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T Beppu

Publications and source records attributed to T Beppu.

At least 55 records · Page 3Linked to original sources

Induction of haem oxygenase-1 nitric oxide and ischaemia in experimental solid tumours and implications for tumour growth.

Induction of haem oxygenase-1 (HO-1) as well as nitric oxide (NO) biosynthesis during tumour growth was investigated in an experimental solid tumour model (AH136B hepatoma) in rats. An immunohistochemical study showed that the inducible isoform of NO synthase (iNOS) was localized in monocyte-derived macrophages, which infiltrated interstitial spaces of solid tumour, but not in the tumour cells. Excessive production of NO in the tumour tissue was unequivocally verified by electron spin resonance spectroscopy. Tumour growth was moderately suppressed by treatment with either Nomega-nitro-L-arginine methyl ester (L-NAME) or S-methylisothiourea sulphate (SMT). In contrast, HO-1 was found only in tumour cells, not in macrophages, by in situ hybridization for HO-1 mRNA. HO-1 expression in AH136B cells in culture was strongly enhanced by an NO (NO+) donor S-nitroso-N-acetyl penicillamine. HO-1 mRNA expression in the solid tumour in vivo decreased significantly after treatment with low doses of NOS inhibitors such as L-NAME and SMT (6-20 mg kg(-1)). However, the level of HO-1 mRNA in the solid tumour treated with higher doses of NOS inhibitor was similar to that of the solid tumour without NOS inhibitor treatment. Strong induction of HO-1 was also observed in solid tumours after occlusion or embolization of the tumour-feeding artery, indicating that ischaemic stress which may involve oxidative stress triggers HO-1 induction in the solid tumour. Lastly, it is of great importance that an HO inhibitor, zinc protoporphyrin IX injected intra-arterially to the solid tumour suppressed the tumour growth to a great extent. In conclusion, HO-1 expression in the solid tumour may confer resistance of tumour cells to hypoxic stress as well as to NO-mediated cytotoxicity.

Animals↗

Establishing the independent culture of a strictly symbiotic bacterium Symbiobacterium thermophilum from its supporting Bacillus strain.

Symbiobacterium thermophilum is a strictly symbiotic thermophile, the growth of which is dependent on the coexistence of an associating thermophilic Bacillus sp., strain S. S. thermophilum grows only in mixed culture with the Bacillus strain in liquid media, and does not form visible colonies on solid media. To measure the growth of this symbiotic bacterium and to analyze its growth requirements, we developed a quantitative PCR method by using its specific sequences in a putative membrane translocator gene tnaT as primers. According to this method, independent growth of S. thermophilum was first confirmed in a dialyzing culture physically separated from Bacillus strain S with a cellulose membrane. Independent growth of S. thermophilum was also managed by adding conditioned medium prepared from the culture filtrate of the Bacillus strain, but the growth in the conditioned medium stopped at a very limited extent with appearance of filamentous cells, suggesting the uncoupling of cellular growth and cell division. Formation of micro-colonies of S. thermophilum was observed on the conditioned agar medium under both aerobic and anaerobic conditions, but the colony-forming efficiencies remained below 1%. Several other bacterial species, such as Bacillus stearothermophilus, Bacillus subtilis, Thermus thermophilus, and even Escherichia coli, were also found to support the growth of S. thermophilum. These results indicate that S. thermophilum essentially requires some ubiquitous metabolite(s) of low molecular weight produced by various bacterial species as growth factor(s) but coexistence of the living partner cells is still required, probably to maintain an effective level of the putative factor(s) in the medium.

Bacillus↗

[Experimental study on direct toxicity of combined cisplatin and methotrexate for normal and neoplastic cell lines].

The combination effect of cisplatin (CDDP) and methotrexate (MTX) on the cytotoxicity against normal fibroblast and malignant cell line were investigated utilizing MTT assay. In case of normal fibroblast, the optical density (OD) value in CDDP + MTX was significantly higher and remained at a consistently higher value in various mixture rates than that in CDDP alone. Such low cytotoxicity may be due to MTX because the addition of Leucovorin resulted in an apparent decrease in the OD value. The combination of the two drugs was thought to alleviate the toxicity of CDDP on fibroblast, in contrast to its increase on cancer cells.

Animals↗

[A case of unresectable advanced gall bladder cancer successfully treated by hepatic arterial chemotherapy with reservoir (HACR) using CDDP and 5-FU].

A 64-year-old female was admitted for treatment of a huge tumor (10 cm in diameter) in segment S4-S5 of the liver. The lymph node (2 cm in diameter) was located posterior to the pancreas head. The patient was diagnosed with an unresectable advanced gall bladder cancer with direct invasion of the liver bed and lymph node metastasis. At first, hepatic arterial infusion of CDDP, MMC and ADM through the hepatic artery was performed. Then, hepatic arterial chemotherapy with reservoir (HACR) using CDDP and 5-FU (CDDP 20 mg/body/day, 5-FU 750 mg/body/day) was started. As a result, the primary tumor and enlarged lymph node almost disappeared in two years. Mild bone marrow suppression, nausea and vomiting were encountered, but no severe side effects were noted. We conclude that this strategy is effective for unresectable advanced cancer of the gall bladder with lymph node metastasis.

Antineoplastic Combined Chemotherapy Protocols↗

[A long-term surviving case of multiple metastatic liver tumors from rectal cancer treated with microwave coagulation therapy (MCT)].

We experienced a long-term surviving case from excellent control of a multiple metastatic liver tumor from rectal cancer. The patient was a 38-year-old male, and his chief complaint was pain at defecation. The primary lesion was diagnosed as rectal cancer (Rb), and it was histologically found to be well-differentiated adenocarcinoma. The preoperative enhanced CT demonstrated 8 metastatic lesions in bilateral lobes of the liver. Low anterior resection for rectum and open microwave coagulation therapy (MCT) for liver metastasis were synchronously performed. The coagulated areas after MCT revealed no enhancement. The serum CEA levels returned to normal for 9 months. Nine months after the first operation, we detected 6 recurrent lesions in the other sites of the remnant liver. We used second open MCT because the hepatic arterial chemotherapy was ineffective. We performed percutaneous MCT for the next new lesions. The patient was diagnosed with lung metastasis 2 years after the first operation, and died of cancer growth 2 years and 9 months after the first operation. This long-term surviving case of nine metastatic liver tumors achieved adequate quality of life by a combination therapy mainly consisting of MCT.

Adenocarcinoma↗

Application of nitrite reductase from Alcaligenes faecalis S-6 for nitrite measurement.

The enzymatic reaction of nitrite reductase (NIR) from Alcaligenes faecalis S-6 was applied to the measurement of nitrite. NIR was immobilized on the surface of a gold electrode using filter paper and a dialysis membrane, and used as a working electrode in a three-electrode system. Amperometric methods were applied using NIR and the electron mediator 1-methoxy PMS (1-methoxy-5-methylphenazinium methylsulfate). The decrease in cathodic current showed a correlation to nitrite concentration over the range 0-1 mg/l. Measurements using a batch-flow type system gave a lower detection limit of 0.01 mg/l. This is sufficient for the detection of nitrite in natural waters.

Alcaligenes↗

Investigation of genetic alterations associated with the grade of astrocytic tumor by comparative genomic hybridization.

Comparative genomic hybridization (CGH) is a technique that allows the detection of losses and gains in DNA copy number across the entire genome. We used CGH to study the genetic alterations that occur in primary astrocytomas, including 14 glioblastomas (GBM), 12 anaplastic astrocytomas (AA), and 7 low-grade astrocytomas (LGA). The average numbers of total aberrations in GBM, AA, and LGA were 9.7, 5.4, and 4.0, respectively. The average number of DNA sequence losses in GBM was significantly higher than that in AA or LGA (P < 0.01). Frequently altered regions (> eight cases) observed in all grades of astrocytoma were 7p13-p12 (gain), 7q31 (gain), 8q24.1-q24.2 (gain), 9p21 (loss), 10p12-p11 (loss), 10q22-qter (loss), 13q21-q22 (loss), and 20q13.1-q13.2 (gain). Loss of 9p, 10p, or 10q, and the gain or amplification of 7p, were observed frequently in GBM (64%, 57%, 64%, and 50% of cases, respectively). Frequent alterations found in AA were losses of 9p, 10q, and 13q, and gains of 1q, chromosome 7, 11q, and Xq. Whereas 7p13-p11 amplification occurred exclusively in cases with the loss of all or part of chromosome 10, this change never occurred in cases having an increase in copy number of 8q, which was the most frequent change observed in LGA (four of seven cases). These results may indicate that an increase in copy number of 8q is an important event in GBM, with a genetic pathway, which is distinct from that in GBM with 7p amplification.

Adult↗

Pathological analyses of early recurrence and malignant transformation in meningiomas.

We investigated factors of the early recurrence and malignant transformation of histologically benign meningiomas using immunohistochemistry for MIB-1 positive indices (PI) and p53 protein expression, a flow cytometric DNA analysis, and the examination of numerical chromosomal aberrations detected by fluorescence in situ hybridization using an alpha-satellite DNA probe and a bcr gene locus-specific probe. Twenty-six meningiomas of 23 patients were classified into two groups: the 3 patients in whom a recurrence was defined within two years after initial surgery and who showed histologically malignant features were classified as the early recurrent group, and the other 20 patients in whom recurrence did not develop during the same period were classified as the nonrecurrent group. DNA aneuploidy was observed in 40% of the nonrecurrent patients and in 67% of the early recurrent patients. Loss of chromosome 22 was the most common numerical aberration, but the aberrations characteristic of early recurrent meningiomas were not detected. The MIB-1 PI values of the early recurrent meningiomas were higher than those of nonrecurrent meningiomas, suggesting that MIB-1 PI is very important for biological and histopathological analyses and prediction of the future recurrence of meningiomas.

Aneuploidy↗

Overexpression of high-molecular-mass nitrile hydratase from Rhodococcus rhodochrous J1 in recombinant Rhodococcus cells.

High-molecular-mass nitrile hydratase (H-NHase, 530 kDa) is a cobalt-containing enzyme produced by Rhodococcus rhodochrous J1. For efficient production of H-NHase in R. rhodochrous ATCC12674, several plasmids were constructed. The enzyme was produced in the recombinant Rhodococcus cells only in the presence of an upstream region (approximately 4 kb) of the H-NHase gene under the control of the promoter for the amidase-NHase gene cluster from Rhodococcus sp. N-774. Although H-NHase was produced as a soluble protein in the cells, the protein did not show NHase activity. However, when the recombinant R. rhodochrous ATCC12674 cells were cultured in the presence of amide compounds, such as crotonamide and methacrylamide, markedly high NHase activity was detected, Gel-filtration chromatography revealed that the NHases produced by the cells grown in the presence and absence of the amide compounds had a molecular mass of more than 500 kDa and 50-80 kDa respectively. These results suggest that the amide compounds are essential for subunit assembly to form an enzymatically active multimer. By the use of the recombinant expression system, NHase activity 1.7 times higher than that of the original strain, R. rhodochrous J1, was achieved.

Dose-Response Relationship, Drug↗

Long-term prognosis of non-shunt operation for idiopathic portal hypertension.

This report presents 46 Japanese patients with idiopathic portal hypertension (IPH) in whom non-shunt operation was performed for the management of esophageal varices. Non-shunt operation included transthoracic esophageal transection (Sugiura's procedure) in 37 patients, transabdominal esophageal transection (TAET) in 3 patients, and Hassab's procedure in 6 patients. Rates of postoperative variceal eradication were: 78.4% by Sugiura's procedure; 100% by TAET; and 50% by Hassab's procedure. The cumulative rates for recurrent varices and recurrent bleeding were 3.9%, and 5.1%, respectively, at 5 years, and 8.9% and 9.8% at both 10 and 15 years. Only 3 patients required additional endoscopic injection sclerotherapy to treat recurrent varices. Although 3 patients developed upper gastrointestinal bleeding, the source of hemorrhage was esophageal varices in 1, and portal hypertensive gastropathy in 2; none of the patients died from bleeding. Actuarial survival for all patients was 87.5% at 5 years, 77.9% at 10 years, and 58.8% at 15 years. There were no deaths within the first 30 days after surgery. These results show that non-shunt operation is useful in preventing bleeding from esophageal varices in patients with IPH.

Adolescent↗

Complications and management of microwave coagulation therapy for primary and metastatic liver tumors.

Microwave coagulation therapy (MCT) has been widely used, both percutaneously and directly, as effective minimal invasive therapy for liver tumors. To facilitate the use of MCT, we describe the complications we have encountered, and their possible management and prophylaxis. MCT was performed for 42 patients with hepatocellular carcinoma (HCC) and for 29 with metastatic liver tumors, following which complications developed in 14.2% and 20.6% of the HCC and metastatic groups, respectively. The complications included abscess, biloma, bleeding, hepatic failure, and dissemination of cancer cells. In the HCC group, the mean value of tumor size and the clinical stage of patients with complications were significantly larger (P = 0.006) and higher (P = 0.032), respectively, than those of patients without complications. The incidence of complications increased significantly when the tumor size was more than 4cm (P = 0.008). Abscesses and bleeding were successfully treated using percutaneous drainage and interventional angiography, respectively, but as the other serious complications were not able to be treated effectively once induced, prophylaxis is important to facilitate MCT. Transcatheter cooling of the intrahepatic bile duct during MCT and the administration of an anticancer agent into the abdominal cavity are recommended to prevent biloma and dissemination, respectively. MCT is indicated for tumors less than 4 cm in diameter to reduce the risk of complications. The prophylaxis and treatment of these complications enhance the safety of MCT.

Aged↗

Characterization of an A-factor-responsive repressor for amfR essential for onset of aerial mycelium formation in Streptomyces griseus.

A-factor (2-isocapryloyl-3R-hydroxymethyl-gamma-butyrolactone) is essential for the initiation of aerial mycelium formation in Streptomyces griseus. amfR is one of the genes which, when cloned on a low-copy-number plasmid, suppresses the aerial mycelium-negative phenotype of an A-factor-deficient mutant of S. griseus. Disruption of the chromosomal amfR gene resulted in complete abolition of aerial mycelium formation, indicating that amfR is essential for the onset of morphogenesis. Cloning and nucleotide sequencing of the region upstream of amfR predicted an operon consisting of orf5, orf4, and amfR. Consistent with this idea, Northern blotting and S1 mapping analyses suggested that these three genes were cotranscribed mainly by a promoter (PORF5) in front of orf5. Furthermore, PORF5 was active only in the presence of A-factor, indicating that it is A-factor dependent. Gel mobility shift assays showed the presence of a protein (AdpB) able to bind PORF5 in the cell extract from an A-factor-deficient mutant but not from the wild-type strain. AdpB was purified to homogeneity and found to bind specifically to the region from -72 to -44 bp with respect to the transcriptional start point. Runoff transcriptional analysis of PORF5 with purified AdpB and an RNA polymerase complex isolated from vegetative mycelium showed that AdpB repressed the transcription in a concentration-dependent manner. It is thus apparent that AmfR as a switch for aerial mycelium formation and AdpB as a repressor for amfR are members in the A-factor regulatory cascade, leading to morphogenesis.

4-Butyrolactone↗

CT appearance of hepatic tumors after microwave coagulation therapy.

OBJECTIVE: The purpose of this study was to evaluate the changes in treated lesions and surrounding parenchyma of the liver as well as associated findings on CT in patients who underwent microwave coagulation therapy for hepatic tumors. MATERIALS AND METHODS: We retrospectively reviewed the findings on helical dynamic CT scans obtained before and after percutaneous or intraoperative microwave coagulation therapy for 74 lesions in 63 patients with hepatocellular carcinoma or metastatic hepatic tumors. Indications for microwave coagulation therapy included primary hepatic tumors in 54 patients and hepatic metastasis in nine patients. Sixty percent nonionic contrast material, infused at 3 ml/sec, was followed by sequential arterial phase, portal venous phase, and equilibrium phase helical CT of the entire liver in all patients. RESULTS: All lesions were hypodense and extended to the liver capsule. The lesions treated with percutaneous microwave coagulation therapy were teardrop-shaped, whereas those treated with intraoperative microwave coagulation therapy were round. Peripheral enhancement was seen on contrast-enhanced CT in 93% of the treated lesions immediately after microwave coagulation therapy; however, such enhancement disappeared on follow-up CT. Hemorrhage within the lesions and pleural effusion were found in nine patients. Complications detected on CT included intratumoral abscess (n = 4), subcapsular hematoma (n = 2), tumor dissemination (n = 3), ascites (n = 5), and portal vein thrombosis (n = 1). CONCLUSION: CT of the liver in patients undergoing microwave coagulation therapy showed findings that were dependent on the technique of therapy. Thus, CT scans must be carefully analyzed to avoid confusing results of therapy with findings that indicate complications requiring further treatment.

Aged↗

Tuberculosis associated with pulmonary sequestration.

We describe a case of intralober pulmonary sequestration in association with tuberculosis. Sequestrations of the lung are classically divided into two types of extralober and intralober. Intralober pulmonary sequestration in association with tuberculosis is rare. We diagnosed the present case to be Pryce type 1 with tuberculosis infection.

Bronchopulmonary Sequestration↗

[Clinical evaluation of Azasetron Hydrochloride: a new selective 5-HT3 receptor antagonist--antiemetic profile and plasma concentration in transcatheter arterial chemoembolization using CDDP for unresectable hepatocellular carcinoma].

We performed a clinical evaluation on the antiemetic profile and the plasma concentration of Azasetron Hydrochloride (a new selective 5-HT3 receptor antagonist), in transcatheter arterial chemoembolization using CDDP for unresectable hepatocellular carcinoma. Antiemetic effects were examined in 32 patients in the serotone group (administration of serotone 10 mg + methylprednisolone 125 mg) and in 77 patients of the control group (administration of metoclopramide 20-30 mg + methylprednisolone 500 mg). The response rate and the CR ratio in serotone group was 97% and 66%, respectively. These results were statistically higher than in the control group. Although all patients had chronic liver diseases, no side effects and complications related to administration of serotone were observed. The average area under the concentration (AUC) curve of plasma serotone in five patients with liver cirrhosis was 531 ng.h/ml, which was greater than that of a healthy volunteer. In conclusion, serotone is a new, safe and useful antiemetic drug in TACE therapy for hepatocellular carcinoma.

Aged↗

[Intraoperative local infusion chemotherapy (ILIC) for gastric cancer].

In order to provide a high dose of cis-diammine dichloro platinum (CDDP) into the regional lymph nodes and surrounding organs during operation, "intraoperative local infusion chemotherapy (ILIC)" was devised and has been applied to advanced gastric cancer patients. The aims of this method are 1) to reduce the possibility of metastasis by affecting the cancer cells before flowing out; 2) to administer drugs to the cancer cells which evade surgical resection; 3) to administer drugs to the lymphatic flow; and 4) to reduce the systemic side effects. After the laparotomy, the part of the stomach for gastrectomy was isolated from the blood supply, applying clamps to the proximal and distal parts of the stomach and hemostats to feeding blood vessels. Through a feeding artery to the tumor, 50 mg of CDDP was injected. Twenty-four patients underwent ILIC from June 1986 to December 1993. The 5-year survival rate was significantly better in the ILIC group compared to the control group which was selected by the matched pair method. The newly devised ILIC chemotherapy is a promising way to improve the prognosis of advanced gastric cancer patients. A randomized prospective study should be undertaken.

Animals↗

[Efficacy of microwave coagulation therapy (MCT) in patients with liver tumors].

We evaluated the efficacy of microwave coagulation therapy (MCT) in 84 patients with hepatocellular carcinomas (HCC) and 40 with metastatic liver tumors (MLT). The response rates calculated with diagnostic imaging were 92% in HCC and 80% in MLT. The regional recurrence rates were relatively higher in patients with MLT (33%) than in HCC (14%). The average surgical margin in operative MCT group was 11 mm. The cumulative survival rates at three and five years were 63% and 38% in HCC and 43% and 33% in MLT, respectively. The complications were similarly encountered in HCC and MLT (12% versus 13%). When these observations are taken together, MCT is a radical and safe locoregional therapy which can keep an adequate surgical margin and assure long survival.

Adolescent↗