Citations

SUMMARY Normative values were established for results of tests of blood coagulation and platelet function in swine. In swine that have von Willebrand's disease, bleeding time was prolonged, platelet retention was decreased glass bead column), and factor VIII concentration was low.

SUMMARY Factor VIII concentrations in plasma, platelet retention, and ear bleeding times were determined on 35 normal pigs, 40 obligate carriers of porcine von Willebrand's disease, and 25 bleeders. The bleeders could be distinguished from the normal pigs by each of the 3 tests. At most, only one-third of the carriers could be distinguished from the normal pigs by any one test. A hemostatic score, derived from the results of the 3 tests, increased the discrimination to slightly more than half. The degrees of abnormality on the 3 diagnostic tests seemed to vary from family to family and might have been related to the sire of the bleeder.

SUMMARY Copper (Cu) was assayed in serial liver biopsy specimens of 5 pups resulting from a mating of 2 Bedlington Terrier carriers of inherited Cu toxicosis; the latter were sibling offspring of an affected Bedlington Terrier and a normal dog. Between 5 and 7 months of age, 1 of the pups had acceptable hepatic Cu values in each of 6 specimens. The hepatic concentration of Cu in another pup increased steadily from 801 to 3,874 μg/g dry weight. The other 3 pups may be heterozygotes (carriers); in 1—the hepatic Cu peaked at 1,043 μg/g at 9 months, in the 2nd—at 636 μg/g at 7 months, and in the 3rd—at 492 μg/g at 7 months. Acceptable concentrations were present in these 3 dogs at 9 to 14 months. Results in the present study indicate that heterozygotes may have 1 normal and 1 abnormal controller gene for regulating their hepatic Cu metabolism, thus accounting for the increased hepatic Cu concentration only in the early months of life. The affected Bedlington Terrier with 2 abnormal genes was unable to suppress the progressive hepatic accumulation of Cu. Paired liver biopsy specimens obtained at 5 to 7 months and at 14 or 15 months of age might distinguish the heterozygote from the normal and the affected Bedlington Terrier pups.

A case is described in which oxalosis occurred in an 11-year-old boy. The patient had experienced the formation of numerous calculi and multiple operations for removal of the calculi. The clinical, pathologic and histochemical findings in the case are presented. The unusual features of the case are extensive deposits of calcium oxalate crystals in the kidneys, bone marrow, spleen, liver, blood vessels, and adrenal cortex. Calcium oxalate, a relatively inert substance, appears to effect renal damage by virtue of its deposition in the renal tissue. While many aspects of oxalate metabolism remain obscure, it is generally presumed that oxalosis represents an as yet undefined metabolic defect.

Abstract In 12 normal subjects, DNA and RNA synthesis by individual marrow cells was studied in vitro by autoradiography after short-term incubation with tritiated nucleosides. The DNA labeling index and RNA synthesis rate were highest in normal immature cells. The DNA index was zero in all mature cells, including small lymphocytes and plasma cells. In the most actively proliferating normal immature cells, the RNA synthesis rate was about 5 times higher than in normal plasma cells. Since both normal immature cells and plasma cells are characterized by a high content of RNA and active protein synthesis, the results of the present study suggest that a high RNA turnover may not be necessary for protein synthesis to proceed in nonproliferating, protein-producing marrow cells. In 10 patients with myeloma and in two patients with primary macroglobulinemia, the abnormal plasma cells were found to be labeled with H3thymidine in each instance. The RNA synthesis rate was about 3 times greater in plasmocytoid myeloma cells than in mature plasma cells of normal marrows, and also about 3 times greater in lymphocytoid myeloma cells than in mature lymphocytes of normal marrows. The abnormal cells in the lymphoplasmocytic disorders apparently differ from their counterparts in normal marrows not only by a higher proliferative potential, but also by a much greater rate of RNA synthesis. In actively dividing normal bone marrow cells, high values for both DNA and RNA synthesis were found. By contrast, in the neoplastic lymphoplasma cells studied, a discrepancy was noted between relatively low values of DNA synthesis and high values of RNA synthesis. Production of abnormal proteins within long-lived neoplastic plasmocytic cells may account for this finding.

Abstract When oxalated or resin-decalcified human plasma was adsorbed with barium sulfate, equilibrated with 0.0175M phosphate buffer (pH 6.3), and chromatographed through diethylaminoethyl (DEAE) cellulose, most of the plasma’s fibrinogen emerged from the column and factor XII was detected. No factor VIII was found. A second buffer phase, in which 0.04M phosphate buffer (pH 5.9) was used, removed more protein but not fibrinogen or factor VIII. A third phase, 0.10M phosphate buffer (pH 5.6), produced additional fibrinogen and, unlike the first fibrinogen fraction, factor XIII; but again, no factor VIII. A fourth and final phase, 0.40 to 0.50M phosphate buffer (pH 5.3), removed factors VIII and V, and the eluate contained no fibrinogen. Although separation of fibrinogen into two components required the four-buffer system, maximal yields of factor VIII were achieved by compressing the first three buffer phases into one. Specific activities of about 50-fold, from large volumes of plasma, and 200-fold, from small volumes, were obtained. Refined factor VIII was unstable unless citrate was added to a concentration of 0.4 per cent.