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Biomedical subjects

M Konno

Publications and source records attributed to M Konno.

At least 73 records · Page 4Linked to original sources
PubMed1991

Enhancement of the grafting efficiency of transplanted marrow cells by preincubation with interleukin-3 and granulocyte-macrophage colony-stimulating factor.

To improve the grafting efficiency of transplanted murine hematopoietic progenitors, we briefly preincubated mouse bone marrow cells with interleukin-3 (IL-3) or granulocyte-macrophage colony-stimulating factor (GM-CSF) ex vivo before their transplantation into irradiated recipients. This treatment was translated into an increase in the seeding efficiency of colony-forming unit-spleen (CFU-S) and CFU-GM after transplantation. Not only was the concentration of CFU-S in the tibia increased 2 and 24 hours after transplantation, but the total cell number and CFU-S and CFU-GM concentrations were persistently higher in IL-3- and GM-CSF-treated groups 1 to 3 weeks after transplantation. In addition, the survival of animals as a function of transplanted cell number was persistently higher in IL-3- and GM-CSF-treated groups compared with controls. The data indicate that the pretreatment of marrow cells with IL-3 and GM-CSF before transplantation increases the seeding efficiency of hematopoietic stem cells and probably other progenitor cells after transplantation. This increased efficiency may be mediated by upward modulation of homing receptors. Therefore, ex vivo preincubation of donor marrow cells with IL-3 and GM-CSF may be a useful tactic in bone marrow transplantation.

Animals↗
PubMed1991

[Cytogenetic studies on 53 childhood acute nonlymphocytic leukemia].

Cytogenetic study in 53 children (aged less than 15 years) with acute non-lymphocytic leukemia (ANLL) were studied. The cytogenetic findings were compared with those of ANLL patients (136 aged less than 19 years and 747 aged over 20 years) in the Fourth International Workshop on Chromosomes in Leukemia (IV IWCL) and also with those of childhood acute lymphoblastic leukemia (ALL) cases (previously reported as our 124 ALL case). Of the ANLL patients, 77.4% had acquired chromosomal clonal abnormalities. As abnormalities, t(15;17), all cases which were seen in M3 or M3V cases, t(8;21), which was seen in M1 or M2, and rearrangements of 11q23, which were seen in M5, were more frequently seen than was reported at the IV IWCL (20.8%, 17.0% and 7.5% vs 6.3%, 6.3% and 3.2% respectively). 5q-, monosomy 7, t(6;9) and t(9;22), which have been noted previously in this disease, were not seen. Besides structural abnormalities, some cytogenetic differences in numerical abnormality between ALL and ANLL were observed as follows: 1) Hyperdiploidy of greater than 51 chromosomes noted in ALL was not found in ANLL. 2) Isolated trisomy 8 was frequently found in ANLL, but not in ALL. 3) Loss of a sex chromosome was frequently found in ANLL, but not in ALL. Our study revealed a different frequency of non-random chromosome abnormality in children with ANLL as compared with that of adults, and clarified the differences in numerical abnormalities, as well as structural abnormalities, between ALL and ANLL.

Adolescent↗
PubMed1991

[Significance of the 14q32 translocations in childhood acute lymphoblastic leukemia].

To assess the frequency and significance of 14q32 translocation abnormalities in childhood acute lymphoblastic leukemia (ALL) and the differences between the clinical and cytogenetic features of patients with the 8; 14 translocation and those of patients with other 14q32 translocations, we analyzed our experience with 124 consecutive cases with completely banded karyotype. Eight cases (6.5%) with 14q32 translocation were identified :5 with the 8; 14 translocation and 3 with other 14q32 translocations. As compared with ALL children lacking 14q32 translocations, these 8 cases had a higher serum lactic dehydrogenase (LDH) level, more L3 (FAB classification), and a poorer outcome. On the other hand, in comparison with ALL patients with other 14q32 translocations, patients with the 8:14 translocation were likely to be younger (median age 4.5 years vs 10.4 years), to have a higher serum LDH level (median 5832 IU/l vs 504 IU/l), to have more L3 (3/5 vs 0/3), to have a higher induction failure rate (4/5 vs 1/3), and to have more partial duplication of the long arm of chromosome 1 (4/5 vs 0/3). These results helped clarify the characteristic features of ALL children with 14q32 translocations and showed that ALL children with the 8 ; 14 translocation have different clinical and cytogenetic findings from those of ALL children with other 14q32 translocations.

Adolescent↗
PubMed1991

[Inhibition of hemopoiesis by nitrous oxide].

Inhibition of hemopoiesis by nitrous oxide was studied in mice and the following results were obtained. 1) During exposure to N2O, the numbers of pluripotent hemopoietic stem cells (CFU-S) and granulocyte-macrophage progenitor cells (GM-CFC) decreased significantly in the murine spleen and bone marrow, but the former more than the latter. 2) The recovery of CFU-S and GM-CFC was delayed in mice that were given low-dose irradiation followed by continuous exposure to N2O. The delay of recovery was significantly more in the spleen than in the bone marrow. 3) The levels of serum granulocyte-macrophage colony stimulating factor (CSF) in N2O exposed mice, induced by endotoxin, decreased significantly compared with those of control mice. Prolonged N2O administration to mice appears to impair the hemopoietic inductive microenvironment as well as hemopoietic stem cells and hence results in hemopoietic death and delay of hemopoietic recovery after irradiation.

Animals↗
PubMed1990

Homology of mecA gene in methicillin-resistant Staphylococcus haemolyticus and Staphylococcus simulans to that of Staphylococcus aureus.

A penicillin-binding protein of molecular weight 76,000 inducible by beta-lactams was detected in methicillin-resistant Staphylococcus haemolyticus and Staphylococcus simulans. DNA from these strains hybridized to the mecA gene from Staphylococcus aureus; however, the chromosomal HindIII fragments containing the mecA genes were 3.4 kilobases in S. haemolyticus and 4.3 kilobases in S. simulans.

Bacterial Proteins↗
PubMed1990

In vitro activity of LJC10,627, a new carbapenem antibiotic with high stability to dehydropeptidase I.

The in vitro activity of LJC10,627, a new carbapenem, was compared with those of imipenem and ceftazidime. LJC10,627 had broad-spectrum activity against gram-positive and gram-negative clinical isolates. The MICs of this compound for 90% of members of the family Enterobacteriaceae tested (MIC90s), including strains resistant to ceftazidime, ranged from 0.1 to 25 micrograms/ml. LJC10,627 inhibited Pseudomonas aeruginosa at an MIC90 of 3.13 micrograms/ml; it thus was twofold more active than imipenem. This compound inhibited Haemophilus, Neisseria, and Branhamella species at MIC90s of 3.13, 0.1, and 0.1 micrograms/ml, respectively. LJC10,627 was two- to fourfold less active than imipenem against methicillin-susceptible Staphylococcus aureus and Staphylococcus epidermidis at MIC90s of 0.1 and 0.39 microgram/ml. However, the compound was found to be twofold more active than imipenem against Bacteroides fragilis at an MIC90 of 1.56 microgram/ml. LJC10,627 was very stable to various beta-lactamases except for Xanthomonas maltophilia oxyiminocephalosporinase type II. LJC10,627 was minimally hydrolyzed by swine renal dehydropeptidase I; its residual activity was 93.0% after 2 h. Killing kinetics of this compound for Escherichia coli and Pseudomonas aeruginosa showed that bactericidal action occurred at concentrations above the MIC (0.05 and 0.39 microgram/ml, respectively). LJC10,627 had a high affinity for penicillin-binding proteins 2, 4, and 1B(s) of Escherichia coli and Pseudomonas aeruginosa and penicillin-binding proteins 1 and 4 of Staphylococcus aureus.

Animals↗
PubMed1990

Nucleotide sequence and characterization of the Staphylococcus aureus norA gene, which confers resistance to quinolones.

The norA gene cloned from chromosomal DNA of quinolone-resistant Staphylococcus aureus TK2566 conferred relatively high resistance to hydrophilic quinolones such as norfloxacin, enoxacin, ofloxacin, and ciprofloxacin, but only low or no resistance at all to hydrophobic ones such as nalidixic acid, oxolinic acid, and sparfloxacin in S. aureus and Escherichia coli. The 2.7-kb DNA fragment containing the norA gene had a long open reading frame coding for 388 amino acid residues with a molecular weight of 42,265, which was consistent with the experimental value of about 49,000 obtained on DNA-directed translation. The deduced NorA polypeptide has 12 hydrophobic membrane-spanning regions and is partly homologous to tetracycline resistance protein and sugar transport proteins. The uptake of a hydrophilic quinolone, enoxacin, by S. aureus harboring a plasmid carrying the norA gene was about 50% that by the parent strain lacking the plasmid, but it increased to almost the same level as that by the latter strain with carbonyl cyanide m-chlorophenyl hydrazone. On the other hand, the uptake of a hydrophobic quinolone, sparfloxacin, was similar in the two strains. These results suggest that the NorA polypeptide may constitute a membrane-associated active efflux pump of hydrophilic quinolones.

Amino Acid Sequence↗
PubMed1990

Effects of prolonged nitrous oxide exposure on hemopoietic stem cells in splenectomized mice.

We have demonstrated in previous papers that prolonged nitrous oxide exposure suppresses murine hemopoiesis more in the spleen than in the bone marrow and that this is caused by the suppression of the hemopoietic supportive activity of the microenvironment. In the present study, we used splenectomized mice as an experimental model to investigate the direct effect on bone marrow function of prolonged nitrous oxide inhalation. All of the experimental mice were splenectomized at the age of 4 wk. Half of the experimental mice were continuously exposed to 50% nitrous oxide, and the remainder were continuously exposed to air as controls, starting 3 wk after splenectomy and lasting 14 days, and the numbers of pluripotent hemopoietic stem cells (CFU-S) and granulocyte-macrophage progenitor cells (GM-CFC) in bone marrow were counted. The numbers of pluripotent hemopoietic stem cells and granulocyte-macrophage progenitor cells in the bone marrow of mice exposed to air showed no significant change. The numbers of these two types of cells found in nitrous oxide-exposed mice were approximately 60% of control levels. These data are almost the same as our previously reported bone marrow data obtained in nonsplenectomized mice exposed to nitrous oxide for 14 days. The present results suggest that the marked decrease in the number of splenic hemopoietic stem cells in our previous data is not a result of migration of the cells to bone marrow, and that nitrous oxide directly affects murine bone marrow hemopoiesis.

Animals↗
PubMed1990

[Clinical and cytogenetic features in childhood acute lymphoblastic leukemia with 1; 19 translocation].

We studied the clinical and cytogenetic features of 14 acute lymphoblastic leukemia (ALL) patients with 1; 19 translocation. Ten patients had poor prognostic factors such as age over 10 years, hyperleukocytosis over 5 X 10(4)/microliters or high serum lactic dehydrogenase levels over 5,000 IU/l. Two patients had relapsed within 12 months after the onset, but their 5-year survival rate was 84.6%. Cytogenetically, 6 of 14 patients had multiple subclones. Two had the clones with hyperdiploidy greater than 50 chromosomes, which was known to be one of the favorable prognostic factors in childhood ALL. These findings show ALL children with 1; 19 translocation have a more favorable outcome in spite of some high-risk features than hitherto been thought.

Adolescent↗
PubMed1990

Murine spleen culture: homing of hemopoietic progenitor cells to spleen is not mediated by a similar mechanism to that in marrow.

We have previously shown that in long-term bone marrow cultures (LTMC) the specific recognition and binding of hemopoietic stem cells to stroma, which we call "homing," is mediated by a recognition mechanism involving a surface membrane lectin with galactosyl and mannosyl specificities. Subsequent in vivo studies in lethally irradiated mice confirmed that homing to the marrow similarly involves a galactosyl- and mannosyl-specific recognition mechanism. However, these in vivo studies suggested that homing of hemopoietic progenitor cells to spleen was based upon a different molecular recognition mechanism. In the present study splenic homing was investigated in a cell culture system composed of an adherent layer of splenic stromal cells inoculated with stroma-free stem cells from the supernate of LTMC. In this system, splenic stroma supported proliferation and differentiation of hemopoietic precursors for a few weeks. When stem cells were added to the cultures in the presence or absence of inhibitory concentrations of neoglycoprotein reagents specific for galactosyl, mannosyl, or fucosyl lectins, the pattern of production of total cells, pluripotential stem cells (CFU-S), and granulocyte-macrophage committed progenitors (CFU-GM) remained the same. These data support our in vivo observations that homing of stem cells to splenic stroma is not mediated by a surface lectin with galactosyl and mannosyl specificities as it is in bone marrow, but rather by a different molecular mechanism.

Animals↗
PubMed1990

Interaction of late murine erythroid progenitors and stroma involves a recognition mechanism with fucosyl specificity.

We have previously reported that the specific recognition and binding of murine hemopoietic progenitors spleen colony-forming units (CFU-S) and granulocyte-macrophage CFU (CFU-GM) to hemopoietic stroma is dependent upon a membrane recognition system with galactose and mannose specificities. By using synthetic neoglycoproteins with galactose, mannose, or fucose covalently bound to bovine serum albumin (BSA) in standard long-term bone marrow cultures (LTBMC), galactosyl-BSA (gal-BSA) and mannosyl-BSA (man-BSA) but not fucosyl-BSA (fuc-BSA) inhibited the binding of CFU-S and CFU-GM to the stromal layer. In the present work it was shown that binding of erythroid burst-forming units (BFU-E) to stroma in standard LTBMC is also inhibited by gal-BSA and man-BSA. We then studied a different system of LTBMC that favored erythropoiesis and allowed the production of erythroid CFU (CFU-E) for 4 weeks. In the presence of the fuc-BSA as well as gal-BSA and man-BSA, total cell production and CFU-E production were halted in the supernate as well as the adherent layer. These results indicate the presence of a fucosyl recognition system on the surface of the late erythroid precursors, CFU-E.

Animals↗
PubMed1990

[Hyperdiploidy (greater than 50 chromosomes) has the most favorable prognosis among the major karyotypic subgroups of childhood acute lymphoblastic leukemia].

Thirty-four children, including nine relapsed cases with acute lymphoblastic leukemia (ALL) having hyperdiploidy (greater than 50 chromosomes) were studied on clinical and cytogenetic characteristics. The majority of children initially with hyperdiploidy (greater than 50 chromosomes), who showed favorable prognostic features such as lower leukocyte counts, lower serum lactic dehydrogenase levels, ages between 2 and 10 years, or the presence of common ALL antigen, had the most favorable outcome among childhood ALL (5-year survival rate was 100%). Even nine children, who showed poor prognostic features such as ages over 10 years, leukocyte counts over 2 X 10(4)/mm3 or lymphomatous signs, had also the same favorable outcome. There were no differences in clinical features between 6 patients with additional chromosomal structural abnormalities and 19 patients without them. Duplication of the long arm of chromosome 1 was frequently observed as additional chromosomal structural abnormalities. Patients with hyperdiploidy (greater than 50 chromosomes) observed at relapse, who had the same favorable clinical features as those at diagnosis, had a poorer prognosis. These findings show that initial hyperdiploidy (greater than 50 chromosomes) is an independent favorable prognostic sign in childhood ALL and additional chromosomal structural abnormalities may not indicate a poor prognosis among childhood ALL with hyperdiploidy (greater than 50 chromosomes). On the other hand, relapsed children with hyperdiploidy (greater than 50 chromosomes) have not a favorable outcome after the onset of relapse.

Child↗
PubMed1989

Prolonged nitrous oxide exposure inhibits settlement of transplanted hemopoietic stem cells in murine spleen.

In order to clarify the mechanism of hemopoietic depression induced by nitrous oxide inhalation, effects of prolonged nitrous oxide exposure on the settlement of transplanted bone marrow cells were investigated. Mice were continuously exposed to mixed gas containing 50% nitrous oxide, 21% oxygen and 29% nitrogen for 7 days and then they were irradiated with 850 rads. By the irradiation, endogenous pluripotent hemopoietic stem cells (CFU-S) almost disappeared in the mice. Normal syngenic murine bone marrow cells were injected intravenously and the numbers of CFU-S, which settled in the bone marrow and spleen 2 hr after injection, were measured. There was no difference of the numbers of CFU-S settled in the bone marrow between nitrous oxide and control gas exposed mice. In contrast, the numbers of CFU-S in the spleen of nitrous oxide exposed mice were approximately 60% of the control. These results and our previous data suggest that hemopoietic inhibitory effects of nitrous oxide in mice are due to a damage of splenic hemopoietic microenvironment, that supports the settlement of hemopoietic stem cells.

Journal Article↗
PubMed1989

Erythropoiesis in murine long term marrow cultures.

We utilized a system of long-term bone marrow cultures that favored erythropoiesis and allowed the production of CFU-E for four weeks. Certain conditions of culture were crucial for erythropoiesis to occur. These conditions have been discussed. This system should allow further in vitro study of the regulation of erythropoiesis.

Animals↗
PubMed1989

Cloning and expression of the norA gene for fluoroquinolone resistance in Staphylococcus aureus.

The norA gene for fluoroquinolone resistance in Staphylococcus aureus TK2566 was cloned from chromosomal DNA into fluoroquinolone-susceptible Escherichia coli TG1. The resulting transformant, NY11, contained a recombinant plasmid, designated pTUS1, with a cloned 5.5-kilobase (kb) HindIII fragment of staphylococcal DNA. The MIC of norfloxacin for the strain increased from 0.1 to 3.13 micrograms/ml. Furthermore, when the fragment was recloned into S. aureus, the transformant NY12, containing recombinant plasmid pTUS20, had the same level of resistance to norfloxacin as did the original strain, although it was less resistant to ofloxacin and ciprofloxacin. A single KpnI-HaeIII fragment was found to be the minimum size able to express norfloxacin resistance, suggesting that the norA gene is located within the 2.6- to 3.2-kb region of the original 5.5-kb fragment. The 5.5-kb fragment hybridized to DNA from a fluoroquinolone-susceptible S. aureus strain.

Anti-Infective Agents↗
PubMed1989

Restriction maps of the regions coding for methicillin and tobramycin resistances on chromosomal DNA in methicillin-resistant staphylococci.

Chromosomal BamHI DNA fragments containing both the mecA gene encoding the penicillin-binding protein responsible for methicillin resistance and the aadD gene encoding 4',4"-adenylyltransferase responsible for tobramycin resistance were cloned from three methicillin- and tobramycin-resistant strains of Staphylococcus aureus and one strain of Staphylococcus epidermidis. Physical maps of the fragments were similar, suggesting their unique origin.

Blotting, Southern↗
PubMed1989

Expression and inducibility in Staphylococcus aureus of the mecA gene, which encodes a methicillin-resistant S. aureus-specific penicillin-binding protein.

A beta-lactam-sensitive strain of Staphylococcus aureus could be converted to methicillin resistance by the introduction of a plasmid carrying the 4.3-kilobase HindIII chromosomal DNA fragment which encoded the mecA gene from a methicillin-resistant S. aureus. Transformant cells produced methicillin-resistant S. aureus-specific penicillin-binding protein constitutively, and additional insertion of an inducible penicillinase plasmid caused production of the pencillin-binding protein to become inducible.

Bacterial Proteins↗