Fidgetin-like 1 gene inhibited by basic fibroblast growth factor regulates the proliferation and differentiation of osteoblasts.

The FIGNL1 gene was proven to be a new subfamily member of ATPases associated with diverse cellular activities (AAA proteins). In this in vitro study, the AAA proteins inhibited osteoblast proliferation and stimulated osteoblast differentiation. We showed that FIGNL1 may play some regulatory role in osteoblastogenesis. INTRODUCTION: The fidgetin-like 1 (FIGNL1) gene encodes a new subfamily member of ATPases associated with diverse cellular activities (AAA proteins). Although the FIGNL1 protein localizes to both the nucleus and cytoplasm, the function of FIGNL1 remains unknown. In a previous study, we identified several genes that mediate the anabolic effects of basic fibroblast growth factor (bFGF) on bone by using microarray data. FIGNL1 was one of the genes that downregulated >2-fold in MC3T3-E1 cells after treatment with bFGF. Therefore, this study was aimed to identify and confirm the function of FIGNL1 on osteoblastogenesis. MATERIALS AND METHODS: We examined the effect of the FIGNL1 gene on proliferation, differentiation, and apoptosis in mouse osteoblast cells (MC3T3-E1 and mouse primary calvarial cells) using flow cytometry, RT-PCR, cell proliferation assay, and cell death assay. MC3T3-E1 cells and mouse calvarial cells were transfected with small interfering RNA (siRNA) directed against the FIGNL1 or nontargeting control siRNA and examined by cell proliferation and cell death assays. Also, FIGNL1 was fused to enhance green fluorescent protein (EGFP), and the EGFP-fused protein was transiently expressed in MC3T3-E1 cells. RESULTS: Reduced expression of FIGNL1 by bFGF and TGF-beta1 treatment was verified by RT-PCR analysis. Overexpression of FIGNL1 reduced the proliferation of MC3T3-E1 and calvarial cells, more than the mock transfected control cells did. In contrast, siFIGNL1 transfection significantly increased the proliferation of osteoblasts, whereas overexpression of FIGNL1 did not seem to alter apoptosis in osteoblasts. Meanwhile, overexpression of FIGNL1 enhanced the mRNA expression of alkaline phosphatase (ALP) and osteocalcin (OCN) in osteoblasts. In contrast, siFIGNL1 decreased the expression of ALP and OCN. A pEGFP-FIGNL1 transfected into MCT3-E1 cells had an initially ubiquitous distribution and rapidly translocated to the nucleus 1 h after bFGF treatment. CONCLUSIONS: From these results, we proposed that FIGNL1, a subfamily member of the AAA family of proteins, might play some regulatory role in osteoblast proliferation and differentiation. Further analyses of FIGNL1 will be needed to better delineate the mechanisms contributing to the inhibition of proliferation and stimulation of osteoblast differentiation.     

Hydrolysis of phenyl esters in cyclodextrin-polymer systems

The catalytic hydrolysis of phenyl esters in systems containing ß-cyclodextrin (ß-CD) and polyelectrolytes was investigated. Poly(methacrylic acid) was found to exhibit an inhibition effect on the hydrolysis, while poly(sodium styrenesulfonate) (NaPSS) shows a pronounced acceleration effect on the hydrolysis: the larger the molecular weight and the lower the degree of substitution, the greater is the acceleration effect. On the other hand, sodium ethylbenzenesulfonate and sodium dodecylbenzenesulfonate inhibit the reaction. The acceleration of the reaction in presence of NaPSS is attributed to the concentration of ß-CD and the substrate esters near to the chain of the macromolecule, through inclusion effects and hydrophobic interactions.     

Effects of ONO-3708, an antagonist of the thromboxane A2/prostaglandin endoperoxide receptor, on platelet aggregation and thrombosis

The beneficial effects of an antagonist of the thromboxane A2/prostaglandin endoperoxide receptor, 7-[2 alpha,4 alpha-(dimethylmethano)-6 beta-(2-cyclopentyl-2 beta- hydroxyacetamido)-1 alpha-cyclohexyl]-5(Z)-heptenoic acid (ONO-3708) on thrombosis were examined. ONO-3708 at 0.1-3 microM inhibited the human platelet aggregation induced by thromboxane A2, prostaglandin H2, collagen, ADP (secondary phase) and epinephrine (secondary phase) without affecting prostanoid synthesis and the content of cyclic AMP in platelets. The in vivo effects, on coronary thrombosis in this case, were examined in two canine models. ONO-3708, 3 to 300 micrograms/kg i.v., prevented dose dependently the coronary thrombosis induced by partial obstruction of the coronary artery. ONO-3708, 3 micrograms/kg per min i.v., significantly prevented electrically stimulated coronary thrombosis without affecting systemic blood pressure and heart rate. These results indicate that the thromboxane A2/prostaglandin endoperoxide receptor could play an important role in the pathogenesis of thrombosis and that ONO-3708 may have therapeutic advantages in preventing thrombosis.     

Normothermic cardiopulmonary bypass: effect on the incidence of persistent postoperative neurological dysfunction following coronary artery bypass graft surgery

We retrospectively reviewed the records of 250 consecutive patients undergoing coronary artery bypass graft surgery (CABG) from January 1994 through January 1996 to determine the incidence of persistent postoperative neurological dysfunction after CABG and to compare normothermic and moderate hypothermic cardiopulmonary bypass (CPB). Normothermic CPB was used in 128 patients (36°–37°C) and hypothermic CPB (27°–28°C) in 122 patients. Postoperative neurological dysfunction included focal motor deficits, delayed recovery of consciousness (>24h) after surgery, and seizures within 1 week postoperatively. Persistent neurological dysfunction was diagnosed if complete resolution had not occurred within 10 days of surgery. The incidence of persistent postoperative neurological dysfunction was 4.1% in the hypothermic CPB group and 2.3% in the normothermic CPB group. There were no statistically significant differences between the two groups (P=NS). These results suggest that normothermic CPB did not increase the incidence of persistent postoperative neurological dysfunction compared to hypothermic CPB.     

Partial hepatic resection under intermittent hepatic inflow occlusion in patients with chronic liver disease.

A partial hepatic resection was performed in 13 patients with chronic liver disease using intermittent hepatic inflow occlusion. Eleven patients had liver cirrhosis and two had chronic hepatitis. Seven patients were classified as Child's grade A and six as Child's grade B before operation. Dissection of the hepatic parenchyma was performed during intermittent inflow occlusion. The time of clamping and declamping was 10-20 min and 5-8 min, respectively. Postoperative data on liver function showed recovery to preoperative levels by about 10 days after operation. There were no life-threatening complications. These results indicate that intermittent hepatic inflow occlusion can be achieved easily and safely to allow non-anatomical resection in patients with chronic liver disease.     

Takayasu's arteritis and mitral stenosis

A 44-year-old housewife was found to have coarctation of the abdominal aorta secondary to Takayasu's arteritis. Since she also had mitral stenosis, possible etiological relation between Takayasu's arteritis and mitral stenosis is suspected.     

Tumor-specific binding of radiolabeled G-22 monoclonal antibody in glioma patients.

Iodine-131-labeled G-22 monoclonal antibody F(ab')2 fragment reaching specifically with a glioma-associated surface glycoprotein was administered to 12 glioma patients to investigate its use in radioimaging of intracranial gliomas. No immediate or delayed side effects were attributable to antibody injection. Nine patients received the radiolabeled complex intravenously. The images of low-grade gliomas were generally poor and disappeared within 4 days. High-contrast images were obtained beyond the 7th day in high-grade gliomas except one case in the pineal region. Three patients received intraventricular or intratumoral administration. Clear images of all tumors were demonstrated from the 2nd until later than the 7th day. One patient with cerebrospinal fluid (CSF) dissemination of brainstem glioma demonstrated negative CSF cytology after intraventricular administration.     

Haemorrhagic fever with renal syndrome: Clinical aspects

Based on clinical and pathological features a typical case of haemorrhagic fever with renal syndrome passes through five phases: (1) febrile phase, (2) hypotensive phase, (3) oliguric phase, (4) diuretic phase and (5) convalescent phase. The major manifestations are fever, pain in the back and abdomen, flushed face, prostration, proteinuria, purpura and haemorrhage and acute renal failure. Selective right auricular haemorrhage, marked congestion and haemorrhage in the renal medulla and necrosis of the anterior lobe of the pituitary gland are the three prominent pathological findings. The clinical severity depends upon the causative agents, namely Hantaan virus, Seoul virus and the European form in that order. Specific serological diagnosis of haemorrhagic fever with renal syndrome is made by demonstrating a rise in titre of specific immunofluorescent antibody against Hantaan and related viruses. The management is supportive, based on an understanding of the pathophysiology of the disease.