A chemoenzymatic synthesis of UDP-(2-deoxy-2-fluoro)-galactose and evaluation of its interaction with galactosyltransferase

The left internal mammary artery-to-the left pulmonary artery shunt was created in a 16-year-old boy with single ventricle, severe pulmonary stenosis palliated by Glenn shunt at the age of two. Four years follow-up angiogram demonstrated a significant increase of the diameter of the left internal mammary artery from 4 to 7 mm. The internal mammary artery is a good alternative conduit for a systemic-to-pulmonary artery shunt for a cyanotic heart disease because of its growth potential.     

Mutation of the htrB gene in a virulent Salmonella typhimurium strain by intergeneric transduction: strain construction and phenotypic characterization

The htrB gene product of Haemophilus influenzae contributes to the toxicity of the lipooligosaccharide. The htrB gene encodes a 2-keto-3-deoxyoctulosonic acid-dependent acyltransferase which is responsible for myristic acid substitutions at the hydroxy moiety of lipid A beta-hydroxymyristic acid. Mass spectroscopic analysis has demonstrated that lipid A from an H. influenzae htrB mutant is predominantly tetraacyl and similar in structure to lipid IV(A), which has been shown to be nontoxic in animal models. We sought to construct a Salmonella typhimurium htrB mutant in order to investigate the contribution of htrB to virulence in a well-defined murine typhoid model of animal pathogenesis. To this end, an r- m+ galE mutS recD strain of S. typhimurium was constructed (MGS-7) and used in inter- and intrastrain transduction experiments with both coliphage P1 and Salmonella phage P22. The Escherichia coli htrB gene containing a mini-Tn10 insertion was transduced from E. coli MLK217 into S. typhimurium MGS-7 via phage P1 and subsequently via phage P22 into the virulent Salmonella strain SL1344. All S. typhimurium transductants showed phenotypes similar to those described for the E. coli htrB mutant. Mass spectrometric analysis of the crude lipid A fraction from the lipopolysaccharide of the S. typhimurium htrB mutant strain showed that for the dominant hexaacyl form, a lauric acid moiety was lost at one position on the lipid A and a palmitic acid moiety was added at another position; for the less abundant heptaacyl species, the lauric acid was replaced with palmitoleic acid.     

Global phylogeography of the ridley sea turtles (Lepidochelys spp.) as inferred from mitochondrial DNA sequences

BACKGROUND: The cardiovascular applications of magnetic resonance (MR) techniques in coronary artery disease have increased considerably in recent years. Technical advantages of MR imaging are the excellent spatial resolution, the characterization of myocardial tissue, and the potential for three-dimensional imaging. These characteristics allow the accurate assessment of left ventricular mass and volume, the differentiation of infarcted from normal tissue, and the determination of systolic wall thickening and regional wall motion abnormalities. METHODS: In addition to the conventionally used spin-echo and cine-echo techniques, newer techniques such as myocardial tagging, ultrafast MR imaging and MR coronary angiography have been developed. These newer techniques allow a more accurate assessment of ventricular function (tagging), myocardial perfusion (ultrafast imaging), and evaluation of stenosis severity (MR coronary angiography). Particularly early detection and flow assessment of stenosed coronary arteries and bypasses by MR angiography would constitute a major breakthrough in cardiovascular MR imaging. Apart from the MR imaging techniques, cardiac metabolism may be well assessed using MR spectroscopy. This provides unique information on the metabolic behaviour of the myocardium under conditions stress-induced ischemia. However, the definite niche of cardiac MR spectroscopy has still to be settled. CONCLUSION: Currently, MR techniques allow the evaluation of anatomy and function (accepted use), perfusion and viability (development phase), and coronary angiography (experimental phase). A particular strength of MR imaging is that one single MR test may encompass cardiac anatomy, perfusion, function, metabolism and coronary angiography. The replacement of multiple diagnostic tests with one MR test may have major effects on cardiovascular healthcare economics and would outweight the cost inherent to the MR angiography procedure.     

Association and colocalization of the Kvbeta1 and Kvbeta2 beta-subunits with Kv1 alpha-subunits in mammalian brain K+ channel complexes

The differential expression and association of cytoplasmic beta-subunits with pore-forming alpha-subunits may contribute significantly to the complexity and heterogeneity of voltage-gated K+ channels in excitable cells. Here we examined the association and colocalization of two mammalian beta-subunits, Kvbeta1 and Kvbeta2, with the K+ channel alpha-subunits Kv1.1, Kv1.2, Kv1.4, Kv1.6, and Kv2.1 in adult rat brain. Reciprocal coimmunoprecipitation experiments using subunit-specific antibodies indicated that Kvbeta1 and Kvbeta2 associate with all the Kv1 alpha-subunits examined, and with each other, but not with Kv2.1. A much larger portion of the total brain pool of Kv1-containing channel complexes was found associated with Kvbeta2 than with Kvbeta1. Single- and multiple-label immunohistochemical staining indicated that Kvbeta1 codistributes extensively with Kv1.1 and Kv1.4 in cortical interneurons, in the hippocampal perforant path and mossy fiber pathways, and in the globus pallidus and substantia nigra. Kvbeta2 codistributes extensively with Kv1.1 and Kv1.2 in all brain regions examined and was strikingly colocalized with these alpha-subunits in the juxtaparanodal region of nodes of Ranvier as well as in the axons and terminals of cerebellar basket cells. Taken together, these data provide a direct demonstration that Kvbeta1 and Kvbeta2 associate and colocalize with Kv1 alpha-subunits in native tissues and provide a biochemical and neuroanatomical basis for the differential contribution of Kv1 alpha- and beta-subunits to electrophysiologically diverse neuronal K+ currents.     

Intraoperative echocardiography is indicated in high-risk coronary artery bypass grafting

BACKGROUND: Intraoperative echocardiography is a valuable monitoring and diagnostic technology used in cardiac surgery. This reports our clinical study of the usefulness of intraoperative echocardiography to both surgeons and anesthesiologists for high-risk coronary artery bypass grafting. METHODS: From March to November 1995, 82 consecutive high-risk patients undergoing coronary artery bypass grafting were studied in a four-stage protocol to determine the efficacy of intraoperative echocardiography in management planning. Alterations in surgical and anesthetic/hemodynamic management initiated by intraoperative echocardiography findings were documented in addition to perioperative morbidity and mortality. RESULTS: Intraoperative echocardiography initiated at least one major surgical management alteration in 27 patients (33%) and at least one major anesthetic/hemodynamic change in 42 (51%). Mortality and the rate of myocardial infarction in this consecutive high-risk study population using intraoperative echocardiography and in a similar group of patients without the use of intraoperative echocardiography was 1.2% versus 3.8% (not significant) and 1.2% versus 3.5% (not significant), respectively. CONCLUSIONS: We conclude that when all of the isolated diagnostic and monitoring applications of perioperative echocardiography are routinely and systematically performed together, it is a safe and viable tool that significantly affects the decision-making process in the intraoperative care of high-risk patients undergoing primary isolated coronary artery bypass grafting and may contribute to the optimal care of these patients.     

Mesocosm study of Mytilus edulis larvae and postlarvae, including the settlement phase, exposed to a gradient of tributyltin

In a mesocosm study, the effects of a gradient of tributylin (TBT) (nominal TBT concentrations of 0.3, 2.3, 18.5, 146, and 1150 ng Sn liter-1) on Mytilus edulis larvae and postlarvae, including the settlement phase, were investigated over 15 days. Effects of TBT on mortality, growth measured as increase in shell length, shell dimensions, and settlement were evaluated. In general, mortality was high in all mesocosms including the control; during the first 24 h of the experiment, mortality was 63% at the highest TBT concentration (26% in the control). An LC50 (24 h) of 254 ng Sn liter-1 was estimated. The mortality rate of larvae/postlarvae increased 40% at 18.5 ng Sn liter-1 (0.41 day-1) compared with the control (0.30 day-1). For postlarvae, the growth rate decreased with increasing TBT concentration. The mean shell length at 2.3 ng Sn liter-1 was significantly reduced in comparison to the control on Day 15. Then EC10 (15 days) for shell growth was estimated to be 5.4 ng Sn liter-1. This is the lowest effect concentration ever reported in the literature. For postlarvae, shell dimensions in terms of shell length-shell width relations were affected by TBT at 1150 ng Sn liter-1, because the reduced growth led to the failure of adult mussels to secret a dissochonch shell. During the first days of exposure, the settlement monitored on polyethylene settling strips was stimulated by TBT, after which the settlement decreased due to the high mortality. Only a small portion of the population survived to the end of the test period. By comparison of the biotic conditions (in terms of larval abundance and particle concentration reflecting larval food) in the control mesocosm with those in the cove where the experiment was conducted, it was concluded that the mesocosm had successfully simulated the field conditions.     

Enhancement of 5-aminolaevulinic acid-induced photodynamic therapy in normal rat colon using hydroxypyridinone iron-chelating agents

Currently, the clinical use of 5-aminolaevulinic acid (ALA)-induced protoporphyrin IX (PPIX) for photodynamic therapy (PDT) is limited by the maximum tolerated oral ALA dose (60 mg kg(-1)). This study investigates whether hydroxypyridinone iron-chelating agents can be used to enhance the tissue levels of PPIX, without increasing the administered dose of ALA. Quantitative charge-coupled device (CCD) fluorescence microscopy was employed to study PPIX fluorescence pharmacokinetics in the colon of normal Wistar rats. The iron chelator, CP94, when administered with ALA was found to produce double the PPIX fluorescence in the colonic mucosa, compared with the same dose of ALA given alone and to be more effective than the other iron chelator studied, CP20. Microspectrofluorimetric studies demonstrated that PPIX was the predominant porphyrin species present. PDT studies conducted on the colonic mucosa showed that the simultaneous administration of 100 mg kg(-1) CP94 i.v. and 50 mg kg(-1) ALA i.v. produced an area of necrosis three times larger than similar parameters without the iron-chelating agent with the same light dose. It is possible, therefore, to increase the amount of necrosis produced by ALA-induced PDT substantially, without increasing the administered dose of ALA, through the simultaneous administration of the iron-chelating agent, CP94.