Martin C. Carey

Bio: Martin C. Carey is an academic researcher from Brigham and Women's Hospital. The author has contributed to research in topics: Micelle & Cholesterol. The author has an hindex of 73, co-authored 207 publications receiving 18001 citations. Previous affiliations of Martin C. Carey include University of New Hampshire & Boston Medical Center.

The physical chemistry of cholesterol solubility in bile. Relationship to gallstone formation and dissolution in man.

Abstract: We determined the maximum solubilities of cholesterol in aqueous conjugated bile salt-egg lecithin-cholesterol systems as a function of several physical-chemical variables including those of physiological importance employing phase equilibria techniques. Equilibration rates are influenced by time and the method of sample preparation in that metastable supersaturation is readily induced at high bile salt: lecithin ratios, and equilibrium saturation by dissolution is achieved sluggisly at low bile salt:lecithin ratios. Equilibrium values for cholesterol saturation vary with the bile salt species, bile salt: lecithin ratio, temperature, ionic strength, and, in particular, with the total concentration of biliary lipids. Within physiological bile salt:lecithin ratios at 37 degreesC the influence of bile salt type and ionic strength is small, whereas the effects of bile salt:lecithin ratio and the total lipid concentration are major factors. We plotted on triangular coordinates a family of cholesterol solubility curves for each total lipid concentration (0.30--30 g/dl) and computed fifth-degree polynomial equations for each curve. With both the curves and the polynomial equations the "per cent cholesterol saturation" of fasting gallbladder and hepatic biles from patients with and without gallstones was calculated and both methods gave similar values. These results deomonstrate that by employing cholesterol saturation values appropriate to the total lipid concentration (range 0.2--24.9 g/dl) of individual biles, all cholesterol stone patients have supersaturated gallbladder biles, (mean, 132% [normal weight individuals], and 199% [morbidly obese individuals]). With controls and pigment stone patients the mean values were 95 and 98%, respectively, and in both approximately 50% of biles were supersaturated. Fasting hepatic biles were significantly more supersaturated than gallbladder biles (means 228--273%). Cholesterol monohydrate crystals were found in the majority of gallbladder (83%) and hepatic (58%) biles of cholesterol gallstone patients but were not observed in pigment stone patients or controls. We conclude that of the several factors in addition to the bile salt:lecithin ratios which can influence the cholesterol saturation of bile the total lipid concentration is the predominant determinant physiologically. Our results demonstrate that (a) metastable supersaturation is frequent in both normal and abnormal biles, (b) cholesterol gallstone patients have supersaturated gallbladder and hepatic biles without exception, and (c) the predominant driving force for cholesterol precipitation appears to be the absolute degree of cholesterol supersaturation.

Quasielastic light-scattering studies of aqueous biliary lipid systems. Mixed micelle formation in bile salt-lecithin solutions.

Abstract: From measurements of the autocorrelation function and time-averaged intensity of light scattered from aqueous bile salt-lecithin solutions, we deduced the mean hydrodynamic radius (Rh), shape, and polydispersity of bile salt-lecithin mixed micelles as functions of bile salt species, lecithin to bile salt (L/BS) molar ratio, total lipid concentration (0.625-10 g/dL), temperature (20-60 degrees C), and NaCl concentration (0.15-0.6 M). Our data suggest that at low L/BS ratios (0 to approximately 0.6) simple bile salt micelles coexist in varying proportions with minimum-sized mixed micelles (Rh, 18-35 A). These solutions are highly polydisperse and display features dependent upon the particular bile salt species. At high L/BS ratios (greater than 0.6), only mixed micelles are present, and their sizes increase markedly (Rh, 20 leads to 300 A) with increases in L/BS ratio and appear to diverge as the lecithin-bile salt phase limit is approached. The shape of the mixed micelles as deduced from light-scattering measurements and confirmed by transmission electron microscopy is disklike. The radii of the disks, however, are not compatible with Small's model of mixed micellar structure [Small, D.M. (1967a) Gastroenterology 52, 607-a1 but are consistent with a new model proposed here in which bile salts and lecithin interact to form a mixed bilayer disk which is surrounded on its perimeter by bile salts. The inclusion of bile salts in a fixed stoichiometry within the interior of the bilayers is shown to provide a quantitative explanation for the divergence of the mixed micellar sizes, their temperature dependence, and the origin of the lecithin-bile salt phase limit. The influence of total lipid concentration on both mixed micellar size and the lecithin-bile salt phase limit is explained by the "mixed disk" model by taking account of the equilibrium between mixed micelles and bile salt monomers in the intermicellar solution. By use of this concept, deductions of the intermicellar bile salt concentration in taurocholate-lecithin solutions are made and are shown to vary as a function of mixed micellar size and temperature. The range of values obtained, 3-6 mM, is comparable in magnitude to the critical micellar concentration of the pure bile salt.

Gut Microbiota in Health and Disease

Abstract: Gut microbiota is an assortment of microorganisms inhabiting the length and width of the mammalian gastrointestinal tract. The composition of this microbial community is host specific, evolving throughout an individual's lifetime and susceptible to both exogenous and endogenous modifications. Recent renewed interest in the structure and function of this "organ" has illuminated its central position in health and disease. The microbiota is intimately involved in numerous aspects of normal host physiology, from nutritional status to behavior and stress response. Additionally, they can be a central or a contributing cause of many diseases, affecting both near and far organ systems. The overall balance in the composition of the gut microbial community, as well as the presence or absence of key species capable of effecting specific responses, is important in ensuring homeostasis or lack thereof at the intestinal mucosa and beyond. The mechanisms through which microbiota exerts its beneficial or detrimental influences remain largely undefined, but include elaboration of signaling molecules and recognition of bacterial epitopes by both intestinal epithelial and mucosal immune cells. The advances in modeling and analysis of gut microbiota will further our knowledge of their role in health and disease, allowing customization of existing and future therapeutic and prophylactic modalities.

Pathogenesis of Helicobacter pylori Infection

Abstract: Helicobacter pylori is the first formally recognized bacterial carcinogen and is one of the most successful human pathogens, as over half of the world's population is colonized with this gram-negative bacterium. Unless treated, colonization usually persists lifelong. H. pylori infection represents a key factor in the etiology of various gastrointestinal diseases, ranging from chronic active gastritis without clinical symptoms to peptic ulceration, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. Disease outcome is the result of the complex interplay between the host and the bacterium. Host immune gene polymorphisms and gastric acid secretion largely determine the bacterium's ability to colonize a specific gastric niche. Bacterial virulence factors such as the cytotoxin-associated gene pathogenicity island-encoded protein CagA and the vacuolating cytotoxin VacA aid in this colonization of the gastric mucosa and subsequently seem to modulate the host's immune system. This review focuses on the microbiological, clinical, immunological, and biochemical aspects of the pathogenesis of H. pylori.

Hyperhomocysteinemia: an independent risk factor for vascular disease.

Abstract: Background. Hyperhomocysteinemia arising from impaired methionine metabolism, probably usually due to a deficiency of cystathionine β-synthase, is associated with premature cerebral, peripheral, and possibly coronary vascular disease. Both the strength of this association and its independence of other risk factors for cardiovascular disease are uncertain. We studied the extent to which the association could be explained by heterozygous cystathionine β-synthase deficiency. Methods. We first established a diagnostic criterion for hyperhomocysteinemia by comparing peak serum levels of homocysteine after a standard methionine-loading test in 25 obligate heterozygotes with respect to cystathionine β-synthase deficiency (whose children were known to be homozygous for homocystinuria due to this enzyme defect) with the levels in 27 unrelated age- and sex-matched normal subjects. A level of 24.0 μmol per liter or more was 92 percent sensitive and 100 percent specific in distinguishing the two groups. The ...