Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gallstones are composed principally of cholesterol monohydrate crystals (cholesterol stones) or the acid salt of calcium bilirubinate (pigment stones). Cholesterol stones and the black variety of pigment gallstones form in sterile gallbladder bile whereas brown pigment gallstones form in infected bile. Biliary supersaturation is the principal pathophysiological defect and is hepatic in origin. Supersaturation results from excessive secretion of cholesterol or bilirubin conjugates, the precursors of unconjugated bilirubin, and/or, deficient secretion of bile salt and lecithin, the solubilizers of these otherwise insoluble lipids. As has now being clarified for cholesterol stones, an imbalance in pro- and antinucleating biliary proteins, hypersecretion of gallbladder mucin and gallbladder dysmotility possibly from cholesterol "toxicity" to sarcolemma, all interact to promote nucleation. Crystallisation results in suspension of cholesterol crystals or bilirubinate salts in gallbladder mucin gel and is known as "biliary sludge". It is believed today that this stage is essential for evolution of both cholesterol and pigment stones. Brown pigment gallstones form principally in the bile ducts. These stones result from infection of the biliary tree, most commonly due to obstruction from migrating gallbladder stones. Chemical compositions of brown and black pigment stones are different: In black stones, calcium bilirubinate is polymerized and oxidatively degraded but in brown stones, calcium bilirubinate is present as the unpolymerised salt. Brown stones differ also from black stones in containing calcium fatty acid soaps, a result of bacterial phospholipase A1 hydrolysis of biliary lecithin. Both types of pigment gallstones may contain crystalline inorganic calcium salts especially carbonate (gallbladder stones) and phosphate (bile ducts stones). Since a molecular understanding of the multiple defects that lead to cholesterol and pigment gallstones is becoming a reality, the future holds much promise for gallstone prevention.
 ...
PMID:Pathogenesis of gallstones. 152 52

There are two types of gallstones; cholesterol and pigment or bilirubinate. Cholesterol stones are formed in the gallbladder as a consequence of altered hepatocellular and gallbladder function. Overproduction of cholesterol by the liver is the major metabolic precedent of cholesterol gallstones and this may occur because of obesity, drugs, or other factors. Gallbladder factors which promote stone formation include hypomotility and the secretion of nucleating factors such as mucus glycoprotein. It is possible that both of these two factors are mediated by an increase in the prostaglandin production by the gallbladder mucosa. Pigment stones are either brown or black. Brown stones are formed of calcium bilirubinate and are usually associated with biliary infection. They occur in both the gallbladder and the bile ducts. Black pigment stones are extremely hard bilirubin polymers and are found mainly in the gallbladder. Biliary sludge is a necessary precedent of gallstones. It comprises cholesterol monohydrate crystals, glycoproteins and granules of calcium bilirubinate.
 ...
PMID:The formation of gallstones. 158 12

To understand 31P relaxation processes and hence molecular dynamics in the phospholipid multilayer it is important to measure the dependence of the 31P spin-lattice relaxation time on as many variables as the physical system allows. Such measurements of the 31P spin-lattice relaxation rate have been reported both as a function of Larmor frequency and temperature for egg phosphatidylcholine liposomes (Milburn, M.P., and K.R. Jeffrey. 1987. Biophys. J. 52:791-799). In principle, the spin-lattice relaxation rate in an anisotropic environment such as a bilayer will be a function of the angle between the bilayer normal and the magnetic field. However, the measurement of this angular dependence has not been possible because the rapid (on the time-scale of the spin-lattice relaxation rate) diffusion of the lipid molecules over the curved surface of the liposome average this dependence (Milburn, M.P., and K.R. Jeffrey. 1987. Biophys. J. 52:791-799; Brown, M.F., and J.H. Davis. 1981. Chem. Phys. Lett. 79:431-435). This paper reports the results of the measurement of the 31P spin-lattice relaxation rate as a function of this angle, beta', (the angle between the bilayer normal and the external magnetic field) using samples oriented between glass plates. These measurements were made at high field (145.7 MHz) where the spin-lattice relaxation processes are dominated by the chemical shielding interaction (Milburn, M.P., and K.R. Jeffrey. 1987. Biophys. J. 52:791-799). A model of molecular motion that includes a fast axially symmetric rotation of the phosphate group (tau i approximately 10(-9) s) and a wobble of the head group tilt with respect to this rotation axis has been used to describe both the angular dependence of the spin-lattice relaxation and the spectral anisotropy. Cholesterol is seen to have a negligible effect on the motional properties of the phospholipid phosphate segment as measured by the orientation dependence of the spin-lattice relaxation.
 ...
PMID:Dynamics of the phosphate group in phospholipid bilayers. A 31P angular dependent nuclear spin relaxation time study. 279 Jan 37

Recently, the influence of acyl structure on galactosylceramide's (GalCer) interfacial phase behavior was studied [Ali, S., Smaby, J. M., & Brown, R.E. (1993) Biochemistry 32, 11696-11703]. Here, we show that acyl structure is a key parameter controlling GalCer's ability to interact with cholesterol. Different chain-pure GalCer species containing saturated (24:0, 18:0, or 10:0), or unsaturated (24:1 delta 15, 22:1 delta 13, or 18:2 delta 9, 12) acyl chains were synthesized. After measurement of the force-area behavior of mixed cholesterol/GalCer films at 24 degrees C, the average molecular area and average compressibility were determined as a function of film composition. Cholesterol exerts only a slight condensing effect when the GalCer species are liquid-ordered [liquid-condensed], with maximum condensation occurring near 0.25 mole fraction. However, cholesterol exerts a marked condensing effect on liquid-disordered (liquid-expanded) GalCer species regardless of whether the acyl chain is saturated or unsaturated. Maximum condensation occurs at cholesterol mole fractions between 0.3 and 0.4. We also compared cholesterol's relative condensing effect on liquid-expanded GalCer versus sphingomyelin. Cholesterol's condensation of either bovine brain or egg sphingomyelin is 25-30% greater than that observed with different liquid-expanded GalCer species. Aside from average area behavior, we assessed cholesterol's interfacial interactions with the various sphingolipids by determining the average compressibility as a function of composition. The compressibility of condensed GalCer derivatives changes very little upon addition of cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Cholesterol's interfacial interactions with galactosylceramides. 813 Feb 3

The National Cholesterol Education Program (NCEP) has identified a need to convey practical approaches for the management of high blood cholesterol (BC) to physicians. Our study was a joint effort between the Pawtucket Heart Health Program and the Brown University Department of Family Medicine to improve family medicine residents' attitudes, knowledge, self-efficacy, and practices regarding cholesterol screening and management. Thirty-six resident physicians received a BC screening and management training program. This program included training in BC screening using the fingerstick method and a desktop analyzer, diet assessment and counseling, and a management protocol for evaluation and treatment of high BC based on NCEP guidelines. The training program also included evaluation of residents' BC screening activity, incentives, chart audits, and biweekly articles in the departmental newsletter. We administered a survey to residents before and one year after the training program began to assess self-reported knowledge, attitudes, self-efficacy, and practices for BC management. Survey results indicated that the residents significantly improved their reported knowledge and attitudes about BC management. In addition, they significantly increased their reported self-efficacy and practices in dietary counseling and patient education. Residents also indicated that the training program was worthwhile, necessary, and practical and that many would use the materials and protocols in their future practices.
 ...
PMID:Changing physicians' attitudes, knowledge, and self-efficacy regarding cholesterol screening and management. 847 Dec 66

It was confirmed that the main source of energy for growth and development in the neonatal period was fat. Considerable attention was paid to the development of both white adipose tissue (WAT) and brown adipose tissue (BAT) in the rat and human newborn. Cholesterol metabolism during development was studied in the liver, the small intestine and both WAT and BAT. Brown adipose tissue of rats and adipose tissue from human newborns require carnitine for optimum respiration and fatty acid oxidation. Surprisingly, carnitine enhanced lipolysis in human newborn adipose tissue, intravenously-fed newborn patients exhibited a rapid decrease of plasma level of carnitine and its esters, indicating a greater requirement for exogenous carnitine than in adult subjects (52 references).
 ...
PMID:Developmental aspects of lipid metabolism. 879 69

The American Heart Association (AHA) Consensus Panel Statement for Preventing Heart Attack and Death in Patients with Coronary Disease provides recommendations for the secondary prevention of heart disease in at-risk patients. Blackstone Cardiology Associates of Pawtucket, Rhode Island, undertook an initiative in their practice implementing secondary-prevention guidelines in patients with coronary artery disease. This retrospective study evaluates practice patterns for the management of hyperlipidemia for a cardiology group in an ambulatory and hospital setting after the institution of a physician-supervised, nurse-based disease management program. Practice patterns in patients with established coronary heart disease treated in a lipid center compared with non-lipid-center settings were evaluated. Parameters evaluated included documenting low-density lipoprotein (LDL) cholesterol, presence of lipid-lowering therapy, and achieving the National Cholesterol Education Program II (NCEP II) goal of LDL-cholesterol levels < or =100 mg/dL in patients with preexisting coronary artery disease. A total of 352 patients met inclusion criteria in the lipid-center setting and were compared with 289 non-lipid-center consecutively chosen patients. Age and gender differences were also evaluated. Inpatient medical records from a 254-bed Brown University-affiliated teaching hospital were also evaluated for lipid profile, achievement of NCEP II goal, and use of lipid-lowering medication on admission and discharge. The most recent LDL-cholesterol values of patients followed in the lipid-center and in the non-lipid-center setting of the Blackstone Cardiology Associates were compared. Blackstone Cardiology Associates consists of 4 cardiologists and 4 advanced-practice nurses. Achievement of LDL-cholesterol goal was higher in both the lipid-center and non-lipid-center settings compared with baseline. A smaller percentage of patients at goal in the lipid setting is likely due to referral bias resulting in patients with more difficult-to-manage mixed dyslipidemias and behavior-management issues ending up in the lipid center. There were no apparent sex differences at goal, and more elderly (age > or =65 years) achieved goal in the lipid clinic center. In the non-lipid-center setting, more males were at goal and had a lower mean LDL-cholesterol level.
 ...
PMID:Secondary prevention in a cardiology group practice and hospital setting after a heart-care initiative. 1069 4

Cholesterol research was one of the key areas of scientific investigation in the 20th century. Little was known about the structure of cholesterol until the pioneering research of A. Windaus and H. Wieland in the first part of the century. The structure of cholesterol was completely elucidated in 1932. With the development of isotopic tracers in the 1930s studies on cholesterol biosynthesis were initiated. In 1942 K. Bloch and D. Rittenberg showed that deuterium-labeled acetate was incorporated into the ring structure and side chain of cholesterol. Another important discovery from Bloch's laboratory was that squalene was a precursor of cholesterol. In 1956, the main elements of the biosynthetic pathway became known when isopentenyl pyrophosphate was discovered as a precursor. In 1966, J. Cornforth and G. Popjak predicted that there were 16234 possible stereochemical pathways by which mevalonate could be converted into squalene. They subsequently showed which of these pathways was correct. In the 1970s and 1980s K. Bloch was able to provide intriguing evidence for an evolutionary advantage of cholesterol over lanosterol or some of the intermediates in the conversion of lanosterol to cholesterol. The last quarter of the 20th century was when M. Brown and J. Goldstein showed that the low density lipoprotein receptor was a key regulator of cholesterol homeostasis. They have also demonstrated that cholesterol balance in the cell is transcriptionally regulated via the sterol regulatory element binding protein. In the later part of the 20th century drugs were developed that effectively lower plasma cholesterol and lessen the risk of atherosclerosis and cardiovascular disease.
 ...
PMID:Cholesterol in the year 2000. 1111 Oct 73

Renal cortical brush-border (BBM), basolateral membrane (BLM), and medullary plasma membrane (mPM) preparations were analyzed to assess the effects of life-long food restriction in aged rats on membrane lipid content. Young male Fischer 344 x Brown-Norway F1 rats consumed food ad libitum (young AL) or were food-restricted (FR, 60% of AL consumption) for either 6 weeks (young FR) or until the age of 30 months old (old FR). Senescent FR rats had 50 per cent decreases in fractional excretion of Na and K (p < 0.001) as compared with the young AL rats. Long-term FR reduced phosphate and titratable acid excretion by 80 per cent (p < 0.001). These values were not significantly different from those observed in young rats during 6 weeks of FR. Food restriction decreased renal Na, K-ATPase activity by 50 per cent (p < 0.001) in both old and young FR animals. Reduction of food intake, in old and young rats, decreased all BBM phospholipid concentrations (phosphatidylserine, phosphatidylcholine, phosphatidylethanolamine, and sphingomyelin) by 50 per cent than in the AL rats (p < 0.001). In BLM, chronic FR resulted only in lower phosphatidylcholine concentration (by 21%, p < 0.05) while phosphatidylethanolamine was increased approximately 80 per cent (p < 0.001). Total phospholipid content in mPM was progressively decreased by 23 per cent (p < 0.05) in the young FR group to be 55 per cent (p < 0.001) in the old FR rats. Cholesterol content was reduced in BBM and mPM by 38 per cent and 25 per cent (p < 0.05), respectively, during long-term FR. Both total phospholipid and cholesterol contents detected in mPM of the old FR rats were significantly lower than those obtained from the young FR animals (by 42%, p < 0.001 and 12%, p < 0.05, respectively). Plasma glucose, blood urea nitrogen, and body weight maintained at significantly lower levels during chronic FR. That life-long FR could prevent renal membrane lipid deposition and could lower renal work may explain the mechanisms that FR can delay the onset and diminish the severity of age-associated renal diseases.
 ...
PMID:Life-long food restriction prevents renal membrane lipid deposition and lowers renal work in rats. 1152 48

The seminal studies of Brown and Goldstein (Science 1986;232:34-47) coupled with the findings of the Framingham study revolutionized our understanding of the metabolic basis for vascular disease. These studies led to the widespread use of the coronary risk lipid profile, which uses the total cholesterol/high-density lipoprotein (HDL) ratio (or low-density lipoprotein [LDL]/HDL ratio) in predicting risk for vascular disease and as a tool for therapeutic management of patients at risk for vascular disease. However, although these methods are predictive of coronary artery disease (CAD) in general, it is also well known that the extent of occlusive disease and CAD varies greatly between individuals with similar cholesterol and HDL lipid profiles. For this reason, the National Cholesterol Education Program Expert Panel revised these guidelines and now recommends monitoring LDL and HDL cholesterol in the context of coronary heart disease risk factors and "risk equivalents." In addition, more recent findings indicate that specific alterations in individual lipoprotein subclasses may account for the variations in CAD in subjects with similar lipid profiles. For example, a preponderance of small, dense LDL particles correlates with a marked increase in risk for myocardial infarction independent of LDL levels. In particular, the association of small, dense LDL with elevated triglycerides (large, less dense VLDL) and reduced HDL has been defined as the atherogenic lipoprotein profile, and the key metabolic defect driving this profile may be elevated levels of triglycerides, specifically large, less dense VLDL. In an attempt to explain the physiologic basis for lipoprotein variations, this review describes the basic metabolic scheme underlying the traditional view of lipoprotein metabolism and physiology. It then examines the identity and role of the various lipoprotein subfractions in an attempt to distill a working model of how lipoprotein abnormalities might account for vascular disease in general and the metabolic syndrome in particular.
 ...
PMID:The physiology of lipoproteins. 1246 89


1 2 Next >>