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  • Oxford University Press (OUP)  (9)
  • 1
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 1993
    In:  Clinical Chemistry Vol. 39, No. 6 ( 1993-06-01), p. 980-985
    In: Clinical Chemistry, Oxford University Press (OUP), Vol. 39, No. 6 ( 1993-06-01), p. 980-985
    Abstract: We administered reduced L-homocysteine perorally (67 mumol/kg of body wt) to 12 healthy subjects and injected the same dose into one person, and determined the kinetics of the alterations in reduced, oxidized, and protein-bound concentrations of homocysteine, cysteine, and cysteinylglycine. After oral intake, reduced homocysteine increased rapidly (tmax & lt; or = 15 min), reaching concentrations [3.97 (SD 2.99) mumol/L] 20-fold above fasting values, and then declined towards the normal concentration within 2 h. There was a similar increase in reduced cysteine and a moderate increase in reduced cysteinylglycine. During this response, we observed a positive correlation between the reduced/total ratio for homocysteine and cysteine. When homocysteine was injected, the increase in reduced homocysteine preceded the increase in reduced cysteine by about 3 min. After oral loading, oxidized homocysteine showed a transient increase (tmax = 30 min) that lagged behind the increase of reduced homocysteine. Oxidized cysteine and cysteinylglycine were stable or decreased slightly. Protein-bound homocysteine increased the least rapidly after homocysteine administration (tmax = 1-2 h), and returned to normal values slowly. Changes in protein-bound homocysteine essentially mirrored a concurrent decrease in protein-bound cysteine, suggesting displacement of bound cysteine. These data show that plasma homocysteine has a pronounced, direct effect on the redox status and protein binding of other plasma thiol components. Such effects should be recognized when studying the mechanisms behind the atherogenic effect of increased plasma homocysteine.
    Type of Medium: Online Resource
    ISSN: 0009-9147 , 1530-8561
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 1993
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  • 2
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 1992
    In:  Clinical Chemistry Vol. 38, No. 7 ( 1992-07-01), p. 1316-1321
    In: Clinical Chemistry, Oxford University Press (OUP), Vol. 38, No. 7 ( 1992-07-01), p. 1316-1321
    Abstract: We used a newly developed procedure to determine reduced, oxidized, and protein-bound forms of homocysteine, cysteine, cysteinylglycine, and glutathione to measure the plasma concentrations of these species during methionine loading in six young healthy men with normal fasting concentrations of plasma homocysteine and cysteine. The methionine loading induced a transient increase in total homocysteine, which peaked after approximately 6-8 h. All six subjects showed a concurrent significant increase in reduced homocysteine and cysteine, which peaked 2 h after loading, and a rapid decrease in protein-bound cysteine and cysteinylglycine. The concentration of reduced cysteinylglycine was not altered. Plots of protein-bound cysteine and cysteinylglycine vs total homocysteine formed hysteretic loops, showing a time-dependent relation between these analytes. After the initial decrease, protein-bound cysteine and cysteinylglycine showed a slight, transient increase. From 12 to 24 h after loading, protein-bound cysteine approached preloading concentrations in two subjects and declined further in four subjects. The response pattern was similar for cysteine and cysteinylglycine in each subject. Simple displacement could not account for these effects, which suggests that plasma homocysteine may affect the disposition of other thiols through complex mechanisms. The presence of reduced homocysteine and the dynamic relation that exists between homocysteine, cysteine, and related compounds in plasma should be taken into account when evaluating plasma homocysteine as an indicator or causative agent of human disease.
    Type of Medium: Online Resource
    ISSN: 0009-9147 , 1530-8561
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 1992
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  • 3
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2001
    In:  Clinical Chemistry Vol. 47, No. 8 ( 2001-08-01), p. 1505-1505
    In: Clinical Chemistry, Oxford University Press (OUP), Vol. 47, No. 8 ( 2001-08-01), p. 1505-1505
    Type of Medium: Online Resource
    ISSN: 0009-9147 , 1530-8561
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2001
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  • 4
    In: Molecular Biology and Evolution, Oxford University Press (OUP), Vol. 37, No. 4 ( 2020-04-01), p. 1100-1113
    Abstract: The adaptive radiation of cichlid fishes in East African Lake Malawi encompasses over 500 species that are believed to have evolved within the last 800,000 years from a common founder population. It has been proposed that hybridization between ancestral lineages can provide the genetic raw material to fuel such exceptionally high diversification rates, and evidence for this has recently been presented for the Lake Victoria region cichlid superflock. Here, we report that Lake Malawi cichlid genomes also show evidence of hybridization between two lineages that split 3–4 Ma, today represented by Lake Victoria cichlids and the riverine Astatotilapia sp. “ruaha blue.” The two ancestries in Malawi cichlid genomes are present in large blocks of several kilobases, but there is little variation in this pattern between Malawi cichlid species, suggesting that the large-scale mosaic structure of the genomes was largely established prior to the radiation. Nevertheless, tens of thousands of polymorphic variants apparently derived from the hybridization are interspersed in the genomes. These loci show a striking excess of differentiation across ecological subgroups in the Lake Malawi cichlid assemblage, and parental alleles sort differentially into benthic and pelagic Malawi cichlid lineages, consistent with strong differential selection on these loci during species divergence. Furthermore, these loci are enriched for genes involved in immune response and vision, including opsin genes previously identified as important for speciation. Our results reinforce the role of ancestral hybridization in explosive diversification by demonstrating its significance in one of the largest recent vertebrate adaptive radiations.
    Type of Medium: Online Resource
    ISSN: 0737-4038 , 1537-1719
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2024221-9
    SSG: 12
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  • 5
    In: Carcinogenesis, Oxford University Press (OUP), Vol. 12, No. 2 ( 1991), p. 241-247
    Type of Medium: Online Resource
    ISSN: 0143-3334 , 1460-2180
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 1991
    detail.hit.zdb_id: 1474206-8
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  • 6
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 1995
    In:  Clinical Chemistry Vol. 41, No. 8 ( 1995-08-01), p. 1164-1170
    In: Clinical Chemistry, Oxford University Press (OUP), Vol. 41, No. 8 ( 1995-08-01), p. 1164-1170
    Abstract: We constructed a fully automated assay for the cobalamin-dependent enzyme methylmalonyl coenzyme A (CoA) mutase. The assay involves preincubation of the enzyme with adenosylcobalamin, incubation with substrate, termination of the reaction by adding trichloroacetic acid, filtration to remove precipitated protein, and finally analysis of the filtrate (containing methylmalonyl CoA and the product succinyl CoA) by HPLC. These steps were carried out by an inexpensive programmable autosampler equipped with thermostated sample racks and mobile disposable extraction column racks used here as a sample filtering device. A central element in the developmental work was to measure stability of reagents, enzyme, and product against the storage conditions during unattended analysis and the time table of the program. We evaluated the performance of the method by measuring methylmalonyl CoA mutase activity in rat liver, human fibroblasts, and human glioma cells. The within-run imprecisions (CV) were 2-10% for measuring enzyme activity in 20 replicate samples of a homogenate (test of the automated assay), and 7-12% for measuring enzyme activity in homogenates from 20 culture dishes (test of the total procedure). The method allows the unattended analysis of 56 samples per 24 h. This strategy for automation may be easily adapted for other enzyme assays.
    Type of Medium: Online Resource
    ISSN: 0009-9147 , 1530-8561
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 1995
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  • 7
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 1989
    In:  Clinical Chemistry Vol. 35, No. 9 ( 1989-09-01), p. 1921-1927
    In: Clinical Chemistry, Oxford University Press (OUP), Vol. 35, No. 9 ( 1989-09-01), p. 1921-1927
    Abstract: Homocysteine exists in human plasma as various (mixed) disulfides. Most plasma homocysteine (about 70%) is protein bound, probably via a disulfide bond to albumin, whereas homocysteine-cysteine mixed disulfide is the predominating form in the free fraction. We here present a method for the determination of total homocysteine, which includes both fractions. Plasma was initially treated with sodium borohydride to reduce the disulfide bonds, and the liberated thiols were derivatized with monobromobimane. The derivatized sample, still containing the plasma proteins, was injected onto a strong cation-exchange column, from which the homocysteine derivative was directed by column switching into a cyclohexyl silica (CH) column. The homocysteine derivative was top-concentrated on the CH column, then rapidly eluted with a steep gradient of methanol. Both the derivatization procedure and chromatography were performed with a combined sample processor and sample injector from Gilson (Model 232-401). Within-run and between-run precision (CV) was less than 4%, and the detection limit of 0.2 pmol was sufficiently low for monitoring homocysteine in plasma. We verified the assay against two established manual methods for the determination of total homocysteine in plasma. This, the first fully automated assay for total plasma homocysteine, allows the unattended analysis of 70 samples per 24 h.
    Type of Medium: Online Resource
    ISSN: 0009-9147 , 1530-8561
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 1989
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  • 8
    In: Clinical Chemistry, Oxford University Press (OUP), Vol. 46, No. 3 ( 2000-03-01), p. 385-391
    Abstract: Background: Increased concentrations of both plasma total homocysteine and copper are separately associated with cardiovascular disease. Correlations between plasma total homocysteine, trace elements, and vitamins in patients with peripheral vascular disease have not been investigated. Methods: The concentrations of trace elements in plasma were determined by the multielement analytical technique of total-reflection x-ray fluorescence spectrometry. Plasma total homocysteine was determined by HPLC. Results: In the univariate and multivariate regression analyses, copper was positively correlated with plasma total homocysteine in all subjects (coefficient ± SE, 0.347 ± 0.113; P = 0.0026 and coefficient ± SE, 0.422 ± 0.108; P = 0.0002, respectively), and in patients with peripheral vascular disease (coefficient ± SE, 0.370 ± 0.150; P = 0.016; and coefficient ± SE, 0.490 ± 0.151; P = 0.0025, respectively). Correlation between copper and plasma total homocysteine was not detected in healthy control subjects. The concentration of calcium in plasma (67.5 vs 80.8 μg/g) was significantly lower in the patients than in the control subjects (P = 0.02). When the patients were divided into groups, the patients with suprainguinal lesions had significantly higher copper concentrations (P = 0.04) and significantly lower selenium and calcium concentrations (P = 0.01 and 0.008, respectively) than the healthy subjects. Patients had higher concentrations of autoantibodies against oxidized LDL and concentrations of thiobarbituric acid-reactive substance than the healthy subjects (P & lt;0.0001 and P = 0.001, respectively). The concentrations of plasma total homocysteine and α-tocopherol were significantly higher, and the concentrations of vitamin B6 and β-carotene were lower in the patients than the healthy subjects. Conclusion: Our findings suggest that the atherogenicity of homocysteine may be related to copper-dependent interactions.
    Type of Medium: Online Resource
    ISSN: 0009-9147 , 1530-8561
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2000
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  • 9
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 1991
    In:  JNCI Journal of the National Cancer Institute Vol. 83, No. 15 ( 1991-08-07), p. 1092-1098
    In: JNCI Journal of the National Cancer Institute, Oxford University Press (OUP), Vol. 83, No. 15 ( 1991-08-07), p. 1092-1098
    Type of Medium: Online Resource
    ISSN: 0027-8874 , 1460-2105
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 1991
    detail.hit.zdb_id: 2992-0
    detail.hit.zdb_id: 1465951-7
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