Simultaneous primary infections with Epstein-Barr virus and measles virus in fatal acute encephalitis.
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Biomedical subjects
Publications and source records attributed to N Jacobsen.
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2 patients with coexistent polycythaemia vera and chronic lymphocytic leukaemia are described. A 61-year-old man presented with an increased packed cell volume (PCV) and a leucoerythroblastic blood picture, which was reversible upon treatment, neutrophil leucoytosis, bone marrow lymphocyte infiltration and splenomegaly, and subsequently developed lymphomas, blood lymphocytosis and thrombocytosis. The second case was a 58-year-old female presenting with increased PCV and leucocyte alkaline phosphatase score. She later had neutrophil leucocytosis, thrombocytosis, lymphocytosis, lymphomas and splenomegaly. These cases, together with 6 cases published by others, suggest that an association exists between the two diseases.
Incubation of the non-adherent low density cells from normal human bone marrow with an antiserum to DR antigens markedly inhibited their capacity to form granulocytic colonies in fibrin clot diffusion chambers implanted intraperitoneally into irradiated mice. The inhibitory effect of antiserum was abrogated after absorption of antiserum with B cells. Inhibition was obtained both with and without complement treatment. Neutrophilic colony formation exhibited a higher sensitivity to diluted antiserum to DR antigens as compared with eosinophilic colony formation. These results suggest that DR determinants are expressed on the neutrophilic and eosinophilic progenitor cells (CFUd) which give rise to colonies in diffusion chambers.
Bone marrow and peripheral blood cells of patients with non-leukemic neutropenia contain and elaborate a granulocyte-progenitor cell inhibitory activity. The inhibitory activity is common to the neutropenias of the various etiologies studied, which included congenital, idiopathic, autoimmune, cyclical, common variable immuno-deficiency with hypogammaglobulinemia and drug induced states. It derives from non-adherent, low density, slowly sedimenting and non-E-rosetting cells and appears to require RNA and protein synthesis, but not cell division, for its production. The material is not species specific, inhibits autologous and allogeneic normal CFUgm and leukemic CFUgm, is not cell-cycle specific in action and is most effective against granulocyte colony forming cells (CFUg), less effective against mixed granulocyte-macrophage colony forming cells (CFUgm) and least or non-effective against macrophage colony forming cells (CFUm). This inhibitory activity has no influence on cells which generate CFUc in suspension culture or on the erythroid colony forming (CFUe) and burst forming (BFUe) units. It is different from other known inhibitory activities such as lactoferrin, leukemia inhibitory activity, E type prostaglandins, interferon and immunoglobulins. This inhibitory activity, while at present an in vitro phenomenon, may be produced as a secondary response within a compromised host.
The presence of Ia-like antigens on human CFU-C and BFU-e is confirmed and a cell type that lacked immediate capacity for granulocytic colony formation but generated CFU-c after brief incubation in simple suspension culture is identified. This pre-CFU-c, and its immediate progeny, was extremely sensitive to killing by anti-Ia serum with complement. In contrast, anti-Ia serum plus complement treatment of human bone marrow, while eliminating 93%-97% of all CFU-c and BFU-e, did not prevent the rapid regeneration of these progenitor cells and their production for some weeks under the conditions of continuous marrow culture. These studies suggest that the human equivalent of the pluripotential stem cell can replicate for some weeks in culture and generate committed progenitors, such as CFU-c and BFU-e. Furthermore, it would appear that Ia-like antigen is absent on the pluripotential stem cell, is rapidly gained as commitment to the various progenitor cell types occur, and is subsequently lost as these latter undergo differentiation within the marrow.
Bone-marrow cells from patients with acute leukemia in remission were tested for their capacity to produce a substance (leukemia-associated inhibitory activity, LIA) that inhibits the formation of granulocyte and macrophage colonies in cultures of normal, but not of leukemic, bone marrow. LIA was detected in extracts of whole marrow in only eight of 83 patients in remission. However, extracts of slowly sedimenting cells, separated by velocity sedimentation from the marrows of eight patients in remission whose whole marrow had produced no LIA, produced inhibitory material in all cases. Extracts of the more rapidly sedimenting cells from these marrows contained an inactivator of LIA. Three of six patients in remission whose unfractionated marrow was unresponsive to LIA had a subpopulation of colony-forming cells that was sensitive to the inhibitor. These observations suggest that certain cellular functions dot not completely return to normal during remission of acute leukemia.
An series of experiments was performed to elucidate the relationship between cells that form granulocytic colonies in fibrin clot diffusion chambers implanted into the peritoneum (i.p.) of irradiated mice (CFU-d) and day 7 and day 14 CFU-U which give rise to colonies after 7 and 14 days in agar cultures in vitro, respectively. Normal human bone marrow cells were cultured in suspension in vitro or in diffusion chambers implanted into irradiated or non-irradiated mice. During these culture conditions there was an initial decrease in the number of CFU-c per culture. This was followed by an increase between day 2 and day 7 of culture. No similar increase of neutrophilic CFU-d was observed. When CFU-d, day 14 and day 7 CFU-c in normal marrow were separated by velocity sedimentation and cultured in suspension culture or in diffusion chambers for 7 days, the maximum increase of day 7 and day 14 CFU-c was observed in slowly sedimenting cell fractions which contained the majority of CFU-d. After 3 days in suspension culture, the maximum increase of day 14 CFU-c was found in fractions which also gave rise to maximum numbers of CFU-c after 7 days. However, day 7 CFU-c were found in fractions which initially contained the majority of day 14 CFU-c. No increase in CFU-d was found in fractions initially containing peak numbers of CFU-c. Between 53 and 71% of CFU-c harvested from diffusion chambers in irradiated mice or from suspension cultures were sensitive to pulse incubation with tritiated thymidine, suggesting that the cells were proliferating during these culture conditions. In diffusion chambers implanted into non-irradiated mice, however, CFU-c were found to be relatively resistant to this treatment (3-11% sensitive to tritiated thymidine). Thus marked increases in CFU-c were also observed during experimental conditions, where no significant DNA synthesis was detected. A reproducible time sequence of increase in CFU-c populations in culture was observed. Day 14 CFU-c and cells that gave rise to clusters on day 7 in agar increased between day 2 and day 4, whereas day 7 CFU-c increased between day 4 and day 7. The results suggested that CFU-d gave rise to CFU-c in culture and that day 14 CFU-c were precursors of day 7 CFU-c.
The concentration of granulocytic progenitor cells in the bone marrow of 2 patients with cyclic neutropenia was assessed at intervals during the cycle. Syncroneous oscillations were observed for cells forming neutrophilic and megakaryocytic colonies in diffusion chambers in vivo (CFU-D), suggesting a close relationship between the two cell types. However, an almost reverse relationship was observed between CFU-D and cells forming colonies in agar culture in vitro (CFU-C), which cycled out of phase with CFU-D. This supports the concept that CFU-D and CFU-C denote different cell types.
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Radioactive isotopes of strontium or nickel (89Sr and 63Ni) were injected ip as chlorides on adult female mice and the distribution and retention studied in several soft and hard tissues, including tissues of fetuses and sucklings. The strontium concentration was comparable in liver, kidney and heart and higher than that of brain tissue. The acid soluble part of the mineralized tissues showed a strontium concentration 100-1000 times that of the soft tissues. Progeny receiving strontium through placenta or through mammary glands showed a distribution pattern similar to that of their mother, with retention of strontium in mineralized tissue. The nickel concentration was larger in the kidney than in other organs investigated. No nickel affinity was found for mineralized tissues. Nickel was readily passed through placenta and mammary glands. Contrary to findings for strontium, the nickel concentration in tissues of fetuses was higher than that of their mother.
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To obtain gingival cell cultures, human gingival tissue was minced and/or subjected to trypsin treatment with or without prior separation into epithelial and connective tissue portions. The tissues were then incubated in Eagle/Earle's MEM with 10% fetal calf serum in a humidified atmosphere of 5% CO2 in air. Fibroblast-like cell cultures were regularly obtained, and one culture showed epithelial-like cell islets that could be transferred and kept in continuous culture. These epithelial-like cells exhibited bone resorption stimulating activity as seen in gingival tissue and retained their growth pattern after prolonged storage. They were able to grow at serum concentrations down to 2.5% and with equal doubling time (about 17h) in rich or minimum essential media. Exposure to nickel gave toxic effects on the growth at concentrations down to 2.5 microgram/ml of nickel. In spite of the affinity of nickel to certain serum components, the serum concentration did not appear to be of specific importance to protect or aggravate the toxicity. It is felt that these cells may be of value for research on cytotoxicity of dental materials.
In vitro cultivation of human submandibular gland tissue resulted in release of salivary proteins corresponding to about 50% of the total content after 48 hours. The admixture of plasma proteins as judged by single radial immunodiffusion took place early in the incubation period, and could be reduced by discarding the first washing medium. Hydroxyproline measurements in the medium indicated that the autolysis increased significantly after two days of incubation. Isoelectric focusing of human submandibular proteins resulted in fractions with isoelectric points closely resembling those demonstraded earlier for monkey submandibular gland proteins, but with larger acid fractions and smaller basic fractions. Virus haemagglutination inhibition (HAI) activity and sulphate incorporation was demonstrated in the most acidic, viscous fractions, whereas L-leucine incorporation was found in all fractions of the isoelectric scale. No sulphate affinity to submandibular proteins, independant of the in vitro protein synthesis, could be detected by equilibrium dialysis or other control measures.