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Biomedical subjects

T Kanamaru

Publications and source records attributed to T Kanamaru.

At least 37 records · Page 2Linked to original sources
PubMed1996

Hamster liver cytochrome P450 (CYP2A8) as a 4-hydroxylase for 2,5,2',5'-tetrachlorobiphenyl.

Metabolism of 2,5,2',5'-tetrachlorobiphenyl (TCB) was studied using liver microsomes of hamsters and two hamster P450 isoforms, CYP1A2 and 2A8. CYP2A8 catalyzed selectively 4-hydroxylation of 2,5,2',5-TCB at a rate of 21.7 pmol/min/nmol P450. In contrast, CYP1A2 showed no activity for hydroxylation of 2,5,2',5'-TCB. Immunological study revealed that rabbit antiserum against CYP2A8 almost completely inhibited the microsomal 4-hydroxylation but that against CYP1A2 did not. It was also shown that the induction pattern of CYP2A8 protein by P450 inducer was similar to that of the 4-hydroxylase activity in hamster liver microsomes. These results suggest that CYP2A8 plays a major role in the 4-hydroxylation of 2,5,2',5'-TCB in hamster liver.

Animals↗
PubMed1996

Resected acinar cell carcinoma of the pancreas with tumor thrombus extending into the main portal vein: report of a case.

The incidence of acinar cell carcinoma has been reported to be about 1% of all pancreatic neoplasms, and pancreatic cancer combined with tumor growth extending into the portal vein is a rare condition. We herein report a case of acinar cell carcinoma of the pancreas with a tumor thrombus extending into the main portal trunk. Preoperative imaging of the portal vein, consisting of computed tomography (CT), magnetic resonance imaging (MRI), and angiography, revealed an oval shadow defect in the main portal trunk along with an irregular mass in the pancreatic head. At operation, we confirmed a tumor thrombus extending from a tumor in the pancreatic head into the main portal trunk via the pancreatoduodenal veins. A pancreatoduodenectomy combined with partial resection of the portal vein was thus performed under a temporary portal vein shunt from the ileocecal vein to the umbilical vein. Immunohistochemical examination for alpha 1-antichimotrypsin and electron microscopic examination confirmed the diagnosis of acinar cell carcinoma of the pancreas with a tumor thrombus in the portal vein. Surgical excision combined with portal vein resection may therefore improve the prognosis of selected patients with portal tumor thrombus.

Carcinoma, Acinar Cell↗
PubMed1996

Effect of a parenteral nucleoside-nucleotide mixture on hepatic metabolism in partially hepatectomized cirrhotic rats.

After hepatectomy, purine and pyrimidine metabolism is a key process in synthesis of DNA and RNA and in energy metabolism. To supply nucleosides for salvage synthesis, nucleoside-nucleotide mixture solutions have been developed, and they have been found to improve protein metabolism and hepatic regeneration after partial hepatectomy in normal rats. However, the effect of the solution in cirrhotic liver, common in patients with hepatocellular carcinoma, has not been reported. The aim of this study was to evaluate the metabolic effect of the nucleoside-nucleotide mixture on cirrhotic rats after partial hepatectomy. Seventy percent partial hepatectomy was performed in thioacetamide-administered cirrhotic rats. The fractional protein synthetic rate, nitrogen balance, hepatic content of nucleic acid, and blood chemistry after the administration of the nucleoside-nucleotide mixture solution (OG-VI) with total parenteral nutrition was evaluated at 7 d after partial hepatectomy. OG-VI increased hepatic RNA level and hepatic fractional protein synthetic rate (p < 0.05). It is concluded that the nucleoside-nucleotide mixture solution is an effective nutritional supplement to the metabolism of cirrhotic rats after partial hepatectomy.

Animals↗
PubMed1996

Uptake characteristics of oligonucleotides in the isolated rat liver perfusion system.

The objective of this study was to examine the hepatic disposition characteristics of 20-mer model phosphodiester oligonucleotide (PO) and its partially phosphorothioated (PS3) and fully phosphorothioated (PS) derivatives in the single-pass isolated rat liver perfusion system. [32P]-labeled oligonucleotides were momentarily introduced into this system through the portal vein as a bolus input mode, and the venous outflow patterns were evaluated using statistical moment analysis. The apparent volumes of distribution of these oligonucleotides were greater than those of reference substances for vascular space (erythrocytes) and extracellular space (human serum albumin), indicating a significant interaction between oligonucleotides and the liver. Significant hepatic uptake of oligonucleotides was also observed. About 20%, 36%, and 52% of the injected dose (3 micrograms/rat) was taken up by the liver during a single passage after bolus injection of PO, PS3, and PS, respectively. In the case of PS injection, slow efflux from the liver was observed in the latter phase of perfusion. This suggests that the hepatic uptake process of these oligonucleotides greatly depended on their types. The results of collagenase perfusion experiments suggest that PS3 oligonucleotides were taken up by both liver parenchymal and nonparenchymal cells. The amount of total recovery in the liver decreased substantially by coadministration of polyinosinic acid, dextran sulfate, polycytidic acid and 4-acetamido-4'-isothiocyano-stilbene-2,2'-disulfonic acid. This suggests that PS3 was taken up by the liver as an anionic molecule in a nonspecific manner.

Animals↗
PubMed1996

[The effect of high-dose intraarterial chemotherapy with percutaneous hepatic venous isolation and charcoal hemoperfusion (HVI.CHP) for unresectable multiple hepatocellular carcinoma--comparison with other therapeutic modalities].

We evaluated the therapeutic effect of HVI.CHP in 11 patients with Stage III and IVA multiple hepatocellular carcinoma (group H) in comparison with conventional intraarterial chemotherapy (group S, 12 patients) and transarterial embolization (TAE; group T, 15 patients). The patients in each group had the same background as group H in terms of liver function tests. The Vp3 positive rates in group H (37%) and group S (47%) were significantly higher than group T (0%). One-year survival rates of groups H, S and T were 63. 6%, 8.3% and 46.7%, respectively, and 2-year survival rates were 63.6%, 0% and 20%, respectively. A significant difference was seen between the survival curves of groups H and S (p < 0.01), whereas no significant differences were detected between those of groups H and T. The survival rates for stage IVA patients in groups H, S and T were 55.6%, 10% and 40%, respectively, for 1 year and 55.6%, 0% and 10%, respectively, for 2 years. The difference of survival curves between Stage IVA patients of each group was analogous to those between overall patients of each group. Although 4 patients with Vp3 were included in group H but none in group T, the survival rates of group H were rather higher than in group T at 2 years. These data suggest that HVI.CHP could be the treatment of choice for unresectable multiple hepatocellular carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

[Effect of ulinastatin on delayed neuronal death in the gerbil hippocampus].

The effect of ulinastatin on delayed neuronal death was studied in the gerbil. The animals were divided into 2 groups according to the temperatures of the temporalis muscle, tympanic membrane, and the rectum. One group consisted of 36 animals in whom the temperature was maintained at 36.5 degrees C and the another was at 38 degrees C. They were anesthetized with isoflurane and injected intravenously with 5 ml.kg-1 of normal saline solution, 100 mg.kg-1 of alpha-tocopherol, 250,000 units.kg-1 of ulinastatin, or 500,000 units.kg-1 of ulinastatin, respectively. Transient ischemia was then induced by occluding bilateral common carotid arteries for 5 min. Six days later, they were sacrificed, and the brain tissues were fixed and stained for histopathological analysis of hippocampal CA1 regions. alpha-Tocopherol and ulinastatin prevented delayed neuronal death in the 36.5 degrees C group, but did not in the 38 degrees C group. alpha-tocopherol is recognized as an intrinsic radical scavenger, and known to prevent delayed neuronal death. Compared with 100 mg.kg-1 of alpha-tocopherol, 500,000 units.kg-1 of ulinastatin had the same protective effect on delayed neuronal death at 36.5 degrees C. We concluded that administration of ulinastatin prevented delayed neuronal death at 36.5 degrees C.

Animals↗
PubMed1996

Clinical significance of telomerase activity in hepatocellular carcinoma.

Telomerase is a ribonucleoprotein enzyme that elongates telomeric DNA. It has been reported that most immortal cell lines express telomerase, whereas in adult normal tissues telomerase activity is not detected. So, in malignant tumors telomerase is thought to be activated to maintain their immortality. In this study, we examined telomerase activity in 12 cases of hepatocellular carcinoma (HCC) with the use of PCR-based assay and analyzed the relationship of telomerase activity to clinicopathological features. In 11 of 12 HCC nodules telomerase activity was detected, of which 9 cases showed strong activity. There was no significant correlation between telomerase activity and clinicopathological features of HCC. Telomerase activity among 6 well-differentiated HCCs was strong in 3 (50%), weak in 2 (33%), and undetected in 1 (17%). All of 6 moderately-differentiated HCCs (100%), however, showed strong activity. As regards tumor size, 4 of 5 HCCs (80%) less than 3 cm in diameter showed strong telomerase activity. On the other hand, weak telomerase activity was detected in only 2 of 12 (17%) noncancerous liver tissues surrounding HCC nodules. The assay of telomerase activity may be a useful diagnostic marker of HCC regardless of tumor size, and the activity may be expressed even at early stage.

Carcinoma, Hepatocellular↗
PubMed1995

[A case of p-ANCA positive necrotizing vasculitis associated with Graves' disease].

A 22-year-old female who had been suffering from Graves' disease developed p-ANCA positive necrotizing vasculitis. Her Graves' disease has been treated with propylthiouracil (PTI) for 6 years, which failed to improve serum TSH. She developed transient and recurrent polyarthralgia 4 years before. Because of microscopic hematuria and polyarthralgia, She visited our hospital last year. She had hypergammaglobulinemia and microhematuria at that time. But no autoantibody was noted except anti-microsomal antibody at that time. Skin biopsy from her finger subdermal nodule revealed necrotizing vasculitis of small vessels. Serum p-ANCA was positive. She was admitted under the diagnosis of p-ANCA positive necrotizing vasculitis. Renal biopsy revealed mesangium proliferative glomerulonephritis. Since she developed telescoped sediments after admission, predonisolone (PSL) 50 mg daily was started. Clinical and laboratory findings improved quite well. PSL was gradually tapered after 6 weeks. She is being maintained in good condition on tapering doses of both PSL and PTI. The coincidence of Graves' disease and vasculitis is rare. This case may provide some important immunological insights into the study of pathogenesis of necrotizing vasculitis and Graves' disease.

Adult↗
PubMed1994

Direct hemoperfusion under infrahepatic inferior vena caval isolation for the intraarterial chemotherapy of pelvic tumors.

A new simple technique consisting of direct hemoperfusion under infrahepatic inferior vena caval isolation for intraarterial chemotherapy of pelvic tumors is herein described. The inferior vena cava is occluded at the infrahepatic level by means of balloon inflation using a balloon-tipped catheter (16F), which is placed through the right greater saphenous vein. The isolated infrahepatic vena caval blood is withdrawn by a centrifugal pump through a catheter (16F) in the contralateral greater saphenous vein and is filtered by direct hemoperfusion during intraarterial infusion of anticancer drugs. Venous reentry is provided by the central lumen of the balloon-tipped catheter. This procedure was used sequentially on two different occasions to treat a patient with an extensive pelvic tumor. Good hemodynamic stability and a reduction of the systemic drug toxicities were confirmed in both trials. Therefore, we believe that this technique is technically feasible and highly effective in reducing systemic toxicities during high-dose intraarterial chemotherapy for pelvic tumors.

Aged↗
PubMed1994

Effect of nucleosides and a nucleotide mixture on proliferation of human gastric cancer cells (KATO III).

The effect of the nucleotides and a nucleotide mixture (OG-VI), consisting of inosine, guanosine 5'-monophosphate (5'-GMP), cytidine, uridine, thymidine (TdR) (4:4:4:3:1 in molar ratio), and TdR co-administration on proliferation of KATO III human gastric cancer cells in culture was evaluated. Consumption of purine and pyrimidine by cancer cells and changes in cell number with OG-VI or TdR were compared with the control culture medium (Williams E) after 72 hour-culture. Addition of OG-VI or TdR did not enhance the cellular proliferation, but inhibited growth when given in higher concentrations (0.3-3 mM inosine, 0.3-3 mM 5'-GMP, 0.22-2.2 mM uridine, 74-740 microM TdR). Consumption rate of TdR in the medium was less in the TdR group, 33.7%, than in the OG-VI group, 72.2% (p < 0.05). This suggests that TdR metabolism is modulated by other nucleosides and nucleotide included in OG-VI. Under the coadministration of 5-fluorouracil (FUra), addition of OG-VI or TdR suppressed cellular proliferation (p < 0.05). The inhibition rate of cellular proliferation in the OG-VI group was slightly higher than the TdR group, but there was no statistically significant difference between the two groups. The combination of FUra with OG-VI or TdR enhances the antitumor effect of FUra. It is concluded that the OG-VI does not enhance the tumor cell proliferation and it is a potential biochemical modulator of FUra metabolism in human cancer cells.

Cell Division↗
PubMed1993

TAN-1120, a new anthracycline with potent angiostatic activity.

A potent angiogenesis-inhibitory compound TAN-1120 was found to be produced by a Streptomyces species isolated from a soil sample. The producing organism was characterized as a new subspecies of S. triangulatus and named S. triangulatus subsp. angiostaticus subsp. nov. due to its specific ability to produce the compound. This substance was isolated as a red powder by a combination of organic solvent extraction, silica gel column chromatography and preparative HPLC using an ODS column. Its structure was elucidated by chemical reactions and spectral analyses to be a new baumycin-group anthracycline. Reduction of TAN-1120 gave two compounds, a deoxy derivative and baumycin A1. TAN-1120 showed remarkably potent angiostatic activity in two conventional angiogenesis assay systems in vivo, while doxorubicin and daunomycin had far weaker activity. It strongly inhibited proliferation of vascular endothelial cells did not prevent capillary cord formation in vitro by the endothelial cells on extracellular matrix-coated plates. TAN-1120 is one of the most potent angiostatic agents reported.

3T3 Cells↗
PubMed1993

[A comparative study of tumor responses of hepatocellular carcinoma and colorectal hepatic metastasis to cytotoxic anticancer drug].

We investigated the characteristics of tumor responses of hepatocellular carcinoma (HCC, n = 14) and colorectal hepatic metastasis (CHM, n = 10) to high dose hepatic arterial chemotherapy using direct hemoperfusion under hepatic venous isolation. Adriamycin was given at doses ranging from 100 to 150 mg/m2. During drug infusion, two patients with HCC and three with CHM were treated by balloon-occluded arterial infusion (BOAI). Computerized tomographic findings after treatment were compared between the two diseases. In addition, response characteristics in each disease were investigated in relation to tumor factors such as size, capsule formation, vascularity and macroscopic type. Eight (57%) out of 14 patients with HCC showed either size reduction (n = 5) or liquefaction (n = 3), while the remaining six patients showed no apparent changes. On the other hand, seven (70%) of 10 patients with CHM showed liquefaction without any evidence of tumor size reduction. Regardless of the disease, all patients treated with BOAI had liquefaction as a sign of tumor responses. Based on these observations, it is concluded that response characteristics may differ depending on tumor factors such as vascularity and the nature of the treatment as represented by BOAI.

Adult↗
PubMed1992

[Suppressive effect of sevoflurane on somato-sympathetic reflexes in cats].

Effects of sevoflurane on the reflex activity of the sympathetic nervous system in cats were investigated by observing alteration of the amplitudes of somato-sympathetic medullary reflex potentials. These reflex potentials consist of two components, A- and C-reflex potentials, which are induced from the lumbar sympathetic trunk by electric stimulation of the ipsilateral femoral nerve. It is known that A- or C-reflex potential is induced by stimulating peripheral A-fiber group or C fiber group, respectively. Sevoflurane 1, 2 and 3% in oxygen for 30 minutes for each concentration by incremental fashion, were inhalated. Neither A nor C reflex potentials were suppressed by 1 and 2% sevoflurane but 3% sevoflurane caused a significant suppression of both reflex potentials in brain intact cats. Concentration-dependent suppression of C-reflex potentials and a tendency of concentration-dependent suppression of A-reflex potentials were observed in decerebrate cats. Mean arterial blood pressure showed a concentration-dependent decrease in both brain intact and decerebrate groups. These results indicate that sevoflurane with concentrations higher than 1 MAC (2.5% for cats) significantly suppresses somato-sympathetic reflex activities. The results suggest, however, that this agent with concentrations lower than 1 MAC suppresses the descending inhibitory system from supra-medullary centers so that the integrated sympathetic outflow from the medulla oblongata are not suppressed significantly. The results also suggest that direct depressive effect on the cardiovascular system by sevoflurane rather than through suppressive effect on sympathetic reflexes may play a major role in hypotension during inhalation of concentrations below 1 MAC.

Action Potentials↗
PubMed1991

TAN-931, a novel nonsteroidal aromatase inhibitor produced by Penicillium funiculosum No. 8974. I. Taxonomy, fermentation, isolation,characterization and biological activities.

A novel nonsteroidal aromatase inhibitor, TAN-931, was isolated from the culture filtrate of a soil isolate fungus, No. 8974. The strain was identified as Penicillium funiculosum No. 8974. TAN-931 inhibited human placental and rat ovarian aromatase activity, and the IC50 value was 17.2 and 162 microM, respectively. The inhibition of human placental aromatase was uncompetitive with respect to androstenedione conversion with a Ki value of 40 microM. When TAN-931 was subcutaneously administered at doses of 25, 50 and 100 mg/kg (once/day, x4) to 20-day-old female Sprague-Dawley rats treated with gonadotropin, the plasma estradiol-17 beta level and the weight of ovaries and uterus were markedly reduced in a dose-dependent manner. The in vivo inhibitory activity of TAN-931 was more potent than that of 4-hydroxyandrostenedione. Consecutive administration of TAN-931 (100 mg/kg, sc, twice/day, x 7) to 9-week-old male Sprague-Dawley rats did not induce any adrenal hypertrophy even though administration of aminoglutethimide caused 2-fold enlargement of the adrenal under the same conditions. Specific binding of TAN-931 to the estrogen receptor from a human breast cancer cell line, MCF-7, was not detected.

Adrenal Glands↗