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T Ninomiya

Publications and source records attributed to T Ninomiya.

At least 37 records · Page 2Linked to original sources
PubMed2001

An autopsy case of primary biliary cirrhosis with severe interstitial pneumonia.

A 74-year-old woman was admitted to our hospital because of interstitial pneumonia. She had a 14-year history of primary biliary cirrhosis (PBC) diagnosed histologically, with a positive test for anti-mitochondrial antibodies and elevated biliary enzyme activity. She also had a 7-year history of rheumatoid arthritis and a 26-year history of Sjögren's syndrome. Though the symptoms of these complications improved, the interstitial pneumonia deteriorated very quickly and the patient died of respiratory failure due to acute exacerbation of interstitial pneumonia when the activity of PBC decreased. We report this case because it is relatively rare for PBC to be complicated by severe interstitial pneumonia, and it may offer insight into the etiology of these diseases.

Aged↗
PubMed2001

Non-invasive approach for diagnosing atrophic gastritis using the 13C-bicarbonate breath test.

The experiments presented here were done to evaluate whether the levels of CO2 in respiratory air during the 13C-bicarbonate breath test (13C-BBT) may be used as a marker of non-invasive diagnosis of the levels of atrophic gastritis. Twenty-eight patients with chronic gastritis and five healthy volunteers were enrolled in the study. Moreover, experimental gastritis was induced in rats by N-methy-N-nitro-N-nitrosoguanidine. In human, the levels of atrophic gastritis were evaluated from the vascular pattern of the gastric fornix. Total delta 13CO2 calculated from the 13C-BBT and the mucosal thickness ratio (MTR) were measured in rats with experimental gastritis. The levels of 13CO2 were significantly higher from patients with a vascular pattern at the fornix than in those without a vascular pattern (p<0.01). There was a good correlation between MTR and the levels of 13CO2, in rats with experimental gastritis (p<0.01). These findings indicate that the levels of 13CO2 during 13C-BBT reflect the levels of atrophic gastritis and show its clinical significance for non-invasive evaluation of atrophic gastritis. This has important clinical implications in selecting Helicobacter pylori-positive cases for therapy and follow-up.

Age Factors↗
PubMed2000

Sodium overload through voltage-dependent Na(+) channels induces necrosis and apoptosis of rat superior cervical ganglion cells in vitro.

Using the failure to exclude trypan blue as a criterion for cell death, we found that veratridine, the voltage-dependent Na(+) channel activator, exerted its toxicity to cultured sympathetic neurons in a dose-dependent manner (half-maximal toxicity occurred at 2 microM). The co-presence of tetrodotoxin completely reversed the toxicity only at concentrations of veratridine < 20 microM. Veratridine neurotoxicity was due to the influx of Na(+); a medium low in Na(+) (36 mM) completely abolished its neurotoxicity, whereas a Ca(2+)-free medium did not attenuate its neurotoxicity. Furthermore, the buffering action of 1, 2-Bis-(2-aminophenoxy)ethane-N,N,N',N',-tetraacetate (BAPTA) on veratridine-induced increase in intracellular Ca(2+) levels neither blocked veratridine neurotoxicity in normal medium, nor attenuated the low Na(+) effect. Elevated K(+) effectively blocked veratridine neurotoxicity in a Ca(2+)-dependent manner. Cytoplasmic pH measurements using a fluorescent pH indicator demonstrated that cellular acidification (from pH 7.0 to pH 6.5) occurred upon treatment with veratridine. Both veratridine-induced acidification and cell death were ameliorated by 5-(N-ethyl-N-isopropyl)amiloride, the specific inhibitor of the Na(+)/H(+) exchanger (IC(50) = 0.5 microM). Finally, necrosis occurred predominantly in veratridine neurotoxicity, but both staining with bis-benzimide and TUNEL analysis showed nuclear features of apoptosis in sympathetic neurons undergoing cell death.

Animals↗
PubMed2000

Alteration of veratridine neurotoxicity in sympathetic neurons during development in vitro.

Neurotoxic effects of veratridine, the activator of voltage-dependent Na+ channels, were examined at various stages of in vitro development of superior cervical ganglion cells dissociated from newborn rats. Veratridine neurotoxicity did not occur in 1DIV (days in vitro) neurons, but occurred in 7DIV neurons, both of which depend on NGF for survival, but elevated K+ supports only the latter. TUNEL and electron microscopic analyses revealed that 7DIV neurons underwent both apoptotic and necrotic cell death. Veratridine was also toxic to 21DIV neurons which are independent of NGF for survival. Nuclear features of apoptosis, however, were greatly reduced in these neurons undergoing cell death, suggesting that nuclear vulnerability is also subject to developmental regulation in vitro.

Animals↗
PubMed2000

Absence of CD83-positive mature and activated dendritic cells at cancer nodules from patients with hepatocellular carcinoma: relevance to hepatocarcinogenesis.

Mature and activated dendritic cells (CD83-positive DCs) are essential for the recruitment and survival of activated tumor-specific lymphocytes during carcinogenesis. The frequencies of CD83 positive DCs were almost same in peripheral blood from patients with hepatocellular carcinoma (HCC) and cirrhosis of liver (LC). However, the numbers of CD83 positive DCs in liver tissues were significant lower in HCC compared with LC (6.6+/-10.9 vs. 33.3+/-24 DCs/specimen, P<0.05). Most importantly, there were no CD83-positive DCs at cancer nodules in HCC. A role of infiltration of activated DCs in liver during hepatocarcinogenesis is shown.

Antigens, CD↗
PubMed2000

Alteration of the membrane lipid environment by L-palmitoylcarnitine modulates K(ATP) channels in guinea-pig ventricular myocytes.

Sarcolemmal adenosine 5'-triphosphate-sensitive K+ channels (K(ATP)) are dramatically up-regulated by a membrane phospholipid, phosphatidyl-inositol-4,5-bisphosphate (PIP2). During ischaemia, L-palmitoylcarnitine (L-PC), a fatty acid metabolite, accumulates in the sarcolemma and deranges the membrane lipid environment. We therefore investigated whether alteration of the membrane lipid environment by L-PC modulates the K(ATP) channel activity in inside-out patches from guinea-pig ventricular myocytes. L-PC (1 microM) inhibited KATP channel activity, without affecting the single channel conductance, through interaction with Kir6.2. L-PC simultaneously enhanced the ATP sensitivity of the channel [concentration for half-maximal inhibition (IC50) fell from 62.0+/-2.7 to 30.3+/-5.5 microM]. In contrast, PIP2 attenuated the ATP sensitivity (IC50 343.6+/-54.4 microM) and restored Ca2+-induced inactivation of KATP channels (94.1+/-13.7% of the control current immediately before the Ca2+-induced inactivation). Pretreatment of the patch membrane with 1 microM L-PC, however, reduced the magnitude of the PIP2-induced recovery to 22.7+/-6.3% of the control (P<0.01 vs. 94.1+/-13.7% in the absence of L-PC). Conversely, after the PIP2-induced recovery, L-PC's inhibitory action was attenuated, but L-PC partly reversed the PIP2-mediated decrease in the ATP sensitivity (IC50 fell from 310+/-19.2 to 93.1+/-9.8 microM). Thus, interaction between L-PC and PIP2 in the plasma membrane appears to regulate K(ATP) channels.

Adenosine Triphosphate↗
PubMed2000

Ineffective control of murine cytomegalovirus by IE1-specific cytotoxic T lymphocytes during protracted infection in the lung.

Interstitial pneumonia caused by cytomegalovirus (CMV) is a fatal disease in immunocompromised patients. In order to examine the defense mechanism against the virus in the lung, we employed an intratracheal infection model in susceptible mice. In mice infected intratracheally with murine CMV, a protracted infection was observed where infectious virus was detected up to 21 days of infection. During this prolonged infection, massive accumulation in the lung of CD8+ T cells with activated phenotypes occurred and these CD8+ T cells showed direct ex vivo cytolytic activity against target cells pulsed with the nonamer peptide derived from IE1 protein of the virus, which has been shown to be the dominant epitope recognized by most of virus-specific CTL. Moreover, adoptive transfer of in vitro induced IE1 peptide-specific CTL line showed no anti-virus effect in the lung, although they were effective in the spleen. Hence, there is reason to assume the IE1-specific CTL induced in vivo or in vitro plays limited roles during the prolonged infection in the lung.

Animals↗
PubMed2000

Recurrence of gastric ulcer dependent upon strain differences of Helicobacter pylori in urease B gene.

To evaluate the role of different strains of Helicobacter pylori on the recurrence of gastric ulcer, we divided H. pylori into four types (I, II, III, and IV) according to the urease B gene using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The relationship between the recurrence of gastric ulcer and the prevalence of H. pylori types was studied in 32 patients with benign open gastric ulcers using upper gastrointestinal endoscopy. The rate of recurrence was significantly lower in patients with type II than in patients with types I, III, and IV (P<0.05). Using Mongolian gerbils, an animal model of H. pylori infection, we also showed that the occurrence of gastric ulceration following restraint water-immersion stress was significantly lower in type II compared with types I and III. These data indicate that in the context of ulcer recurrence, it is not necessary to eradicate H. pylori during infection with type II.

Aged↗
PubMed2000

Localization and characterization of antigen-presenting dendritic cells in the gastric mucosa of murine and human autoimmune gastritis.

BACKGROUND: Activated CD4+ T cells and inflammatory cytokines are implicated in the pathogenesis of experimental autoimmune gastritis. However, there is a paucity of information about the cells that induce them. Antigen-presenting dendritic cells (DCs) play a cardinal role in the formation and survival of activated lymphocytes. MATERIALS AND METHODS: Autoimmune gastritis was induced in neonatal BALB/c mice by thymectomy. DCs were detected in situ in the gastric mucosa from thymectomized mice and in patients with autoimmune gastritis, by immunohistochemistry and immunoelectron microscopy. The expression of MHC class II and CD86 antigens on DCs in the gastric mucosa and spleen was evaluated in dual-colour flow cytometry. RESULTS: DCs were detected in the gastric mucosa of mice with autoimmune gastritis, and the number of DCs increased as the levels of gastritis became more severe as time passed following thymectomy. Flow cytometric analyses revealed that more than 60% of the DCs in the gastric mucosa had a mature phenotype (expressed MHC class II and/or CD86 antigens) both at 4 and 16 weeks after thymectomy. Activated and mature DCs were localized in the gastric mucosa from patients with autoimmune gastritis. CONCLUSIONS: This is the first report on the localization and phenotypes of DCs in the gastric mucosa of autoimmune gastritis. The presence of mature DCs in the gastric mucosa of murine and human autoimmune gastritis, in spite of their absence in the gastric mucosa of normal mice, suggests that mature DCs play a role in the pathogenesis of autoimmune gastritis.

Animals↗
PubMed2000

Characterization of CD4- CD8- CD3+ T-cell receptor-alphabeta+ T cells in murine cytomegalovirus infection.

In this study, we have investigated that after the intraperitoneal infection with murine cytomegalovirus (MCMV), the CD3+ CD4- CD8-(double negative; DN) T-cell receptor (TCR)alphabeta+ T cells increased in peritoneal cavity, liver and spleen in both resistant C57BL/6 and susceptible BALB/c mice. The total cellular population of these cells showed peak levels around day 5 after infection in all the three investigated organs and the following phenotypical and functional characteristics emerged. The peritoneal DN TCRalphabeta+ T cells expressed highly skewed TCRVbeta8 on day 5 after infection compared with the uninfected mice, but those in spleen and liver showed moderate and low skewed TCRVbeta8, respectively. The percentages of NK1.1+ DN TCRalphabeta+ T cells gradually decreased as did modulation of some of their activation markers consistent with an activated cell phenotype. The peritoneal DN TCRalphabeta+ T cells on day 5 after infection expressed the genes of interferon-gamma (IFN-gamma), tumour necrosis factor-alpha, Eta-1 (early T-cell activation-1) and MCP-1 (monocyte chemoattractant protein 1) but lacked expression of interleukin-4 (IL-4). After in vitro stimulation with phorbol 12-myristate 13-acetate and calcium ionophore in the presence of Brefeldin A, higher frequencies of intracellular IFN-gamma+ DN TCRalphabeta+ T cells were detected in all three investigated organs of infected mice compared with those of uninfected mice. Stimulation of peritoneal DN TCRalphabeta+ T cells with plate-bound anti-TCRbeta monoclonal antibodies showed proliferation and also produced IFN-gamma but not IL-4. These results suggest that DN TCRalphabeta+ T cells were activated and may have an antiviral effect through producing IFN-gamma and some macrophage-activating factors during an early phase of MCMV infection.

Animals↗
PubMed2000

Vgamma1+ gammadelta T cells play protective roles at an early phase of murine cytomegalovirus infection through production of interferon-gamma.

Cytomegalovirus (CMV) causes severe opportunistic infection in immunocompromised hosts. The importance of conventional alphabeta T cells in protection against CMV infection has been well documented. However, the role of the second T-cell population (which express the gammadelta T-cell receptor) in CMV infection is not known. In the present study, we analysed the function and protective role of gammadelta T cells in a murine cytomegalovirus (MCMV) infection model. After intraperitoneal infection with MCMV, the number of gammadelta T cells increased in the liver and peritoneal cavity from day 3, and reached a peak on day 5. The gammadelta T cells showed an activated T-cell phenotype and predominantly expressed Vgamma1, which is known to be expressed by heat-shock protein 65 (hsp 65)-specific gammadelta T cells. Analysis of cytokine expression demonstrated that the MCMV-induced gammadelta T cells expressed interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) but not interleukin-4 (IL-4), implying their participation in the cell-mediated immune response against MCMV. Depletion of gammadelta T cells by anti-T-cell receptor (TCR) gammadelta monoclonal antibody (mAb) treatment resulted in significant increase of virus titre and decrease of IFN-gamma in the liver on day 3 after MCMV infection, which further supports the importance of gammadelta T cells in early protection against infection. Finally, the MCMV-induced gammadelta T cells produced IFN-gamma in vitro in response to hsp 65. Our results suggest that gammadelta T cells participate in early protection against MCMV infection through recognition of hsp 65 and production of IFN-gamma.

Animals↗
PubMed2000

Interleukin-1alpha-dependent regulation of matrix metalloproteinase-9(MMP-9) secretion and activation in the epithelial cells of odontogenic jaw cysts.

Interleukin-1alpha (IL-1alpha) and matrix metalloproteinase-9 (MMP-9) are thought to be involved in odontogenic cyst expansion. In this study, we investigated the effects of IL-1alpha on the secretion and activation of MMP-9 in odontogenic jaw cysts. An active form of MMP-9 was present in odontogenic keratocyst (6 of 8 cases) fluids more frequently than dentigerous cyst (3 of 10 cases) and radicular cyst (3 of 10 cases) fluids, although proMMP-9 was present in all cyst fluids. Odontogenic keratocyst fragments in explant culture secreted a larger amount of IL-1alpha than dentigerous cyst and radicular cyst fragments in explant culture, and spontaneously secreted both proMMP-9 and an active form of MMP-9. The fragments of dentigerous cysts and radicular cysts secreted a small amount of proMMP-9, but no active form of MMP-9. Exogenously added recombinant human IL-1alpha (rhlL-1alpha) increased the secretion and activation of proMMP-9 in the fragments of dentigerous cysts and radicular cysts. The epithelial cells isolated from odontogenic keratocysts secreted IL-1alpha and proMMP-9 without stimulation. Under the cultivation on a fibronectin-coated dish, rhIL-1alpha increased the secretion of proMMP-9 from the epithelial cells in a dose-dependent manner. Moreover, rhIL-1alpha induced the secretion of proMMP-3 and plasminogen activator urokinase (u-PA) from the epithelial cells, and converted the secreted proMMP-3 to the active form in the presence of plasminogen. The secreted proMMP-9 was also activated in the presence of rhIL-1alpha and plasminogen. Hence, our results suggest that IL-1alpha may up-regulate not only proMMP-9 secretion but also proMMP-9 activation by inducing proMMP-3 and u-PA production in the cyst epithelial cells by autocrine/paracrine regulatory mechanisms.

Autocrine Communication↗
PubMed1999

Effects of adrenergic stimulus on the activities of Ca2+ and K+ channels of dorsal root ganglion neurons in a neuropathic pain model.

We hypothesized that abnormal activity and adrenergic sensitivity in injured dorsal root ganglion (DRG) neurons are due to an intrinsic alteration of the cell body membrane. We investigated the effects of adrenergic stimulus on the activities of Ca2+ and K+ channels of DRG neurons in a rat chronic constriction injury (CCI) model. At first, we demonstrated thermal hyperalgesia and sprouting sympathetic nerve fibers in the ipsilateral L4-L5 DRGs. Using whole-cell patch clamp techniques, we found that alpha2-adrenergic stimulus by 10 microM norepinephrine (NE) inhibited inward currents (IBa, Ba2+ as a charge carrier) through voltage-dependent Ca2+ channels (VDCCs) of DRGs in the CCI model by 42%, whereas it enhanced the IBa by 18% in control animals. The inhibitory effect of NE disappeared by pretreatment with the N-type VDCC antagonist omega-conotoxin GVIA (1 microM). NE shifted the inactivation curve to a more negative potential, showing that it has inhibitory effects on IBa both in activated and in inactivated states. alpha2-Adrenergic stimulus also inhibited outward K+ currents by 24% in the CCI model, while it had no effect on the currents in control animals. The inhibitory effect of NE was blocked by pretreatment with the Ca2+-activated K+ (KCa) channel antagonist charybdotoxin (40 nM). The NE-induced inhibitory effects both on N-type VDCC and on KCa channels in injured DRG neurons of the CCI model could lead to cell membrane depolarization, resulting in a spontaneous discharge of action potential and an increase in sensitivity to adrenergic stimulus.

Animals↗
PubMed1999

DNA pooling and dense marker maps: a systematic search for genes for cognitive ability.

Pooling DNA from subjects within a group and comparing the pooled DNA across groups for a dense map of DNA markers offers a solution to the conundrum that linkage is systematic but not powerful whereas allelic association is powerful but not systematic. We used DNA pooling to screen 66 markers on chromosome 22 in original and replication samples of children of high general cognitive ability (g) and controls of average g. Although none of these markers survived our three-stage screening design (original pooling, replication pooling, individual genotyping), the results of DNA pooling were largely confirmed by individual genotyping. We can therefore exclude associations of major effect size on chromosome 22 for g, a key variable for cognitive neuroscience research on learning and memory.

Alleles↗
PubMed1999

Protective effects of hochu-ekki-to, a Chinese traditional herbal medicine against murine cytomegalovirus infection.

The innate immunity against murine cytomegalovirus (MCMV) at the early phase of infection is mediated by NK cells and macrophages. We studied the effects of hochu-ekki-to (HET), a traditional Chinese herbal medicine, on the regulation of innate immunity mediated by NK cells and macrophages. We found the oral administration of HET to increase both the number of leukocytes in the spleen and liver and the splenic NK cell cytotoxicity associated with the increased induction of serum IFN-alpha/beta after an MCMV infection but it had no effect on liver NK cells. However, no differences were found in the serum IL-12, IFN-gamma, TNF-alpha and nitric oxide (NO) production in the culture of macrophages between the HET- and PBS-treated mice on day 2 after MCMV infection. In addition, HET-treated splenic and peritoneal macrophages were found to show a higher intrinsic resistance against in vitro MCMV infection than that of PBS-treated mice. Therefore, the HET-induced effects on NK cells and macrophages selectively reduced the viral load in the spleen but not in the liver at an early phase of MCMV infection. HET may thus be useful in the treatment of human cytomegalovirus infection which commonly occurs in HIV-infected AIDS patients.

3T3 Cells↗
PubMed1999

Dendritic cells with immature phenotype and defective function in the peripheral blood from patients with hepatocellular carcinoma.

BACKGROUND/AIMS: Defects and dysfunctions in antigen-presenting dendritic cells have been shown during carcinogenesis. The phenotype and function of dendritic cells have been studied in patients with hepatocellular carcinoma to explore the possibility of dendritic cell-based immune therapy in hepatocellular carcinoma. METHODS: The stimulatory capacity of dendritic cells in allogenic mixed leukocytes reaction, the expression of surface makers on dendritic cells, the production of cytokines and nitric oxide by dendritic cells and the levels of maturation of dendritic cells from 17 patients with hepatocellular carcinoma, 10 patients with liver cirrhosis and 10 normal controls were compared. RESULT: Dendritic cells from hepatocellular carcinoma had significantly lower capacity to stimulate allogenic T cells in allogenic mixed leukocytes reaction compared with dendritic cells from liver cirrhosis and normal controls (p<0.05). Dendritic cells from hepatocellular carcinoma expressed significantly lower levels of HLA DR and induced decreased amounts of interleukin-12 compared with dendritic cells from normal controls (p<0.05). On the other hand, dendritic cells from hepatocellular carcinoma produced significantly higher levels of nitric oxide and tumor necrosis factor-a compared with dendritic cells from liver cirrhosis and normal controls (p<0.05). The uptake of fluorescein isothiocyanate-labeled dextran revealed an immature phenotype of dendritic cells from hepatocellular carcinoma compared with dendritic cells from liver cirrhosis (p<0.05). CONCLUSION: The results of this study on the function of dendritic cells in hepatocellular carcinoma, and the prevalence of immature dendritic cells in hepatocellular carcinoma in the microenvironment of high levels of inflammatory cytokines indicate a specific defect of dendritic cell maturation during hepatocarcinogenesis. These data show that induction of dendritic cell maturation might be an approach to dendritic cell-based immune therapy during hepatocellular carcinoma.

Biomarkers↗
PubMed1999

Improvement of molar ratio of branched-chain amino acids to tyrosine (BTR) associated with liver fibrosis in chronic hepatitis C patients treated with interferon-alpha.

The molar ratio of branched-chain amino acids (BCAA) to tyrosine (BTR), which has recently been possible to easily determine by an enzymatic method, can be clinically used as a substitute for that of BCAA to aromatic amino acids (AAA). We used this method to investigate the diagnostic implications of serum BTR in patients with chronic hepatitis C treated with interferon-alpha. There was a good correlation between BTR and staging (fibrosis) scores both before and after treatment. BTR increased significantly at 24 months after treatment in the responder group (P < 0.01). Moreover, a significant increase in BTR was observed in patients with improved staging (P = 0.015), but not grading (necroinflammatory), scores. BTR in chronic hepatitis C patients seems to be reflected by the extent of liver fibrosis, and, in the responder group, it can be improved, together with liver fibrosis, by interferon-alpha treatment.

Adult↗