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Long-term glycemic control measurements in diabetic patients receiving hemodialysis.

Cardiovascular morbidity is increased in patients with diabetes mellitus and there is a great prevalence of diabetes and cardiovascular disease among patients with end-stage renal disease (ESRD). Control of glycemia can decrease cardiovascular and end-organ damage. Because the validity of glycemic control tests have not been rigorously studied in patients with ESRD, we evaluated the value of various measures in these patients. The overall clinical goal was to investigate whether hemoglobin A1C (A1C) accurately reflects actual glycemic control as compared with other measures in light of the importance of attaining appropriately controlled blood glucose (BG). The commonly used tests of total glycated hemoglobin (GHb) and A1C may be unreliable in patients with ESRD because of the presence of anemia, shortened red blood cell (RBC) survival, and assay interferences from uremia. The primary aim of this study was to assess the relationship of capillary BG measurements to A1C, GHb, total glycated plasma proteins (GPP), and fructosamine (Fr) in diabetic patients receiving hemodialysis. Twenty-three patients were instructed to obtain BG evaluations twice daily for 7 days by using the Elite glucometer (Bayer Corporation, Elkhart, IN). These determinations included 6 fasting, 6 preprandial, and 3 separate 2-hour postprandial levels. Blood was obtained on day 7 for measurement of A1C, GHb, GPP, and Fr. A1C was analyzed by an immunoassay, GPP and GHb were assayed by affinity high-performance liquid chromatography (HPLC), and Fr by automated nitroblue colorimetric assay. Scatter plots were generated by plotting the average BG versus A1C, GHb, GPP, or Fr. Linear regression was performed for each plot showing the following relationships: A1C = 0.0174 (BG) + 4.76 (r = 0.58; P < 0.05): GHb = 0.0371 (BG) + 3.57 (r = 0.584; P < 0.05): GPP = 0.0083 (BG) + 26.13 (r = 0.065; P = 0.77): Fr = 0.6865 (BG) + 250 (r = 0.345; P = 0.11). Despite anemia and shortened RBC lifespan in patients with ESRD, A1C in the range of 6% to 7% estimates glycemic control similarly to patients without severe renal impairment. A1C values above 7.5% may overestimate hyperglycemia in patients with ESRD. Thus, diabetic patients receiving hemodialysis may have long-term BG that are more properly controlled than previously determined, reducing their risks of the macro- and microvascular complications of diabetes mellitus.

Blood Glucose↗

DRUG RESISTANCE OF ENTERIC BACTERIA. 3. ACQUISITION OF TRANSFERABILITY OF NONTRANSMISSIBLE R(TC) FACTOR IN COOPERATION WITH F FACTOR AND FORMATION OF FR(TC).

Harada, Kenji (Gunma University, Maebashi, Japan), Mitsuo Kameda, Mitsue Suzuki, and Susumu Mitsuhashi. Drug resistance of enteric bacteria. III. Acquisition of transferability of nontransmissible R(TC) factor in cooperation with F factor and formation of FR(TC). J. Bacteriol. 88:1257-1265. 1964.-Transmissible drug-resistance factor R, which confers resistance to tetracycline, chloramphenicol, streptomycin, and sulfonamide, was previously found to be transduced in the system of the Salmonella E group with phage epsilon. The R factor of R(+) transductants was nontransmissible by cell-to-cell contact, and it was not eliminated by treatment with acridine dye. When R(+) transductants were infected with F factor, the nontransmissible R factor acquired transferability by conjugation. The R(+) conjugants, to which only the R factor was separately transmitted by conjugation from the (F(+)R(+)) donor, were still unable to transfer their R factor by conjugation. However, the (FR)(+) conjugants, to which both F and R factor were transmitted simultaneously by conjugation, were also capable of transferring their F and R factors by conjugation. From the present study, it was concluded that the recombinant (FR) factor was formed as a result of an interaction between F and R factors present in a host bacterium, and that one of the mechanisms of acquisition of transferability is accounted for by the formation of recombinant (FR) factor. The recombinant (FR) factor was transferable by conjugation, and it conferred both the drug-resistance and F(+) characters to the recipient cells. The (FR) factor was eliminated by treatment with acridine dye and also transduced as one unit into Escherichia coli K-12 by P1kc phage.

Acridines↗

The effect of two schedules of primary and conditioned reinforcement.

Of 23 pigeons, 11 received continuous reinforcement for key pecking, and 12 received an FR 10 schedule of reinforcement. The birds were then tested without food, but with potential conditioned reinforcers presented either on the same schedule as in training, on the other schedule, or not at all. Each bird in the subgroup trained on CRF and tested with S(r)'s at FR 10 not only gave more responses in testing than did each bird in both subgroups receiving no S(r)'s, but also gave more responses than did each bird in the S(r) subgroup receiving CRF training and S(r)'s at CRF. Cumulative records are presented to show the effects of different schedules of conditioned reinforcers.

Animals↗

Seed germination of Arabidopsis thaliana phyA/phyB double mutants is under phytochrome control.

We examined the photocontrol of seed germination in the phyA/phyB double mutants of Arabidopsis thaliana seeds. Dormant phyA/phyB seeds showed a red/far-red light (R/FR)-reversible induction of seed germination. This suggests the involvement of at least one other phytochrome, phyC, D, and/or E, in controlling seed germination. We designated this spectrally active phytochrome in phyA/phyB as phyX. The full reversibility of the R-induced germination by subsequent FR pulses, and the observation that the response is reversible by FR, even after a 3-h R treatment, indicates that this phyX response belongs to the low-fluence-response type. Thus, this phyX response is functionally related to phyB-mediated responses. However, in contrast to phyB-controlled seed germination, this phyX-mediated response needs a prolonged imbibition period and exhibits reversibility kinetics different from that needed for phyB. Furthermore, this phyX response requires a prolonged irradiation time and shows a fluence rate response dependency, showing a similarity to the high irradiance response of photomorphogenesis. Thus, phyX, with regard to its control of seed germination, is a functionally new phytochrome that shares some characteristics of both phyA- and phyB-mediated responses.

Arabidopsis↗

Functional reach and single leg stance in patients with peripheral vestibular disorders.

The purpose of this study was to compare functional reach distance and right single leg stance time in patients who had peripheral vestibular disease. Twenty-eight patients (15 female, 13 male) between the ages of 35 and 84 were asked to perform 3 trials each of functional reach (FR) and right single leg stance (SLS). SLS times were measured by a Kistler static force platform on line with a Caspar personal computer. FR distance was measured by using a free-standing 147-cm rule. In addition, each subject filled out the Dizziness Handicap Inventory (DHI). Trials were randomized to prevent fatigue or practice effects. A Pearson product-moment correlation was performed between FR and SLS (r = 0.59, P = 0.001). Post hoc analyses of the first, the best, and the average scores highlighted the importance of using means for comparison in a population as variable as the vestibularly impaired. Post hoc analyses showed no correlation between the DHI score and either functional reach distance or single leg stance time. However, when the subjects were divided into groups based on DHI score (group 1 with DHI < or = 49/100, group 2 with DHI > or = 50/100) and a pooled two-sample t-test was performed, a significant difference (P = 0.05) was found in functional reach distance; the subjects who reported less perception of handicap reached farther than those who reported more perception of handicap. No difference was found between the two DHI groups in single leg stance time. Post hoc correlations of functional reach and single leg stance time. Post hoc correlations of functional reach and single leg stance within the two DHI groups showed a higher correlation in group 1 (DHI < or = 49/100), with r equals 0.65 (P < or = 0.01), than in group 2 (DHI > or = 50/100), with r equals 0.38 (P = 0.20). The study found a highly significant, moderate correlation between functional reach distance and single leg stance times in patients with peripheral vestibular disease. These results support the use of FR as an additional assessment tool with patients who have peripheral vestibular disease.

Adult↗

Blue-light promotion of flowering is absent in hy4 mutants of Arabidopsis.

Loss of a blue-light photoreceptor in the hy4 mutants of Arabidopsis thaliana (L.) Heynh substantially delayed flowering (> 100 d to flower vs. 40-50 d), especially with blue light exposure from lamps lacking much red (R) and/or far-red (FR) light. Red night breaks were promotory but flowering was still later for the hy4-101 mutant. However, with exposure to light from FR-rich lamps, flowering of all mutants was early and no different from the wild type. Thus, flowering of Arabidopsis involves a blue-light photoreceptor and other, often more effective photoreceptors. The latter may involve phytochrome photoresponses to R and FR, but with little or no phytochrome response to blue wave-lengths.

Arabidopsis↗

Solid residues from Ruminococcus cellulose fermentations as components of wood adhesive formulations.

Residues from the fermentation of cellulose by the anaerobic bacteria Ruminococcus albus (strain 7) or Ruminococcus flavefaciens (strains FD-1 or B34b) containing residual cellulose, bacterial cells and their associated adhesins, were examined for their ability to serve as components of adhesives for plywood fabrication. The residues contained differing amounts of protein (0.4-4.2% of dry weight), but the ratios of monosaccharides recovered following two-stage treatment of the residue with detergent (pH 7) and TFA were similar for all three strains (0.71 glucose:0.18 xylose:0.08 mannose:0.02 galactose), suggesting similarities in exopolysaccharide composition. Three-ply aspen panels prepared with fermentation residues (FR) displayed better shear strength and wood failure under dry conditions than following a vacuum/pressure/soak/dry treatment, but adhesive properties were inferior to those prepared with conventional phenol-formaldehyde (PF) adhesives. However, panels prepared by incorporating the R. albus 7 FR into PF formulation, at 73% by weight of the total adhesive, exhibited shear strength and wood failure similar to that obtained with PF adhesive alone. Use of residues from fermentations by these bacteria as components of adhesives may add value to biomass fermentations aimed primarily at producing ethanol and other chemical products.

Adhesives↗

Changes in dopamine D(2)-receptor modulation of the hypoxic ventilatory response with chronic hypoxia.

Modulation of the hypoxic ventilatory response (HVR) by dopamine D(2)-receptors (D(2)-R) in the carotid body (CB) and central nervous system (CNS) are hypothesized to contribute to ventilatory acclimatization to hypoxia. We tested this with blockade of D(2)-R in the CB or CNS in conscious rats after 0, 2 and 8 days of hypoxia. On day 0, CB D(2)-R blockade significantly increased VI and frequency (fR) in hyperoxia (FI(O(2))=0.30), but not hypoxia (FI(O(2))=0.10). CNS D(2)-R blockade significantly decreased fR in hypoxia only. On day 2, neither CB nor CNS D(2)-R blockade affected VI or fR. On day 8, CB D(2)-R blockade significantly increased hypoxic VI and fR. CNS D(2)-R blockade significantly decreased hypoxic VI and fR. CB and CNS D(2)-R modulation of the HVR decreased after 2 days of hypoxia, but reappeared after 8 days. Changes in the opposing effects of CB and CNS D(2)-R on the HVR during chronic hypoxia cannot completely explain ventilatory acclimatization in rats.

Animals↗

Parametric analysis of cocaine self-administration under a progressive-ratio schedule in rhesus monkeys.

The present study was designed to investigate parameters and quantitative analysis of cocaine self-administration under a progressive-ratio (PR) schedule of reinforcement, with the goal of enhancing the resolution of PR schedules for measuring reinforcing efficacy. Six rhesus monkeys were prepared with chronic intravenous catheters and trained to self-administer cocaine under a PR schedule. The schedule consisted of five components, each made up of four trials (i.e., 20 trials total). Each trial within a component had the same response requirement. Three initial response requirements were tested: fixed-ration (FR) 60, FR 120 and FR 240. The response requirements doubled in successive components to a maximum of FR 960, FR 1920 or R 3840, respectively, in the fifth component. A trial ended with an injection or the expiration of a 12- or 24-min limited hold (LH). The inter-trial interval (ITI) was 15 or 30 min. Four dependent measures were assessed: break point (last FR completed), injections/session, responses/session and response rate (responses/s). For the three initial FRs, the break point, number of injections/session, responses/session and rate increased with dose of cocaine (0.013-0.1 mg/kg per injection) at both ITI/LH values. At the ITI15/LH12, responding decreased at higher doses, i.e., the dose-response functions were biphasic. In contrast, at the ITI30/LH24, responding reached an asymptote at higher doses. In general, cocaine maintained significantly higher break points, injections/session, responses/session and rate at ITI30/LH24 than at ITI15/LH12. However, at both ITI/LHs, as initial FR was increased, injections/session at the higher doses decreased while break point, total responses/session and rate did not change. A ceiling on performance, as assessed by break point, total responses/session and response rate, may have limited the number of cocaine injections an animal could take in a session. The results of this study indicate that optimal conditions for measuring the reinforcing efficacy of cocaine were obtained at the longer ITI/LH and at initial FRs above 60.

Animals↗

Serological relatedness of the ribonucleic acid-containing coliphages.

The serological relationship of the ribonucleic acid (RNA)-containing coliphages MS-2, M-12, R-17, f(2), beta, fr, f(4), and Qbeta was determined. Antisera against MS-2, R-17, f(2), fr, and Qbeta neutralized the infectivity of all of these RNA phages to varying degrees. Although each phage was serologically distinct, the antisera cross-reacted with certain phages to approximately the same degree, indicating the antigenic relationship of the coat proteins of these phages. Adsorption of anti-MS-2 sera with varying concentrations of all of the phages demonstrated that these viruses contain similar yet unique antigenic determinants. It is suggested that these RNA phages are mutants of two related phages rather than of the same phage.

Antigen-Antibody Reactions↗

Co-action between phytochrome B and HY4 in Arabidopsis thaliana.

A combination of physiological and genetic approaches was used to investigate whether phytochromes and blue light (BL) photoreceptors act in a fully independent manner during photomorphogenesis of Arabidopsis thaliana (L.) Heynh. Wild-type seedlings and phyA, phyB and hy4 mutants were daily exposed to 3 h BL terminated with either a red light (R) or a far-red light (FR) pulse. In wild-type and phyA-mutant seedlings, BL followed by an R pulse inhibited hypocotyl growth and promoted cotyledon unfolding. The effects of BL were reduced if exposure to BL was followed by an FR pulse driving phytochrome to the R-absorbing form (Pr). In the wild type, the effects of R versus FR pulses were small in seedlings not exposed to BL. Thus, maximal responses depended on the presence of both BL and the FR-absorbing form of phytochrome (Pfr) in the subsequent dark period. Impaired responses to BL and to R versus FR pulses were observed in phyB and hy4 mutants. Simultaneous irradiation with orange light indicated that BL, perceived by specific BL photoreceptors (i.e. not by phytochromes), required phytochrome B to display a full effect. These results indicate interdependent co-action between phytochrome B and BL photoreceptors, particularly the HY4 gene product. No synergism between phytochrome A (activated by continuous or pulsed FR) and BL photoreceptors was observed.

Arabidopsis↗

Twilight-zone and canopy shade induction of the Athb-2 homeobox gene in green plants.

We present evidence that a novel phytochrome (other than phytochromes A and B, PHYA and PHYB) operative in green plants regulates the "twilight-inducible" expression of a plant homeobox gene (Athb-2). Light regulation of the Athb-2 gene is unique in that it is not induced by red (R)-rich daylight or by the light-dark transition but is instead induced by changes in the ratio of R to far-red (FR) light. These changes, which normally occur at dawn and dusk (end-of-day FR), also occur during the daytime under the canopy (shade avoidance). By using pure light sources and phyA/phyB null mutants, we demonstrated that the induction of Athb-2 by changes in the R/FR ratio is mediated for the most part by a novel phytochrome operative in green plants. Furthermore, PHYB plays a negative role in repressing the accumulation of Athb-2 mRNA in the dark and a minor role in the FR response. The strict correlation of Athb-2 expression with FR-induced growth phenomena suggests a role for the Athb-2 gene in mediating cell elongation. This interpretation is supported by the finding that the Athb-2 gene is expressed at high levels in rapidly elongating etiolated seedlings. Furthermore, as either R or FR light inhibits cell elongation in etiolated tissues, they also down-regulate the expression of Athb-2 mRNA. Thus, these data support the notion that changes in light quality perceived by a novel phytochrome regulate plant development through the action of the Athb-2 homeobox gene.

Journal Article↗

Modulation of carotenoid biosynthesis during tomato fruit ripening through phytochrome regulation of phytoene synthase activity.

The accumulation of carotenoids greatly influences the quality of ripe tomato (Solanum lycopersicum) fruit because these compounds contribute to their color and functional food value. The regulatory properties and gene expression of phytoene synthase (PSY), a key enzyme involved in carotenoid biosynthesis, was analyzed in tomato fruit. PSY activity was detected in the soluble fraction showing a time- and a protein-dependent increase in the formation of phytoene from geranylgeranyl pyrophosphate (GGPP). The enzyme was stimulated by Mg(2+) and ATP, and was inhibited by Tween 20 and Triton X-100. The enzyme followed typical Michaelis-Menten kinetics with increasing GGPP. During in vivo studies, pericarp discs from breaker stage tomatoes were ripened in darkness (D), or D interrupted by daily pulses of red (R) light, or R followed by far red (FR) light. After 14 days incubation, R-treated discs had accumulated 12 mg carotenoids/100 g fresh weight; nearly a 50% increase over D- and R/FR-treated discs. This R/FR reversibility of carotenoid accumulation was also observed in PSY activity 8 days post breaker, where it showed peak activity. However, this R/FR regulation of PSY activity was not reflected in PSY1 transcript levels, suggesting that PSY may be subject to post-translational regulation.

Adenosine Triphosphate↗

Different phototransduction kinetics of phytochrome A and phytochrome B in Arabidopsis thaliana.

The kinetics of phototransduction of phytochrome A (phyA) and phytochrome B (phyB) were compared in etiolated Arabidopsis thaliana seedlings. The responses of hypocotyl growth, cotyledon unfolding, and expression of a light-harvesting chlorophyll a/b-binding protein of the photosystem II gene promoter fused to the coding region of beta-glucuronidase (used as a reporter enzyme) were mediated by phyA under continuous far-red light (FR) and by phyB under continuous red light (R). The seedlings were exposed hourly either to n min of FR followed by 60 minus n min in darkness or to n min of R, 3 min of FR (to back-convert phyB to its inactive form), and 57 minus n min of darkness. For the three processes investigated here, the kinetics of phototransduction of phyB were faster than that of phyA. For instance, 15 min R h-1 (terminated with a FR pulse) were almost as effective as continuous R, whereas 15 min of FR h-1 caused less than 30% of the effect of continuous FR. This difference is interpreted in terms of divergence of signal transduction pathways downstream from phyA and phyB.

Arabidopsis↗

Phytochrome-mediated agravitropism in Arabidopsis hypocotyls requires GIL1 and confers a fitness advantage.

Plants use specialized photoreceptors to detect the amount, quality, periodicity and direction of light and to modulate their growth and development accordingly. These regulatory light signals often interact with other environmental cues. Exposure of etiolated Arabidopsis seedlings to red (R) or far-red (FR) light causes hypocotyls to grow in random orientations with respect to the gravitational vector, thus overcoming the signal from gravity to grow upwards. This light response, mediated by either phytochrome A or phytochrome B, represents a prime example of cross-talk between environmental signalling systems. Here, we report the isolation the mutant gil1 (for gravitropic in the light) in which hypocotyls continue to grow upwards after exposure of seedlings to R or FR light. The gil1 mutant displays no other phenotypic alterations in response to gravity or light. Cloning of GIL1 has identified a novel gene that is necessary for light-dependent randomization of hypocotyl growth orientation. Using gil1, we have demonstrated that phytochrome-mediated randomization of Arabidopsis hypocotyl orientation provides a fitness advantage to seedlings developing in patchy, low-light environments.

Amino Acid Sequence↗

Phytochrome Regulation of the Response to Exogenous Gibberellins by Epicotyls of Vigna sinensis.

The elongation rate of cowpea epicotyls from whole cowpea (Vigna sinensis) seedlings and derooted and debladed plants (explants) increased after the main light period (8-hour duration) was extended with either continuous low intensity tungsten light or brief (5 minutes) far-red (FR) irradiation. This end-of-day FR effect was reversed by red (R) irradiation suggesting the involvement of phytochrome. These results confirm and extend those obtained previously with other species. Localization studies indicate the epicotyl to be the site of the photoreceptor. Treatment of cowpea seedlings with paclobutrazol, a gibberellin (GA) biosynthetic inhibitor, abolished the FR promoted epicotyl elongation, indicating a role for GAs in this process. There was no significant difference in epicotyl elongation rates of R plus FR irradiated explants treated with GA(1) or GA(20) and R irradiated explants treated with GA(1). However, R irradiation inhibited subsequent epicotyl elongation of GA(20) treated explants. Moreover, the observation, using GC-MS, that GA(1) and GA(20) are native GAs in cowpea lends support to the concept that phytochrome may control the conversion of endogenous GA(20) to GA(1) in cowpea.

Journal Article↗

Phytochrome-like responses in Euglena: A low fluence response that reorganizes the spectral dependence of the high irradiance response in long-day photoperiodic induction of cell division.

Irradiance spectra change spatiotemporally, and angiosperms adapt accordingly, mainly through phytochromes. This study challenges the long-held belief that the flagellated alga Euglena gracilis lacks phytochromes and is therefore unaffected by spectral changes. We photoautotrophically cultured the alga under continuous light (LL), then transferred it to darkness. After about 26h in darkness, different irradiations for 3h enabled cell division in dark-arrested G2 cells evoking a high-irradiance response (HIR). The spectral characteristics of the irradiation during the LL period (pre-irradiation) defined the spectral sensitivity in the subsequent dark period. LL with light rich in the red spectrum led to a HIR to the red spectrum (R-HIR), whereas light rich in the far-red spectrum (FR) led to a FR-HIR. Finishing the period of pre-irradiation consisting of continuous cool-white fluorescent light (rich in R) by a FR pulse enhanced the characteristics of the FR-HIR 26h later. By contrast, a R pulse given at the end of the pre-irradiation rich in FR potentiated the R-HIR. The effects were completely photoreversible between R and FR with critical fluences of about 2mmolm(-2), satisfying the classic diagnostic feature of phytochromes. The action spectrum of the FR effect at the end of pre-irradiation consisting of continuous cool-white fluorescent light (rich in R) had a main peak at 740nm and a minor peak at 380nm, whereas antagonization of the FR effect had a main peak at 640nm and a minor peak at 480nm. Wavelengths of 610 and 670nm appeared in both spectra. We also demonstrated the photoreversibility of 380/640, 480/740, and (610 and 670)/(640 and 740) nm. We conclude that Euglena displays phytochrome-like responses similar to the 'shade avoidance' and 'end-of-day FR' effects reported in angiosperms.

Animals↗

Probing the molecular structure of phytochrome with immobilized Cibacron blue 3GA and blue dextran.

Phytochrome was shown to bind to agarose-immobilized Cibacron blue 3GA. A higher affinity of the dye for the putative biologically active form (P(fr)) than the inactive form (P(r)) of phytochrome was observed. Effective general eluants of P(r) included 40% (vol/vol) ethylene glycol, 1% Triton X-100, or 0.5 M potassium iodide. Increasing ionic strength (1 M KCl) did not effectively elute phytochrome. Of the natural cofactors that have been reported to be analogues of the dye, NAD(+), NADH, NADP(+), cyclic AMP, AMP, ADP, ATP, and coenzyme A at a concentration of 10 mM would not elute phytochrome. At 10 mM, FMN eluted at least 65% of the bound P(r), whereas FAD eluted 40%. Blue dextran/agarose was found to bind P(fr) but exhibited essentially no affinity for P(r). Phytochrome that was bound as P(fr) could be subsequently released by photoconversion to P(r). Because of the high degree of selectivity that the blue dye and its dextran conjugate exhibit for the P(fr) form of phytochrome and the known property of the dye as an analogue of natural ligands of proteins, it is proposed that the dye and its conjugate may be used as probes of a binding domain on the phytochrome protein that is important to its biochemical action.

Journal Article↗