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Biomedical subjects

H Kitayama

Publications and source records attributed to H Kitayama.

At least 73 records · Page 4Linked to original sources
PubMed1992

[Apico-aortic conduit repair for the subaortic stenosis in the long-term period after correction of Taussig-Bing malformation].

Apico-abdominal-aortic bypass operation was successfully performed for the left ventricular outflow tract obstruction 17 years after correction of Tausig-Bing malformation. At the age of 14 months old, a 18-year-old patient underwent total correction of Taussig-Bing malformation according to Kawashima's intraventricular re-routing. The right ventricular hemodynamics were normal throughout, however, systolic ejection murmur due to aortic stenosis appeared 3 years after repair. Seventeen years postoperatively, marked aortic valve and subaortic obstruction was detected corresponding with the internal conduit made from the duplicated autopericardial baffle. A composite graft containing 23A-SJM valve was interposed between the left ventricular apex and infrarenal abdominal aorta. After the bypass operation, thickness of the posterior wall of the left ventricle and interventricular septum was significantly reduced and symptoms were remarkably improved. The present paper is concerned with the subaortic stenosis after repair of Taussig-Bing malformation and technique of apico-aortic bypass operation.

Adolescent↗
PubMed1991

Proliferation of human myeloid leukemia cell line associated with the tyrosine-phosphorylation and activation of the proto-oncogene c-kit product.

We investigated the expression, degree of phosphorylation, and activation of the proto-oncogene c-kit product before and after stimulation with the c-kit ligand in a human factor-dependent myeloid leukemia cell line, MO7E. The culture supernatant of the BALB/3T3 fibroblast cell line, which contains the ligand for the murine c-kit product, was found to stimulate proliferation of the MO7E cell line in a dose-dependent manner. The proliferation was significantly inhibited by a tyrosine kinase inhibitor, genistein. An immunoblot technique with a monoclonal antibody specific for phosphotyrosine, showed that there was rapid, dose-dependent tyrosine-phosphorylation of the c-kit product in response to murine c-kit ligand. Furthermore, the murine c-kit ligand increased autokinase activity of the c-kit product in vitro. Similar results were obtained with human stem cell factor (SCF), a recombinant human ligand for the c-kit product. These results suggest that the phosphorylation and activation of the c-kit product are involved in proliferative signals of some human leukemia cells, as well as of normal hematopoietic cells.

Blotting, Northern↗
PubMed1991

Expression and functional role of the proto-oncogene c-kit in acute myeloblastic leukemia cells.

The c-kit proto-oncogene encodes a receptor tyrosine kinase that is thought to play an important role in hematopoiesis. In a series of human acute myeloblastic leukemia (AML), the expression of the c-kit proto-oncogene and its product was studied by means of Northern blot and immunoblot analyses. The c-kit mRNA was expressed in 20 of 25 cases of AML, and in those cases the product of the c-kit proto-oncogene was detected by immunoblotting with anti-c-kit antibody. The expression of c-kit transcripts and protein was barely detectable in normal bone marrow cells as a control. The expression of c-kit transcript did not correlate with the French-American-British classification nor clinical manifestations. In 6 of 11 cases that expressed c-kit product, AML cells were found to proliferate in response to recombinant human stem cell factor (rhSCF), the ligand for c-kit, and the synergistic stimulation of AML cells was observed by rhSCF and granulocyte-macrophage colony-stimulating factor. Immunoblotting with anti-phosphotyrosine antibody showed that the c-kit receptor protein was detectably phosphorylated in 7 of 12 cases tested before the stimulation with rhSCF, while the rhSCF treatment resulted in an increased tyrosine phosphorylation of c-kit in AML cells. These results indicate that c-kit proto-oncogene is expressed in most cases of AML and is functional in terms of supporting proliferation.

Blotting, Northern↗
PubMed1991

Genetic analysis of the K-rev-1 transformation-suppressor gene.

Flat revertants with reduced malignancy in vivo can be isolated from Kirsten sarcoma virus-transformed NIH 3T3 cells (DT line) following transfection with a normal human fibroblast cDNA expression library. We have recovered from one such revertant a 1.8-kb cDNA clone, K-rev-1, that exhibits an activity of inducing flat revertants at certain frequencies (2-5% of total transfectants) when transfected into DT cells. The K-rev-1 cDNA has the capacity to encode a protein with a calculated molecular weight of 21,000, having strong structural similarity to ras proteins (approximately 50% homology), especially in their guanosine triphosphate/guanosine diphosphate-binding, effector-binding, and membrane-attachment domains. Toward understanding the mechanism of action of K-rev-1 protein, we constructed a series of point mutants of K-rev-1 cDNA and tested their biological activities. Substitutions of the amino acid residues in the putative guanine nucleotide-binding regions (Asp17 and Asn116), in the putative effector-binding domain (residue 38), at the putative acylation site (Cys181), and at the unique Thr61 all decreased the transformation-suppressor activity. On the other hand, substitutions including Gly12 to Val12, Ala59 to Thr59, and Gln63 to Glu63 were found to significantly increase the transformation-suppressor activity of K-rev-1. These findings are consistent with the idea that K-rev-1 protein is regulated like many other G-proteins by guanine triphosphate/guanine diphosphate-exchange mechanism probably in response to certain negative growth-regulatory signals.

3T3 Cells↗
PubMed1991

Hemorrhagic cystitis after bone marrow transplantation: importance of a thin sectioning technique on urinary sediments for diagnosis.

We used a thin-sectioning technique for the electron microscopic detection of viral particles within the cells of urinary sediments in three recipients who developed hemorrhagic cystitis after allogeneic bone marrow transplantation. Results of viral cultures of urine and electron microscopic (EM) observations on urinary sediments were consistent in only one recipient. In this recipient, EM observations revealed many viral particles within the cells of urinary sediments with diameter of about 80 nm corresponding to adenovirus, of which type 11 was produced in viral cultures. In one of the other two recipients many viral particles with a mean diameter of 41.6 nm corresponding to papovavirus were observed, but viral cultures using conventional cells were negative. Re-cultures using HEK cells produced polyomavirus BK. EM observation was a clue to the correct diagnosis. In the remaining recipient, no viral particles were observed within the cells of urinary sediments, suggesting the hemorrhagic cystitis to be of non-viral origin, despite a positive result of viral culture. These results suggest that a thin-sectioning technique on the cells of urinary sediments is important for the differential diagnosis between a viral-induced and non-viral hemorrhagic cystitis.

Adenoviridae↗
PubMed1990

Genetic analysis of the Kirsten-ras-revertant 1 gene: potentiation of its tumor suppressor activity by specific point mutations.

Kirsten-ras-revertant 1 (Krev-1) cDNA encodes a ras-related protein and exhibits an activity of inducing flat revertants at certain frequencies (2-5% of total transfectants) when introduced into a v-K-ras-transformed mouse NIH 3T3 cell line, DT. Toward understanding the mechanism of action of Krev-1 protein, we constructed a series of point mutants of Krev-1 cDNA and tested their biological activities in DT cells and HT1080 human fibrosarcoma cells harboring the activated N-ras gene. Substitutions of the amino acid residues in the putative guanine nucleotide-binding regions (Asp17 and Asn116), in the putative effector-binding domain (residue 38), at the putative acylation site (Cys181), and at the unique Thr61 all decreased the transformation suppressor activity. On the other hand, substitutions such as Gly12 to Val12 and Gln63 to Glu63 were found to significantly increase the transformation suppressor/tumor suppressor activity of Krev-1. These findings are consistent with the idea that Krev-1 protein is regulated like many other G proteins by the guanine triphosphate/guanine diphosphate-exchange mechanism probably in response to certain negative growth-regulatory signals.

Amino Acid Sequence↗
PubMed1990

A domain responsible for the transformation suppressor activity in Krev-1 protein.

Krev-1 cDNA encodes a ras-related protein and exhibits an activity of inducing flat revertants at certain frequencies (2-5% of total transfectants) when introduced into a v-K-ras-transformed mouse NIH3T3 cell line, DT. To explore the functional organization of Krev-1 protein, we constructed a series of chimeric genes consisting of fragments of H-ras and Krev-1 cDNAs, and tested their biological activities in DT cells. The results indicated that the determinant for the transformation suppressor activity resides in the N-terminal one-third of the Krev-1 encoded polypeptide within which a highly conserved, putative effector-binding domain is present.

Chromosome Mapping↗
PubMed1990

[A successful arterial switch operation for a patient with pulmonary venous obstruction and pulmonary hypertension five years after the Mustard procedure].

A five year and six month old boy, who had undergone Mustard operation for complete transposition of the great arteries with intact ventricular septum at two months of age, was reoperated on for pulmonary venous obstruction and pulmonary hypertension (PLV/RV = 0.96). The other complications which he had were moderate tricuspid regurgitation and various supra-ventricular arrhythmias. After the atrial baffle of the Mustard procedure was taken down, atrial septum was reconstructed and arterial switch operation was performed at the same time. One month after the operation, Pp/Ps was 0.41 and no tricuspid regurgitation and arrhythmias were found. He was discharged and his quality of life was ameliorated surprisingly.

Child, Preschool↗
PubMed1989

A ras-related gene with transformation suppressor activity.

A 1.8 kb cDNA clone, Krev-1, with revertant-inducing activity on Kirsten sarcoma virus-transformed NIH/3T3 cells, has been isolated from a human fibroblast cDNA expression library. In Krev-1 transfectants, there is a correlation between the levels of specific mRNA and the degrees of suppression of the transformed phenotype. The cDNA encodes a protein of 21,000 daltons that unexpectedly shares around 50% amino acid identities with ras proteins. The Krev-1 homologs are found in mouse, rat, and chicken DNA, and their transcripts are ubiquitously expressed in many rat organs. Thus, the Krev-1 gene seems to play an important role(s) in a wide variety of tissues, and may be involved in the negative growth regulation of certain cell types.

Amino Acid Sequence↗
PubMed1989

Detection of genes with a potential for suppressing the transformed phenotype associated with activated ras genes.

Seven morphologically nontransformed (flat) revertants with reduced tumorigenicity in vivo have been isolated from populations of Kirsten sarcoma virus-transformed NIH 3T3 cells transfected with a cDNA expression library of normal human fibroblasts. Each revertant harbors 1-10 recombinant plasmids per cell and retains a rescuable transforming virus as well as high level expression of v-Ki-ras-specific RNA and the viral oncogene product, p21v-Ki-ras. Transformed phenotypes are suppressed in cell hybrids generated by fusing each revertant to v-Ki-ras-transformed NIH 3T3 cells. From two of the revertant lines, plasmids capable of giving rise to flat secondary transfectants have been recovered. Thus, in some, if not all, of the revertants, transfected cDNAs seem to be responsible for the suppression of specific transformed phenotypes.

Animals↗
PubMed1989

Clinical effects of recombinant human granulocyte colony-stimulating factor in leukemia patients: a phase I/II study.

A phase I/II study of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in 24 leukemia patients was conducted at our institute. Recombinant human G-CSF (50-200 micrograms/m2/day) was administered i.v. In seven allogeneic bone marrow transplantation (BMT) recipients, treatment with rhG-CSF was started 5 days after BMT. Neutrophils began to increase within 3 days after the start of rhG-CSF administration in five of seven patients. The mean duration necessary for recovery of neutrophils to greater than 500/microliters was 11.3 days after BMT with rhG-CSF; 26.8 days is the figure for recovery without rhG-CSF from Japanese historical data. In seven out of eight patients who received rhG-CSF administration after the first remission-induction chemotherapy, the neutrophil counts increased from less than 300/microliters to greater than 4000/microliters within 10 days. Blasts did not increase in all patients including four acute nonlymphocytic leukemia (ANLL) patients. Severe infections such as septicemia and pneumonia, which were unable to be controlled by antibiotics only, were successfully treated with rhG-CSF and antibiotics. rhG-CSF either stimulated or inhibited myeloid leukemic cells in some refractory cases. Mild bone pain occurred in one patient while receiving rhG-CSF i.v. rhG-CSF seems to have the ability to shorten the period of neutropenia, prevent infections after allogeneic BMT and remission-induction chemotherapy for acute leukemia, and support therapy for infections.

Acute Disease↗
PubMed1989

Granulocyte colony-stimulating factor in allogeneic bone marrow transplantation.

A Phase II study of recombinant granulocyte colony-stimulating factor (G-CSF) in allogeneic bone marrow transplantation (BMT) was performed. The recovery of leukocytes and neutrophils was markedly accelerated in G-CSF-administered recipients. The days to WBC count greater than 1,000/microliters (11.5 +/- 1.9) and the days to neutrophil count greater than 500/microliters (11.5 +/- 1.4) were significantly shorter than those of the monocyte-CSF (M-CSF) and CSF(-) groups. In the G-CSF group the WBC count at nadir was higher than in other groups, and neutrophil recovery preceded monocyte recovery. After the discontinuation of G-CSF, the WBC count first decreased for a few days and then increased again slowly. The short duration of leukopenia brought about a reduction in the number of febrile (greater than 38 degrees C) days which, until day 30, were 1.8 +/- 1.9 in the G-CSF group, also significantly shorter than in others. Acute graft-versus-host disease (greater than grade II) appeared in two of eight patients from the G-CSF group, this incidence being comparable to those found in the other groups. A side effect of G-CSF-mild bone pain-was observed in one patient, but it was tolerable. Six of eight patients in the G-CSF group survived for between five and 13 months after BMT with a Karnofsky score greater than 90%. No relapses were observed in the six, including one patient with chronic myelogenous leukemia and two with acute non-lymphoblastic leukemia. To determine the final influence of G-CSF on myeloid leukemia, further long-term follow-up studies are needed. G-CSF was well tolerated and seemed promising against allogeneic BMT.

Adolescent↗
PubMed1989

Transformation suppressor genes.

Flat revertants with reduced malignancy in vivo can be isolated from Kirsten sarcoma virus-transformed NIH3T3 cells following transfection with a normal human fibroblast cDNA expression library. We have recovered from one such revertant a 1.8 kb cDNA clone, "Krev-1", that possesses revertant-inducing activity in transfection assay. The Krev-1 cDNA has the capacity to encode a protein with a calculated molecular weight of 21,000 having strong structural similarity to ras proteins (ca. 50% homology), especially in their GTP/GDP-binding, effector-binding and membrane attachment domains. Point-mutations of Krev-1 protein at the 12th and the 59th amino acid positions from the aminoterminus potentiated the transformation suppressor activity by 2-5 times, and point-mutations within the putative effector-binding domain and at the C-terminal acylation site reduced the activity.

Amino Acid Sequence↗
PubMed1989

[Specific cardiomyopathy caused by high dose cyclophosphamide immediately after bone marrow transplantation].

An 11-year-old girl with CML in chronic phase was treated with allogeneic bone marrow transplantation (BMT). She had had no episode of heart disease, and her chest roentgenogram and electrocardiogram were within normal ranges. She had no anthracycline, but 120 mg/kg (2.01 g/m2/d x 2 days) of cyclophosphamide (CY) for conditioning of BMT. She suffered from an acute heart failure on 14 days after BMT and died 2 days later. Autopsy revealed "specific heart muscular disease" with apparent degeneration and necrosis of heart muscle cells. More than 30 fatal cases of CY cardiotoxicity after BMT have been reported, and most patients developed acute heart failure within 10 days after CY dosing. Goldberg et al. reviewed 14 cases of CY cardiotoxicity, and considered more than 1.55 g/m2/day to be the critical doses for the onset of fatal cardiomyopathy. This case was considered to be first case in Japan. CY cardiomyopathy is an early fatal complication of BMT when CY used for conditioning. The dosing schedule may be considered.

Bone Marrow Transplantation↗
PubMed1988

Possible involvement of two signaling pathways in induction of neuron-associated properties by v-Ha-ras gene in PC12 cells.

Harvey sarcoma virus induces a number of neuron-associated properties in a nerve growth factor-responsive cell line, PC12 (Noda, M., Ko, M., Ogura, A., Liu, D., Amano, T., Takano, T., and Ikawa, Y. (1985) Nature 318, 73-75). We investigated the mechanism of this phenomenon using PC12 sublines cotransfected with a plasmid containing v-Ha-ras gene under control of a hormone-responsive enhancer/promoter element of the mouse mammary tumor virus long terminal repeat (pM14-1) and a plasmid encoding G418 resistance (pSV2neo). Extent of the expression of neuron-associated properties in several cell clones after the addition of dexamethazone (DEX) seems to correlate well with the levels of the v-Ha-ras gene expression. After the induction of v-Ha-ras expression with DEX in these cell lines, sustained elevation of the levels of cAMP as well as of phosphatidylinositol (PtdIns) metabolites, inositol trisphosphate, and diacylglycerol, is observed. Physiological significance of this phenomenon is confirmed by the observation that dibutyryl cAMP and phorbol-12-myristate 13-acetate synergistically induces the expression of neuron-associated properties in PC12 cells. In control PC12 sublines transfected with pSV2neo alone, DEX shows no effects on their cell morphology and the levels of cAMP and the PtdIns metabolites, although these control cell lines are competent to the effects of dibutyryl cAMP and phorbol ester. The priming activity known to be associated with nerve growth factor is also observed with v-Ha-ras as well as with dibutyryl cAMP plus phorbol ester but not with dibutyryl cAMP or phorbol ester alone. The observations suggest that the role of v-Ha-ras gene product in this system may involved simultaneous activation of the two signaling pathways, those mediated by cAMP and by PtdIns turnover.

Acetylcholinesterase↗