Integrin‐Mediated Expression of Bone Formation‐Related Genes in Osteoblast‐Like Cells in Response to Fluid Shear Stress: Roles of Extracellular Matrix,Shc, and Mitogen‐Activated Protein Kinase

Integrins play significant roles in mechanical responses of cells on extracellular matrix (ECM). We studied the roles of integrins and ECM proteins (fibronectin [FN], type I collagen [COL1], and laminin [LM]) in shear‐mediated signaling and the expression of bone formation‐related genes (early growth response‐1 [Egr‐1], c‐fos, cyclooxygenase‐2 [Cox‐2], and osteopontin [OPN]) in human osteosarcoma MG63 cells. MG63 cells on FN, COL1, and LM were kept as controls or subjected to shear stress (12 dynes/cm²), and the association of α_vβ₃ and β₁ integrins with Shc, phosphorylation of mitogen‐activated protein kinases (MAPKs, i.e., extracellular signal‐regulated kinase [ERK], c‐jun‐NH₂‐terminal kinase [JNK], and p38), and expressions of Egr‐1, c‐fos, Cox‐2, and OPN were determined. In MG63 cells, shear stress induces sustained associations of α_vβ₃ and β₁ with Shc when seeded on FN, but sustained associations of only β₁ with Shc when seeded on COL1/LM. Shear inductions of MAPKs and bone formation‐related genes were sustained (24 h) in cells on FN, but some of these responses were transient in cells on COL1/LM. The shear activations of ERK, JNK, and p38 were mediated by integrins and Shc, and these pathways differentially modulated the downstream bone formation‐related gene expression. Our findings showed that β₁ integrin plays predominant roles for shear‐induced signaling and gene expression in osteoblast‐like MG63 cells on FN, COL1, and LM and that α_vβ₃ also plays significant roles for such responses in cells on FN. The β₁/Shc association leads to the activation of ERK, which is critical for shear induction of bone formation‐related genes in osteoblast‐like cells.     

Diagnosis of vasculogenic impotence: combination of penile xenon-133 washout and papaverine tests

The present study evaluates both penile xenon-133 washout (XWT) and papaverine tests (PT) in the diagnosis of vasculogenic impotence. XWT was accomplished by subcutaneous injection of xenon-133 (1-2 mCi in 0.1 mL saline solution) into the dorsal coronal prepuce. Abnormal XWT was suggested in patients whose clearance time (T1/2) was longer than 7.5 minutes and whose penile blood flow rate (Q) was less than 6 mL/100 g tissue/min. PT was done by intracavernous injection of papaverine (60 mg in 20 mL normal saline). Abnormal PT was indicated in patients whose onset of full erection was more than ten minutes after papaverine injection and whose duration of erection was less than one hour. Ten young and 11 older normal volunteers were examined with XWT only; all showed normal results. A total of 60 impotent patients were examined with both XWT and PT and were classified into four groups: in 2 patients (3.3%) both XWT and PT were normal (group I); in 8 (13.3%) XWT was abnormal and PT normal (group II); in 14 (23.3%) XWT was normal and PT abnormal (group III); and in 36 (60%) both XWT and PT were abnormal (group IV). On further examination with bilateral hypogastric arteriography in 10 XWT-abnormal patients and on surgical correction of abnormal curvature in 5 XWT-abnormal patients, all (100%) were proved to have penile arterial insufficiency. Erection cavernosography performed in 15 PT-abnormal patients confirmed penile venous insufficiency in 80 percent. We conclude both XWT and PT are simple and effective for evaluation of the penile arterial blood flow and venous competence, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Correlation between iodine-131 MIBG imaging and biological markers in advanced neuroblastoma

I-131 metaiodobenzylguanidine (MIBG) imaging was performed in 38 patients with advanced neuroblastoma. Abnormal images were found in patients with elevations of urinary vanillylmandelic acid and dopamine and high serum neuron-specific enolase levels. Normal or minimal elevation of markers was seen in patients with negative images. In follow-up studies after chemotherapy, the disappearance of abnormal uptake was noted in those patients with normal marker values. A persistently abnormal uptake occurred in patients with high marker values. Conversion from a normal image to an abnormal image also occurred in patients whose markers became elevated. I-131 MIBG imaging is sensitive in detecting active foci of a neuroblastoma and is useful in monitoring chemotherapy in these patients.     

Catheter-related complications of continuous ambulatory peritoneal dialysis.

OBJECTIVE--To assess the effectiveness of continuous ambulatory peritoneal dialysis (CAPD) with particular reference to morbidity. DESIGN--Open study. SETTING--Two city general hospitals. SUBJECTS--104 Adults and 11 children with end stage renal failure. MAIN OUTCOME MEASURE--Morbidity. RESULTS--There were 29 complications (25%), the most common being obstruction of the tube (n = 8, 7%), and migration of the tube (n = 7, 6%). Others were peritonitis (n = 5), haemorrhage (n = 4), infection at the exit site (n = 3), and leakage of fluid (n = 2). All were readily treatable. CONCLUSIONS--Fixing the catheter in two places may prevent its migration. The complication rate of CAPD is acceptable, and in children with end stage renal failure it is a suitable alternative to haemodialysis while they are waiting for renal transplantation.