The lactose transporter of Staphylococcus aureus--overexpression, purification and characterization of the histidine-tagged domains IIC and IIB

Epidemiological studies have shown lipoprotein(a) (Lp(a)) to be an independent risk factor for cardiovascular disease. Lp(a) is a cholesterol-rich, low-density lipoprotein (LDL)-like particle to which a large glycoprotein, apolipoprotein(a) (apo(a)) is attached. Plasma Lp(a) levels are highly genetically determined and influenced to a minor degree by environmental factors. In an effort to determine whether Lp(a) might be associated with longevity, we have evaluated Lp(a) levels and apo(a) isoform sizes in a population of French centenarians (n = 109) compared to a control group (n = 227). The mean age of centenarians was 101.5 +/- 2.4 years while the control group was 39.4 +/- 7.2 years. Plasma levels of total cholesterol and triglyceride were within the normal range in both centenarian and control subjects. Lp(a) levels were higher in centenarians (both male and female) than in the normolipidemic control group (mean Lp(a) level = 0.33 +/- 0.42 and 0.22 +/- 0.27 mg/ml, respectively, P < 0.005). The distribution of apo(a) isoforms was significantly shifted towards small isoform size in the centenarian population as compared to the controls (54.4 and 41.4% of isoforms < or = 27 kringles (kr), respectively, P = 0.04). Nonetheless, the apo(a) size distribution in centenarians did not entirely explain the high Lp(a) levels observed in this population. Factors other than apo(a) size, and which may be either genetic or environmental in nature, appear to contribute to the elevated plasma Lp(a) levels of our centenarian population. We conclude therefore that high plasma Lp(a) levels are compatible with longevity.     

Lipoprotein (a) in children with chronic renal failure treated conservatively

The aim of this study was to evaluate serum lipid abnormalities, particularly lipoprotein (a), [Lp(a)] as an independent risk factor for cardiovascular disease in children with mild and moderate renal failure. Study were performed on 14 children of whom serum creatinine levels were above 265.3 mumol/l and 32 patients with serum creatinine levels below 265.3 mumol/l. Control group consisted of 27 healthy age-matched subjects. All children were tested for concentration of serum Lp(a), total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (C-LDL) and high density lipoprotein cholesterol (C-HDL). It was found a significantly increase in Lp(a), TC, C-LDL and significantly decrease in C-HDL in children with more advanced renal insufficiency compared to the control. In children with mild renal failure concentration of serum Lp(a) also increased but not significantly. Patients in this group had elevated serum TC and decreased C-HDL. These results suggest that even in the early stages of renal insufficiency in children abnormalities of lipoprotein are present. Such abnormalities, particularly Lp(a) might contribute to accelerated atherosclerosis in this patients.     

Lipoprotein(a) levels in the Japanese population: influence of age and sex, and relation to atherosclerotic risk factors. The Jichi Medical School Cohort Study

The authors studied the distribution of lipoprotein(a) (Lp(a)) levels with stratification for age and sex, as well as the relation between Lp(a) and atherosclerotic risk factors in a large Japanese population between 1992 and 1993. The subjects were 1,235 males and 1,762 females over 30 years old. Lp(a) was measured by an enzyme-linked immunosorbent assay. Lp(a) levels were higher in females than in males. The increase in Lp(a) with age was statistically significant, and the proportion of subjects with Lp(a) levels > 30 mg/dl also increased with age. In the obese subjects (body mass index (BMI) (kg/m2) > 26), Lp(a) levels were lower than in the non-obese subjects (BMI < or = 26) (p < 0.01 in males; p < 0.05 in females). Male alcohol drinkers had lower Lp(a) levels than nondrinkers (p < 0.05). Age, low density lipoprotein subtracting Lp(a) cholesterol [Lp(a) x 0.3], and fibrinogen level were all positively correlated with Lp(a) in both sexes. Alcohol consumption (g/day) and triglycerides were inversely correlated with Lp(a) in males, while total cholesterol subtracting Lp(a) cholesterol [Lp(a) x 0.3], high density lipoprotein, and factor VII were positively correlated in females. Multiple logistic regression analysis showed that triglycerides in males and BMI and fibrinogen in females were significant independent variables. The authors conclude that Lp(a) level is affected by various factors, such as alcohol drinking, BMI, sex, and age, and is not only correlated with lipid levels but also with hemostatic factors such as fibrinogen and factor VII.     

Apolipoprotein(a) genetic polymorphism and serum lipoprotein(a) concentration in patients with peripheral vascular disease

Serum lipoprotein(a) (Lp(a)) levels were measured in 89 men with peripheral vascular disease (PVD) and 129 (100 male and 29 woman) healthy controls. Apolipoprotein(a) genetic polymorphism was determined by immunoblotting in all subjects. Patients with PVD had significantly higher serum Lp(a) levels than controls. Apolipoprotein(a) phenotype frequencies in patients with PVD did not differ from those of the control group. Both patients and controls with phenotype S2 had higher serum Lp(a) levels than those with phenotype S4. It should be emphasized that serum Lp(a) levels were significantly higher in PVD patients than controls for those with phenotype S2, S3/S4 and S4. Raised serum Lp(a) levels together with other lipoprotein abnormalities in patients with PVD imply a high cardiovascular risk. Genetic polymorphism clearly influences serum Lp(a) levels both in patients and controls. In patients with PVD, environmental and/or other genetic factors must play a role in raising Lp(a) levels.     

Analysis on the interaction among agents in arteriosclerotic cerebral infarction

An 1:1 matched case-control study including 105 arteriosclerotic cerebral infarction cases and 105 controls was carried out to estimate the etiologic interaction, in Yi-xing city, March 1997. Results showed that the major risk factors were high levels of serum TG, Lp(a) and BMI while serum level of HDL-C was the only protective factor. When several levels were divided on Lp(a) and BMI, a significantly dose response relation was found. Considering the correlation among serum concentration of lipids, we analysed the interaction of different factors, using Log-Linear models. Results showed that there were significant interactions between arteriosclerotic cerebral infarction and TC, TG, HDL-C and Lp(a). There were also interactions between TC, TG, HDL-C and LDL-C. However, the strongest interaction is expected to happen at what level remains further investigations.     

Bioplastique as a complement in conventional plastic surgery

BACKGROUND: Calcified aortic value disease is increasing with explosively in the elderly. Elevated serum lipoprotein(a) (Lp(a) plays an important role in the pathogenesis of atherosclerosis. Thus, we investigated the relationship between aortic valve sclerosis and serum Lp(a) levels in elderly patients. METHODS: Echocardiography was performed in 97 subjects (77 +/- 7 years, 48 males and 49 females), Lp(a), fasting plasma glucose, and blood pressure were measured at the time of the study. Aortic valve sclerosis was assessed using echocardiography. RESULTS: Aortic valve sclerosis was observed in 63 patients (sclerosis group; 24 males and 39 females) and not in 34 subjects (non-sclerosis group; 24 males and 10 females). Univariable analysis revealed that age, Lp(a) level, and the number of females were higher in the sclerosis group than in the non-sclerosis group (age; 78 +/- 7 vs 74 +/- 7 years, p = 0.0090, Lp(a); cholesterol, triglyceride, and fasting blood glucose did not seem to affect aortic valve sclerosis. In all of 9 patients with serum Lp(a) greater than 60mg/dl aortic valve sclerosis was present. In discriminative analysis, gender (female) (lambda = 0.9038, p = 0.0020) and Lp(a) (lambda = 0.8316, p = 0.0053) were related to aortic valve sclerosis. CONCLUSION: Elevated serum Lp(a) was observed in elderly patients with aortic valve sclerosis.     

Effects of fluvastatin, a new inhibitor of HMG-CoA reductase, and niceritrol on serum lipids, lipoproteins and cholesterol ester transfer activity in primary hypercholesterolemic patients

Effects of a combination therapy of fluvastatin, a new inhibitor of HMG-CoA reductase, and niceritrol on lipid metabolism were investigated measuring a wide range of parameters in 42 patients with primary hypercholesterolemia. After a wash-out period patients were randomly allocated to 1 of the 2 groups, the fluvastatin-preceding group (G-1) and the niceritrol-preceding group (G-2). In G-1 fluvastatin monotherapy (30 mg/day) significantly decreased total cholesterol (TC) and LDL-cholesterol (LDL-C). There was no significant change in HDL-cholesterol (HDL-C), triglyceride (TG) and lipoprotein (a) (Lp(a)). Further effect in HDL-C and TG was observed after the addition of niceritrol (750 mg/day). On the other hand, in G-2, while niceritrol alone (750 mg/day) produced no significant change in TC, LDL-C, HDL-C, TG and Lp(a), the addition of fluvastatin (30 mg/day) reduced TC and LDL-C levels significantly. Cholesterol ester transfer (CET) activity was significantly reduced by niceritrol monotherapy. After the concomitant use of the 2 drugs CET activity was significantly reduced only in G-2. No significant change in lipoprotein lipase and hepatic triglyceride lipase activities were observed in the 2 groups at either point in time. No serious adverse effect was observed in this study. It is concluded that fluvastatin is an effective drug for lowering LDL-cholesterol and causes no adverse alteration in lipid metabolism. Combination with niceritrol at a dose of 750 mg/day dose not appear to augment or attenuate beneficial effects of fluvastatin.     

Lipoprotein(a) is an independent risk factor for coronary artery disease in NIDDM patients in South India

OBJECTIVE: Asian Indians have been reported to have very high prevalence rates of coronary artery disease (CAD) in the absence of traditional risk factors. Recently, elevated levels of lipoprotein(a) [Lp(a)] have been reported to be associated with premature CAD in migrant Asian Indians. However, there are very little data regarding Lp(a) in CAD patients from the Indian subcontinent and virtually none in individuals with NIDDM. The objective of this study was to assess the role of Lp(a) as a marker for CAD in South Indian NIDDM patients. RESEARCH DESIGN AND METHODS: We estimated serum Lp(a) in 100 control subjects, 100 NIDDM patients without CAD, and 100 NIDDM patients with CAD. Lp(a) values were transformed into natural logarithms. Statistical analysis included Student's t test, one-way analysis of variance, and chi2 test. Multiple logistic regression analysis was used to identify associations with CAD. RESULTS: Lp(a) levels were significantly higher in NIDDM patients with CAD compared with NIDDM patients without CAD and control subjects (geometric mean 24.6, 15.1, and 19.4 mg/dl, respectively, P < 0.05). Results of logistic regression analysis showed that Lp(a), age, and HDL were associated with CAD. In NIDDM patients with CAD, there was no correlation between Lp(a) and serum cholesterol, triglyceride, or HDL cholesterol levels, but there was a weak association with LDL cholesterol and systolic blood pressure. CONCLUSIONS: The data suggests that serum Lp(a) is an independent risk factor for CAD in NIDDM patients in South India.     

Diazepam-sensitive GABA(A) receptors in the NTS participate in cardiovascular control

Lipoprotein (a) [Lp(a)] is synthesised by liver cells, and patients with liver cirrhosis (LC) show low serum levels of Lp(a) associated with the degree of liver failure. On the contrary, increased serum levels of Lp(a) have been reported in patients with cancer. In this report, the behaviour of Lp(a) serum levels in patients with hepatocarcinoma (HC), a complication of LC, has been evaluated with the aim to study whether HC cells were able to cause an increase of serum concentrations of this lipoprotein when impaired liver protein synthesis is present. We selected eighteen patients affected by LC + HC, eighteen patients matched for sex, age and degree of liver failure with LC only, and eighteen patients with other cancer types. A significant increase of serum levels of Lp(a) was observed in patients affected by LC + HC or other cancer types compared with healthy subjects. Forty-four percent of LC + HC patients showed Lp(a) values more than 70.4 Units/dl, i.e., the upper limit of values observed in patients with LC only. Lp(a) serum concentrations were significantly associated with serum albumin both in LC and in LC + HC but not in other cancer-type patients. Thus, comparing patients with similar serum albumin concentrations, Lp(a) serum levels were significantly higher in patients with LC + HC than in patients with only LC and quite similar to those observed in patients with other cancer types. In conclusion, HC cells, in vivo, seem able to produce a greater amount of Lp(a) despite the reduced liver protein synthesis typical of LC.     

Plasma lipid, apolipoprotein and Lp(a) levels in elderly normolipidemic women: relationships with coronary heart disease and longevity

The relation between plasma lipids and coronary heart disease (CHD) in the elderly is still debated, as well as the proposed role of lipoproteins as markers of longevity. In this study both normolipidemic elderly and middle-aged women with CHD showed higher triglycerides and apolipoprotein B levels and lower high-density lipoprotein (HDL)-cholesterol and apolipoprotein A-I levels in comparison with age-matched subjects without CHD. In the middle-aged group, hypertension and HDL-cholesterol levels and, in the elderly group, only HDL-cholesterol levels were independently associated with CHD. No significant difference was found between a group of healthy centenarians and elderly and middle-aged subjects without CHD. These data suggest that plasma lipids are also related to CHD in the elderly and that, even if at present we are not able to consider them as predictors of longevity, some lipoprotein features may contribute to select subgroups of subjects in which other factors play a further role in life expectancy.     

New special research data on over 100-year-old and older probands and problems (II)

The critical evaluation of all so-called correlation factors of the absolute longevity of centenarians lead to the assumption that those of extreme age among the oldest elderly remain as a biological selection of the total population. Due to an unfavorable biological total constellation, the comparable oldest elderly have already died. To solve these selection problems, research reports in this country and abroad are helpful in relation to this special category of centenarians. New findings in laboratory diagnostics, the genetic privileged position of long-living persons regarding their expectancy re arteriosclerosis, as well as the modern molecular biological and neuropathological cerebral studies of deceased persons of the oldest category can be regarded in the sense of a selection of elderly people. The characteristics of the central nervous system, the cardiovascular and pulmonary system of the elderly, give an indication (e.g., of a 100-years-old smoker) of the extreme living conditions of the oldest elderly. A large number of curiosities found in the literature and personally observed unexplainable findings illustrate the remarkable lifestyle of individually selected oldest elderly. The final section discusses the biological, social and psychological special position of the oldest elderly.     

Proton magnetic resonance spectroscopy of linear nevus sebaceus syndrome

OBJECTIVE: The potential effect of ethnicity on the serum lipid profile and lipoprotein(a) [Lp(a)] was studied in a population with chronic spinal cord injury (SCI). STUDY DESIGN: The distribution and correlates of high density lipoprotein (HDL) cholesterol and Lp(a) were studied in a population of 600 subjects with chronic SCI. RESULTS: Mean +/- SEM serum HDL cholesterol was significantly higher in the African American group than in the white and Latino groups (47 +/- 1 vs 40 +/- 1 and 38 +/- 1 mg/dL, p < .0001, respectively). The African American group had a lower serum total to HDL cholesterol ratio than white and Latino groups (4.46 +/- .153 vs 5.18 +/- .168 and 5.40 +/- .140 mg/dL, p < .01, respectively). Mean serum Lp(a) levels were significantly higher in the African American group than in Latino or white groups (29 +/- 2 vs 18 +/- 1 and 15 +/- 1 mg/dL, p < .0001, respectively). Age, duration of SCI, and level and completeness of lesion had no significant effect on serum Lp(a) level. CONCLUSIONS: In a population with chronic SCI, those in the African American group had the highest serum HDL cholesterol concentrations, the lowest serum total to HDL cholesterol ratios, and elevated levels of serum Lp(a) compared with the Latino and white groups. In a population of individuals with chronic SCI, ethnicity was shown to have a major effect on serum lipids and may be used to assist in the determination of cardiovascular risk.     

Attribution, the attractiveness stereotype, and the elderly.

The applicability of the physical attractiveness stereotype to perceptions of the elderly was tested in two studies. In the first study, college age and old observers rated the physical attractiveness of faces of elderly people (age 60–93). On the basis of these ratings, faces at three distinct levels of attractiveness were selected for use in the second study. In the second study, 72 young adult and 72 old volunteers viewed the selected faces and rated them in three areas of perceived social characteristics: personality factors, success in life experiences, and occupational achievements. The typical physical attractiveness stereotype was found for both groups of observers and in each of three areas of judgment. Multivariate analyses of variance for linear trends showed higher favorability of perceived social characteristics for faces with high perceived physical attractiveness. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

High serum lipoprotein(a) levels in Korean type 2 diabetic patients with proliferative diabetic retinopathy

OBJECTIVE: To examine the possible association between serum lipoprotein(a) [Lp(a)] concentration and proliferative diabetic retinopathy (PDR) in Korean patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 412 Korean outpatients with type 2 diabetes were examined. Diabetic retinopathy was determined by an ophthalmologist using fundoscopic examination. Serum Lp(a) levels were measured by two-site sandwich enzyme-linked immunosorbent assay. RESULTS: The patients with PDR had higher serum Lp(a) levels than those with no diabetic retinopathy or with nonproliferative diabetic retinopathy (NPDR). Multiple logistic regression analysis showed that high serum Lp(a) levels and the presence of diabetic nephropathy were independent variables having a statistically significant association with PDR. CONCLUSIONS: Korean type 2 diabetic patients with PDR had higher serum Lp(a) levels versus those with no diabetic retinopathy or with NPDR. Although these results suggest that Lp(a) might play a role in the occlusion of retinal capillaries leading to PDR, further prospective studies are required to prove the causal relationship.     

Lipoprotein(a) interactions with lipid and nonlipid risk factors in early familial coronary artery disease

An interaction between high plasma lipoprotein(a) [Lp(a)], unfavorable plasma lipids, and other risk factors may lead to very high risk for premature CAD. Plasma Lp(a), lipids, and other coronary risk factors were examined in 170 cases with early familial CAD and 165 control subjects to test this hypothesis. In univariate analysis, relative odds for CAD were 2.95 (P < .001) for plasma Lp(a) above 40 mg/dL. Nearly all the risk associated with elevated Lp(a) was found to be restricted to persons with historically elevated plasma total cholesterol (6.72 mmol/L [260 mg/dL] or higher) or with a total/HDL cholesterol ratio > 5.8. Nonlipid risk factors were also found to at least multiply the risk associated with Lp(a). When Lp(a) was over 40 mg/dL and plasma total/HDL cholesterol > 5.8, relative odds for CAD were 25 (P = .0001) in multiple logistic regression. If two or more nonlipid risk factors were also present (including hypertension, diabetes, cigarette smoking, high total homocysteine, or low serum bilirubin), relative odds were 122 (P < 1 x 10(-12)). The ability of nonlipid risk factors to increase risk associated with Lp(a) was dependent on at least a mildly elevated total/HDL cholesterol ratio. In conclusion, high Lp(a) was found to greatly increase risk only if the total/HDL cholesterol ratio was at least mildly elevated, an effect exaggerated by other risk factors. Aggressive lipid lowering in those with elevated Lp(a) therefore appears indicated.     

Growth properties and growth factor responsiveness in skin fibroblasts from centenarians

Human fibroblast cultures, which have a finite replicative lifespan in vitro, are the most widely used model for the study of senescence at the cellular level. An inverse relationship between replicative capability and donor age has been reported in human fibroblast strains. We studied the growth capacity of fibroblast primary cultures derived from people whose lifespan was as closer as possible to the expected maximum human lifespan, i.e. people over one hundred. Our data suggest that outgrowth of fibroblasts from biopsies, growth kinetics at different population doubling levels, capability to respond to a classical mitogenic stimulus (such as 20% serum) and a variety of growth factors, were remarkably similar in fibroblasts from centenarians and young controls. On the whole, our data challenge the tenet of a simple and strict relationship between in vivo aging and in vitro proliferative capability of human fibroblasts, at least at the individual level.     

Do increased lipoprotein(a) levels in euthyroid autoimmune thyroid diseases predict an increased risk of arteriosclerosis?

Elevated serum levels of lipoprotein(a) [Lp(a)] represent an independent risk factor in the development of arteriosclerosis and coronary heart disease. In overt but also in subclinical hypothyroidism a reversible increase of Lp(a) occurs. We compared Lp(a) serum levels, cholesterol, triglyceride, HDL- and LDL-cholesterol in 19 hypothyroid patients prior to and following the state of euthyroidism (group 1). On the other hand in group 2 we investigated 20 euthyroid patients having elevated thyroid antibodies as against 50 euthyroid normolipemic control subjects without detectable thyroid antibodies. Group 1: The elevated Lp(a) serum levels of the hypothyroid patients decreased significantly in the euthyroid state (37.9 +/- 8.24 vs. 28.1 +/- 6.13 mg/dl, mean +/- SEM). Group 2: The mean Lp(a) serum levels of the patients with increased thyroid antibodies were significantly higher than those of the control group (24.8 +- 5.78 vs. 9.6 +/- 1.56 mg/dl, mean +/- SEM). In other parameters of lipid metabolism and thyroidal function no significant differences between both groups could be seen. The question arises whether such isolated Lp(a) elevation will lead to an increased arteriosclerotic risk. To minimize this possible risk regular controls of thyroid function should be carried out in euthyroid patients with elevated thyroid antibodies. In this way hypothyroidism may be detected and treated at an early stage.     

Different change in lipoprotein(a) levels from lipid levels of other lipoproteins with improved glycemic control in patients with NIDDM

OBJECTIVE: To evaluate change both in lipoprotein(a) [Lp(a)] and lipid levels in other lipoproteins in non-insulin-dependent diabetes mellitus (NIDDM) after short-term improvement of glycemic control. RESEARCH DESIGN AND METHODS: We compared Lp(a) levels in 210 NIDDM patients with those in 46 control subjects and evaluated the relationship between glycemic control and Lp(a) levels in diabetic patients. In addition, changes in Lp(a) levels and lipid levels were assessed after the improvement of glycemic control in 54 poorly controlled NIDDM patients. RESULTS: In NIDDM, Lp(a) levels in all patients, 62 patients with HbA1c < 6.0%, and 75 patients with HbA1c between 6.0 and 8.0%, were significantly higher than those in control subjects (19.1 [1.7-106.6], 19.2 [6.0-106.6], and 20.3 [2.7-75.3] vs. 15.4 [2.0-61.7] mg/dl, median [range], P < 0.05). Lp(a) levels in 73 patients with HbA1c of > or = 8.0% (18.7 [1.7-58.8] mg/dl) were not significantly different from those in control subjects. After glycemic control, lipid levels in plasma and in other lipoproteins fell significantly, but Lp(a) did not change (from 18.3 [1.7-58.8] to 18.4 [6.6-95.3] mg/dl). Changes in lipid levels, including Lp(a), did not correlate with those in fasting plasma glucose or HbA1c. CONCLUSIONS: These results suggest that elevated Lp(a) levels do not reflect poor glycemic control and that Lp(a) levels are independent of lipid levels in other lipoproteins after improved glycemic control in NIDDM.     

The results of primary radiotherapy in vaginal carcinoma

The results of two previous and two recent studies of middle-aged males and females are presented to exemplify the clinical importance of lipoprotein(a) (Lp(a)) as a risk factor for atherosclerosis and coronary heart disease. In these studies various conventional and recently suggested risk factors were included and different methods for Lp(a) quantification were used. Lp(a) was a significant risk factor in all four studies. In the recent prospective case-control study, Lp(a) and cholesterol were found to act synergistically and predict primary acute myocardial infarction in Swedish males. A cholesterol level above 6.5 mmol/l increased the risk of acute myocardial infarction if the Lp(a) level was above 200 mg/l. The plasma apo A-I level was a protective factor. In the other recent case-control study, an Lp(a) level above 500 mg/l was a highly significant risk factor in Black and White US women with myocardial infarction or advanced coronary artery disease in addition to low density lipoprotein cholesterol levels above 130 mg/dl. A high apo A-I level was a protective factor. In these studies no other factors tested reached significance in multivariate logistic regression analysis. A hypothetical association between high Lp(a) levels and intracellular infection with Chlamydia pneumoniae is discussed. The results suggest that the Lp(a) level is useful in identifying high-risk individuals. Lowering low density lipoprotein cholesterol below 100 mg/dl (<2.6 mmol/l) seems to be most important in both males and females with high-risk Lp(a) levels.