Effects of dexamethasone on the expression of myelin basic protein, proteolipid protein, and glial fibrillary acidic protein genes in developing rat brain.

Effects of dexamethasone (DEX) on the relative abundance of myelin basic protein (MBP), proteolipid protein (PLP) and glial fibrillary acidic protein (GFAP) mRNAs in the developing rat brain were examined. After DEX (1.0 mg/kg body weight) or saline was administered intraperitoneally to 3-day-old rats for 7 consecutive days, wet weight, DNA content and the relative abundance of the glia-specific mRNAs in cerebrum and cerebellum were analyzed at postnatal days (P) 10, 20 and 30. DEX decreased both wet weight and DNA content in cerebellum more profoundly than in cerebrum. The appearance of MBP, PLP and GFAP mRNAs in cerebellum preceded that in cerebrum in the control group. In cerebrum, the relative abundance of MBP and PLP mRNAs was significantly less in the DEX group than that in the control group at P20 and P30. The relative abundance of the GFAP mRNA was significantly less in the DEX group than in the control group at P10 and P20, but there was no significant difference at P30. In cerebellum, a significant decrease in the abundance of MBP, PLP and GFAP mRNAs in the DEX group was observed only at P10 but not at P20 and P30. Our findings indicate that DEX suppresses expression of genes related to glial functions, especially myelination when administered in the early postnatal period.     

Characterization of polypeptides in Rickettsia tsutsugamushi: effect of preparative conditions on migration of polypeptides in polyacrylamide gel electrophoresis.

The polypeptide compositions and antigenic components of Rickettsia tsutsugamushi were analyzed by modifying the solubilization conditions prior to polyacrylamide gel electrophoresis and by using monoclonal antibodies in immunoblotting experiments. Several polypeptides were converted to larger or smaller molecules by using various conditions for rickettsial sample preparation. Solubilization of a sample in 2-mercaptoethanol-containing buffer resulted in conversion of high-molecular-weight polypeptides to smaller polypeptides and conversion of some of the 43-kilodalton (43K) polypeptide to a 46K polypeptide. The heat modifiability of selected polypeptides was shown by heating samples at 100 degrees C. A major polypeptide on the rickettsial surface which showed strain-specific antigenicity appeared at the 43K position in samples solubilized at 37 degrees C but moved to the 56K position after samples were heated at 100 degrees C. Immunoblotting with an anti-56K polypeptide monoclonal antibody demonstrated that the reactive antigens existed predominantly as the higher-molecular-weight polypeptides. These polypeptides were converted to 43K polypeptides at 37 degrees C or the 56K polypeptides at 100 degrees C by cleavage of disulfide linkages with 2-mercaptoethanol treatment.     

Aneurysms of the anterior communicating artery and subclavian artery in association with congenital absence of unilateral internal carotid artery]

We encountered a rare case of unilateral internal carotid arterial defect complicated with anterior communicating aneurysm and subclavian artery aneurysm. The patient was a 56-year-old man in whom cerebral angiography and 3D-CTA revealed defects in the right internal carotid artery and the right carotid canal, and an unruptured aneurysm in the anterior communicating artery. In addition, the patient was also found to have an unruptured aneurysm in the right subclavian artery. As both the aneurysms were considered to have a high risk of rupture and such subclavian aneurysms were likely to cause an embolism, radical surgery was performed for each aneurysm. The postoperative course was uneventful, and the patient was discharged without ambulatory limitations. Although the defect in the internal carotid artery is a relatively rare vascular deformity, the incidence of cerebral aneurysm is about 30% in such cases due to the marked hemodynamic stress involved. On the other hand, there have been only two previous case reports of internal carotid arterial defect complicated with a subclavian aneurysm. Moreover, there have been no previous reports of internal carotid arterial defect complicated with both an intracranial aneurysm and a subclavian aneurysm, as observed in the present case. Thus, this case was very rare and is reported here.     

Evaluation of cardiac functions in patients with progressive systemic sclerosis (PSS)]

Cardiac functions in 20 female patients with PSS were measured by ultrasound cardiography and compared with those of 10 healthy age-matched controls. The following results were obtained: 1) The patients with PSS showed the increases in left ventricular mass (LVmass), interventricular septal thickness (IVS) and left ventricular posterior wall thickness (LVPW) more than those of controls. 2) Diastolic descent rate (DDR) of patients decreased significantly in comparison with the healthy controls. 3) Right ventricular dimension (RVD) of patients were demonstrated to dilate more than those of controls. Conclusively ultrasound cardiography (UCG) is an available method for detecting the cardiac lesion of PSS. Abnormal signs were recognized even though their clinical features were limited to the extremities.     

A double-blind dose-ranging study of risedronate in Japanese patients with osteoporosis (a study by the Risedronate Late Phase II Research Group)

To determine the clinical recommended dosage regimen of risedronate for the treatment of involutional osteoporosis in Japanese patients, dose-response relationships for the efficacy and safety of this drug were investigated using a multi-center, randomized, double-blind, parallel group comparative design with four dose levels of risedronate (placebo, 1 mg, 2.5 mg and 5 mg per day). A total of 211 patients diagnosed with involutional osteoporosis according to the criteria proposed by the Japanese Society for Bone and Mineral Research were randomized and received one of the four doses once daily for 36 weeks. All patients were supplemented with 200 mg of calcium daily in the form of calcium lactate. The primary efficacy endpoint was the percent change in bone mineral density of the lumbar spine (L2-L4 BMD) determined by dual-energy X-ray absorptiometry (DXA) from baseline to the time of final evaluation. Changes in biochemical markers of bone turnover and safety profile were also compared. Percent changes in L2-L4 BMD at final evaluation in the placebo, and 1-, 2.5-, and 5-mg risedronate groups were 0.79+/-5.30, 2.71+/-4.93, 5.29+/-3.96, and 5.15+/-4.25% (mean+/-SD), respectively. A linear dose-response relationship was obtained up to a dose of 2.5 mg, whereas no further increase in BMD was observed at 5 mg. The decrease in bone turnover markers, including N-terminal osteocalcin, phosphorus, and urinary deoxypyridinoline, also showed a linear dose-response relationship up to a dose of 2.5 mg. Alkaline phosphatase level decreased linearly up to a dose of 5 mg. Risedronate was well tolerated in this 36-week study with 1- to 5-mg doses. Neither the overall incidence of adverse events nor the percentage of patients without problem in overall safety assessment differed significantly among the dose groups including the placebo group. Based on these results, a once-daily dose of 2.5 mg of risedronate, which is half that used in Caucasians, is recommended for the treatment of involutional osteoporosis in Japanese patients.     

Development and Initial Testing of a Permanently Implantable Centrifugal Pump

Abstract: To be able to salvage heart failure patients, the need for an economical permanent ventricular assist device is increasing. To meet this increasing demand, a miniaturized centrifugal blood pump has been developed as a permanently implantable device. The Gyro permanently implantable model (PI-601) incorporates a sealless design with a blood stagnation free structure. The pump impeller is magnetically coupled to the driver magnet in a sealless manner. This pump is atraumatic and antithrombogenic and incorporates a double pivot bearing system. A miniaturized actuator was utilized in this system in collaboration with the University of Vienna. The priming volume of this pump is 20 ml. The overall size of the pump actuator package is 53 mm in height and 65 mm in diameter, 145 ml of displacement volume, and 305 g in weight. Testing to date has included in vitro hydraulic performance and hemolysis. This pump can provide 5 L/min against a 110 mm Hg total pressure head at 2,000 rpm and 8 Limin against 150 mm Hg at 2,500 rpm. The normalized index of hemo-lysis (NIH) value of this pump was 0.0028 g/100 L at 5 Limin against 100 mm Hg. A preliminary anatomical study revealed the possibility of the implantability of 2 such systems in biventricular bypass at a preperitoneal location. This system is feasible for use as a permanently implantable biventricular assist device.     

Clinical studies on the measurement of urinary tissue polypeptide antigen (TPA) levels using Prolifigen TPA kit "Daiichi"-II in urothelial cancers

We have investigated the clinical significance of urinary tissue polypeptide antigen (TPA) as a tumor marker for urothelial cancers. Urinary TPA levels were determined by the immunoradiometric assay of Prolifigen TPA Kit "Daiichi"-II in 486 healthy controls and 1835 patients with various diseases including 526 with urothelial cancers and 140 with prostatic cancer. The mean value of urinary TPA was 199 +/- 213 (1SD)U/1 in 486 healthy controls. 95% of them having a level below 600 U/l. Therefore, 600 U/l was applied as a cut-off level. Positive rates of urothelial cancers and reactivated prostatic cancer were 57.6% (148 of 248 cases) and 45.5% (5 of 11 cases) respectively. On the other hand, the false positive rate of most urological benign diseases was only about 20% except for the acute stage of urinary tract infections and upper urinary tract stones with hydronephrosis. There was no significant difference in the positive rate between urinary TPA level and urinary cytology in urothelial cancers. The combination of both tests raised the positive rate to 73.1%. Therefore, urinary TPA may be useful in the monitoring of urothelial cancers, and the combination of urinary TPA and urinary cytology may increase the diagnostic accuracy.