Brain nitric oxide synthase messenger RNA in central mineralocorticoid hypertension

The mechanism underlying the central hypertensinogenic effects of mineralocorticoids remains unclear. Given that nitric oxide (NO) is thought to act at autonomic sites in the brain to regulate arterial blood pressure, the effects of the potent mineralocorticoids aldosterone and 19-noraldosterone on the abundance of neuronal NO synthase (nNOS) mRNA in the brain were investigated. Wistar-Kyoto rats received a continuous intracerebroventricular infusion of aldosterone or 19-noraldosterone (5 ng/h) from an implanted osmotic minipump for 4 weeks. Total RNA was purified from microdissected tissue blocks containing the hypothalamus, dorsal medulla, rostral ventrolateral medulla, or caudal ventrolateral medulla, and changes in the abundance of nNOS mRNA were determined with a semiquantitative competitive polymerase chain reaction method. Blood pressure was significantly increased in rats 2, 3, and 4 weeks after the onset of intracerebroventricular aldosterone or 19-noraldosterone infusion compared with that in animals receiving vehicle. Subcutaneous infusion of either mineralocorticoid had no effect on blood pressure. Compared with controls, rats treated with aldosterone or 19-noraldosterone for 4 weeks showed significant decreases in the amount of nNOS mRNA in the hypothalamus and rostral and caudal ventrolateral medulla. These data suggest that reduced nNOS activity may contribute to the increase in blood pressure in rats with central mineralocorticoid-induced hypertension.     

A 0.8-dB insertion-loss, 17.4-dBm power-handling, 5-GHz transmit/receive switch with DETs in a 0.18-/spl mu/m CMOS process

An optimized single-pole double-throw (SPDT) transmit/receive (T/R) switch has been fabricated using depletion-layer-extended transistors (DETs) in a 0.18 /spl mu/m CMOS process. The switch features the highest performance to date of any switch using a CMOS process, of a 0.8 dB insertion-loss, 23 dB isolation and 17.4 dBm power-handling capability at 5 GHz. The low insertion-loss has been achieved with the effects of junction capacitance decrease and substrate resistance increase in the DET, the adoption of low-loss shielded-pads, and several layout optimizations. The high power-handling capability is owing to the combined effect of the adoption of the source/drain dc biasing scheme and the high substrate resistance in the DET.     

Proton-cotransport of pravastatin across intestinal brush-border membrane

PURPOSE: The purpose of the present study is to clarify the intestinal brush-border transport mechanism of a weak organic acid, pravastatin, an HMG-CoA reductase inhibitor. METHODS: The transport of pravastatin was studied by using intestinal brush-border membrane vesicles prepared from rabbit jejunum, and uptake by the membrane vesicles was measured using rapid filtration technique. RESULTS: The initial uptake of [14C]pravastatin was markedly increased with decreases in extravesicular pH and showed a clear overshoot phenomenon in the presence of a proton gradient (pHin/out = 7.5/5.5). A protonophore, carbonylcyanide p-trifluoromethoxyphenylhydrazone, significantly reduced the uptake of [14C]pravastatin. In addition, an ionophore for sodium, potassium and proton, nigericin, stimulated the uptake of [14C]pravastatin in the presence of a potassium gradient ([K+]in/[K+]out = 0/145 mM). On the other hand, neither the imposition of an inwardly directed sodium gradient nor an outwardly directed bicarbonate gradient stimulated the uptake of [14C]pravastatin. In the presence of a proton gradient (pHin/out = 7.5/5.5), the initial uptake of pravastatin was saturable with the apparent Kt of 15.2 +/- 3.2 mM and Jmax of 10.6 +/- 1.21 nmol/mg protein/10 sec. The uptake of pravastatin was significantly inhibited by monocarboxylic acid compounds such as acetic acid and nicotinic acid in a competitive manner but not by di- or tricarboxylic acids, or acidic amino acid. CONCLUSION: It was concluded that a pH-dependent transport of pravastatin across the brush-border membrane occurs by a proton-gradient dependent carrier-mediated mechanism rather than by simple diffusion of its unionized form.     

Two distinct populations of primary cytotoxic cells infiltrating into allografted tumor rejection sites: infiltration of macrophages cytotoxic against allografted tumor precedes that of multiple sets of cytotoxic T lymphocytes with distinct specificity to alloantigens

The majority of cases with familial Alzheimer's disease (FAD) are linked to mutations of the presenilin (PS) genes. These genes show considerable sequence similarity to the sel-12 gene of Caenorhabditis elegans, which has been postulated to function in the facilitated signalling by lin-12 and glp-1. In order to analyse the functional conservation of the presenilins, we introduced the human PS-1 cDNA, as well as clinical and deletion mutant proteins, into sel-12 mutant animals and tested their potential to rescue the egg-laying defect. Human PS-1 expressed from the sel-12 promoter fully rescued the sel-12 phenotype, whereas two missense mutations, C410Y and A246E, identified in pedigrees with FAD, exhibited a strongly decreased rescuing activity. The large hydrophilic loop and transmembrane domain 7 are required for the biological activity of PS-1. PS-1 protein was proteolytically cleaved in C. elegans as it is in human cells. A PS-1 splice variant (FAD mutation deltaexon9) that does not undergo proteolytic cleavage also substituted for sel-12. The conservation of function of human PS-1 and C. elegans sel-12 suggests that presenilin proteins are required, directly or indirectly, for the proper operation of the Notch signalling pathway. FAD-associated mutant proteins tested showed different rescuing activities, indicating that they might affect different functional or regulatory aspects of PS-1. Proteolytic processing is not a prerequisite for PS-1 function in C. elegans.     

Identification of Fuzzy Relations with Multiple Hyperplanes by Genetic Algorithm in Structural Design

Abstract: This paper proposes a method for formulation and quantification of human subjective evaluations and uncertain numerical values by using multiple hyperplanes based on the results of questionnaires distributed to structural designers that are composed of four questions about structural design and planning, i.e., ( Q 1) structural damage , ( Q 2) structural economy in a macroscopic sense , ( Q 3) structural safety, and ( Q 4) opening patterns in facade. In this paper, some hyperplanes in multidimensional spaces are used as a method to identify fuzzy relations (states) in intelligent fuzzy networks for seismic structural planning. A genetic algorithm is employed as a search method for optimal formulations and is proved to be very effective as a method for such an identification.     

Regulation of distinct steps of angiogenesis by different angiogenic molecules

This study was designed to determine the relative activity of basic fibroblast growth factor (bFGF), vascular endothelial growth factor/vascular permeability factor (VEGF/VPF), platelet-derived growth factor (PDGF), platelet-derived endothelial cell growth factor (PD-ECGF), hepatocyte growth factor (HGF), and interleukin-8 (IL-8) in regulating endothelial cell division, migration, degradation of the extracellular matrix (ECM), morphogenesis, and survival. Human umbilical vein endothelial cells (HUVEC) were treated with different concentrations of the six cytokines. bFGF was the most potent mitogen followed by VEGF/VPF and PD-ECGF. VEGF/VPF and bFGF also enhanced the survival of the endothelial cells in serum-free medium. Interstitial collagenase (MMP-1) and urokinase plasminogen activator (uPA) were significantly upregulated only by bFGF. HGF, bFGF, and VEGF/VPF induced chemotactic migration of the endothelial cells, but only HGF (scatter factor) enhanced nondirectional motility. The organization of endothelial cells to form tubes on Matrigel was induced by bFGF and, to a lesser extent, by VEGF/VPF and IL-8. Permeability across endothelial cell monolayers was induced only by VEGF/VPF. These data demonstrate that different angiogenic molecules differentially regulate distinct steps in the process of angiogenesis, suggesting that any given molecule may be necessary but in itself insufficient for establishment of a viable vasculature.     

High-precision voltage-measuring method using fast sampled data for electric power systems

Control and protection equipment in power systems requires higher sensitivity and operational reliability to meet today's changing power system requirements. The voltage-measuring deviation requirement for advanced voltage and var control equipment is less than 0.1 percent under conditions of harmonic distortion in the voltage waveform and power-system frequency variation. Studies on digital signal processing suitable for electric power systems showed that these requirements are satisfied using fast sampling and very fast 32-bit floating point operations by a Digital Signal Processor (DSP). This paper describes the design philosophy of a high-precision power system voltage-measuring method using fast sampled data. In addition, total voltage-measuring deviation characteristics under a combination of the techniques are described along with digital filter characteristics, frequency-measuring deviation characteristics, frequency variation versus gain-compensation characteristics of a digital filter, and peak value operating principles.     

Pryce type I interlobar pulmonary sequestration with anomalous return to the left inferior pulmonary vein

A 50-year-old woman was examined because of chest discomfort. Chest X-ray films disclosed a tumorous shadow behind the heart. Chest computed tomography (CT) scans revealed a mass connected to the descending aorta, with increased blood flow in the left basal segment. The patient was admitted for further examination. Chest CT scans and cardioscintigrams were very useful as diagnostic tools, but the final diagnosis was made on the basis of angiography. An anomalous tortuous artery ran from the descending aorta into the left basal segment and returned to the left inferior pulmonary vein. The left pulmonary arterial trunk had no basal branch (A8-A10). A loop corresponding to the superior vein (V6) ran beneath the anomalous tortuous artery. To our knowledge, this is the second case of Pryce type-I interlobar pulmonary sequestration with anomalous return to the left inferior pulmonary vein to be reported in Japan. A left inferior lobectomy was performed. Histological finding from the excised tissues showed prominent interstitial fibrosis, atypical adenomatous hyperplasia, and atherosclerosis. Following surgery, the patient's PaO2 increased from 80.4 Torr to 95.8 Torr, suggesting that left inferior lobectomy was an appropriate treatment.     

Lack of point mutation of the APP gene in sporadic Alzheimer's disease in Japanese

We investigated point mutations of the APP gene in 66 patients with sporadic Alzheimer's disease (AD) and 180 normal individuals by use of the PCR (polymerase chain reaction) method. Both the AD patients and the normal individuals were Japanese. We extracted DNA from blood samples using the phenol-chloroform method and amplified exons 16 and 17 of the APP gene by PCR. PCR products were digested by MBO-II (exon 16) and BCL-1(exon 17). Electrophoresis was carried out with 3% agarose gel and the separated fragments were stained with ethidium bromide. In addition we investigated other point mutations of exons 16 and 17 by use of the PCR-SSCP (single stranded conformation polymorphisms) method, and found no fragments that exhibited point mutations in the AD patients and normal individuals. These findings indicate that the presence of point mutation of the APP gene is not a major cause of AD in the Japanese population.