Increased expression of CYR61, an extracellular matrix signaling protein, in human benign prostatic hyperplasia and its regulation by lysophosphatidic acid

Lysophosphatidic acid (LPA) is an endogenous lipid growth factor that is thought to play important roles in cell proliferation and antiapoptosis and therefore may have roles in the development and progression of benign prostatic hyperplasia (BPH). CYR61 (CCN1), on the other hand, is a growth factor-inducible immediate early gene that functions in cell proliferation, differentiation, and extracellular matrix synthesis. Here we show the close relationship between LPA-induced expression of CYR61 and prostate enlargement. CYR61 mRNA and protein were dramatically up-regulated by 18:1 LPA (oleoyl-LPA) within 1 and 2 h, respectively, in both stromal and epithelial prostatic cells. G protein-coupled receptors, i.e. Edg-2, Edg-4, and Edg-7, for LPA were also expressed in both stromal and epithelial prostatic cells. Furthermore, on DNA microarray analysis for normal and BPH patients, CYR61 was found to be related to the development and progression of BPH, regardless of symptoms. Although CYR61 mRNA was synthesized in hyperplastic epithelial cells, in many cases of BPH, CYR61 protein was detected in both the epithelial and stromal regions of BPH patient tissues. The functional contribution of CYR61 to prostatic cell growth was demonstrated by recombinant CYR61 protein and anti-CYR61 neutralizing antibodies, which inhibited CYR61-dependent cell spreading and significantly diminished cell proliferation, respectively. In conclusion, these data support the hypothesis that LPAs induce the expression of CYR61 by activating G proteincoupled receptors and that CYR61 acts as a secreted autocrine and/or paracrine mediator in stromal and epithelial hyperplasia, demonstrating the potential importance of this signaling mechanism in the disease.     

Gastric Mucosal Injury Induced by Local Ischemia-Reperfusion in Rats (Role of Endogenous Endothelin-1 and Free Radical)

We investigated the role of an endogenousvasoconstrictor peptide endothelin-1 (ET-1) and freeradicals in local gastric ischemia-reperfusion injury inrats. Local gastric ischemia was induced by clamping the left gastric artery for 15 min andreperfusion was done for 10-30 min in the presence of150 mM exogenous HCl intragastrically. Local gastricischemia and reperfusion resulted in significantmacroscopic and microscopic gastric mucosal damage togetherwith elevation of gastric tissue ET-1 concentration.Gastric tissue ET-1 was found to increase after 15 minof ischemia alone and also with 30 min of reperfusion. A novel nonpeptide endothelin receptorantagonist, bosentan, or a combination of radicalscavengers (superoxide dismutase, catalase, anddeferoxamine) both attenuated gastric mucosal injury.However, the greater protection observed with bosentan thanwith radical scavengers might reflect a preferentialrole of endothelin-1 in this type of injury.     

Serum inhibition of complement derived leukocyte chemotaxis and levels of immunoglobulin A subclass in alcoholic liver disease

Serum inhibition of complement-derived leukocyte chemotaxis was examined in alcoholic liver disease with or without cirrhosis. Chemotactic inhibitory activity (CIA) was detected with higher frequency and degree in alcoholic liver disease, especially with liver cirrhosis compared with normal subjects and non-alcoholic liver cirrhosis. CIA was found in anti-IgA adsorbed fractions in the sera of patients with alcoholic liver cirrhosis. Serum concentrations of IgAl and IgA2 in alcoholic liver disease were statistically higher than in non-alcoholic liver cirrhosis. However, no correlation between CIA and the concentrations of IgA subclasses was demonstrated in alcoholic liver disease. This serum inhibitor may partly explain the high susceptibility to bacterial infection in alcoholic liver disease.     

Relationship between efficacy of antiarrhythmic drug therapy and structural remodeling in patients with paroxysmal atrial fibrillation

OBJECTIVES: To evaluate whether the response to antiarrhythmic drug therapy in patients with paroxysmal atrial fibrillation affects the development of structural remodeling in the left atrium and ventricle. METHODS: This study included 230 patients (158 men and 72 women, mean age 67 +/- 11 years) in whom antiarrhythmic drug therapy was attempted for > or = 12 months to maintain sinus rhythm (mean follow-up period 45 +/- 27 months). The patients were divided into three groups according to the response to antiarrhythmic drug therapy: group A consisted of 78 patients without recurrence of atrial fibrillation, group B consisted of 87 patients with recurrence of atrial fibrillation and electrical and/or pharmacological cardioversion to restore sinus rhythm, and group C consisted of 65 patients with permanent conversion despite antiarrhythmic drug therapy. RESULTS: In group A, left atrial dimension (LAD), left ventricular end-diastolic dimension (LVDd), and left ventricular ejection fraction (LVEF) did not change after antiarrhythmic drug therapy. In group B, LAD increased significantly after antiarrhythmic drug therapy (from 32.6 +/- 6.4 to 36.0 +/- 6.5 mm, p < 0.01), Whereas either LVDd or LVEF did not change after antiarrhythmic drug therapy. In group C, LAD increased significantly after antiarrhythmic drug therapy (from 37.3 +/- 7.0 to 40.5 +/- 7.9 mm, p < 0.01) and LVEF was significantly reduced after antiarrhythmic drug therapy (from 69.4 +/- 6.2% to 66.5 +/- 8.9%, p < 0.05). LVDd did not change after antiarrhythmic drug therapy. The plasma concentration of human atrial natriuretic peptide during sinus rhythm at the initiation of antiarrhythmic drug therapy in group A (30.5 +/- 26.7 pg/ml) was significantly lower than those in group B (48.0 +/- 49.7 pg/ml) and group C (49.7 +/- 39.5 pg/ml). CONCLUSIONS: The development of structural remodeling in human myocardium can be prevented with antiarrhythmic drug therapy if sinus rhythm is maintained without recurrence of atrial fibrillation in patients with paroxysmal atrial fibrillation.     

Combined semi-nested polymerase chain reaction and heteroduplex analysis for detecting monoclonality of IgH rearrangement in patients with follicular lymphoma

A new, sensitive method combining seminested polymerase chain reaction (PCR) and heteroduplex analysis was used to detect follicular lymphoma (FL) cells in peripheral blood. Based on the detection of IgH rearrangement in DNA from peripheral blood leukocytes, the method demonstrated the presence of monoclonal B cells in FL patients with high frequency.     

Case of multiple intrapulmonary lymph nodes]

A 45-year-old man who had hypertension, hyperthyroidism, and bronchial asthma was admitted to our hospital because of a low-grade fever and chest pain. The physical findings and laboratory data were almost all within normal limits except for evidence of mild inflammation and liver dysfunction. The chest X-ray findings seemed normal, but a computed tomography (CT) scan showed multiple nodules in both lower lung fields. We suspected the cryptococcosis or lung cancer. Biopsy by video-assisted thoracoscopic surgery (VATS) yielded a diagnosis of multiple intrapulmonary lymph nodes. In cases with the above radiologic findings, careful attention should be paid to making the differential diagnosis between intrapulmonary lymph nodes and primary lung cancer. The promotion of diagnostic imaging and advances in techniques have made it easier to identify small peripheral nodules in the lungs, and we now know of their existence. Solitary intrapulmonary lymph nodes are encountered frequently, but multiple or increasing numbers of nodes, as in our case, are very rare. Moreover, because cases with elevated CEA levels have been reported, differentiation from lung cancer appears to be important.     

HLA-associated cellular response to GAD in type 2 diabetes with antibodies to GAD

Proliferative response of peripheral blood mononuclear cells (PBMC) to glutamic acid decarboxylase (GAD), which has been reported in patients with type 1 diabetes, was measured in type 2 diabetes, especially in patients with antibodies to GAD initially diagnosed as having type 2 diabetes (anti-GAD+ type 2 diabetes). We studied 12 patients with type 1 diabetes, 22 with anti-GAD+ type 2 diabetes, 31 with type 2 diabetes who were negative for anti-GAD (anti-GAD+ type 2 diabetes), and 30 healthy control subjects for cellular responses in vitro to GAD. The mean stimulation index (SI) in response to GAD was significantly higher in type 1 diabetes than in anti-GAD+ type 2 diabetes or healthy controls (1.47+/-0.35 vs. 1.11+/-0.35, P<0.05, and 1.06+/-0.07, P<0.05, respectively). The mean