Fos-like immunoreactivity in the medulla after acute and chronic angiotensin II infusion

Acute and chronic angiotensin (Ang) II hypertension are reported to have different mechanisms that involve differential contributions of the peripheral vasculature and the nervous system. Acute Ang II hypertension is mediated primarily by Ang acting at vascular smooth muscle, whereas chronic Ang II hypertension appears to have a neural component. In our experiments, the transition from a peripheral to a neural effect occurs over 10 hr of Ang II infusion in rats. To identify the role of the central nervous system in this transition, we measured Fos immunoreactivity, an indicator of neural activity, in the nucleus of the solitary tract (NTS), caudal ventrolateral medulla (CVL) and rostral ventrolateral medulla (RVL) in normal, sinoaortic denervated (SAD) and sham SAD rats after 2- or 18-hr Ang II infusion (50 ng/kg/min intravenously). Vehicle (5% dextrose) was infused in normal rats as control. Comparable increases in arterial pressure were produced by 2- and 18-hr Ang II infusion in all groups. Fos was increased in the NTS in sham SAD rats by 2- and 18-hr Ang II infusion (P < .05 vs. vehicle control). In the CVL, only 2-hr Ang II infusion was associated with increased Fos in normal and sham SAD rats (P < .05 vs. vehicle control) but not in SAD rats. In the RVL, 18-hr Ang II infusion elevated Fos in all groups (P < .05 vs. vehicle control). Activation of NTS during Ang II infusion is baroreceptor mediated and independent of infusion duration. Acute Ang II infusion produced a baroreceptor-mediated activation of the CVL, a region associated with baroreflex sympathoinhibition. Chronic Ang II infusion produced a baroreceptor-independent activation of the RVL, a brain area associated with sympathoexcitation, suggesting a centrally mediated increase in sympathetic outflow that may be associated with chronically infused Ang II.     

Characteristic T helper 2 T cell cytokine abnormalities in autoimmune lymphoproliferative syndrome, a syndrome marked by defective apoptosis and humoral autoimmunity

Autoimmune lymphoproliferative syndrome (ALPS) is marked by massive lymphadenopathy, hepatosplenomegaly, autoimmunity and the presence of increased numbers of circulating and tissue TCR-alpha beta, CD4- CD8- T cells. The underlying defect is that of decreased T cell and B cell apoptosis, due in most, but not all, cases to heterozygous mutations of the Fas gene and corresponding defective Fas signaling function. Here we measure in vivo and in vitro cytokine secretion in ALPS to shed light on the relation of apoptosis defects to the development of autoimmunity. In in vivo studies, ALPS patients manifested greatly increased circulating levels of IL-10 (> 100-fold), compared with both healthy individuals and various disease controls; in contrast, their levels of IL-1 beta, IL-4, and IFN-gamma were normal and their levels of IL-2 and TNF-alpha were marginally increased. In parallel in vitro studies, ALPS patients CD4+ DR+ T cells stimulated either with anti-CD3/CD28 or anti-CD2/CD28 produced increased amounts of IL-4 and IL-5 (10 to 20-fold) and decreased amounts of IFN-gamma (4-fold) as compared with those of control CD4+ DR+ T cells. In contrast, ALPS patients' CD4-/CD8- T cells produced very low amounts of cytokines. Finally, ALPS patients' peripheral monocytes/macrophages produced decreased amounts of IL-12 (30-fold) and increased amounts of IL-10 (5-fold). In conclusion, ALPS is marked by the presence of DR+ T cells that exhibit a skewed Th2 cytokine response upon various forms of stimulation. This cytokine response, in the presence of increased circulating IL-10 levels, is likely to define the cytokine milieu that accounts for the humoral autoimmune features of ALPS and, perhaps, of other humoral autoimmune states.     

芯片业2004年增长强劲存储器市场风光再现

iSuppli公司公布的全球半导体厂商市场份额排名结果显示，尽管半导体产业在2004年第4季度营收增长明显趋缓，但对于大多数芯片厂商来说，2004年仍是一个业绩卓著之年。     

Comparative assessment of Australian fly ash and conventional concrete bricks

A comparative study of the chemical composition, mineralogy, morphology and crushing strengths of fly ash bricks, conventional concrete bricks and fly ash samples has been undertaken. The main chemicals present in the products were silica and alumina while their main minerals were quartz, mullite, illite, vaterite, and calcite. Elemental analysis by XPS showed that the major elements in the samples were oxygen, silicon, carbon, calcium and aluminium; and scanning electron microscopy revealed that the fly ash samples consist of spherically‐shaped particles with surface attachment containing needle‐like particles. Compared with conventional concrete bricks, fly ash bricks generally have higher atomic silicon and crushing strengths but lower crystalline silica. The implication of the results on the suitability of fly ash bricks as replacements for conventional concrete bricks in the building industry is discussed from the point of view of human health and occupational safety. Copyright © 2004 Society of Chemical Industry     

Strategies for capillary electrophoresis: method development and validation for pharmaceutical and biological applications

This review is in support of the development of selective, reproducible and validated capillary electrophoretis (CE) methods. Focusing on pharmaceutical and biological applications, the successful use of CE is demonstrated by more than 800 references, mainly from 1994 until 1998. Approximately 80 recent reviews have been catalogued. These articles sum up the existing strategies for method development in CE, especially in the search for generally accepted concepts, but also looking for new, promising reagents and ideas. General strategies for method development were derived not only with regard to selectivity and efficiency, but also with regard to precision, short analysis time, limit of detection, sample pretreatment requirements and validation. Standard buffer recipes, surfactants used in micellar electrokinetic capillary chromatography (MEKC), chiral selectors, useful buffer additives, polymeric separation media, electroosmotic flow (EOF) modifiers, dynamic and permanent coatings, actions to deal with complex matrices and aspects of validation are collected in 20 tables. Detailed schemes for the development of MEKC methods and chiral separations, for optimizing separation efficiency, means of troubleshooting, and other important information for key decisions during method development are given in 19 diagrams. Method development for peptide and protein separations, possibilities to influence the EOF and how to stabilize it, as well as indirect detection are considered in special sections.     

Standardized aerobic walking on the treadmill by healthy probands and patients with mitochondrial and non-mitochondrial myopathies

Mitochondrial myopathies are characterized by an abnormal aerobic metabolism. The present study examines the serum lactate concentration during standardized aerobic treadmill ergometry and evaluates its relevance for the diagnosis of mitochondrial myopathies. The present study includes 50 volunteers without neuromuscular disorders (control group), 13 patients with mitochondrial, and 14 patients with non-mitochondrial neuromuscular disorders. All members of the control group were able to walk 15 minutes on the treadmill at a constant velocity of at least 5 km/h without exceeding the aerobic threshold (2 mMol/l lactate, venous blood). Ten patients with mitochondrial myopathies and 4 patients with non-mitochondrial myopathies already exceeded the aerobic threshold at walking velocities of 4 or 5 km/h. Though indicating a reduced aerobic endurance, a pathological test result does not prove the diagnosis of a mitochondrial myopathy. Sensitivity and specificity of treadmill ergometry did not differ significantly from those reported for bicycle ergometry. Thus, using the most common aerobic activity in daily life, treadmill ergometry can be considered as an alternative to bicycle exercise tests in the assessment of mitochondrial abnormalities.     

Early expression of a novel nucleotide receptor in the neural plate of Xenopus embryos

Extracellular ATP functions as a neurotransmitter and neuromodulator in the adult nervous system, and a signaling molecule in non-neural tissue, acting either via ligand-gated ion channels (P2X) or G-protein-coupled receptors (P2Y). ATP can cause an increase in intracellular Ca2+ (Ca2+i) in embryonic cells and so regulate cell proliferation, migration, and differentiation. We have isolated a Xenopus cDNA encoding a novel P2Y receptor, XlP2Y, which is expressed abundantly in developing embryos. Recombinant XlP2Y responds equally to all five naturally occurring nucleoside triphosphates (ATP, UTP, CTP, GTP, and ITP), which elicit a biphasic Ca2+-dependent Cl- current (ICl,Ca) where the second phase persists for up to 60 min. XlP2Y also causes a continuous release of Ca2+i and a low level persistent activation of ICl,Ca in Xenopus oocytes through the spontaneous efflux of ATP. mRNAs for XlP2Y are expressed transiently in the neural plate and tailbud during Xenopus development, coincident with neurogenesis. This restricted pattern of expression and novel pharmacological features confer unique properties to XlP2Y, which may play a key role in the early development of neural tissue.     

The structure of lead stabilizers. I: Basic lead carboxylates

Infrared and nuclear magnetic resonance spectra of basic lead carboxylates used as heat stabilizers for halogenated polymers indicate that these salts are not complexes or double compounds of lead oxide, as suggested in most textbooks, but rather unique compounds of interesting structure. Lead stabilizers probably function in these polymers by converting hydrogen chloride to water, interfering with acid catalysis of the elimination reaction.