In response to invading pathogens, the body immune system develops an immediate defense mechanism, i.e., innate immune response, which is detected in almost all living organisms including mammals, plants, insects, etc. Recent studies have identified numerous innate immune receptors that are able to recognize pathogen-associated molecular patterns and transduce the essential intracellular signaling cascades to mount early and successful host defenses against infectious challenge. Among innate immune receptors, we will focus on two important receptors, toll-like receptors (TLRs) and nucleotide binding oligomerization domain (Nod)-like receptors, and their major intracellular signaling pathways that culminate to activate innate immune effectors and inflammatory mediators during pathogen infection. In this review, we address the recent advances of understanding intracellular signaling mechanisms by which TLRs and NLRs activate host immune defense and inflammation. The role and regulatory mechanisms by which a subet of NLRs-associated inflammasome activation induce interleukin-1beta secretion and their relevance with host defense will be also discussed. Both TLR- and NLR-mediated intracellular signaling networks serve crucial roles in mounting resistance to bacterial and viral infection through synthesis of immune mediators and antimicrobial chemicals during infection.
Immune System ; Immunity, Innate ; Inflammation ; Insects ; Interleukin-1beta ; Mammals ; Toll-Like Receptors*

No abstract available.

Early gastric cancer(EGC) is defined as carcinoma limited to the mucosa or submucosa, regardless of whether metastasis to lymph nodes have occurred, and the frequency of lymph node metastasis varies from 7 to 18%. The incidence of early gastric cancer has been increasing recently, probably with advance in the diagnostic procedure. Multiple gastric cancer, now cosidered to be a sort of multiple primary cancer by Moertels classification, is a special type of cancer in which two or more tumor lesions arise independently from the stomach. Multiple carcinoma was found in about 8.3% of 500 early gastric cancer cases at the National Cancer Center Hospital in Japan. In 77% of these, two lesions roexisted in the stomach. Coexistence of three lesions were found in 20% and more than four lesions in 3%. We report a case of multiple early gastric cancer of different histologic types in which two adenoma coexisted in the stomach.
Adenoma ; Classification ; Incidence ; Japan ; Lymph Nodes ; Mucous Membrane ; Neoplasm Metastasis ; Stomach ; Stomach Neoplasms*

Early gastric cancer(EGC) is defined as carcinoma limited to the mucosa or submucosa, regardless of whether metastasis to lymph nodes have occurred, and the frequency of lymph node metastasis varies from 7 to 18%. The incidence of early gastric cancer has been increasing recently, probably with advance in the diagnostic procedure. Multiple gastric cancer, now cosidered to be a sort of multiple primary cancer by Moertels classification, is a special type of cancer in which two or more tumor lesions arise independently from the stomach. Multiple carcinoma was found in about 8.3% of 500 early gastric cancer cases at the National Cancer Center Hospital in Japan. In 77% of these, two lesions roexisted in the stomach. Coexistence of three lesions were found in 20% and more than four lesions in 3%. We report a case of multiple early gastric cancer of different histologic types in which two adenoma coexisted in the stomach.
Adenoma ; Classification ; Incidence ; Japan ; Lymph Nodes ; Mucous Membrane ; Neoplasm Metastasis ; Stomach ; Stomach Neoplasms*

BACKGROUND AND OBJECTIVE: Normal gut immune response to ingestive food proteins is induction of immune tolerance rather than sensitization, even in atopic individuals. Very restricted kinds of food antigens have been known to cause allergic sensitization in humans. To evaluate the differences of systemic T-cell immune responses to sensitized antigen and regular chow-protein, we performed this study. SUBJECTS AND METHODS: Eight naive female, 5-week-old C3H/HeJ mice were grown under the regular mouse chow feeding condition for 4 weeks. During that period, Group I mice were sensitized with buckwheat extract(1mg/dose) mixed with cholera toxin(10 microgram/dose) by intragastric administration at day1, 2, 3, 7, and 21. The sera were obtained at weekly intervals to measure buckwheat-specific and chow-protein-specific IgE, IgG1 and IgG2a antibodies. Splenocyte proliferation assays and cytokine productions were evaluated with buckwheat. chow-protein. and Con A stimulation. Levels of antibodies (IgE, IgG1, IgG2a) and cytokines (IL-4, IL-10, IL-12, INF-gamma were measured by ELISA. RESULTS: The levels of buckwheat specific IgE, IgG1 and IgG2a were markedly increased in Group I mice, but not in Group II mice. Chow-protein specific IgE and IgG1 antibodies were not increased in both groups of mice. The degrees of buckwheat-specific and chow-protein-specific splenocyte proliferations showed low-grade(SI: 6.68 and 4.48. respectively) compared to those by Con A stimulation(SI : 58). Buckwheat stimulated IL-4 productions were markedly increased in Group I mice, which were higher than Con A stimulated production. INF-gamma production was increased in Group I mice by buckwheat stimulation, and in both groups of mice by Con A stimulation. IL-12 production was shown in Con A stimulated culture supernatants in both groups of mice, but in Group I mice with buckwheat stimulation. IL-10 productions were increased in Group I mice with buckwheat, Con A, and chow-protein stimulations, furthermore, markedly increased IL-10 levels were also shown in chow-protein stimulated splenocyte cultures in both groups of mice. CONCLUSION: While Th1 and Th2 immune responses were induced by intragastricly sensitized buckwheat extract, only regulatory immune responses were dominated by regular chow proteins in this system. The minimum ability of chow-protein specific splenocyte proliferation was preserved and IL-10 was the unique cytokine produced by chow-protein simulation.
Animals ; Antibodies ; Cholera ; Cytokines ; Enzyme-Linked Immunosorbent Assay ; Fagopyrum* ; Female ; Humans ; Immune Tolerance ; Immunoglobulin E ; Immunoglobulin G ; Interleukin-10 ; Interleukin-12 ; Interleukin-4 ; Mice* ; T-Lymphocytes

BACKGROUND: The target of the treatment of metabolic syndrome and diabetes is an improvement of insulin resistance. D-chiro-inositol (DCI) plays a role in a phospholipid mediating intracellular insulin action. In the previous studies, the urine level of DCI were decreased in the diabetic animal with insulin resistance. Some clinical studies showed that DCI improved a glucose level and HbA1c. Therefore we studied the relationship between DCI and glucose metabolism, especially insulin resistance. METHODS: To investigate the mechanism of DCI affecting the glucose metabolism, we examined the effects of DCI on 2-deoxyglucose uptake, gene expression of adipocytokines and AMPK pathway by using RT-PCR and western blot in 3T3-L1 cells. RESULTS: Insulin-stimulated 2-deoxyglucose uptake increased in DCI-treated cells by about 1.2-fold (relative to the control) and was inhibited by phosphoinositide 3-kinase (PI3 Kinase) inhibitors (Wortmanin, LY294002) and AMPK inhibitor (STO-609). In Western blot analysis, it didn't show the difference of phosphorylation of Akt and AMPK between DCI-treated group and control in 3T3-L1 cells. However, DCI decreased the gene expression of resistin in 3T3-L1 cells. CONCLUSION: DCI may involve other pathway of insulin signaling, but not PI3 Kinase and AMPK signaling pathways and it may be useful in managing metabolic syndrome by improving insulin resistance through increasing glucose uptake and decreasing resistin relevant to insulin resistance.
3T3-L1 Cells ; Adipokines ; Animals ; Blotting, Western ; Deoxyglucose ; Gene Expression ; Glucose ; Insulin ; Insulin Resistance ; Negotiating ; Phosphorylation ; Phosphotransferases ; Resistin

Lymphocytic hypophysitis is a rare inflammatory disorder in the pituitary gland. The lesion is usually confined to the adenohypophysis. Although the involvement of the posterior pituitary gland or the stalk is rare, such patients with diabetes insipidus have been reported. Surgery has been used to make the definitive diagnosis. Recent studies suggest, however, that the pathologic diagnosis may not be necessary always. We reported a case of Lymphocytic hypophysitis managed by methylprednisolone pulse therapy. A 50-year-old premenopausal woman with Lymphocytic hypophysitis and diabetes insipidus was treated with methylprednisolone pulse therapy. Her adenopituitary lesion disappeared and the diabetes insipidus resolved. The optimal management for patients with lymphocytic hypophysitis may be the high index of the suspicion prior to the extensive surgical resection. In addition, methylprednisolone pulse therapy may improve the clinical and MRI findings.
Anti-Inflammatory Agents/*administration & dosage ; Diabetes Insipidus/*drug therapy/etiology ; Female ; Humans ; Lymphocytosis/complications/*drug therapy ; Methylprednisolone/*administration & dosage ; Middle Aged ; Pituitary Diseases/complications/*drug therapy ; Pulse Therapy, Drug

BACKGROUND: Although emerging evidence suggests that intra-abdominal hypertension (IAH) is a predictor of the development of acute kidney injury (AKI), it remains unclear whether the presence of IAH is a predictor of prognosis in patients with AKI. The purpose of this study was to assess whether the presence of IAH could predict prognosis in critically ill patients with AKI. The prognostic value of urinary biomarkers was also determined. METHODS: In this prospective observational study, we enrolled 57 patients with established AKI, who were admitted to the intensive care unit between February 2012 and June 2014. IAH was defined as a sustained elevation in intra-abdominal pressure of > or =12 mmHg, in three consecutive measurements performed daily on the first 3 days. Urinary neutrophil gelatinase-associated lipocalin (NGAL), liver-type fatty acid-binding protein, and simplified acute physiology score II score at the time of admission were also examined. RESULTS: IAH was observed in 78.9% of patients. The in-hospital mortality was 21.1%, and renal recovery during hospitalization was achieved in 40.4% of patients. Although high urinary NGAL [odds ratio (OR), 1.015] and liver-type fatty acid-binding protein (OR, 1.003) were found to be independent predictors of renal recovery, IAH was not. High urinary NGAL (OR, 1.003) and a high simplified acute physiology score II score (OR, 1.102) were independent predictors of in-hospital mortality, while IAH or urinary liver-type fatty acid-binding protein was not. CONCLUSION: Although IAH is prevalent in critically ill patients with AKI, it did not predict AKI prognosis. However, urinary NGAL was found to be a useful predictor of both renal recovery and in-hospital mortality.
Acute Kidney Injury* ; Biomarkers ; Critical Illness* ; Hospital Mortality* ; Hospitalization ; Humans ; Intensive Care Units ; Intra-Abdominal Hypertension* ; Lipocalins ; Neutrophils ; Observational Study ; Physiology ; Prognosis ; Prospective Studies

BACKGROUND: Pulmonary hypertension (PHT) is a recently recognized complication of chronic kidney disease. In this study, we investigated the association between PHT, peripheral vascular calcifications (VCs), and major cardiovascular events. METHODS: In this retrospective study, we included 172 end-stage renal disease (ESRD) patients undergoing dialysis [hemodialysis (HD)=84, peritoneal dialysis=88]. PHT was defined as an estimated pulmonary artery systolic pressure >37 mmHg using echocardiography. The Simple Vascular Calcification Score (SVCS) was measured using plain radiographic films of the hands and pelvis. RESULTS: The prevalence of PHT was significantly higher in HD patients (51.2% vs. 22.7%). Dialysis patients with PHT had a significantly higher prevalence of severe VCs (SVCS> or =3). In multivariate analysis, the presence of severe VCs [odds ratio (OR), 2.68], mitral valve disease (OR, 7.79), HD (OR, 3.35), and larger left atrial diameter (OR, 11.39) were independent risk factors for PHT. In addition to the presence of anemia, severe VCs, or older age, the presence of PHT was an independent predictor of major cardiovascular events in ESRD patients. CONCLUSION: The prevalence of PHT was higher in HD patients and was associated with higher rates of major cardiovascular events. Severe VCs are thought to be an independent risk factor for predicting PHT in ESRD patients. Therefore, in dialysis patients with PHT, careful attention should be paid to the presence of VCs and the occurrence of major cardiovascular events.
Anemia ; Blood Pressure ; Cardiovascular Diseases ; Dialysis* ; Echocardiography ; Hand ; Humans ; Hypertension, Pulmonary* ; Kidney Failure, Chronic ; Mitral Valve ; Multivariate Analysis ; Pelvis ; Prevalence ; Pulmonary Artery ; Renal Insufficiency, Chronic ; Retrospective Studies ; Risk Factors ; Vascular Calcification* ; X-Ray Film

BACKGROUND AND OBJECTIVES: Despite significant improvement in the field of angioplasty, restenosis remains a major obstacle to the long-term success of the procedure. Radiation can effectively inhibit neointimal hyperplasia by causing the arrest of mitosis during cell division and limiting proliferation by reducing the number of regenerating clonal progenitors. Balloon injury could induce the cell adhesion molecule, ICAM-1 and VCAM-1, on SMCs and regenerating endothelial cells (ECs). ICAM-1 and/or VCAM-1 may play a role in the progression of neointimal hyperplasia induced by balloon injury and external radiation may effectively inhibit neointimal hyperplasia by attenuating their expression. The purpose of this study was to examine the effect of external radiation against ICAM-1 and VCAM-1 on neointimal hyperplasia after balloon injury in rat carotid arteries. MATERIAL AND METHODS: A standardized carotid balloon catheter arterial injury was produced in 51 rats and external beam radiation with doses from 5-20 Gy were delivered in 28 rats (radiation treated group) at 24 hours after injury. To investigate the effect of the external radiation on neointimal hyperplasia, the intima area and the intima/medial area of arteries were measured at day 14 after injury. The expressions of ICAM-1 and VCAM-1 at day 2, day 7, and day 10 after injury were studied in control group and radiation treated group by immunohistochemistry. RESULTS: Means of intimal area and intima/medial ratio in radiation treated group were significantly lower than those in control group and significantly reduced with increasing radiation dosage. At day 2 after injury, medial SMCs of injury group extensively expressed ICAM-1, while it was focally expressed with 10 Gy radiation treated group. At day 7 and day 10 after injury, ICAM-1 expression on medial SMCs was attenuated and neointimal ICAM-1 expression was increased. As compared with control group, ICAM-1 expression after radiation was weak and focal just around the internal elastic lamina. At 2 days after injury, medial SMCs moderately expressed VCAM-1, which was weakly and focally expressed with 10 Gy radiation treated group. At day 7 and day 10 after injury, focal expression of VCAM-1 was noted around the internal elastic lamina, but there was no VCAM-1 expression on neointima with radiation. CONCLUSION: External radiation after carotid arterial injury may potentially inhibit SMC proliferation and neointimal hyperplasia, and balloon injury-induced or upregulated expressions of ICAM-1 and VCAM-1 may be attenuated with external radiation.
Angioplasty ; Animals ; Arteries ; Carotid Arteries ; Catheters ; Cell Adhesion* ; Cell Division ; Endothelial Cells ; Hyperplasia* ; Immunohistochemistry ; Intercellular Adhesion Molecule-1* ; Mitosis ; Neointima ; Radiation Dosage ; Rats* ; Vascular Cell Adhesion Molecule-1