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Biomedical subjects

J Abels

Publications and source records attributed to J Abels.

At least 73 records · Page 4Linked to original sources

The uptake of R-type cobalamin-binding protein by isolated rat liver cells.

The uptake of R-type cobalamin-binding protein from human granulocytes and plasma by isolated parenchymal rat liver cells has been studied. When [57Co] cyanocobalamin-saturated granulocyte-binding protein or transcobalamin III was incubated with the liver cells in a concentration of 500 pM, more than 80% of the vitamin was taken up in 1 h. Vitamin B-12 bound to plasma transcobalamin I, however, was not taken up unless the protein was desialylated by neuraminidase from Vibrio cholerae. The uptake of iodinated pure granulocyte-binding protein, saturated with cobalamin, reached 100% and was accompanied by increasing intracellular proteolytic degradation of the binding protein. EGTA and asialo-orosomucoid completely inhibited this process of uptake and degradation, whereas partial inhibition was caused by chloroquine and colchicine. These observations provide evidence that these (asialo)-R-type cobalamin-binding proteins are taken up by the cell through the plasma membrane receptor for asialoglycoproteins by means of endocytosis followed by proteolysis of the binding protein in the lysosomes.

Animals↗

Analysis of the breakpoints in translocation (15;17) observed in 4 patients with acute promyelocytic leukemia.

Four patients with acute promyelocytic leukemia (APL) and the chromosomal translocation (15;17) are described in detail. One of the patients presented with the microgranular variant form of APL and the standard translocation. Another patient is the third reported case with isochromosome formation of the 17q-derivative. Use of high resolution culture technique with methotrexate treatment allowed us to define the breakpoints at 15q2200 and 17q12.

Adolescent↗

An improved method for large scale purification of human holo-transcobalamin II.

25 mg of human holo-transcobalamin II with a specific cobalamin-binding capacity of 0.95 mol cobalamin/mol TC II was purified from 122 kg Cohn fraction III with a yield of 73% and a purification factor of 9.34 . 10(5). Consecutive purification steps comprised CM-Sephadex batchwise ion-exchange chromatography, affinity chromatography, using cyanocobalamin as a ligand, thermolability attached to 3.3'-diaminodipropylamine-substituted CH-Sepharose, and gel filtration. The high yield of the purification procedure was achieved by improving the stability of apo-transcobalamin II in the eluate of the CM-Sephadex, and by a few other modifications of a former procedure. In the latter, rapid denaturation of apo-transcobalamin II prohibited the use of long term affinity chromatography, which is obligatory for processing large amounts of Crohn fraction. In addition, subfractionation of transcobalamin II into smaller fragments which occurred in SDS-polyacrylamide gel electrophoresis in previous studies, was now reduced, indicating that proteolysis in the CM-Sephadex eluate had been prevented effectively.

Animals↗

Delayed alloimmunisation by random single donor platelet transfusions. A randomised study to compare single donor and multiple donor platelet transfusions in cancer patients with severe thrombocytopenia.

The effects of single-donor (SD) and multiple-donor (MD) platelet transfusions in 34 cancer patients with severe thrombocytopenia and haemorrhages were compared in a randomised study. Platelet recovery values in both groups were similar after the first transfusion. After the second transfusion platelet recovery values were significantly better in those receiving SD transfusions. Platelet recovery values gradually declined with subsequent MD transfusions. These results suggest early alloimmunisation in the MD transfused patients only. MD transfusions were estimated to be no longer effective after about nine transfusions. Platelet recovery values were better indicators of early sensitisation than was the lymphocytotoxicity test. Restriction of the number of donors per transfusion may postpone the development of refractoriness to random-donor platelet transfusions in thrombocytopenic patients.

Blood Donors↗

Cytogenetic follow-up of patients with nonlymphocytic leukemia. II. Acute nonlymphocytic leukemia.

Bone marrow (BM) karyotypes of 86 patients with acute nonlymphocytic leukemia (ANLL) were studied at the time of diagnosis: 39 of them (45%) were normally diploid and 47 (55%) showed acquired abnormalities. The median survival was no longer in the diploid group than in the aneuploid one. Nonrandom aberrations were often found: trisomy 8 (15 times), monosomy 7 (7 times), and t(8;21) (7 times). Two patients with acute promyelocytic leukemia presented with the t(15;17) in BM cells. Serial cytogenetic studies performed in 17 cases showed that karyotypic evolution closely followed the clinical evolution. Complete remission, obtained in 10 cases, was characterized by BM metaphases with a normal karyotype. Relapse after a period of complete remission was documented four times; the BM metaphases then showed the original abnormal karyotype with additional changes that, in three cases, were limited to a new structural aberration.

Acute Disease↗

Translocation (5p; 17q) in blast crisis of chronic myeloid leukemia.

A new abnormality of chromosome 17, distinct from i(17q), was observed in bone marrow cells of two patients with CML during a blast crisis. The marker was identified as a translocation of the short arm of chromosome 5 onto the long arm of chromosome 17, i.e., t(5p; 17q). In one case, the marker was clearly dicentric. The clinical history of these two patients showed some similarities. A slightly different marker has previously been observed in a cell line derived from a solid tumor.

Adult↗

Purification of human transcobalamin II-cyanocobalamin by affinity chromatography using thermolabile immobilization of cyanocobalamin.

Transcobalamin II-cyanocobalamin was isolated from Cohn fraction III of pooled human plasma by affinity chromatography on cyanocobalamin-Sepharose and some conventional separation methods. The affinity ligand cyanocobalamin was coupled to AH-Sepharose by a thermolabile linkage. The unsaturated binding protein was absorbed at 4 degrees C and eluted from the column at 37 degrees C as transcobalamin II-cyanocobalamin complex. The final preparation had a specific cyanocobalamin-binding capacity of 0.98 mol cyanocobalamin/mol transcobalamin II, the yield was 55% and the purification index amounted to 1.1 . 10(6). In dodecyl sulphate polyacrylamide gel electrophoresis one major protein band was observed at a molecular weight of 37 000 and a faint band at a molecular weight of 29 000. In polyacrylamide gel isolectric focusing the pure preparation turned out to be heterogeneous with isoelectric points ranging from pH 6.2 to 6.8, possibly by the occurrence of isoproteins.

Blood Proteins↗

Preparation of vitamin B-12-free serum for the use in vitamin B-12 radioassays.

In radioassays for serum vitamin B-12, the separation of free and bound vitamin is usually made with charcoal absorption. The specificity of this separation depends on the amount of charcoal and the protein content and constitution of the medium. The large difference in protein concentration between the samples for the dilution curve and the serum samples introduces an uncontrolled variable in the test. In order to equalize the experimental circumstances, the standard dilutions were made in serum freed from vitamin B-12 after boiling the serum for 20 min in a 4-fold dilution with glutamic acid buffer at pH 3.3 and subsequent passage over a CH-Sepharose 4-B column complexed with hog intrinsic factor (IF). The vitamin B-12-binding capacity of such an affinity column prepared from 1 g CH-Sepharose and 20 mg IF, suffices for the absorption of vitamin B-12 in 3000 ml serum from which 300 series of vitamin B-12 standard solutions can be made. Our first results with this method confirm that the charcoal absorption radioassay has become more accurate by the use of vitamin B-12-free serum in the standard dilutions.

Charcoal↗

Factor VIII inhibitor postpartum.

Acquired factor VIII deficiency in women postpartum due to a factor VIII inhibitor is rare and the etiology is unknown. In this study a case report and a review of the literature are given. The haemorrhagic diathesis resembles classic haemophilia, with the exception that ecchymoses and tissue bleeding occur more frequently. The potency of the inhibitor may vary from weak to strong and the inactivation of factor VIII coagulant activity (factor VIII-C) by the inhibitor is of a non-linear type. Severe bleeding has been fatal in a few cases, but factor VIII concentrate substitution has usually been successful without anamnestic response of inhibitor activity. There is no convincing evidence that immunosuppression is effective, also because the natural history of the disease is characterised by a spontaneous disappearance of the factor VIII-C inhibitor. Treatment of bleeding symptoms with factor VIII concentrate should therefore not be reserved for life threatening haemorrhages only.

Adult↗

Evaluation of a radioassay for serum folate and the effects of ascorbate and methotrexate.

In this study a competitive binding assay for serum folate is evaluated with special attention to storage conditions of the serum samples and the effect of methotrexate on the assay results. Average serum folate levels were 31 nmol/1 +/- 8 (S.D.) in 59 nromal sera and 19 nmol/1 +/- 12 (S.D.) in 354 sera from hospitalized patients of which 43 values were lower than 9 nmol/1. Serum folate appeared to be stable at - 20 degrees C for at least 5 weeks. The addition of ascorbate, which is said to stabilize serum folate, caused a non-specific increase of the measured folate. Methotrexate acted competitively with the tracer folate in the assay sytem when added in vitro and elevated the folate readings. The same occurred in the serum of a patient after intravenous methotrexate.

Ascorbic Acid↗