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Biomedical subjects

M Naruszewicz

Publications and source records attributed to M Naruszewicz.

At least 19 recordsLinked to original sources
PubMed2002

Von Willebrand factor, fibrinogen and other risk factors of thrombosis in patients with a history of cerebrovascular ischemic stroke and their children.

BACKGROUND AND AIM: Von Willebrand factor (vWF) and fibrinogen (Fb) have recently emerged as plausible familial determinants of atherothrombosis. We investigated whether the vWF and Fb levels in patients with ischemic cerebrovascular stroke (ICS) correlate with those in their children. METHODS AND RESULTS: The study group consisted of 28 families (56 parents and 34 children) with one parent who had suffered an ICS at least three months before the study. All of the ICS patients had hyperlipoproteinemia and most arterial hypertension. The control group consisted of 15 families (30 parents and 20 children). The age of the parents and children did not exceed 55 and 16 years. The ICS parents had significantly higher vWF, Fb and protein C (PC) levels than the controls (vWF--fathers: 121.0 +/- 42.5% vs 79.2 +/- 23.4%; vWF--mothers: 110.7 +/- 40.1% vs 82.4 +/- 20.9%; Fb--fathers: 4.12 +/- 0.74 g/L vs 3.01 +/- 0.54 g/L; Fb--mothers: 3.64 +/- 0.84 gL vs 2.98 +/- 0.35 g/L; PC--fathers: 116.0 +/- 12.3% vs 105.6 +/- 13.7%; PC--mothers: 114.4 +/- 15.8% vs 105.0 +/- 12.2%). The children of the ICS parents had significantly higher PC and body mass index (BMI) values than the controls (PC: 102.6 +/- 13.7% vs 92.7 +/- 10.7%; BMI: 20.6 +/- 3.8 vs 17.8 +/- 3.5 Kg/m2), as well as an atherogenic lipid profile, higher blood pressure (BP) and a tendency toward higher vWF levels. Correlations between the ICS parents and their children were found for vWF, factor VIIc, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and BP, which were closer in the case of fathers. CONCLUSION: Regardless of gender, the parents with a history of ICS had a procoagulant state, with high levels of vWF, Fb and PC. In terms of inheritance, the most adverse risk factor profile was found in the children of ICS fathers.

Adult↗
PubMed2001

Selective inhibition by probucol of vascular cell adhesion molecule-1 (VCAM-1) expression in human vascular endothelial cells.

An early event in atherogenesis is the adhesion of monocytes to endothelium via adhesion molecules, such as VCAM-1 and intracellular adhesion molecule-1 (ICAM-1). It has been suggested that VCAM-1 plays a very important role in the recruitment of monocytes in atherosclerosis. Probucol is a potent inhibitor of atherosclerosis in animal models. However, the mechanism of its antiatherogenic effect is poorly understood. The aim of our study was to evaluate whether probucol can influence the expression of endothelial cell adhesion molecules and endothelial adhesiveness. The study was performed on cultured human umbilical vein endothelial cells (HUVEC). HUVEC were pretreated with probucol (50 microM) at different time periods before stimulation with TNFalpha (100 U ml(-1)) or IL-1beta (100 U ml(-1)). The protein expression of VCAM-1 and ICAM-1 was measured by flow cytometry. VCAM-1 mRNA expression was measured by reverse transcription polymerase chain reaction (RT PCR). Probucol time dependently reduced agonist-induced VCAM-1 ( approximately 45%, 48 h) surface protein and mRNA expression ( approximately 40%, 48 h) in HUVEC, but not ICAM-1 surface protein expression. Decreased VCAM-1 expression was associated with reduction ( approximately 40%) of adherence between cytokine-stimulated HUVEC and peripheral blood mononuclear leukocytes (PBMC). Our results suggest that the antiatherogenic effect of probucol may, in part, be due to a downregulation of VCAM-1 expression.

Anticholesteremic Agents↗
PubMed2001

Homocysteine, fibrinogen, and lipoprotein(a) levels are simultaneously reduced in patients with chronic renal failure treated with folic acid, pyridoxine, and cyanocobalamin.

Ischemic heart disease and other complications of atherosclerosis are the usual cause of death in patients with chronic renal failure. Important factors associated with early onset of atherosclerosis in these patients are hyperhomocysteinemia, hyperfibrinogenemia, and elevated levels of lipoprotein(a) (Lp(a)). Folic acid (15 mg/d), pyridoxine (150 mg/d), and cyanocobalamin (1 mg/wk) were administered for 4 weeks in 21 patients receiving dialysis, and a simultaneous, statistically significant reduction in the concentration of homocysteine, fibrinogen, and Lp(a) was found. A positive correlation between decreasing homocysteine and fibrinogen levels was also noted. The parameters studied approached presupplementation values 6 months after vitamins were discontinued. The results suggest that vitamin supplementation has a favorable effect on risk factors of atherosclerosis in patients with renal failure and that interactions may exist between homocysteine, fibrinogen, and Lp(a).

Adult↗
PubMed2001

[Reduction of the plasma LDL-cholesterol level among young healthy men as a result of the change from butter to soft margarine in the unbalanced diet].

The aim of the study was to evaluate the level of lipid profile on 83 healthy males consuming soft type margarine instead of butter, in their unbalanced diet. For this purpose double blind, cross-over methodology was applied. After stabilization period of consuming the diet, the whole sample was randomly divided into two subgroups (A n--37; B n--46). First group was consuming 15 g of the butter twice a day (30 g in total) and the second identically packed soft type margarine (also twice a day 15 g; 30 g in total) containing high level (33.3 g/100 g) of polyunsaturated fatty acids. After four weeks, the diet of subgroups was mutually exchanged--group consuming margarine consumed butter and the opposite. The feeding pattern of both groups was monitored with the aid of FOOD 2 computer programme. The group under investigation consisted of healthy males at the age 23.3 +/- 2.5, BMI 24.4 +/- 3.9 kg/m2; WHR 0.82 + -0.06 and normal blood pressure. Exchange of butter into soft margarine caused the increase of P/S ratio from 0.30 to 0.78 in their diet. Both investigated groups shoved average decrease of 10.7% of blood cholesterol content (in group A 13.8%), LDL cholesterol of about 9.8% and triglycerides ca 12.7% (higher decrease in group B--16.7%). Both groups while on margarine diet shoved small decrease of HDL cholesterol (3.9%). It can not be the matter of serious concern due to average HDL content in both groups was ca 52 mg/dl (ca 1.4 mmol/l)--it means considerably excessive the limited risk (35 mg/dl; 0.90 mmol/l). Application of the margarine diet in group A caused the decrease the ratios of total cholesterol to HDL cholesterol from 3.84 into 3.52; whereas in group B from 4.15 into 3.75. It was also concluded, that the low trans isomer margarine show no effect on lipoprotein Lp(a). Back to the diet with butter after 4 weeks carry down the beneficial effects of diet with margarine on lipid profile. The results indicate that for lipid profile the consumption of soft margarine was more beneficial than butter, even for unbalanced diet.

Adult↗
PubMed2001

Rapid quantification of human ABCA1 mRNA in various cell types and tissues by real-time reverse transcription-PCR.

BACKGROUND: The ABCA1 gene encodes for a member of subfamily A of the ATP-binding cassette transporters that plays an important role in cellular export of cholesterol and phospholipids; therefore, quantification of the ABCA1 mRNA is critical in many studies related to its expression and regulation by metabolic factors, nutritional status, and new antiatherogenic drug candidates. We developed a rapid, sensitive, specific, and reproducible real-time reverse transcription-PCR (RT-PCR) method for detection and quantification of ABCA1 transcripts in total RNA isolated from cultured human cells and tissues. METHODS: To quantify ABCA1 mRNA, we generated a calibration curve from serial dilutions of in vitro-transcribed RNA corresponding to an amplified ABCA1 cDNA 205-bp fragment (homologous calibrator). Two pairs of fluorescent hybridization probes were used to detect the ABCA1 and porphobilinogen deaminase (PBGD) mRNAs; the latter served as an internal control. PCR was performed as real-time amplification of ABCA1 mRNA in 100 ng of total RNA isolated from various human tissues, and cultured cells were calculated from the calibration curve. In addition, normalized values of target (ABCA1/PBGD ratio) were calculated. RESULTS: Using this method, we quantified ABCA1 transcripts in various human tissue samples as well as in monocytes, THP-1 cells, fibroblasts, and adipocytes. We demonstrated ABCA1 mRNA up-regulation during human adipocyte and monocyte differentiation. In addition, we examined the effect of cholesterol loading and deloading on ABCA1 expression in monocytes, THP-1 cells, and fibroblasts. CONCLUSIONS: Our RT-PCR assay allows the specific and highly reproducible detection and quantification of minute amounts of human ABCA1 mRNA. This new method is more accurate, more informative, and less laborious than the classic RT-PCR methods and Northern blot; it therefore could simplify all studies on ABCA1 mRNA expression.

ATP Binding Cassette Transporter 1↗
PubMed2001

[Fibrinogen (Fb) concentrations in patients with ischaemic heart disease undergoing coronary angiography].

Increasing evidence suggests the role of hemostatic risk factors in the development of ischemic heart disease (IHD). A raised plasma fibrinogen has been related to increased risk of IHD. The aim of the study was to determine the relationship between plasma fibrinogen and the coronary vessels state based on the coronary angiogram. 119 patients undergoing coronary angiography were classified into 5 groups according the severity of IHD: Group 0 without significant atherosclerotic lesions (control group), Group 1 with single vessel disease, Groups 2, 3 with multivessel disease (two and three affected arteries, respectively) and Group 4 with positive history of myocardial infarction. A statistically nonsignificant rise in fibrinogen levels in Groups 1, 2, 3 (3.9 +/- 0.8 g/l, 4.0 +/- 0.9 g/l, 4.1 +/- 0.9 g/l, respectively) as compared to control Group 0 (3.7 +/- 0.7 g/l) was found. In Group 4 plasma fibrinogen was significantly lower (2.8 +/- 0.6 g/l) comparing to Group 0 (p < 0.05). In addition plasma fibrinogen was positively correlated with blood pressure. These results supports the role of raised plasma fibrinogen in the pathogenesis and development of IHD.

Adult↗
PubMed2001

Lp(a), homocysteine and a family history of early ischemic cerebral stroke.

BACKGROUND AND AIM: High plasma lipoprotein(a) [Lp(a)] and homocysteine (HCY) levels are now considered to be independent risk factors for cerebro- and cardiovascular atherosclerotic occlusive disease, but little is known about the influence of Lp(a) and HCY on the early events of ischemic disease or their significance in subjects with a positive family history of ischemia. The aim of this study was to evaluate the relationship between HCY levels and the severity of ischemic cerebral stroke, and investigate whether there was a correlation between Lp(a) and HCY levels in the stroke patients and their children. METHODS: The study involved 35 patients with early ischemic cerebral stroke aged 46.1 +/- 6.6 years and their 50 children aged 17.2 +/- 5.5 years. The patients were grouped on the basis of the form of the stroke (transient, progressive or complete stroke), and their levels of Lp(a), HCY, uric acid (UA), fibrinogen (Fb) and factor VII (FVII) activity were measured. RESULTS: HCY and Lp(a) concentrations increased with the severity of the ischemia, being highest in the patients with complete stroke (15.1 +/- 2.9 mumol/L and 32.9 +/- 37.6 mg/dL respectively). A similar trend was found in the offspring, with the highest HCY and Lp(a) values in the children of complete stroke patients (12.6 +/- 4.4 mumol/L and 23.0 +/- 24.6 mg/dL). The control values were respectively 8.7 +/- 1.6 mumol/L and 5.35 +/- 7.05 mg/dL. The following correlations between the parents and children were noted: Lp(a) (r = 0.87 p < 0.0001), UA (r = 0.71 p < 0.001), HCY (r = 0.45 p < 0.05), FVII (r = 0.45 p < 0.05), and Fb (r = 0.42 p = 0.06). Correlations between Lp(a) and HCY (r = 0.47 p < 0.05) and Fb and FVII (r = 0.60 p < 0.01) were found in the children. Multiple regression analysis revealed that only Lp(a) and Fb significantly influenced HCY levels in the offspring with a positive family history. CONCLUSIONS: HCY levels correlate with the severity of ischemic cerebral stroke and, in families with a history of ischemic cerebral stroke, the levels of the risk factors in children are determined by the levels in their parents.

Adolescent↗
PubMed2000

Selective inhibition by alpha-tocopherol of vascular cell adhesion molecule-1 expression in human vascular endothelial cells.

An early event in atherogenesis is the adhesion of monocytes to endothelium via adhesion molecules such as VCAM-1 and intracellular adhesion molecule-1 (ICAM-1). It has been suggested that VCAM-1 plays a very important role in recruitment of monocytes in atherosclerosis. Several studies suggest that vitamin E has antiatherosclerotic properties. However, the mechanism of its antiatherogenic effect awaits elucidation. The aim of our study was to evaluate whether alpha-tocopherol can influence expression of endothelial cell adhesion molecules and endothelial adhesiveness. The study was performed on cultured human umbilical vein endothelial cells (HUVEC). HUVEC were pretreated with alpha-tocopherol (50 micromol/l) in different times before stimulation with TNFalpha (100 U/ml) or IL-1beta (100 U/ml). Protein expression of VCAM-1 and ICAM-1 was measured by flow cytometry. mRNA expression of VCAM-1 was measured by reverse transcription polymerase chain reaction (RT-PCR). alpha-Tocopherol time dependently reduced agonist-induced VCAM-1 in both surface protein (about 40%, 48 h) and mRNA (about 35%, 48 h) expression in HUVEC but not ICAM-1 surface protein expression. Inhibitory effect of alpha-tocopherol was dependent on culture condition of HUVEC. Decreased VCAM-1 expression was associated with reduction (about 40%) of adherence between cytokine-stimulated HUVEC and peripheral blood mononuclear leukocytes (PBMC). Our results suggest that the antiatherogenic effect of alpha-tocopherol may in part be due to a downregulation of VCAM-1 expression.

Arteriosclerosis↗
PubMed2000

Ibuprofen inhibits adhesiveness of monocytes to endothelium and reduces cellular oxidative stress in smokers and non-smokers.

BACKGROUND: Cigarette smoking is a major risk factor in atherosclerosis and a useful model from which to study chronic inflammation. We compared monocyte function, lipid profiles and inflammatory markers in smokers and non-smokers, before and after oral ibuprofen intake. The adhesion of freshly isolated monocytes to native and tumour necrosis factor alpha (TNFalpha) stimulated human umbilical vein endothelial cells (HUVEC), as well as superoxide anion (O2-) levels and hydrogen peroxide (H2O2) production in resting and phorbol myristate acetate (PMA) stimulated monocytes were determined. MATERIALS AND METHODS: A group of nine smokers without any other coronary risk factor was compared with an age-matched group of 9 non-smokers. Tests were performed before and after a two-week course of oral ibuprofen (600 mg day-1). RESULTS: In smokers before ibuprofen, monocyte adhesion to native and TNFalpha-stimulated HUVEC was increased (P < 0001 and P < 0.01, respectively), and so were O2- levels in native and PMA-stimulated monocytes (P < 0.01 and P < 0.001, respectively). Ibuprofen reduced the adhesion of monocytes to native and stimulated HUVEC (P < 0.001) and O2- generation by resting and PMA-stimulated cells (P < 0.01) in both groups. H2O2 production by resting and PMA-stimulated monocytes was reduced in smokers and non-smokers (P < 0.01). Interestingly, ibuprofen increased HDL cholesterol levels in smokers (P < 0.01) and non-smokers (P < 0.001), and reduced the level of triglycerides in smokers (P < 0.05). CONCLUSION: Oral administration of ibuprofen reduced the adhesion of monocytes to HUVEC, suppressed oxidative stress and increased HDL cholesterol levels in smokers and non-smokers.

Adult↗
PubMed2000

Is abnormal postprandial lipemia a familial risk factor for coronary artery disease in individuals with normal fasting concentrations of triglycerides and cholesterol?

OBJECTIVE: To assess the postprandial response to a fat load in patients with coronary artery disease (CAD) and age-matched controls. METHODS: Postprandial lipemia was assessed in patients with CAD confirmed by angiography (study group, n = 44) and in patients without coronary lesions (control group, n = 20). Family members of patients with CAD were also included (spouses group, n = 22; progeny group, n = 33). Fasting triglyceride and cholesterol concentrations in the control and study groups were less than 2.3 and 6.47 mmol/l, respectively. After initial blood sampling, the patients consumed 30% cream (200 ml/m2 body area). Repeat measurements of triglycerides, total cholesterol and high-density lipoprotein were made after 2, 4, 6, and 8 h. RESULTS: Changes were most marked in triglyceride concentrations. Peak values were observed after 4 h in the spouses, progeny, and control groups, and after 6 h in the study group. To compensate for the large age span (8-40 years) of the progeny, two subgroups were formed, taking 25 years as the cut-off value. Triglycerides continued to increase until the 4th hour in both subgroups, but the subgroups differed as to the absolute concentration of triglycerides. During the first 6 h of the test, the concentrations were significantly greater in the subgroup of older progeny than in their fathers with CAD. CONCLUSIONS: These findings indicate that triglycerides are metabolized at a slower rate and remain longer in the circulation of patients with CAD, as compared with patients without CAD. A significantly greater level of postprandial lipemia has been observed in adult progeny of patients with CAD, suggesting a genetic disorder of triglyceride metabolism in these individuals.

Adult↗
PubMed1999

Ibuprofen protects low density lipoproteins against oxidative modification.

Oxidative modification of LDL by vascular cells has been proposed as the mechanism by which LDL become atherogenic. The effect of ibuprofen on LDL modification by copper ions, monocytes and endothelial cells was studied by measuring lipid peroxidation products. Ibuprofen inhibited LDL oxidation in a dose-dependent manner over a concentration range of 0.1 to 2.0 mM. Ibuprofen (2 mM, 100 microg/ml LDL) reduced the amount of lipid peroxides formed during 2 and 6 h incubation in the presence of copper ions by 52 and 28%, respectively. Weak free radical scavenging activity of ibuprofen was observed in the DPPH test. The protective effect of ibuprofen was more marked when oxidation was induced by monocytes or endothelial cells. Ibuprofen (1 mM, 100 microg/ml LDL) reduced the amount of lipid peroxides generated in LDL during monocyte-mediated oxidation by 40%. HUVEC-mediated oxidation of LDL in the absence and presence of Cu2+ was reduced by 32 and 39%, respectively. More lipid peroxides appeared when endothelial cells were stimulated by IL-1beta or TNFalpha and the inhibitory effect of ibuprofen in this case was more pronounced. Ibuprofen (1 mM, 100 microg/ml LDL) reduced the amount of lipid peroxides formed during incubation of LDL with IL-1beta-stimulated HUVEC by 43%. The figures in the absence and presence of Cu2+ for HUVEC stimulated with TNFalpha were 56 and 59%, respectively. To assess the possibility that ibuprofen acts by lowering the production rate of reactive oxygen species, the intracellular concentration of H2O2 was measured. Ibuprofen (1 mM) reduced intracellular production of hydrogen peroxide in PMA-stimulated mononuclear cells by 69%. When HUVEC were stimulated by IL-1beta or TNFalpha the reduction was 62% and 66%, respectively.

Antioxidants↗
PubMed1999

Etofibrate decreases factor VII and fibrinogen levels in patients with polymetabolic syndrome.

Etofibrate is a hypolipemic drug belonging to the fibrate class. By improving the lipid profile, these drugs often exert a favorable influence on hemostatic risk factors of ischemic heart disease. We present a pilot study on the influence of etofibrate on lipids and lipoproteins in serum, as well as on factor VII and fibrinogen. The study group was comprised of 18 males, aged 52.5 +/- 7.3 years, with hypertriglyceridemia or mixed hyperlipoproteinemia and other risk factors of atherosclerosis, particularly insulin-dependent diabetes and arterial hypertension. The group was further divided into two subgroups depending on the coexistence of arterial hypertension. All patients received etofibrate 500 mg daily for 3 months. In comparison with initial values, a decrease in the following was noted for the whole study group: triglyceride level (226.0 +/- 27.1 vs. 288.0 +/- 51.9 mg/dl; p < 0.05), percent LDL-cholesterol (72.4 +/- 1.8 vs. 75.8 +/- 1.7; p < 0.05), apolipoprotein B (111.2 +/- 4.6 vs. 115.3 +/- 5.4 mg/dl; p < 0.05), atherogenic indices: LDL/HDL (5.06 +/- 0.58 vs. 5.95 +/- 0.50; p < 0.02) and apolipoprotein B and A (apoB/apoA) (0.92 +/- 0.04 vs. 1.02 +/- 0.06; p < 0.05). There was an increase in percent HDL-cholesterol (14.7 +/- 1.1 vs. 12.8 +/- 0.7; p < 0.05) and apoA (121.0 +/- 4.8 vs. 111.2 +/- 2.4 mg/dl; p < 0.05). A marked decrease in the level of factor VII (FVIIc) (114 +/- 5.9 vs. 136 +/- 5.3%; p < 0.001) and fibrinogen (2.95 +/- 0.17 vs. 3.58 +/- 0.17 g/l; p < 0.01) was found. Fibrinogen levels fell notably (3.09 +/- 0.30 vs. 3.87 +/- 0.34 g/l; p < 0.05) in the subgroup with arterial hypertension, and F1 + 2 markers tended to decline (2.32 +/- 0.53 vs. 2.74 +/- 0.37 nmol/l; NS). Patients with normals arterial pressure maintained their fibrinogen levels (3.23 +/- 0.24 vs. 3.36 +/- 0.26 g/l; NS). A positive correlation between FVIIc and F1 + 2 was observed during treatment. All results were expressed as arithmetic means +/- SE. The present study has demonstrated that etofibrate has hypolipemic, antithrombotic and antiatherosclerotic properties in patients with polymetabolic syndrome.

Arteriosclerosis↗
PubMed1999

Increased levels of factor VII, fibrinogen and activity of plasminogen activator inhibitor during postprandial triglyceridemia in patients with ischemic heart disease confirmed by angiography.

BACKGROUND AND AIM: Impaired elimination of triglycerides (TG) after postprandial lipemia is often observed in patients with ischemic heart disease (IHD). Longer retention of TG-rich lipoproteins in the circulation may in turn be the cause of hemostatic disturbances in the form of hypercoagulation. The aim of this study was to evaluate the influence of postprandial lipemia on the hemostatic system in normolipemic patients with angiographically documented atherosclerotic changes of coronary arteries. METHODS AND RESULTS: 20 males under 60 years of age with IHD and 10 healthy males matched for age were studied. Hemostatic and lipid parameters were determined in blood collected before (fasting) and after (2, 4, 6 and 8 hours) an oral fat load (200 ml of 30% cream). A statistically significant increase in factor VII (FVIIc-%) was found during postprandial lipemia in comparison with fasting. Although in patients with IHD the area under the curve for FVIIc was not significantly different than in the control group, it was observed that FVIIc in the IHD group exceeded the fasting level earlier (4, 6 and 8 h) than in controls (8 h). Levels of FVIIc reached for the IHD group: fasting value = 96.3 +/- 16.3; postprandial 4 h = 103.2 +/- 21.3, 6 h = 105.2 +/- 21.8, 8 h = 106.0 +/- 21.4; for the controls: fasting value = 96.8 +/- 17.2; postprandial 8 h = 107.7 +/- 22.0. In the IHD group, unlike in controls, postprandial lipemia was accompanied by a statistically significant rise in fibrinogen levels (Fb-g/l) as compared with fasting (fasting value = 3.69 +/- 0.59; postprandial 2 h = 3.89 +/- 0.65, 4 h = 3.93 +/- 0.63). Mean values for PAI-1 were lower in the IHD than in the control group, but PAI-1 activity during postprandial lipemia rose earlier in the IHD group (4 and 6 h) than in the controls (6 h). PAI-1 levels were in the IHD: fasting values = 1.4 +/- 1.2; postprandial 4 h = 2.3 +/- 1.6, 6 h = 2.5 +/- 1.7; in the control: fasting value 2.9 +/- 1.7; postprandial 6 h = 3.9 +/- 2.0. The level of fragment 1 + 2 (F1 + 2) during postprandial lipemia decreased in both groups. CONCLUSIONS: The lipemic stimulus in fasting normolipemics induces a hypercoagulant effect with greater changes in patients with ischemic heart disease than in healthy subjects. Longer periods of postprandial lipemia might constitute an additional factor promoting thrombus formation in patients with dysfunction of the vascular endothelium.

Adult↗
PubMed1998

LDL-R and Apo-B-100 gene mutations in Polish familial hypercholesterolemias.

A group of 30 Polish families with clinical signs of familial hypercholesterolemia was studied for the presence of germ-line mutations in the LDL-R and ApoB-100 genes. Screening of the LDL-R gene was performed at the genomic DNA level by single-strand conformation polymorphism analysis of all 18 exons and extended by sequencing of polymerase chain reaction (PCR) products showing abnormalities. The occurrence of large LDL-R gene alterations was evaluated by analysis of restriction enzyme patterns on Southern blots and using the long-PCR technique. The ApoB-100 gene was studied by combined allele-specific and asymmetric PCR for the occurrence of the common B-3500 missense mutation G to A at nucleotide position 10,708. Germ-line mutations were found in 17 families. In 12 of them LDL-R gene mutations were detected. Three of 11 different mutations had previously been described in other populations (3-bp deletion of codon 197; Ser156Leu; Gly571Glu). Of the mutations not previously recognized and identified in Polish families, there were three small deletions (2-bp deletion AG at codon 291; 4-bp deletion CCCT at codons 661-662; 1-bp deletion A at codon 830), and four point mutations (Arg239Stop, Cys331Stop, Asn543Ser, Gln665Stop). Additionally, one large (approximately 1-kb) LDL-R gene deletion between exons 6 and 9 was identified. In five families, the B-3500 mutation within the ApoB-100 gene was revealed.

Apolipoproteins B↗
PubMed1998

Leptin receptor isoforms expressed in human adipose tissue.

Leptin and its structural gene, Ob, are exclusively expressed in adipose tissue. Leptin is secreted into the blood and is responsible for fat mass regulation via leptin receptors in the hypothalamus. This has been considered the major role of leptin, but leptin receptor isoforms are expressed not only in the brain but also in most other tissues in humans and rodents: heart, placenta, lung, liver, muscle, kidney, pancreas, spleen, thymus, prostate, testes, ovary, small intestine, and colon. This implicates leptin regulation in other systems apart from fat mass regulation, and leptin action has been demonstrated in human fetal development and reproductive development, liver metabolism, hematopoiesis, and insulin secretion. Four splice variants of the leptin receptor have been identified in humans: the long isoform huOb-R and the shorter isoforms B219.1 to B219.3. It is known that the long isoform has full intracellular signaling capacity, and is responsible for anorectic action in the hypothalamus. The roles of the other isoforms are yet to be elucidated. Here, we report the identification by reverse transcriptase-polymerase chain reaction (RT-PCR) of three leptin receptor isoforms coexpressed in human visceral adipose tissue: the long isoform huOb-R and the short isoforms huB219.1 and huB219.3. The possible roles of these isoforms are discussed.

Adipose Tissue↗