Characteristics of young-onset hypertension identified by targeted screening performed at a university health check-up.

Since the prevalence and clinical characteristics of young-onset hypertension are still to be elucidated, we performed targeted-screening at an annual university health check-up for two consecutive years. Out of 16,464 subjects in 2003 and 17,032 in 2004 that were aged less than 30 years, 22 and 26 students (all males) exhibited high blood pressure (BP), respectively, on three occasions during casual BP measurements at the Tohoku University Health Center (systolic and diastolic BP of 140 and/or 90 mmHg or greater, respectively). These students were asked to measure their BP at home, and 9 subjects in total were diagnosed as having essential hypertension (EH). The remaining students were diagnosed as having white coat hypertension (WCH). In 8 out of 9 EH students, their father and/or mother had also been treated with antihypertensive medication. Adjustment by attendance ratio for each BP measurement suggested that the incidence of EH was around 0.1% and that of hypertension (EH and WCH) was around 0.5% in university students aged less than 25 years, since most of the subjects and hypertensive students were between 18 and 24 years old. Body mass index of the EH, which was more than 25 kg/m2 (overweight), was significantly higher than that with WCH. In conclusion, the combination of repeated casual BP measurements and home BP effectively identified young-onset EH. The clinical parameters indicated that male gender, genetic background, and excessive weight were risk factors for young-onset hypertension.     

Reduction by Fentanyl of the Cp sub 50 Values of Propofol and Hemodynamic Responses to Various Noxious Stimuli

Background: Propofol and fentanyl infusion rates should be varied according to the patient's responsiveness to stimulation to maintain satisfactory anesthetic and operative conditions. However, somatic and autonomic responses to various noxious stimuli have not been investigated systematically for intravenous propofol and fentanyl anesthesia.

Methods: Propofol and fentanyl were administered via computer-assisted continuous infusion to provide stable concentrations and to allow equilibration between plasma-blood and effect-site concentrations. The propofol concentrations needed to suppress eye opening to verbal command and motor responses after 50-Hz electric tetanic stimulation, laryngoscopy, tracheal intubation, and skin incision in 50% or 95% of patients (Cp50 and Cp95) were determined at fentanyl concentrations of 0.0, 1.0, 2.0, 3.0, and 4.0 ng/ml in 133 patients undergoing lower abdominal surgery. The ability of propofol with fentanyl to suppress hemodynamic reactions in response to various noxious stimuli also was evaluated by measuring arterial blood pressure and heart rate before and after stimulation.

Results: The various Cp50 values for propofol alone (no fentanyl) for the various stimuli increased in the following order: Cp sub 50loss of consciousness, 4.4 micro gram/ml (range, 3.8-5.0); Cp50tetanus, 9.3 micro gram/ml (range, 8.3-10.4); Cp50laryngoscopy, 9.8 micro gram/ml (range, 8.9-10.8); Cp50skin incision, 10.0 micro gram/ml (range, 8.1-12.2); and Cp50intubation, 17.4 micro gram/ml (range, 15.1-20.1; 95% confidence interval). The reduction of Cp50loss of consciousness, with fentanyl was minimal; 11% at 1 ng/ml of fentanyl and 17% at 3 ng/ml of fentanyl. A plasma fentanyl concentration of 1 ng/ml (3 ng/ml) resulted in a 31-34% (50-55%) reduction of the propofol Cp50 s for tetanus, laryngoscopy, intubation, and skin incision. Propofol alone depresses prestimulation blood pressure but had no influence on the magnitude blood pressure or heart rate increase to stimulation. Propofol used with fentanyl attenuated the systolic blood pressure increases to various noxious stimuli in a dose-dependent fashion.     

Changes in thrombomodulin level in plasma of endotoxin-infused rabbits.

Changes in the plasma thrombomodulin (TM) level were examined in endotoxin-infused rabbits. The plasma TM level in normal rabbits was 143.8 +/- 8.4 ng/ml (n = 67) and the molecular weight of the major TM was about 55 kd. Endotoxin (lipopolysaccharide, LPS, E. Coli B8:0127) was intravenously infused. LPS infusion increased the plasma TM level dose-dependently between 0.2 mg/kg and 5 mg/kg. When 5 mg/kg LPS was infused, the plasma TM level started to increase immediately and was 2.3 times higher than the control value within 1 hr. The molecular weight of the major TM was about 75 kd. This rapid increase in TM occurred before the decrease in fibrinogen content and the prolongation of prothrombin time. To examine the effect of circulating leukocytes on the TM increase in endotoxin-infused rabbits, 5 mg/kg LPS was infused into rabbits with leukocytopenia induced by X-ray irradiation. The maximum plasma level of TM was significantly lower than in the untreated rabbits given LPS. These data suggest that the increase in plasma TM is caused by LPS-stimulated leukocyte's prior to hemostaseological changes. It is well known that endothelial cells can be injured by stimulated leukocytes, so this increase in plasma TM probably reflects the deterioration of endothelial cells. This deterioration decreases the ability of endothelial cells to inhibit thrombosis, which would, in turn, contribute to the development of disseminated intravascular coagulation in endotoxin-infused rabbits.     

Specificity of sulfated polysaccharides to accelerate the inhibition of activated protein C by protein C inhibitor

The ability of various sulfated polysaccharides to activate protein C inhibitor (PCI) and the effect of molecular weight (Mr) and sulfur content of dextran sulfates were investigated. Besides dextran sulfate, highly sulfated polysaccharides such as chondroitin polysulfates 1 and 5, and pentosan polysulfate were more active than heparin in enhancing the activated protein C inhibition by PCI. The molecular weight and the sulfur content of dextran sulfate were critical for the second-order rate constant of the reaction and for the optimal concentration of the polysaccharide, respectively. These results suggest that the carboxyl groups of polysaccharides are not necessarily required, but some sulfate groups within polymers may play a critical role in the interaction with PCI.     

A nephropathy induced by immunization of rats with EHS tumour.

Immunization of rats with Engelbreth-Holm-Swarm tumour induced a nephropathy immunohistopathologically similar to Heymann nephritis except that IgG was deposited along the tubular basement membranes. Autoantibodies against both brush border and basement membranes of proximal tubules were found in the sera. Immunoperoxidase staining of the tumour cells and absorption studies suggested that the tumour cells produced the FX1A-related antigens. Immunodiffusion analysis suggested that the antigens which induced this nephropathy differed from gp 330 and gp 600 which have been reported to be responsible for Heymann nephritis.     

Overexpression of the Del1 gene causes dendritic branching in the mouse mesentery

In the present study, we established transgenic mice overexpressing Del1, a ligand of integrins, to examine the effect of overexpression of Del1 on vascular morphogenesis. In the wild-type mouse, mesenteric vessels are shaped like rakes consisting of a long stalk and short branches at the periphery. In contrast, those in transgenic mice showed typical dendritic architecture consisting of a few large primary branches with smaller spreading branches. The phenotype of mice overexpressing Del1 suggests the existence of a tissue-specific mechanism for branching morphogenesis in the mesentery.     

BOVINE SERUM ALBUMIN (BSA) NEPHRITIS IN RATS IV. A SEQUENTIAL EVALUATION OF MONONUCLEAR PHAGOCYTE SYSTEM (MPS) FUNCTION

A clearance kinetic study of intravenously administered ¹²⁵I-labeled aggregated human IgG (¹²⁵I-AHIgG) from the circulation and its distribution in various organs was performed weekly during the course in a model of experimental immune complex glomerulonephritis which was induced in rats immunized 8 weeks previously with 6 times a week administration of 2 mg of bovine serum albumin (BSA) for 4 weeks from week 8 to 12. The removal rates of the injected ¹²⁵I-AHIgG from the circulation were retarded in nonproteinuric rats of week 9 and 10, at almost every checked point (p-value was <0.01). The clearance in those rats with severe proteinuria returned to the level of the control and of rats in week 8. The distribution of ¹²⁵I-AHIgG in the liver 4 hours after the administration revealed a considerable decrease in non-overt proteinuric rats of weeks 9, 10, and 11. A similar tendency of decreasing depositions of the radioactivity was shown in the spleen at each 4 hours. In contrast, the uptakes in the kidney and lung at the final week of 12 were larger. Delayed clearance from the circulation and a decreasing handle of the injected macromolecule in the liver and possibly in the spleen may suggest the presence of some impairment of the MPS function in the course of this experimental glomerulonephritis.