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Biomedical subjects

T Joh

Publications and source records attributed to T Joh.

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

Role of T cells in development of chronic pancreatitis in male Wistar Bonn/Kobori rats: effects of tacrolimus.

We assessed T cell association with acinar cell apoptosis and a preventive effect of tacrolimus, a T cell suppressant, on the development of chronic pancreatitis in male Wistar Bonn/Kobori rats. At 15 wk, cellular infiltrates composed of F4/80-positive cells (monocytes/macrophages), CD4-positive cells, and CD8-positive cells were extensive in the interlobular connective tissue and parenchyma. In particular, CD8-positive cells invaded pancreatic lobules and formed close associations with acinar cells, some of which demonstrated features of apoptosis. At 20 wk, CD8-positive cells were still abundant in the fibrotic tissue formed with loss of acinar cells. Repeated subcutaneous injection of 0.1 mg x kg(-1) x day(-1) but not 0.025 mg x kg(-1) x day(-1) of tacrolimus for 10 wk completely prevented the occurrence of acinar cell apoptosis, infiltration of CD4- and CD8-positive cells, and development of pancreatitis at the age of 20 wk, but these maneuvers did not recover the decreased plasma corticosterone levels, which may be responsible for the development of disease. We demonstrated that T cells, possibly CD8-positive cells, are involved in inducing apoptosis of acinar cells, raising the possibility that tacrolimus might find clinical application in the treatment of autoimmune chronic pancreatitis.

Animals↗
PubMed2001

Successful extracorporeal shock wave lithotripsy for sibling pancreatic duct stones.

We present a case of 2 brothers with idiopathic chronic pancreatitis associated with pancreatic duct stones which could be successfully disintegrated by extracorporeal shock wave lithotripsy (ESWL). An obvious etiology for the pancreatolithiasis, like alcohol or biliary disease, was lacking and point mutations of the cationic trypsinogen gene exons 2 and 3 were not detected in the long arm of the 7th chromosome. However, a hereditary etiology could not be precluded since pancreatolithiasis occurred in the siblings. There has been no recurrence of pancreatic stones during 42 months of follow-up periods, for both. ESWL, the least invasive therapy, appeared applicable and effective for pancreatolithiasis in the present cases.

Adult↗
PubMed2001

Induction and secretion of RNA-degrading enzymes by phosphate deficiency in Pholiota nameko.

Changes in activity of RNA-degrading enzyme and amounts of phosphorus in mycelia and culture filtrate during Pi-sufficient and -deficient cultures of Pholiota nameko were investigated. The results showed that the intracellular and extracellular activities are controlled by the Pi concentration in the medium. Moreover, the induction and secretion of RNA-degrading enzymes under the Pi-deficient condition were analyzed by activity staining.

Acid Phosphatase↗
PubMed2001

Vascular endothelial growth factor and cellular chemotaxis: a possible autocrine pathway in adult T-cell leukemia cell invasion.

Our previous report (T. Hayashibara et al., Leukemia, 13: 1634-1635, 1999) revealed a possible link between high plasma vascular endothelial growth factor (VEGF) concentration and leukemic cell invasion in adult T-cell leukemia (ATL). However, the biological mechanism of this link has not been elucidated. The purpose of this study was to address that mechanism. Our present observations showed that VEGF mRNA was expressed in ATL cell lines. The corresponding protein was secreted into the extracellular environment, which suggested that the major source of plasma VEGF is ATL cells themselves. More interestingly, all of the cell lines examined were found to express the mRNA and protein for fms-like tyrosine kinase-1 (Flt-1), which is one of the receptors for VEGF. Cytofluorometric analysis demonstrated the VEGF binding potency of these cells. In clinical specimens, expression of VEGF and Flt-1 mRNAs was detected in all (100%) of 11 and 8 (73%) of 11 ATL patients, respectively. Cytofluorometric analysis revealed that VEGF effectively bound only to Flt-1-expressing cells. These findings are highly suggestive of an autocrine pathway involving VEGF operating in ATL. The proliferation of ATL cell lines was not affected by treatment with an anti-VEGF antibody or exogenous VEGF, which indicated that VEGF has no mitogenic effect on ATL cells. In contrast, we made the interesting finding that treatment with exogenous VEGF enhanced the chemotactic activities of some ATL cell lines, which may play a key role in ATL cell invasion. Collectively, these data lead us to propose a possible autocrine mechanism involving VEGF operating by way of Flt-1, in which ATL cells up-regulate their own chemotaxis to facilitate their invasion into various organs.

Adult↗
PubMed2000

Suppressive effects of DNA vaccines encoding heat shock protein on Helicobacter pylori-induced gastritis in mice.

We investigated the effect of DNA vaccines encoding H. pylori-heat shock protein A and B (pcDNA3.1-hspA and -hspB) on inducing immune responses against H. pylori in mice. C57BL/six mice aged 5 weeks were immunized by single injection of 10 microg of pcDNA3.1-hspA and pcDNA3.1-hspB into intracutaneous tissue. Plasmid DNA lacking the inserted hsp were injected as a control. Three months after vaccination, significant specific antibodies against H. pylori were detected by ELISA in the sera of vaccinated mice. Antibody isotypes were predominantly IgG2a (Th1-like) with pcDNA3.1-hspA and mixed IgG1/IgG2a (Th0-like) with pcDNA3.1-hspB. DNA vaccination dramatically suppressed colonies of bacteria in stomach of vaccinated mice (28,400 +/- 21,600/mm(2) for pcDNA3.1-hspA and 6800 +/- 3470/mm(2) for pcDNA3.1-hspB) compared to control mice (128,000 +/- 42,200/mm(2)). Histological analysis of the gastric mucosa demonstrated that the degree of gastritis was significantly lower in the vaccinated mice than in control mice. These results demonstrated that DNA vaccines encoding H. pylori-Hsp induce significant immune response against H. pylori to decrease gastric mucosal inflammation, indicating that a DNA vaccine can be a new approach against H. pylori in humans.

Animals↗
PubMed2000

HIV-1 Tat increases endothelial solute permeability through tyrosine kinase and mitogen-activated protein kinase-dependent pathways.

OBJECTIVE: HIV-1 infection is associated with alterations of several vascular endothelial functions including adhesion molecule expression, growth, and vascular permeability. The bases of these errors are not known, but might involve secretion of the HIV-1 derived transcription factor 'Tat-1'. This study investigated Tat-1 mediated endothelial barrier changes and second message regulation of this phenomenon. METHODS: We exposed human umbilical vein endothelial cell monolayers to Tat-1 (0-150 ng/ml) for up to 48 h and measured resulting changes in monolayer permeability. We also investigated the role of tyrosine and mitogen activated protein (MAP) kinases, and protein kinase G using the pharmacological blockers genistein, PD98059 and KT5823 respectively. RESULTS: Tat-1 significantly reduced monolayer barrier and increased albumin permeability within 24 h. Tat-1 also stimulated tyrosine phosphorylation of multiple endothelial proteins, disorganized junctional phosphotyrosine staining and increased the number of these immunostaining structures. The increased permeability produced by Tat-1 was blocked by genistein and PD98059, but not by KT5823. Genistein and PD98059 pretreatment also prevented the changes in phosphotyrosine immunostaining produced by Tat-1 and blocked phosphorylation of several proteins including MAP kinase. CONCLUSION: These results suggest that HIV may dysregulate endothelial barrier through the effects of Tat-1. These blocker experiments suggest that the effects of Tat are transcription/translation-dependent. These data demonstrate that Tat increases endothelial albumin permeability in vitro through tyrosine kinase and MAP kinase, but not protein kinase G pathways.

Blotting, Western↗
PubMed2000

The MAR-binding protein SATB1 orchestrates temporal and spatial expression of multiple genes during T-cell development.

SATB1 is expressed primarily in thymocytes and can act as a transcriptional repressor. SATB1 binds in vivo to the matrix attachment regions (MARs) of DNA, which are implicated in the loop domain organization of chromatin. The role of MAR-binding proteins in specific cell lineages is unknown. We generated SATB1-null mice to determine how SATB1 functions in the T-cell lineage. SATB1-null mice are small in size, have disproportionately small thymi and spleens, and die at 3 weeks of age. At the cellular level, multiple defects in T-cell development were observed. Immature CD3(-)CD4(-)CD8(-) triple negative (TN) thymocytes were greatly reduced in number, and thymocyte development was blocked mainly at the DP stage. The few peripheral CD4(+) single positive (SP) cells underwent apoptosis and failed to proliferate in response to activating stimuli. At the molecular level, among 589 genes examined, at least 2% of genes including a proto-oncogene, cytokine receptor genes, and apoptosis-related genes were derepressed at inappropriate stages of T-cell development in SATB1-null mice. For example, IL-2Ralpha and IL-7Ralpha genes were ectopically transcribed in CD4(+)CD8(+) double positive (DP) thymocytes. SATB1 appears to orchestrate the temporal and spatial expression of genes during T-cell development, thereby ensuring the proper development of this lineage. Our data provide the first evidence that MAR-binding proteins can act as global regulators of cell function in specific cell lineages.

Aging↗
PubMed2000

Decay-accelerating factor in guinea pig stomachs following ischemia reperfusion stress.

A complement regulatory protein, decay-accelerating factor (DAF, CD55), is known to protect host tissues from autologous complement activation. DAF is present on the apical side of human gastric epithelial cells, and its expression increases during gastritis. To develop an animal model for analysis of DAF expression on gastric cells, a mAb to guinea pig DAF was successfully used. Although DAF expression in the mucosal epithelium of the stomach is weak, as judged by immunohistochemical staining with the mAb, it was temporarily up-regulated at 12 and 24 h, and at 3 days after ischemia reperfusion (I/R) (p < 0.05). The DAF mRNA level in gastric tissues was determined by Northern blot analysis and found to be highest at 6 h after I/R, returning to the baseline at 24 h. Strong DAF mRNA expression was observed in the cytoplasm of cells beneath the eroded tissues 6 h after I/R. In guinea pigs, alternative splicing of DAF mRNA generates both GPI-anchored types and transmembrane types of DAF. RT-PCR analysis revealed that mRNAs of the transmembrane types had become significantly dominant by 6 h after I/R, whereas levels for the GPI-anchored types remained unchanged. In guinea pigs depleted of complement by cobra venom factor treatment, the area of erosion and the up-regulation of DAF expression in gastric epithelial cells after I/R were significantly limited compared with the normocomplementemic group, indicating that DAF may be up-regulated by an inflammatory stress.

Animals↗
PubMed2000

AT motif binding factor 1-A (ATBF1-A) negatively regulates transcription of the aminopeptidase N gene in the crypt-villus axis of small intestine.

This is the first study to demonstrate that the AT motif binding factor 1-A (ATBF1-A) is expressed in the crypts and the bases of villi of the small intestine and negatively regulates transcription of brush-border enzyme gene, aminopeptidase-N (APN). In situ hybridization visualized a limited ATBF1-A mRNA expression in the crypts and the bases of villi. Transient transfection and dual luciferase-reporter assay demonstrated that ATBF1-A suppressed the activity of APN promoter, but did not that of AT motif deleted promoter. These results imply that ATBF1-A inhibits the transcription of APN gene through its direct binding to the AT motif element. Furthermore, butyrate-induced differentiation of Caco-2 cells, retaining the enterocytic phenotypes such as a villus structure and the expression of brush-border enzymes, leads to a reduced expression of ATBF1-A mRNA. We proposed that ATBF1-A regulating APN gene expression in the crypt-villus axis of the small intestine is a landmark of enterocyte differentiation and maturation.

Animals↗
PubMed2000

Lactacystin activates FLICE (caspase 8) protease and induces apoptosis in Fas-resistant adult T-cell leukemia cell lines.

Lactacystin (LC) is a specific inhibitor of the proteasome, and has recently been shown to induce apoptosis in certain cell lines. In the present study, we established Fas-resistant adult T-cell leukemia (ATL) cell subclones RSO4 and RST1 from their parental Fas-sensitive cell lines SO4 and ST1, and examined whether LC can overcome Fas resistance. LC completely inhibited proteasome function as determined by a peptidyl-MCA substrate (LLVY-MCA and LLE-MCA), and induced apoptosis in these cell lines irrespective of Fas sensitivity at low concentrations (approximately 10 microM). LC induced the activation of caspase 3 (CPP32/Yama) and caspase 6 proteases in an identical manner to Fas-mediated apoptosis. Moreover, LC induced the activation of caspase 8 (FLICE) protease, which is the initiator of the Fas-mediated apoptotic cascade. Synthesized proteasome inhibitory peptide MG-115 (ZLLnV-CHO) also induced apoptosis in these cell lines. These results indicated that proteasome inhibitors overcome Fas-resistance by bypassing the proximal part of the Fas signal. Inhibition of the proteasome function may be a new strategy for the treatment of ATL.

Acetylcysteine↗
PubMed2000

What are the appropriate indications for endoscopic mucosal resection for early gastric cancer? Analysis of 256 endoscopically resected lesions.

BACKGROUND AND STUDY AIMS: Although endoscopic mucosal resection (EMR) for early gastric cancer (EGC) without ulceration or scarring has been very popular in Japan and thought to be beneficial, curability by EMR is still lower than that for surgical resection. We investigated patients whose EGCs were resected endoscopically in order to identify the factors affecting curability by EMR. PATIENTS AND METHODS: We investigated retrospectively 256 EGC lesions (251 patients) which were subjected to EMR between 1989 and 1998 with respect to patient profile, macroscopic type, location, maximum diameter of tumors, resection method and histological typing. The prognoses of the patients were also investigated as far as possible. RESULTS: The curative total resection rate for EMR of EGC was 74.2 %. Concerning the factors affecting curability, the size of the lesion (over 15 mm), the method of resection (divisional resection), and histological typing (poorly differentiated) had a statistically significant effect on the complete resection rate. Multivariate analysis of the factors confirmed these results. Submucosal invasion was suspected in 16 patients after EMR, but submucosal cancer was found in only one patient after further surgery. Where there was recurrence, the longest recurrence-free period after EMR of EGC was 48 months, whereas the mean recurrence-free period was 195.4 days. CONCLUSIONS: The appropriate indication for EMR for EGC is thought to be an intramucosal differentiated-type adenocarcinoma without ulceration or scarring, and no more than 15 mm in size regardless of macroscopic type. Periodic follow-up for at least 5 years is necessary.

Adenocarcinoma↗
PubMed2000

Importance of gap junction in gastric mucosal restitution from acid-induced injury.

Evidence is accumulating that gap junctional intercellular communication (GJIC) plays an important role in the gastric mucosal defense system. This study was conducted to determine whether GJIC mediates a restitution process in gastric mucosa. Male Sprague-Dawley rats were fasted and anesthetized. Gastric injury was induced by luminal perfusion with 0.2N HCl for 10 minutes. Mucosal integrity was continuously monitored by measuring the clearance of chromium 51-labeled ethylenediaminetetraacetic acid, which was used for analysis of recovery from the injury. Perfusion with 0.25% octanol (OCT; inhibitor of GJIC) was started after acid injury to assess its effect on restitution. The effect of irsogladine (IG; activator of GJIC) was also tested. Gastric mucosal GJIC was immunohistochemically evaluated with monoclonal antibody gap junction protein (connexin 32). Recovery from acid-induced mucosal injury occurred rapidly when acid perfusion was discontinued (within about 60 minutes). OCT, which didn't cause any injury to normal gastric mucosa, significantly inhibited the restitution. IG reversed this inhibition in a dose-dependent manner. In an immunohistochemical study, OCT-induced damage of gap junction was demonstrated, but not after IG pre-treatment. These findings suggest that GJIC may play a critical role in restitution in rat gastric mucosa and that gap junction function may be one of the important factors for the mucosal defense system.

Animals↗
PubMed2000

Apoptosis of acinar cells is involved in chronic pancreatitis in Wbn/Kob rats: role of glucocorticoids.

The involvement of pancreatic acinar cell apoptosis and its relation to glucocorticoid exposure were investigated in spontaneously occurring chronic pancreatitis in male Wistar Bonn/Kobori (WBN/Kob) rats. Although most lobules were not inflamed in 10-week-old WBN/Kob, increased apoptosis of pancreatic acinar cells, confirmed by TUNEL staining was focally observed (0.10 +/- 0.10 vs. 0.05 +/- 0.10/field in 10-week Wistar rats). Localized hemorrhagic lesions and brown foci in the splenic lobes were apparent, with significant decrease in pancreas weight in 20-week WBN/Kob rats along with marked apoptosis (1.95 +/- 0.31 vs. 0.07 +/- 0.04/field in 20-week Wistar rats). Electron microscopy revealed apoptotic bodies to be present in acinar cells. Pancreatic myeloperoxidase activities, indirect indices of granulocyte infiltration, as well as histologic scores were significantly increased at 15 and 20 weeks, and endogenous corticosterone levels were significantly decreased at 10, 15, and 20 weeks as compared with values for age-matched Wistar rats. Prednisolone in the drinking water (0.01 mg/mL; calculated dose, 1.03 0.03 mg/kg/d) for 10 weeks significantly attenuated increases in numbers of apoptotic acinar cells and pancreatic myeloperoxidase activities and tended to reduce the histologic scores in 20-week WBN/Kob rats as compared with the vehicle group. In summary, (a) apoptosis of pancreatic acinar cells is involved in chronic pancreatitis, (b) endogenous corticosterone is decreased, and (c) prednisolone treatment attenuates both apoptosis of pancreatic acinar cells and chronic pancreatitis in male WBN/Kob rats. We conclude that apoptosis of acinar cells related to decreased corticosterone may be a trigger of chronic pancreatitis in this model.

Adrenocorticotropic Hormone↗
PubMed2000

Modulation of IL-18 production in the adrenal cortex following acute ACTH or chronic corticosterone treatment.

Interleukin (IL)-18 is a proinflammatory cytokine and a stimulator of cell-mediated immune responses. We have previously reported that acute stress stimulates the production of IL-18 mRNA in the glucocorticoid (GC)-producing cells of the adrenal cortex. In order to investigate the mechanisms governing the expression of IL-18 in the adrenal cortex, the effects of acute ACTH or chronic corticosterone treatment on the levels of IL-18 mRNA and protein were examined by in situ hybridization and Northern and Western blot assays. Adult male Sprague-Dawley rats received a subcutaneous injection of ACTH or subcutaneous implantation of slow-release corticosterone pellets followed by an injection of saline or ACTH. After 4 h, ACTH induced a 4-fold increase in IL-18 mRNA levels and elevated the content of pro-IL-18 peptide. Six days of chronic corticosterone treatment did not alter the basal levels of IL-18 mRNA and reduced those of pro-IL-18. Finally, ACTH treatment of animals under the corticosterone regimen induced a 2-fold increase in IL-18 mRNA and elevated the levels of the pro-IL-18 protein. The levels of the precursor, p45, and the active subunit p10 peptides of the IL-18-processing enzyme, IL-1beta-converting enzyme (ICE), showed no substantial differences in all the conditions tested. IL-1beta was not detected under these experimental conditions. These data demonstrate that the production of IL-18 in the adrenal cortex is stimulated by ACTH treatment and is not inhibited by the direct action of corticosterone. In contrast to the anti-inflammatory action of GCs, IL-18 may have an immunostimulatory role during acute stress.

Adrenal Cortex↗
PubMed2000

Cryoprotective activities of group 3 late embryogenesis abundant proteins from Chlorella vulgaris C-27.

The nucleotide sequence of hiC12, isolated as a cDNA clone of hardening-induced Chlorella (hiC) genes, was identified. The clone encodes a late embryogenesis abundant (LEA) protein having six repeats of a 11-mer amino acid motif, although in a slightly imperfect form. To overexpress the hiC61) and hiC12 genes, their coding regions were PCR amplified and subcloned into a pGEX-1lambdaT vector. The HIC6 and HIC12 proteins were expressed as GST fusion proteins in E. coli, then purified. The two HIC proteins were found to be effective in protecting a freeze-labile enzyme, LDH, against freeze-inactivation. On a molar concentration basis, they were about 3.1 x 10(6) times more effective in protecting LDH than sucrose and as effective as BSA. Cryoprotection tests with five kinds of chain-shortened polypeptides, synthesized based on the 11-mer amino acid motif of the HIC6 protein showed that the cryoprotective activity decreased with a decrease in the repeating units of the 11-mer motif. In fact, cryoprotective activities of three kinds of single 11-mer amino acids were very low even at high concentrations. All the results suggested that the sufficiently repeated 11-mer motif is required for the cryoprotective activities of Chlorella LEA proteins.

Amino Acid Sequence↗