No description available.

No description available.

It has been suggested that membrane characteristics associated with carcinomas could be related to an altered molecular structure of lipids in the plasma membrane. The microsomal fraction, mitochondria and soluble fractions of the cell are major sites of de novo synthesis and elongation of fatty acids. It was the purpose of this study to compare the utilization of AcSCoA in the biosynthetic pathway for saturated fatty acids in tumor and normal tissue, and discern if any deviations in the initial steps of the pathway were responsible forr the observed differences in the plasma membrane of tumors. Labeled 14C-AcSCoA was incorporated into saturated fatty acids in both adenocarcinomas and normal mammary tissue. The distribution and degree of incorporation of labeled 14C-AcSCoA was hoped to demonstrate any deviations in the pathway.Crude supernate, microsomal fraction, mitochondria and soluble fractions were isolated from mammary adenocarcinomas and from normal mammary tissue of Strain A female mice by differential centrifugation. The activity of fatty acid synthetase in the soluble fraction was determined. The crude supernate, the soluble fraction, the mitochondria + soluble fraction and the microsomal fraction + soluble fraction of both the adenocarcinoma and normal mammary tissue were incubated with labeled 14C-AcSCoA, Ma1SCoA and all necessary cofactors. The now labeled fatty acids were extracted from these incubation mixtures. The total percent of incorporated labeled 14C-AcSCoA in each fraction was determined. The percent of incorporation of label into individual saturated fatty acids in each fraction was determined by gas liquid chromatography and liquid scintillation counting. Carrier mixtures of known fatty acids were added to the samples used for GLC analysis to confirm the identity of the labeled fatty acids.Results of this study show that the percent of labeled i4C-AcSCoA incorporated into the various saturated fatty acids was similar in tumor and normal tissue. However, the total uptake of AcSCoA was nearly twice as great in normal tissue. The activity of fatty acid synthetase appearsto be characteristic of each individual mouse. In tumored mice fatty acid synthetase activity appears to be related to tumor weight, that is the larger the tumor the greater the activity. These results do not demonstrate support for a shift in the biosynthesis of saturated fatty acids in carcinomas. It may be that the altered lipid composition of the plasma membrane of tumor cells arises from the carcinoma's ability to utilize exogenous fatty acids.

No description available.

Thesis (M.Phil.)--Chinese University of Hong Kong. / Bibliography: leaves 73-84.

Among NAFLD patients without known diabetes or high fasting plasma glucose at or above 7.0 mmol/I, 21% had undiagnosed diabetes and 29% had impaired glucose tolerance. In this population, post-challenge hyperglycemia was associated with NASH and liver fibrosis. Oral glucose tolerance test should be considered in the evaluation of NAFLD patients. / NAFLD is closely related to metabolic syndrome. Using the ethnic-specific IDF criteria, 70% of NAFLD patients had metabolic syndrome, compared to 7% of the general population. A significant proportion of NAFLD patients had body mass index between 23 and 25 kg/m2. The diagnosis of NAFLD may predate the development of different components of metabolic syndrome. / NAFLD patients have lower serum adiponectin level than healthy controls. NASH patients have higher serum tumor necrosis factor alpha (TNF-alpha) level than those with simple steatosis. The differences in adipokines remained significant after adjustment for traditional metabolic risk factors. These suggest that abnormalities in adipokines may be involved in the pathogenesis of NAFLD and NASH. On the other hand, genetic polymorphisms of the adiponectin and TNF-alpha genes are not associated with histological severity. / Since advanced fibrosis is less common in Chinese NAFLD patients, performing liver biopsies on every NAFLD patient for disease staging does not appear to be essential or cost-effective. Recently, the NAFLD fibrosis score is developed using 6 clinical parameters including age, BMI, impaired fasting glucose or diabetes, AST/ALT ratio, platelet count and albumin. The score had high negative predictive value of 91% in excluding advanced fibrosis in Chinese NAFLD patients. It may also reduce the burden of liver biopsies in the majority of cases. / Through a series of clinical studies in Chinese nonalcoholic fatty liver disease (NAFLD) patients in Hong Kong, we demonstrated that nonalcoholic steatohepatitis (NASH) and advanced fibrosis do occur in Chinese, with around 10% of NAFLD patients having advanced fibrosis, and 80% having necroinflammation. Importantly, up to half of the patients had progression of liver fibrosis upon long-term follow-up. / by Wong Wai Sun. / Adviser: Lik Yuen Henry Chan. / Source: Dissertation Abstracts International, Volume: 70-09, Section: B, page: . / Thesis submitted in: May 2008. / Thesis (M.D.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 219-263). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / School code: 1307.

The class B scavenger receptor CD36, or fatty acid translocase (FAT), is an 88 kDa plasma membrane glycoprotein that is the founding member of the class B scavenger receptor family. It has a number of natural ligands and has different functions at various locations in the body. It contributes to adhesion of platelets via its binding to thrombospondin-1. In monocytes and macrophages, it contributes to recognition and phagocytosis of apoptotic cells and it mediates the binding and uptake of oxidatively damaged low-density lipoproteins (oxLDL). In adipose and muscle tissues, FAT/CD36 mediates high-affinity binding and uptake of long-chain fatty acids (LCFAs) and is therefore a key regulator of lipid storage (particularly in adipocytes) and mitochondrial beta oxidation (particularly in muscle). Interestingly FAT/CD36 also binds native lipoproteins (including high-density lipoproteins [HDL]) with high affinity in vitro, although the physiological significance of this is unclear at present. Expression of FAT/CD36 by hepatocytes has not been recognised until recently, mainly because it is gender-regulated in both humans, and rats. However, the primary function of FAT/CD36 in the liver is unknown. The work described in this thesis has used various transfected cell lines to examine the possibility that FAT/CD36 contributes to hepatic LCFA uptake and/or the uptake of cholesteryl esters (and other lipids) from HDL. The subcellular localization of FAT/CD36 has been explored in rat liver and in cell lines of hepatic and non-hepatic origin, especially with respect to its association with specialized plasma membrane lipid raft microdomains known as caveolae. Furthermore, the importance of the cytoplasmic carboxyl-terminus of FAT/CD36 in both subcellular localization of the molecule and its activity as a LCFA transporter has been examined using truncated mutants and chimeric variants of FAT/CD36. The results indicate that FAT/CD36 contributes to LCFA uptake by hepatocyte-derived cell lines. In these cells it resides in both non-raft and lipid raft domains of the plasma membrane that may not always include caveolae. The studies also indicate that the cytoplasmic C-terminus of FAT/CD36 contributes to the attachment of FAT/CD36 to membranes, including raft-derived detergent-resistant membranes. This domain is necessary also for correct targeting of the receptor to the plasma membrane and for its activity as a LCFA transporter. Finally, DNA constructs have been prepared and tested, with the objective of producing transgenic mice in which expression of FAT/CD36 can be induced and over-expressed specifically in the liver. This model could be used to confirm whether FAT/CD36 has a role as a LCFA transporter in the liver and to explore whether it has additional significance as a hepatic transporter of HDL-derived cholesteryl esters or as a scavenger of oxidised LDL. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1294862 / Thesis (Ph.D.) -- School of Molecular and Biomedical Science, 2007

Thesis (M.S.)--Oregon State University, 2007. / Printout. Includes bibliographical references (leaves 101-107). Also available on the World Wide Web.

Patients diagnosed with malignant glioma tumours have median survivals of 1.6 yrs and 5 months, respectively, highlighting the deadly nature of this disease. Despite aggressive multimodal treatment, patients with malignant glioma often present with secondary brain tumours at sites distal to the primary tumour mass. These secondary tumours are a consequence of renegade neoplastic cells that infiltrate the surrounding normal brain, a hallmark feature of malignant glioma. Brain fatty acid-binding protein (FABP7), which binds omega-3 docosahexaenoic acid (DHA) and omega-6 arachidonic acid (AA), is overexpressed and associated with a poor prognosis in patients with malignant glioma compared with normal brain. These data suggest that FABP7 plays an important role in gliomagenesis; however, the mechanism(s) underlying a role for FABP7 in malignant glioma has, until now, been unexplored. Here, we demonstrate that expression of FABP7 in malignant glioma cells is accompanied by increased cell migration. Consistent with our in vitro results, we show that expression of FABP7 in astrocytoma tumours is associated with sites of tumour infiltration and tumour recurrence. Furthermore, we demonstrate that the fatty-acid ligands of FABP7 affect cell migration in an FABP7-dependent manner. More specifically, DHA inhibits migration, whereas AA stimulates cell migration. Finally, we reveal that uptake and incorporation of DHA and AA in the phospholipids of malignant glioma cells is enhanced by FABP7 expression, suggesting a mechanism by which DHA and AA may affect cell migration by altering signal transduction at the cell membrane. We propose that the inherent ability of malignant glioma cells to express the radial glial marker FABP7 underlies their infiltrative capacity, allowing tumour cells to migrate long distances from the main tumour mass. We propose a model whereby FABP7 expression and relative levels of DHA and AA determine tumour infiltrative potential. Our findings provide insight into the role of FABP7 and its fatty acid ligands in controlling the migration of malignant glioma cells and point to the potential use of DHA as a natural anti-infiltrative agent in the treatment of malignant glioma. We believe that targeting FABP7-expressing cells may make a significant impact on the treatment of high grade astrocytomas. / Experimental Oncology

Three studies were conducted to determine the effects of cyclopropenoid fatty acids (CPFA) on the membrane components of livers of rainbow trout (Salmo gairdneri). In the first study, ¹⁴C-sterculic acid was administered by intraperitoneal injection into rainbow trout and the trout maintained for 72 hours. The labelled sterculic acid was found in choline phospholipids (CP) and ethanolamine phospholipids (EP). Smaller amounts of label were found in other microsomal membrane lipid components. No label was found associated with the proteins of the microsomal membrane. Phospholipase A₂ treatment of isolated CP and EP showed ¹⁴C-sterculic acid to be preferentially esterified to the 1-position of the glycerol backbone. In the second study, the cleavable bifunctional protein crosslinking reagent dimethyl 3,3'-dithiobispropionimidate-2HCl (DTBP) was used in an attempt to study alterations in the spatial arrangement of proteins in liver microsomal and plasma membranes that might be induced by dietary CPFA. The use of this reagent failed to yield a clear picture of protein-protein interactions in the microsomal membrane due to the formation of high molecular weight aggregates that were not resolvable on polyacrylamide gels. On the other hand, the use of DTBP failed to crosslink the proteins of the plasma membrane. In the third study, two-dimensional polyacrylamide gel electrophoresis was used to assess the effects of dietary CPFA on protein composition of trout liver microsomal and plasma membranes. Proteins were separated in the first dimension on the basis of their isoelectric points and in the second dimension on the basis of their molecular weights. No major alterations in the composition of liver microsomal or plasma membranes were found to be induced by dietary CPFA. / Graduation date: 1983