Midkine, a heparin-binding growth factor, is fundamentally involved in the pathogenesis of rheumatoid arthritis

OBJECTIVE: Midkine (MK), a heparin-binding growth factor, promotes growth, survival, and migration of various cells. The essential role of MK in migration of inflammatory cells has been shown using mice deficient in the MK gene (Mdk(-/-) mice). We undertook this study to investigate the role of MK in the pathogenesis of rheumatoid arthritis (RA). METHODS: MK levels in specimens from patients were determined by enzyme-linked immunosorbent assay, and localization of MK was revealed by immunohistochemical analysis. Susceptibility to antibody-induced arthritis was compared between Mdk(-/-) and wild-type (WT) mice. Osteoclast differentiation was monitored using macrophage-like cells isolated from human synovial tissue and macrophages from mouse bone marrow. RESULTS: MK levels in sera and synovial fluid were increased in most RA patients, indicating a strong correlation between MK expression and RA. MK was expressed in macrophage-like cells and fibroblast-like cells in synovial membranes from the patients. In antibody-induced arthritis, Mdk(-/-) mice seldom developed the disease, while most of the WT mice did. Administration of MK to the Mdk(-/-) mice increased the frequency of antibody-induced arthritis. Migration of inflammatory leukocytes to the synovial membranes in the disease model was suppressed in the Mdk(-/-) mice. Furthermore, MK was found to promote the differentiation of osteoclasts from macrophages. CONCLUSION: MK participates in each of the two distinct phases of RA development, namely, migration of inflammatory leukocytes and osteoclast differentiation, and is a key molecule in the pathogenesis of RA.     

Evolution to dilated cardiomyopathy from acute eosinophilic pancarditis in Churg-Strauss syndrome

Summary We describe the clinical manifestations of a patient with Churg-Strauss syndrome who presented with severe acute cardiac involvement and whose disease evolved to dilated cardiomyopathy (DCM), with special reference to the histopathological findings. Endomyocardial biopsies, conducted sequentially, three times within 10 months, revealed severe eosinophilic endomyocarditis in the acute phase, interstitial fibrosis in the subacute phase, and endocardial thickening with mural thrombi, at 10 months. Although acute inflammation associated with elevation of eosinophil granule proteins subsided with steroid therapy, left ventricular dilatation with reduced contractility progressed. A subgroup of DCM is not considered to be idiopathic but, rather, an aftereffect of hypereosinophilic heart disease.     

Complement and polymorphonuclear leukocyte activation each play a role in determining myocardial ischemia-reperfusion injury.

Cobra venom factor (CVF) transiently activates polymorphonuclear leukocytes (PMN) by complement activation, followed by rapid complement depletion and gradual reversal of PMN activation. Utilizing these sequential changes caused by CVF, the individual and combined effects of complement and PMNs on myocardial infarct size (IS) were investigated. Rats were treated with CVF, and/or anti-PMNs. Complement was depleted, but circulating PMNs were being activated at 4h after CVF administration, and at 36h after, complement was depleted, but PMNs were in a near basal condition. Under anesthesia, the rats had a 30-min coronary occlusion followed by 6h of reperfusion. The IS was assessed by tetrazolium staining. CVF, as well as anti-PMNs, reduced myeloperoxidase (MPO) activity in the risk area and the reduced MPO resulted in a reduced IS, which was also the effect of anti-PMNs, but complement depletion by CVF, during which circulating PMNs were activated, failed to reduce the IS despite low MPO activity. These results suggest that complement and the condition of PMNs each play a role in determining the IS, and ischemic reperfusion injury might be produced even by relatively low myocardial MPO activity.     

Current role of ultrasound for the management of hepatocellular carcinoma

Hepatocellular carcinoma （HCC） has a decisive influence on the prognosis of cirrhotic patients. Although α-fetoprotein （AFP） is a known and specific tumor maker for HCC, it is not suitable for the screening and surveillance of HCC because of its poor predictive value and low sensitivity. The use of imaging modalities is essential for the screening, diagnosis and treatment of HCC. Ultrasound （US） plays a major role among them, because it provides real-time and non-invasive observation by a simple and easy technique. In addition, US-guided needle puncture methods are frequently required for the diagnosis and/or treatment process of HCC. The development of digital technology has led to the detection of blood flow by color Doppler US, and the sensitivity for detecting tumor vascularity has shown remarkable improvement with the introduction of microbubble contrast agents. Moreover, near realtime 3-dimensional US images are now available. As for the treatment of HCC, high intensity focused ultrasound （HIFU） was developed as a novel technology that provides transcutaneous ablation effect without needle puncture. These advancements in the US field have led to rapid progress in HCC management, and continuing advances are expected. This article reviews the current application of US for HCC in clinical practice.     

Endoscopic studies on the minute structures of colonic mucosa in the follow-up observation of ulcerative colitis

Journal of Gastroenterology - Thirty cases of ulcerative colitis were examined endoscopically by means of magnifying colonoscope with dye spraying method (the combined method), and their minute...