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11. |
Cholesterol biosynthesis in dermal fibroblasts from patients with metabolic disorders of peroxisomal origin |
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European Journal of Clinical Investigation,
Volume 25,
Issue 1,
1995,
Page 59-67
E. MALLE,
K. OETTL,
W. SATTLER,
G. HOEFLER,
G. M. KOSTNER,
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摘要:
Abstract.As peroxisomes possess some of the integral enzymes for cholesterol biosynthesis, the role of these organelles in cholesterol formation was studied in dermal fibroblasts with three types of peroxisomal defect: group I, characterized by the absence of intact peroxisomes (neonatal adrenoleukodystrophy, cere‐brohepatorenal syndrome of Zellweger); group II, showing impaired activity of a single peroxisomal enzyme (X‐linked adrenoleukodystrophy, adrenomye‐loneuropathy); and group III, defective in more than one peroxisomal enzyme (rhizomelic chondrodysplasia punctata). Cells were incubated with three different radioactive precursors, namely [14C]‐octanoate, [14C]‐acetate, and [3H]‐mevalonate, and incorporation of these radiolabels into cholesterol was determined. All fibroblasts with peroxisomal defects were able to form cholesterol at concentrations comparable or higher than those in controls dependent on the radioactive substrate. Binding properties (KDand bmaxvalues) of LDL to fibroblasts with peroxisomal defects and downregulation of intracellular cholesterol biosynthesis were similar to those found in fibroblasts from normolipidaemic controls, but different to those observed in LDL‐receptor negative fibroblasts. As our studies revealed that cholesterol biosynthesis is not impaired in fibroblasts from patients with metabolic disorders of peroxisomal origin, we conclude that peroxisomes play little or no role in the pathway of cholesterol synthesis beyond mevalonate. In earlier steps of the cholesterol synthesis pathway, peroxisomal and mitochondrial defects in parallel may alter cholesterol synthes
ISSN:0014-2972
DOI:10.1111/j.1365-2362.1995.tb01527.x
出版商:Blackwell Publishing Ltd
年代:1995
数据来源: WILEY
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12. |
Assessment of interferon cardiotoxicity with quantitative radionuclide angiocardiography |
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European Journal of Clinical Investigation,
Volume 25,
Issue 1,
1995,
Page 68-70
M. SARTORI,
S. ANDORNO,
G. LA TERRA,
G. POZZOLI,
M. RUDONI,
G. M. SACCHETTI,
E. INGLESE,
M. AGLIETTA,
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PDF (256KB)
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摘要:
Abstract.Three different types of cardiovascular sequelae attributed to interferon therapy have been reported: arrhythmia, ischaemic heart disease and cardiomyopathy. We evaluated the left ventricular ejection fraction (LVEF) during alpha interferon therapy (3 MU administered subcutaneously three times a week for 6 months) in 11 patients with chronic viral hepatitis. LVEF was within the normal range in all patients (mean value ± SD 64.6 ± 10.7%) before interferon was started, but decreased after 1 month of therapy (mean value± SD 59.7 ± 8.3%) (P= 0.015). An LVEF reduction of more than 10% was observed in five of the 11 patients. Three months after therapy was stopped, nine of the 11 patients showed an LVEF close to the pre‐treatment level (mean value ± SD 62.1 ± 8.3%). In our patients with chronic C hepatitis, low subcutaneous doses of interferon alpha often decreased the LVEF. It is not clear whether this finding is due to the direct effect of interferon on cardiac cells, or to the peripheral vascular effects of the drug. As LVEF reduction could be critical in patients with previously reduced myocardial contractility, our results further highlight the need for careful cardiac analysis before starting interferon
ISSN:0014-2972
DOI:10.1111/j.1365-2362.1995.tb01528.x
出版商:Blackwell Publishing Ltd
年代:1995
数据来源: WILEY
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