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Biomedical subjects

W S Yang

Publications and source records attributed to W S Yang.

At least 37 records · Page 2Linked to original sources
PubMed1999

Association of plasma fibrinogen concentration with vascular access failure in hemodialysis patients.

BACKGROUND: Elevated plasma fibrinogen is an important risk factor for coronary artery disease in the general population and patients with chronic renal failure. High plasma fibrinogen may trigger thrombus formation in arteriovenous fistulas. We performed a prospective, cohort study to evaluate the association of plasma fibrinogen concentration with vascular access failure in patients undergoing long-term haemodialysis. METHODS: Between September 1989 and October 1995, 144 patients underwent a vascular access operation. In March 1997, 102 patients (56 M, 46 F) who had been followed up for more than 18 months (median; 37 months, range; 18-102 months) were included in the study. The median age of the patients was 52 years (range; 19-78 years). In 35 patients, renal disease was secondary to diabetes mellitus. The type of vascular access was a polytetrafluoroethylene (PTFE) graft in 17 patients. Seventy-seven patients received recombinant human erythropoietin (r-HuEPO) therapy during the follow-up period. Plasma fibrinogen, albumin, total cholesterol, hematocrit, platelets and creatinine were measured at the time of operation. Vascular access failure was defined as the occurrence of complications requiring transluminal angioplasty, thrombolytic therapy or surgical repair. RESULTS: Thirty-eight patients had at least one vascular access failure and the incidence was 0.3 (range; 0-2.4) episodes per patient-year. The survival rate of vascular access was 78% (native fistula; 80%, PTFE graft; 71%) after 12 months and 70% (native fistula; 73%, PTFE graft; 51%) after 24 months. Older age, a PTFE graft, r-HuEPO therapy, higher hematocrit, lower albumin and higher fibrinogen levels were significantly associated with vascular access failure, whereas gender, diabetes mellitus, total cholesterol and platelet count were not. Plasma fibrinogen was inversely correlated with albumin (r=-0.38, P=0.001). The cumulative vascular access survival was significantly lower in patients with high plasma fibrinogen levels (> or = 460 mg/dl) compared with patients with low levels (< 460 mg/dl) (P=0.007). Independent risk factors for vascular access failure analysed by Cox's proportional hazards model were older age (RR; 1.36 by 10-year increment), higher fibrinogen level (RR; 1.20 by 100 mg/dl increment), PTFE graft (RR; 2.28) and r-HuEPO therapy (RR; 3.79). CONCLUSION: High plasma fibrinogen level is an independent risk factor for vascular access failure in haemodialysis patients.

Adult↗
PubMed1999

Hyperfibrinogenemia is an independent risk factor for atherosclerotic renal artery stenosis.

It is important to identify patients at risk for atherosclerotic renal artery stenosis because renal artery stenosis is a progressive disease and a potentially correctable problem. To determine the risk factors for atherosclerotic renal artery stenosis, we performed renal arteriography at the time of cardiac catheterization in 270 patients (M:F, 193:77, mean age: 59 years) with clinical ischemic heart disease. Before the procedure, demographic data, medical history, physical findings and laboratory data were obtained. The degree of coronary artery stenosis and renal artery stenosis was quantified with automatic edge detection technique. Significant renal artery stenosis, defined as a narrowing of the diameter by more than 50%, was identified in 28 (10%) patients. Three patients (1%) had bilateral disease. Significant coronary artery disease, defined as a narrowing of the diameter by more than 50%, was present in 231 patients (85%). By univariate logistic regression analysis, older age (68 +/- 8 vs. 58 +/- 10 years), the presence of hypertension (61% vs. 38%), the extent of coronary artery disease, a high fibrinogen level (391 +/- 93 mg/dl vs. 335 +/- 109 mg/dl), a low albumin level (3.9 +/- 0.4 g/dl vs. 4.1 +/- 0.4 g/dl), and a low hemoglobin level (12.5 +/- 1.6 g/dl vs. 13.5 +/- 1.6 g/dl) were associated with the presence of renal artery stenosis (p < 0.05). Serum lipids, lipoprotein(a), creatinine, sex, smoking, or diabetes were not associated. By multivariate logistic regression analysis, older age (OR: 2.43 analyzed by 10 years increment, p = 0.0001), the presence of hypertension (OR: 2.68, p = 0.039) and a higher fibrinogen level (OR: 1.63 analyzed by 100 mg/dl increment, p = 0. 038) were significant risk factors of renal artery stenosis. Fibrinogen level was negatively correlated with albumin level (r = -0.18, p = 0.004). These results suggest that hyperfibrinogenemia as well as old age and hypertension are independent risk factors for atherosclerotic renal artery stenosis.

Aged↗
PubMed1999

Individual or combined effects of enalapril and verapamil on chronic cyclosporine nephrotoxicity in rats.

Previous studies have demonstrated that enalapril and verapamil seem to attenuate the cyclosporine nephrotoxicity. However, the mechanisms have not been completely understood, especially on molecular events. The aim of this study was to examine the effect of individual or combined treatment on osteopontin, TGF-beta, endothelin-1 and procollagen alpha 1(I) mRNA expressions. Enalapril (50 mg/L in drinking water) and verapamil (0.5 mg/kg/day, subcutaneously), alone or in combination, were administered to rats with chronic cyclosporine nephrotoxicity (cyclosporine, 25 mg/kg/day, subcutaneously) (n = 5 each). Five rats treated with olive oil vehicle were used as control. After 4 weeks, biochemical parameters were measured, and renal cortical mRNA levels were evaluated by Northern blot analysis. Cyclosporine reduced renal creatinine clearance significantly and induced renal cortical osteopontin, TGF-beta, endothelin-1 and procollagen alpha 1(I) gene expressions around 13.5 +/- 1.3, 2.4 +/- 0.2, 1.5 +/- 0.1, 1.9 +/- 0.1 folds, respectively. Individual treatment with enalapril or verapamil significantly suppressed the osteopontin and TGF-beta mRNA expression, but not endothelin-1 and procollagen alpha 1(I). Combined treatment also inhibited the osteopontin and TGF-beta mRNA expression but there was no difference between combined and individual treatment. In conclusion, enalapril or verapamil significantly blunted the cyclosporine-induced osteopontin and TGF-beta gene expressions. However, combined treatment did not show any additive effect.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1999

Role of hypoalbuminemia in the genesis of cardiovascular disease in dialysis patients.

Our objective was to review the articles about the association between hypoalbuminemia and atherosclerotic or thrombotic cardiovascular disease (CVD) and to look for possible explanations for the role of hypoalbuminemia. Increased incidences of CVD were reported in patients with hypoalbuminemia owing to renal or other diseases. Hypoalbuminemia increases plasma levels of lipoprotein(a), fibrinogen, and arachidonic acid metabolites; it also increases platelet aggregability and blood viscosity, all of which may contribute to the development of CVD. This cause effect association is thought to be "dependent." Changes in atherogenic lipoproteins or lipids, such as LDL cholesterol, triglycerides, and apolipoprotein B, are controversial in hypoalbuminemic dialysis patients, possibly because coexistent malnutrition and volume status can affect both albumin and lipids. In our recent study, there was a negative correlation between serum albumin and C-reactive protein, D-dimer (an index of intravascular thrombogenesis), and von Willebrand factor (a marker for endothelial cell injury), but infusion of albumin did not affect the level of these parameters, which suggests that the correlations may be an effect-effect association by a confounding variable, such as inflammation. In conclusion, hypoalbuminemia is associated with cardiovascular disease via two pathways: one, a "dependent" cause-effect association; the other, an effect-effect association.

Arteriosclerosis↗
PubMed1998

Treatment of chronic hepatitis B with lamivudine in renal transplant recipients.

BACKGROUND: Lamivudine is a potent inhibitor of hepatitis B virus replication. Little has been reported about the efficacy and safety of lamivudine in the treatment of chronic hepatitis B in the setting of renal transplantation. METHODS: Two patients were treated for chronic hepatitis B with lamivudine and subsequently underwent renal transplantation. Four other patients were treated with lamivudine for reactivation of hepatitis B after renal transplantation. Chronic hepatitis B was proven histologically in all the patients. The doses of lamivudine ranged from 100 to 150 mg/day. Hepatic enzyme and viral markers were monitored. RESULTS: Lamivudine was well tolerated for a median duration of 8 months (range, 4-14 months) without significant side effects. Viral replication was suppressed, as evidenced by negative conversion of serum hepatitis B virus DNA in all the patients. Hepatic enzyme was also normalized. Modification of doses of immunosuppressant regimen was not required in using lamivudine in all patients. One patient experienced acute rejection and responded to solumedrol pulse therapy with normalization of graft function. Normal graft function was maintained in other patients while they were treated with lamivudine. CONCLUSION: Lamivudine was a safe and effective therapy for activated hepatitis B in renal transplant recipients in the short term.

Adult↗
PubMed1998

Effect of increasing serum albumin on haemostatic factors synthesized in the liver in CAPD patients.

BACKGROUND: This study was performed to evaluate the relationship between serum albumin and plasma concentration of haemostatic factors and the effect of raising serum albumin on haemostatic factors synthesized in the liver in CAPD patients. METHODS: We measured blood levels of albumin, fibrinogen, factor II, factor VII, protein C, free protein S, plasminogen, alpha2-antiplasmin and antithrombin III in 103 CAPD patients and 30 normal controls. Twenty-two patients with albumin < 3.5 g/dl were divided into two groups. In the experimental group (n = 11), haemostatic factors and albumin were measured before, after repeated infusion of 20% albumin 100 ml three times per week for 2 weeks, and 4 weeks after withdrawal of albumin infusion. The same parameters were measured in the control group (n = 11) which did not receive albumin infusion. C-reactive protein and haematocrit were followed in both groups as an indicator of acute phase reactant and an indirect measure of volume status. RESULTS: CAPD patients as a whole had lower albumin and higher fibrinogen and factor VII than normal controls. A significant inverse correlation was present between fibrinogen and albumin (r = -0.27, P < 0.01). Albumin in the experimental group increased from 2.7 +/- 0.4 to 3.5 +/- 0.6 g/l at the end of its repeated infusion and haematocrit decreased from 26.6 +/- 4.4 to 24.9 +/- 5.2%. Fibrinogen and factor VII decreased significantly, even after correction for haematocrit (624 +/- 96 vs 556 +/- 91 mg/dl, 160 +/- 36 vs 121 +/- 44%, P < 0.05). Four weeks after withdrawal of albumin infusion, serum albumin decreased to 2.7 +/- 0.5 g/dl, whereas fibrinogen and factor VII increased to 619 +/- 78 mg/dl and 158 +/- 32%, respectively (P < 0.05). Albumin, haematocrit and haemostatic factors in the control group did not change. CRP was stable during the study period in both groups. CONCLUSION: These findings indicate that hypoalbuminaemia is an important trigger factor in the elevation of fibrinogen, and possibly factor VII, in CAPD patients.

Adolescent↗
PubMed1998

Chemokines, osteopontin, ICAM-1 gene expression in cultured rat mesangial cells.

To investigate whether MCP-1, CINC, RANTES, osteopontin and ICAM-1 mRNA could be induced in cultured rat mesangial cells by interleukin-1beta(IL-1beta), tumor necrosis factor-alpha (TNF-alpha) and lipopolysaccharide (LPS), and whether MCP-1 and CINC gene expression could be modulated by dexamethasone, Northern blot assays were performed. IL-1beta induced MCP-1, CINC, RANTES and ICAM-1 gene expression in a time dependent manner. IL-1beta-induced MCP-1, CINC and ICAM-1 mRNA amount were maximal at 3 hours exposure around 14.5, 15.7, 2.2 folds increase and IL-1beta-induced RANTES mRNA at 24 hours around 2.0 folds. TNF-alpha and LPS also induced MCP-1 and ICAM-1 gene expression. TNF-alpha also induced RANTES gene expression but LPS did not. On the other hand, IL-1beta, TNF-alpha and LPS had little effect on osteopontin gene expression but fetal calf serum could increase osteopontin mRNA. Dexamethasone suppressed the IL-1beta-induced MCP-1 and CINC mRNA. These results suggest that, through these gene expressions, mesangial cells are able to communicate directly or indirectly with macrophages or neutrophils, which may lead to glomerulosclerosis.

Animals↗
PubMed1998

Sp1 and Sp3 transactivate the human lipoprotein lipase gene promoter through binding to a CT element: synergy with the sterol regulatory element binding protein and reduced transactivation of a naturally occurring promoter variant.

Lipoprotein lipase (LPL) is a key enzyme in lipoprotein and energy metabolism and, therefore, regulation of its expression could have an important bearing on these processes. We have identified an evolutionarily conserved 5'-CCTCCCCCC-3' motif (from -91 to -83, CT element) in the human LPL gene promoter, deletion or mutation of which caused approximately 70-80% decrease in promoter activity. We found that Sp1 and Sp3 in THP-1 nuclear protein extracts bind specifically to this element. Co-transfection with Sp1 and Sp3 expression plasmids transactivated the LPL promoter via the CT element in Drosophila SL2 cells devoid of Sp proteins. Sp3 moderately repressed Sp1-mediated LPL promoter activation when both were co-expressed in SL2 cells. Furthermore, co-expression of an active sterol regulatory element binding protein (SREBP-1), with Sp1, but not with Sp3, synergistically activated the LPL promoter in SL2 cells. We previously reported a naturally occurring T-->G substitution at position -93 of the human LPL promoter which reduces promoter activity by 40-50% in transient transfection assays. In this study, we showed that this substitution results in reduced binding affinity to Sp1/Sp3 and in diminished transactivation by Sp1/Sp3 alone and by the synergistic action of Spl and SREBP-1 In conclusion, recruitment of Sp1/Sp3 by the CT element may play an important role in expression of the human lipoprotein lipase gene. Synergistic transcriptional activation by Sp1 and SREBP-1 may provide a mechanism for cross-talk between cholesterol and triglyceride metabolic pathways.

Base Sequence↗
PubMed1997

Effect of increasing serum albumin on serum lipoprotein(a) concentration in patients receiving CAPD.

Lipoprotein(a) [Lp(a)], an independent risk factor for atherosclerotic cardiovascular disease in the general population, is known to be elevated in patients with renal disease accompanied by hypoalbuminemia such as nephrotic syndrome and end-stage renal disease. In this study, the role of hypoalbuminemia in the elevation of serum Lp(a) was investigated in 20 continuous ambulatory peritoneal dialysis (CAPD) patients with serum albumin below 3.5 g/dL. The patients were divided into two groups. In group 1 (n = 10), fasting serum Lp(a) and albumin were measured before, after repeated infusion of 20% albumin 100 mL three times per week for 2 weeks, and 4 weeks after withdrawal of albumin infusion. In group 2 (n = 10), serum albumin and Lp(a) were measured similarly without albumin infusion. C-reactive protein was monitored in both group as an indicator of acute-phase reactant. Serum Lp(a) was also measured in 20 age- and sex-matched normal controls. Apolipoprotein(a) [apo(a)] phenotype was determined in all the subjects. CAPD patients as a whole (n = 20; median, 70.2 mg/dL; interquartile range, 45.0 to 86.2 mg/dL) had higher serum Lp(a) than normal controls (n = 20; median, 9.9 mg/dL; interquartile range, 2.4 to 24.3 mg/dL) (P < 0.0001), although the distribution of apo(a) phenotype was similar. Serum albumin in group 1 increased from 2.6+/-0.5 g/dL to 3.5+/-0.6 g/dL (P < 0.0005) at the end of repeated infusion of albumin, whereas serum Lp(a) decreased from 73.7 mg/dL (range, 43.2 to 89.0 mg/dL) to 25.6 mg/dL (range, 10.7 to 71.7 mg/dL) (P < 0.01). Four weeks after withdrawal of albumin infusion, serum albumin decreased again to 2.9+/-0.5 g/dL (P < 0.001), whereas serum Lp(a) increased to 65.2 mg/dL (range, 43.3 to 106.0 mg/dL) (P < 0.05). Serum albumin in group 2 was 2.8+/-0.6 g/dL, 3.0+/-0.4 g/dL, and 2.9+/-0.7 g/dL, respectively. The change of serum Lp(a) was not significant (67.0 mg/dL [range, 46.8 to 84.8 mg/dL], 62.8 mg/dL [range, 45.1 to 81.0 mg/dL], and 63.0 mg/dL [range, 44.7 to 74.0 mg/dL]). C-reactive protein was stable during the study period in both groups. These findings support the hypothesis that hypoalbuminemia is one of the important trigger factors in the elevation of serum Lp(a) in CAPD patients.

Albumins↗
PubMed1997

Paramyotonia congenita and hyperkalemic periodic paralysis associated with a Met 1592 Val substitution in the skeletal muscle sodium channel alpha subunit--a large kindred with a novel phenotype.

Paramyotonia congenita (PC) and Hyperkalemic periodic paralysis (HyperPP) are caused by amino acid substitutions in the alpha subunit of the human skeletal muscle sodium channel. One such substitution, methionine for valine at position 1592, has been associated with HyperPP with myotonia and cold sensitivity. We report clinical, electromyographic (EMG), genetic and pathological features of a large kindred with the Met1592Val substitution. Affected members were phenotypically heterogenous and had episodic potassium-sensitive paralysis, and stiffness and weakness induced by exercise and cold, which was confirmed by EMG studies. These features indicate a combined PC-HyperPP phenotype not previously described with this mutation.

Adult↗
PubMed1997

Treatment of hepatitis B virus associated glomerulonephritis with recombinant human alpha interferon.

To evaluate the therapeutic effect of recombinant human alpha-interferon (alpha-IFN) on hepatitis B virus associated glomerulonephritis (HBV-GN) and the relationship between the seroconversion of viral antigens and the change of proteinuria, the hepatitis B viral markers and urinary protein were monitored during alpha-IFN treatment in 8 male adult patients who (1) were positive in serum HBsAg and HBeAg, (2) had chronic hepatitis, (3) had persistent proteinuria > 1 g/day, and (4) showed glomerulonephritis on kidney biopsy. alpha-IFN was given at a dose of 3 million units, subcutaneously, three times a week for 6 months. Kidney biopsy specimens showed membranoproliferative glomerulonephritis (MPGN) in 4 patients, mesangial proliferative glomerulonephritis (MesPGN) in 2, and membranous glomerulonephritis (MGN) in 2 patients. Seven of the 8 patients received a 6-month course of alpha-IFN therapy; 1 patient with MGN quitted therapy 2 months after the initial dose because of side effects. In 5 of the 7 patients who received a 6-month therapy, serum HBeAg disappeared, and anti-HBe appeared during the therapy. In 2 of these 5 patients, HBeAg reappeared, in 1 during alpha-IFN therapy and in 1 9 months after the last dose of alpha-IFN. The hepatitis B viral markers of the patient who received a 2-month therapy did not change. HBs antigenemia persisted in all patients. In all 4 patients with MPGN, serum HBeAg was transiently or persistently converted to negative, but the proteinuria persisted. Both patients with MesPGN showed remission of proteinuria; however, only 1 patient had seroconversion of HBeAg. In 2 patients with MGN, proteinuria persisted. In conclusion, alpha-IFN at the doses given was not effective in MPGN type of HBV-GN. Improvement of proteinuria was achieved in MesPGN patients without disappearance of HBs antigenemia which is the finding against the possible role of HBsAg in the pathogenesis of this type of HBV-GN.

Adult↗
PubMed1997

Protein intake and the nutritional status in patients with pre-dialysis chronic renal failure on unrestricted diet.

OBJECTIVES: Malnutrition is known to be highly associated with morbidity and mortality in dialysis patients. Malnutrition may begin to develop in patients with chronic renal failure(CRF) before they need dialysis. In this study, the nutritional status of patients with moderate to severe CRF on unrestricted diet was evaluated. METHODS: We measured dietary protein intake (DPI, g/kg/day) in 64 patients with CRF and 42 normal controls(N). Nutritional indices such as serum albumin(SA, g/dl), transferrin(TF, mg/dl), prealbumin(PA, mg/dl) and insulin-like growth factor-1(IGF-1, ng/ml) were measured to evaluate the visceral proteins, and creatinine-height index(C-H, g/d/m) to evaluate the somatic proteins. RESULTS: Mean DPI was 0.80 +/- 0.27(S.D) in CRF and 1.07 +/- 0.30 in N(p < 0.0001). DPI was lower than 0.6 in 15 CRF patients(23%). Serum albumin, transferrin and C-H were significantly lower in CRF patients than in N(p < 0.01). In patients with CRF, nutritional indices were significantly worse with lower DPI(< 0.6 g/kg/d, n = 15) than higher DPI(> 0.6 g/kg/d, n = 49)(SA 2.9 +/- 0.7 vs. 3.6 +/- 0.8, p < 0.005; TF 147 (134-179) vs. 220(182-264), p < 0.0005; PA 24 +/- 8 vs. 32 +/- 9, p < 0.001; IGF-1 123 (66-261) vs. 226(140-344), p < 0.05; C-H 0.52 +/- 0.15 vs. 0.87 +/- 0.23, p < 0.0001). CRF patients with nephrotic range proteinuria (> 3.5 g/d, n = 19) had lower SA (2.8 +/- 0.6 vs. 3.8 +/- 0.8, p < 0.0001) and PA(27 +/- 9 vs. 32 +/- 9, p < 0.05). CRF patients with diabetes mellitus (n = 20) showed worse nutrition than non-diabetic patients(SA 2.8 +/- 0.6 g/dl vs. 3.8 +/- 0.8 g/dl, p < 0.0001; TF 176 mg/dl(148-214) vs. 220 mg/dl(175-266), p < 0.05; PA 24 +/- 10 mg/dl vs. 33 +/- 8 mg/dl, p < 0.0005; IGF-1 138 ng/ml(69-269) vs 231 ng/ml(140-364), p < 0.05; C-H 0.66 +/- 0.23 vs. 0.85 +/- 0.5, p < 0.005). CONCLUSION: A significant protein malnutrition prevails in patients with pre-dialysis CRF on unrestricted diet, especially with low protein intake. The effort to detect and correct malnutrition should be made in patients with CRF even before initiation of maintenance dialysis.

Adult↗
PubMed1996

Risk factors of sudden infant death in Chinese babies.

The influence of social and biologic factors on sudden infant death was studied in a large Chinese population. Data from all birth certificates in Taiwan from 1988 to 1992 were merged with death certificate data for postneonatal deaths from sudden infant death syndrome and suffocation. The Cox's proportional hazard model was used to compute multivariate adjusted relative risk estimates and 95% confidence intervals. Age difference of parents of more than 10 years was associated with a relative risk (RR) of 1.8 (multivariate adjusted, 95% confidence interval (CI) 1.3-2.3). Better than elementary education for the father was protective (adjusted RR 0.8, 95% CI 0.7-1.0, p < 0.05), and college education of the mother elevated the risk (adjusted RR 1.2, 95% CI 1.0-1.4, p < 0.05). Infants born second to fourth had an adjusted RR of 1.7 (95% CI 1.5-1.9), and infants born fifth or higher had a RR of 2.3 (95% CI 1.5-3.4). The multivariate adjusted RR for low birth weight and prematurity were 2.3 (95% CI 1.9-2.8) and 1.2 (95% CI 1.0-1.5), respectively. Data from this 5-year cohort in Taiwan emphasize biologic and social variables as important risk factors of sudden infant death in Chinese babies.

Asphyxia↗
PubMed1996

Gender differences in postneonatal infant mortality in Taiwan.

Numerous studies have indicated that gender discrimination influencing child survival is widespread in Asia. Therefore, we have investigated gender and cause-specific postneonatal mortality in Taiwan. Mortality data derived from death certificates and demographic statistics in Taiwan between 1981 and 1990 were analyzed. Postneonatal mortality decreased from 9.4 per 1000 live births to 5.5 per 1000 live births for males, and from 8.3 to 5.0 for females. The trends for cause-specific mortality for male and female infants were similar during the study period. The male-to-female ratio of overall death rates was 1.11. It was slightly higher in cities and lower in rural areas, and lowest in the least developed eastern region of Taiwan. Mortality from congenital diseases had the lowest male-to-female ratio, specifically in the North, the cities and areas of indigenous people. Infectious disease mortality showed low male-to-female ratios in the rural areas and in the eastern region. The place of death from infectious diseases as a measure for the use of sophisticated medical care showed that more female than male deaths occurred at home in the rural areas, cities, and central regions. It was concluded that a high level of socio-economic development created conditions of gender equality, whereas in situations of low socio-economic development males were favoured. The tendency to discriminate according to gender is very subtle in Taiwan, much less so than in other regions of Asia, including Thailand and India.

Cultural Characteristics↗
PubMed1996

Lipocortin-1 inhibits proliferation of cultured human mesangial cells.

Lipocortin-1, a 37-kDa member of the annexin family of proteins, originally evoked interest as one of the second messengers for the anti-inflammatory actions of glucocorticoids. Studies showed that glucocorticoids inhibited the proliferation of various cell types and lipocortin-1 mediated growth inhibition of glucocorticoids in a human lung adenocarcinoma cell line. The presence of specific lipocortin-1-binding sites (receptor-like molecules) on monocytic cells has been demonstrated. This study was performed to evaluate the effects of hydrocortisone and recombinant human lipocortin-1 on cultured human mesangial cells (CHMC), and the effects of anti-lipocortin-1 antibody on the hydrocortisone-induced inhibition of CHMC proliferation. The existence of specific binding sites for lipocortin-1 was also investigated. Lipocortin-1 inhibited CHMC proliferation in a dose-dependent manner as determined by [3H]thymidine uptake and cell count. Growth of CHMC was inhibited to 18% of the control in the presence of 5 micrograms/ml of lipocortin-1. Similar growth-inhibitory activity by lipocortin-1 was observed in CHMC activated by platelet-derived growth factor. Hydrocortisone also inhibited cell proliferation in a dose-dependent manner. One to 5,000 dilution of anti-lipocortin-1 antibody reversed hydrocortisone-induced inhibition of CHMC proliferation partially, whereas concentrations over 1:1,000 reversed the inhibition completely. Flow cytometry analysis as well as indirect immunofluorescent microscopy revealed specific binding sites on the surface of CHMC. These results support the hypothesis that corticosteroids act by inducing CHMC to synthesize or secrete lipocortin-1, and that lipocortin-1 generates proliferation-suppressive signal(s) through specific binding sites on CHMC.

Annexin A1↗
PubMed1996

Regulatory mutations in the human lipoprotein lipase gene in patients with familial combined hyperlipidemia and coronary artery disease.

We previously reported a compound heterozygote [T(-39)C/T(-93)G] in the human lipoprotein lipase (LPL) gene promoter in one out of 19 patients with familial combined hyperlipidemia (FCHL) and reduced post-heparin plasma LPL levels. The T(-39)C substitution resulted in 85% decrease in LPL promoter activity. Further screening of Caucasian patients with FCHL, coronary artery disease (CAD), and of unselected Caucasian subjects revealed four additional LPL promoter variants. Among the same 19 FCHL patients with reduced LPL levels, we found one heterozygote for a G(-53)C substitution. Among 115 CAD patients, we found five heterozygotes and one homozygote for the T(-93)G substitution and one heterozygote for a CC insertion between +13 and +19 of the 5' untranslated region. In a group of 183 unselected subjects, three heterozygotes with the T(-93)G substitution were found. The G(-53)C substitution led to approximately 70-75% decrease in promoter activity as assayed by transient transfections of THP-1 (macrophage-like) and C2C12 (myotube-like) cells. The T(-93)G substitution resulted in reduction of promoter activity by approximately 40-50%. The CC insertion between +13 and +19 caused a decrease in promoter activity by 20% in THP-1 and 50% in C2C12. Substitutions at -79 and -95, which had no effect on promoter function, were also discovered in the population samples studied. The finding of two promoter mutations (-39 and -53) among 19 FCHL patients with diminished LPL, but not among the other groups of subjects, suggests a potential role of regulatory mutations of the LPL gene in the development of dyslipidemia in FCHL.

Coronary Disease↗