| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| A case of intrahepatic cholesterol stones associated with cholangiocarcinoma Mitake, M., S. Okamura, et al. (1994), Nippon Shokakibyo Gakkai Zasshi 91(7): 1268-71. |
| A case of multiple cholesterol polyps of the gallbladder with intermittent jaundice of frequent occurrence Matsui, Y., T. Higashino, et al. (1997), Nippon Shokakibyo Gakkai Zasshi 94(5): 376-80. |
| A case of renal failure due to primary cholesterol atheroembolism Matsubara, M., Y. Taguma, et al. (1991), Nippon Jinzo Gakkai Shi 33(4): 417-21. Abstract: We report a patient presenting rapid deterioration of renal function due to primary cholesterol atheroembolism. The patient was 75-year-old hypertensive male and was admitted to a hospital because of rt. hemiplegia which developed 2 weeks earlier. On admission, his blood pressure was 200/100 mmHg and serum creatinine level was 2.9 mg/dl with urinalysis 1+ both for protein and hematuria. 2 weeks later, an angiotensin converting enzyme inhibitor (ACE inhibitor, delapril 15 mg/day) was given to control high blood pressure. Immediately after this medication, his renal failure rapidly progressed with a fall in blood pressure (110/60 mmHg) and oliguria (100 ml/day). Although he was transferred to our hospital and was treated with hemodialysis, he died of an attack of acute myocardial infarction in a week. At post-mortem examination, microscopic findings of the kidney disclosed numerous occlusions of medium-sized artery by cholesterol emboli. These emboli were also observed in other organs, but not so prominent as in the kidney. The coronary arteries exhibited severe sclerosis. In this presented case, acute deterioration of renal function was caused by ACE-inhibitor, although which was administered in a volume depleted condition. Therefore, further study would be necessary whether or not ACE-inhibitors predispose the patients with this disease to acute renal failure. |
| A caveolin dominant negative mutant associates with lipid bodies and induces intracellular cholesterol imbalance Pol, A., R. Luetterforst, et al. (2001), J Cell Biol 152(5): 1057-70. Abstract: Recent studies have indicated a role for caveolin in regulating cholesterol-dependent signaling events. In the present study we have analyzed the role of caveolins in intracellular cholesterol cycling using a dominant negative caveolin mutant. The mutant caveolin protein, cav-3(DGV), specifically associates with the membrane surrounding large lipid droplets. These structures contain neutral lipids, and are accessed by caveolin 1-3 upon overexpression. Fluorescence, electron, and video microscopy observations are consistent with formation of the membrane-enclosed lipid rich structures by maturation of subdomains of the ER. The caveolin mutant causes the intracellular accumulation of free cholesterol (FC) in late endosomes, a decrease in surface cholesterol and a decrease in cholesterol efflux and synthesis. The amphiphile U18666A acts synergistically with cav(DGV) to increase intracellular accumulation of FC. Incubation of cells with oleic acid induces a significant accumulation of full-length caveolins in the enlarged lipid droplets. We conclude that caveolin can associate with the membrane surrounding lipid droplets and is a key component involved in intracellular cholesterol balance and lipid transport in fibroblasts. |
| A cDNA encoding a rat mitochondrial cytochrome P450 catalyzing both the 26-hydroxylation of cholesterol and 25-hydroxylation of vitamin D3: gonadotropic regulation of the cognate mRNA in ovaries Su, P., H. Rennert, et al. (1990), DNA Cell Biol 9(9): 657-67. Abstract: A cDNA expression library prepared from rat liver RNA was screened with a polyclonal antibody specific for mitochondrial vitamin D3 25-hydroxylase and a cDNA for rabbit liver mitochondrial cytochrome P450c26 (CYP 26), yielding cDNA clones with identical sequences. The deduced amino acid sequence derived from a 1.9-kb full-length cDNA was 73% identical to that of rabbit cytochrome P450c26. A monoclonal antibody was used to demonstrate that the product of the 1.9-kb cDNA clone was targeted to the mitochondrial compartment when expressed in COS cells. Mitochondrial membranes containing the expressed protein showed both vitamin D3 25-hydroxylase and cholesterol 26-hydroxylase activities when reconstituted with ferredoxin reductase and ferredoxin, demonstrating that the same P450, designated as P450c26/25, can catalyze both reactions. Northern blot analysis revealed that the P450c26/25 cDNA hybridizes with a 2.4-kb RNA from rat liver and unstimulated ovaries. Treatment of rats with pregnant mare's serum gonadotropin resulted in a fivefold increase in the 2.4-kb mRNA as well as the appearance of a 2.1-kb mRNA species in the ovaries. Our findings document the presence of a regulated bifunctional mitochondrial cytochrome P450 capable of catalyzing the 25-hydroxylation of vitamin D3 and the 26-hydroxylation of cholesterol. |
| A cell culture system for screening human serum for ability to promote cellular cholesterol efflux. Relations between serum components and efflux, esterification, and transfer de la Llera Moya, M., V. Atger, et al. (1994), Arterioscler Thromb 14(7): 1056-65. Abstract: A cell culture system was employed to test a large number of samples of human serum for the ability to stimulate the efflux of cell cholesterol. The extent of efflux obtained with each specimen was correlated with the serum concentrations of cholesterol, triglycerides, apoprotein (apo) B, apo A-I, apo A-II, and lipoprotein subfractions (ie, high-density lipoprotein2 HDL2, HDL3, lipoprotein Lp A-I, and LpA-I:A-II). In addition, the subsequent esterification of the released cholesterol and the distribution of the synthesized exogenous cholesteryl esters between HDL and low-density lipoprotein/very-low-density lipoprotein provided estimates of the lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) activities of each serum. The values for these activities were analyzed for correlations with cell efflux and the various serum parameters. Cell cholesterol efflux best correlated with serum total HDL cholesterol values. HDL2 and HDL3 correlated about equally well with efflux, whereas LpA-I demonstrated a much greater association with efflux than did LpA-I:A-II. Analysis of the data by partial correlation analysis indicated that HDL3 and LpA-I were the HDL subfractions most closely associated with efflux. Esterification of the released radiolabeled cholesterol was strongly and positively correlated with serum triglyceride concentrations and negatively related to the serum concentrations of HDL2. There was no relation between esterification values, which reflect LCAT activity, and efflux. The transfer of the labeled cholesteryl esters between HDL and apoB-containing lipoproteins was used as a measure of CETP activity and demonstrated a pattern in which all apoB-related parameters were positively correlated to transfer of esterified cholesterol, and all HDL associated parameters, particularly HDL3, were negatively related to transfer. No relations were observed between efflux, esterification, and transfer. |
| A cell line derived from sphingomyelinosis mouse shows alterations in intracellular cholesterol metabolism similar to those in type C Niemann-Pick disease Ohno, K., E. Nanba, et al. (1992), Cell Struct Funct 17(4): 229-35. Abstract: Cell lines derived from the sphingomyelinosis (gene symbol, spm) mouse were established from homozygous (spm/spm) and heterozygous (spm/+) embryos according to a rigid 3T3 transfer schedule. The SPM-3T3 cells derived from a homozygous embryo showed extensive accumulation of intracellular cholesterol, attenuated esterification of exogenously added cholesterol and increased de novo cholesterol synthesis, when compared to SPMH-3T3 cells derived from a heterozygous embryo. The phenotypic abnormalities were very similar to those observed in fibroblasts from patients with Niemann-Pick disease type C (NP-C), in which a defect in the intracellular transport of unesterified cholesterol is suggested. The genetic defect in SPM-3T3 cells should be closely related to that in NP-C. The SPM-3T3 cell line is useful for biochemical and genetic studies on the regulation of intracellular cholesterol metabolism. |
| A cholesterol embolism following coronary angioplasty. A case report Barrabes Riu, J. A., C. Tolosa Vilella, et al. (1991), Rev Esp Cardiol 44(6): 411-3. Abstract: Cholesterol embolism is a rare but serious complication of heart catheterization. We report a patient in whom cholesterol embolization syndrome developed after coronary angioplasty complicated by an acute myocardial infarction which was treated with streptokinase and heparin. The clinical outcome was satisfactory. Cholesterol embolism occurrence might have been precipitated in this patient by thrombolytic and anticoagulant therapy. |
| A cholesterol granuloma in the maxillary sinus: report of case Tzerbos, F. H., A. Mavrogeorgis, et al. (1994), J Oral Maxillofac Surg 52(11): 1205-7. |
| A cholesterol intervention program for public health nurses in the rural southeast: description of the intervention, study design, and baseline results Keyserling, T. C., A. S. Ammerman, et al. (1999), Public Health Nurs 16(3): 156-67. Abstract: Residents of the rural South are at high risk for heart disease and are frequently identified as having high blood cholesterol, but sources for nutrition counseling in rural areas are often limited. To increase the availability of high quality nutrition counseling, the Food for Heart Program was developed for public health nurses and is designed to circumvent many of the obstacles common to dietary counseling. We conducted a randomized trial to assess the effectiveness of this program to lower blood cholesterol. In this report, we describe the study design, intervention program, and baseline characteristics of participants. Nurses at 17 health departments screened 781 subjects to enroll 468 with high blood cholesterol: three-quarters of the subjects were female, the mean age was 55, and 80% were white. Participants were at high risk for heart disease: 60% had two or more risk factors for coronary disease, the majority were overweight with a mean BMI of 29, and the mean cholesterol was 257 mg/dL. Reported baseline dietary intake included relatively modest consumption of high fat meats and snack foods, excessive consumption of sweets, modest intake of complex carbohydrates, and inadequate consumption of fruits and vegetables. |
| A cholesterol reducing diet is not useful Boot, C. P. (1997), Ned Tijdschr Geneeskd 141(52): 2539-42. Abstract: In daily practice a cholesterol-lowering diet with intensive monitoring by dieticians leads to a mean decrease of the serum cholesterol level by 2%. Once the monitoring is discontinued, the serum cholesterol level as a rule returns to baseline. Were it possible to maintain a 5% cholesterol reduction throughout life, occurrence of coronary heart disease would in theory be postponed by one to a few months. In diet studies, with observation lasting from 6 to 15 years, no clear favourable effect on the development of coronary heart disease was demonstrated. Prescription of a cholesterol-reducing diet and referral to a dietician are therefore fairly useless. |
| A cholesterol reduction demonstration project: results from a challenge between two cities Muscat, J. E., R. E. Harris, et al. (1992), J Miss State Med Assoc 33(3): 87-94. Abstract: A competition was conducted between Jackson, MS and Lansing, MI to reduce blood cholesterol levels among self-selected individuals who were generally at high risk for elevated coronary heart disease. Baseline plasma cholesterol levels were measured and risk factor data were recorded for 13,710 participants in Jackson and 6,719 in Lansing (6.8% and 5.1% of the total populations, respectively). A six month educational campaign was conducted in both cities which included nutritional seminars, television shows, newspaper advertisements etc. From Jackson, 6,244 participants returned for the follow-up screening, and 2,404 from Lansing (46% and 36%). Subjects who reported changes in their diets had an average cholesterol reduction of 19 mg/dl (9%) in Jackson, and 2 mg/dl (1%) in Lansing (after adjustment for sex, baseline level, and age, P less than 0.01). In Lansing, participants were less likely to have college degrees, and were more likely to have participated because of concern with previously determined elevated cholesterol levels than Jackson participants. |
| A cholesterol screening and health assessment of medical students Girard, J. and B. Wang (1990), Acad Med 65(6): 422. |
| A cholesterol-binding and transporting protein from rat liver mitochondria Campbell, A. M., A. Capuano, et al. (2002), Biochim Biophys Acta 1567(1-2): 123-32. Abstract: In this communication, we present results indicating a protein isolated from rat liver mitochondrial intermembrane space that is capable of binding cholesterol and transporting it between the inner and outer mitochondrial membranes. This protein has a molecular weight of 57.5 kDa by SDS-PAGE; however, under native conditions, there is cholesterol-binding capability only as a 115 kDa dimer. Our data show that this dimeric protein may play a role in the regulation of mitochondrial membrane cholesterol levels, a prerequisite for the optimal activity of inner mitochondrial membrane-associated enzyme complexes. In addition, it appears that this protein is largely responsible for the differences in membrane cholesterol levels observed in normal and hepatoma mitochondria, a discrepancy which may help to explain the lack of energy production via oxidative phosphorylation in malignant tumor mitochondria. |
| A cholesterol-dependent CD20 epitope detected by the FMC7 antibody Polyak, M. J., L. M. Ayer, et al. (2003), Leukemia 17(7): 1384-9. Abstract: Accurate diagnosis of lymphoid malignancies is essential for appropriate therapeutic intervention. In conjunction with other diagnostic determinants, immunophenotypic analysis of differentially expressed cell surface markers, such as CD5, CD20, CD23 and FMC7, is useful in the subclassification of lymphomas and leukemias arising from the B-cell lineage. Recent evidence suggesting that CD20 predicts FMC7 expression has prompted reappraisal of the utility of monitoring both markers. Here, we report that the FMC7 monoclonal antibody (mAb) specifically and strongly recognized CD20 ectopically expressed in hematopoietic and nonhematopoietic cell lines. The reactivity of FMC7 was abolished by mutations in the extracellular domain of CD20. These data confirm the CD20 specificity of FMC7. Like other CD20 mAbs, FMC7 binding was temperature dependent and induced detergent insolubility of CD20. Of significant interest, the CD20 epitope recognized by FMC7 was unusual in that it was exceptionally sensitive to membrane cholesterol. Cholesterol depletion profoundly reduced expression of the FMC7 epitope, whereas cholesterol enrichment enhanced its expression. FMC7 mAb binding thus appears to be a sensitive indicator of the level of plasma membrane cholesterol and reveals a conformational state of CD20 that is regulated by cholesterol. |
| A cholesterol-enriched diet enhances egg production and egg viability without altering cholesterol Content of biological membranes in the copepod Acartia hudsonica Crockett, E. L. and R. P. Hassett (2005), Physiol Biochem Zool 78(3): 424-33. Abstract: Copepods may lack the capacity for de novo synthesis of cholesterol, while at the same time their dietary levels of sterol vary. We tested the hypothesis that copepods maintain the cholesterol contents of their biological membranes despite varying dietary levels of cholesterol. Acartia hudsonica were acclimated for 5 d to phytoplankton alone or phytoplankton supplemented with cholesterol, at a level sufficient to induce a maximal response on egg production rates. Biological membranes were prepared from the copepods and cholesterol contents assayed. Egg production and hatch rates were measured (the former to confirm that supplemented cholesterol was being assimilated). Analyses of marker enzymes indicate that the majority of membrane-associated cholesterol in the copepod resides in the plasma membrane. In membranes fractions, cholesterol normalized to protein or activity of Na+/K+-ATPase is not significantly different for supplemented and unsupplemented groups (29 and 33 mu g cholesterol mg(-1) protein, respectively; 0.24 and 0.25 mg cholesterol U(-1) Na+/K+-ATPase, respectively). At the same time, acclimating animals to a diet enriched with cholesterol enhances egg production by up to 1.8-fold and egg viability by 1.5-fold. We conclude that a cholesterol-enriched diet stimulates both egg production and hatching rates without altering cholesterol contents of plasma membranes in the copepod A. hudsonica. |
| A cholesterol-lowering diet does not produce adverse psychological effects in children: three-year results from the dietary intervention study in children Lavigne, J. V., K. M. Brown, et al. (1999), Health Psychol 18(6): 604-13. Abstract: The Dietary Intervention Study in Children (DISC), a 2-arm, multicenter intervention study, examined the efficacy and safety of a diet lower in total fat, saturated fatty acids, and cholesterol than the typical American child's diet. A total of 663 8- to 10-year-old children with elevated low-density lipoprotein cholesterol levels were randomly assigned to either an intervention or a usual-care group. Intervention included group and individual counseling sessions to assist participants in adopting a dietary pattern containing 28% or less of calories from total fat (<8% as saturated fat, up to 9% as polyunsaturated fat, and 11% as monounsaturated fat) and dietary cholesterol intake of less than 75 mg/1,000 kcal. The dietary intervention reduced low-density lipoprotein cholesterol levels, and 3-year results showed no adverse effects for children in the intervention group in terms of academic functioning, psychological symptoms, or family functioning. |
| A cholesterol-lowering drug reduces beta-amyloid pathology in a transgenic mouse model of Alzheimer's disease Refolo, L. M., M. A. Pappolla, et al. (2001), Neurobiol Dis 8(5): 890-9. Abstract: Clinical, epidemiological, and laboratory studies suggest that cholesterol may play a role in the pathogenesis of Alzheimer's disease (AD). Transgenic mice exhibiting an Alzheimer's beta-amyloid phenotype were treated with the cholesterol-lowering drug BM15.766 and tested for modulation of beta-amyloid levels. BM15.766 treatment reduced plasma cholesterol, brain Abeta peptides, and beta-amyloid load by greater than twofold. A strong, positive correlation between the amount of plasma cholesterol and Abeta was observed. Furthermore, drug treatment reduced the amyloidogenic processing of the amyloid precursor protein, suggesting alterations in processing in response to cholesterol modulation. This study demonstrates that hypocholesterolemia is associated with reduced Abeta accumulation suggesting that lowering cholesterol by pharmacological means may be an effective approach for reducing the risk of developing AD. |
| A cholesterol-lowering gene maps to chromosome 13q Knoblauch, H., B. Muller-Myhsok, et al. (2000), Am J Hum Genet 66(1): 157-66. Abstract: A cholesterol-lowering gene has been postulated from familial hypercholesterolemia (FH) families having heterozygous persons with normal LDL levels and homozygous individuals with LDL levels similar to those in persons with heterozygous FH. We studied such a family with FH that also had members without FH and with lower-than-normal LDL levels. We performed linkage analyses and identified a locus at 13q, defined by markers D13S156 and D13S158. FASTLINK and GENEHUNTER yielded LOD scores >5 and >4, respectively, whereas an affected-sib-pair analysis gave a peak multipoint LOD score of 4.8, corresponding to a P value of 1.26x10-6. A multipoint quantitative-trait-locus (QTL) linkage analysis with maximum-likelihood binomial QTL verified this locus as a QTL for LDL levels. To test the relevance of this QTL in an independent normal population, we studied MZ and DZ twin subjects. An MZ-DZ comparison confirmed genetic variance with regard to lipid concentrations. We then performed an identity-by-descent linkage analysis on the DZ twins, with markers at the 13q locus. We found strong evidence for linkage at this locus with LDL (P<.0002), HDL (P<.004), total cholesterol (P<.0002), and body-mass index (P<.0001). These data provide support for the existence of a new gene influencing lipid concentrations in humans. |
| A cholesterol-regulated PP2A/HePTP complex with dual specificity ERK1/2 phosphatase activity Wang, P. Y., P. Liu, et al. (2003), Embo J 22(11): 2658-67. Abstract: The acute depletion of membrane cholesterol causes the concentration of pERK1/2 in caveola/raft lipid domains and the cytosol of human fibroblasts to dramatically increase. This increase could be caused by either the activation of MEK-1 or the inhibition of a pERK phosphatase. Here we describe the isolation of a high molecular weight (approximately 440 kDa), cholesterol-regulated pERK phosphatase that dephosphorylates both the phosphotyrosine and the phosphothreonine residues in the activation loop of the enzyme. The dual activity in the complex appears to be due to the combined activities of the serine/threonine phosphatase PP2A and the tyrosine phosphatase HePTP. Acute depletion of cholesterol causes the disassembly of the complex and a concomitant loss of the dual specificity pERK phosphatase activity. The existence of a cholesterol-regulated HePTP/PP2A activity provides a molecular explanation for why ERK activity is sensitive to membrane cholesterol levels, and raises the possibility that ERK plays a role in regulating the traffic of cholesterol to caveolae/rafts and other membranes. |