The detection of apolipoproteins AI and B in the liver of patients with and without hyperlipoproteinemia (author's transl)

Liver sections as well as isolated liver cells from 5 patients with a normal liver and normal serum lipids and patients with familial hyperlipoproteinemia type IIa (n=6), type IIb (n=11), type IV (n=13) and type V (n=2) were studied for the presence of apolipoprotein (apo) AI and B by immunofluorescence technique. At the time of liver biopsy the actual serum concentrations of HDL- and LDL-cholesterol and triglycerides were determined. In patients without metabolic disturbances apo AI was detectable in hepatocytes in 2 out of 5 cases. Apo B was not found in the liver of these patients. The non-parenchymal liver cells did not show depositions of apoproteins. In the group of 32 patients with hyperlipoproteinemia 6 cases showed in the liver apo AI and 2 cases apo B. The apoproteins exhibited a granular fluorescence pattern in the cytoplasm of hepatocytes. There was no correlation between the apoproteins in the liver and the degree of fat depositions in hepatocytes or the concentrations of serum lipids. The results indicate that the fat droplets in hepatocytes of patients with hyperlipoproteinemia represent lipid particles free of apoproteins. The lack of apoproteins in the liver with elevation of lipids in serum can be explained with a disturbed hepatic clearance function for lipoproteins.     

Mechanism of CO(2) retention in patients with neuromuscular disease

BACKGROUND: In many studies of patients with muscle weakness, chronic hypercapnia has appeared to be out of proportion to the severity of muscle disease, indicating that factors other than muscle weakness are involved in CO(2) retention. In patients with COPD, the unbalanced inspiratory muscle loading-to-strength ratio is thought to trigger the signal for the integrated response that leads to rapid and shallow breathing and eventually to chronic hypercapnia. This mechanism, although postulated, has not yet been assessed in patients with muscular dystrophy. SUBJECTS: Twenty consecutive patients (mean age, 47.6 years; range, 23 to 67 years) were studied: 11 patients with limb-girdle dystrophy, 3 with Duchenne muscular dystrophy, 1 with Charcot-Marie-Tooth syndrome, 1 with Becker muscular dystrophy, 1 with myotonic dystrophy, 1 with facioscapulohumeral dystrophy, and 2 with amyotrophic lateral sclerosis, without any respiratory complaints. Seventeen normal subjects matched for age and sex were studied as a control group. METHODS: Routine spirometry and arterial blood gases, maximal inspiratory and expiratory muscle pressures (MIP and MEP, respectively), and pleural pressure during maximal sniff test (Pplsn), were measured. Mechanical characteristics of the lung were assessed by evaluating lung resistance (RL) and dynamic elastance (Eldyn). Eldyn was assessed as absolute value and as percent of Pplsn; Eldyn (%Pplsn) indicates the elastic load per unit of inspiratory muscle force. Breathing pattern was assessed in terms of time (inspiratory time [TI]; respiratory frequency [Rf]) and volume (tidal volume [VT]) components of the respiratory cycle. RESULTS: A rapid shallow breathing pattern, as indicated by a greater Rf/VT ratio and a lower TI, was found in study patients compared to control subjects. Eldyn was greater in study patients, while MIP, MEP, and Pplsn were lower. PaCO(2) inversely related to VT, TI, and Pplsn (p = 0.012, p = 0.019, and p = 0.002, respectively), whereas it was directly related to Rf, Rf/VT, Eldyn, and Eldyn (%Pplsn) (p < 0.004 to p < 0.0001). Also Eldyn (%Pplsn) inversely related to TI, and the latter positively related to VT. In other words, increase in Eldyn (%Pplsn) was associated with decrease in TI, and the latter was associated with lower VT and greater PaCO(2). Mechanical and breathing pattern variables were introduced in a stepwise multiple regression that selected Eldyn (%Pplsn) (p < 0.0001; r(2) = 0.62) as a unique independent predictor of PaCO(2). CONCLUSIONS: The present study shows that in patients with neuromuscular disease, elastic load and respiratory muscle weakness are responsible for a rapid and shallow breathing pattern leading to chronic CO(2) retention.     

Serum lipid pattern and apolipoproteins (A1 and B100) in active rheumatoid arthritis

Cardiovascular diseases and atherosclerotic manifestations have been reported to be the most common causes of death in rheumatoid arthritis (RA). In the present investigation the levels of serum lipids, apolipoproteins (A1 and B100), total proteins, and albumin were studied in 35 female patients affected by active RA. Apolipoproteins A1 and B100 were significantly lower in RA patients than in controls. No significant difference was observed in total cholesterol, LDL cholesterol, or triglycerides. In contrast, HDL cholesterol and serum albumin were significantly lower in RA patients compared to controls. The finding of reduced apolipoproteins and HDL-cholesterol levels may represent an important factor in the etiology of cardiovascular and atherosclerotic disease in RA. Reduced levels of albumin in active RA may indicate a reduced rate of proteins like lipoproteins in the liver.     

Plasma apolipoproteins B and AI in healthy individuals and patients with coronary atherosclerosis in a male population from Lithuania]

The paper discusses the results from a study into apolipoproteins B (apo-B) and AI (apo-AI) and apoB/apo-AI ratios in the blood of 188 healthy donors and 122 male patients with coronary atherosclerosis. Atherosclerotic lesions were coronary angiographically documented. The study was performed (in two age groups of patients: 1) those under 45 years and 2) those over 45 years. A relationship was examined between the levels of apolipoproteins and the lesion of one, two, three or more coronary arteries in the two age groups. The studies indicate that there are various mechanisms responsible for the pathogenesis of atherosclerosis in the age groups in question. It is concluded that the younger a patient is, the higher probability that elevated blood apo-B levels are essential in the pathogenesis of coronary atherosclerosis is. Determination of plasma apo-B and apo-AI levels and apo-B/apo-AI ratios enables a potential number of diseased coronary arteries to be predicted.     

Serum apolipoproteins AI and B and lipoproteins in middle aged men with and without previous myocardial infarction

The serum high density lipoprotein (HDL) subfractions, HDL2, and HDL3, and serum apolipoprotein AI and B (apo AI and B) were evaluated as potential indicators of the risk of ischaemic heart disease in men aged less than 60 years who had previously had a myocardial infarction and in controls with a similar socioeconomic background who had no history of myocardial ischaemia. Discriminant analysis confirmed that the combination of serum cholesterol, triglycerides, and total HDL cholesterol distinguished poorly between patients and controls. The best single discriminating variable was apo B. Stepwise discriminant analysis showed that this discrimination could be improved to a small extent by combining apo B with apo AI and parental history, but nothing was gained by measurement of serum cholesterol triglycerides, very low density lipoprotein cholesterol, low density lipoprotein cholesterol, HDL cholesterol, HDL2 or HDL3 cholesterol. Significantly more patients than controls with type IV hyperlipoproteinaemia had raised concentrations of serum apolipoprotein B, but the frequency of raised apolipoprotein B concentrations was no greater in patients with type IV hyperlipoproteinaemia than in those with normal serum lipids. The value of apo B as an indicator of cardiovascular risk should be assessed in prospective studies.     

Serum apolipoproteins AI and B and lipoproteins in middle aged men with and without previous myocardial infarction.

The serum high density lipoprotein (HDL) subfractions, HDL2, and HDL3, and serum apolipoprotein AI and B (apo AI and B) were evaluated as potential indicators of the risk of ischaemic heart disease in men aged less than 60 years who had previously had a myocardial infarction and in controls with a similar socioeconomic background who had no history of myocardial ischaemia. Discriminant analysis confirmed that the combination of serum cholesterol, triglycerides, and total HDL cholesterol distinguished poorly between patients and controls. The best single discriminating variable was apo B. Stepwise discriminant analysis showed that this discrimination could be improved to a small extent by combining apo B with apo AI and parental history, but nothing was gained by measurement of serum cholesterol triglycerides, very low density lipoprotein cholesterol, low density lipoprotein cholesterol, HDL cholesterol, HDL2 or HDL3 cholesterol. Significantly more patients than controls with type IV hyperlipoproteinaemia had raised concentrations of serum apolipoprotein B, but the frequency of raised apolipoprotein B concentrations was no greater in patients with type IV hyperlipoproteinaemia than in those with normal serum lipids. The value of apo B as an indicator of cardiovascular risk should be assessed in prospective studies.     

Lipoprotein lipids and apolipoproteins (AI, AII, B, CII, CIII) in type 1 and type 2 diabetes mellitus in young Kuwaiti women.

Plasma lipid and apolipoprotein levels of Type 1 and Type 2 young Kuwaiti diabetic women on insulin therapy were investigated to elucidate the relationship between coronary artery disease risk factors and lipid levels. Forty Type 1 and 52 Type 2 diabetic women and 45 and 62 corresponding control subjects (matched for age and body mass index) were investigated. In comparison with control subjects, both groups of diabetic patients showed marked increases in total-cholesterol, LDL-cholesterol, triglycerides, very low density triglycerides, apolipoprotein B, glucose, fructosamine, and glycosylated haemoglobin HbA1c (all p less than 0.001). However, apolipoprotein CIII was significantly elevated in Type 2 diabetic patients (p less than 0.001) but not in Type 1 patients. Concentrations of apolipoproteins CII and AII in both diabetic groups were not significantly different from those in control subjects. Levels of HDL-, HDL2- and HDL3-cholesterol and plasma apolipoprotein AI were markedly decreased in both the diabetic groups compared with their control groups (all p less than 0.001 except HDL3-cholesterol in Type 1 diabetic vs control, p less than 0.05). In Type 2 diabetic patients, HbA1c correlated positively with triglycerides (r = 0.70, p less than 0.001), cholesterol (r = 0.60, p less than 0.001), apolipoprotein B (r = 0.77, p less than 0.001), and apolipoprotein CIII (r = 0.55, p less than 0.001) and negatively with apolipoprotein AI (r = -0.49, p less than 0.001). In Type 1 diabetic patients HbA1c correlated positively only with apolipoprotein CIII (r = 0.50, p less than 0.001).     

Variable phenotypic expression of chylomicron retention disease in a kindred carrying a mutation of the Sara2 gene

Chylomicron retention disease is a recessive inherited disorder characterized by fat malabsorption and steatorrhea and is associated with failure to thrive in infancy. We describe a kindred carrying a mutation of Sara2 gene causing a chylomicron retention phenotype. The proband was a 5-month-old baby, born of consanguineous, apparently healthy parents from Morocco, with failure to thrive. There was a large quantity of fats in feces and malabsorption of fat-soluble vitamins. Intestinal biopsies showed a diffused enterocyte vacuolization with large cytosolic lipid droplets. Chylomicron retention disease or Anderson disease was hypothesized, and the Sara2 gene was analyzed by direct sequencing. Analysis of the Sara2 gene in the proband identified a 2-nucleotide homozygous deletion in exon 3 leading to a premature stop codon (c.75-76 del TG-L28fsX34). The father was heterozygous for the same mutation, whereas the proband's mother was homozygous, suggesting a variable phenotypic expression of the molecular defect. More studies are needed to understand the reasons of the phenotypic variability of the same molecular defect in the same family.     

apoB基因EcoRI、XbaI、MspI及apoAI基因-75bp、+83bp位点多态性与哈萨克族冠心病的相关性

目的:分析载脂蛋白B(apoB)基因EcoRI、XbaI、MspI位点和载脂蛋白AI(apoAI)基因-75bp、+83bp位点多态性与哈萨克族人冠心病的关系.方法:采用聚合酶链式反应-限制性片段长度多态性分析法检测185例哈萨克族冠心病患者和216例哈萨克族非冠心病对照者的这些位点多态性.结果:①TC、TG及apoA...     

Lipid pattern,apolipoproteins A1 and B and lipoprotein (a) in type 1 diabetic patients with microalbuminuria

The plasma lipid changes commonly observed in patients with diabetic nephropathy may play a major role in determining the increased cardiovascular risk in these patients. Contrasting results have been reported on the patterns of lipids and lipoproteins in diabetic subjects with microalbuminuria. We examined 20 patients with type 1 (insulin-dependent) diabetes who had a urinary albumin excretion >30 mg/24 h (11 males and 9 females, age range 16–45 years, mean diabetes duration 11.7 years) and 20 type 1 diabetic patients without microalbuminuria matched for sex, age, diabetes duration, daily insulin requirement and degree of metabolic control. In all patients we measured plasma total cholesterol, highdensity lipoprotein (HDL)-cholesterol, triglycerides, apolipoproteins A₁ and B and lipoprotein (a) [Lp(a)]. No significant differences were found for any parameter between subjects with a urinary albumin excretion <20 mg/ 24 h and microalbuminuric patients. Moreover in nondiabetic controls the levels of plasma Lp(a) and of the other parameters measured were not significantly different from those of the two diabetic groups. Our results suggest that in type 1 diabetic patients with fairly good glycaemic control microalbuminuria is not associated with significant changes in the lipoprotein pattern.     

Serum S100B levels in patients with cerebral and extracerebral infectious disease

S100B has been shown to increase in cerebrospinal fluid (CSF) and serum after various neurological diseases and it has been postulated that S100B could serve as a serum marker for brain damage. However there is limited information concerning serum S100B levels in infectious diseases of the brain. Blood samples were collected from patients at the Department of Infectious Diseases at or soon after admission. The different diagnoses studied were bacterial meningitis, pneumonia, viral meningitis, cerebral abscess, enteritis, erysipelas, viral encephalitis and neuroborreliosis. A serum S100B level > 0.15 microg/l was defined as increased. 57 patients were included in the study. S100B was elevated in 33% of patients (19/57). 73% (8/11) of patients with bacterial meningitis showed increased levels compared to 7% (1/14) of patients with viral meningitis. Viral encephalitis showed the highest mean S100B levels (mean 0.58 microg/l). 25% (6/24) of patients with extracerebral infections showed raised S100B levels. S100B levels were generally higher in patients with cerebral infections than in extracerebral infections. However, both false negative and false positive S100B levels were observed which may limit the use of S100B as a brain specific serum marker.     

The metabolism of apolipoproteins (a) and B-100 within plasma lipoprotein (a) in human beings

The metabolism of apolipoproteins (apo) (a) and B-100 within plasma lipoprotein (a) [Lp(a)] was examined in the fed state in 23 subjects aged 41 to 79 years who received a primed-constant infusion of [5,5,5-2H3] leucine over 15 hours. Lipoprotein (a) was isolated from the whole plasma using a lectin affinity-based method. Apolipoprotein (a) and apoB-100 were separated by gel electrophoresis, and tracer enrichment of each apolipoprotein was measured using gas chromatography/mass spectrometry. Data were fit to a multicompartmental model to determine fractional catabolic rates (FCRs) and secretion rates (SRs). The FCRs of apo(a) and apoB-100 (mean +/- SEM) within plasma Lp(a) were significantly different (0.220 +/- 0.030 pool/d and 0.416 +/- 0.040 pool/d, respectively; P < .001). Apolipoprotein (a) SR (0.50 +/- 0.08 mg/[kg per d]) was significantly lower than that of apoB-100 SR (1.53 +/- 0.22 mg/[kg per d]; P < .001) of Lp(a). Plasma concentrations of Lp(a) were correlated significantly with both apo(a) SR and apoB-100 SR (r = 0.837 and r = 0.789, respectively; P < .001) and negatively with apo(a) FCR and Lp(a) apoB-100 FCR (r = -0.547 and r = -0.717, respectively; P < .01). These data implicate different metabolic fates for apo(a) and apoB-100 within Lp(a) in the fed state. We therefore hypothesize that apo(a) does not remain covalently linked to a single apoB-100 lipoprotein but that it rather reassociates at least once with another apoB-100 particle, probably newly synthesized, during its plasma metabolism.     

Retarded chylomicron apolipoprotein-B catabolism in Type 2 (non-insulin-dependent) diabetic subjects with lipaemia

Summary To define the kinetics of chylomicron apolipoprotein-B catabolism in diabetic subjects with lipaemia, autologous chylomicrons (S_f 400) harvested from plasma following an oral fat load were radioiodinated and re-injected. The radioactivity in the tetramethylurea-insoluble, non-lipid S_f>400 lipoprotein fraction was followed in serial samples over 60–72h on a fat-free, isocaloric diet in: (1) five normal subjects; (2) four hypertriglyceridaemic, non-diabetic subjects; and (3) five diabetic patients (one subject, No. 3, was studied twice). The plasma apolipoprotein-B decay curve for the Sf 400 fraction disclosed biphasic disappearance: a rapid first phase (residence time 0.8–1.9 h) accounting for the large majority of removal (60%–95%) and a slower second phase (residence time 3.6–47.6 h), accounting for the remainder. Total chylomicron apolipoprotein-B residence times were similar in normolipidaemic (1.8–7.3 h) and hypertriglyceridaemic (2.3–10.3 h) non-diabetic subjects and the mildly hypertriglyceridaemic diabetic patients (5.6 and 5.8 h). In the untreated lipaemic diabetic subjects (Nos. 1 and 2), only a single, much slower phase was observed (total chylomicron apolipoprotein-B residence time 38.5–58 h). Adipose tissue biopsy in one of these subjects (No. 1) disclosed profoundly low lipoprotein lipase activity. The lipaemic diabetic subject (No. 3) studied early during treatment showed an intermediate pattern. These studies suggest a key role for insulin-dependent, lipoprotein lipase-mediated triglyceride hydrolysis in the removal of chylomicrons from plasma.     

Biopsy rate and nonalcoholic steatohepatitis (NASH) in patients with nonalcoholic fatty liver disease (NAFLD)

Abstract

Background: Licensed therapies for nonalcoholic fatty liver disease (NAFLD) do not yet exist, but clinical trials are testing treatment options. Inclusion criteria often require liver biopsy showing fibrosis (F2/3) or cirrhosis (F4) and nonalcoholic steatohepatitis (NASH). However, histological criteria pose a serious obstacle for recruitment.

Aims: Characterize the relevance of liver biopsies in the selection of patients with NAFLD.

Methods: Patients between 2013 and 2018 with the ICD-10 code K76.0 were analyzed. Fibrosis was defined by the NASH clinical research network (CRN) fibrosis staging system, NASH by a NAFLD activity score (NAS) ≥4. Predictive factors were determined by logistic regression.

Results: Liver biopsy was performed in 87/638 (13.6%) patients (49% female, age 52.5?±?14.0, BMI 30.4?±?5.9?kg/m²). Fibrosis stage F0/F1/F2/F3/F4 was observed in N?=?7/47/7/17/9, an NAS ≥4 in N?=?27. Fibrosis stage F2/F3 and F4 along with NAS ≥4 was found in 1.7% and 0.5% of cases. Liver stiffness measurement, LSM (OR 2.3 per doubling of value; CI 1.3–4.4, p?=?.005) and FIB-4 (OR 2.3 per doubling of value; CI 1.2–4.4, p?=?.012) were significant predictors for fibrosis?≥?F2. Predictive factors for NASH were not identified.

Conclusion: The biopsy rate in NAFLD patients is low and fibrosis?≥?F2 along with NAS ≥4 only present in a few cases. Transient elastography and FIB-4 are useful to select patients at risk for fibrosis for liver biopsy.     

Coronary heart disease and urinary albumin excretion rate in Type 2 (non-insulin-dependent) diabetic patients

Summary Associations between overnight urinary albumin excretion rate and prevalent coronary heart disease and its major risk factors were examined in a cross-sectional study of 141 Type 2 (non-insulin-dependent) diabetic patients. Mean albumin excretion rate was higher in men (geometric mean 13.5 g/min; 95% confidence interval 10.3–17.6) than women (7.5 g/min; 5.7–9.8, p<0.01). In diabetic men and women mean albumin excretion rate was higher in those with electrocardiographic and/or symptomatic evidence of coronary heart disease than in those without (men, 23.1 g/ min; 95% confidence interval 13.7–39.0 versus 10.6 g/min; 7.9–14.2, p<0.01, women, 13.7 g/min; 8.0–23.5 versus 5.4 g/min; 4.2–6.8, p<0.01). Multiple logistic regression analysis was used to allow for confounding between variables. In the diabetic group as a whole, raised albumin excretion rate (p<0.001), gender (p<0.05) and systolic blood pressure (p=0.06) entered the best model for coronary heart disease prediction. In women, albumin excretion rate alone (p<0.01) and in men albumin excretion rate (p<0.01) and age (p=0.05) entered the best models. We conclude that albumin excretion rate is significantly associated with coronary heart disease morbidity after taking into account the confounding effects of raised blood pressure and other cardiovascular risk factors.     

Relationships of apolipoprotein B(100) with the metabolic syndrome in Type 2 diabetes mellitus

The current study assessed whether features of the metabolic syndrome are associated with higher apolipoprotein B(100) (apoB(100)) levels in people with Type 2 diabetes (n = 298) not taking lipid-lowering drugs. Body-mass index (BMI), waist:hip ratio (WHR), urinary albumin excretion rate, presence or absence of hypertension, uric acid levels, and apoB(100) levels were assessed. Both higher BMI and urinary albumin excretion rate were associated with higher apoB(100) levels (1.02 +/- 0.25 ( +/- S.D.) g/l in normal weight, 1.07 +/- 0.22 g/l in overweight and 1.14 +/- 0.25 g/l in obese individuals; P < 0.01; 1.09 +/- 0.23 g/l in normoalbuminuric patients, 1.06 +/- 0.22 g/l if urinary albumin excretion rate 20-50 microg/min and 1.17 +/- 0.27 g/l if urinary albumin excretion rate > 50 microg/min; P < 0.05). An association between the number of features of the metabolic syndrome and higher apoB(100) levels was found (1.03 +/- 0.22 g/l if no features, 1.08 +/- 0.25 g/l if one feature, 1.11 +/- 0.20 g/l if two features and 1.15 +/- 0.27 g/l if > 2 features; P for trend < 0.01). Thus apoB(100) levels show an association with the metabolic syndrome and, hypothetically, to insulin-insensitivity in Type 2 diabetes. BMI (but not WHR) and urinary albumin excretion rate accounted for most of the power of this relationship.     

Serum apolipoprotein AI, B levels in patients with coronary diseases

The levels of total cholesterol, triglyceride, LDL-C, HDL-C, apolipoprotein A1 and apolipoprotein B in the serum were measured in a selected series of 100 CAD patients (77 men and 23 women) who underwent coronary angiography and 141 non-CAD controls. Mean values of those variables differed significantly between the CAD and non-CAD groups matched in age, body weight, hypertension and smoking. There are significant difference in apolipoproteins A1, B and the ratio of apolipoprotein B to A1 between angina and myocardial infarction groups. Using stratified and multivariate stepwise regression analysis, it was shown that the apo A1, apoB/apoA1 are more sensitive and specific than the ordinary indices (e.g. total cholesterol, triglycerides, LDL-C and HDL-C) in estimating the degree of coronary artery stenosis and the differentiation of CAD from other diseases.