Regional 5-hydroxyindoleacetic acid production in humans

Veno-arterial plasma concentration differences and regional organ plasma flows were used to quantify the relative amounts of 5-hydroxyindoleacetic acid (5-HIAA) contributed by various sites into the peripheral circulation. Positive venoarterial concentration gradients were found in the hepatosplanchnic, forearm, cardiac and jugular vessels in the healthy subjects. The renal circulation was determined to be the principal site of 5-HIAA clearance, extracting 18 +/- 2 nmol/min. The gut was the greatest contributor to the total 5-HIAA plasma pool with the relative contributions of the various organs being as follows: hepatosplanchnic organs 58%, skeletal muscle 26%, brain 6% and the heart 3%. The source of 5-HIAA stemming from these regional beds remains unknown, it may derive from serotonin taken up by and deaminated in ubiquitous endothelial cells, enterochromaffin cells of the gut, peripheral serotonergic nerves, serotonin turnover in platelets or perhaps the metabolism of serotonin taken up by sympathetic nerves. To test the latter hypothesis we examined 23 patients with chronic congestive heart failure and 9 patients with pure autonomic failure to investigate the possible effects of sympathetic nervous system overactivity and underactivity on peripheral 5-HIAA production and plasma 5-HIAA concentration. The resting arterial plasma 5-HIAA concentration in the heart failure patients was increased three-fold. This elevated plasma 5-HIAA concentration was attributable to an increased rate of whole body 5-HIAA production. The arterial 5-HIAA plasma concentration in the autonomic failure patients was paradoxically elevated, being 70% greater than that of the healthy subjects. The increased 5-HIAA plasma concentration in these patients was accounted for by a reduction in 5-HIAA plasma clearance. In all subjects studied there was a weak relationship only between total body norepinephrine spillover to plasma and the arterial 5-HIAA plasma concentration. We found that in healthy subjects the overflow of 5-HIAA into the hepatic vein was significantly related to the underlying degree of sympathetic activity. It can be concluded that 5-HIAA is produced at a number of sites throughout the body with the arterial plasma concentration being dependent on both the level of production and plasma clearance. By far the majority of 5-HIAA in plasma is derived from the gut with only minimal contribution from the brain.     

Extensive direct-tandem organization of a long repeat DNA sequence on the Y chromosome of chinook salmon (Oncorhynchus tshawytscha)

A long repetitive DNA sequence (OtY8) has been cloned from male chinook salmon and its genomic organization has been characterized. The repeat has a unit length of 8 kb and is present approximately 300 times per diploid male nucleus. All internal fragments within the 8-kb repeat segregate from father to son, suggesting that the entire repeat unit is located on the Y chromosome. The organization of this sequence into an 8-kb repeat unit is restricted to the Y chromosome, as are several male-specific repeat subtypes identified on the basis of restriction-site variation. The repeat possesses only weak internal sequence similarities, suggesting that OtY8 has not arisen by duplication of a smaller repeat unit, as is the case for other long tandem arrays found in eukaryotes. Based on a laddered pattern arising from partial digestion of genomic DNA with a restriction enzyme which cuts only once per repeat unit, this sequence is not dispersed on the Y chromosome but is organized as a head-to-tail tandem array. Pulse-gel electrophoresis reveals that the direct-tandem repeats are organized into at least six separate clusters containing approximately 12 to 250 copies, comprising some 2.4 Mb of Y-chromosomal DNA in total. Related sequences with nucleotide substitutions and DNA insertions relative to the Y-chromosomal fragment are found elsewhere in the genome but at much lower copy number and, although similar sequences are also found in other salmonid species, the amplification of the repeat into a Y-chromosome-linked tandem array is only observed in chinook salmon. The OtY8 repetitive sequence is genetically tightly associated with the sex-determination locus and provides an opportunity to examine the evolution of the Y chromosome and sex determination process in a lower vertebrate.     

Synthesis of corneal keratan sulfate proteoglycans by bovine keratocytes in vitro

Keratan sulfate proteoglycans (KSPGs) are the major proteoglycans of the cornea and are secreted by keratocytes in the corneal stroma. Previous studies have been able to show only transient secretion of KSPG in cell culture. In this study, cultures of bovine keratocytes were found to secrete the three previously characterized KSPG proteins into culture medium. Reactivity with monoclonal antibody I22 demonstrated substitution of these proteins with keratan sulfate chains. KSPG constituted 15% of the proteoglycan metabolically labeled with [35S]sulfate in keratocyte culture medium. This labeled KSPG contained keratan sulfate chains of 4700 Da compared to 21,000 Da for bovine corneal keratan sulfate. Labeled keratan sulfate from cultures contained nonsulfated, monosulfated, and disulfated disaccharides that were released by digestion with endo-beta-galactosidase or keratanase II. Nonsulfated disaccharides were relatively more abundant in keratan sulfate from culture than in corneal keratan sulfate. These results show that cultured bovine keratocytes maintain the ability to express all three of the known KSPG proteins, modified with keratan sulfate chains and sulfated on both N-acetylglucosamine and galactose moieties. KSPG made in vitro differs from that found in vivo in the length and sulfation of its keratan sulfate chains. The availability of cell cultures secreting corneal keratan sulfate proteoglycans provides an opportunity to examine biosynthesis and control of this important class of molecules.     

Multiregional estimation of gross internal migration flows

"A multiregional model of gross internal migration flows is presented in this article. The interdependence of economic factors across all regions is recognized by imposing a non-stochastic adding-up constraint that requires total inmigration to equal total outmigration in each time period. An iterated system estimation technique is used to obtain asymptotically consistent and efficient parameter estimates. The model is estimated for gross migration flows among the Canadian provinces over the period 1962-86 and then is used to examine the likelihood of a wash-out effect in net migration models. The results indicate that previous approaches that use net migration equations may not always be empirically justified."     

Synthesis and Processing Characteristics of Ba0.65Sr0.35TiO3 Powders from Catecholate Precursors

Powders of composition Ba_0.65Sr_0.35TiO₃ were prepared from catecholate precursor phases, BaTi(C₆H₄O₂)₃ and SrTi (C₆H₄O₂)₃. The physical and chemical properties of the base powders, and those doped with 0.2 wt% manganese, are reported in detail. The dimensions of the primary particles in the starting powders were of the order of 20–50 nm, but the occurrence of abnormal grain growth during sintering promoted grain sizes in the ceramic of up to ∼100 μm. In some microstructures, coarse grains coexisted with a ∼1-μm fraction to produce a characteristic bimodal grain size distribution. By contrast, under comparable sintering conditions, namely 1350° or 1400°C for 1 h, grain growth in Mn-doped samples was suppressed, leading to uniform microstructures with a grain size of only a few micrometers. The pellet densities were nevertheless similar, 97% of theoretical in both doped and undoped samples. No significant difference was observed in the dielectric permittivity of the two compositions: the peak relative permittivity occurred at ∼20°C, with a maximum value of ∼22 000.     

Solutions of the general equations for the radiation dose dependence of the molecular weights of irradiated polymers with an initial Schulz-Zimm distribution

Summary The general equations for the radiation dose dependence of irradiated polymer molecular weights have been solved exactly. For an initial most probable molecular weight distribution (=1), the solutions are analytical and exact. For the general case (1) the solutions are numerical and exact. The present approach has resulted in the solutions for both =1 and 1 being incorporated into a group of FORTRAN computer programs which will solve experimental data for scission and crosslinking yields by both minimization and exact treatments. Simulated data treated using these FORTRAN programs are give. The FORTRAN programs are available from the authors.     

Inhibition of neuronal calcium channels by a novel peptide spider toxin, DW13.3

Peptide toxins have proved to be useful agents, both in discriminating between different components of native calcium channel currents and in the molecular isolation and designation of their cloned channel counterparts. Here, we describe the isolation and characterization of the biochemical and physiological properties of a novel 74-amino acid peptide toxin (DW13.3) extracted from the venom of the spider Filistata hibernalis. The subtype specificity of DW13.3 was investigated using calcium channel currents recorded from two separate expression systems and several different cultured mammalian cell preparations. Overall, DW13.3 potently blocked all native calcium channel currents studied, with the exception of T-type currents recorded from GH3 cells. Examination of transiently expressed calcium channels in oocytes showed that DW13.3 had the highest affinity for alpha1A, followed by alpha1B > alpha1C > alpha1E. The affinity of DW13.3 for alpha1B N-type currents varied by 10-fold between expressed channels and native currents. Although block occurred in a similar 1:1 manner for all subtypes, DW13.3 produced a partial block of both alpha1A currents and P-type currents in cerebellar Purkinje cells. Selective occlusion of the P/Q-type channel ligand omega-conotoxin MVIIC (but not omega-agatoxin IVA) from its binding site in Purkinje neurons suggests that DW13.3 binds to a site close to the pore of the channel. The inhibition of different subtypes of calcium channels by DW13.3 reflects a common "macro" binding site present on all calcium channels except T-type.     

Alcohol inhalation in asthma therapy

As part of the search for anticomplementary active components from natural products, the anticomplementary properties of methanolic extracts from the flower buds of Magnoliafargesii have been investigated. Bioassay-guided chromatographic separation of the active constituents led to the isolation of compound 1, whose structure was identified by spectroscopic methods to be kaempferol 3-O-beta-D-(6"-O-coumaroyl)glucopyranoside (tiliroside). Tiliroside showed very potent anti-complement activity (IC50=5.4 x 10(-5) M) on the classical pathway of the complement system, even higher than rosmarinic acid, which is a well-known inhibitor against the complement system. On the other hand, the hydrolysates of tiliroside, kaempferol, astragalin and p-coumaric acid showed very weak activity on this system.     

Fire protection of critical circuits-a life and property preserver

This paper examines the importance of fire-resistant electrical circuit feeders in saving lives and property. It discusses sophisticated fire fighting and evacuation systems and the electrical energy requirements to ensure their operation in commercial high-rise, hospital and other at-risk buildings. The influence of cost, ease of installation and subsequent inspection of fire-resistant circuits in a consulting engineer's specifications decision is considered. Analysis of the impact of building code modifications that require increased fire protection for feeders to emergency systems is presented. The paper cites examples of devastating fires and resultant code upgrades. Implications of the 1996 National Electrical Code (NEC) sections concerning emergency electrical feeders are reviewed. Specification writers and product installers have primary influence over these systems. Their roles and responsibilities are discussed. The paper also reviews the various methods of providing fire-resistive protection to circuit feeders