Tetsuo Morishita

Enhanced plasma ghrelin levels in patients with functional dyspepsia: ENHANCED PLASMA GHRELIN LEVELS IN FUNCTIONAL DYSPEPSIA

Ghrelin, growth‐hormone‐releasing peptide, has been reported to accelerate food intake and gastrointestinal motility.

Fasting gastric pH of Japanese subjects stratified by IgG concentration against Helicobacter pylori and pepsinogen status.

Background:u2002 The clinical significance of Helicobacter pylori antibody titer has been controversial, and the association between the extent of gastric atrophy or acid secretion and H. pylori antibody concentration has not been elucidated.

EFFECTS OF DIESEL EXHAUST PARTICLES ON HUMAN NEUTROPHIL ACTIVATION

Diesel exhaust particles (DEP) are associated with respiratory disease and exposure to diesel exhaust induces an inflammatory response associated with marked leukocytic infiltration in the lung. This study examined whether neutrophils are activated by the active component of DEP (methanol extract of DEP [me-DEP]). The authors demonstrated that neutrophils exposed to me-DEP had increased levels of the f-actin content, the surface expression of adhesion molecules, and the release of interleukin (IL-8) and leukotriene B4 (LTB4), superoxide, and matrix metalloproteinase (MMP-9). Thus, the author conclude that DEP exposure activates neutrophils and that these activated neutrophils could contribute to the adverse respiratory health effects associated with DEP and to the pathogenesis of chronic inflammatory lung diseases.

ADAMTS5 Is a Biomarker for Prediction of Response to Infliximab in Patients with Rheumatoid Arthritis

Objective. To identify a biomarker for prediction of the response to infliximab (IFX) in patients with rheumatoid arthritis (RA), we focused on a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) that seems to play a key role in aggrecan degradation in cartilage. Methods. Seventy-three randomly selected patients with active RA were treated with IFX. Peripheral blood samples were collected at baseline and ADAMTS5 messenger RNA (mRNA) was quantified using real-time polymerase chain reaction. Results. Baseline ADAMTS5 mRNA levels in the good responder group were significantly lower (1.84 ± 1.56; p = 0.0408) than those in the moderate and nonresponder groups (2.54 ± 1.70) at 38 weeks of treatment with IFX. The 28-joint count Disease Activity Score (DAS28) at 38 weeks of treatment was significantly lower in the low ADAMTS5 group (2.30 ± 1.28; p = 0.0038) than in the high ADAMTS5 group (3.90 ± 1.61). The percentage reduction of the DAS28 was significantly higher in the low ADAMTS5 group (52.5% ± 28.8%; p = 0.0156) than in the high ADAMTS5 group (29.4% ± 27.2%). Further, the Δ Health Assessment Questionnaire (ΔHAQ) score, an estimate of the improvement in the HAQ score, at 38 weeks of treatment was significantly higher in the low ADAMTS5 group (1.18 ± 0.60; p = 0.0102) than in the high ADAMTS5 group (0.21 ± 0.78). The positive predictive value of a low baseline ADAMTS5 level for predicting good response and remission (DAS28 < 2.6 at 38 weeks) was 90.0% and 70.0%, respectively. Conclusion. The baseline ADAMTS5 mRNA level is a candidate biomarker for prediction of the response to IFX in patients with RA.

Persistent hiccups followed by cardiorespiratory arrest

In January, 2011, a 78-year-old man was referred to us with syncope and persistent hiccups. He had had nausea and continuous hiccups 9 days earlier, and had fainted while visiting a local clinic. At our hospital, he had an immediate reduction in systolic blood pressure of 40 mm Hg and loss of consciousness after standing up after lying in a supine position for 5 min. Neurological evaluation showed a right hypoglossal nerve palsy, but MRI of the brain and spinal cord and cerebrospinal fl uid were normal. Chest radiography, gastroendoscopy, ECG, and echocardiography showed no abnormalities. Metoclopramide was prescribed for hiccups and amezinium metilsulphate for orthostatic hypotension. He was discharged because his symptoms improved. 2 weeks later he developed muscle weakness, and after 3 days could not walk. On readmission, he had dysarthria and dysphagia. Ophthalmoscopy showed no abnormalities. He had severe muscle weakness in his upper and lower limbs. CSF white blood cell count was 78 μL (99% lymphocytes) and protein concentration 1·03 g/L. MRI of the brain showed lesions in the medulla oblongata. We suspected acute disseminated encephalomyelitis, herpes simplex virus encephalitis, or neuromyelitis optica (NMO) spectrum disorder, and he was given methylprednisolone pulse therapy (1 g per day) and acyclovir 1500 mg per day. Despite treatment, his muscle weakness worsened. 1 week after completion of methylprednisolone pulse therapy, he had dyspnoea. Arterial blood gas fi ndings were unremarkable while on 2 L oxygen, so we planned MRI of the spinal cord the same day. His blood saturation level started decreasing, while he was in the

Gastric cancer associated with Dieulafoy's lesion: case report

Dieulafoy’s lesion, also known as a caliber-persistent artery of the stomach, is an uncommon cause of GI bleeding; it accounts for only 2% of episodes of acute and chronic bleeding.1,2 This mucosal lesion, usually occurring along the lesser curvature of the proximal stomach, is small and shallow but can be associated with a massive, life-threatening hemorrhage. Dieulafoy’s lesion may be difficult to diagnose, especially when bleeding is absent. Although initial descriptions were based on surgically resected specimens, endoscopy is a sensitive and accurate means of diagnosis. Dieulafoy’s lesion is now almost always treated endoscopically, with hemostasis achieved in most patients.3,4 A patient is described with gastric cancer who presented with massive upper GI hemorrhage from a Dieulafoy’s lesion in the stomach; hemostasis was established endoscopically. To the investigators’ knowledge, there is only one other report of gastric cancer associated with a histopathologically proven Dieulafoy’s lesion.5 Whenever the slightest suspicion of malignancy is present in cases with atypical endoscopic findings for Dieulafoy’s lesion, follow-up endoscopy with biopsies should be performed for accurate diagnosis.

Lipopolysaccharides stimulate adrenomedullin synthesis in intestinal epithelial cells: release kinetics and secretion polarity

Adrenomedullin (AM), a potent vasodilator peptide initially isolated from a human pheochromocytoma, functions as an antimicrobial peptide in host defense. In this study, we investigated changes in AM levels in intestinal epithelial cells and the mechanism of its secretion and cellular polarity after exposure to lipopolysaccharides (LPS). When a rat small intestinal cell line (IEC-18 cells) was exposed to LPS, enzyme-linked immunosorbent assay revealed a dose-dependent increase in AM together with an increase in AM mRNA expression, as determined by real-time polymerase chain reaction. Up-regulation of AM by LPS was dose-dependently inhibited by LY294002, PD98059, SP600125 and calphostin-C, suggesting the involvement of the phosphatidylinositol 3 kinase, extracellular signal-regulated kinase, c-Jun NH2-terminal kinase and protein kinase C pathways, respectively, in this process. When polarized IEC-18 cells in a Transwell chamber were stimulated with LPS, AM secretion was directed primarily toward the side of LPS administration (either the apical or basolateral side). In situ hybridization revealed that AM mRNA was expressed in epithelial cells and in the connective tissue in the lamina propria of the jejunum after intraperitoneal or oral administration of LPS. Higher levels of AM mRNA expression were observed in rats treated with LPS via the intraperitoneal route, compared with those treated via the oral route. These findings suggest that intestinal AM plays an important role in mucosal defense in the case of intestinal luminal infection, as well as in the modulation of hemodynamics in endotoxemia.

MAGNIFYING ENDOSCOPY OF THE DUODENUM WITH DYE SCATTERING METHOD IN A CASE WITH CELIAC DISEASE

AIMnTo know the more detailed findings of the small intestinal mucosa with the use of a magnifying endoscope and a vital dye, and the efficacy of the both tools.nnnPATIENT AND METHODSnA 54-year old female patient with celiac disease. The duodenal mucosa downward as far as the descending portion was observed with a magnifying endoscope (Olympus GIF HM) before and after spraying the mucosa with 0.1% indigo carmine.nnnRESULTSnThe endoscopy clarified the atrophy and edema of each villus, and scattering of the dye revealed shorter villi with the relatively longer villi remaining in islands.nnnCONCLUSIONnThe combination of magnifying endoscopy and the dye scattering method is useful for closer observation of the intestinal mucosa in celiac diseases.

The Role of Granulysin in Cancer Immunology

Granulysin is a cytotoxic granule expressed in cytotoxic T cells and natural killer cells. Although its cytotoxic effect against a number of tumor cell lines has been demonstrated in vitro, recent studies with transgenic mice, and a number of clinical studies, have further established its significance in cancer immunology. Furthermore, granulysin-induced in vitro chemotaxis and activation of both human and mouse dendritic cells have been reported. Given the results in recent clinical studies, granulysin may offer a useful indicator in the prognosis of cancer. Taken together, an understanding of the mechanism by which granulysin destroys target cells would provide vital information in the development of new therapies for the treatment of this disease.

Serum Nitrate/Nitrite Concentration Correlates with Gastric Juice Nitrate/Nitrite: A Possible Marker for Mutagenesis of the Proximal Stomach

Background/Aims: In the normal acid-secreting stomach, luminally generated nitric oxide, which contributes to carcinogenesis in the proximal stomach, is associated with the concentration of nitrate plus nitrite (nitrate/nitrite) in gastric juice. We investigated whether the serum nitrate/nitrite concentration is associated with that of gastric juice and whether it can be used as a serum marker. Methods: Serum and gastric juice nitrate/nitrite concentration, Helicobacter pylori antibody, and gastric pH were measured in 176 patients undergoing upper endoscopy. Results: Multiple regression analysis revealed that serum nitrate/nitrite concentration was the best independent predictor of gastric juice nitrate/nitrite concentration. On single regression analysis, serum and gastric juice nitrate/nitrite concentration were significantly correlated, according to the following equation: gastric juice nitrate/nitrite concentration (µmol/l) = 3.93 – 0.54 × serum nitrate/nitrite concentration (µmol/l; correlation coefficient = 0.429, p < 0.001). In analyses confined to subjects with gastric pH less than 2.0, and in those with serum markers suggesting normal acid secretion (pepsinogen-I >30 ng/ml and negative H. pylori antibody), the serum nitrate/nitrite concentration was an independent predictor of the gastric juice nitrate/nitrite concentration (p < 0.001). Conclusion: Measuring the serum nitrate/nitrite concentration has potential in estimating the gastric juice nitrate/nitrite concentration. The serum nitrate/nitrite concentration could be useful as a marker for mutagenesis in the proximal stomach.