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T Ninomiya

Publications and source records attributed to T Ninomiya.

At least 55 records · Page 3Linked to original sources
PubMed1999

Potent synergistic effect of sho-saiko-to, a herbal medicine, during vaccine therapy in a murine model of hepatitis B virus carrier.

BACKGROUND: Traditional herbal medicine, sho-saiko-to (TJ-9), improves subjective symptoms, and a recently developed vaccine therapy reduces the viral replication in some chronic hepatitis B virus (HBV)-carriers. The study presented here considers the impact of a combination of vaccine therapy and TJ-9 and the mechanism underlying the therapeutic effect of TJ-9. MATERIALS AND METHODS: HBV-transgenic mice (HBV-Tg) expressing similar levels of HBV-related antigens and HBV DNA were used as an animal model of HBV-carrier state, and were assigned to receive either a TJ-9-enriched diet or a monthly injection of vaccine containing hepatitis B surface antigen (HBsAg), or both, for 12 consecutive months. RESULTS: Twelve months after starting the therapy, 9% (1 of 11), 61% (11 of 18), and 100% (10 of 10) of HBV-Tg receiving only the TJ-9-treatment, only the monthly vaccine, and both the TJ-9 and vaccine, respectively, responded to therapy and became completely negative for HBsAg. Spleen lymphocytes and antigen presenting cells (APC) from TJ-9-treated HBV-Tg produced significantly higher levels of IgM, IgG and antibodies to keyhole limpet hemocyanin (KLH) and showed significantly higher stimulatory capacity in allogenic mixed leukocyte reaction (MLR) compared with the spleen cells and APC from HBV-Tg receiving normal diet without TJ-9 (P < 0.05). CONCLUSION: These data confirm the therapeutic role of TJ-9 during HBV infection and inspire optimism of a widespread use of TJ-9 during immune therapies.

Adjuvants, Immunologic↗
PubMed1999

Inflammatory pseudotumor of the liver in a patient with chronic hepatitis C: difficulty in differentiating it from hepatocellular carcinoma.

A case of an inflammatory pseudotumor of the liver in a 75-year-old female with chronic hepatitis C whose radiologic features simulated that of hepatocellular carcinoma (HCC) is presented. On imaging studies, hypervascularity by CO2 ultrasound (US) angiography, enhancement at an early phase and isodensity at a late phase by incremental dynamic computed tomography (CT), perfusion defect by CT during arteriography (CTAP), and clinical background of hepatitis C virus (HCV) infection strongly suggested HCC. A US-guided needle biopsy revealed a mainly diffuse and polyclonal proliferation of lymphocytes positive for leukocyte common antigen (pan-lymphocyte cells), L-26 (B cell lymphocytes), and UCHL-1 (T cell lymphocytes), negative for both kappa and lambda light chains and sparsely distributed neutrophils and histiocytes. No lymphoid follicles were observed. The liver tissue around this tumor showed chronic hepatitis with mild activity and mild fibrosis. These histopathologic findings suggested that the diagnosis of inflammatory pseudotumor of the liver was tenable. As it is difficult to differentiate between inflammatory pseudotumor of the liver and HCC by imaging studies alone, supplemental biopsy, where possible, should be obtained when diagnostic imaging of tumors suggesting HCC is carried out. We emphasize that histopathology is a true gold standard in the diagnosis of this disease.

Aged↗
PubMed1999

Liver enriched transcription factors and differentiation of hepatocellular carcinoma.

The development of a complex organism relies on the precise temporal and spacial expression of its genome in many different cell types. The unique phenotype of hepatocytes arises from the expression of genes in a liver specific fashion, which is controlled primarily at the level of mRNA synthesis. By analysing DNA sequences implicated in liver specific transcription, it has been possible to identify members of the nuclear proteins, such as the liver enriched transactivating factors, hepatic nuclear factor 1(HNF-1), HNF-3, HNF-4, HNF-6, CCAAT/enhancer binding protein (C/EBP), and D binding protein (DBP), which are key elements in the liver specific transcriptional regulation of genes. Each of these factors is characterised by DNA binding domains that bind to unique DNA sequences (cis-acting factors) in the promoter and enhancer regions of genes expressed in terminally differentiated hepatocytes (such as, albumin, alpha 1-antitrypsin, transthyretin, alpha-fetoprotein). The determination of the tissue distribution of these factors and analysis of their hierarchical relations has led to the hypothesis that the cooperation of liver enriched transcription factors with the ubiquitous transactivating factors is necessary, and possibly even sufficient, for the maintenance of liver specific gene transcription. With the increase in information about transcriptional regulation, it should be possible to evaluate fully the clinicopathological usefulness of transcription factors in the diagnosis and treatment of hepatocellular carcinoma.

Carcinoma, Hepatocellular↗
PubMed1998

Positive selection of extrathymically developed T cells by self-antigens.

Most T cells develop through the thymus, where they undergo positive and negative selection. Some peripheral T cells are known to develop in the absence of thymus, but there is insufficient information about their selection. To analyze the selection of extrathymically developed T cells, we reconstituted thymectomized male or female recipient mice with bone marrow cells of mice transgenic for male H-Y antigen-specific T cell receptor (TCR). It was revealed that the T cells bearing self-antigen-specific TCR were not deleted in thymectomized male recipients. More importantly, the absence of H-Y antigen-specific T cells in thymectomized female recipients suggests positive selection of extrathymically developed T cells by the self-antigen. The extrathymically developed T cells in male mice expressed interleukin (IL)-2 receptor beta chain (IL-2Rbeta) and intermediate levels of CD3 (CD3(int)) but were natural killer cell (NK)1.1(-). They rapidly produced interferon gamma but not IL-4 after TCR cross-linking. Furthermore, a similar pattern of cytokine production was observed in CD3(int)IL-2Rbeta+NK1.1(-) cells in normal mice which have been shown to develop extrathymically. These results suggest that extrathymically developed CD3(int)IL-2Rbeta+NK1. 1(-) cells in normal mice are also positively selected by self-antigens.

Animals↗
PubMed1998

Direct evidence for the role of nitric oxide on the glutamate-induced neuronal death in cultured cortical neurons.

It has been reported that glutamate-induced neurotoxicity is related to an increase in nitric oxide (NO) concentration. An NO-sensitive electrode has been developed to measure NO concentration directly. Using this electrode, we examined NO concentration and neuronal survival after glutamate application in rat cultured cortical neurons. We also examined the effects of NMDA receptor antagonists, MK-801 and ketamine, and the NO synthetase inhibitor, L-NMMA on NO production and neuronal death. After 7 days in culture, application of glutamate (1 mM) or L-arginine (0.3 mM) to the cultured medium increased NO concentration, and decreased the number of anti-microtubule-associated protein 2 positive neurons. Both pretreatment with MK-801 (300 microns) and ketamine (300 microns) prevented glutamate-, but not L-arginine-induced increase in NO concentration and neuronal death. L-NMMA prevented both glutamate- and L-arginine-induced NO production and neuronal death. The nitric oxide donor, S-nitroso-N-acetyl-D,L-penicillamine (SNAP) also caused neuronal death, and MK-801, ketamine and L-NMMA did not prevent SNAP-induced toxicity. We have demonstrated excitatory amino acid-induced changes of NO concentration and the parallel relationship between changes of NO concentration and neuronal death. In conclusion, an increase in NO concentration does induce neuronal death, and the inhibition of the production of NO prevents glutamate-induced neuronal death.

Animals↗
PubMed1998

Expression of HNF-1 alpha and HNF-1 beta in various histological differentiations of hepatocellular carcinoma.

Hepatic nuclear factor 1 (HNF-1) regulates genes in a hepatocyte-specific manner. It has been previously reported that the ratio of HNF-1 alpha and HNF-1 beta mRNA is related to histological differentiation hepatocellular carcinoma (HCC). In this study, the expression levels of the HNF-1 alpha and HNF-1 beta proteins were analysed relatively and quantitatively in various histologically differentiated HCC and surrounding non-cancerous tissues, and HNF-1 alpha binding activity for the AT element of the B domain of the human alpha-fetoprotein enhancer was examined. Western blot analysis demonstrated that HNF-1 alpha protein was expressed at a higher level in well-differentiated HCC tissues than in the surrounding non-HCC tissues; on the other hand, the HNF-1 alpha protein was expressed at lower levels in moderately and poorly differentiated HCCs than in the surrounding non-HCC tissues. The levels of HNF-1 beta expression in well-differentiated and poorly differentiated HCCs were similar to and higher than those found in the respective surrounding non-cancerous portions. In binding assays, HNF-1 binding activity was high in well-differentiated HCC and lower in moderately and poorly differentiated HCCs. Most well-differentiated HCC cases showed immunohistochemical expression of HNF-1 alpha. These findings show that poor histological differentiation of HCC correlates with decreases in the level and activity of HNF-1 alpha proteins.

Blotting, Western↗
PubMed1998

Three patients with autoimmune cholangiopathy treated with prednisolone.

We describe three patients with autoimmune cholangiopathy, i.e., anti-mitochondrial antibody-negative and anti-nuclear antibody-positive primary biliary cirrhosis, who were treated with prednisolone. Serum anti-mitochondrial antibody and anti-pyruvate dehydrogenase-E2 component antibody were determined by immunofluorescence of frozen sections and enzyme-linked immunosorbent assay, respectively. Immunoblotting using mitochondria prepared from rat liver was performed to analyze anti-mitochondrial antibody in detail. Serum from one patient reacted with a 48-kilodalton protein, but sera from the other two patients failed to react with the mitochondrial proteins. There was a marked improvement in liver function test results after prednisolone treatment. Before treatment, liver biopsy in all three patients showed histological features of primary biliary cirrhosis with hepatocellular necrosis. Repeat biopsy during treatment showed marked amelioration of hepatocellular damage in all three patients, although bile duct involvement persisted in two patients. These findings suggest that prednisolone is an effective treatment for hepatocellular damage in patients with autoimmune cholangiopathy, but has little impact on the bile duct involvement.

Anti-Inflammatory Agents↗
PubMed1998

Control of hemorrhage during AVM surgery--with special reference to treatment of dilated capillaries and arteries around the nidus.

Control of hemorrhage during AVM surgery is one of the key issues to prevent NPPB. Inadequate procedures for hemostasis of feeders and drainers, so-called dilated capillaries and arteries (moja moja blood vessels) that are located on the side facing the normal brain, and inappropriate surgical strategies for intraoperative hemorrhage from these blood vessels are frequently the main cause of the difficulty in achieving hemostatic control. We conclude that it is important to aggressively reduce the occurrence of intraoperative hemorrhage and prevent or minimize the dilatation of abnormal capillaries and arteries due to inappropriate surgical procedures on the basis of the fundamental surgical strategy, i.e., feeder-->nidus-->drainer. Adequately securing the length and adequate coagulation of hemorrhagic blood vessel, employing a skillful bipolar coagulator technique aimed at controlling intraluminal pressure and blood flow on the central side, are believed to be key factors in hemorrhage treatment.

Blood Loss, Surgical↗
PubMed1998

Clinical significance of serum hyaluronic acid as a fibrosis marker in chronic hepatitis C patients treated with interferon-alpha: histological evaluation by a modified histological activity index scoring system.

The aim of the present study was to investigate the histological changes effected by interferon (IFN) treatment and to evaluate the clinical significance of serum hyaluronic acid (HA) as a marker of fibrosis. Forty-nine patients with chronic hepatitis C treated with IFN-alpha were divided into three groups according to the existence of viraemia: sustained complete responders (CR), complete responders with relapse (PR) and non-responders (NR). Needle biopsy sections of the liver taken before and at the end of IFN treatment were assessed according to the modified histological activity index (HAI) scoring system. Serum fibrosis markers, including HA, were measured at needle biopsies. Biopsies of CR at the end of treatment showed a significant improvement in fibrosis and necroinflammatory scores. More significant correlation was observed between fibrosis scores and serum levels of HA before IFN treatment (r = 0.607, P < 0.0001) than those between fibrosis scores, on the one hand, and peptide of type III procollagen (PIIIP; r = 0.531, P = 0.0004) or type IV collagen 7S domain (type IV-C; r = 0.241, P = 0.1062) on the other. Moreover, serum HA levels fell significantly in patients in whom fibrosis improved (P = 0.011). This is the first paper describing the advantages of the modified HAI scoring system over others in estimating the effect of IFN-alpha; the results also indicate that serum HA can be useful in monitoring liver fibrosis in chronic hepatitis C patients treated with IFN-alpha.

Adult↗
PubMed1997

Classification and treatment of vertebral dissecting aneurysm.

BACKGROUND: For many years, dissecting aneurysms of the intracranial vertebral artery were believed to be quite rare. In recent years, because vascular disorders have been studied more thoroughly by three dimensional-computed tomography (3D-CT), angiographically and pathologically, these aneurysms are being reported with more frequency. METHODS: Among the 45 patients diagnosed to have aneurysms arising from the vertebral artery or its branches over a 20-year period, 16 had dissecting aneurysms. The authors present their therapeutic strategy for these patients. Surgery was performed in the 16 patients, the most common technique being clip-occlusion or trapping of the parent artery wherever feasible, in an attempt to optimize cerebral blood flow. The dissecting aneurysms of the vertebral artery were classified into two groups for the purpose of determining a therapeutic approach, namely unilateral and circumferential groups. In the unilateral group, the dissection seemed to involve only on one side of the vessel according to the conventional cerebral angiogram. These patients underwent surgical reconstruction of the vertebral artery by direct clipping. In the circumferential group, the dissection was all around the artery. Proximal clipping or trapping was performed in this group. RESULTS: In six out of eight patients with unilateral dissecting aneurysms, vascular reconstruction was possible by direct clipping. Of these six patients, the surgical outcome was considered excellent in four, fair in one, and one patient died of cardiac failure after 12 days as his preoperative morbid condition remained the same after surgery. Two other patients with unilateral dissecting aneurysms were treated with trapping technique and the surgical outcome was excellent in one patient and good in the other patient. Both patients resumed a normal social life. In five out of eight patients with circumferential dissecting aneurysms, trapping or proximal clipping was performed and the surgical outcome was excellent in two patients, good in one and fair in one patient. One patient with preoperative brain stem infarction died of aspiration pneumonitis after 8 months. Two patients who were noted to have an increase in the size of aneurysm during follow-up angiography underwent a craniotomy with clipping and wrapping of the aneurysm. There was a favorable surgical outcome in both patients. The remaining three patients had Grade IV subarachnoid hemorrhage (SAH) prior to surgery and at autopsy a disturbed vascular wall was detected. CONCLUSION: The authors' experience suggests that when surgically feasible, direct clipping is an effective alternative approach in the treatment of dissecting aneurysms of the vertebral artery in which blood flow in the parent artery is to be preserved.

Adult↗
PubMed1997

Clinical study of 16 fully grown cerebral aneurysms.

The mechanismus of recurrence and enlargement of 16 cerebral aneurysms have been analyzed: 2 dissecting aneurysms, 6 fully grown aneurysms after neck clipping, 1 case after treatment with dome clip, 3 ruptured aneurysms that developed at the same sites and 4 cases that developed at other sites. From our investigation we concluded it was fundamentally important that the factor of the elastic lamina interna must attach in whole around the neck with precise neck clipping or adequate tight embolization involving positioning of the remaining elastica lamina interna in coil embolization.

Aortic Dissection↗
PubMed1997

A functioning black adenoma of the adrenal gland.

A 53-year-old female had clinical and laboratory findings suggestive of Cushing's syndrome. In contrast to the Cushing's syndrome caused by cortical adenoma, a high level of urinary 17-ketosteroids (17-KS) was also noted. Imaging studies revealed a right adrenal tumor. Right adrenectomy was performed; the surgical specimen revealed a black adenoma consisting of compact cells with numerous pigments which seemed to be lipofuscin in nature. The present case indicates that black adenoma as well as adrenocortical carcinoma should be suspected, when patients with Cushing's syndrome show an increased level of urinary 17-KS excretion.

17-Ketosteroids↗
PubMed1997

Restricted expression of cell adhesion kinase-beta in rat tissues.

Cell adhesion kinase-beta (CAK-beta) is a protein tyrosine kinase of the focal adhesion kinase subfamily, which contains large amino- and carboxyl-terminal domains. We studied the tissue distribution of CAK-beta and its mRNA by immunohistochemical staining and in situ hybridization. In rat brain, CAK-beta was mainly found in the medulla whereas CAK-beta mRNA was expressed in most neurons, especially pyramidal cells and Purkinje cells. In the small intestine, CAK-beta protein and mRNA were detected in the absorptive epithelial cells, and the protein was concentrated in the brush border. Double immunostaining for CAK-beta and actin showed that they co-localized in the brush border of small intestine cells. Immunoelectron micrography revealed that the anti-CAK-beta antibody localized within microvilli. In the kidney, the protein was mainly expressed in proximal tubular cells, which have well developed microvilli, although CAK-beta mRNA was observed in most urinary tubular cells. In other tissues, the ciliated cells of the epididymis strongly expressed CAK-beta mRNA and CAK-beta localized in the cilia. In addition, alpha- and beta-tubulin were identified in the rat brain lysates immunoprecipitated with anti-CAK-beta antibody. The present results demonstrate that CAK-beta is present at relatively high levels in cilia, axons, and microvilli. This suggests that CAK-beta may play important roles in the functions of these structures or that the CAK-beta-related signaling pathway is closely associated with cytoskeletal components.

Animals↗
PubMed1996

Intracellular signaling pathway of substance P-induced superoxide production in human neutrophils.

We examined the intracellular mechanisms of substance P-induced superoxide anion (O2-) production in human neutrophils. Addition of substance P (30 microM) caused O2- production and biphasic increases in intracellular Ca2+ concentrations ([Ca2+]i) (early transient and subsequent sustained components) associated with the formation of inositol 1,4,5-trisphosphate (IP3). O2- and [Ca2+]i were assayed by using ferricytochrome C and fura 2-AM, respectively. These responses were abolished by tachykinin NK1 receptor antagonists, [D- Pro9[spiro-gamma-lactam],Leu10,Trp11]physalaemin-(1-11) (GR82334) or [D-Arg1,D-Trp7,9,Leu11]substance P (spantide), and an intracellular Ca2+ chelator, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA-AM). Inhibition of IP3 formation by GTP-binding protein (G-protein) inactivators such as guanosine 5'-O-(2-thiodiphosphate) (GDP beta S) and islet-activating protein (IAP), or a phospholipase C inhibitor, 1-[6-[[17 beta-3-methoxyestra-1,3,5(10)- trien-17-yl]amino]hexyl]1 H-pyrrole-2,5-dione (U-73122), blocked the substance P-induced O2- production and biphasic increases in [Ca2+]i. An IP3 receptor antagonist, heparin, reduced both the substance P-induced O2- production and the transient increase in [Ca2+]i without any significant effects on the sustained increase in [Ca2+]i. Protein kinase C inhibitors, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7) and calphostin C, only slightly suppressed O2- production, and abolished the sustained increase in [Ca2+]i without any significant effects on the transient increase in [Ca2+]i. A Ca2+ entry blocker, nicardipine, completely inhibited the sustained increase in [Ca2+]i without affecting O2- production and the transient increase in [Ca2+]i. These results suggest that the tachykinin NK1 receptor/G-protein-linked IP3 formation with the resulting IP3-induced transient increase in [Ca2+]i is the main signal transduction pathway for substance P-stimulated O2- production in neutrophils.

Calcium↗
PubMed1996

Synthesized surface anatomy scanning (SSAS) for surgical planning of brain metastasis at the sensorimotor region: initial experience with 5 patients.

Surface anatomy scanning (SAS) is a powerful technique that uses T2-weighted magnetic resonance images (MRI) to visualize brain surface structures, and to precisely localize subcortical lesions. To overcome technical limitations of this method, synthesized SAS (SSAS) superimposes MR angiography (MRA) data on the SAS images. We describe our initial experience with surgical planning for the resection of metastases at the sensorimotor region in 5 patients using SSAS. Neurological deficits were assessed before and after surgical resection. Although 4 of 5 patients had mild to severe neurological deficits before surgery, three became symptom-free and no patient had an increased deficit after surgery. Our results undoubtedly provide palliative surgery for sensorimotor metastases. As SSAS is non-invasive and requires a short scanning time, this method could become a useful technique for the routine pre-operative simulation for surgery on brain surface lesions such as sensorimotor metastases.

Adenocarcinoma↗
PubMed1996

Expression ratio of hepatocyte nuclear factor-1 to variant hepatocyte nuclear factor-1 in differentiation of hepatocellular carcinoma and hepatoblastoma.

BACKGROUND/AIMS: Liver-specific protein genes have multiple cis-/trans-acting elements, but those accountable for hepatocytic differentiation are unclear. An AT-rich core sequence (AT motif) is essential as a cis-acting element for the hepatic transcription. Homologous proteins hepatocyte nuclear factor-1 (HNF-1) and variant HNF-1 (vHNF-1) bind to this motif. The ratio of HNF-1 to vHNF-1 mRNA was examined in various liver tissues with respect to their differentiation. METHODS: The competitive reverse transcriptional polymerase chain reaction was employed to amplify HNF-1 and vHNF-1 mRNA simultaneously and to examine their expression ratio in total RNA extracted from frozen liver tissues of 37 patients with hepatocellular carcinoma, five patients with hepatoblastoma, and 15 non-neoplastic liver tissues. RESULTS: The ratio of HNF-1 to vHNF-1 mRNA was higher in well-differentiated cases than in poorly-differentiated and undifferentiated cases, except that one poorly-differentiated hepatoblastoma displayed a high ratio. Non-neoplastic liver tissues had low ratios similar to poorly-differentiated hepatocellular carcinoma, the reason for which remained unknown. However, chronic hepatitis and liver cirrhosis cases also demonstrated low ratios, and hence degenerative changes themselves displayed no obvious influence on such ratios. Thus, the gene expression of HNF-1 and vHNF-1 seemed to be differentially regulated in neoplastic and non-neoplastic hepatocytes. CONCLUSIONS: These results suggested that the ratio of HNF-1 to vHNF-1 mRNA correlated with histological differentiation of HCC and hepatoblastoma.

Adult↗
PubMed1996

Infective endocarditis caused by Campylobacter fetus after allogeneic tooth transplantation: a case report.

A patient developed infective endocarditis caused by Campylobacter fetus. He gave a history of recent dental extraction and allogeneic tooth transplantation. He was treated with various antibodies to which the organism was said to be sensitive, but it was not until the transplanted tooth was removed that he started to improve. The mode of infection was thought to be blood borne through the open tooth socket from the raw chicken that he ate regularly.

Animals↗