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Biomedical subjects

L O Martinez

Publications and source records attributed to L O Martinez.

At least 19 recordsLinked to original sources

Cell surface adenylate kinase activity regulates the F(1)-ATPase/P2Y (13)-mediated HDL endocytosis pathway on human hepatocytes.

We have previously demonstrated on human hepatocytes that apolipoprotein A-I binding to an ecto-F(1)-ATPase stimulates the production of extracellular ADP that activates a P2Y(13)-mediated high-density lipoprotein (HDL) endocytosis pathway. Therefore, we investigated the mechanisms controlling the extracellular ATP/ADP level in hepatic cell lines and primary cultures to determine their impact on HDL endocytosis. Here we show that addition of ADP to the cell culture medium induced extracellular ATP production that was due to adenylate kinase [see text] and nucleoside diphosphokinase [see text] activities, but not to ATP synthase activity. We further observed that in vitro modulation of both ecto-NDPK and AK activities could regulate the ADP-dependent HDL endocytosis. But interestingly, only AK appeared to naturally participate in the pathway by consuming the ADP generated by the ecto-F(1)-ATPase. Thus controlling the extracellular ADP level is a potential target for reverse cholesterol transport regulation.

Adenosine Diphosphate↗

The nucleotide receptor P2Y13 is a key regulator of hepatic high-density lipoprotein (HDL) endocytosis.

Cell surface receptors for high-density lipoprotein (HDL) on hepatocytes are major partners in the regulation of cholesterol homeostasis. We recently identified a cell surface ATP synthase as a high-affinity receptor for HDL apolipoprotein A-I (apoA-I) on human hepatocytes. Stimulation of this ectopic ATP synthase by apoA-I triggered a low-affinity-receptor-dependent HDL endocytosis by a mechanism strictly related to the generation of ADP. This suggests that nucleotide G-protein-coupled receptors of the P2Y family are molecular components in this pathway. Only P2Y1 and P2Y13 are present on the membrane of hepatocytes. Using both a pharmacological approach and small interference RNA, we identified P2Y13 as the main partner in hepatic HDL endocytosis, in cultured cells as well as in situ in perfused mouse livers. We also found a new important action of the antithrombotic agent AR-C69931MX as a strong activator of P2Y13-mediated HDL endocytosis.

Adenosine Diphosphate↗

New insight on the molecular mechanisms of high-density lipoprotein cellular interactions.

High-density lipoprotein (HDL) cholesterol is an independent negative risk factor for coronary artery disease and thus represents today the only protective factor against atherosclerosis. The protective effect of HDL is mostly attributed to its central function in reverse cholesterol transport (RCT), a process whereby excess cell cholesterol is taken up and processed in HDL particles, and is later delivered to the liver for further metabolism and bile excretion. This process relies on specific interactions between HDL particles and cells, both peripheral (cholesterol efflux) and hepatic (cholesterol disposal) cells, and on the maturation of HDL particles within the vascular compartment. The plasma level of HDL cholesterol will thus result also from the complex interplay with cellular partners. Among them, some contribute to HDL formation - for instance ATP binding cassette AI protein - while others are mostly involved in HDL catabolism, the scavenger receptor-class B type I or the recently described membrane-bound ATP synthase/hydrolase. The last decade has seen major breakthroughs in the identification and elucidation of the role of cellular partners of HDL metabolism, and in their transcriptional regulations, opening up new perspectives in the modulation of HDL cholesterol.

ATP Binding Cassette Transporter 1↗

Characterization of two high-density lipoprotein binding sites on porcine hepatocyte plasma membranes: contribution of scavenger receptor class B type I (SR-BI) to the low-affinity component.

Two HDL(3) high- and low-affinity binding sites are present on the human hepatoma cell line (HepG(2)). Recently, we have suggested that the high-affinity binding sites might modulate the endocytosis of HDL through the low-affinity binding sites [Guendouzi, K. (1998) Biochemistry 37, 14974-14980], highlighting the physiological importance of this family of HDL high-affinity binding sites. The present data demonstrate the presence of HDL(3) high-affinity (K(d) = 0.37 microg/mL, B(max) = 260 ng/mg of protein) and low-affinity (K(d) = 86.2 microg/mL, B(max) = 14 300 ng/mg of protein) binding sites on purified porcine hepatocyte plasma membranes. By contrast, free apoA-I was strictly specific to the high-affinity sites (K(d) = 0.2 microg/mL and B(max) = 72 ng/mg of protein). Competition experiments between (125)I-labeled HDL(3) and either LDL, oxidized LDL, or anti-SR-BI IgG as competitors show that SR-BI is mostly responsible (70% displacement) for the binding of HDL(3) to the low-affinity binding sites. By contrast, the same competition experiments using (125)I-labeled free apoA-I clearly excluded SR-BI as the high-affinity binding receptor. We conclude that the binding of HDL onto hepatocyte plasma membranes involves: (1) two low-affinity binding receptors, one being SR-BI; (2) one family of high-affinity binding sites unrelated to SR-BI.

Amino Acid Sequence↗

World Health Organization--basic radiographic system (WHO-BRS) unit: experimental clinical evaluation.

The basic radiographic system (BRS) is a simplified version of a standard radiographic unit designed by the World Health Organization and the Pan American Health Organization. The design of the BRS includes the requirement that it should be able to perform routine radiographic examinations with a minimum of operator training. This report describes the performance of a BRS manufactured by Siemens. The physical parameters of this BRS were very good and operation should require a minimum of training. A small number of BRS films were compared with films obtained using the standard equipment in the department. The BRS films were generally regarded as satisfactory. Radiation exposure to patients is equal to, and in some cases less than, exposures with conventional X-ray units.

Developing Countries↗

Empty right iliac fossa.

In the diagnosis of intra-abdominal disease, absence of gas or fecal shadows from the right iliac fossa is an important but nonspecific finding on plain roentgenograms. We found the empty right iliac fossa most commonly associated with acute appendicitis, Crohn's disease, and carcinoma of the cecum. Retrospective analysis of 137 confirmed cases of disease in the right lower quadrant yielded 21 (15.4%) with an empty right iliac fossa. In an additional 21 cases, an empty right iliac fossa was prospectively identified, and 13 of these patients (61.9%) had confirmed disease in a particular area.

Adolescent↗

Charcoal-containing empyema complicating treatment for overdose.

A 25-year-old man was treated with gastric lavage and activated charcoal for alcohol and drug overdose; immediately following the initial treatment he developed tension pneumothorax successfully managed with a chest tube. The patient presented four weeks later with a charcoal-containing empyema, an unreported condition heretofore.

Adult↗

Thickening of the posterior wall of the bronchus intermedius in right lung pneumonia.

A recent paper in the literature described thickening of the posterior wall of the bronchus intermedius (PWBI) in patients with congestive heart failure, and/or enlarged lymph nodes and neoplastic infiltrations. At this institution we have seen two recent cases of right upper lobe viral pneumonia demonstrating abnormal thickening of the posterior wall of the bronchus intermedius on lateral chest radiographs. A retrospective survey of our museum cases supported the hypothesis that pneumonia of the right lung, involving the right upper, middle, lower or any combination of these lobes may show thickening of the posterior wall of the bronchus intermedius.

Adult↗

Diagnostic considerations in urinary bladder wall calcification.

Though a relatively uncommon finding in general radiologic practice, urinary bladder wall calcification has relatively few etiologies. A series of 19 patients with radiographically visible bladder wall calcification encompassing most of the known causes is presented and other reported causes are discussed. Eight patients had schistosomiasis, six had primary carcinoma of the bladder, two had encrustation cystitis, and one each had amyloidosis, cyclophosphamide-induced cystitis, and tuberculosis. While a correct diagnosis is often not possible solely on the basis of the appearance of the calcification, such a diagnosis can usually be obtained expediently from a combination of history, clinical examination, appropriate laboratory studies, and radiographic evaluation of the bladder calcification and remaining urinary tract. Cystoscopy with biopsy of involved tissues is almost necessary, however, for confirmation and to rule out bladder neoplasia.

Calcinosis↗

Malignant fistulae of the gastrointestinal tract.

Internal malignant fistulae of the gastrointestinal tract involving two or more loops of different segments of the bowel are rare. The colon is frequently one of the participating loops. Observations on four such cases indicate that the fistulous tract connecting the two bowel loops is usually linear, somewhat wide, and does not produce significant approximation of the bowel loops involved. These radiographic features help to differentiate such fistulae from the benign type.

Aged↗

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Education, Medical, Continuing↗

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Florida↗