Studies on reversible dehydrogenase systems: The reversibility of the hydrogenase system of Bact. coli.
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Chondrocytes from the vertebral columns of 11-day chick embryos were cultured in the continuous presence of 5-bromodeoxyuridine (BUdR) Under these conditions the cells form multilayers but synthesize little extracellular matrix as determined by toluidine blue metachromasia or sulfate-(35)S incorporation into polysaccharide. Myogenic cells from the breast muscles of 11-day chick embryos formed myotubes when plated into BUdR-treated chondrocyte cultures. When plated on untreated chondrocyte multilayers or on multilayers which had been permitted to recover from BUdR treatment for 3 days, myogenic cells failed to form myotubes Since extracellular matrix is present in untreated chondrocyte cultures and reappears in multilayers recovering from BUdR treatment, it is suggested that extracellular matrix is the active agent in the suppression of myogenesis An attempt was made to duplicate the suppressing activity of multilayer cultures by using ion exchange resins as substrates for myogenic cells Myotubes formed on acidic and basic resin particles If extracellular matrix is the active suppressing agent, it may have to fulfill certain spatial distributional requirements before its activity is expressed
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Simple buy and sell relationships are no longer enough for health care organizations. Like other industries have done, they need to rethink and redesign their interactions with suppliers and customers in order to realize the full potential of those relationships. By establishing and managing partnerships with selected suppliers and customers, we can realize a whole new set of mutual benefits.
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1. The plasma concentrations and urinary excretion of nedocromil sodium have been determined following single dose administration in six healthy volunteers dosed orally (1 mg kg-1) and intravenously (0.2 microgram kg-1 for 30 min). Similar parameters were measured in six volunteers and twelve asthmatic patients dosed by inhalation (4 mg). Multiple dose kinetic measurements were also made. 2. The intravenous data demonstrated that nedocromil sodium is a high clearance drug (10.2 +/- 1.3 ml min-1 kg-1). The data were fitted by a two compartment model with very rapid elimination from the central compartment (k10 = 0.088 +/- 0.021 min-1; beta = 0.013 +/- 0.002 min-1). 81% of the dose was excreted in the urine. 3. Oral absorption was low (2-3% of the dose) and contributed negligibly to the plasma profile after inhalation. 4. After inhalation of single doses of 4 mg in volunteers and patients plasma concentration rose rapidly, plateaued and then fell monoexponentially with a half-life of approximately 2 h. The data fitted a 'flip-flop' model with two absorption components. The extent of absorption was up to 6% of the dose with less in patients. 5. After multiple dosing with 4 mg four times daily for 7 days in volunteers negligible accumulation was observed. The pattern was similar in patients treated with 4 mg four times daily after 1, 6 and 12 months.
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The effect of amino acids and derivatives, Krebs cycle acids and related compounds, fatty acids, and vitamins and related compounds on the toxicity of 8-quinolinol and bis(8-quinolinolato)copper(II) to Aspergillus oryzae (ATCC 1011) was studied. Only aliphatic thiol-containing compounds (cysteine, glutathione, dithioerythritol, and dithiothreitol) and DL-alpha-lipoic acid protected against 8-quinolinol but not its copper(II) bischelate. It is suggested that 8-quinolinol inhibits lipoic acid biosynthesis, and the mode of fungitoxicity of 8-quinolinol is different from that of bis(8-quinolinolato)copper(II).
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The first and essential step in normal sexual differentiation takes place during the 5th-6th week of gestation. The testis determining factor (TDF) directs the undifferentiated gonad into a testis, which secretes hormones responsible for normal male development. A new candidate for TDF has recently been reported, and it has been called the sex determining region of the Y (SRY). The hypothesis has been supported by the finding of XX individuals with SRY, and two females with 46,XY karyotype and a mutation in SRY. However, XX males without SRY has been reported, and the role of SRY still has to be determined. We have tested three human females with 46,XY karyotype and gonadal dysgenesis and two 46,XX males for the presence of SRY using the polymerase chain reaction and subsequent DNA sequencing. Both 46,XX males contained SRY, whereas one of the 46,XY females had suffered a point mutation in SRY changing a codon for lysine to a stop codon. This information supports the hypothesis that SRY is significant in normal male sex differentiation. The two remaining 46,XY individuals had an intact HMG box, but it is possible that a mutation may be found in a regulatory gene or further downstream in the gene regulatory cascade. Two patients including the one with a mutation in SRY had gonadoblastomas supporting the hypothesis that another gene on the Y-chromosome is involved in the pathogenesis of this neoplasia.
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