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Biomedical subjects

U Sawada

Publications and source records attributed to U Sawada.

72 records · Page 4Linked to original sources
PubMed1982

Colony stimulating factor in human mixed leukocyte cultures.

Colony stimulating factor (CSF) is important for granulocyte/macrophage proliferation and differentiation. We investigated the relationship between the immune reactivity and the production of CSF by using two-way mixed leukocyte cultures (MLC) prepared from human peripheral mononuclear cells obtained with the aid of a blood cell separator. Assessed over 9 days of MLC incubation, the level of CSF in the supernatant reached a maximum at day 7 and then decreased. Optimal number of MLC cells ranged from 1 X 10(6)/ml to 2 X 10(6)/ml; CSF activity decreased at a cell concentration of 4 X 10(6)/ml. There was a differential sensitivity between cluster formation and colony formation to MLC-CSF. MLC-CSF is not species specific and hence, can stimulate both human and mouse CFU-c. MLC-conditioned medium (MLC-CM) appears to be a potentially useful source of CSF.

Animals↗
PubMed1980

In vitro hemopoiesis of W/WV and +/+ marrow cells cultured alone and with thymocytes.

To evaluate the effects of thymocytes from anemic W/WV mice on hemopoiesis in vitro, we co-cultured thymocytes from W/WV mice or from their non-anemic +/+ littermates with W/WV or +/+ marrow cells in semi-solid systems designed to foster colonial growth from neutrophil/macrophage (CFUNM), early erythroid (BFUE), late erythroid (CFUE) precursors. The marrow cell to thymocyte ratios in the cultures were 1:3 and 1:20 (1:175 for CFUNM). Untreated or anti-theta serum (ATS) or mock (control) AT treated marrow cells were cultured with the thymocytes. We found that marrow from +/+ and W/WV mice contain equivalent concentrations of CFUNM but W/WV marrow has a lower concentration of BFUE than +/+ marrow. Neither +/+ nor W/WV thymoctyes, in the concentrations used, effected any increase in the numbers of CFUNM or CFUE colonies formed from untampered or antiserum treated marrow cells. In two groups, thymocytes effected a slight increase in the numbers of bursts (BFUE colonies) formed from marrow cell suspensions and in both of these groups W/WV thymocytes were as effective as +/+ thymocytes. Thus, under the conditions studied, W/WV thymocytes were not more inhibitory or less stimulatory for in vitro hemopoiesis than were normal thymocytes.

Anemia, Hemolytic, Congenital↗
PubMed1980

Hemopoietic support capacity of W/WV femurs and tibias.

We evaluated the capacity of "stromal stem cells" of the bones of W/WV mice to effect regeneration of functional "stromal" tissue by implanting femurs and tibias from congenic W/WV and +/+ mice subcutaneously into congenic mice of normal hematologic phenotypes. Eight weeks after implantation, we assayed the hemopoietic progenitor cell contents of the bones. Pluriopotent hemopoietic stem cells (CFUs) were assayed by the spleen colony forming assay in lethally irradiated CAF1 mice. Granulocyte/macrophage progenitor cells (CFUGM) and early erythroid (BFUe) and late erythroid (CFUE) progenitor cells were assayed in agar and methylcellulose semi-solid culture systems, respectively. total cellularity was greater in implanted W/WV femurs and tibias than in +/+ femurs. Although there was substantial variation in the repopulation of W/WV femurs compared to that of +/+ femurs, on the whole, in the W/WV implanted femurs, the numbers of CFUs may have been slightly less and the numbers of maturer progenitor cells slightly greater than they were in the +/+ femurs. All of the progenitor cells assayed were more numerous in the implanted W/WV tibias than in the +/+ tibias. These findings suggest that "stromal stem cells" of W/WV marrow are not defective. In addition, the fact that there were more CFUs in th W/WV that in the +/+ tibias suggests that the CFUs which are native to the implanted bones are not needed to effect reconstitution of normal numbers of CFUs in the implants as all of the CFUs detected in W/WV femurs must have come from the host, for W/WV CFUs do not form surface spleen colonies and, therefore, would not have been counted.

Anemia, Hemolytic, Congenital↗
PubMed1979

Effect of human serum from patients with haematological disorders on mouse pluripotent haemopoietic stem cells (CFU-S).

Sera from 25 individuals (9 healthy subjects, 6 patients with systemic lupus erythematosus, and 10 patients with a variety of haematological disorders) were tested for anti-CFU-S by incubating suspensions of mouse marrow cells with serum and then assaying the cell suspensions for their capacity to form spleen nodules in lethally irradiated mice. The sera from 2 patients (1 with a preleukaemic disorder and the other with a malignant 'histio'-lymphoproliferative neoplasm) had anti-CFU-S activity which behaved like antibodies, rather than like the non-specific cytotoxic activity found in various sera for heterologous tissues, which in the past has been attributed to 'natural antibodies' and which, in recent years, has, in some cases, been found to be related to activation of the alternative pathway of complement. The anti-mouse tissue activity in the sera of the 2 patients may be related either to cross-reactivities between certain mouse and human tissues or to cross-reactivities between exogenous agents such as bacteria and mouse tissues.

Absorption↗
PubMed1978

Hemopoiesis on macrophage-coated cellulose acetate membranes (CAMS) in mice: an immunological study.

Macrophage-coated cellulose acetate membranes (CAMS), implanted into the peritoneal cavities of sublethally irradiated mice, support the growth of hemopoietic colonies. To investigate the nature of the precursor cells (CFU-ML) which form colonies on CAMS, we pre-treated marrow cells with rabbit anti-mouse brain serum (RAMBS), a known anti-pluripotent stem cell (CFU-S) serum, plus complement (C) and studied the number of colonies formed and the distribution of their sizes among the various histological types. Marrow cells pre-treated with RAMBS + C, even with the opportunity for interaction with macrophages in vivo, did not form fewer or smaller colonies than those formed from CRS + C treated cells, suggesting that most of the CFU-ML are antigenically distinct from CFU-S.

Animals↗
PubMedDate not supplied

Expression of beta 1 integrins (very late antigens-4 and -5) on myeloma cells and clinical correlates in patients with multiple myeloma.

beta 1 Integrins are considered to be essential for the differentiation of bone-marrow B cells through an interaction with fibronectin-expressed bone-marrow stromal cells. The expression of very late antigens-4 (VLA-4) and -5 (VLA-5) by CD38bright bone-marrow cells in patients with multiple myeloma was measured by flow cytometry using specific monoclonal antibodies. The percentage of CD38bright bone-marrow cells appeared to correlated with that of bone-marrow plasma cells as judged by examination of bone-marrow smears (r = 0.911, P < 0.0001). Expression of VLA-4 and VLA-5 by CD38bright cells varied between patients, but the expression of VLA-4 was always equal to or greater than that of VLA-5. The ratio of VLA-4 to VLA-5 expression (VLA-4:VLA-5 ratio) was calculated and compared with the clinical features of the myeloma patients. A high VLA-4:VLA-5 ratio (> 2.0) was associated with the presence of plasmacytomas and urinary Bence-Jones protein was more common in this group. No other correlations between the clinical features of the disease and the expression of beta 1 integrins were found.

ADP-ribosyl Cyclase↗
PubMedDate not supplied

Huge IgD plasmacytoma in the abdomen presenting coagulation necrosis.

A 65-year-old Japanese woman was diagnosed in 1996 with a pathological fracture of the left femur caused by immunoglobulin D-type myeloma (IgD myeloma). She responded well to combination chemotherapy followed by irradiation. The patient experienced renal failure and became dependent on haemodialysis. In 1999, large plasmacytomas developed in the abdomen and left humerus. The abdominal tumour appeared to induce gastroduodenal ulcers and jejunal obstruction. We initiated irradiation therapy without chemotherapy to prevent further growth of the plasmacytoma, although treatment-resistant gastroduodenal ulcers developed. Continued blood loss from the gastroduodenal ulcers resulted in a deterioration in the patient's health, which prevented successful haemodialysis. An autopsy showed that the plasmacytoma had undergone coagulation necrosis. We conclude that the use of combination chemotherapy with topical irradiation was an acceptable treatment measure against IgD plasmacytoma; irradiation without chemotherapy was the most likely cause of the coagulation necrosis seen in the plasmacytoma at autopsy.

Abdominal Neoplasms↗
PubMedDate not supplied

Pure red cell aplasia and myelofibrosis in B-cell neoplasm.

We describe an unusual case of B-cell neoplasm accompanied by pure red cell aplasia (PRCA) and myelofibrosis in a 67-year-old male presenting with severe anaemia. A few unclassified, myeloperoxidase-negative blastoid cells were seen on bone marrow aspiration, and erythroid cell hypoplasia and myelofibrosis on bone marrow biopsy. An autoimmune PRCA was suspected, as serum CH50, C3 and C4 levels were consistently low. Ciclosporin was effective in treating the anaemia, but anaemia returned when the drug was discontinued. Thirteen months later, the patient was admitted with pleural effusion and ascites that contained monoclonal CD19+ CD20+ immature blast cells with a complex karyotype, thought to be neoplastic B-cells. The unclassified blastoid cells seen earlier may therefore have been from the same origin. The patient deteriorated rapidly and died. Only one case of non-Hodgkin's lymphoma with PRCA and myelofibrosis has been reported previously. We discuss the possibility that dysregulated T-cells induced by neoplastic B-cells may have given rise to concomitant PRCA and myelofibrosis.

Aged↗
PubMedDate not supplied

Durable molecular complete remission induced by low-dose imatinib plus low-dose interferon alpha in a patient with chronic myelogenous leukaemia.

A 50-year-old male was diagnosed with chronic myelogenous leukaemia (CML) in chronic phase in March 2000. He was treated initially with hydroxyurea, administered orally. This was changed to interferon alpha (IFN) 5 million units (5 MIU) subcutaneously daily in May 2000; complete cytogenetic response was achieved 11 months later. IFN dosage was reduced to 5 MIU, alternate days, in June 2001 and a cytogenetic relapse occurred 3 months later. Since April 2002, he has received IFN 5 MIU three times weekly in combination with imatinib 200 mg/day. The Philadelphia chromosome disappeared from his peripheral blood cells in July 2002 and a complete molecular response was achieved in January 2003. Serial molecular studies between January 2004 and January 2005 showed no detectable major BCR/ABL chimeric transcript. Grade 2 neutropenia and grade 1 non-haematological adverse effects have been observed. This case report suggests the combination of low-dose imatinib and IFN would be tolerable and effective for CML patients in chronic phase.

Antineoplastic Agents↗