Human glioblastomas overexpress ADAMTS-5 that degrades brevican

Selective cleavage of the Glu³⁹⁵-Ser³⁹⁶ bond of brevican, one of the major proteoglycans in adult brain tissues, is thought to be important for glioma cell invasion. Our previous biochemical study demonstrated that ADAMTS-4, a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family, has such an activity. In the present study, we examined brevican-degrading activities of ADAMTS-1, -4 and -5 at the cellular level, and their expression and localization in human glioma tissues. In 293T transfectants expressing ADAMTS-4 or ADAMTS-5, brevican was cleaved into two major fragments in an identical pattern, but no such degradation was observed with ADAMTS-1 transfectants. When the expression levels of these ADAMTS species were examined by real-time quantitative PCR, only ADAMTS-5 was found to be overexpressed in glioblastoma tissues compared to control normal brain tissues (P <0.05). In situ hybridization and immunohistochemistry demonstrated that ADAMTS-5 is expressed predominantly in glioblastoma cells. Forced expression of ADAMTS-5 in glioma cell lines stimulated cell invasion. These results demonstrate for the first time that ADAMTS-5 is capable of degrading brevican and is overexpressed in glioblastoma cells, and suggest that ADAMTS-5 may play a role in glioma cell invasion through the cleavage of brevican.     

Oxygen pressure measurement during grip exercise reveals exercise intolerance after radial harvest

BACKGROUND: Exercise intolerance of the hand after harvest of the radial artery is not well understood, although mild reductions of blood flow to the hand are reported. To ascertain its prevalence, patient symptoms implying potential exercise intolerance were evaluated by measuring transcutaneous oxygen pressure of the hand during grip exercise. For ascertaining predictive values, we verified ulnar flow reserve measured by Doppler ultrasonography before the harvest of radial artery. METHODS: Forty patients whose radial artery was harvested for coronary bypass graft, were interviewed and tested 1 year after operation, and their preoperative ultrasonographic data compared. RESULTS: Five patients (12.5%) had mild symptoms implying exercise intolerance. Exercise tests revealed severe decreases in tissue oxygenation in 7 patients (17.5%), but in accordance with symptoms (p = 0.0018). Tissue oxygenation in the operated hand was lower than in the nonoperated even in asymptomatic patients (p = 0.0011). Preoperative Doppler echography revealed that ulnar arteries of symptomatic patients were smaller (p = 0.0019) and carried lower blood flows during manual compression of the radial artery (p = 0.0004) compared with those of asymptomatic patients. Smaller ulnar arteries (less than 1.4 mm/m(2)) with poor flow reserves (less than 60 mL x min(-1) x m(-2) during radial compression) appear to indicate risks for exercise intolerance (p = 0.0004). CONCLUSIONS: More than 10% of patients after harvest of radial arteries had mild symptoms implying exercise-intolerance, which accorded with abnormal tissue oxygenation during grip exercise. Work habits of patients should be considered in radial harvest decisions, especially if preoperative Doppler echography indicates lower flow reserves for the ulnar artery.     

TNP-470, an angiogenesis inhibitor, suppresses the progression of peritoneal fibrosis in mouse experimental model

BACKGROUND: In patients on long-term peritoneal dialysis (PD), angiogenesis and vasculopathy are observed in the peritoneum, and the degree of vascularization correlates with the area of fibrotic tissue, suggesting the involvement of angiogenesis in the progression of peritoneal fibrosis. The aim of the present study was to evaluate the effect of TNP-470, an anti-angiogenic compound, on the development of peritoneal fibrosis induced by chlorhexidine gluconate (CG). METHODS: Peritoneal fibrosis was induced by injection of CG into peritoneal cavity of Institute for Cancer Research (ICR) mice. TNP-470 was injected subcutaneously with CG. Mice were sacrificed, and peritoneal tissues were dissected out at days eight and 16 after CG and TNP-470 injection. The expression patterns of CD31 (as a marker of endothelial cells), vascular endothelial cell growth factor (VEGF), alpha-smooth muscle actin (as a marker of myofibroblasts), heat shock protein 47 (HSP47), type III collagen, F4/80 (as a marker of mice macrophages), proliferating cell nuclear antigen (PCNA), and cyclin-dependent kinase 2 (Cdk2) were examined by immunohistochemistry. RESULTS: CG-injected mice showed thickening of the submesothelial zone and increased number of vessels, myofibroblasts, and infiltrating macrophages. The expression levels of VEGF, type III collagen, and HSP47 were increased, and a large number of PCNA-positive cells and Cdk2-expressing cells were observed in the thickened submesothelial area. Treatment with TNP-470 suppressed the submesothelial zone thickening and reduced collagen III expression as well as angiogenesis. TNP-470 also decreased the number of VEGF-expressing cells, myofibroblasts, macrophages, PCNA-positive cells, and Cdk2-expressing cells. CONCLUSION: Our results indicate the involvement of angiogenesis in the progression of peritoneal fibrosis, and suggest that TNP-470 may be potentially useful for the prevention of peritoneal fibrosis through inhibition of angiogenesis and suppression of myofibroblast proliferation.     

High expression of PKC-MAPK pathway mRNAs correlates with glomerular lesions in human diabetic nephropathy

BACKGROUND: Activation of protein kinase C (PKC) is a major signaling pathway for transforming growth factor (TGF)-beta to induce extracellular matrix (ECM) production in diabetic nephropathy (DN). PKC also activates mitogen-activated protein kinase (MAPK), which is called the PKC-MAPK pathway. The PKC-MAPK pathway is probably responsible for PKC-related abnormalities in diabetic glomeruli. To confirm the involvement of this pathway, we determined the localization and expression of mRNAs in glomeruli by in situ hybridization method. METHODS: In the present study, we examined expression of PKCbeta1, MAPK/ERK kinase (MEK) 1, MEK2, extracellular signal-regulated protein kinase (ERK) 1, ERK2, and TGF-beta1 mRNAs using renal tissue samples from kidneys affected by DN (N= 21) and from normal human kidney (NHK; N= 6). We also performed an immunohistochemical study using anti-phosphorylated MEK1/2 (P-MEK) and ERK1/2 (P-ERK) antibodies. The glomerular severity of DN was classified into three groups according to mesangial expansion: D1 (N= 4), D2 (N= 13), and D3 (N= 4). We analyzed differences and correlations between variables. RESULTS: In the glomeruli, the number of cells that stained for these mRNAs in DN was significantly higher than in NHK. The expression of PKC-MAPK pathway mRNAs tended to be inversely proportional to the degree of mesangial expansion. The P-MEK and P-ERK signal intensity were parallel to its mRNA expression pattern. Furthermore, there were significant correlations among the P-MEK, P-ERK signal intensity, PKCbeta1 mRNA expression. CONCLUSION: Our results suggest that high expression of PKC-MAPK pathway mRNAs plays an important role in the development and/or progression of early tissue damage in DN.     

A case of chronic renal insufficiency due to vascular injury of systemic sclerosis

A 48-year-old woman with systemic sclerosis (SSc) and rheumatoid arthritis was admitted to our hospital because of renal dysfunction. She had no hypertension at the time of admission and mild hypertension for only one and a half months until the time of admission. After admission, she received angiotensin-converting enzyme-inhibitor, but her renal dysfunction did not improve. She then had thrombotic microangiopathy with thrombocytopenia, and was treated with plasma exchange five times, but her renal dysfunction persisted. The renal biopsy specimens showed an arteriosclerotic lesion with intimal thickening and luminal narrowing and ischemic glomerular changes. These findings suggest that there is chronic vascular injury in a patient who has no hypertension with SSc and that once hypertension supervenes, whether severe or not, exacerbation of the vascular injury and renal dysfunction may occur.     

Intra-aortic balloon pumping is effective for hemodynamic management of catecholamine resistant ampulla (Takotsubo) cardiomyopathy

Ampulla (Takotsubo) cardiomyopathy resembles acute myocardial infarction, with absent coronary stenosis. We report a case of catecholamine resistant ampulla cardiomyopathy, successfully managed using intra-aortic balloon pumping (IABP). After laparotomy, the patient developed circulatory collapse. T wave inversion was observed on electrocardiogram. In spite of circulatory support using high dose cathecholamines, the hemodynamics of the patient showed no improvement. Upon starting IABP, the patient's hemodynamics were improved and the dose of catecholamines could be reduced. Because the ampulla cardiomyopathy is considered a subtype of 'stunned myocardium' and the hemodynamic disorder is temporary and reversible, IABP appears effective for hemodynamic management.     

Endovascular treatment of dural sinus malformation with arteriovenous shunt in a low birth weight neonate--case report

A boy was born at 36 weeks gestation weighing 2,135 g, with a prenatal diagnosis of dural sinus malformation with arteriovenous shunts. Congestive heart failure and anuria at birth prompted emergency intervention. Transfemoral-transvenous coil embolization was performed on day 1, resulting in partial occlusion of the huge venous pouch with a total length of 2,355 cm of detachable coils. Transarterial glue embolization on days 7, 23, and 42 was required due to persistent heart failure. Transarterial embolization was performed by common carotid puncture because the transfemoral route could not be used due to the small size and compromised blood flow of the femoral artery. Transarterial embolization reduced the arteriovenous shunts markedly and resulted in clinical improvement. Early treatment of a high flow dural arteriovenous fistula in a low birth weight neonate can achieve an excellent result with an acceptable neurological outcome.     

Detection of white spot syndrome virus in shrimp by loop-mediated isothermal amplification

Loop-mediated isothermal amplification (LAMP) method is a novel, sensitive and rapid technique which can be applied for disease diagnosis in aquaculture. Using the LAMP method, a highly specific and sensitive diagnostic system for white spot syndrome virus (WSSV) detection was designed. A set of four primers, two outer and two inner primers, were designed from WSSV genome DNA. Reaction time and temperatures were optimized for 60 min at 65 degrees C, respectively. The detection limit (DL) using the LAMP method was up to 1 fg, when compared to 10 fg by nested polymerase chain reaction (PCR). Thus, standardized LAMP procedure was used to detect the presence of WSSV in the heart, stomach and lymphoid organ from infected shrimp. The study has developed a diagnostic procedure which is a rapid and highly sensitive for WSSV detection in shrimp.     

Secondary nephrotic syndrome due to cardiovascular disease

Cardiovascular diseases ralely evoke nephrotic syndrome. Especially hypertensive renal disease (nephroscrelosis) and renovascular hypertension occasionally may lead to nephrotic syndrome. We reported a case of nephrotic syndrome with renovascular hypertension successfully treated with candesartan. In eldery patients cardiovascular diseases are appeared. It is very important for clinicians to detect the mechanism of nephrotic syndrome caused by cardiovascular diseases.