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Biomedical subjects

N Wakimoto

Publications and source records attributed to N Wakimoto.

29 records · Page 2Linked to original sources
PubMed1997

Properties of primary murine stroma induced by macrophage colony-stimulating factor.

The ability of purified human macrophage colony-stimulating factor (M-CSF) to accelerate the formation of stromal cells from murine bone marrow cells was investigated. The liquid culture of the marrow cells with M-CSF resulted in the formation of monolayers of macrophages on day 7. When the M-CSF was removed on that day and the residual adherent cells were cultured in the absence of M-CSF for an additional 7 days, many colonies appeared with cells that were morphologically distinguishable from M-CSF-derived macrophages. The appearance of the colonies was dependent on the concentration of M-CSF used at the beginning of the culture. Each colony was isolated as a single clone and analyzed. All clones were negative for esterase staining. These cells did not express M-CSF receptor mRNA and did not show a mitogenic response to M-CSF. On the contrary, these cells could be stimulated to proliferate by fibroblast growth factor and platelet-derived growth factor. The polymerase chain reaction analysis of these cells demonstrated constitutive expression of mRNA for M-CSF, stem cell factor, and interleukin (IL)-1, but not IL-3. Some clones expressed mRNA for granulocyte/M-CSF and IL-6. We also examined the ability of the cells to maintain murine bone marrow high proliferative potential colony-forming cells (HPP-CFC) in a coculture system. Most of the clones showed a significant increase in total HPP-CFC numbers after 2 weeks of coculture, although the extent of stimulation differed among clones. These results suggested that the colonies established by M-CSF were composed of functional stromal cells that were phenotypically different from macrophages.

Animals↗
PubMed1996

Cyclic change of cytokines in a patient with cyclic thrombocytopenia.

The serial change of various cytokines in the serum from a patient with cyclic thrombocytopenia is described. Interleukin 7, stem cell factor, and transforming growth factor beta 1 synchronized with the platelet count, and there was a significant positive correlation between the three cytokines and the platelet count. Levels of macrophage colony-stimulating factor, thrombopoietin, platelet-associated IgG and erythropoietin changed reciprocally with the platelet count, and there was a significant negative correlation between the platelet count and these cytokines except erythropoietin. No cyclic change was observed in IL-3, IL-6, IL-11, granulocyte-macrophage colony-stimulating factor, or leukaemia inhibitory factor. These observations suggest that this disease involves two cyclic changes: megakaryocytopoiesis and platelet destruction, in both of which the cytokines play an important role.

Adult↗
PubMed1996

An aggressive nasal lymphoma accompanied by high levels of soluble Fas ligand.

Fas ligand (FasL), either in the membrane bound form or soluble form, has cytotoxic activity against Fas-expressing cells. We report a case of nasal lymphoma accompanied by liver damage and pancytopenia. The serum level of soluble FasL (sFasL) was very high on admission, but rapidly decreased to normal levels after chemotherapy for lymphoma. Liver damage and pancytopenia also improved with the decrease in serum sFasL. Since Fas is expressed on both hepatocytes and haemopoietic cells, these facts suggest that FasL was expressed on lymphoma cells and directly associated with pathogenesis of liver damage and pancytopenia through its cytotoxic activity.

Enzyme-Linked Immunosorbent Assay↗
PubMed1994

Structural analysis of proteoglycan macrophage colony-stimulating factor.

Proteoglycan macrophage colony-stimulating factor (PG-M-CSF) was recently reported as a high molecular type of macrophage colony-stimulating factor (M-CSF). We analyzed its structure by determining the expression of mutant M-CSF cDNA in Chinese hamster ovary cells. PG-M-CSF contained two types of molecules, a homodimeric 150-200-kDa subunit and a heterodimeric form of a 43-kDa subunit and the 150-200-kDa subunit. The 150-200-kDa subunit carries a chondroitin sulfate chain, and its amino-terminal amino acid sequence was identical to that of the 43-kDa subunit, which is known to form the conventional M-CSF molecule (85-kDa M-CSF). The results obtained with the carboxyl-terminal deleted mutants showed that the PG-M-CSF-specific 150-200-kDa subunit had a large part of the precursor sequence at its carboxyl terminus removed in the 43-kDa subunit by proteolytic processing. The expression of mutagenized cDNA, in which Arg220 was replaced by an alanine residue, resulted in the disappearance of the 43-kDa subunit but not that of the 150-200-kDa subunit, indicating that Arg220-Pro-Pro-Arg is essential to process PG-M-CSF to 85-kDa M-CSF. Truncated mutation analysis showed that the carboxyl terminus of the 150-200-kDa subunit lay downstream of Arg412. We also showed that the chondroitin sulfate binding site in the 150-200-kDa subunit was Ser277, since conversion of Ser277 to the alanine residue resulted in complete loss of the chondroitin sulfate substitution.

Amino Acid Sequence↗
PubMed1993

Delayed catabolism of high density lipoprotein apolipoproteins A-I and A-II in human cholesteryl ester transfer protein deficiency.

Deficiency of the cholesteryl ester transfer protein (CETP) in humans is characterized by markedly elevated plasma concentrations of HDL cholesterol and apoA-I. To assess the metabolism of HDL apolipoproteins in CETP deficiency, in vivo apolipoprotein kinetic studies were performed using endogenous and exogenous labeling techniques in two unrelated homozygotes with CETP deficiency, one heterozygote, and four control subjects. All study subjects were administered 13C6-labeled phenylalanine by primed constant infusion for up to 16 h. The fractional synthetic rates (FSRs) of apoA-I in two homozygotes with CETP deficiency (0.135, 0.134/d) were found to be significantly lower than those in controls (0.196 +/- 0.041/d, P < 0.01). Delayed apoA-I catabolism was confirmed by an exogenous radiotracer study in one CETP-deficient homozygote, in whom the fractional catabolic rate of 125I-apoA-I was 0.139/d (normal 0.216 +/- 0.018/d). The FSRs of apoA-II were also significantly lower in the homozygous CETP-deficient subjects (0.104, 0.112/d) than in the controls (0.170 +/- 0.023/d, P < 0.01). The production rates of apoA-I and apoA-II were normal in both homozygous CETP-deficient subjects. The turnover of apoA-I and apoA-II was substantially slower in both HDL2 and HDL3 in the CETP-deficient homozygotes than in controls. The kinetics of apoA-I and apoA-II in the CETP-deficient heterozygote were not different from those in controls. These data establish that homozygous CETP deficiency causes markedly delayed catabolism of apoA-I and apoA-II without affecting the production rates of these apolipoproteins.

Adult↗
PubMed1993

[A double-blind dose ranging study of weekly subcutaneous administration of rHuEPO (KRN5702) on post-phlebotomy anemia of patients scheduled for predeposit autologous blood transfusion (multicenter late PhII study)].

Preoperative blood reservation for autologous blood transfusion generally causes anemia. We performed a double blind controlled study to determine the optimal dose of subcutaneous rHuEPO (recombinant human erythropoietin, KRN5702) for preventing preoperative anemia due to blood reservation. Patients received KRN5702 subcutaneously once a week in a doses of 12000, 24000 or 36000 IU by a double blind technique. After storage of 1200 ml of their own blood right before surgery, their hemoglobin (Hb) averaged about 1 and was about 0.5 g/dl lower than the level before administration of KRN5702 in doses of 12000 and 24000 IU, respectively. This fall was significant. In patients receiving KRN5702 in a dose of 36000 IU, the level of Hb rose instead of a fall; Hb immediately before surgery was 1.1% higher than that before administration which, however, was not significant. This elevation indicates a possibility of abnormal elevation of Hb at this dose. The mean Hb value right before surgery was significantly lower in patients receiving 12000 IU KRN5702 than in patients of the other two groups. The recovery rate of Hb was an indicator to reflect improvement of anemic conditions, and increased as the dose increased after the blood reservation. The rate in the 12000 IU group was significantly lower than that in the other two groups; there was not much difference between the other two rates. We estimated that to reserve 1200 ml of autologous blood, 24000 IU of KRN5702 is adequate but not excessive. One patient receiving 24000 IU showed side effects including an elevation of body temperature, rash, and edema.

Adult↗
PubMed1990

Recombinant human erythropoietin corrects anemia of blood loss: a study in the dog.

In order to evaluate the possibility of using recombinant human erythropoietin (rhEpo) for the prevention and correction of anemia due to blood loss and as an adjuvant for autologous blood transfusion, its preventive and therapeutic effects were evaluated in beagles in which anemia was induced by repeated phlebotomies. Two hundred U/kg of rhEpo were administered i.v. four or nine times every two weeks for six weeks. Phlebotomies (25 ml/kg of body weight) were conducted three times at two-week intervals. rhEpo was found to successfully prevent and correct anemia caused by the phlebotomies. Concurrent administration of iron increased efficacy. The findings obtained in the present study suggest that rhEpo is useful both for the treatment of anemia caused by blood loss due to surgery and as an adjuvant therapy for pre-deposit autologous blood transfusion.

Anemia↗
PubMedDate not supplied

A survey of autologous blood collection and transfusion in Japan in 1997.

BACKGROUND: In spite of the fact that autologous blood is safest for a patient to receive, it is not generally appreciated that adverse reactions during donation and transfusion may occur. This study was conducted to assess the state and the risk of autologous blood transfusion in Japan in 1997. STUDY DESIGN AND METHODS: Results of a nation-wide questionnaire-based survey are presented. The questionnaire assessed the number of autologous blood donations, donation procedures, and the adverse reactions associated with donation, preservation, recombination erythropoietin administration and transfusion. RESULTS: Between November 1996 and October 1997, 10,697,000 ml (or 53,485 units, 200 ml = 1 unit) prestorage blood donation were made by 14,200 patients (averages; 1.9 donations/patient, 753 ml/patient, 398 ml/donation). Of these, 87% were transfused to the patients and the remainder were discarded. Using hemodilution and blood salvage intra- or postoperatively some 2,540,000 ml of blood was collected and > 70% of patient-donors received such blood. Adverse reactions were observed with 1.6% (428/26,905) of donations including 6 angina and 2 asthma attacks. There were 63 (0.2%) problems with 28,705 donations and 117 (0.5%) errors/problems reported for 24,929 units transfused; the most frequent problems were clotting on the units and breakage of the bags during storage. Hypotension using hemodilution (3.7%), coagulation (0.9%) or bacterial contamination (0.4%) using salvage were often observed. A 10-20 ml volume of autologous fresh-frozen plasma was transfused to the wrong recipient. CONCLUSION: Autologous blood transfusion accounts for at least 1.1% (2.8% estimated) of the red cell supply in Japan. Errors and adverse reactions are not infrequent in autologous blood programmes. By introducing systematic safety policies, we will be able to make autologous blood transfusion safer.

Adolescent↗