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Biomedical subjects

M Tashima

Publications and source records attributed to M Tashima.

At least 37 records · Page 2Linked to original sources
PubMed1994

Inhibition of erythroid differentiation by stem cell factor in K562 cells expressing the c-kit gene.

We found a K562 subclone (K562YO) that highly expressed the c-kit gene. K562YO had a higher capability of erythroid differentiation by hemin and cytosine arabinoside (Ara-C) than its parent K562 (KIT-). We obtained the transfectant expressing c-kit by introducing c-kit cDNA into K562 (KIT-). The differentiation of the transfectant was similar to that of the parent cell. Thus the difference described above was not due to the expression of c-kit. Next, we investigated the effects of stem cell factor (SCF) on the differentiation of the K562 cell expressing c-kit. SCF did not enhance the cell growth of K562YO. On the other hand, SCF suppressed induction of benzidine-positive cells when c-kit-positive cells were treated with hemin and Ara-C, especially at a low concentration. Furthermore, c-kit mRNA and protein were down-regulated during erythroid differentiation. SCF also downregulated the c-kit proteins. Our results suggest that the SCF/c-kit signals could act negatively for erythroid differentiation of the K562 cells expressing c-kit. K562YO is also useful for studying the mechanism that controls the expression of the c-kit gene because there is a K562 counterpart cell line that does not express this gene.

Blotting, Northern↗
PubMed1993

[Clinical study of patients with deep-seated fungal infection associated with hematological diseases].

An assessment has been made regarding usefulness of measuring beta-D-glucan (beta-glucan) as fungal serodiagnosis in 50 cases of fungal infection with hematological diseases. Further, an assessment has been made regarding relation between hematological findings and therapeutic effect by administering miconazole, an antifungal agent (MCZ: Florid, clinically to the subjects. Positivity of beta-glucan (beta-glucan > or = 10 pg/ml) was observed in 54.5% (24/44), and the effective rate of MCZ in the positive cases was 75.0% (18/24). In the cases in whom fungus was detected, beta-glucan-positive rate was 50.0% (8/16), and MCZ-effective rate in beta-glucan-positive cases was 62.5% (5/8). The total effective rate of MCZ was 80% (40/50). Side effects were observed in 3 cases, but continual administration of MCZ was possible in all of the 3 cases. By the assessment regarding the relation between hematological findings and therapeutic effect of MCZ, it was found that the effective rates in the cases who underwent a transition with neutrophil and lymphocyte counts less than 500/microliters during the period of MCZ administration were 64.7% (11/17) and 50% (5/10), respectively, and large effects were observed in the cases who underwent a transition with the neutrophil and lymphocyte counts more than 500/microliters was 86.7% (19/22) and 91.7% (22/24), respectively. These results suggested that lymphocytes rather than neutrophils had an important role in the morbidity of fungal infection. It was noteworthy that MCZ was effective for the treatment of deep seated mycosis and significant effective rate was obtained in the group of patients who had neutrophils and lymphocytes less than 500/microliters.

Adolescent↗
PubMed1993

Okadaic acid biologically mimics the role of calcium/phospholipid dependent kinase inhibitors in the process of HL-60 cell differentiation.

Okadaic acid, a newly recognized protein phosphatase inhibitor and a non-TPA type tumor promoter, enhanced 1 alpha 25(OH)2D3(D3)-induced HL-60 cell differentiation into monocyte/macrophage lineage but did not affect dibutyryl cyclic AMP (dbcAMP)-induced differentiation into granulocytic lineage. Okadaic acid alone did not induce any differentiation. The process of D3-induced HL-60 cell differentiation on cultivation in magnesium deficient medium can be divided into two steps namely commitment and phenotypic expression as we have previously reported (J Cell Physiol 1987;131:50; Cell Growth Diff 1991;2:415), and the effect of okadaic acid on each step was studied. The results obtained indicated that okadaic acid inhibited commitment and enhanced phenotypic expression. We have previously shown that PKC has a dual action in the process of differentiation, i.e. as a positive regulatory signal in commitment and as a negative one in phenotypic expression. Thus, although okadaic acid has been reported to enhance the phosphorylation of various proteins that are also phosphorylated by PKC, we found that it mimics the role of PKC inhibitors such as H7 and staurosporine in D3-induced HL-60 cell differentiation.

Calcitriol↗
PubMed1993

Retroperitoneal laparoscopic renal biopsy.

We describe a technique for renal biopsy using laparoscopic guidance. Retroperitoneal laparoscopic dissection and exposure is facilitated by a simple balloon-expanding device made of a rubber glove tied around a catheter. Laparoscopic renal biopsy is associated with less morbidity than open renal biopsy and is ideal when percutaneous renal biopsy is contraindicated or is not feasible.

Aged↗
PubMed1993

Laparoscopic nephroureterectomy for end-stage reflux nephropathy in a child.

End-stage renal disease secondary to vesicoureteral reflux often necessitates removal of the affected kidney and its refluxing ureter. Advances in laparoscopic techniques have made nephroureterectomy through the laparoscope possible in a minimally invasive way. We describe our surgical steps for laparoscopic nephroureterectomy in all 11-year-old girl with end-stage reflux nephropathy. Reduced trauma of surgical access, minimal postoperative morbidity, shorter hospital stay, and minimal scarring make laparoscopic nephroureterectomy a comparatively desirable surgical approach, especially in pediatric patients.

Child↗
PubMed1991

Dephosphorylation of specific proteins in HL-60 cells by 1 alpha, 25-dihydroxyvitamin D3: possible involvement of cAMP-dependent protein kinase.

Changes of phosphoprotein patterns in HL-60 cells were studied during short exposures to 1 alpha, 25-dihydroxyvitamin D3 [1,25(OH)2D3]. One hundred nanometers 1,25(OH)2D3 dephosphorylated at least three proteins in 6 h: phosphoproteins with molecular weights of 82 kD (pp82), 33 kD (pp33), and 31 kD (pp31). Phosphorylation of pp33 and pp31 was also suppressed by 1 mM dbcAMP, and dephosphorylation of the two protein by 1,25(OH)2D3 was inhibited by 8 microM H-8, an inhibitor of cAMP-dependent protein kinase (PKA). Furthermore, 8 microM H-8 inhibited dephosphorylation of the two proteins when it was added with 1,25(OH)2D3. On the other hand, 10 nM TPA gave no significant change to these two phosphoproteins. These results suggest the possibility that PKA is involved in the early stages of 1,25(OH)2D3-induced HL-60 cell differentiation through specific protein dephosphorylation.

Bucladesine↗
PubMed1991

Use of ofloxacin in prevention and treatment of secondary infections in hematological malignancies.

We evaluated the effectiveness of ofloxacin (OFX) administered for prophylactic purposes during 77 episodes of neutropenia (less than 500/mm3) in 54 patients with hematological malignancies and to combat infection in 17 patients with both hematological malignancies and secondary infections. The prophylactic effect of OFX was demonstrated by the absence of febrile episodes in 73.3% of patients during the neutropenic phase. Of 16 patients who developed secondary infections, 13 showed good responses with other antibiotics. The overall efficacy rate of OFX in secondary infections was 64.7%. Although 4 patients developed elevated SGOT and SGPT levels and 1 showed an elevated BUN level, OFX was generally well tolerated.

Adolescent↗
PubMed1991

Effects of protein kinase A and calcium/phospholipid-dependent kinase modulators in the process of HL-60 cell differentiation: their opposite effects between HL-60 cell and K-562 cell differentiation.

We have previously shown that HL-60 cells treated with 1 alpha, 25-(OH)2D3 in magnesium-deficient medium are committed to differentiate but do not express differentiation-related phenotypes. In the present study, we demonstrated that Mg2+ deprivation blocked the process of differentiation before the induction of lysozyme mRNA and that the process of HL-60 cell differentiation could be divided into two steps, i.e., a commitment step and a phenotypic expression step. We studied the effects of protein kinase A (PKA) and calcium/phospholipid-dependent protein kinase (PKC) modulators at each step. The results indicated that agonists of PKA enhanced both steps but that N-(2-[methylamino]ethyl-5-isoquinolinesulfonamide inhibited them. On the other hand, 1-oleyl-2-acetylglycerol and 12-O-tetradecanoylphorbol-13-acetate enhanced the commitment step but inhibited that of phenotypic expression. Staurosporine and 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine inhibited the commitment step and enhanced that of phenotypic expression. These results indicate that PKA acts as a positive regulatory signal and that PKC has a dual role in the process of HL-60 cell differentiation, i.e., as a positive regulatory signal in the commitment step and as a negative one in the phenotypic expression step. Recently, we have also shown that in K-562 cell differentiation into erythroid lineage, PKA may serve as a negative regulatory signal in both steps; however, PKC may act dually, namely as a negative regulatory signal in the commitment step and as a positive one in the phenotypic expression step.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaloids↗
PubMed1990

Effect of second-messenger modulators in K-562 cell differentiation: dual action of calcium/phospholipid-dependent protein kinase in the process of differentiation.

We investigated the roles of second messengers in K-562 cell differentiation induced by either commitment-inducing agents (Ara-C, thymidine), or a noncommitment-inducing agent (hemin). Cell differentiation induced by both types of agents was inhibited by dbc-AMP, staurosporine, and H-7. In contrast, OAG enhanced hemin-induced cell differentiation, but it inhibited that due to Ara-C or thymidine. When K-562 cells were incubated with 4 x 10(-6)M hemin or 2 x 10(-7)M Ara-C for 2 days, an increase of epsilon-mRNA occurred. The addition of cycloheximide (1 microgram/ml) completely blocked this change, suggesting that de novo protein synthesis was necessary for the increase of epsilon-mRNA. Simultaneous treatment with Ara-C and cycloheximide for 2 days did not block either the increase of epsilon-mRNA or that of benzidine-positive cells, which were measured after 5 days of further incubation without additives. This suggested that the process of Ara-C-induced K-562 cell differentiation could be divided into two steps, i.e., a commitment step and a phenotypic expression step, and that the commitment step was at least partly resistant to cycloheximide. We investigated the roles of second messengers in each step. Our results suggested that PKC may act as a negative regulator of commitment step and as a positive regulator of the phenotypic expression. This may explain the differing effects of OAG on hemin- and Ara-C-induced K-562 cell differentiation.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1990

In-vitro and in-vivo antibacterial activities of E1040, a new cephalosporin with potent antipseudomonal activity.

E1040 is a new parenteral cephalosporin with a broad antibacterial spectrum and potent activity against Gram-negative bacteria including Pseudomonas aeruginosa. The in-vitro activities of E1040 against clinical isolates of Enterobacter cloacae, Ent. aerogenes, Providencia rettgeri, and Morganella morganii were superior to those of ceftazidime, cefoperazone, cefmenoxime, and cefuzonam. The activities of E1040 against Gram-positive cocci were comparable with those of ceftazidime, but it was less active than cefmenoxime, cefuzonam, and cefoperazone. Against Ps. aeruginosa, E1040 was more potent than the other compounds, with an MIC90 of 0.39 mg/l, 1/16 that of ceftazidime. The in-vitro activity of E1040 was well sustained in vivo as shown by results obtained in experimental infections in mice. In particular, E1040 was the most active drug against Ps. aeruginosa including gentamicin-resistant and beta-lactamase-overproducing strains. Morphological studies using a scanning electron microscope and a phase-contrast microscope showed that E1040 caused spheroplast and bulge formation in Ps. aeruginosa at low concentrations.

Animals↗
PubMed1989

Heterogeneous features of Ph-negative CML--possible existence of Ph-negative, bcr-rearrangement-negative CML.

We have examined eight patients with Ph-negative chronic myelocytic leukemia (CML). Two of the patients had the same molecular abnormalities as well as the same clinical and hematological features as those of Ph-positive CML. The other six patients showed no genomic rearrangement. This group was hematologically divided into four subgroups, namely chronic myelomonocytic leukemia, undifferentiated chronic myeloproliferative disorder, chronic neutrophilic leukemia and CML-like syndrome. This last subgroup resembled Ph-positive CML in many points except for rather moderate proliferation of granulocyte lineage, and it was difficult to clinically separate it from Ph-positive CML.

Adult↗
PubMed1988

Evidence of intracellular and trans-acting differentiation-inducing activity in human promyelocytic leukemia HL-60 cells: its possible involvement in process of cell differentiation from a commitment step to a phenotype-expression step.

We previously reported that human promyelocytic leukemia HL-60 cells, when treated with various inducers in magnesium-deficient medium, became committed to differentiate but did not express the differentiation-related phenotypes (Okazaki et al., J. Cell. Physiol., 131:50-57, 1987). In the present study we demonstrated the existence of an intracellular differentiation-inducing activity (int-DIA) in differentiation-committed phenotype-nonexpressing HL-60 cells by using cybrid formation between untreated HL-60 cells and cytoplasts from HL-60 cells treated in magnesium-deficient medium with 100 nM 1 alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3). Cell extracts from similarly treated HL-60 cells also showed int-DIA, which when added (10 mg total protein/ml) to culture of untreated HL-60 cells, could increase the percentages of nitroblue tetrazolium (NBT)- and nonspecific esterase (NSE)-positive cells from 1% to 53%, and from 0 to 32%, respectively. They also induced differentiation of human monoblastic leukemia U-937 cells and of human myeloblastic leukemia KG-1 cells but not of erythroleukemia K-562 cells. These results suggested that the int-DIA had a common effect on differentiation induction in several human myeloid cell lines and may be involved in inducing cells to proceed from a commitment to a phenotype-expression step during human myeloid cell differentiation.

Calcitriol↗
PubMed1988

Staurosporine, a novel protein kinase inhibitor, enhances HL-60-cell differentiation induced by various compounds.

The effect of staurosporine, a novel calcium/phospholipid-dependent protein kinase (protein kinase C) inhibitor, on differentiation of human promyelocytic leukemic HL-60 cells, was investigated. Staurosporine inhibited HL-60-cell proliferation in a concentration-dependent manner, but did not induce HL-60-cell differentiation by itself. When staurosporine was added to HL-60 cells treated with a suboptimal concentration (1 nM) of 1 alpha,25 dihydroxyvitamin D3 (1,25(OH)2D3), cell differentiation was enhanced in a concentration-dependent manner and the percentages of nitro blue tetrazolium reducing ability and nonspecific esterase activity-positive cells increased from 6% to 51% and from 8% to 54%, respectively, on day 4 at a concentration of 5 nM. Staurosporine (5 nM) achieved almost the same enhancement effect in cultures treated with suboptimal concentrations of 1 nM all-trans-beta-retinoic acid (RA), 3 ng/ml actinomycin D (Act D), 100 microM dibutyryl cyclic adenosine 3':5'-monophosphate (dbc AMP), and 50 microM prostaglandin E1 (PG E1). These results suggest that the inhibition of protein kinase C activity by staurosporine exerts an important role in HL-60-cell differentiation induced by various compounds. Moreover, staurosporine (5 nM) completely inhibited optimal concentrations (50 nM) of [12-o-tetradecanoyl phorbol-13-acetate (TPA)]-induced cell differentiation, but enhanced optimal concentrations of dbc AMP (1 mM)-induced cell differentiation. On the other hand, 1-(5-isoquinolinyl-sulfonyl)-2-methylpiperazine, which has been reported to inhibit cyclic adenosine 3':5'-monophosphate-dependent protein kinase (protein kinase A) as much as protein kinase C, completely inhibited both cell differentiations induced by optimal concentrations of TPA (50 nM) and induced by optimal concentrations of dbc AMP (1 mM), and did not significantly enhance HL-60-cell differentiation induced by suboptimal concentrations of 1,25(OH)2D3, RA, and dbc AMP. Therefore, these results suggest that the inhibition of protein kinase C, which is not accompanied by that of protein kinase A, is concerned with the induction of HL-60-cell differentiation.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1988

Restriction fragment length polymorphism of bcr in Japanese patients with hematological malignancies.

We surveyed DNAs from patients with various hematological malignancies by Southern blot hybridization to analyze bcr rearrangements, and detected a new restriction fragment length polymorphism (RFLP) of the breakpoint cluster region at a BamHI site in three patients. By using a 1.2-kb HindIII-BglII 3' bcr probe, unusual BamHI restriction enzyme fragments (1.9 kb and 1.4 kb) were detected from the DNAs of three patients with hematological malignancies. DNAs from cultured fibroblasts derived from the skin of a patient, as well as from peripheral leukocytes of the father of a patient and the mother of another patient, showed identical 1.9- and 1.4-kb additional bands, besides a 3.3-kb germline band, establishing that polymorphism, rather than gene arrangement, was responsible for these additional restriction enzyme fragments. However, RFLP was not detected in the DNAs of 40 normal unrelated individuals.

Blotting, Southern↗
PubMed1988

[A cancer of unknown primary site with diffuse metastasis to the bone marrow treated effectively with FAM combination chemotherapy].

A patient with cancer of unknown primary site suffering from diffuse bone marrow metastasis and DIC, was treated with FAM (5-fluorouracil, adriamycin and mitomycin C) combination chemotherapy. She was a 58-year-old housewife. Bone marrow biopsy revealed that her marrow tissue was completely replaced by cancer cells, and bone scintigraphy showed diffuse bone marrow metastasis in all the vertebrae, sternum, pelvic bones and skull. After 5 months administration of 3 courses of FAM therapy, the cancer cells were completely eradicated in the bone marrow upon biopsy taken at almost the same position as the previous one. The values of CEA, CA 19-9 and CA 125 were normalized, suggesting that this therapy was very effective.

Anemia, Myelophthisic↗