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Kazuichi Okazaki

Publications and source records attributed to Kazuichi Okazaki.

At least 19 recordsLinked to original sources
PubMed2006

Rapid development of diffuse large B-Cell lymphoma after successful eradication of Helicobacter pylori for gastric MALT lymphoma.

Primary low-grade mucosa-associated lymphoid tissue (MALT) lymphoma of the stomach has a potential to transform to high-grade diffuse large B-cell lymphoma (DLBCL). However, the clonal relation between MALT lymphoma and de novo DLBCL is still controversial. We report here three patients with Helicobacter pylori (H. pylori)-positive gastric MALT lymphoma rapidly progressing to DLBCL at the same site after successful eradication of H. pylori. Although MALT lymphomas in our cases did not possess t(11; 18)(q21;q21), sequence analysis of the rearranged immunoglobulin heavy chain gene showed no clonal relation between preceding MALT lymphoma cells and de novo DLBCL cells at the same site. These findings question the scenario of direct clonal progression of low-grade MALT lymphomas without t(11; 18)(q21;q21) to DLBCL and serve as a reminder of the risk of the progression of DLBCL with a distinct clonality immediately after H. pylori eradication for low-grade MALT lymphoma.

Adult↗
PubMed2006

Human thioredoxin-1 ameliorates experimental murine colitis in association with suppressed macrophage inhibitory factor production.

BACKGROUND & AIMS: Thioredoxin-1 (TRX) is a small multifunctional protein with antioxidative and redox-regulating functions. In this study, we investigated the significance of TRX in patients with inflammatory bowel disease (IBD) and the ability and mechanism to ameliorate experimental colitis. METHODS: Serum TRX and macrophage migration inhibitory factor (MIF) levels were measured in patients with IBD. The effects of TRX were evaluated in a dextran sulfate sodium (DSS)-induced colitis model by comparing TRX-overexpressing transgenic (TRX-TG) and control mice. We further evaluated the effect of recombinant human TRX (rhTRX) administration on DSS-induced colitis and colonic inflammation of interleukin (IL)-10 knockout (IL-10 KO) mice. Colonic inflammation was examined clinically and histologically. Proinflammatory cytokine levels were examined in colonic tissues, and MIF levels were measured in colonic tissues and sera in mice. The effect of TRX on MIF production was also analyzed in vitro. RESULTS: Serum TRX and MIF levels were significantly higher in patients with IBD than normal controls, and TRX levels correlated with disease activity. TRX significantly ameliorated DSS-induced colitis and colonic inflammation of IL-10 KO mice. Increase of tumor necrosis factor-alpha and interferon-gamma in colonic tissues was significantly suppressed in TRX-TG mice compared with wild-type mice. MIF levels in colonic tissues and sera were significantly lower in TRX-TG mice than in wild-type mice, irrespective of DSS administration. Anti-TRX treatment exacerbated DSS-induced colitis. In vitro studies demonstrated that rhTRX suppressed MIF production in human monocyte cells. CONCLUSIONS: TRX might have a potential as a novel therapeutic agent for the treatment of IBD.

Animals↗
PubMed2006

Consensus of primary care in acute pancreatitis in Japan.

The incidence of acute pancreatitis in Japan is increasing and ranges from 187 to 347 cases per million populations. Case fatality was 0.2% for mild to moderate, and 9.0% for severe acute pancreatitis in Japan in 2003. Experts in pancreatitis in Japan made this document focusing on the practical aspects in the early management of patients with acute pancreatitis. The correct diagnosis of acute pancreatitis and severity stratification should be made in all patients using the criteria for the diagnosis of acute pancreatitis and the multifactor scoring system proposed by the Research Committee of Intractable Diseases of the Pancreas as early as possible. All patients diagnosed with acute pancreatitis should be managed in the hospital. Monitoring of blood pressure, pulse and respiratory rate, body temperature, hourly urinary volume, and blood oxygen saturation level is essential in the management of such patients. Early vigorous intravenous hydration is of foremost importance to stabilize circulatory dynamics. Adequate pain relief with opiates is also important. In severe acute pancreatitis, prophylactic intravenous administration of antibiotics at an early stage is recommended. Administration of protease inhibitors should be initiated as soon as the diagnosis of acute pancreatitis is confirmed. A combination of enteral feeding with parenteral nutrition from early stage is recommended if there are no clear signs and symptoms of ileus and gastrointestinal bleeding. Patients with severe acute pancreatitis should be transferred to ICU as early as possible to perform special measures such as continuous regional arterial infusion of protease inhibitors and antibiotics, and continuous hemodiafiltration. The Japanese Government covers medical care expense for severe acute pancreatitis as one of the projects of Research on Measures for Intractable Diseases.

Acute Disease↗
PubMed2006

Transforming growth factor-beta during carcinogenesis: the shift from epithelial to mesenchymal signaling.

Transforming growth factor-beta (TGF-beta) activates not only TGF-beta type I receptor (TbetaRI) but also c-Jun N-terminal kinase (JNK), changing unphosphorylated Smad3 to its phosphoisoforms: C-terminally phosphorylated Smad3 (pSmad3C) and linker phosphorylated Smad3 (pSmad3L). While the TbetaRI/pSmad3C pathway inhibits growth of normal epithelial cells, JNK/pSmad3L-mediated signaling is involved in invasion by activated mesenchymal cells. During sporadic human colorectal carcinogenesis, TGF-beta signaling confers a selective advantage on tumor cells by shifting from the TbetaRI/pSmad3C pathway characteristic of mature epithelial cells to the JNK/pSmad3L pathway, which is more characteristic of the state of flux shown by the activated mesenchymal cells. JNK acts as a regulator of TGF-beta signaling by increasing the basal level of pSmad3L available for action in the nuclei of the invasive adenocarcinoma, in the meantime shutting down TGF-beta-dependent nuclear activity of pSmad3C. Loss of epithelial homeostasis and acquisition of a migratory, mesenchymal phenotype are essential for tumor invasion. From the viewpoint of TGF-beta signaling, a key therapeutic aim in cancer would be restoration of the lost tumor suppressor function observed in normal colorectal epithelial cells at the expense of effects promoting aggressive behavior of the adenocarcinoma. Specific inhibitors of the JNK/pSmad3L pathway might prove useful in this respect. In the case of molecularly targeted therapy for human cancer, pSmad3L and pSmad3C could be assessed as biomarkers to evaluate the likely benefit from specific inhibition of the JNK/pSmad3L pathway.

Biomarkers, Tumor↗
PubMed2006

Specific antibodies against recombinant protein of insertion element 900 of Mycobacterium avium subspecies paratuberculosis in Japanese patients with Crohn's disease.

BACKGROUND: Mycobacterial avium subspecies paratuberculosis (MAP) infection has been hypothesized as an etiological factor of Crohn's disease (CD). However, the involvement of MAP in the pathophysiology of CD is controversial. The aim of this study is to investigate whether MAP is involved in the pathogenesis of CD with the glutathione S-transferase fusion recombinant protein encoding a portion of insertion element (IS) 900 (IS900-GST), which is specific for MAP. METHODS: Serum samples from the patients with CD (n = 50), ulcerative colitis (n = 40), colonic tuberculosis (n = 20), and non-IBD controls (n = 44), were applied for solid-phase enzyme-linked immunosorbent assay (ELISA) to detect antibodies against MAP and Saccharomyces cerevisiae. IS900-GST, which was made by the pGST-4T-2 vector inserted with polymerase chain reaction-amplified IS900DNA, was used as an antigen of MAP. Moreover, we studied the relationship between antibodies against IS900-GST and clinical characteristics. RESULTS: ELISA showed that the serum level of immunoglobulin G and immunoglobulin A antibodies against IS900-GST (anti-IS900) in patients with CD were significantly higher than those with ulcerative colitis, colonic tuberculosis, and control subjects. The levels of anti-IS900 tended to be higher in CD patients with small intestinal involvement than with colonic involvement alone. Anti-IS900 in patients with penetrating- and stricture-type CD was significantly higher than with inflammatory-type CD. Furthermore, a negative correlation was found between the titer of anti-IS900 and disease duration. Anti-IS900 was not associated with surgical treatment nor was it associated with the use of immunosuppressants. No significant correlation was observed between the serum levels of anti-IS900 and anti-S cerevisiae antibody. CONCLUSIONS: This is the first demonstration of the ELISA system of detecting antibodies against IS900 in IBD patients. MAP could be involved in the pathophysiology of Japanese patients with CD.

Adult↗
PubMed2006

Clinical significance of serum thioredoxin 1 levels in patients with acute pancreatitis.

OBJECTIVE: Thioredoxin 1 (TRX-1), a redox-regulating protein with antioxidant activity, is induced by oxidative stress, and serum TRX-1 levels are recognized as an oxidative-stress marker. The aim of this study was to clarify the clinical significance of serum TRX-1 levels in patients with acute pancreatitis (AP) and evaluate the usefulness of this measurement in assessing disease severity. METHODS: Serum TRX-1 levels were determined on admission in 18 patients with severe AP and 36 patients with mild AP. We also investigated the relationship between serum TRX-1 levels and clinical and laboratory data. RESULTS: The median serum TRX-1 levels on admission were 54.9 ng/mL in mild AP and 118.8 ng/mL in severe AP. When the cutoff value for TRX-1 in predicting severe AP was determined to be 100 ng/mL, its sensitivity, specificity, and accuracy were 83.3%, 94.4%, and 90.7%, respectively. A significant correlation was observed between serum TRX-1 levels and Ranson score (r = 0.674), C-reactive protein (r = 0.718), interleukin 6 (r = 0.712), leukocyte count (r = 0.642), and serum amylase (r = 0.436). CONCLUSIONS: Serum TRX-1 levels significantly correlate with AP severity. TRX-1 should constitute a reliable oxidative-stress marker for the evaluation of AP severity in relation to oxidative stress.

Acute Disease↗
PubMed2006

Identification of a novel autoantibody against pancreatic secretory trypsin inhibitor in patients with autoimmune pancreatitis.

OBJECTIVES: Although autoimmune pancreatitis (AIP) has been recently recognized as a new disease entity of chronic pancreatitis, the clinical diagnosis of the disease remains disputed. Autoantibodies against carbonic anhydrase II and lactoferrin are detected in most patients with AIP, but not in about 10%. We undertook this study to determine whether additional autoantibodies are present in the serum level of AIP patients. METHODS: We recruited 26 patients with AIP for the study. For comparison, we also recruited 53 patients with various pancreatic diseases and 12 healthy subjects. We immunoscreened human pancreatic cDNA library using patients' sera. Positive clones were analyzed by DNA sequencing and were constructed into a pGEX-4T-1 expression vector. The recombinant proteins were used as antigens in enzyme-linked immunosorbent assay to screen the subjects' sera for autoantibodies. RESULTS: We cloned a cDNA encoding the pancreatic secretory trypsin inhibitor (PSTI). Among 26 patients with AIP, autoantibodies against PSTI were significantly positive in 11 (42.3%) by western blotting and in 8 (30.8%) by enzyme-linked immunosorbent assay, respectively. However, none of control subjects was positive for anti-PSTI antibodies. CONCLUSIONS: These findings suggest that PSTI may be related to the pathogenesis of AIP, and autoantibodies against PSTI can be a useful diagnostic marker for the disease.

Aged↗
PubMed2006

Establishment of animal models for three types of pancreatitis and analyses of regeneration mechanisms.

OBJECTIVES: To investigate the mechanisms underlying the onset and progress of pancreatitis, 3 animal models (chronic, acute, and severe pancreatitis) were established by double ligature of the pancreatic duct, injection with cerulein, or injection with cerulein + double ligature of the pancreatic duct. METHODS: We prepared a control and 3 experimental groups: group 1 (untreated control), group 2 (a chronic pancreatitis model; the pancreatic tail was exposed through a midline incision, and the pancreatic duct from this part was double-ligated), group 3 (an acute pancreatitis model; cerulein was intraperitoneally injected 7 times on day 0), and group 4 (a severe pancreatitis model; the double ligature of the pancreatic duct plus injection of cerulein). RESULTS: Kinetic observations of survival rate, relative pancreatic weight, and the macroscopical and microscopical diagnoses and observations of the changes in endocrine function clearly show that these 3 murine models of pancreatitis can serve as human models for chronic, acute, and severe pancreatitis. Furthermore, pancreas duodenum homeobox 1, cytokeratin 19, and Ki67 are expressed at the site of injury in the pancreas, resulting from the injection with cerulein and/or double ligature of the pancreatic ducts and indicating that there remains a tissue-regenerative capacity. CONCLUSIONS: These 3 mouse models could serve as human models for chronic, acute, and severe pancreatitis. Furthermore, cells of the epithelial lineage might participate in tissue regeneration in chronic, acute, and severe pancreatitis.

Amylases↗
PubMed2006

Intrapancreatic axonal hyperbranching of dorsal root ganglia neurons in chronic pancreatitis model rats and its relation to pancreatic pain.

OBJECTIVES: Increase in number of intrapancreatic nerve bundles has been implicated in the generation of persistent pain in chronic pancreatitis. To examine the origin of these nerve fibers and the mechanisms linking neural morphological change to pain generation, we used neuronal tracing techniques in combination with immunohistochemistry in spontaneous chronic pancreatitis in the Wistar Bonn/Kobori (WBN/Kob) rats. METHODS: For retrograde tracing, horseradish peroxidase was injected into the pancreas, and labeled neurons in the sensory ganglia were counted. For anterograde tracing, biotinylated dextran amine was injected into the dorsal root ganglia (DRGs), and labeled intrapancreatic sensory fibers were histochemically assessed. For assessment of pain generation, we evaluated c-Fos-positive neurons in the spinal dorsal horn and behavioral changes of the animals. RESULTS: In WBN/Kob rats, the numbers of horseradish peroxidase-labeled neurons were decreased in the DRGs, and the numbers of biotinylated dextran amine-labeled intrapancreatic nerve fibers and terminals were increased. Biotinylated dextran amine-labeled nerve fibers contained growth-associated protein 43. The number of c-Fos-positive neurons in the dorsal horn was also increased and was correlated with intrapancreatic growth-associated protein 43 immunoreactivity. Grooming behavior was reduced in WBN/Kob rats, and this reduction was facilitated by exocrine stimulation. CONCLUSIONS: Axonal branching in DRG neurons innervating the pancreas increases in WBN/Kob rats, and these morphological changes are likely involved in pain generation in chronic pancreatitis.

Animals↗
PubMed2006

Endoscopic ultrasonograph evaluation of vascular structures in the gastric cardia predicts esophageal variceal recurrence following endoscopic treatment.

BACKGROUND AND AIM: In patients with portal hypertension, early recurrence of esophageal varices often occurs following endoscopic variceal ligation therapy or ligation and injection-sclerotherapy combined treatment. To assess the recurrence risk following endoscopic treatment, this study investigated the association between recurrence-free time and severity of esophagogastric vascular structures before treatment as determined by endoscopic ultrasonography. METHODS: Sixty-three patients with esophageal varices at high bleeding risk were treated by endoscopic variceal ligation therapy or ligation and injection-sclerotherapy combined treatment. Before the treatment, conventional endoscopy and endoscopic ultrasonography with a 20-MHz catheter probe were performed. Submucosal, perforating and adventitial veins in the esophagus and gastric cardia were examined. According to the endoscopic ultrasonography findings, the vascular structures were classified into two grades: mild and severe. The relationships between the endoscopic ultrasonography grades and variceal recurrence-free time were analyzed by the Kaplan-Meyer method. RESULTS: Patients with severe as opposed to mild grade perforating veins in the gastric cardia had a significantly shorter recurrence-free time (P < 0.05). Those with severe paracardial veins also had a significantly shorter recurrence-free time (P < 0.01). CONCLUSION: Endoscopic ultrasonography analysis for gastric cardial vascular structures before endoscopic treatment can be useful to predict the recurrence of esophageal varices.

Aged↗
PubMed2005

Protective roles of redox-active protein thioredoxin-1 for severe acute pancreatitis.

Severe acute pancreatitis is a disease with high mortality, and infiltration of inflammatory cells and reactive oxygen species have a crucial role in the pathophysiology of this disease. Thioredoxin-1 (TRX-1) is an endogenous redox-active multifunctional protein with antioxidant and anti-inflammatory effects. TRX-1 is induced in various inflammatory conditions and shows cytoprotective effects. The aim of the present study was to clarify the protective roles of TRX-1 in the host defense mechanism against severe acute pancreatitis. Experimental acute pancreatitis was induced by intraperitoneal administration of cerulein, a CCK analog, and aggravated by lipopolysaccharide injection in transgenic mice overexpressing human TRX-1 (hTRX-1) and control C57BL/6 mice. Transgenic overexpression of hTRX-1 strikingly attenuated the severity of experimental acute pancreatitis. TRX-1 overexpression suppressed neutrophil infiltration as determined by myeloperoxidase activity, oxidative stress as determined by malondialdehyde concentration, and cytoplasmic degradation of inhibitor of kappaB-alpha, thereby suppressing proinflammatory cytokines, tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6; a neutrophil chemoattractant, keratinocyte-derived chemokine; and inducible nitric oxide synthase in the pancreas. Administration of recombinant hTRX-1 also suppressed neutrophil infiltration, reduced the inflammation of the pancreas and the lung, and improved the mortality rate. The present study suggests that TRX-1 has potent antioxidant and anti-inflammatory actions in experimental acute pancreatitis and might be a new therapeutic strategy to improve the prognosis of severe acute pancreatitis.

Acute Disease↗
PubMed2005

Appendix is a priming site in the development of ulcerative colitis.

AIM: The role of the appendix has been highlighted in the pathogenesis of ulcerative colitis (UC). The aims of this study were to elucidate the immuno-imbalances in the appendix of UC patients, and to clarify the role of the appendix in the development of UC. METHODS: Colonoscopic biopsy specimens of the appendix, transverse colon, and rectum were obtained from 86 patients with UC: active pancolitis (A-Pan; n = 15), active left-sided colitis (A-Lt; n = 25), A-Lt with appendiceal involvement (A-Lt/Ap; n = 10), inactive pancolitis (I-Pan; n = 14), and inactive left-sided colitis (I-Lt; n = 22), and from controls. In the isolated mucosal T cells, the CD4/CD8 ratio and proportion of activated CD4+ T cells were investigated, and compared with controls. RESULTS: In the appendix, the CD4/CD8 ratio significantly increased in A-Lt and A-Lt/Ap. The ratio in the appendix also tended to increase in A-Pan. In the rectum, the ratio significantly increased in all UC groups. In the appendix, the proportion of CD4+CD69+ (early activation antigen) T cells significantly increased in all UC groups. In the rectum, the proportion of CD4+CD69+ T cells significantly increased only in A-Pan. The proportion of CD4+HLA-DR+ (mature activation antigen) T cells significantly increased only in the rectum of A-Pan, but not in the other areas of any groups. CONCLUSION: The increased CD4/CD8 ratio and predominant infiltration of CD4+CD69+ T cells in the appendix suggest that the appendix is a priming site in the development of UC.

Adult↗
PubMed2005

A case of autoimmune pancreatitis associated with sclerosing cholangitis, retroperitoneal fibrosis and Sjögren's syndrome.

We report a very rare case of autoimmune pancreatitis (AIP) associated with sclerosing cholangitis, retroperitoneal fibrosis and Sjögren's syndrome. The patient had an enlarged pancreas, and autoantibodies were detected in the serum. Serum IgG and IgG4 concentrations were also elevated. Endoscopic retrograde cholangiopancreatography revealed an irregular narrowing of the main pancreatic duct from the head to the body and sclerotic change in the intrapancreatic common bile duct, which later extended to the intrahepatic bile ducts. In addition, histological examination of the liver revealed lymphocytic sclerosis around the bile ducts, similar to the histology in the pancreas of AIP. Retroperitoneal tumors were diagnosed as retroperitoneal fibrosis by histological examination. Serological and functional abnormalities suggestive of Sjögren's syndrome were detected, and histological findings of the lip were compatible with Sjögren's syndrome. Immunohistochemistry of each lesion disclosed that most of the infiltrating lymphocytes were T cells with similar levels of both CD4+ and CD8+ cells. Moreover, some of the infiltrating plasma cells were positive for anti-IgG4 monoclonal antibody. These diseases were dramatically improved by steroid therapy. Although the pathophysiology of AIP is still unclear, the present case suggests a common pathophysiological mechanism for AIP, sclerosing cholangitis, retroperitoneal fibrosis and Sjögren's syndrome.

Aged↗