2. In July 1993, recurrent tumors were observed at S5 and S3. PEIT was performed for each lesion. In December 1994, multiple recurrence was observed and 4 mg SMANCS was injected through the proper hepatic artery. In July 1995, another 4 mg of SMANCS was injected into the tumors. In June 1996, only a 20 mm lesion at S5 remained while the other lesions disappeared. Under general anesthesia, the patient underwent percutaneous microwave tumor coagulation. In December 1997, the AFP level was normal, and imaging revealed disappearance of the recurrent tumor. Selection of local therapy for hepatocellular carcinoma achieved long survival in our case considering the QOL and frequent therapy administration.

Antineoplastic Agents↗

[Correlation between pyrimidine nucleoside phosphorylase (PyNPase)/platelet-derived endothelial cell growth factor and histological prognostic factor, and influences of 5'-deoxy-5-fluorouridine (5'-DFUR) administration on PyNPase levels. 5'-DFUR Joint Research Group in the Osaka Area for Gastric Cancer].

PURPOSE: Pyrimidine nucleoside phosphorylase (PyNPase), among which thymidine phosphorylase (dThdPase) exists mainly in human tumor tissues, is an enzyme to convert 5'-deoxy-5-fluorouridine (5'-DFUR) to 5-fluorouracil. Recently, it was reported that dThdPase was identical to platelet-derived endothelial cell growth factor, angiogenetic factor. Therefore, we expect that there is possibility of dThdPase being a prognostic factor. METHODS: We investigated for a possible correlation between PyNPase activities in tumor tissues and prognostic factors of histological findings, examined the influences of preoperative oral 5'-DFUR administration to PyNPase levels and investigated for a correlation between HPLC methods and ELISA methods in patients with gastric cancer. RESULTS: Higher levels of PyNPase were observed in patients with advanced t,n,v, and ly factors. PyNPase levels decreased by 5'-DFUR in patients with differentiated cases. A high correlation was found between HPLC and ELISA methods. CONCLUSION: This study suggests that we must investigate possibility of PyNPase being a prognostic factor in more detail.

Antineoplastic Agents↗

An evaluation of CA125 levels in 291 normal postmenopausal and 20 endometrial adenocarcinoma-bearing women before and after surgery.

Two hundred ninety-one normal postmenopausal women without hormone replacement therapy were studied for their blood levels of CA125. The levels ranged from 0.1 to 31.8 U/ml (mean+/-SEM 5.5+/-0.3 U/ml). Twenty patients with endometrial adenocarcinoma who had preoperative CA125 levels below 50 U/ml were also studied. The levels of CA125 in the latter group ranged from 2.1 to 43.0 U/ml (17.2+/-2.3 U/ml) and the difference of the mean value of the two groups was statistically significant (P < 0.001). The CA125 levels in normal postmenopausal women have a weak negative correlation with their age (CA125 = -0.025 x age + 6.9, P < 0.001), whereas in cancer patients, a positive correlation was seen (CA125 = 0.6 x age + 11.5, P < 0.05). Patients with endometrial cancer showed a decrease in their CA125 levels after a hysterectomy and salpingo-oophorectomy (6.5+/-1.2 U/ml, P < 0.0001). These results confirmed that the normal range of the CA125 of menopausal women is much lower than that of cycling women and each laboratory should establish its own normal range for the population. Also, it was suggested that CA125 levels which apparently fall within the normal range but are high, however, for the respective age, may indicate that an extensive search for an endometrial malignancy is necessary.

Adenocarcinoma↗

Ca2+-ATPase inhibitors and Ca2+-ionophore induce osteoclast-like cell formation in the cocultures of mouse bone marrow cells and calvarial cells.

Osteoclasts which derive from hemopoietic cells are multinucleated cells responsible for bone resorption. We found that cyclopiazonic acid (CPA), thapsigargin (TG), and 2,5-di-(t-butyl)-1,4-hydroquinone (BHQ) induced osteoclast-like cell (OCL) formation in cocultures of mouse calvaria-derived stromal cells and hemopoietic cells such as bone marrow cells and spleen cells. OCLs induced by these compounds showed typical characteristics of osteoclasts such as tartrate-resistant acid phosphatase activity and pit forming activity. These compounds are known as endoplasmic reticulum (ER)/sarcoplasmic reticulum (SR) Ca2+-ATPase inhibitors that increase intracellular Ca2+ levels by inhibiting Ca2+-ATPase activity located in the membrane of ER/SR. Ca2+-ionophores such as ionomycin which increase intracellular Ca2+ levels also stimulated OCL formation in the cocultures. Differentiation of hemopoietic cells into OCLs induced by these compounds required the presence of calvarial cells. These results indicate that an increase of intracellular Ca2+ levels may be a part of signaling pathways to induce osteoclast differentiation in the presence of calvarial cells.

Animals↗