Biomedical subjects
M Asaka
Publications and source records attributed to M Asaka.
Cytokine network in peripheral blood mononuclear cells after allogeneic bone marrow transplantation.
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[A puerperal woman received massive ABO-incompatible blood transfusion: a case report rescued by exchange transfusion therapy].
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[Transverse lesion of the spinal cord due to mucormycosis in an AML patient].
A 54 year old man complained exertional dyspnea and palpitation since November 1989. As he was diagnosed with marked anemia, leukocytosis and thrombocytopenia by his work place doctor, he was admitted to our hospital. Acute myelogenous leukemia was diagnosed based on laboratory findings. BHAC-DMP, BHAC-MEP and A triple V therapies were only partially effective. Fine nodular shadows in all lung fields and a semicircular mass in the right lower lobe next to the thoracic vertebra were evident on the chest X-P since the end of March 1990. He was treated with antibiotics and amphotericin B but the abnormal lung shadows did not disappear. He had sudden onset of paraplegia and loss of all sensation below Th6 on May 1. Aparavertebral mass in the right lower lobe was detected by CT and MRI, for which radiotherapy was performed but without improvement. He died of respiratory failure on May 12. Autopsy showed that the semicircular paravertebral mass continued to the main pulmonary vein and epidural area of the thoracic cord (Th6-8). Microscopically, mucormycosis was found. Necrosis due to mucor embolism was found in the thoracic cord. It is usually difficult to diagnose mucormycosis in immunocompromised patients while they are alive. It is important to suspect mucormycosis if any infarction symptoms or infections resistant to antibiotics develop in immunocompromised patients.
In vitro expansion of murine hematopoietic progenitor cells by leukemia inhibitory factor, stem cell factor, and interleukin-1 beta.
Murine hematopoietic progenitor cells were markedly expanded in the presence of leukemia inhibitory factor (LIF), interleukin (IL)-1 beta and/or stem cell factor (SCF), although SCF+IL-1 beta +IL-3, LIF+SCF+IL-3, and SCF+IL-1 beta showed an appreciable effect on the in vitro expansion of hematopoietic progenitor cells as well. In the presence of LIF+SCF+IL-1 beta, highly proliferative potential colony-forming units (CFU-HPP) and colony forming units of mixed lineages (CFU-Mix) were more efficiently expanded than colony forming units granulocytes/macrophage (CFU-GM) and burst-forming units of erythroid lineage (BFU-E) compared with the colony formations of freshly obtained bone marrow cells. The cell yield on day 5 in the presence of LIF+SCF+IL-1 beta was comparable to that in SCF+IL-1 beta and SCF+IL-1 beta +IL-3. Nevertheless, colony formations were marked in LIF+SCF+IL-1 beta, thus suggesting that this combination can generate hematopoietic progenitor cells that possess greater potential for CFU-HPP, CFU-Mix, CFU-GM, and BFU-E colony formations. Hematopoietic cells expanded in the presence of LIF+SCF+IL-1 beta showed increased mRNA expressions of IL-1 beta, IL-3, IL-6, granulocyte colony-stimulating factor (G-CSF), granulocyte/macrophage (GM)-CSF, interferon gamma (IFN-gamma), and LIF compared with those of nontreated hematopoietic cells. Furthermore, LIF+SCF+IL-1 beta induced increased IL-3 and GM-CSF mRNA expression in hematopoietic cells but induced decreased macrophage inflammatory protein 1 alpha (MIP1 alpha) mRNA expression as compared with SCF+IL-1 beta +IL-3. These results suggest that the balance between stimulatory and inhibitory cytokines plays an important role in in vitro expansion of hematopoietic progenitor cells.
Renal Salmonella enteritidis abscess in a patient with severe aplastic anemia after allogeneic stem cell transplantation.
We describe an unusual case of a renal abscess by Salmonella enteritidis in a 32-year-old man with severe aplastic anemia undergoing allogeneic stem cell transplantation. He was receiving immunosuppressive therapy with CsA and corticosteroids for chronic GVHD. He was not neutropenic and had no history of enterocolitis or cholelithiasis before the onset. Four months after the transplantation, he developed an abscess in the upper pole of his right kidney from which Salmonella enteritidis was isolated in culture. He was successfully treated with a combination of percutaneous drainage and washing the cyst through the catheter using piperacillin sodium-containing solution. The possibility of salmonellosis should be considered in the differential diagnosis of such patients.
[Natural history of peptic ulcers].
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Clinical application of allogeneic peripheral blood stem cells transplantation.
Recombinant human granulocyte colony-stimulating factor (rhG-CSF)-mobilized peripheral blood stem cells (PBSC) are now widely used for autologous transplantation to provide hematopoietic stem cells after intensive chemoradiotherapy. However, PBSC which contain a large number of T cells represent a potential risk for graft-versus-host disease (GVHD) in allogeneic (allo) transplantation. There are about 50 case reports of clinical trials of rhG-CSF-mobilized allo PBSC transplantation (PBSCT) with relatively rapid hematological recovery, without severe acute GVHD except in a few cases. Therefore, the risk of inducing severe acute GVHD is not as high as was expected when allo PBSCT began. However, whether allo PBSCT will increase the risk of chronic GVHD is not clear, because the period of observation has been too short. Also, it will be of interest to determine the clinical effect of allo PBSCT on relapse of hematological malignancy post-transplant. Whether allo PBSCT will increase life-threatening acute and chronic GVHD, and whether PBSC allografting will result in permanent hematological and immunological reconstitution has to be determined by prospective randomized clinical trials.
Enhancing and suppressive effects of immunosuppressants cyclosporin A, FK506, and KM2210 on the colony formation of murine bone marrow cells.
Immunosuppressants cyclosporin A (CsA), FK506, and KM2210 modulated colony formations of murine hematopoietic progenitor cells. In a 4-h treatment with CsA, 10 micrograms/ml increased the formation of colony-forming units of mixed lineages (CFU-Mix) but decreased the formation of highly proliferative potential colony-forming units (CFU-HPP); 1 microgram/ml of CsA increased the formations of CFU-HPP, CFU-Mix, and colony-forming units of granulocytes/macrophages (CFU-GM); 0.1 microgram of CsA increased the formation of CFU-Mix and burst-forming units of erythroid lineage (BFU-E). Lower doses of CsA appeared to induce an increase in various colony formations. FK506 increased CFU-HPP and CFU-Mix formations at lower doses. Another immunosuppressant, KM2210, increased CFU-HPP and CFU-GM formations but decreased CFU-Mix and BFU-E formations. In a 24-h treatment, 10 micrograms/ml and 1 microgram/ml of CsA inhibited all the colony formations, but 0.1 microgram/ml of CsA increased CFU-Mix, CFU-GM, and BFU-E formations. Similarly, 100 ng/ml and 10 ng/ml of FK506 decreased all the colony formations but 1 ng/ml of FK506 increased CFU-HPP and CFU-GM formations. KM2210 inhibited all the colony formations. These findings showed that lower doses of CsA and FK506 appeared to increase the colony formations, although higher doses of these drugs decreased the colony formations, similar to the findings in a 4-h treatment. On the other hand, KM2210 showed opposing effects on colony formation with 4-h and 24-h treatments.
Analysis of the p53 gene mutations in acute myelogenous leukemia: the p53 gene mutations associated with a deletion of chromosome 17.
In order to determine the relevance of the p53 tumor suppressor gene mutations in acute myelogenous leukemia (AML), we analyzed the p53 gene in genomic DNA of 18 unselected cases of AML by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and direct sequencing. We detected three cases (16.7%) with the p53 gene mutations showing only the mutant alleles; the high incidence in cases with loss of a whole chromosome 17 (two of three) contrasted with the low incidence in cases without abnormalities of chromosome 17 (one of 15). These cases containing the mutations of the p53 gene showed a poor prognosis. Although we analyzed a rather small series of patients, these findings suggest that the p53 gene mutations might be involved in the progression and prognosis of at least some cases of AML.
Megakaryocytic differentiation of a leukemic cell line, MC3, by phorbol ester: induction of glycoprotein IIb/IIIa and effects on expression of IL-6, IL-6 receptor, mpl and GATA genes.
We investigated megakaryocytic differentiation in a newly-established Ph1-positive leukemic cell line, MC3, which showed tri-lineage immunophenotypes (myeloid antigens2+, CD19(1+) and CD41a1+) and was positive for CD34 and CD38. TPA induced MC3 cells to differentiate to an early stage of megakaryocyte lineage exhibiting an increase in the expression of platelet glycoproteins (GP) IIb/IIIa (CD41a), and an increase in cell size and nuclear ploidy. TPA treatment also enhanced the expression of GPIIb mRNA, and induced the expression of interleukin-6 (IL-6) and its receptor mRNAs, while it did not induce transcripts of the genes IL-11 and mpl ligand, and further decreased the transcript of the mpl gene. Consistent with these findings, MC3 cells treated with TPA showed an increased expression of GATA-1, but not GATA-3 transcripts, whereas those without TPA treatment expressed only the GATA-2 transcript. These results provide an insight into the study for the regulatory mechanism of megakaryocytopoiesis and leukemic cell differentiation.
Evaluation of the effect of lansoprazole in suppressing acid secretion using 24-hour intragastric pH monitoring.
The acid-inhibitory effect of lansoprazole was evaluated in comparison with that of famotidine and omeprazole by using 24-h intragastric pH monitoring in 10 young, healthy Japanese volunteers. Lansoprazole 20 mg once daily in the morning was superior to famotidine 20 mg twice daily, omeprazole 20 mg once daily in the morning in reducing 24-h intragastric acidity. Unlike famotidine, whose acid-inhibitory effect was observed mainly at night, both lansoprazole and omeprazole inhibited both daytime and nocturnal acid secretion, with the maximal effect occurring in the afternoon. Although the daily profile of acid-inhibitory action of lansoprazole was similar to that of omeprazole, the acid-inhibitory effect of lansoprazole was more potent than that of omeprazole at any time of the day. These results indicate that lansoprazole at a dosage of 30 mg once daily in the morning produced the most potent inhibition of acid secretion in young Japanese volunteers, compared with famotidine 20 mg twice daily and omeprazole 20 mg once in the morning.
Clinical efficacy of lansoprazole in eradication of Helicobacter pylori.
A randomized, single-blind study was designed to assess the effect of lansoprazole alone and lansoprazole plus amoxicillin on the healing and eradication rates in Helicobacter pylori-associated peptic ulcer disease. Seventy-nine patients with gastric ulcers and 54 patients with duodenal ulcers were randomly assigned to two treatment groups. Group 1 received lansoprazole 30 mg daily for 8 weeks for gastric ulcers or 6 weeks for duodenal ulcers. Group 2 received the group 1 regimen plus amoxicillin 2 g daily for 2 weeks. Healing rates at 8 weeks for the gastric ulcer patients were 92 and 84% in groups 1 and 2, respectively (p = not significant). Healing rates at 6 weeks for duodenal ulcers were 96% in group 1 and 100% in group 2 (p = not significant). The eradication rates of H. pylori for gastric ulcer patients were 21 and 54% in groups 1 and 2, respectively (p < 0.05). The H. pylori eradication rates for duodenal ulcer patients were 5 and 73% in groups 1 and 2, respectively (p < 0.001). The H. pylori eradication rates in group 2 were significantly higher than in group 1. Lansoprazole was effective for eradicating H. pylori in this study.
Soluble c-kit levels in acute GVHD after allogeneic bone marrow transplantation.
Serum soluble c-kit concentrations were measured in 11 patients with or without acute graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation. The serum soluble c-kit levels in the patients with moderate to severe acute GVHD (grade II-IV) were significantly lower than those in the patients with no or mild acute GVHD (grade 0-I) following the onset. The data from this study indicate that measurement of serum soluble c-kit concentration is a useful indicator of severe acute GVHD.
Possible role of T-cell surface molecule gene expression in the mixed lymphocyte culture for predicting transplantation-related complications after allogeneic bone marrow transplantation.
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Cytokine receptor gene expression in peripheral blood mononuclear cells during graft-versus-host disease after allogeneic bone marrow transplantation.
Interleukin-1 receptor type 1 (IL-1R), IL-2 receptor alpha subunit (IL-2R) and IL-6 receptor alpha subunit (IL-6R) mRNA expression in peripheral blood mononuclear cells (PBMC) in 17 patients who underwent allogeneic bone marrow transplantation (allo BMT) and 2 patients who underwent autologous transplantation were analyzed using a semiquantitative reverse-transcriptase polymerase chain reaction (RT-PCR). There were several exceptions in some cases and IL-1R expression was found to vary in a rather wide range, however, the expression of IL-2R and IL-6R mRNA tended to increase during the development of graft-versus-host disease (GVHD). In particular, IL-2R mRNA expression was increased in four patients with GVHD and graft failure. In contrast, IL-2R and IL-6R mRNA expression was not increased in autologous (auto) BMT and auto peripheral blood stem cell transplantation (PBSCT) patients. These findings suggest that IL-2R and maybe IL-6R mRNA expression in PBMC play an important role in the development of an allo response and GVHD. Therefore, the analysis of cytokine receptor mRNA expression in PBMC after allo BMT may provide important information concerning the immune response and the cytokine network system in marrow transplants.
[Advance of endoscopic surgery--practical technique by video and its replacement of conventional surgery].
The recent phenomenal success of laparoscopic cholecystectomy has led to replacement of conventional abdominal surgery as the standard treatment of gall bladder diseases. In an enterprising attempt to expand clinical indications for this minimally invasive form of surgery, physicians and surgeons of the various specialties have been looking to endoscopic operations for benign and/or malignant diseases. Endoscopic surgery usually combines the advantages of less postoperative pains and early return to routine activities with clinical efficacy equivalent to the conventional operation whenever its indication is right. This Symposium was held to discuss the practical technique demonstrated by videotape and its operative effectiveness in the areas of esophageal/gastric/colorectal cancers and intrathoracic/hepatobilliary/gynecological diseases, as well as in the fields of endourology and arthroscopic surgery in shoulder and knee joint. The physicians and even surgeons, a decade ago, seemed to have no inkling of the update endoscopic/laparoscopic revolution. We have, similarly, no imagination of knowing what comes to our surprise being stored in the 21st century. In evaluating any new surgical technique, randomized clinical trials are necessary to be carried out, comparing the new technique with the conventional one. Furthermore, we have to ask ourselves not only what we can do but why we should do it for the quality of life of our patients.
[A familial case of ADPKD with intracranial aneurysms detected by MR angiography].
The management and screening of unruptured asymptomatic intracranial aneurysm (ICA) in patients with ADPKD and those with a family history of ICA remains a subject of considerable controversy. In recent years, it has been revealed that MRA (magnetic resonance angiography) can define the circle of Willis to allow detection of ICA as small as 3-4 mm. We report a case of a 63-year-old man with ADPKD and his family. No definite aneurysm was observed by angiography screening at 46 years of age, when he was referred for hemodialysis. For the past three years, his family history revealed that three relatives were suffering from subarachnoid hemorrhage at the ages of 32, 36 and 39 years, respectively, two of whom had ICA and one had arterio-venous malformation detected by angiography. Whether they had ADPKD was unknown, but two were suggestive of ADPKD. Therefore, our case underwent MRA as screening for ICA, which showed an ICA with a diameter of 5mm in the anterior communicating artery. The ICA was confirmed as being 6 mm in diameter by conventional angiography. His niece and her son, who had ADPKD, also underwent MRA, which showed a suspicious image of a 2 mm ICA in the latter case. These results suggest that prophylactic screening for ICA is important in an ICA clustering family. MRA is useful in screening for ICA and in the follow-up study on the natural course of ICA.