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  • 1990-1994  (4)
  • cholesterol  (3)
  • Apolipoprotein B-48  (1)
  • De novo design  (1)
  • Chemical Engineering
  • Nuclear reaction
  • Nuclear reactions
Materialart
Erscheinungszeitraum
Jahr
Schlagwörter
  • 1
    ISSN: 1432-0428
    Schlagwort(e): Type 2 (non-insulin-dependent) diabetes mellitus ; LDL ; cholesterol ; esterification ; glycosylation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary This study investigates the relationship between Type 2 (non-insulin-dependent) diabetes mellitus and hypercholesterolaemia with regard to delivery of cholesterol to cells and regulation of endogenous cholesterol synthesis. The ability of LDL, from hypercholesterolaemic and Type 2 diabetic patients, to suppress cellular cholesterologenesis and to enhance mitogen-stimulated lymphocyte proliferation was compared. Cholesterol synthesis was estimated by measuring [14C]-acetate incorporation into cholesterol and lymphocyte proliferation was assessed by [3H]-thymidine incorporation into mitogen-stimulated normal lymphocytes. The results indicate that LDL from both Type 2 diabetic patients in poor metabolic control and hypercholesterolaemic patients was significantly less effective (p 〈 0.001) than LDL from non-diabetic normocholesterolaemic subjects in suppressing cholesterol synthesis in lymphocytes. LDL from all hypercholesterolaemic patients enhanced lymphocyte proliferation to a greater extent than LDL from normocholesterolaemic subjects and this effect was significantly increased using LDL from Type 2 diabetic, hypercholesterolaemic patients. Both suppression of [14C]-acetate incorporation and enhancement of [3H]-thymidine uptake could be related to an increased esterified/free cholesterol ratio in the LDL particle. The fact that cholesterol synthesis and cell proliferation were markedly altered by the above changes in LDL composition suggests a mechanism for cellular cholesterol accumulation in the Type 2 diabetic patient, even in the absence of elevated serum cholesterol levels.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    Digitale Medien
    Digitale Medien
    Springer
    Diabetologia 37 (1994), S. 1259-1264 
    ISSN: 1432-0428
    Schlagwort(e): Key words Apolipoprotein B-48 ; triglyceride-rich lipoproteins ; NIDDM ; cholesterol ; triglyceride.
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The intestine is a major site of cholesterol synthesis and produces apolipoprotein B-48, which is critical for intestinal cholesterol absorption and secretion. The purpose of this study was to examine postprandial changes in apolipoprotein B-48 in diabetes. Six non-insulin-dependent diabetic patients and six non-diabetic control subjects were given a high-fat meal (1300 kcal) and blood samples were taken pre- and postprandially, from which the triglyceride-rich lipoprotein fraction was isolated by ultracentrifugation (density 〈 1.006 g/ml). Apolipoprotein B-48 was separated on 4–15 % gradient gels and quantified as a percentage of the fasting concentration by densitometric scanning. Total protein, triglyceride and cholesterol in the triglyceride-rich lipoprotein fraction, blood glucose, and serum insulin were also measured. Diabetic patients exhibited a postprandial triglyceride-rich apolipoprotein B-48 profile significantly different from that of control subjects (p 〈 0.05). The triglyceride and total protein concentration in the triglyceride-rich lipoprotein fraction mirrored the post-prandial profile and apolipoprotein B-48 in both groups. Significantly different patterns for triglyceride (p 〈 0.02) and total protein (p 〈 0.05) following the fat-rich meal were observed in the two groups. Fasting and postprandial triglyceride-rich lipoprotein cholesterol and total apolipoprotein B were significantly higher in diabetic patients than in control subjects (p 〈 0.05). Since apolipoprotein B-48 is the structural protein of intestinally-derived lipoprotein particles, these studies suggest an abnormality in intestinal lipoprotein metabolism in diabetes. [Diabetologia (1994) 37: 1259–1264]
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 3
    Digitale Medien
    Digitale Medien
    Springer
    Diabetologia 37 (1994), S. 1259-1264 
    ISSN: 1432-0428
    Schlagwort(e): Apolipoprotein B-48 ; triglyceride-rich lipoproteins ; NIDDM ; cholesterol ; triglyceride
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The intestine is a major site of cholesterol synthesis and produces apolipoprotein B-48, which is critical for intestinal cholesterol absorption and secretion. The purpose of this study was to examine postprandial changes in apolipoprotein B-48 in diabetes. Six non-insulin-dependent diabetic patients and six non-diabetic control subjects were given a high-fat meal (1300 kcal) and blood samples were taken pre- and postprandially, from which the triglyceride-rich lipoprotein fraction was isolated by ultracentrifugation (density〈1.006 g/ml). Apolipoprotein B-48 was separated on 4–15% gradient gels and quantified as a percentage of the fasting concentration by densitometric scanning. Total protein, triglyceride and cholesterol in the triglyceride-rich lipoprotein fraction, blood glucose, and serum insulin were also measured. Diabetic patients exhibited a postprandial triglyceride-rich apolipoprotein B-48 profile significantly different from that of control subjects (p〈0.05). The triglyceride and total protein concentration in the triglyceride-rich lipoprotein fraction mirrored the post-prandial profile and apolipoprotein B-48 in both groups. Significantly different patterns for triglyceride (p〈0.02) and total protein (p〈0.05) following the fat-rich meal were observed in the two groups. Fasting and postprandial triglyceride-rich lipoprotein cholesterol and total apolipoprotein B were significantly higher in diabetic patients than in control subjects (p〈0.05). Since apolipoprotein B-48 is the structural protein of intestinally-derived lipoprotein particles, these studies suggest an abnormality in intestinal lipoprotein metabolism in diabetes.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 4
    Digitale Medien
    Digitale Medien
    Springer
    Journal of computer aided molecular design 7 (1993), S. 127-153 
    ISSN: 1573-4951
    Schlagwort(e): Artificial intelligence ; De novo design ; Molecule design ; Enzyme inhibitors
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Summary SPROUT is a new computer program for constrained structure generation that is designed to generate molecules for a range of applications in molecular recognition. It uses artificial intelligence techniques to moderate the combinatorial explosion that is inherent in structure generation. The program is presented here for the design of enzyme inhibitors. Structure generation is divided into two phases: (i) primary structure generation to produce molecular graphs to fit the steric constraints; and (ii) secondary structure generation which is the process of introducing appropriate functionality to the graphs to produce molecules that satisfy the secondary constraints, e.g., electrostatics and hydrophobicity. Primary structure generation has been tested on two enzyme receptor sites; the p-amidino-phenyl-pyruvate binding site of trypsin and the acetyl pepstatin binding site of HIV-1 protease. The program successfully generates structures that resemble known substrates and, more importantly, the predictive power of the program has been demonstrated by its ability to suggest novel structures.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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