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Biomedical subjects

R Corrocher

Publications and source records attributed to R Corrocher.

At least 163 records · Page 9Linked to original sources

Evidence for a folic acid binding protein in human cell membrane.

Cell membranes were prepared by sucrose discontinuous gradient from human liver and human peripheral leukocytes and erythrocytes and from circulating leukocytes from patients with chronic granulocytic leukemia (CGL) and acute myeloblastic leukemia (AML). The membrane preparations from liver and from leukemic leukocytes were shown to bind tritiated folic acid. The membranes from normal leukocytes and erythrocytes did not show this binding capacity. The membrane preparation from liver and CGL leukocytes showed two peaks of binding eluting with proteins from Sephadex G-200. However, protein extracts of these membrane preparations showed only a single peak for labelled folic acid, eluting near but just after albumin. The binding capacity of the membranes for folic acid was partially inhibited by reduced folate analogues. It is concluded that the liver plasma cell membrane and the membranes of myeloblasts in AML and circulating leukocytes in CGL contain a binding protein for folic acid which may be concerned in the transport of folates into these cells.

Animals↗

Alternative pathway for complement activation triggered by human liver plasma membranes.

Liver plasma membranes (LPM) prepared from normal hepatocytes by centrifugation in sucrose discontinuous gradient, are capable of haemolysing PNH-like cells in the presence of complement or complement plus EGTA or MG2+ ions. In contrast, EDTA or Ca2+ ions inhibit the lysis. The total complement lytic activity is reduced by some 40% when fresh serum is incubated with LPM, whereas the total amount of C4 remains constant. The cross-immunoelectrophoresis studies of fresh serum incubated with LPM demonstrate the appearance of C3 breakdown products, which suggests the activation of the alternative complement pathway. In contrast, the sucrose test, which proceeds mainly through the classical complement pathway, is inhibited by LPM. The possible role of complement in liver disease is discussed.

Cell Membrane↗

Different binding proteins for folic acid in serum of patients with acute hepatitis.

Serum from 44 volunteers and 21 patients with acute hepatitis and 18 with cirrhosis were tested for the total and unsaturated folate binding capacity (TFBC-UFBC). A high level of TFBC was noted in acute hepatitis (p < 0.001) and in cirrhosis (p < 0.05), whereas only in the last case a reduced UFBC was present (p < 0.05). When serum from patients with acute hepatitis was eluted on Sephadex G-200 after incubation with radio-active folic acid (500 pg), two main peaks were observed, one in the exclusion peak of protein and the second in the position of the only binder found in normal serum (MW 43,000). A third small peak was also present in the position corresponding to a MW of 20,000. These findings documented the release of binders from hepatic cell when a massive necrosis of liver occurs.

Acute Disease↗

In vitro production of PNH-like red blood cells by 2-mercaptopropionylglycine.

2-Mercaptopropionylglycine (2-MPG) transformed normal red blood cells (RBCs) into paroxysmal nocturnal haemoglobinuria (PNH)-like RBCs in vitro, depending on the concentration, pH and time of incubation. The incorporation of radioactive choline in the presence of acetylcholine was reduced, as in RBCs treated with aminoethylisothiouronium salt (AET). In contrast, the uptake in the presence of choline differed when the RBCs were incubated with the two compounds, being reduced in AET-treated RBCs and increased in 2-MPG-treated ones. As true PNH RBCs incorporated to a higher extent the radioactivity in the presence of both acetylcholine and choline, 2-MPG-treated RBCs seemed to resemble the PNH RBCs better than the AET-treated ones. Present results suggest the possibility of modifying selectively the activity of acetylcholinesterase and the transport of choline through the cell membrane.

Acetylcholine↗

Glutathione-peroxidase and glutathione-reductase activities of normal and pathologic human liver: relationship with age.

Liver glutathione-peroxidase (L-GSH-Px) and glutathione-reductase (GSSG-Red) activities were measured in supernatants of liver tissues obtained from a total of 36 subjects. Sixteen of these patients had a functionally normal liver (control group), whereas of the remaining 20 patients, 10 were cirrhotic and 10 had a liver disease other than cirrhosis. The mean value of L-GSH-Px of the control group was 33.12 +/- 12.66 U/g protein, a value similar to that found in patients with liver disease. The L-GSH-Px of the control group was positively correlated with the age of the subjects (r = 0.620; p less than 0.02). In contrast, in patients with liver disease an opposite behaviour of the two parameters was noted (r = -0.497; p less than 0.05). L-GSH-Px activity tended to be higher in males than in females, whereas the erythrocyte glutathione-peroxidase (E-GSH-Px) of the same patients was higher in females, albeit not significantly. L-GSH-Px and E-GSH-Px were not correlated either in normal or in liver disease. The mean GSSG-Red of the control group was 40.63 +/- 11.10 U/g protein, which is not different from that of the group of liver patients. GSSG-Red was not correlated with L-GSH-Px or with the age of patients. In two patients with hepatoma, the GSH-Px activity of the cancer tissue was low and the GSSG-Red activity high.

Adult↗

Serum folate binding capacity in leukemias, liver diseases and pregnancy.

Total and unsaturated folate binding capacity (TFBC, UFBC) have been measured in sera of selective groups of patients to study the role of cell turnover, cell necrosis and the effect of pregnancy in determining their concentrations in blood. The mean value of TFBC in 35 normal sera was 151 +/- (SD) 53 pg/ml with a saturation of 88%. The TFBC was raised in chronic granulocytic leukemia (CGL), in acute hepatitis, in cirrhosis, and in pregnancy (third trimester). The normal mean value of TFBC was found in chronic lymphocytic leukemia (CLL) and inthe first trimester of pregnancy. The mean UFBC in the normal sera was 19 +/- 18 pg/ml. In all the pathological conditions studied the mean UFBC was significantly greater than normal and it was particularly high in CGL (85 +/- 78 pg/ml).

Female↗

Activation of complement by stroma from normal and paroxysmal nocturnal haemoglobinuria red cells.

Stroma from normal, AET-treated and PNH red cells and their KC1-extracts (partially purified on Sephadex G-200) are able to trigger the activation of the alternative complement pathway. This fact has been demonstrated by: 1 - the lysis of PNH cells incubated in serum treated with stroma from normal or PHN-RBC or with their extracts; the addition of Mg2+ or Ca2+ or of their chelators (EDTA, EGTA) to the extract-treated serum enhances or abolishes the lysis 2 - the reduction of complement acitvity in fresh serum incubated for 60' with PNH-extract 3 - the appearance of C3 breakdown products in serum incubated with PNH-extract, demonstrated by crossed immunoelectrophoresis. In contrast, the same stroma (or extract) inhibits the sucrose lysis test, in which the lysis takes place through the classical complement pathway. No differences on the complement activation were observed between PNH and normal RBC stroma and between their chromatographic extracts. These findings may suggest the possible role of diurnal variation of Mg2+ and Ca2+ concentration in precipitating haemolytic attacks and the possibility that small amount of circulating red cell stroma might maintain the haemolysis on PNH RBC.

Acetylcholinesterase↗

Specific and non-specific folate binding protein in normal and malignant human tissues.

Binding of tritiated folic acid by supernatants prepared from extracts of normal and leukaemic leucocytes, normal mucosa, and malignant tumours from different parts of the gastrointestinal tract has been measured using Sephadex-gel filtration and albumin-coated charcoal techniques. Non-specific binding (measured by Sephadex G-75 gel filtration) was almost invariably greater than specific binding measured by albumin-coated charcoal separation of bound and unbound folate. In nine normal leucocyte extracts, binding measured by Sephadex G-75 filtration ranged from 1.3 to 18.2 (mean 8.2) pg/mg protein and by albumin-coated charcoal from 1.0 to 14.8 (mean 6.7) pg/mg protein. Raised specific binding was found in the extracts from leucocytes of eight of 14 patients with chronic granulocytic leukaemia, in four substantially so (389, 121, 108, 59.7 pg/mg protein), but was only marginally increased in one of eight cases of acute myeloid leukaemia and in two of five cases of chronic lymphocytic leukaemia. Binding was normal in the extracts of all three cases of acute lymphoblastic leukaemia tested. Among the tissues of the gastrointestinal tract binding was greatest by the duodenal mucosa and liver. Extracts of carcinoma of the stomach and colon bound greater amounts of (3)H-folic acid than the corresponding normal mucosal extracts but the differences were not large. Sephadex G-200 gel chromatography showed more than one binding peak in the extracts of liver and duodenum but only one peak in the other tissues of the gastrointestinal tract, and only one peak, of molecular weight either about 50 000 or over 200 000, in the leucocyte extracts.

Adolescent↗