Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although Trypanosoma brucei brucei fatally infects livestock in much of sub-Saharan Africa, humans are innately resistant to infection, apparently because high-density lipoproteins (HDL) in human serum lyse this unicellular protozoan parasite. Recently, we demonstrated that purified human apolipoprotein (apo) A-I, the major protein (M(r) 28,016) constituent of HDL, had full trypanolytic activity in vitro whereas the apoA-I of cattle and sheep was non-lytic. In the present study, we have sought to confirm the trypanocidal capability of human apoA-I by studying four lines of transgenic mice expressing (supra)physiological serum levels of this polypeptide. Although trypanolysis in vitro by sera from transgenic mice (15.1 +/- 1.3% [mean +/- SEM], n = 30) was considerably less than by human sera (typically 60-80%), it was nevertheless significantly greater than by control sera (8.5 +/- 1.1%, n = 10; P < 0.001) and correlated with the concentration of human apoA-I (r = 0.56, P < 0.001). When trypanosomes were incubated at 37 degrees C with human serum or with human apoA-I for 30 min (i.e., within the pre-lytic period) they lost their ability to subsequently infect mice; trypanosomes incubated with transgenic mice serum remained infective. Furthermore, transgenic mice were fully susceptible to infection when inoculated with 10(3) trypanosomes; both the initial detection of trypanosomes in the blood (3-4 days) and the time to death (5-6 days) were no longer than control mice. This apparent paradox between the action of human apoA-I in human serum and in mouse serum was investigated further.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Transgenic mice expressing human apolipoprotein A-I have sera with modest trypanolytic activity in vitro but remain susceptible to infection by Trypanosoma brucei brucei. 146 47

Obesity commonly accompanies hypertriglyceridemia, and weight reduction is widely recommended for treatment of elevated triglyceride levels. To determine whether weight reduction will normalize lipoprotein metabolism in overweight, hypertriglyceridemic patients, 10 such male patients underwent weight loss until their body weights were within the desirable range. After reestablishment of a steady state in body weight at the lower level, measurements were made of plasma lipid, lipoprotein, and apolipoprotein levels and the kinetics of low density lipoprotein (LDL) apolipoprotein B-100 (apo B) and apolipoprotein A-I (apo A-I). The patients lost an average of 10.6 +/- 2.1 kg (mean +/- SEM). Plasma triglyceride concentrations fell from 431 +/- 42 mg/dl to 248 +/- 27 mg/dl (p less than 0.001), whereas concentrations of total cholesterol, LDL cholesterol, total apo B, and high density lipoprotein (HDL) cholesterol were unchanged after weight loss. On average, the fractional catabolic rates (FCRs) for LDL were much higher in the patients after weight loss than in 16 normal control subjects (0.55 +/- 0.06 versus 0.31 +/- 0.06 pool/day), and input rates for LDL also were higher for hypertriglyceridemic patients after weight loss (22.2 +/- 2.4 versus 12.8 +/- 2.3 mg/kg.day). Compared with 20 normal control subjects, hypertriglyceridemic patients after weight reduction had persistent low HDL cholesterol levels (32 +/- 2 versus 54 +/- 3 mg/dl) as well as low apo A-I levels (99 +/- 5 versus 122 +/- 4 mg/dl).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Persistence of abnormalities in metabolism of apolipoproteins B-100 and A-I after weight reduction in patients with primary hypertriglyceridemia. 163 97

To investigate whether increased endogenous lipogenesis contributes to elevated plasma lipid levels in individuals with apolipoprotein (apo) E2-associated hyperlipidemia (E2-HL), plasma pool cholesterol and triglyceride fatty acid syntheses were measured in subjects with E2-HL and in those with normal lipid levels. Subjects were given a priming dose of deuterium oxide (D2O) followed by maintenance doses over 48 hours. During the first 24 hours, subjects consumed prepared meals, whereas during the 24-48 hour interval, they consumed water only. Blood samples were drawn every 12 hours, and cholesterol and triglyceride fatty acid formation rates were determined from the change in deuterium enrichment. The free cholesterol fractional synthesis rate over 0-24 hours of E2-HL subjects (0.057 +/- 0.010 day-1, mean +/- SEM) was not significantly different from that of normolipidemics (0.075 +/- 0.005 day-1). Calculated cholesterol net synthesis was not different between the two groups (0.56 +/- 0.07 and 0.75 +/- 0.05 g/day, respectively). Mean free cholesterol synthesis for all subjects was higher in the fed (0-24 hour) compared with the fasted (24-48-hour) condition. Initial 12-hour triglyceride fatty acid fractional synthesis was significantly (p less than 0.01) increased in E2-HL subjects (0.143 +/- 0.012 day-1) compared with controls (0.082 +/- 0.0013 day-1). These findings suggest that in E2-HL, elevated plasma cholesterol levels are due to factors other than increased sterol synthesis, while higher de novo fatty acid synthesis contributes to the observed hypertriglyceridemia.
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PMID:Cholesterol and triglyceride fatty acid synthesis in apolipoprotein E2-associated hyperlipidemia. 173 53

Although lipoprotein changes after cardiac transplantation have been documented, the effects of transplantation and subsequent immunosuppressive therapy (particularly the combination of prednisone, azathioprine and cyclosporine) on apolipoprotein levels and lipoprotein(a) have not been reported. Fasting cholesterol, triglycerides, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, apolipoprotein A-1 and B-100 and lipoprotein(a) were evaluated in 69 consecutive patients during the waiting period before cardiac transplantation. There were 28 deaths before donor organ identification and 41 patients received a cardiac allograft. The lipoprotein levels of transplant recipients were again assayed 3 months postoperatively. Mean (+/- SEM) values increased for total plasma cholesterol (from 180 +/- 8 to 228 +/- 8 mg/dl, p less than or equal to 0.001), triglycerides (from 126 +/- 11 to 207 +/- 14 mg/dl; p less than or equal to 0.001), HDL cholesterol (from 39 +/- 2 to 49 +/- 3 mg/dl; p less than or equal to 0.002) and LDL cholesterol (from 119 +/- 7 to 138 +/- 7 mg/dl; p less than 0.02). Apolipoprotein A-1 and B-100 also increased, but lipoprotein(a) decreased from 11.7 +/- 1.7 to 6.8 +/- 1.1 mg/dl; p less than or equal to 0.0001) after transplantation. Although total cholesterol, triglycerides, LDL cholesterol, apolipoprotein A-1 and B-100 increased dramatically after cardiac transplantation, so did HDL cholesterol, thereby keeping the LDL/HDL cholesterol ratio constant. The surprising decrease in lipoprotein(a) after cardiac transplantation suggests that metabolism of lipoprotein(a) is independent of LDL cholesterol and that immunosuppressive drugs either decrease the synthesis or increase catabolism of lipoprotein(a).
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PMID:Lipoprotein(a) and apolipoprotein changes after cardiac transplantation. 183 99

Diet-induced coronary artery atherosclerosis develops in rhesus monkeys (Macaca mulatta). The goal of this study was to establish the rhesus monkey as an animal model of coronary heart disease (CHD). From a colony of 160 rhesus monkeys fed an atherogenic diet, we identified 14 monkeys with electrocardiographic and echocardiographic evidence of CHD. When compared with 14 rhesus monkeys matched for age, gender, and dietary history with normal electrocardiograms and echocardiograms, monkeys with CHD had higher arterial blood pressures (mean +/- SEM, 92 +/- 4 mm Hg vs 75 +/- 5 mm Hg, respectively), lower high-density lipoprotein cholesterol concentrations (mean +/- SEM, 1.70 +/- 0.25 mmol/L vs 2.32 +/- 0.28 mmol/L [66 +/- 10 mg/dL vs 90 +/- 11 mg/dl]), and lower A-l apolipoprotein concentrations (mean +/- SEM, 200 +/- 17 mg/dL vs 252 +/- 15 mg/dL). Monkeys with CHD tended to have higher total plasma cholesterol concentrations (mean +/- SEM, 11.6 +/- 1.55 mmol/L vs 9.36 +/- 0.93 mmol/L [450 +/- 60 mg/dL vs 362 +/- 36 mg/dL]) and higher low-density lipoprotein cholesterol concentrations (mean +/- SEM, 8.71 +/- 1.75 mmol/L vs 6.12 +/- 0.90 mmol/L [337 +/- 68 mg/dL vs 237 +/- 35 mg/dl]) than monkeys with normal electrocardiograms and echocardiograms. We conclude that rhesus monkeys, like human beings, develop CHD as a complication of coronary artery atherosclerosis. Furthermore, risk factors for CHD in rhesus monkeys and human beings are similar.
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PMID:Coronary heart disease in rhesus monkeys with diet-induced coronary artery atherosclerosis. 141 50

We measured the serum lathosterol level, a reflection of the rate of whole body cholesterol synthesis, in 15 patients with manifest type III hyperlipoproteinemia (HLP), in 20 subjects with apolipoprotein (apo) E2/2 phenotype, but without type III HLP, in 21 patients with type IIA and 10 patients with type IIB HLP. A group of 100 subjects with apo E3/3 phenotype served as reference. Using ANCOVA, lathosterol was adjusted for serum cholesterol and triglyceride concentrations, since these parameters were found to independently correlate with lathosterol. The adjusted means (+/- SEM), in mumol/L, in these groups were 12.9 +/- 1.1, 8.2 +/- 1.1, 4.8 +/- 0.9, 9.8 +/- 1.4, and 7.8 +/- 0.4, respectively. Type III HLP patients had significantly higher lathosterol levels than all other groups except type IIB HLP. In addition, lathosterol was significantly lower in type IIA patients than in all other groups. The serum levels of plant sterols, used as a reflection of cholesterol absorption, did not differ among the various groups after adjustment for serum cholesterol. These findings suggest that an overproduction of cholesterol is one factor discriminating E2/2 homozygotes with type III HLP from those without the disease.
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PMID:Lathosterol level in plasma is elevated in type III hyperlipoproteinemia, but not in non-type III subjects with apolipoprotein E2/2 phenotype, nor in type IIa or IIb hyperlipoproteinemia. 200 34

Mechanisms that might be responsible for the low levels of high density lipoprotein (HDL) associated with hypertriglyceridemia were studied in an animal model. Specific monoclonal antibodies were infused into female cynomolgus monkeys to inhibit lipoprotein lipase (LPL), the rate-limiting enzyme for triglyceride catabolism. LPL inhibition produced marked and sustained hypertriglyceridemia, with plasma triglyceride levels of 633-1240 mg/dl. HDL protein and cholesterol and plasma apolipoprotein (apo) AI levels decreased; HDL triglyceride (TG) levels increased. The fractional catabolic rate of homologous monkey HDL apolipoproteins injected into LPL-inhibited animals (n = 7) was more than double that of normal animals (0.094 +/- 0.010 vs. 0.037 +/- 0.001 pools of HDL protein removed per hour, average +/- SEM). The fractional catabolic rate of low density lipoprotein apolipoprotein did not differ between the two groups of animals. Using HDL apolipoproteins labeled with tyramine-cellobiose, the tissues responsible for this increased HDL apolipoprotein catabolism were explored. A greater proportion of HDL apolipoprotein degradation occurred in the kidneys of hypertriglyceridemic than normal animals; the proportions in liver were the same in normal and LPL-inhibited monkeys. Hypertriglyceridemia due to LPL deficiency is associated with low levels of circulating HDL cholesterol and apo AI. This is due, in part, to increased fractional catabolism of apo AI. Our studies suggest that variations in the rate of LPL-mediated lipolysis of TG-rich lipoproteins may lead to differences in HDL apolipoprotein fractional catabolic rate.
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PMID:Role of lipoprotein lipase in the regulation of high density lipoprotein apolipoprotein metabolism. Studies in normal and lipoprotein lipase-inhibited monkeys. 211 22

The aim of this study was to assess the specific correlation of apolipoprotein-AI to hepatic fibrosis in alcoholic patients. Four hundred eighty two patients were prospectively included with serum measurement of apolipoprotein-AI within 10 days before liver biopsy. Pathologic features were semiquantitatively assessed by two observers. In 28 patients liver biopsy was used for histomorphometric assessment of fibrosis and immunohistochemical labeling of apolipoprotein-AI. Serum apolipoprotein-AI was negatively correlated to semiquantitative score of fibrosis (r = -0.50; p less than 0.001), independently of the scores of steatosis and alcoholic hepatitis (r = -0.44; p less than 0.001) and of the value of serum albumin, bilirubin, and prothrombin time (r = -0.22; p less than 0.001) and independently of the nutritional parameters (r = -0.29; p less than 0.009). The mean value of apolipoprotein-AI decreased according to the grade of fibrosis from 220 +/- 6 mg/dl (mean +/- SEM) to 110 +/- 8 mg/dl. Serum apolipoprotein-AI was negatively correlated to the percentage of fibrosis (r = -0.70; p less than 0.001) in the biopsies morphometrically assessed. The labeling was superimposed to the extracellular matrix. In conclusion, this study shows that decrease of apolipoprotein-AI is a serum and tissue marker of liver fibrosis independently of steatosis, alcoholic hepatitis, liver function tests, and nutritional parameters.
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PMID:Apolipoprotein AI is a serum and tissue marker of liver fibrosis in alcoholic patients. 251 36

The serum lipoprotein concentrations, including high-density lipoprotein (HDL) subfractions and apolipoproteins Al and B were measured in 21 patients (14 male and seven female) with nephrotic range proteinuria (greater than 3g/24hr), well maintained renal function (creatinine clearance greater than 35 mliter/min/1.73m2) and biopsy-proven primary glomerular disease. In these, and in a further five patients (creatinine clearance greater than 15 mliter/min/1.73m2), urinary apolipoprotein Al output was determined. Total HDL cholesterol was similar in patients and controls, but in male patients, HDL2 was low (0.54 +/- 0.10 mmole/liter, mean +/- SEM) compared to controls (0.75 +/- 0.04 mmole/liter, P less than HDL3 was high (0.81 +/- 0.07 in patients and 0.63 +/- 0.02 mmole/liter in controls, P less than 0.01). In women, there was a similar tendency for HDL2 to be lower in patients (0.68 +/- 0.18 mmole/liter) than in controls (0.85 +/- 0.10 mmole/liter). Multiple regression analysis revealed that major determinants of the urinary apolipoprotein Al output were the urinary protein output and selectivity index (multiple r = 0.85). Furthermore, some patients lost apolipoprotein Al into their urine at rates indicating increased production of apolipoprotein Al in the nephrotic syndrome. The serum HDL subfraction concentrations in the nephrotic syndrome could be explained by a combination of increased HDL production and increased urinary loss of low molecular wt HDL.
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PMID:Serum and urinary high density lipoproteins in glomerular disease with proteinuria. 309 2

A series of thirty-three Venezuelan men with premature myocardial infarction (mean age (M +/- SEM) 45 +/- 1.5 yrs) and with greater than 50% occlusion of at least 2 coronary arteries, and 19 weight matched control men (age 44 +/- 2 yrs) with normal coronary arteries on coronary angiography were studied. The percentages of significantly abnormal (greater than +/- 2 S.D. of controls) serum or plasma concentrations of various measurements (in decreasing order) were: estradiol (33%), total apolipoprotein (apo)B (24%), estradiol/testosterone ratio (21%), low density lipoprotein (LDL) apo B (19%), apo AI (17%), apo AI/total plasma apo B ratio (17%), total cholesterol (17%), and LDL-cholesterol (LDL-C) (11%). In addition, a multivariate discriminant function analysis showed that only estradiol, apo AI, LDL-C, estradiol/testosterone ratio and total cholesterol were statistically significant independent markers of myocardial infarction with occlusive coronary disease in these patients. Both serum estradiol and estradiol/testosterone ratio correlated positively with plasma apo B and LDL apo B, and inversely with apo AI; serum testosterone correlated inversely with plasma apo B (p less than 0.05). The data suggest that circulating sex hormones (estrogens, testosterone) are not only independent markers of coronary disease but may be pathogenetically linked to apo B and apo AI metabolism.
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PMID:Estradiol, testosterone, apolipoproteins, lipoprotein cholesterol, and lipolytic enzymes in men with premature myocardial infarction and angiographically assessed coronary occlusion. 643 45


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