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.     

Relationship between children physical activity,inflammatory mediators and lymphocyte activation: possible impact of social isolation (COVID-19)

Sport Sciences for Health - Lifestyle and body composition may be simultaneously responsible for immune response modulation. This study aimed to compare plasmatic adipokines concentration and...     

Ultrasonographic evaluation of gastrointestinal graft‐versus‐host disease after hematopoietic stem cell transplantation

Gastrointestinal graft‐versus‐host disease (GI‐GVHD) is a major and life‐threatening complication of hematopoietic stem cell transplantation (HSCT). This study evaluated the efficacy of ultrasonography (US) for assessing and monitoring GI‐GVHD. GI tract was evaluated by US in 81 patients. US findings were positive in 43 patients, including 11 false positive, and negative in 38 patients. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of US for the diagnosis of GI‐GVHD were 100%, 78%, 74%, 100%, and 86%, respectively. Diffuse wall thickening of the ileum was the most frequent finding in patients with GI‐GVHD. Severity of GI‐GVHD was correlated with the thickness of internal low echoic layer of the wall, the echogenicity of mesenteric fat tissue, and the intensity of Doppler signaling. We classified US findings of GI‐GVHD into four US grades. There was a significant correlation between clinical stage of GI‐GVHD and the US grade. These ultrasonographic abnormalities were improved with clinical improvement of GI‐GVHD upon treatment. Thus, US is an effective and efficient non‐invasive means of identifying the extent and severity of GI‐GVHD and monitoring response to treatment.     

High‐mobility group box‐1 release into fetal circulation from umbilical cord tissue and amniotic epithelium in fetal ischemia

We report the case of a baby with low birthweight born by emergency caesarean section at 33 weeks 2 days' gestation due to placental abruption. High‐mobility group box‐1 (HMGB‐1) and interleukin‐17 concentration in the umbilical cord blood were high at 55.7 ng/mL and 50.7 pg/mL, respectively. On immunostaining of umbilical cord and amniotic epithelium, HMGB‐1 was identified in the nuclei of vascular endothelial cells and cytoplasm of the surrounding cells in the umbilical cord. This suggests that, in the present case of placental abruption and subsequent ischemic placenta and fetus, the high level of HMGB‐1 observed was due to the release of HMGB‐1 into the umbilical cord blood from the vascular endothelial cells of the umbilical cord.     

Sonographic findings of immunoglobulin G4-related sclerosing sialadenitis

Purpose

We evaluated the sonographic findings of immunoglobulin G4-related sclerosing sialadenitis (IgG4-SS).

Methods

Nineteen patients with IgG4-SS and 12 healthy volunteers (controls) were enrolled. The following sonographic features were evaluated: (1) enlargement of the submandibular gland by measurement of the longitudinal diameter and thickness; (2) the contour texture of the submandibular gland (smooth or rough); (3) the internal echo texture, categorized into three sonographic patterns (homogeneous, multiple hypoechoic nodule, and diffuse hypoechoic); and (4) quantitative color Doppler signaling.

Results

The longitudinal diameter and the thickness (mean ± SD) of the submandibular gland were significantly greater in patients than in controls (p = 0.005 and p < 0.001, respectively). Contour roughness was seen in 62.9 and 8.3 % of patients and controls (p < 0.001), respectively. Homogeneous echo textures alone were seen in controls, whereas multiple hypoechoic nodule patterns were seen in 60 % of the patients, and diffuse hypoechoic patterns were seen in 40 %. Color Doppler signaling (mean ± SD) was significantly higher in patients as compared with controls (p < 0.001).

Conclusion

Patients could be distinguished from healthy volunteers using four distinctive sonographic findings, suggesting that ultrasonography would be a useful diagnostic tool for IgG4-SS.

     

Interaction between serum amyloid A and leukocytes - a possible role in the progression of vascular complications in diabetes

Diabetes mellitus is associated with an increased incidence of cardiovascular events and microvascular complications. Serum amyloid A (SAA), a HDL apolipoprotein is a risk marker for cardiovascular disease. A permanent increase in SAA plasma levels is observed in diabetics. Because SAA acts on leukocytes, we evaluated whether the synthesis of proinflammatory cytokines and migration of neutrophils and monocytes induced by SAA is affected in diabetics. Cells, isolated from human blood, were cultured in the presence of SAA. TNF-alpha, IL-1beta, IL-8 and IL-1ra levels were measured by ELISA in the culture supernatants and in serum of subjects. Neutrophils and monocytes migration were followed in a chemotaxis chamber. We make the novel observation that neutrophils and monocytes of diabetics are more responsive to SAA for the induction of the proinflammatory cytokine IL-1beta and the proangiogenic and chemotactic protein IL-8. Incremental TNF-alpha production was also found to occur when monocytes were stimulated with SAA. Cell migration was also increased. The increased production of cytokines and increased migration of leukocytes from diabetics in response to SAA may contribute to a sustained accumulation and activation of inflammatory cells in the disease. Accordingly, the hyper-responsiveness of leukocytes to SAA may be relevant to the proinflammatory conditions associated to vascular complications in diabetic patients.     

A new evaluation method for upper extremity dexterity of patients with hemiparesis after stroke: the 10-second tests

We developed a new, sensitive evaluation method for upper extremity dexterity in patients with hemiparesis after stroke. This evaluation method consists of three types of test: the Finger Individual Movement Test, Hand Pronation and Supination Test, and Finger Tapping Test. In each test, the number of movements that can be performed during a 10-s period is measured. Data obtained by these 10-s tests were compared with those obtained by the Nine-Hole Peg Test (NHPT), and the usefulness of this new method was evaluated. In patients with hemiparesis after stroke, three types of 10-s test and NHPT were performed for the upper extremities on both the affected and unaffected sides. Simple correlation analysis and multiple regression analysis of data obtained by the three types of test and NHPT were performed using the affected/unaffected ratios. Twenty patients participated (54-85 years; 0.23-43.83 months after stroke) with mild upper extremity hemiparesis. Significant correlations exist between Finger Individual Movement Test and NHPT data (r=-0.584, P=0.0068) and between Hand Pronation and Supination Test and NHPT data (r=-0.707, P=0.0005). The multiple regression analysis model using the three types of 10-s test as explanatory variables was significant (P=0.0025) and explained 52.4% of the NHPT results. A significant association was observed between NHPT and the 10-s tests. The 10-s tests require no special examination instruments and can be readily performed in a short period. This evaluation method consisting of the 10-s tests can be a new clinical parameter of dexterity in patients with hemiparesis after stroke.