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Biomedical subjects

M Kasai

Publications and source records attributed to M Kasai.

At least 217 records · Page 12Linked to original sources
PubMed1995

Characteristics of the antitumor activity of M-16 and M-18, major metabolites of a new mitomycin C derivative KW-2149, in mice.

The cell growth inhibitory activity, antitumor activity and toxicity of M-16 and M-18, the major metabolites of a new mitomycin C (MMC) derivative KW-2149, in mouse and human were compared with those of KW-2149 or MMC in vitro and in vivo. The growth inhibitory activity of M-18, a symmetrical disulfide dimer, against human uterine cervix carcinoma HeLa S3 cells was almost equivalent to that of KW-2149 and their IC50 values were about 10-fold smaller than that of MMC. The activity of M-16, a methyl sulfide form, was almost equivalent to that of MMC. The cell-killing activity of MMC and M-16 was augmented in the hypoxic condition, whereas that of KW-2149 and M-18 was reduced. M-16 also exhibited almost equivalent activities to MMC in vivo in terms of many biological profiles, i.e., antitumor activity against murine P388 leukemia, ascitic or solid B16 melanoma or human lung carcinoma xenograft L-27, and bone marrow toxicity in mice. These in vitro and in vivo results indicate that the antitumor activity and toxicity of KW-2149 might not be mediated by M-16 in mice. On the other hand, M-18 exhibited almost equivalent activities to KW-2149 in these regards, suggesting the involvement of M-18 in the biological activities of KW-2149. However, the small values of the area under the curve of M-18 in mice make this unlikely. Thus the biological activities of KW-2149 in mice are not explained by the M-16 or M-18 concentration in plasma and are postulated to be manifested by KW-2149 itself.

Animals↗
PubMed1995

Expression of erythroid-specific genes in acute megakaryoblastic leukaemia and transient myeloproliferative disorder in Down's syndrome.

Acute megakaryoblastic leukaemia (M7) and transient myeloproliferative disorder in Down's syndrome (TMD) are characterized by rapid growth of abnormal blast cells which express megakaryocytic markers. To clarify properties of the blast cells in M7 and TMD cases, we examined erythroid markers expression in blasts from six cases with M7 and seven cases with TMD in this study. Erythroid-specific mRNAs encoding gamma-globin and erythroid delta-aminolevulinate synthase were found to be expressed in blasts from most of these cases, indicating that majorities of the blasts in M7 and TMD cases have erythroid and megakaryocytic phenotypes. We also found that mRNAs encoding GATA-1 and GATA-2 are expressed in all these cases. These results suggest that M7 blasts and TMD blasts correspond to the erythroid/megakaryocytic bipotential progenitor cells.

5-Aminolevulinate Synthetase↗
PubMed1995

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.

Adolescent↗
PubMed1995

Multilocular lymphoepithelial cyst in the thyroid accompanied with a minute thyroid carcinoma.

An aggregate (17 x 13 mm) of a few small cysts was incidentally found in the left lobe of the thyroid of a 42 year old man. The inner surface of the cysts was lined by stratified cuboidal to columnar epithelium, which showed occasional ciliation and keratinization. The cysts were densely surrounded by follicular lymphoid tissue. The lesion was designated as a multilocular lymphoepithelial cyst. Directly adjacent to the cyst-aggregate a minute focus of papillary thyroid carcinoma (6 x 6 mm) existed. Tubular or papillary clusters of cancer cells were occasionally contiguous to the lining epithelium, which had penetrated through the lymphoid mantle of the cysts. Histological features of the lesion in the thyroid suggested an origin of the cysts from the developmental rest of the branchial pouch; probably from the ultimobranchial body remnant.

Adult↗
PubMed1995

PCR and single-strand conformational polymorphism for recognition of medically important opportunistic fungi.

The application of PCR technology to molecular diagnostics holds great promise for the early identification of medically important pathogens. PCR has been shown to be useful for the detection of the presence of fungal DNA in both laboratory and clinical samples. Considerable interest has been focused on the utility of selecting universal primers, those that recognize constant regions among most, if not all, medically important fungi. Once an amplicon, or piece of amplified DNA determined by the unique pair of oligonucleotide primers, has been generated, several different methods may be used to distinguish between genera and between species. The two major approaches have utilized differences in restriction enzyme digestion patterns or hybridization with specific probe. We report the application of single-strand conformational polymorphism (SSCP) as a technique to delineate the differences between fungal species and/or genera. Minor sequence variations in small single-stranded DNA cause subtle changes in conformation, allowing these strands to be separated on polyacrylamide gels by SSCP. We used a 197-bp fragment amplified from the 18S rRNA gene, common to all medically important fungi. After amplification, the fragments were denatured and run on an acrylamide-glycerol gel at room temperature or 4 degrees C for 4.5 or 4 h, respectively. Under room temperature conditions, the SSCP patterns for Candida albicans, Candida tropicalis, and Candida parapsilosis were identical and all strains within each species demonstrated the same pattern. These patterns differed markedly from those of the genus Aspergillus. The SSCP patterns of major and minor bands at room temperature permitted distinction between strains of Aspergillus fumigatus and Aspergillus flavus. There also was consistency of the SSCP banding pattern among different strains of the same Aspergillus species. The SSCP patterns for other medically important opportunistic fungi, such as Cryptococcus neoformans, Pseudallescheria boydii, and Rhizopus arrhizus, were sufficiently unique to permit distinction from those of C. albicans and A. fumigatus. We conclude that the technique of PCR-SSCP provides a novel method by which to recognize and distinguish medically important opportunistic fungi and which has potential applications to molecular diagnosis, taxonomic classification, molecular epidemiology, and elucidation of mechanisms of antifungal drug resistance.

Aspergillus↗
PubMed1995

Calsequestrin is essential for the Ca2+ release induced by myotoxin alpha in skeletal muscle sarcoplasmic reticulum.

Myotoxin alpha (MYTX), a polypeptide toxin purified from the venom of prairie rattlesnakes (Crotalus viridis viridis), induced Ca2+ release from the heavy fraction of skeletal sarcoplasmic reticulum (HSR), using a Ca2+ electrode. The effect of MYTX was nearly abolished by pretreatment with ryanodine, an alkaloid-based Ca2+ channel blocker. In the stopped-flow experiments, MYTX increased the choline+ permeability of HSR in the presence of calsequestrin (CS). Single channel recording experiments showed that in the presence of CS, the channel currents were markedly enhanced by MYTX applied to the cis side, but not to the trans side. However, in the absence of CS, MYTX failed to cause the excitatory effect in both the experiments. These results suggest that CS is essential for MYTX-induced Ca2+ release through the Ca2+ release channels in skeletal HSR.

Adenosine Triphosphate↗
PubMed1995

Cytokine gene expression after allogeneic bone marrow transplantation.

Cytokines produced by T lymphocytes, monocytes/macrophages, and fibroblasts play a central role in the immune response and in the development of graft-versus-host disease (GVHD). Also, it has been reported that dysregulated production of cytokines maybe the primary mediator of clinical manifestation of acute GVHD. Regarding cytokine gene expression after human allogeneic bone marrow transplantation (allo BMT), we have demonstrated increased IL-1 beta, IL-6, and TNF-alpha mRNA expression in peripheral blood mononuclear cells during the development of acute and chronic GVHD and that the degree of the increase was dependent on the severity of the disease. Furthermore, overexpression of these cytokine mRNAs could be detected before the clinical manifestations of GVHD developed. In contrast, IL-2 mRNA expression was not detected in peripheral blood mononuclear cells in GVHD patients. On the other hand, we have reported that increased mRNA expression and protein product of IL-2 and IFN-gamma were evident in the mixed lymphocyte culture of the cases who developed severe lethal transplantation-related complications. Therefore, the detection of increased IL-2 and IFN-gamma gene expression in MLC appeared to be useful for predicting transplantation-related complications in BMT patients. Furthermore, we found increased IL-2 receptor alpha subunit mRNA expression in the peripheral blood mononuclear cells during GVHD. These findings may indicate the important role of inflammatory cytokines such as IL-1 beta, IL-6 and TNF-alpha in the development of the clinical manifestation of GVHD and also may be indicative of the important role of IL-2 and the IL-2 receptor in allo response perhaps mainly as an autocrine effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Marrow Transplantation↗
PubMed1995

Transplantation-related complications predicted by cytokine gene expression in the mixed lymphocyte culture in allogeneic bone marrow transplants.

In this study, we have investigated cytokine (IL-1 beta, IL-2, IL-5, IL-6, IFN-gamma, TNF-alpha) and T cell surface molecule (IL-2 receptor, CD28, CTLA-4) gene expression in two way mixed lymphocyte cultures (MLC) enhanced by concanavalin A (ConA) to assess whether this is a useful predictive method for severe graft-versus-host disease (GVHD) and graft failure in allogeneic bone marrow transplantation (allo BMT) patients. Our present study revealed increased mRNA expression of IL-2, IL-5 and IFN-gamma using this assay in patients with delayed engraftment followed by graft failure and patients who developed grade III acute GVHD. Elevated IL-2 and IFN-gamma levels in MLC medium were also observed in these patients. Concerning T cell surface molecule gene expression in our modified MLC, IL-2 receptor gene expression was not altered so much in allo BMT patients, however, CD28 and CTLA-4 gene expression were elevated in patients with graft failure and severe acute GVHD. The elevated expression of cytokines (IL-2, IL-5 and IFN-gamma) and T cell surface molecules (CD28 and CTLA-4) mRNA in our modified MLC, in patients who developed severe lethal transplantation-related complications may suggest an important role for these molecules in inducing a strong alloresponse. Therefore, the detection of increased gene expression of those molecules, in our modified MLC system, appeared to be useful for predicting transplantation-related complications in allo BMT patients. In addition, this modified MLC assay may also be useful for the selection of the most compatible related and unrelated donors.

Antigens, CD↗
PubMed1995

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.

Acute Disease↗
PubMed1995

Effect of iron as a new type of phosphate binder in hemodialysis patients.

Hyperphosphatemia is one of the major problems requiring management in the majority of hemodialysis patients and they require phosphate-binding agents to control the hyperphosphatemia. Aluminum hydroxide and calcium compounds are used currently as phosphate-binding agents to treat hyperphosphatemia, but these compounds can cause undesirable side effects. Therefore, the development of new phosphate-binding agents is imperative. It is well known that oral and intravenous administration of iron causes hypophosphatemia. We hypothesized that this side effect of iron may be beneficial for the treatment of hyperphosphatemia in hemodialysis patients. Consequently, we conducted a fundamental and clinical investigation of the effects of iron administration. Membrane permeability of phosphorus in a mixture of sodium ferrous citrate and dessicated aluminium hydroxide in the presence of hydrogenated lecithin as a phosporic compound was examined. Fifteen patients undergoing hemodialysis were treated with 150 mg of sodium ferrous citrate given orally for eight weeks. The permeability of the filtering membrane to phosphorus decreased in accordance with the dosage of sodium ferrous citrate and dessicated aluminum hydroxide. The degree of phosphate-binding effect of sodium ferrous citrate was larger than that of dessicated aluminum hydroxide. Serum phosphorus decreased significantly during the experiment. These results suggest that the oral administration of sodium ferrous citrate as a new phosphate binder is a useful therapeutic method for hemodialysis in patients with hyperphosphatemia.

Administration, Oral↗
PubMed1995

[Germ cell tumor].

Germ cell tumor (GCT) is chemotherapy-sensitive, and with the development of a cisplatin combined regimen, the majority of patients can now be cured. Seventy percent to 80% of patients with advanced GCT have a lasting complete response to a cisplatin combined regimen, while 20 to 30% of these patients are refractory to the therapy. Refractory GCT patients need more effective and intense therapy. In order to overcome the conventional dose chemotherapy results, high-dose chemotherapy backed by autologous hematopoietic stem cell transplantation (AHSCT), has been applied to patients with GCT who have relapsed after achieving a complete response by first-line chemotherapy or to those in whom disease progression or the failure to achieve CR had occurred after initial and/or ifosfamide combined salvage therapy. The therapy with a high-dose combination of CBDCA (Carboplatin), VP-16 (Etoposide) and CPM (Cyclophosphamide) or IFM (Ifosfamide), supported with AHSCT is administered to the advanced GCT patients. The response rate (CR+PR) ranges from 40 to 78% by reported groups averaging about 50%, and disease-free survival is possible in about half the survivors thus far. Treatment related morbidity and mortality are observed, but are tolerable with the above dosage. Thanks to the technical development of collecting hematopoietic stem cells using either bone marrow or peripheral blood, and hematopoietic growth factor to lessen hematologic toxicities and obtain early hematological recovery, this method can be performed more safely. High-dose chemotherapy with AHSCT may well become more effective in patients with resistant GCT by a new combination of synergistic drugs or multicycle transplants.

Adult↗
PubMed1995

FK506 treatment of graft-versus-host disease developing or exacerbating during prophylaxis and therapy with cyclosporin and/or other immunosuppressants. Japanese FK506 BMT Study Group.

A phase II study of the efficacy and safety of FK506, a new potent immunosuppressant, has been conducted in 49 patients with GVHD after allogeneic BMT. Eighteen patients with acute GVHD and 31 with chronic GVHD entered the study. FK506 was administered at an initial dose of 0.05 mg/kg i.v. or 0.15 mg/kg orally twice a day to those whose GVHD had become uncontrollable with cyclosporin and/or other immunosuppressants. The response to FK506 was evaluated in 13 patients with acute and 26 with chronic GVHD. A marked response was observed in 5 and a good response in 2 of 13 patients with acute GVHD. For those with chronic GVHD, the response was marked in 2 patients, good in 10 and poor in 8. The most common adverse effects were renal toxicity (53.1%), followed by nausea and vomiting (30.6%) and a feeding of warmth (18.4%). There was a correlation between renal toxicity and whole blood levels of FK506. The dose should be adjusted to keep a trough level between 15 and 25 ng/ml. FK506 is promising in the treatment of both acute and chronic GVHD, even if it is intractable with other immunosuppressants, and may be most effective if administered early in the course of GVHD.

Acute Disease↗
PubMed1995

Comparison of peripheral blood stem cells mobilized with granulocyte colony-stimulating factor with or without prior standard-dose chemotherapy in patients with malignancy.

We studied the effect of granulocyte colony-stimulating factor on the magnitude of peripheral blood stem cell mobilization in patients with malignancy. The leukapheresis products mobilized with granulocyte colony-stimulating factor alone at a steady state (a period of full hematopoietic recovery) (group 1) were compared with those obtained after cytotoxic chemotherapy using granulocyte colony-stimulating factor (group 2). In group 1, six patients underwent six courses of stem cell collection with a median of 20 l leukapheresis. In group 2, 10 patients underwent 12 courses of stem cell collection with a median of 10 l leukapheresis. Median yields of group 1 vs. group 2 were mononuclear cells (x 10(9)), 21.9 vs. 11.6; CD34+ cells (x 10(6)/l), 14.5 vs. 17.1; colony-forming unit for granulocyte-macrophage (/ml), 223 vs. 1193; burst-forming unit for erythroid (/ml), 29 vs. 71; colony-forming unit for erythroid (/ml), 42 vs. 29; colony-forming unit for megakaryocyte (/ml), 26 vs. 59. While there were no statistically significant differences in the number of CD34+ cells between the two groups, granulocyte-macrophage-committed progenitor cells were more enriched in the apheresis products of group 2. The correlation between CD34+ cells and colony-forming unit for granulocyte-macrophage was poor. Our results demonstrate that granulocyte colony-stimulating factor can mobilize a sufficient number of progenitor cells into the peripheral blood for stem cell transplantation with or without prior chemotherapy.

Adolescent↗