Biomedical subjects

H Okuda

Publications and source records attributed to H Okuda.

At least 37 records · Page 2Linked to original sources

PubMed2001

Comparison of clinicopathological features of patients with hepatocellular carcinoma seropositive for alpha-fetoprotein alone and those seropositive for des-gamma-carboxy prothrombin alone.

BACKGROUND: There has been no comparative study of the clinicopathological features of HCC patients who are seropositive for alpha-fetoprotein (AFP) alone and those who are seropositive for des-gamma-carboxy prothrombin (DCP) alone. The authors, thus, performed this comparative study. METHODS: The clinicopathological features of patients with solitary hepatocellular carcinoma (HCC), who underwent a hepatectomy were compared among the four below groups according to the seropositivity of AFP and DCP: group A, seronegative for both AFP below 20 ng/mL and DCP below 40 mAU/mL; group B, seropositive for AFP above 100 ng/mL and seronegative for DCP; group C, seronegative for AFP and seropositive for DCP above 100 mAU/mL; and group D, seropositive for both AFP and DCP. RESULTS: Group B patients showed a higher incidence of HCC with an indistinct margin, and a somewhat higher incidence of small HCC less than 2 cm in greatest dimension compared with group C patients. By contrast, group C patients had a higher frequency of HCC with a distinct margin compared with that of an indistinct margin, large tumors more than 3 cm compared with that of small tumors less than 2 cm, and a somewhat higher frequency of moderately to poorly differentiated HCC compared with that of well-differentiated HCC. Our HCC cases showed advanced clinicopathological features in the order of group C, group B and group A. Groups C and D patients showed similar characteristics. CONCLUSIONS: Hepatocellular carcinoma patients who were seropositive for AFP alone demonstrated clinicopathological features of less advanced HCC compared with those who were seropositive for DCP alone.

Adult↗

PubMed2001

Effects of glutathione depletion by 2-cyclohexen-1-one on excitatory amino acids-induced enhancement of activator protein-1 DNA binding in murine hippocampus.

We have investigated the role of glutathione in mechanisms associated with excitatory amino acid signaling to the nuclear transcription factor activator protein-1 (AP1) in the brain using mice depleted of endogenous glutathione by prior treatment with 2-cyclohexen-1-one (CHX). In the hippocampus of animals treated with CHX 2 h before, a significant increase was seen in enhancement of AP1 DNA binding when determined 2 h after the injection of kainic acid (KA) at low doses. The sensitization to KA was not seen in animals injected with CHX 24 h before, in coincidence with the recovery of glutathione contents to the normal levels. By contrast, CHX did not significantly affect the potentiation by NMDA of AP1 binding under any experimental conditions. Prior treatment with CHX resulted in facilitation of behavioral changes induced by KA without affecting those induced by NMDA. These results suggest that endogenous glutathione may be at least in part involved in molecular mechanisms underlying transcriptional control by KA, but not by NMDA, signals of cellular functions.

Animals↗

PubMed2001

Artery relaxation by chalcones isolated from the roots of Angelica keiskei.

An EtOAc-soluble fraction from a 50% EtOH extract of the roots of Angelica keiskei inhibited phenylephrine-induced vasoconstriction in rat aortic rings, while an EtOAc-insoluble fraction had no effect at 100 micrograms/ml. Five active substances isolated from the EtOAc-soluble fraction of the roots were identified as xanthoangelol (1), 4-hydroxyderricin (2), and xanthoangelols B (3), E (4) and F (5), which inhibited phenylephrine-induced vasoconstriction at the concentrations of 10-100 micrograms/ml. It was found that xanthoangelol (1), 4-hydroxyderricin (2), and xanthoangelols E (4) and F (5) inhibited the phenylephrine-induced vasoconstriction through endothelium-dependent endothelium-derived relaxing factor (EDRF) production and/or nitric oxide (NO) production. Among the five chalcones, xanthoangelol B (3) inhibited the phenylephrine-induced vasoconstriction most strongly, and it inhibited the phenylephrine-induced vasoconstriction in the presence or absence of endothelium and in the presence or absence of NG-monomethyl-L-arginine (L-NMMA) (an NO synthetase inhibitor). Furthermore, 4-hydroxyderricin (2) and xanthoangelol B (3) at concentrations of 10-100 micrograms/ml concentration-dependently inhibited the elevation of intracellular free calcium [Ca2+]i induced by phenylephrine. These results demonstrate that compounds 1, 2, 4 and 5 inhibit phenylephrine-induced vasoconstriction through endothelium-dependent production of EDRF/NO and/or through the reduction of the [Ca2+]i elevation induced by phenylephrine. On the other hand, the inhibitory mechanism of compound 3 on phenylephrine-induced vasoconstriction might involve the direct inhibition of smooth muscle functions through the reduction of [Ca2+]i elevation without affecting EDRF/NO production.

Animals↗

PubMed2001

Effects of baicalein isolated from Scutellaria baicalensis Radix on adhesion molecule expression induced by thrombin and thrombin receptor agonist peptide in cultured human umbilical vein endothelial cells.

We examined the effects of various flavonoids isolated from the roots of Scutellaria baicalensis Georgi on adhesion molecule expression induced by thrombin and thrombin receptor agonist peptide (SFLLRNPNDKYEPF, TRAP) in cultured human umbilical vein endothelial cells. Thrombin and thrombin receptor agonist peptide induced endothelial leukocyte adhesion molecule-1 (ELAM-1) expression. Intercellular adhesion molecule-1 (ICAM-1) expression was also induced by thrombin, but not by TRAP. Baicalein isolated from Scutellariae Radix inhibited ELAM-1 expression induced by thrombin and thrombin receptor agonist peptide dose-dependently, with 50% inhibitory concentrations (IC50) of 5.53 +/- 1.68 microM and 2.44 +/- 1.08 microM, respectively. Furthermore, baicalein inhibited thrombin-induced ICAM-1 expression with an IC50 of 9.67 +/- 1.28 microM. In addition, baicalein inhibited the expressions of ELAM-1 and ICAM-1 stimulated by protein kinase C (PKC) activator phorbol myristate acetate (PMA).

Amino Acid Sequence↗

PubMed2001

Effects of Hachimi-jio-gan in aged rats.

OBJECTIVE: To evaluate the effects of Hachimi-jio-gan, a traditional Japanese Kampo medication composed of eight medicinal herbs used for treating older people. SUBJECTS: Sixteen laboratory-bred Fischer 344 rats DESIGN: The rats were divided into two groups. One was the control group and the other was given chow containing 7% Hachimi-jio-gan powder for a period 110-120 weeks. OUTCOME MEASURES: The rats were assessed for wheel running and an inclined screen test from weeks 119-120; then laboratory and histologic examinations were performed. RESULTS: The group receiving Hachimi-jio-gan was more active in spontaneous mobility during wheel running; they maintained a significantly higher angle of retaining posture than the control group on the inclined screen; there was no significant difference in laboratory and histologic findings. CONCLUSIONS: Aged rats that received Hachimi-jio-gan were more active and stronger than the control group rats. The findings suggest that Hachimi-jio-gan is a safe and effective Kampo prescription for aging rats.

Aging↗

PubMed2001

Isolation of an antitumor compound from Agaricus blazei Murill and its mechanism of action.

The Basidiomycete fungus Agaricus blazei Murill has traditionally been used as a health food for the prevention of cancer, diabetes, hyperlipidemia, arteriosclerosis and chronic hepatitis. In the present study, we examined the antitumor activities of various substances isolated from the lipid fraction of A. blazei. Tumor growth was retarded by the oral administration of the lipid fraction extracted from A. blazei with a chloroform/methanol mixture in sarcoma 180-bearing mice. The substance with the antitumor activity in the lipid fraction was isolated via silica gel column chromatography, eluted with an acetonitrile/methanol (3:2) mixture and identified as ergosterol by direct comparison of the (1)H NMR and mass spectrometry spectral data of an authentic sample. The oral administration of ergosterol to sarcoma 180-bearing mice significantly reduced tumor growth at doses of 400 and 800 mg/kg administered for 20 d without side effects, such as the decreases in body, epididymal adipose tissue, thymus, and spleen weights and leukocyte numbers induced by cancer chemotherapy drugs. Ergosterol had no cytotoxicity against tumor cells. To clarify the antitumor activity of ergosterol, we examined the effects of ergosterol on tumor-induced angiogenesis using two in vivo models. Intraperitoneal administration of ergosterol at doses of 5, 10 and 20 mg/kg for 5 consecutive d inhibited the neovascularization induced by Lewis lung carcinoma cell-packed chambers, suggesting that either ergosterol or its metabolites may be involved in the inhibition of tumor-induced neovascularization. Therefore, we further examined the inhibitory effects of ergosterol on Matrigel-induced neovascularization. Female C57BL/6 mice were subcutaneously inoculated with Matrigel containing acidic fibroblast growth factor and heparin with or without ergosterol. Ergosterol inhibited the Matrigel-induced neovascularization, suggesting that ergosterol directly inhibits Matrigel-induced neovascularization. From these results, it seems likely that the antitumor activity of ergosterol might be due to direct inhibition of angiogenesis induced by solid tumors. This is the first report of ergosterol as an antiangiogenic substance.

Administration, Oral↗

PubMed2001

Resveratrol isolated from Polygonum cuspidatum root prevents tumor growth and metastasis to lung and tumor-induced neovascularization in Lewis lung carcinoma-bearing mice.

Resveratrol is a naturally occurring phytoalexine found in medicinal plants. We found that resveratrol, at doses of 2.5 and 10 mg/kg, significantly reduced the tumor volume (42%), tumor weight (44%) and metastasis to the lung (56%) in mice bearing highly metastatic Lewis lung carcinoma (LLC) tumors, but not at a dose of 0.6 mg/kg. Resveratrol did not affect the number of CD4(+), CD8(+) and natural killer (NK)1.1.(+) T cells in the spleen. Therefore, the inhibitory effects of resveratrol on tumor growth and lung metastasis could not be explained by natural killer or cytotoxic T-lymphocyte activation. In addition, resveratrol inhibited DNA synthesis most strongly in LLC cells; its 50% inhibitory concentration (IC(50)) was 6.8 micromol/L. Resveratrol at 100 micromol/L increased apoptosis to 20.6 +/- 1.35% from 12.1 +/- 0.36% (P < 0.05) in LLC cells, and decreased the S phase population to 22.1 +/- 1.03% and 29.2 +/- 0.27% from 35.2 +/- 1.72% (P < 0.05) at concentrations of 50 and 100 micromol/L, respectively. Resveratrol inhibited tumor-induced neovascularization at doses of 2.5 and 10 mg/kg in an in vivo model. Moreover, resveratrol significantly inhibited the formation of capillary-like tube formation from human umbilical vein endothelial cells (HUVEC) at concentrations of 10-100 micromol/L; the degree of the inhibition of capillary-like tube formation by resveratrol was 45.5% at 10 micromol/L, 50.2% at 50 micromol/L and 52.6% at 100 micromol/L. Resveratrol inhibited the binding of vascular endothelial growth factor (VEGF) to HUVEC at concentrations of 10-100 micromol/L, but not at concentrations of 1 and 5 micromol/L. The degree of inhibition of VEGF binding to HUVEC by resveratrol was 16.9% at 10 micromol/L, 53.2% at 50 micromol/L and 47.8% at 100 micromol/L. We suggest that the antitumor and antimetastatic activities of resveratrol might be due to the inhibition of DNA synthesis in LLC cells and the inhibition of LLC-induced neovascularization and tube formation (angiogensis) of HUVEC by resveratrol

Angiogenesis Inhibitors↗

PubMed2001

Synergistic interaction of integrin and angiotensin II in activation of extracellular signal-regulated kinase pathways in vascular smooth muscle cells.

Integrins, major adhesion receptors and angiotensin II activate extracellular signal-regulated kinase (ERK) pathways and result in a mitogenic response such as the proliferation of vascular smooth muscle cells (VSMCs). We investigated mechanisms of collaboration or synergism between integrins and angiotensin II involving ERK pathways in VSMCs. Integrin activation by cell adhesion to fibronectin increased the phosphorylation level of focal adhesion kinase (FAK) upstream of the ERK pathway. angiotensin II induced a high increase in the phosphorylation level of FAK with integrin activation, but not in suspended cells. Integrin activation increased phosphorylation levels of ERK kinase (MEK) and ERK phosphorylation as well. Angiotensin II-induced MEK and ERK phosphorylation were retained even in suspended cells. Furthermore, with integrin activation, angiotensin II induced a much larger increase in the phosphorylation levels of MEK and ERK. These results suggest that simultaneous stimulation of integrin and angiotensin II receptors cause synergistic interaction in the activation of ERK pathway, possibly via phosphorylation of FAK, which may play a critical role in angiotensin II-mediated mitogenic response in VSMCs.

Angiotensin II↗

PubMed2001

Antitumour activity and adverse reactions of combined treatment with chitosan and doxorubicin in tumour-bearing mice.

We examined the antitumour activity and adverse reactions, such as myelotoxicity, gastrointestinal toxicity and body-weight loss,of the cancer chemotherapy drug doxorubicin when given with chitosan in sarcoma 180-bearing mice. Intraperitoneally administered doxorubicin (5 mg kg(-1)) given on days 1 and 8 with or without orally administered chitosan (200, 400 and 800 mg kg(-1) twice daily) inhibited tumour growth. The orally administered chitosan (400 and 800 mg kg(-1) twice daily) prevented doxorubicin-induced body-weight loss and small-intestinal mucosal injury. Similarly, the reduction of leucocyte number induced by the intraperitoneally administered doxorubicin was restored to normal by the oral administration of chitosan (400 and 800 mg kg(-1) twice daily). It seems likely that the mechanisms by which the orally administered chitosan protects against doxorubicin-induced gastrointestinal toxicity may be due to the formation of doxorubicin-chitosan complex in the small-intestinal mucosa through the diffusion of chitosan into the small-intestinal villi. In conclusion, our data suggest that the oral administration of chitosan prevents the gastrointestinal mucositis associated with doxorubicin therapy.

Animals↗

PubMed2001

[Medicinal plant and its related metabolic modulators].

We suggested a strategy for identifying anti-obesity drugs. The strategy aimed to prevent obesity through inhibiting intestinal absorption of dietary fat. Intestinal absorption of dietary fat was found to be reduced by tea saponin and chitosan through inhibiting pancreatic lipase activity, by chondroitin sulfate through inhibiting both pancreatic lipase activity and fatty acid absorption, and by lactosucrose through inhibiting beta-monoglyceride absorption. All these functional substances reduced plasma triglyceride levels previously elevated by oral administration of a lipid emulsion containing corn oil. Furthermore, these substances were found to cause reduction in perimetrial adipose tissue weight, which had been elevated by oral administration of a high fat diet (containing 40% of beef tallow) to female mice. Based on these results, a strategy for identifying anti-obesity drugs was discussed.

Animals↗

PubMed2001

Gelastic seizures in clusters in a case of West syndrome after perinatal hypothalamic hemorrhage.

We describe a 4-month-old Japanese infant with West syndrome with gelastic seizures in clusters. Smile developed around 3 months and gradually increased in frequency and intensity. Positron emission tomography showed hypoperfusion in bilateral hypothalamus. Interictal electroencephalogram (EEG) showed hypsarrythmia. Simultaneous video/EEG monitoring was performed. At first, a smile-like episode developed every several seconds, gradually increased to an abrupt flexion of the neck and extremities, and gradually decreased to a smile-like episode at the end. Ictal EEG revealed desynchronization. ACTH was effective. Smiles are common emotional responses in infancy. However, EEG and neuroimaging should be considered in a case of perinatal asphyxia and delayed development.

Asphyxia Neonatorum↗

PubMed2001

Augmented hepatocellular carcinoma progression and depressed Kupffer cell activity in rat cirrhotic livers.

To examine the property of hepatocellular carcinoma (HCC), rat HCC cells were implanted into normal and cirrhotic rat livers. Implanted HCC grew much more progressively in cirrhotic livers than in normal livers. Kupffer cells were decreased profoundly in cirrhotic livers, resulting in markedly impaired phagocytic activity. Furthermore, production of Kupffer cell-related cytokines, such as interleukin-1 beta and tumor necrosis factor-alpha, was decreased profoundly in cirrhotic livers. Our results indicate that liver cirrhosis is a prominent promoting factor in HCC progression, and that markedly depressed Kupffer cell activity may play a role in augmented HCC progression in cirrhotic livers.

Animals↗

PubMed2001

Intravenous readministration of an adenoviral vector performed long after the initial administration failed to induce re-expression of the original transgene in rats.

Although most humans have been exposed to wild-type adenoviruses in their childhood, titers of neutralizing antibodies against viruses decrease with the passage of time. In the present study, we infused adenoviruses carrying the lacZ gene into the tail vein of rats, and re-infused the same adenoviruses long after the initial administration. However, development of neutralizing antibodies against adenovirus and proliferation of adenovirus-specific T cells were elicited profoundly by adenoviral readministration, and transgene expression was not induced in rats. Our results may have important implications for efficacy considerations when adenoviral vectors are employed in clinical settings for the treatment of cancer.

Adenoviridae↗

PubMed2001

Adenovirus-mediated gene transfer into tumors: evaluation of direct readministration of an adenoviral vector into subcutaneous tumors of immunocompetent mice.

Because systemic administration of adenoviruses appears to be limited by their immunogenicity, we examined the feasibility of intratumoral administration of adenoviruses. Direct intratumoral administration of adenoviruses resulted in efficient but transient transgene expression. When adenoviruses were readministered directly into tumors, re-expression of the transgene was achieved. Transgene expression induced by the adenoviral readministration was, however, markedly weaker than that induced by the initial administration. Furthermore, intratumoral readministration of adenoviruses elicited profound humoral and cellular immune responses to adenoviruses. These results may have important implications for efficacy considerations when adenoviral vectors are used for clinical cancer gene therapy.

Adenoviridae↗

PubMed2001

Relationships between lipolysis induced by various lipolytic agents and hormone-sensitive lipase in rat fat cells.

Norepinephrine induced lipolysis in rat fat cells, in vitro, in a time- and concentration-dependent manner, without concomitantly increasing hormone-sensitive lipase (HSL) activity. It also induced, time and concentration dependently, HSL translocation from the cytosol to the lipid droplets in fat cells. Isoproterenol, forskolin, dibutyryl cyclic AMP, and theophylline also induced lipolysis in fat cells, but did not stimulate HSL activity. These agents also induced HSL translocation from the cytosol to the lipid droplets in fat cells: about 80% to 90% of all HSL was located in lipid droplets after incubation for 1 h. These results suggest that the critical event in lipolytic activation of fat cells induced by lipolytic agents is not an increase in the catalytic activity of HSL but translocation of HSL to its substrate on the surfaces of lipid droplets in fat cells.-Morimoto, C., K. Kameda, T. Tsujita, and H. Okuda. Relationships between lipolysis induced by various lipolytic agents and hormone-sensitive lipase in rat fat cells. J. Lipid Res. 2001. 42: 120;-127.

Adipocytes↗

PubMed2001

Thrombospondin-1 and -2 messenger RNA expression in invasive cervical cancer: correlation with angiogenesis and prognosis.

PURPOSE: TSP association with clinicopathological features, including microvessel count, regarding prognostic significance was examined in patients presenting with invasive cervical cancer. EXPERIMENTAL DESIGN: Gene expression of TSP-1 and TSP-2 was assessed by reverse transcription-PCR in 10 normal cervix and 78 invasive cervical cancer samples. RESULTS: TSP-1 and TSP-2 mRNA expression was detected in seven (70.0%) of the normal cervical specimens. TSP-2 mRNA expression in normal cervix was significantly higher than that in cases involving cervical cancer (P = 0.032). TSP-1 mRNA expression was significantly lower in tumors characterized by advanced stage (P = 0.047). Fifty-three patients displaying stage Ib-IIb cervical cancer underwent radical hysterectomy and pelvic lymphadenectomy. Expression of TSP-1 and TSP-2 mRNA was significantly lower in tumors exhibiting parametrial invasion (P = 0.016 and P = 0.049, respectively). Microvessel counts were significantly higher when decreased TSP-1 expression was evident (P = 0.029). The microvessel count in patients lacking TSP-2 mRNA expression was higher than that observed in patients displaying TSP-2 mRNA expression, although it was not statistically significant (P = 0.062). Subjects demonstrating TSP-1 mRNA expression exhibited significantly better prognosis than those lacking TSP-1 mRNA expression (P = 0.0038). Furthermore, TSP-1 mRNA expression was an independent prognostic factor in the multivariate analysis. CONCLUSIONS: These findings provide evidence that TSP-1 expression is of value as a prognostic factor in cervical cancer. The inverse correlation between TSP expression and microvessel count also indicates that decreased TSP expression may be associated with an angiogenic phenotype in this class of neoplasm.

Adult↗

PubMed2001

Thiopental enhances human platelet aggregation by increasing arachidonic acid release.

Conflicting results have been reported regarding the effect of thiopental on aggregation and cytosolic calcium levels in platelets. The present study attempted to clarify these phenomena. Using platelet-rich plasma or washed suspensions, platelet aggregation, thromboxane (TX) B2 formation, arachidonic acid (AA) release, and cytosolic free calcium concentrations ([Ca2+]i) were measured in the presence or absence of thiopental (30-300 microM). Platelet activation was induced by adenosine diphosphate (ADP, 0.5-15 microM), epinephrine (0.1-20 microM) arachidonic acid (0.5-1.5 mM), or (+)-9,11-epithia-11,12-methano-TXA2 (STA2, 30-500 nM). Measurements of primary aggregation were performed in the presence of indomethacin (10 microM). Low concentrations of ADP and epinephrine, which did not induce secondary aggregation in a control study, induced strong secondary aggregation in the presence of thiopental (> or = 100 microM). Thiopental (> or = 100 microM) also increased the TXB2 formation induced by ADP and epinephrine. Thiopental (300 microM) increased ADP- and epinephrine-induced 3H-AA release. Thiopental (300 microM) also augmented the ADP- and epinephrine-induced increases in [Ca2+]i in the presence of indomethacin. Thiopental appears to enhance ADP- and epinephrine-induced secondary platelet aggregation by increasing AA release during primary aggregation, possibly by the activation of phospholipase A2.

Arachidonic Acid↗

PubMed2001

[Effects of intraperitoneal injection of low-dose CDDP on 3 patients with ascites owing to peritonitis carcinomatosa of gastric and colorectal carcinoma].

Three patients received intraperitoneal chemotherapy of low-dose CDDP for carcinomatous ascites due to gastric and colorectal carcinoma. Intraperitoneal injection of CDDP (30-50 mg) was given and the patients underwent systemic chemotherapy. As a result, the QOL of all patients was improved. Adverse effects of Grade 1 were observed in 1 case (nausea). This intraperitoneal chemotherapy seems to be safe and effective for ascites due to peritonitis carcinomatosa.

Antineoplastic Agents↗