Effects on prostaglandins F2α, I2, and indomethacin on isolated coronary arteries from healthy and alloxandiabetic dogs

Summary Contractile responses of isolated coronary arteries from healthy and alloxan-diabetic dogs to prostaglandin F₂ were enhanced by indomethacin and inhibited by prostaglandin I₂. The potentiation by indomethacin was more prominent in diabetic vessels than in normal arteries.     

Inhibition ofα-chymotrypsin by 2-halogeno-ethanols; comparison with 2-methyl-ethanols and urea

Summary 2-Halogeno- and 2-methyl-ethanols inhibit-chymotrypsin in the order of their substituted groups: [1] tri>di->mono-, [2] Br->Cl->CH₃->F-. The inhibition by the halogeno-ethanols is mediated differently from that by the methyl-ethanols, ethanol, and urea.     

Effects of PGE2 and PGF2α on the simulation by noradrenaline and oxytocin of human cervical muscle activity at term

Summary Cervical specimens were obtained by needle biopsy in connection with caesarean section at term pregnancy. The preparations were superfused in an organ chamber and contractions were registered isometrically. Prostaglandin (PG) E₂ and F₂ inhibited spontaneous contractions. The stimulatory action of noradrenaline was not influenced by PGF₂ but was reduced by PGE₂ whereas both PGs abolished the excitatory effect of oxytocin.     

An immunohistochemical and ultrastructural comparison of the effects of 2-bromo-α-ergocryptine on intrasellar and transplanted rat pituitaries

Summary Following 2 weeks of administration of 2-bromo--ergocryptine, a marked decrease was observed in prolactin immunoreactivity of the grafted pituitaries, whereas no reduction was noted in the intrasellar pituitaries. No evidence of crinophagy was revealed by electron microscopy in prolactin cells of 2-bromo--ergocryptine-treated rats.Acknowledgments. This work was supported in part by the Medical Research Council of Canada (grant MA-6349). The excellent technical assistance of Mrs Cynthia Edwards and secretarial help of Mrs Wanda Wlodarski are gratefully acknowledged.     

Effects of injury on the concentration ofα 1 andα 2 in the plasmas of male and female rats

Summary The effects of injury on the concentration of ₁-macroglobulin and ₂-macroglobulin in the plasmas of male and female rats has been investigated. At 5 days after injury to the male rats the ₁-macroglobulin concentration increased to 131% of its preinjury value. The ₂-macroglobulin concentration increased more rapidly to a maximum of 86 times its initial value. In the female rats ₂-macroglobulin increased only slightly and ₁-macroglobulin not at all.     

Morphological effects of prostaglandins E1, E2 and F2α on fibroblast-like cultures of human synovial cells

Summary In medium supplemented with serum, PGE₁ and PGE₂ were equally potent in inducing cells with a fenestrated appearance, whereas PGF₂ was comparatively ineffective. In BSA without serum the effects were more persistent and characterized by a high proportion of astrocyte-like cells. The effects were reversed upon removal of the prostaglandins.This work was supported by the National Health and Medical Research Council of Australia.     

Association between pregnancy-associatedα 2-glycoprotein (α 2-PAG) and mixed leucocyte reaction determinants on the leucocyte surface

Summary ₂-PAG is present on the surface of mononuclear blood leucocytes and can be demonstrated predominantly on B-lymphocytes and monocytes. Pretreatment of cells with antibody to ₂-PAG leads to a marked reduction in Fc-rosette formation. Competitive blocking experiments with specific antisera reveal a particularly close asociation between ₂-PAG and MLR (mixed leucocyte reaction) determinants on the cell surface. These findings suggest one mechanism whereby ₂-PAG may modify cell-mediated immune responses.     

TNF-α upregulates adenosine 2b (A2b) receptor expression and signaling in intestinal epithelial cells: a basis for A2bR overexpression in colitis

Adenosine is an endogenous signaling molecule upregulated during inflammatory conditions. Acting through the A2b receptor (A2bR), the predominant adenosine receptor in human colonic epithelia, adenosine has been directly implicated in immune and inflammatory responses in the intestine. Little is known about expression and regulation of A2bR during inflammation. Tumor necrosis factor alpha (TNF-α) is highly upregulated during chronic and acute inflammatory diseases. This study examined the expression of A2bR during colitis and studied effects of TNF-α on A2bR expression, signaling and function. Results demonstrated that A2bR expression increases during active colitis. TNF-α pretreatment of intestinal epithelial cells increased A2bR messenger RNA and protein expression. TNF-α significantly increased adenosine-induced membrane recruitment of A2bR and cyclic adenosine monophosphate downstream signaling. Further, TNF-α potentiated adenosine-induced shortcircuit current and fibronectin secretion. In conclusion, we demonstrated that TNF-α is an important regulator of A2bR, and during inflammation, upregulation of TNF-α may potentiate adenosine-mediated responses. Received 21 July 2005; received after revision 22 August 2005; accepted 19 September 2005 †These authors contributed equally to this work.     

A simple synthesis of (E)-3-formylbut-2-enenitrile,and its use as a precursor of isotope-labelled zeatin and (±) dihydrozeatin

Summary (E)-3-Formylbut-2-enenitrile (4) is synthesized in 2 steps by reacting pyruvaldehyde dimethylacetal and acetonitrile in the presence of sodium methoxide, followed by acid hydrolysis to give 58% overall yield on distillation. The aldehyde4 can be stepwise and selectively reduced to (E)-3-hydroxymethylbut-2-enylamine (7a) in 37% total yield or exhaustivelyb reduced in 1 step to (±)-4-hydroxy-3-methylbutylamine (6) in 46% total yield. Compound7a and6 can be condensed with 6-chloropurine to give zeatin and (±)dihydrozeatin respectively. This provides a readily accessible method for isotope-labelled zeatin and its derivatives at side chain.Contribution No. 1064, Alberta Research CouncilProcess for the Preparation oftrans-3-formylbut-2-enenitrile S. Chen and J. MacTaggart, patent applicatioin registered in Canada and the United States of America.Acknowledgment. The author thanks Mr J. M. MacTaggart and Mrs C. M. Goulet for valuable experimental assistance and Dr R. M. Elofson for helpful discussions.     

17β-estradiol in vitro affects Na-dependent and depolarization-induced Ca2+ transport in rat brain synaptosomes

Effects of 17-estradiol (E₂) in vitro on Na-dependent Ca²⁺ efflux from, and depolarization-induced Ca²⁺ uptake into, the nerve cell were studied with the use of synaptosomes isolated from the brain stem, mesencephalic reticular formation (MRF), caudate nucleus and the hippocampus of long-term ovariectomized adult female rats. It was found that E₂ (1) at a concentration of 10 nM or lower, stimulates Na-dependent Ca²⁺ efflux in the caudate nucleus and hippocampus, and does not affect the efflux in MRF and brain stem; (2) at concentrations above 10 nM has no effect on the Ca²⁺ efflux in any of the four structures investigated; and (3) produces a biphasic effect on the depolarization-induced Ca²⁺ uptake, increasing it in all structures except MRF at 10 nM concentration, and decreasing it at concentrations higher than 10 nM, irrespective of the structure investigated. These results suggest that E₂, acting at extranuclear sites, modulates synaptic transmission via alterations of Ca²⁺ transport mechanisms in nerve endings.     

Host defense against infections and inflammations: Role of the multifunctional IL-6/IFN-β2 cytokine

Summary IL-6/IFN-2 appears to be one of the important mediators of the response to viral and bacterial infections and to shock. The biological effects now associated with IL-6/IFN-2 include: stimulation of immunoglobulin secretion by mature B lymphocytes (BSF-2 activity), growth stimulation of plasmacytomas and hybridomas (HGF activity), activation of T cells, stimulation of hepatic acute phase protein synthesis (HSF activity), stimulation of hematopoiesis, cell differentiation (DIF activity), inhibition of tumor cell growth (AP activity) and other IFN-like effects. As a typical cytokine, IL-6/IFN-2 is secreted by many cell types and acts in various combinations with other interleukins and interferons.     

Correlation between serum dopamine-β-hydroxylase activity and dopamine-β-hydroxylase and tyrosine hydroxylase activities in central and peripheral adrenergic neurons and adrenal glands

Summary Serum dopamine--hydroxylase activity in spontaneously hypertensive rats and Wistar-Kyoto rats had a positive correlation with dopamine--hydroxylase and tyrosine hydroxylase activities in mesenteric vessels, vas deferens, and adrenal glands at 14–16 weeks of age, a negative correlation with dopamine--hydroxylase activity in locus coeruleus at 3 weeks and 14–16 weeks of age, and a positive correlation with tyrosine hydroxylase activity only at 3 weeks of age, but not at 14–16 weeks of age.     

Allozyme polymorphism and linkage disequilibrium ofAdh and α-Gpdh loci in wine cellar and field populations ofDrosophila melanogaster

Summary Over three years, theAdh and -Gpdh loci have been studied in two cellar populations ofDrosophila melanogaster and in two field populations which were each near to one of the cellars. Analyses of gene frequencies indicate that the divergence among subpopulations is greater in theAdh locus than in the -Gpdh locus. Selection for or againstAdh ^S allele acting on theIn(2L)t inversion influences of the -Gpdh alleles. This phenomenon may contribute to explain the maintenance of theAdh and -Gpdh polymorphism and of theIn(2L)t inversion.     

Human Genome and Diseases:¶Cellular and molecular aspects of Zellweger syndrome and other peroxisome biogenesis disorders

Peroxisomes are single-membrane-bound organelles present in virtually all eukaryotic cells. They are involved in numerous metabolic processes, both catabolic and anabolic, including β-oxidation of very long chain fatty acids, metabolism of hydrogen peroxide, plasmalogen biosynthesis and bile acid synthesis. In several genetic diseases, there is either isolated deficiency of a specific peroxisomal protein (single-protein deficiencies) or a defect in the formation of the organelle with loss of multiple peroxisomal functions (peroxisome biogenesis disorders). X-linked adrenoleukodystrophy is an example of the former, and the Zellweger spectrum of the latter. Peroxisome biogenesis disorders are inherited in an autosomal recessive manner and result from mutations in any of at least 12 PEX genes that encode peroxins. This article reviews the peroxisomal system, the clinical, biochemical and molecular aspects of peroxisomal disorders, and discusses recent scientific advances in the understanding of peroxisome biogenesis. Received 16 October 2001; received after revision 2 January 2002; accepted 3 January 2002     

A human homolog of the yeast gene encoding tRNA 2′-phosphotransferase: cloning,characterization and complementation analysis

The Saccharomyces cerevisiae TPT1 gene plays a role in removing the 2-phosphate from ligated tRNA during the maturation of pre-tRNA. Here we reported the cloning and characterization of the human TRPT1 gene as a homolog of yeast TPT1. The TRPT1 gene is located at human chromosome 11q13 and encodes a polypeptide of 253 amino acids. BLAST searches with its amino acid sequence revealed the ubiquitous occurrence of TRPT1 homologs and their functional relationships with the presence of the DUF60/KptA domain. Northern analysis demonstrated that the gene is primarily expressed in heart and skeletal muscle, with lower or undetectable levels in other tissues studied. A plasmid-shuffling experiment showed that the human TRPT1 gene could complement the tpt1 mutation in S. cerevisiaeReceived 19 March 2003; received after revision 25 April 2003; accepted 22 May 2003     

Human Genome and Diseases:¶Double-strand breaks and translocations in cancer

The correct repair of double-strand breaks (DSBs) is essential for the genomic integrity of a cell, as inappropriate repair can lead to chromosomal rearrangements such as translocations. In many hematologic cancers and sarcomas, translocations are the etiological factor in tumorigenesis, resulting in either the deregulation of a proto-oncogene or the expression of a fusion protein with transforming properties. Mammalian cells are able to repair DSBs by pathways involving homologous recombination and nonhomologous end-joining. The analysis of translocation breakpoints in a number of cancers and the development of model translocation systems are beginning to shed light on specific DSB repair pathway(s) responsible for the improper repair of broken chromosomes. Received 19 June 2001; received after revision 6 September 2001; accepted 11 September 2001     

In pre-sterol carrier protein 2 (SCP2) in solution the leader peptide 1 – 20 is flexibly disordered, and residues 21 – 143 adopt the same globular fold as in mature SCP2

The preform of the rabbit sterol carrier protein 2 (pre-rSCP2) was cloned, the uniformly ¹⁵N-labelled protein expressed in Escherichia coli and studied by three-dimensional ¹⁵N-resolved nuclear magnetic resonance spectroscopy. In spite of its low solubility in aqueous solution of only ∼0.3 mM, sequential ¹⁵N and ¹H backbone resonance assignments were obtained for 105 out of the 143 residues. From comparison of the sequential and medium-range nuclear Overhauser effects (NOEs) in the two proteins, all regular secondary structures previously determined in mature human SCP2 (hSCP2) [Szyperski et al. (1993) FEBS Lett. 335: 18–26] were also identified in pre-rSCP2. Near-identity of the backbone ¹⁵N and ¹H chemical shifts and 1 : 1 correspondence of 24 long-range NOEs to backbone amide groups in the two proteins show that the residues 21 – 143 adopt the same globular fold in pre-rSCP2 and mature hSCP2. The N-terminal 20-residue leader peptide of pre-rSCP2 is flexibly disordered in solution and does not observably affect the conformation of the polypeptide segment 21 – 143. Received 11 May 1998; accepted 15 May 1998     

Effect of glucose and phloretin-2′-β-D-glucose (phloridzin) on in vitro fertilization of mouse ova

Summary The fertilization ratio of mouse ova in vitro decreased when glucose concentration in the medium was lowered. However, the addition of phloretin-2--D-glucose (phloridzin), known as a glucose uptake inhibitor, restored the fertilization ratio back to the control level. The glucose moiety of the phloridzin seemed to be responsible for this effect.