Biomedical subjects

Midori Hirai

Publications and source records attributed to Midori Hirai.

16 recordsLinked to original sources

PubMed2005

Nationwide survey on complementary and alternative medicine in cancer patients in Japan.

PURPOSE: To determine the prevalence of use of complementary and alternative medicine (CAM) by patients with cancer in Japan, and to compare the characteristics of CAM users and CAM nonusers. PATIENTS AND METHODS: A questionnaire on cancer CAM and the Hospital Anxiety and Depression Scale were delivered to 6,607 patients who were treated in 16 cancer centers and 40 palliative care units. RESULTS: There were 3,461 available replies for a response rate of 52.4%. The prevalence of CAM use was 44.6% (1,382 of 3,100) in cancer patients and 25.5% (92 of 361) in noncancer patients with benign tumors. Multiple logistic regression analysis determined that history of chemotherapy, institute (palliative care units), higher education, an altered outlook on life after cancer diagnosis, primary cancer site, and younger age were strongly associated with CAM use in cancer patients. Most of the CAM users with cancer (96.2%) used products such as mushrooms, herbs, and shark cartilage. The motivation for most CAM use was recommendation from family members or friends (77.7%) rather than personal choice (23.3%). Positive effects were experienced by 24.3% of CAM users with cancer, although all of them received conventional cancer therapy concurrently. Adverse reactions were reported by 5.3% of cancer patients. CAM products were used without sufficient information by 57.3% of users with cancer and without a consultation with a doctor by 60.7% of users. CONCLUSION: This survey revealed a high prevalence of CAM use among cancer patients, without sufficient information or consultation with their physicians. Oncologists should not ignore the CAM products used by their patients because of a lack of proven efficacy and safety.

Aged↗

PubMed2005

Multiple hypervascular liver nodules in a heavy drinker of alcohol.

A case of hypervascular nodules in the liver, but without hepatitis B or C virus infection in a 38-year-old woman with a history of alcohol abuse is presented. An ultrasound disclosed 1-2-cm hypoechoic tumors in the right and left lobes. Magnetic resonance imaging showed high-intensity tumors at both the T1-weighted and T2-weighted sequences. Incremental dynamic computed tomography and hepatic angiography revealed hypervascular tumors. Ultrasound-guided needle biopsy revealed no evidence of hepatocellular carcinoma, metastatic liver cancer, hemangioendothelioma, inflammatory pseudotumors or pseudolymphoma, but demonstrated stellate-scar fibrosis septa, which contained small unpaired arteries without hyperplasia dividing the nodule. Moreover, marked pericellular fibrosis, neutrophilic infiltration and Mallory bodies were observed in the cytoplasm. There was no evidence of bile duct proliferation. From these findings, the diagnosis of alcohol-induced fibrosis, distinctly different from focal nodular hyperplasia, was tenable. Further studies may provide insights into the pathogenesis of nodule formation and hypervascularity in heavy drinkers of alcohol.

Adult↗

PubMed2005

Structure-activity relationships of the inhibitory effects of flavonoids on P-glycoprotein-mediated transport in KB-C2 cells.

We studied the effects of flavonoids, naringenin (flavanone), baicalein (flavone), kaempferol, quercetin, myricetin, morin, and fisetin (flavonols) as well as two glycosides of quercetin on P-glycoprotein (P-gp) function in multidrug-resistant P-gp overexpressing KB-C2 cells. Flavonoids such as kaempferol and quercetin increased the accumulation of rhodamine-123 dependent on their chemical structure. Analysis by flow cytometry indicated that the increase in substrate accumulation was due to the inhibition of substrate efflux. Naringenin, which lacks the 2,3-double bond in the C ring, had no effect, although it was more hydrophobic than myricetin, fisetin and morin. Therefore, the planar structure of the flavonoids seemed to be important for their interaction with P-gp. The effects of other flavonoids on the accumulation of daunorubicin were in the order of kaempferol>quercetin, baicalein>myricetin>fisetin, morin. Quercetin-3-O-glucoside and rutin had no effect. The order of the effects corresponded with that of the partition coefficients. Difference in the number and position of hydroxyl groups in flavonoid molecules by themselves seemed to have little effect. These results suggested that hydrophobicity as well as planar structure is important for the inhibitory effects of flavonoids on P-gp-mediated transport.

ATP Binding Cassette Transporter, Subfamily B↗

PubMed2004

Phospholipase A2 products retain a neuron specific gamma isoform of PKC on the plasma membrane through the C1 domain--a molecular mechanism for sustained enzyme activity.

To clarify molecular mechanism for sustained activation of gamma protein kinase C (gammaPKC), a neuron-specific subtype, we investigated the involvement of phospholipase A2 (PLA2) products in the membrane association of gammaPKC upon activation of G protein coupled purinoceptors in CHO-K1 and NG 108-15 cells. In addition, the functional domain responsible for PLA2-product mediated retention of gammaPKC on the plasma membrane was determined by simultaneously monitoring two different fluorescence-tagged gammaPKCs and mutants in the same living CHO-K1 cells. Purinoceptor activation by UTP induced a transient translocation of gammaPKC from the cytoplasm to the plasma membrane. Interestingly, PLA2 inhibitors, bromoenol lactone (BEL) and arachidonyl-trifluoromethyl ketone (AACOF3), shortened the retention time of gammaPKC on the plasma membrane in cells treated with UTP, while a DAG kinase inhibitor did not affect it. The C1 domain deficient mutant (DeltaC1-gammaPKC) also showed short membrane association compared with wild type gammaPKC, when cells are treated with UTP or arachidonic acid (AA) plus a Ca(2+) ionophore. However, deletion of C1A or C1B subdomains (DeltaC1A-gammaPKC or DeltaC1B-gammaPKC) did not alter the retention time on the plasma membrane, whereas PLA2 inhibitor shortened the retention times of both mutants. These results indicate that PLA2 products prolong the retention of gammaPKC on the plasma membrane through the C1A and/or C1B subdomain in purinoceptor-stimulated CHO-K1 cells. The importance of PLA2 product and C1 domain for the retention of gammaPKC on the membrane was also confirmed using neuronal cell line, suggesting that these are part of molecular machinery for sustaining enzyme activity in neurons.

Animals↗

PubMed2004

Apoptotic pathway related to oval cell proliferation.

BACKGROUND AND AIM: Oval cells, liver stem cell-derived cells, are generated from the liver periportal region and spread into the parenchyma by an autocrine signaling pathway. The mechanism behind how oval cells take their place among packed silent hepatocytes, however, is not well understood. We hypothesized that apoptosis involves a decrease in hepatocytes surrounding oval cells. METHODS: Male Fisher rats were treated using the AAF/PH protocol to induce oval cells in the liver. Apoptosis was assessed by measuring the activity of caspase-3, -8 and -9, and apoptosis-related molecules such as caspase-3, Fas, Fas-L and Bax were also assessed by immunohistochemical analysis and reverse transcriptase-polymerase chain reaction (RT-PCR). Apoptosis was confirmed by TUNEL staining. Regarding antiapoptotic factors, nuclear factor-kappaB (NF-kappaB) DNA binding activity and proliferating cell nuclear antigen (PCNA) expression were examined. RESULTS: NF-kappaB elevated at the early stage of oval cell proliferation. Conversely, caspase activity increased after NF-kappaB elevation. The mRNA of caspase-3, Fas, Fas-L and Bax was induced during and after AAF/PH treatment. Immunohistochemically, oval cells lacked the expression of these proteins, whereas the hepatocytes, particularly those surrounding oval cells, expressed strongly. CONCLUSIONS: The present study suggests that the apoptosis in hepatocytes through both extrinsic and intrinsic pathways mediates oval cell proliferation.

Animals↗

PubMed2004

Antiproliferative activity of Rhinacanthus nasutus (L.) Kurz extracts and the active moiety, Rhinacanthin C.

Rhinacanthus nasutus (L.) Kurz (Acanthaceae) is a shrub widely distributed in South China and India. In this study, the antiproliferative activity of the ethanol extract of root and aqueous extract of leaves of R. nasutus, and the supposed active moiety rhinacanthin C was assessed in vitro using the human cervical carcinoma cell line HeLa, its MDR1-overexpressing subline Hvr100-6, human prostate carcinoma PC-3 cells and human bladder carcinoma T24 cells. Rhinacanthin C was chemically synthesized and its content in the R. nasutus extracts was determined by HPLC with a photodiode array detector. The antiproliferative activity of the R. nasutus extracts was also assessed in vivo using sarcoma 180-bearing mice. It was suggested that 1) the in vitro antiproliferative activity of rhinacanthin C was comparable with or slightly weaker than that of 5-FU, 2) rhinacanthin C showed antiproliferative activity for MDR1-overexpressing Hvr100-6 cells, similarly to parent HeLa cells, 3) the in vitro antiproliferative activity of the ethanol extract of root R. nasutus was due to rhinacanthin C, whereas that of the aqueous extract of leaves of R. nasutus was due to constituents other than rhinacanthin C, and 4) both of the R. nasutus extracts showed in vivo antiproliferative activity after oral administration once daily for 14 d.

Acanthaceae↗

PubMed2004

Proapoptotic effect of a dietary supplement: water soluble chitosan activates caspase-8 and modulating death receptor expression.

The effect of water-soluble chitosan, a natural polymer used as a dietary supplement, on human bladder-tumor cells was investigated. Apoptotic morphological change was demonstrated by nuclear staining. Chitosan-treated cells showed elevation of caspase-8-like activity, but no significant elevation of caspase-9-like activity, which suggest that proapoptotic effect of chitosan is attributable to death receptor activation and not to activation of the mitochondria-cytochrome c pathway. Chitosan increased expression of TNF-R1, but decreased Fas expression. Use of monoclonal antibodies to inhibit death-receptor signal transduction did not attenuate the proapoptotic activity of chitosan. Examination of death-ligands revealed that TNFalpha mRNA expression was markedly increased by chitosan treatment while FasL mRNA was not affected. Although the direct interaction of chitosan with death receptors remains unidentified, the results suggest that its proapoptotic effect might be related to interaction with TNFalpha or TNF-R1.

Apoptosis↗

PubMed2003

Dominant negative c-Jun inhibits platelet-derived growth factor-directed migration by vascular smooth muscle cells.

The mitogen-activated protein (MAP) kinase pathways has been shown to be necessary for mitogen-stimulated proliferation, but its role in cell migration has not been fully understood. In this study, we investigated the possible contribution of signaling pathways through c-Jun in platelet-derived growth factor (PDGF)-BB directed cell migration in rat aortic vascular smooth muscle cells (VSMCs) infected with a recombinant adenovirus containing the dominant-negative c-Jun (Ad-DN-c-Jun). DN-c-Jun protein was expressed dose-dependently in VSMCs infected with Ad-DN-c-Jun. Expression of DN-c-Jun significantly inhibited VSMC migration induced by PDGF-BB. Our results provide the first evidence that signaling pathways through c-Jun participates in cell migration induced by PDGF-BB in addition to other MAP kinase pathways in VSMCs.

Animals↗

PubMed2003

Different apoptotic regulation of TRAIL-caspase pathway in HBV- and HCV-related hepatocellular carcinoma.

Human hepatocellular carcinoma (HCC) appears to be strongly associated with apoptosis and its breakdown may be involved in the occurrence of HCC. Like the Fas/Fas-L system, the tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) transduces apoptosis in a number of cancers; it is also a clinical candidate for cancer therapy. To examine its applicability in future therapy, the apoptotic pathway through TRAIL was investigated in HBV- and HCV-related HCC that have different mechanisms of hepatocarcinogenesis. Caspase-3 activity and the expression of four types of TRAIL receptor mRNAs were quantitated in tumor and contiguous non-tumor tissues obtained from 27 patients with HCC (HBV-related in 10; HCV-related in 17). The expression of caspase-3 and TRAIL receptors was also examined immunohistochemically. A significantly positive correlation was observed between caspase-3 activity and TRAIL-R1, -R2. Caspase-3 activity and TRAIL-R1, -R2 expression in tumor tissue were significantly lower than those in non-tumor tissue in HBV-related HCC. Some HCV-related HCC cases, however, demonstrated elevated caspase-3 activity and TRAIL-R1, -R2 expression in tumor tissue. HBV-related HCC demonstrated significantly suppressed caspase-3 activity, signifying apoptosis. Both TRAIL-R1 and -R2 showed coefficient correlation with caspase-3 activity, and were strongly associated with apoptosis in human HCC.

Apoptosis↗

PubMed2002

Nanomolar amyloid beta protein activates a specific PKC isoform mediating phosphorylation of MARCKS in Neuro2A cells.

Myristoylated alanine-rich C kinase substrate (MARCKS), a protein associated with cell growth, neurosecretion and macrophage activation, is activated by protein kinase C (PKC) phosphorylation. We reported that amyloid beta protein (Abeta) activated MARCKS through a tyrosine kinase and PKC-delta in rat cultured microglia. Here we report that Abeta signaling pathway through a specific PKC isoform is involved in the phosphorylation of MARCKS in Neuro2A cells. Selective PKC inhibitors but not tyrosine kinase inhibitors significantly inhibited the phosphorylation of MARCKS induced by Abeta. Abeta selectively activated PKC-alpha among the four PKC isoforms localized in Neuro2A cells. PKC-alpha activated by Abeta directly phosphorylated a recombinant MARCKS in vitro, Translocation of PKC-alpha from the cytoplasm to the membrane and accumulation of phospho-MARCKS in the cytoplasm were induced by Abeta. These results suggest involvement of a phosphoinositide signaling system through PKC-alpha in the phosphorylation of MARCKS in neurons, an event which may be associated with mechanisms underlying neurotrophic and neurotoxic effects of Abeta.

Amyloid beta-Peptides↗

PubMed2002

Development of multicentric hepatocellular carcinoma after completion of interferon therapy.

We report a case of multicentric hepatocellular carcinoma that developed in a 74-year-old man 3 and 6 years after interferon (IFN) treatment for chronic hepatitis C, despite sustained virologic, biochemical, and histological improvement. Initially, serum hepatitis C virus RNA was positive and the patients' serum level of alanine aminotransferase (ALT; 82 IU/ml) was abnormal. Hepatitis B virus (HBV) in the serum was negative for surface antigen, surface antibody, core antibody, and DNA. The patient was started on 10 x 10(6) international units (IU) of IFNalpha, 3 days a week for a total of 24 weeks. After the IFN therapy, the patient demonstrated a normal serum ALT level, and was continuously negative for HCV-RNA, and histology improved from chronic active hepatitis to chronic persistent hepatitis. Follow-up studies with ultrasonography (US) every 3 months and computed tomography (CT) every 6 months revealed no space-occupying lesion (SOL) for 3 years after IFN treatment.US-guided biopsies of two 15-mm hypoechoic SOLs in segments eight (S8) and seven (S7) 34 and 74 months, respectively, after IFN treatment showed well-differentiated hepatocellular carcinoma (HCC). Clinical data, imaging studies, and histologic examinations showed that both tumors were multicentric HCC. Further studies may provide insights into the possible role of HCV in hepatocarcinogenesis in patients demonstrating HCV eradication by IFN treatment.

Aged↗

PubMed2002

CEA producing primary hepatic carcinoid.

Imaging studies of a hepatic tumor in a 53-year-old woman with elevated serum levels of neuron-specific enolase (NSE), carcinoembryonic antigen (CEA) and 5-hydroxyindole acetic acid (5HIAA) revealed a hypervascular tumor in the right lobe. Grossly, the brownish tumor was measured 13.5x12 cm with four daughter nodules. Microscopically, the majority of these columnar and round tumor cells had ribbon-or rosette-like patterns with the expression of neuroendocrine marker proteins, such as Grimelius, NSE, chromogranin A, and synaptophysin, and moderate expression of CEA but without the expression of cytokeratin nos 7,8,14,18,19 and OV-6; the minority had glandular patterns with a strong expression of CEA but without the expression of cytokeratin nos 7,8,14,18,19 and OV-6. Ultrastructurally, most tumor cells contained populations of electron-dense core granules ranging between 100 and 200 nm in diameter. After hepatectomy, serum CEA, NSE, and 5HIAA reverted to normal ranges and persisted for 19 months. These findings suggested that the diagnosis of primary hepatic carcinoid was tenable and that the tumor might derive from hepatic stem cells which acquired the additional nature of producing CEA without cytokeratins characteristic of hepatocytes or bile duct cells. Some molecular based approaches have attributed unique biological behavior and histogenesis to this carcinoid tumor.

Journal Article↗

PubMed2002

Eosionophilic pseudotumor of the liver due to Ascaris suum infection.

A case of eosinophilic pseudotumor of the liver due to Ascaris (A) suum is described in a 34-year-old-man with a high serum level of immunoglobulin E and hypereosinophilia ascribed to a history of atopic dermatitis since childhood. Multiple hepatic hypoechoic nodules detected by ultrasound were confirmed as low-density nodules on computed tomography (CT), and as low and high signal intensity lesions on T1-and T2-weighted magnetic resonance imaging (MRI), respectively. CT during arteriography (CTA) and arterial portography revealed multiple nodules with ring-shaped enhancement and perfusion defect, respectively. Biopsied liver tissue specimens did not contain tumor cells or atypical cells; instead, they showed marked infiltration of eosinophils with necrosis and Charcot-Leyden crystals in the portal tracts and hepatic sinusoides, suggesting parasitic infection, although neither larvae nor eggs were detected. The diagnosis of visceral larva migrans (VLM) due to A. suum was based on immunoserological tests. The patient was a habitual consumer of raw bovine liver, which may explain the A. suum infection. After drug therapy with albendazole, the hypoechoic nodules disappeared. Differential diagnoses and the possible transfection route of A. suum are discussed.

Journal Article↗

PubMed2002

MDR1 up-regulated by apoptotic stimuli suppresses apoptotic signaling.

PURPOSE: Recently, MDR1 (P-glycoprotein) and related transporters have been suggested to play a fundamental role in regulating apoptosis, but little information is available concerning the role of MDR1. Here, the effect of apoptotic stimuli on the MDR1 mRNA and apoptotic signaling was examined in MDR1-overexpressing cells. METHODS: The expression levels of mRNA for MDR1, MRP1, MRP2, p53, p21, Bax, and Bcl-2 were measured by real time quantitative polymerase chain reaction in HeLa and its MDR1-overexpressing sublines. The effects of apoptotic stimuli by cisplatin (CDDP) on their levels were also assessed as well as on caspase 3, 8, and 9 activities. RESULTS: MDR1 was rapidly upregulated when the cells were exposed to apoptotic stimuli by CDDP. The increase in Bax mRNA to Bcl-2 mRNA ratio after treatment with CDDP was suppressed in MDR1-overexpressing cells. The increases in caspase 3 and 9 activities after treatment with CDDP were suppressed in MDR1-overexpression cells. CONCLUSION: MDR1 is upregulated by apoptotic stimuli suppressed apoptotic signaling presumably via the mitochondrial pathway.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2002

Pharmaceutical and clinical assessment of hydroquinone ointment prepared by extemporaneous nonsterile compounding.

Ointments of the skin depigmentation agent hydroquinone (HQ) have been prepared by extemporaneous nonsterile compounding in Japan by imitating skin lightening creams commercially available in the U.S.A. and European Union. In our hospital, HQ ointments consisting of 5 or 10% HQ, 1.6% L(+)-ascorbic acid (AsA), 0.5% (w/w) Na2SO3, 10% (v/w) glycerin and hydrophilic ointment have been prepared. However, various problems have been observed including chromatic aberration of HQ ointments, relatively large variability of efficacy, and undesirable side effects although they were mild. Herein, the pharmaceutical and clinical properties of the HQ ointments were evaluated. HQ ointments were highly effective for treatment of various types of skin pigmentation. Chromatic aberration occurred during 3 months of storage, but this could be suppressed by storage at 4 degrees C. Chromatic aberration was independent of prescribed HQ content, and was not explained by alterations of HQ or p-benzoquinone (p-BQ) contents. Unexpectedly, removal of both antioxidants resulted in suppression of chromatic aberration, but an increase in p-BQ content. Acidification by removal of Na2SO3 only was further effective for the suppression of chromatic aberration, but with a decrease of p-BQ content except in the initial period. Chromatic aberration was due to water soluble material and insoluble material both formed by co-existence of HQ and p-BQ at a molecular ratio of 5:3 to 1:1. 1H-NMR analysis elucidated that the water soluble material was not HQ or p-BQ, and the insoluble material was a complex of HQ and p-BQ with non-covalent binding.

Antioxidants↗

PubMed2002

Effects of St John's wort and hypericin on cytotoxicity of anticancer drugs.

St John's wort (SJW) is Hypericum perforatum L., Hypericaceae, a herbaceous perennial plant native to Europe and Asia, and its various preparations are widely used for the treatment of mild-to-moderately severe depressive disorders. With increasingly prevalent use, the interactions with SJW preparations with co-administered drugs have been reported, presumably via MDR1-mediated processes. In this paper, the effects of SJW extract on antiproliferative effects of anticancer drugs and the expression of MDR1 mRNA were examined using HeLa and its MDR1-overexpressing subline. The effects on MDR1-mediated transport were also evaluated using [(3)H]digoxin and LLC-GA5-COL150 cells, which were established by transfection of human MDR1 cDNA into porcine kidney epithelial LLC-PK(1) cells. The content of hypericin, a presumed active moiety within SJW extract, was determined by HPLC with a photo diode array to be 0.085 (w/w)%, and the effects of hypericin were also evaluated and compared with those of SJW extract. It was concluded that SJW extract reversed the cytotoxicity of paclitaxel and slightly of daunorubicin, down-regulated MDR1 mRNA, and inhibited MDR1-mediated transport, presumably due to other components than hypericin.

Journal Article↗