Impaired fibrin formation in a patient with multiple myeloma presenting the "gelation" phenomenon.
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Biomedical subjects
Publications and source records attributed to M Katsuno.
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We examined CFU-S proliferation stimulator, which recruits stem cells in DNA synthesis, in conditioned media prepared from bone marrow cells of patients with regeneration hemopoiesis after chemotherapy induced hypoplasia. This activity was estimated by hydroxyurea sensitivity of CFU-S in mice, under conditions of incubation with human bone marrow conditioned medium (BMCM). We found that CFU-S proliferation stimulator was present to a considerable extent in human regenerating BMCM, but less so in normal BMCM and that the production fluctuated with change of hemopoietic states, in the same patient. This stimulator was heat-labile, trypsin-sensitive and mainly produced by adherent cells. This factor may possibly be involved in regulation of proliferation of stem cells in regenerating bone marrow in humans.
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To clarify the regulatory roles of burst-promoting activity (BPA) in cases of in vivo erythropoiesis, we examined erythroid progenitors and BPA in 18 patients with a regenerating hemopoiesis following intensive chemotherapy. Marrow erythroid progenitors increased remarkably in these patients. Bone marrow-conditioned medium (BMCM) and sera obtained from these patients revealed high levels of BPA. Serial examination of a typical case showed that BPA in BMCM and sera increased during regenerating hemopoiesis, but decreased when the hemopoiesis stabilized. Adherent cell depletion and treatment with monoclonal antibody (OKM1) reduced BPA production from the bone marrow cells, thereby suggesting that bone marrow macrophages are responsible for the BPA production. Fractionation of pooled BMCM with Amicon Diaflo membranes showed that the BPA was mainly present in the 30,000- to 50,000-dalton fraction. BPA in BMCM was heat labile, inactivated by trypsin and protease, but was not inactivated by neuraminidase. Pooled BMCM did not influence the growth of CFU-E-derived colonies. Our results suggest that to repair disturbed erythropoiesis, bone marrow macrophages produce BPA during regenerating hemopoiesis.
Human bone marrow-derived fibroblastoid colony-forming cells (CFU-F) and adipocyte colonies in 36 patients with acute leukemia were studied, and were serially analysed at different clinical stages. At untreated stage, CFU-F number in acute lymphoblastic leukemia (ALL) was lower than that in acute non-lymphoblastic leukemia (ANL). In ANLs, CFU-F number in M1 was lower than that in M2. Adipocyte colonies were frequently developed at regenerating and relapsing stages, but rarely at untreated and remission stages. The adipocyte colony formation did not correlate with any of CFU-F number, marrow cellularity nor number of leukemic cells, but might be associated with hemopoietic regeneration. The favorable prognosis was associated with normal CFU-F number and with adipocyte colony formation at regenerating or bottom stage. As adipocytes in marrow samples were completely removed before cultures, adipocyte colony was probably originated from preadipocytes. Thus, our results suggest that adipocyte precursor cells increase in regenerating marrow and that they are essential in active hemopoiesis.
Bone marrow-derived fibroblastoid colony-forming cells (CFU-F) and granulocyte/macrophage precursor cells (CFU-GM) were studied in patients with acute leukemia. The numbers of CFU-F and CFU-GM were significantly lower in patients with acute myelogenous leukemia (AML) and acute lymphocytic leukemia (ALL) at diagnosis than in normal subjects, although patients with AML had a very wide range of CFU-F colony-forming efficiency. However, a suppressive effect of leukemic cells on normal CFU-F colony formation was not observed. CFU-F and CFU-GM in patients with acute leukemia recovered to normal levels when complete remission (CR) was achieved and decreased again at relapse. Serial studies showed that the increase in CFU-F preceded the recovery of CFU-GM. In AML, furthermore, patients who achieved CR had a higher number of CFU-F than patients without CR, suggesting that the CFU-F level at diagnosis may contribute to the prediction of the likelihood of remission induction in patients with AML.
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Therapeutic effects on cefmenoxime hemihydrochloride (CMX, Bestcall), a new synthetic cephem antibiotic, were examined in the treatment of various infections complicated with hematological diseases. The number of patients treated with CMX was 37 including 5 cases of sepsis or suspected sepsis, 14 cases of pneumonia or suspected pneumonia, 5 cases of upper respiratory diseases, 2 cases of urinary tract infections and 11 cases of other infections. All of these infections were complicated with hematological diseases: Acute leukemia, 13 cases; chronic myelocytic leukemia, 1 case; adult T cell leukemia, 3 cases; malignant lymphoma, 8 cases; Hodgkin's disease, 2 cases and myeloma, 3 cases. CMX were administered by a single intravenous injection or by a drip infusion. The dose was between 2 and 6 grams per day. Good to excellent clinical results were obtained in 25 out of 37 cases, total effective rate of 67.6%. No clinical side effects or abnormal laboratory findings attributable to CMX were observed except for light diarrhea in 2 cases. By the clinical investigation, it was demonstrated that CMX was one of safe and effective antibiotics for treating infections in the compromised hosts complicated with hematological diseases.
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A preadipocyte cell line (K-1) has been established from the adherent cell population of murine bone marrow culture. Using light microscopy, the cells exhibit fibroblast-like morphology and accumulate lipids in their cytoplasm as the cultures become confluent. Ultrastructurally, each cell has a large indented nucleus with prominent nucleoli. The cytoplasm contains a well-defined Golgi complex, numerous mitochondria, some endoplasmic reticulum, microfilaments, and fat droplets. Lysosomal granules are rarely recognizable. Cytochemically, they are positive for acid phosphatase, but negative for nonspecific esterase. Alkaline phosphatase activity is negative to weakly positive. Supernatants from K-1 cell cultures contain granulocyte/macrophage colony-stimulating factors, which stimulate primarily the growth of macrophage colonies, but do not affect proliferation of spleen colony-forming units.
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