Abstract:
BACKGROUND:In mutations of the low-density lipoprotein (LDL) receptor gene, the defect of internalization is caused by a mutation in the cytoplasmic domain of the receptor linked with exons 17 and 18, and the O-linked sugar domain linked with exon 15 has been speculated not to affect the function of the receptor. Here, we describe a novel mutation of the O-linked sugar domain of the LDL receptor gene, designated familial hypercholesterolaemia (FH)-Mishima with Japanese pedigree, which resembles but still differs from classical defective internalization cases. METHODS:LDL metabolism was examined in cultured skin fibroblasts from patients. Immunoprecipitation and immunohistochemical techniques were applied for the detection of the receptor protein size and distribution. Screening of the mutant exon(s) of the LDL receptor gene was performed using the polymerase chain reaction-single-strand conformation polymorphism technique (PCR-SSCP), and sequencing of the mutated alleles was carried out using the dideoxy chain termination method. RESULTS:LDL-binding activity at 4 degrees C in skin fibroblasts from patients was similar to normal, but that at 37 degrees C with the ligand decreased time dependently and was lost at 6 h, resulting in the defect of internalization and degradation of LDL. The receptor protein on the cell surface was detected at 4 degrees C by IgG-C7, an anti-LDL receptor antibody, but was not detected after incubation with LDL at 37 degrees C. The size of the receptor was 112 kD as determined by immunoprecipitation analysis. A deletion of two nucleotides in exon 15 was detected in the DNA sequence of the LDL receptor gene. The deletion results in a shift of the reading frame after Thr-713 of the mutant and makes a stop codon at amino acid 759. CONCLUSION:Deletion of the two nucleotides caused novel amino acid sequences after the O-linked sugar domain, which has the ability of sorting on the cell membrane at 4 degrees C, but not at 37 degrees C in vivo, resulting in the complete cessation of activity of the LDL receptor.
journal_name
Eur J Clin Investjournal_title
European journal of clinical investigationauthors
Tashiro J,Endo M,Bujo H,Shinomiya M,Morisaki N,Saito Ydoi
10.1046/j.1365-2362.1998.00332.xsubject
Has Abstractpub_date
1998-09-01 00:00:00pages
712-9issue
9eissn
0014-2972issn
1365-2362journal_volume
28pub_type
杂志文章abstract::Factors affecting erythrocyte K+ content and plasma electrolytes during light exercise were examined in 8 normal subjects and 27 patients with chronic obstructive lung disease. The patients were classified into bronchitis, emphysema and intermediate groups. Arterial blood was obtained during rest, after 2, 5, and 7 mi...
journal_title:European journal of clinical investigation
pub_type: 杂志文章
doi:10.1111/j.1365-2362.1975.tb00469.x
更新日期:1975-09-12 00:00:00
abstract:BACKGROUND:To compare the administration of furosemide with placebo on the subjective perception of dyspnoea in patients with acute pulmonary oedema because of hypertensive crisis. Design Randomized, controlled and double-blinded clinical trial. SETTING:Municipal emergency medical service system and university-based ...
journal_title:European journal of clinical investigation
pub_type: 杂志文章,随机对照试验
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abstract:BACKGROUND:Clusterin (Apolipoprotein J), a plasma protein with cytoprotective and complement-inhibiting activities, localizes in the infarcted heart during myocardial infarction (MI). Recently, we have shown a protective effect of exogenous clusterin in vitro on ischaemically challenged cardiomyocytes independent of co...
journal_title:European journal of clinical investigation
pub_type: 杂志文章
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更新日期:2010-10-01 00:00:00
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journal_title:European journal of clinical investigation
pub_type: 杂志文章
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abstract:BACKGROUND:Experimental evidence indicates that statins might have direct vascular effects independently from low-density lipoprotein (LDL) cholesterol reduction and we reported that the reduction in urinary albumin excretion rate during Simvastatin treatment in type 2 diabetic patients was not correlated with LDL-chol...
journal_title:European journal of clinical investigation
pub_type: 临床试验,杂志文章
doi:10.1046/j.1365-2362.2000.00735.x
更新日期:2000-11-01 00:00:00
abstract::Reduced glutathione (GSH) and activity of GSH related enzymes play a key role in defence against oxygen free radicals, whose production is, as known, raised in patients affected by diabetes mellitus, and at the same time they may contribute to the process of platelet aggregation. The purpose of this study was to evalu...
journal_title:European journal of clinical investigation
pub_type: 杂志文章
doi:10.1111/j.1365-2362.1995.tb01983.x
更新日期:1995-09-01 00:00:00
abstract::The pathogenesis of alcoholic fatty liver is unknown, but several causes have been proposed based on biochemical findings. These include the metabolism of alcohol leading to a shift in the cytosolic [NAD+]/ [NADH] ratio to reduction, which in turn causes a direct inhibition of beta-oxidation and enhanced triacylglycer...
journal_title:European journal of clinical investigation
pub_type: 杂志文章,评审
doi:10.1046/j.1365-2362.1997.1780727.x
更新日期:1997-09-01 00:00:00
abstract:BACKGROUND:An earlier report described that transgenic mice ubiquitously expressing cryptochrome1 (CRY1) with a mutation in cystein414 (CRY1-AP Tg mice) display diabetes mellitus in addition to anomalous circadian behaviours. This study examined characteristic aspects of symptoms to clarify the diabetes type and pathog...
journal_title:European journal of clinical investigation
pub_type: 杂志文章
doi:10.1111/j.1365-2362.2010.02359.x
更新日期:2010-11-01 00:00:00
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journal_title:European journal of clinical investigation
pub_type: 杂志文章
doi:10.1111/j.1365-2362.1993.tb00969.x
更新日期:1993-09-01 00:00:00
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journal_title:European journal of clinical investigation
pub_type: 杂志文章
doi:10.1111/j.1365-2362.2011.02566.x
更新日期:2012-02-01 00:00:00
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journal_title:European journal of clinical investigation
pub_type: 杂志文章
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更新日期:2005-09-01 00:00:00
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journal_title:European journal of clinical investigation
pub_type: 杂志文章
doi:10.1046/j.1365-2362.1999.00438.x
更新日期:1999-02-01 00:00:00
abstract::Fibronectin is a glycoprotein found in body fluids, loose connective tissue matrix and in basement membranes. Fibronectin in rheumatoid arthritis synovial fluid was immunologically indistinguishable from the plasma form, as shown by double-diffusion analysis. Fibronectin isolated from rheumatoid synovial fluid by affi...
journal_title:European journal of clinical investigation
pub_type: 杂志文章
doi:10.1111/j.1365-2362.1981.tb01842.x
更新日期:1981-06-01 00:00:00
abstract:BACKGROUND:To prospectively evaluate the role of procalcitonin (PCT) in screening of patients with thyroid nodules for medullary thyroid carcinoma (MTC). MATERIALS AND METHODS:We measured PCT in 2705 patients with thyroid nodules referred to our centre between January 2011 and December 2017. Those with a positive PCT ...
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pub_type: 杂志文章
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更新日期:2018-06-01 00:00:00
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journal_title:European journal of clinical investigation
pub_type: 杂志文章
doi:10.1111/j.1365-2362.1993.tb00785.x
更新日期:1993-07-01 00:00:00
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journal_title:European journal of clinical investigation
pub_type: 杂志文章
doi:10.1111/j.1365-2362.2009.02239.x
更新日期:2010-02-01 00:00:00
abstract::The esterolytic activity of mixed and parotid saliva in cystic fibrosis (CF) patients and normal subjects was determined using BAEE (alpha-Benzoyl-1-arginine-ethylester) as the substrate. Using soybean-trypsin-inhibitor the trypsin-like activity (TLA) was measured and plotted as a function of parotid flow rate. In add...
journal_title:European journal of clinical investigation
pub_type: 杂志文章
doi:10.1111/j.1365-2362.1975.tb00441.x
更新日期:1975-04-01 00:00:00
abstract::Plasma glucose concentration is the best predictor for the development of non-insulin-dependent diabetes mellitus (NIDDM). However, obesity is also a recognized risk factor for development of the disease, and is easier to track over time. Thus obesity could be of considerable clinical importance as a predictor of diab...
journal_title:European journal of clinical investigation
pub_type: 杂志文章
doi:10.1046/j.1365-2362.1998.0280s2003.x
更新日期:1998-09-01 00:00:00
abstract::1. The activity of lipoprotein lipase (E.C.3.1.1.3) extracted and released from adipose tissue has been measured in obese subjects with mild or severe hypertriglyceridaemia. The Intralipid tolerance test has been studied as a measure of in vivo clearance of exogenous triglyceride from plasma. 2. Plasma triglyceride cl...
journal_title:European journal of clinical investigation
pub_type: 杂志文章
doi:10.1111/j.1365-2362.1980.tb02072.x
更新日期:1980-04-01 00:00:00
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journal_title:European journal of clinical investigation
pub_type: 杂志文章
doi:10.1111/j.1365-2362.1976.tb00544.x
更新日期:1976-11-30 00:00:00
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journal_title:European journal of clinical investigation
pub_type: 杂志文章
doi:10.1111/j.1365-2362.2011.02492.x
更新日期:2011-09-01 00:00:00
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journal_title:European journal of clinical investigation
pub_type: 杂志文章,评审
doi:10.1111/eci.12764
更新日期:2017-06-01 00:00:00
abstract::Washed cells, from ascitic fluid, which contained predominantly polymorphonuclear leucocytes from casein treated donor mice, induced accelerated amyloid formation in untreated syngeneic recipient animals. A similar transfer model, with lymph node cell suspension, was ineffective. Amyloidogenesis was completely blocked...
journal_title:European journal of clinical investigation
pub_type: 杂志文章
doi:10.1111/j.1365-2362.1980.tb00011.x
更新日期:1980-02-01 00:00:00
abstract::Skeletal muscle glycogen deposition, and the activation of muscle glycogen synthase and pyruvate dehydrogenase during a hyerinsulinaemic euglycaemic clamp have been measured in six young and six elderly males matched for body mass index, physical activity and diet. Clamp glucose requirement (insulin, 0.1 U kg-1 h-1) w...
journal_title:European journal of clinical investigation
pub_type: 杂志文章
doi:10.1111/j.1365-2362.1988.tb01045.x
更新日期:1988-10-01 00:00:00
abstract:BACKGROUND:Recent studies in mice experimental models with acute ischaemic injury revealed that erythropoietin (EPO) has numerous tissue-protective effects in the heart, brain and kidneys. We therefore explored the tissue-protective properties of chronic EPO treatment in an experimental model of the db/db mouse with di...
journal_title:European journal of clinical investigation
pub_type: 杂志文章
doi:10.1111/j.1365-2362.2009.02165.x
更新日期:2009-09-01 00:00:00
abstract::Increased activity of the Na+/H+ antiport may be a major abnormality in essential hypertension. The activity of this transport system was investigated in lymphocytes from 13 patients with untreated essential hypertension (Ht) and 13 normotensive control subjects (Nt) on an ad libitum (130-170 mmol d-1) NaCl intake. Fu...
journal_title:European journal of clinical investigation
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1365-2362.1994.tb01103.x
更新日期:1994-08-01 00:00:00
abstract:BACKGROUND:Chronic hyperglycaemia in diabetes is suggested to be a major cause of diabetic angiopathy. Up until now, the effects of acutely induced hyperglycaemia in non-diabetic subjects as well as hyperglycaemic effects in early diabetes, on mesenteric microcirculation and leucocyte endothelial cell interaction have ...
journal_title:European journal of clinical investigation
pub_type: 杂志文章
doi:10.1046/j.1365-2362.1998.00390.x
更新日期:1998-11-01 00:00:00
abstract:BACKGROUND:To date it is not known whether gastric juice vitamin C levels are influenced by Helicobacter pylori CagA(+) strains. The aim of the present study, therefore, was to study the impact of H. pylori CagA status on gastric juice vitamin C levels. MATERIALS AND METHODS:We studied 30 H. pylori(+) patients, and th...
journal_title:European journal of clinical investigation
pub_type: 杂志文章
doi:10.1046/j.1365-2362.1999.00432.x
更新日期:1999-01-01 00:00:00
abstract::Immunoreactive parathyroid hormone (PTH) levels and nephrogenous cyclic adenosine monophosphate (cAMP) have been reported to be useful parameters in the diagnosis of hyperparathyroidism. Measurements in hyperparathyroid patients usually give values above the normal range when PTH is measured with a carboxyterminal rad...
journal_title:European journal of clinical investigation
pub_type: 杂志文章
doi:10.1111/j.1365-2362.1984.tb01128.x
更新日期:1984-06-01 00:00:00
abstract::The concentration in serum of cathodal trypsinogen has been studied in certain clinical and experimental situations. The concentration correlated with pancreatic amylase activity. Low levels were found in patients with malabsorption due to exocrine pancreatic insufficiency. The concentration rose after endoscopic retr...
journal_title:European journal of clinical investigation
pub_type: 杂志文章
doi:10.1111/j.1365-2362.1978.tb00868.x
更新日期:1978-12-01 00:00:00