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Biomedical subjects

H Furukawa

Publications and source records attributed to H Furukawa.

At least 127 records · Page 7Linked to original sources

A novel hydroxyl radical scavenger, nicaraven, protects the liver from warm ischemia and reperfusion injury.

BACKGROUND: Reactive oxygen species have been considered to be involved in liver injury at the procurement, preservation, and transplantation from donors without beating hearts. A novel hydroxyl radical scavenger, nicaraven with hydrophilic and lipophilic properties, infiltrates both intracellular and extracellular spaces where it effectively scavenges reactive oxygen species. Protection by nicaraven against ischemia and reperfusion damage of the brain, heart, and kidneys has been shown. The effect of this agent on the liver remains unclear. METHODS: Two-hour total hepatic vascular exclusion was used. Eighteen beagle dogs were randomly assigned to 2 groups: 12 animals were not treated (group I) and 6 were treated with nicaraven (group II). Nicaraven was administered intravenously (2mg/kg/min) for 60 minutes before ischemia and for 3 hours, starting 30 minutes before reperfusion. RESULTS: Two-week survival rates were 25% in group I and 100% in group II (P <.01). Nicaraven inhibited lipid peroxidation in the liver, improved hepatic and systemic hemodynamics and energy metabolism, and suppressed liver enzyme release, endothelin-1 elevation in hepatic venous blood, histologic damage, and neutrophil infiltration into the liver. CONCLUSIONS: Nicaraven exerted hepatic protection against warm ischemia and reperfusion injury. This may indicate nicaraven as a potential candidate to attenuate liver injury from warm ischemia and preservation in transplantation from donors without beating hearts.

Adenine Nucleotides↗

Expression of functional M2 muscarinic acetylcholine receptor in Escherichia coli.

The M2 muscarinic acetylcholine receptor mutant (M2 mutant), with a lack of glycosylation sites, a deletion in the central part of the third inner loop, and the addition of a six histidine tag at the C-terminus, was fused to maltose binding protein (MBP) at its N-terminus and expressed in Escherichia coli. The expression level was 0.2 nmol receptor per 100 ml culture, as assessed as [3H]L-quinuclidinyl benzilate ([3H]QNB) binding activity, when the BL 21 strain was cultured at 37 degrees C to a late growth phase and the expression was induced by isopropyl beta-thiogalactoside at 20 degrees C. No [3H]QNB binding activity was detected when it was not fused to MBP or when expression was induced at 37 degrees C instead of 20 degrees C. The MBP-M2 mutant expressed in E. coli showed the same ligand binding activity as the M2 mutant expressed in the Sporodoptera frugiperda (Sf9)/baculovirus system, as assessed as displacement of [(3)H]QNB with carbamylcholine and atropine. The MBP-M2 mutant was solubilized, purified with Co2+-immobilized Chelating Sepharose gel and SP-Sepharose, and then reconstituted into lipid vesicles with G protein Go or Gi1 in the presence or absence of cholesterol. The reconstituted vesicles showed GTP-sensitive high affinity binding for carbamylcholine and carbamylcholine-stimulated [35S]GTP gamma S binding activity in the presence of GDP. The proportion of high affinity sites for carbamylcholine and the extent of carbamylcholine-stimulated [(35)S]GTP gamma S binding were the same as those observed for the M2 mutant expressed in Sf9 cells and were not affected by the presence or absence of cholesterol. These results indicate that the MBP-M2 mutant expressed in E. coli has the same ability to interact with and activate G proteins as the M2 mutant expressed in Sf9, and that cholesterol is not essential for the function of the M2 muscarinic receptor.

ATP-Binding Cassette Transporters↗

Gluteus maximus adipomuscular turnover or sliding flap in the surgical treatment of extensive sacral chordomas.

Two cases with extensive posterior peritoneal defects after high sacral amputation for sacral chordoma are presented. An adipomuscular flap as a modification of the conventional gluteus maximus muscle flap was designed to obliterate an extensive residual posterior peritoneal dead space. The deep adipose tissue beneath the superficial fascia left on the gluteus maximus muscle was effectively used to provide more volume to the flap. The adipomuscular flap was turned over into the posterior peritoneal defect in the first case, and the flap was slid into the cavity in the other case. The adipomuscular flap eventually enabled the successful reconstruction of the posterior peritoneal defect, and the volume of the flap was well maintained behind the rectum, according to the postoperative magnetic resonance imaging findings in both cases.

Buttocks↗

Spinodal decomposition of two-dimensional fluid mixtures: A spectral analysis of droplet growth

The spinodal decomposition of two-dimensional fluid mixture is studied by numerical simulation. For the high viscous fluid mixture it has not been evident whether the interfacial tension is relevant to the droplet growth or not. A length scale R defined by the structure function extracting the effect of the long wavelength mode justifies a rapid growth close to R approximately t, but the length scale energetically defined reveals a much slower growth R approximately t(0.5), where t is time. This discrepancy represents the violation of the dynamical scaling with single length scale. The slow gowth of the length scale is attributed to the accumulation of the number of isolated droplets in phase separating state, whereas the rapid growth represents the relevance of the surface tension as the driving force in two dimensions. For a low viscous fluid mixture the dynamical scaling is a good assumption with the growth law R approximately t(2/3) up to a very large Reynolds number Re approximately 1500, which is the limit in the present simulation.

Journal Article↗

Prions: pathogenesis and reverse genetics.

Spongiform encephalopathies are a group of infectious neurodegenerative diseases. The infectious agent that causes transmissible spongiform encephalopathies was termed prion by Stanley Prusiner. The prion hypothesis states that the partially protease-resistant and detergent-insoluble prion protein (PrPsc) is identical with the infectious agent, and lacks any detectable nucleic acids. Since the latter discovery, transgenic mice have contributed many important insights into the field of prion biology. The prion protein (PrPc) is encoded by the Prnp gene, and disruption of Prnp leads to resistance to infection by prions. Introduction of mutant PrPc genes into PrPc-deficient mice was used to investigate structure-activity relationships of the PrPc gene with regard to scrapie susceptibility. Ectopic expression of PrPc in PrPc knockout mice proved a useful tool for the identification of host cells competent for prion replication. Finally, the availability of PrPc knockout and transgenic mice overexpressing PrPc allowed selective reconstitution experiments aimed at expressing PrPc in neurografts or in specific populations of hemato- and lymphopoietic cells. The latter studies helped in elucidating some of the mechanisms of prion spread and disease pathogenesis.

Animals↗

Evaluation of the therapeutic effect of transcatheter arterial embolization for hepatocellular carcinoma.

Transcatheter arterial embolization (TAE) has been widely performed for patients with hepatocellular carcinoma (HCC). However, the method of evaluating the therapeutic effect of TAE has not been established. We examined the rate of necrotic area to whole tumor (TN) by CT, the tumor regression rate (TR) and the reduction rate in serum alpha-fetoprotein (AFP) levels in patients with HCC who received hepatic resection within 3 months after TAE. In the evaluation of TN, the lipiodol accumulation in tumor was regarded as being necrotic. Rates of necrotic area, which were also examined pathologically (PN) in resected tumors, were compared with TN, TR and AFP reduction rates, respectively. Eighty-eight patients were enrolled in this study, and there was a significant positive correlation between TN and PN (r = 0.80, p < 0.001). Although TR significantly correlated to PN (p = 0.001), the correlation coefficient between them was low (r = 0.34). The correlation coefficients between AFP reduction rate and PN was 0.76 (p < 0.001) in 26 patients (30%) with an AFP level >/=200 ng/ml before TAE. The evaluation method using lipiodol accumulation in CT is the most useful for assessing the therapeutic effect of TAE, particularly when a sufficiently long interval exists between TAE and the evaluation, because of the highest correlation coefficient between TN and PN, and the availability of TN for all patients. The reduction rate in serum AFP levels was also useful in patients with AFP levels >200 ng/ml before treatment.

Adult↗

Chemical constituents of Micromelum minutum. Isolation and structural elucidation of new coumarins.

The chemical constituents of an acetone extract of the stems of Micromelum minutum Wight et Arn (Rutaceae), collected at Nakorn-Rachasima province in Thailand, were studied. Six new coumarins, named micromarin-A (1), -B (2), -C (3), -F (4), -G (5), and -H (6), were isolated along with six known coumarins, and their structures were elucidated by chemical and spectroscopic methods.

Coumarins↗

Chemical constituents of Avicennia alba. Isolation and structural elucidation of new naphthoquinones and their analogues.

Three new naphthoquinones and their analogues, named avicequinone-A (1), -B (2), -C (3), and avicenol-A (4), -B (5), -C (6), respectively, were isolated from the stem bark of Avicennia alba (Avicenniaceae) collected in Singapore, and their structures were elucidated by means of spectral methods. Gillan and co-workers have proposed that the structures of the new phytoalexins isolated from Avicennia marina are 1,2-naphthoquinones 8 and 9. Our synthetic and spectrometric studies showed that these structures should be revised respectively to 1,4-naphthoquinones 2 and 3, named avicequinone-B and -C by us.

Magnetic Resonance Spectroscopy↗

Four new furanone-coumarins from Clausena excavata.

Four new furanone-coumarins, clauslactones-N (4), -O (5), -P (6) and -Q (7) were isolated from the leaves and twigs of Clausena excavata BURM. f. (Rutaceae) collected in Indonesia and their structures were elucidated by spectroscopic analysis.

4-Butyrolactone↗

Chemical constituents of Glycosmis citrifolia (Willd.) Lindl. Structures of four new acridones and three new quinolone alkaloids.

The structures of two new dimeric acridone alkaloids, glycobismine-D (1) and -E (2), having a novel linkage as binary acridones, three monomeric acridones, glycocitrine-IV (3), -V (4), and -VI (5), and three quinolone alkaloids, glycocitlone-A (6), -B (7), and -C (8) from Glycosmis citrifolia (Willd.) Lindl. (Rutaceae) have been elucidated by spectrometric studies.

Acridines↗

Cholangiohepatitis in broiler chickens in Japan: histopathological, immunohistochemical and microbiological studies of spontaneous disease.

Forty-five broiler carcasses from 6 different flocks were condemned due to liver lesions at processing meat inspection, and collected for pathological and bacterial examinations. All affected chickens showed liver enlargement with discolouration and an apparent acinar pattern. The enlarged gallbladder and the extrahepatic bile ducts contained yellow inspissated cream-coloured material. Histopathologically, extensive proliferation of bile ductules with fibrosis was observed in interlobular connective tissue, and it spread to form bridges with adjoining triads. Destruction and obstruction of portal bile ducts with multiple granulomas due to bacterial infection and outflow of the bile were frequently observed. Many Gram-positive bacilli were seen in the lesions, and they were identified as Clostridium perfringens by indirect immunofluorescence staining technique. Clostridium perfringens was isolated from affected livers. These findings are consistent with cholangiohepatitis. Therefore, it is suggested that C. perfringens might be important in the pathogenesis of cholangiohepatitis in broiler chickens.

Animals↗

The risk for second primaries in gastric cancer patients: adjuvant therapy and habitual smoking and drinking.

STUDY PURPOSE: To examine whether adjuvant therapy for gastric cancer increases the risk for second primaries, and whether smoking and drinking increase the risk. SUBJECTS AND METHODS: 1,631 patients who were newly diagnosed with gastric cancer and underwent curative operation at Osaka Medical Center for Cancer and Cardiovascular Diseases during 1978-92. Incidence of second primaries were examined through linkage to Osaka Cancer Registry as of the end of December 1995. Observed number of second primaries (O) was compared with the expected according to the incidence in general population (E). Proportional hazards model was used to estimate hazard rate ratio (HR) for second primaries. RESULTS: 149 second primaries were observed. Seventeen cases, detected within 2 months after diagnosis of gastric cancer, were excluded. O/E ratio was 1.13 for adjuvant chemotherapy, 0.93 for immuno-chemotherapy, and 0.78 for immunotherapy, while 1.14 for operation only (not significant). Age-, sex-, and stage-adjusted HR was 1.02 (95% C.I. 0.69-1.50) for chemotherapy, 0.80 (0.41-1.57) for immuno-chemotherapy, and 0.60 (0.08-4.34) for immunotherapy, as compared with the risk for operation only. Among males, HR for current smokers vs. never smokers was 1.82 (1.02-3.26). CONCLUSIONS: Adjuvant therapy for gastric cancer did not significantly increase the risk for second primaries, while smoking elevated it.

Adolescent↗

Selective intraarterial contrast-enhanced CT of pancreaticoduodenal tumors: early clinical experience in evaluating blood supply and detectability.

OBJECTIVE: The purpose of this study was to compare CT with selective intraarterial contrast enhancement with IV contrast-enhanced CT for diagnostic usefulness in the detection of tumors in the pancreaticoduodenal region. SUBJECTS AND METHODS: intraarterial contrast enhanced CT was performed in 36 patients with tumors of the pancreaticoduodenal region. Feeding arteries of the tumors and distribution of hyperattenuating areas on intraarterial contrast-enhanced CT were analyzed with various routes of contrast material injections. The intraarterial contrast-enhanced CT scans were compared with the IV contrast-enhanced CT scans. RESULTS: In all 29 patients with standard vascular anatomy, the right cephalic portion of the pancreatic head was enhanced on CT during common hepatic or gastroduodenal arteriography and the left caudal portion was enhanced on CT during superior mesenteric arteriography. The enhanced areas were complementary to each other in the whole pancreatic head, including the tumor. Tumor conspicuity from the surrounding pancreatic tissue on intraarterial contrast-enhanced CT was not superior to that on IV contrast-enhanced CT in all but four patients with cystic tumors. After intraarterial contrast-enhanced CT, three patients with tumors less invasive than pancreatic ductal carcinoma underwent local resection of their lesions. CONCLUSION: Intraarterial contrast-enhanced CT for pancreaticoduodenal tumors has potential technical problems and is not valuable in improving the detectability of tumors other than cystic lesions because the enhancement of the wall and septa of the tumor is emphasized. However, the feeding artery of the tumor and its surrounding tissue were clearly depicted.

Adult↗

[Interim report on JFMTC Study no. 21 on the effectiveness of UFT as an adjuvant therapy for semi-advanced cancer of the stomach].

This interim report, for findings as of May, 1998, covers data on 435 gastrectomized patients with semi-advanced stomach cancer collected from 144 institutions between November, 1993 and March, 1996. The active arm of the study involved CDDP i.p. administration of 70 mg/m2 at the time of resective surgery, followed by UFT oral administration for one year at 3-4 capsules daily. A randomized control involved no adjuvant therapy after CDDP i.p. administered as in the active arm. The results obtained indicated no significant difference between the groups in terms of 3 year survival or disease free survival rates. Reports appearing elsewhere have suggested that 3-4 capsules/day of UFT may be insufficient to reach the threshold of the effective tissue level, and that 6 capsules may be necessary to obtain the expected results. (JFMTC: Japanese Foundation of Multidisciplinary Treatment for Cancer).

Antineoplastic Combined Chemotherapy Protocols↗

[Interim report of JFMTC study no. 20 on the effectiveness of high dose CDDP plus 5-FU regimen as an adjuvant therapy for far-advanced cancer of the stomach].

This interim analysis of the JFMTC study as of May, 1998 covers 321 gastrectomized patients with far-advanced stomach cancer from 135 institutions between November, 1993 and March, 1996. The intensive therapy group (I-group) received CDDP i.p. administration on resective surgery with 70 mg/m2 followed by CDDP i.v. of 80 mg/m2 (day 1, i.v.), accompanying 5-FU of 350 mg/m2/day (day 1-5, c.v.i.) in the 4th, 8th and 12th weeks. The I-group was randomly compared with the standard therapy group (S-group) of MMC of 6 mg/m2 i.v. in the 4th, 8th and 12th weeks and UFT of 3-4 capsules daily for postoperative one year. The results obtained were that 1. adverse reactions were found more in the I-group than in the S-group, particularly notable in the decrease in blood cells, loss of appetite and nausea/vomiting, and incidence of grade 3 or more being 13% (neutrophile leukocytes), 26% and 21%, respectively; 2. there was no significant difference between I- and S-groups in terms of 3-year survival or disease-free survival rates. (JFMTC: Japanese Foundation of Multidisciplinary Treatment for Cancer).

Antineoplastic Combined Chemotherapy Protocols↗