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Biomedical subjects

H Miwa

Publications and source records attributed to H Miwa.

At least 217 records · Page 12Linked to original sources

Cellular characteristics of chronic myelocytic leukemia basophilic crisis cells: phenotype, responsiveness to and receptor gene expression for various kinds of growth factors and cytokines.

Leukemic cells from a patient with chronic myelocytic leukemia (CML) basophilic crisis were examined in an in vitro clonogenic assay using recombinant human hematopoietic growth factors to elucidate the proliferative and differentiative behaviors. More than 90% of the leukemic cells showed the morphologic characteristics of basophils and were positive for CD11b and CD13. The phenotype of the leukemic cells was different from that of mast cells. In the clonogenic assay using various recombinant growth factors, the leukemic cells were responsive to interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF), but not to granulocyte-CSF (G-CSF), erythropoietin (Epo), or IL-4. IL-5 showed synergistic effects on colony formations induced by both IL-3 and GM-CSF. Transcripts of the GM-CSF receptor alpha chain gene were detected in the leukemic cells, but transcripts of the IL-4 receptor gene were not. Furthermore, c-kit and IL-7 receptor genes were expressed in the leukemic cells. Our results suggest that the differentiation pathway of basophils is different from that of mast cells, even though the receptor gene for stem cell factor (c-kit) was expressed on the basophilic leukemic cells, as it was on mast cells.

Antigens, CD↗

Frequent gene expression of granulocyte colony-stimulating factor (G-CSF) receptor in CD7+ surface CD3- acute lymphoblastic leukaemia.

Gene expression of various cytokine receptors in CD7+ acute lymphoblastic leukemia (ALL) cells in relation to responsiveness to these cytokines was examined by reverse transcription polymerase chain reaction and Northern blot studies. Leukemic cells from all of seven CD7+ ALL patients examined fulfilled the criteria for ALL according to the FAB classification; surface CD3 was absent in all of these patients, while cytoplasmic CD3 and/or CD3 epsilon mRNA were found in all of them. Samples from six of the seven patients at initial disease expressed the granulocyte colony-stimulating factor receptor (G-CSFR) gene. Leukemic cells with G-CSFR transcripts from one patient at initial disease showed growth response to G-CSF in vitro, and those from two other patients became responsive to G-CSF at relapse. Neither in vitro nor in vivo myeloid differentiation was observed in any samples that responded to G-CSF. Interleukin 3R alpha (IL-3R alpha) gene was expressed in samples from one patient at initial disease and from two patients at relapse. GM-CSFR beta gene mRNA was detected in two patients with IL-3R alpha mRNA. Our results show that the leukemic cells in these CD7+ ALL patients frequently expressed G-CSFR as a functional property, thus calling attention to the appropriate clinical application of G-CSF for ALL patients.

Adolescent↗

Discordant reaction of Leu4 and rabbit anti-human CD3 epsilon in sinonasal 'T'-cell lymphoma.

Twelve cases of sinonasal 'T'-cell lymphoma were studied immunohistologically with a panel of antibodies that included two antibodies to CD3, Leu4 and rabbit anti-human CD3 epsilon. Leu4 was positive in five cases, whereas rabbit anti-human CD3 epsilon was positive in 11. This discordant reaction of the antibodies, suggestive of cytoplasmic CD3 epsilon +, CD3 delta-, and CD3 gamma-, has recently been demonstrated in activated adult natural killer (NK) cells also. Leu4-negative cases had the phenotype CD2+, CD5-, CD7+/-, T-cell receptor (TCR)-, and NK cell markers+, and had non-rearranged TCR genes. These findings suggest that a large group of sinonasal 'T'-cell lymphomas is derived from NK cells.

Adolescent↗

Acute effects of conventional oral dose of disopyramide on left atrial and ventricular functions.

Disopyramide, an antiarrhythmic drug, is known to impair cardiac function, but acute cardiac effects of conventional oral dose of disopyramide are not well known. To examine the extent of acute cardiac effects of daily oral dose of disopyramide, we gave 150 mg of disopyramide to thirteen patients with normal or impaired cardiac function, and observed cardiac function on an hourly basis for 3 hours after baseline period. The serum level of disopyramide reached a therapeutic level (2.0-5.0 micrograms/ml) mostly 1 hour after administration. Doppler-echocardiographically determined left ventricular ejection fraction, and the ratio of the peak early filling velocity to the peak atrial filling velocity in left ventricular inflow velocity remained unchanged throughout the experimental period. Other hemodynamic variables, such as blood pressure and heart rate remained unchanged. We conclude that daily oral dose of disopyramide appears to have no significant effects on cardiac function after administration. Disopyramide seems to be safe and may not be necessarily withheld from patients who need it, when hemodynamic variables are to be measured.

Adult↗

[A 93-year-old woman presenting consciousness disturbance, left hemiplegia, and respiratory distress].

We present a 93-year old female who abruptly developed left hemiplegia on the way to the wash room. She was admitted to another hospital where her consciousness deteriorated and artificial respiration was necessary. She was transferred to our hospital 20 days after the onset of her stroke. On admission, her BP was 60/40 mmHg, and wheezing râle was heard in both lung fields. No heart murmur was present. She was in comatose state, but a small amount of spontaneous movements were present in her eyelids and the jaw. Neurologic examination revealed no papilledema, small non-reactive pupils with the right side being slightly larger than the left, absence of ocular movements, and loss of oculocephalic response and corneal reflex. An intratracheal tube was in situ, and the observation of the pharynx was impossible. No stiff neck was present. No spontaneous movement was observed in her limbs which were flaccid, and all the deep reflexes were lost except for jaw jerk which was weakly positive. Cranial CT scans revealed low density areas in the right anterior and middle cerebral artery territories with patchy areas of high density being consistent with a hemorrhagic infarction. In addition, a small high density mass lesion was noted in the left frontal lobe adjacent to the falx, which was thought to be a small meningioma. Her clinical course was complicated by pneumonia, hypotension and cardiac failure. She expired 2 months after the onset of her stroke. Postmortem examination revealed an extensive hemorrhagic infarction involving the territory of the right internal carotid artery.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Hemiballism-hemichorea caused by a putaminal hemorrhage with worsening after smoking--a case report].

A 65-year-old hypertensive man was admitted because of abnormal involuntary movements which had an onset one month prior to the admission. Neurological examination revealed an alert and intelligent male in no acute distress. Cranial nerves appeared intact except for dysarthria. His gait was wide-based. He had hemiballism-hemichorea in his left upper and lower extremities. Cranial CT scans revealed a high density area confined to the right putamen. After admission, his involuntary movements slowly improved without medication. After near complete disappearance of his abnormal movements two weeks after admission, he noted that smoking induced choreic movement in his left side transiently. The involuntary movement ceased soon after upon stopping smoking. This was repeatedly observed not only by him but also by us. Our observation may indicate that the inhibition of the subthalamic nucleus as the result of the decrease of the putaminal output to the external segment of the globus pallidus will induce hemiballism. The effect of smoking on his involuntary movements can be understood as a result of increase in the dopamine release from the nigrostriatal terminals induced by nicotine.

Aged↗

A granulocytic population with rearranged immunogenotype in chronic myelocytic leukemia blast crisis and Philadelphia-chromosome-positive acute leukemia with cross-lineage nature.

Two patients with chronic myelocytic leukemia (CML) mixed crisis and one with Philadelphia-chromosome-positive (Ph1 +) acute lymphoblastic leukemia (ALL) with cross-lineage nature had a considerable number of granulocytes with monoclonally rearranged immunogenotype. The gene configurations of immunoglobulin heavy chain (IgH), T-cell receptor beta chain (TCR beta), and gamma chain (TCR gamma) in the granulocytic cells were identical to those in the blasts, indicating that both the blasts and the granulocytes were derived from common leukemic progenitors with the IgH gene rearrangements. In a colony assay of cells from in the Ph1 + ALL patient, the leukemic cells showed the potential to differentiate into granulocytes in the presence of either granulocyte-macrophage colony-stimulating factor (GM-CSF) or granulocyte-CSF (G-CSF). Interleukin 7 (IL-7) exerted synergistic effects on colony and cluster formation in cultures with these cytokines. Further, IL-3, GM-CSF, and G-CSF receptor gene expression was found in the leukemic cells. Our findings indicate that the Ph1 + common progenitors in these three patients preserved the potential for granulocytic differentiation even after the occurrence of the Ig (and TCR) gene rearrangements as the first genomic event in lymphocyte differentiation. The phenomenon of cross-lineage in leukemic cells, at least in Ph1 + leukemia, can be considered to demonstrate the potential of leukemic progenitors to differentiate in multiple directions.

Base Sequence↗

Age-related increase in systolic fraction of pulmonary vein flow velocity-time integral from transesophageal Doppler echocardiography in subjects without cardiac disease.

The pulmonary vein flow velocity-time profile would be equivalent to the pulmonary vein flow volume-time profile, provided that the cross-sectional area of the pulmonary vein remains unchanged during 1 cardiac cycle. The systolic fraction of the pulmonary vein flow velocity-time integral, a ratio of velocity-time integral of the S wave to the sum of velocity-time integrals of the S and D waves, represents the ratio of left atrial storage volume to left ventricular stroke volume. This systolic fraction may help early filling of the left ventricle through an appropriate storage of blood and generation of driving pressure in the left atrium. Because early filling of the left ventricle is progressively impaired with age, it was hypothesized that this systolic fraction is increased with age. Forty-four noncardiac surgical patients (age range 17 to 70 years) who underwent transesophageal Doppler echocardiography under general anesthesia were studied, and left upper pulmonary vein flow and mitral inflow velocities were recorded. The ratio of peak velocity of the E wave to that of the A wave of mitral inflow velocity-time profile (y) decreased with age (y = -0.0245 x age + 2.41; r = -0.672, p < 0.01). Systolic fraction (y) increased with age (y = 0.00373 x age + 0.514; r = 0.656, p < 0.01). The age-related increase in the systolic fraction of pulmonary vein flow velocity-time integral may account for the compensation for impaired early filling of the left ventricle in elderly patients.

Adolescent↗

Phenotypical characteristics of acute myelocytic leukemia associated with the t(8;21)(q22;q22) chromosomal abnormality: frequent expression of immature B-cell antigen CD19 together with stem cell antigen CD34.

Twenty-three acute myelocytic leukemia (AML) patients with t(8;21) chromosomal abnormality, all classified as M2 (French-American-British [FAB] classification), were investigated. Blastic cells from all patients were positive for the stem cell-associated antigens, CD34 and HLA-DR, and the immature myeloid antigens, CD13 and CD33. The nonblastic leukemic cells expressed the more mature myeloid antigens, CD11b and CD15, with loss of the immature phenotype. The incidence of positivities for the stem cell-associated antigens, CD34 and HLA-DR, in t(8;21) AML cells was significantly higher in comparison with those in other AML showing granulocytic differentiation (M2 or M3). AML cells with t(8;21) also showed some phenotypic abnormalities. Frequent expression of CD19 was found in the blastic population of t(8;21) AML (18 of 23 cases) without other B-cell antigens and Ig gene rearrangements. CD19 expression was confirmed by immunocytochemistry and Northern blotting. The CD19+ blastic cells coexpressed both CD34 and HLA-DR. In addition, CD33+ cells among the blastic fraction in t(8;21) AML cells were fewer in number than in those of M2 or M3 AML without t(8;21). Our findings indicate that leukemic blasts of t(8;21) AML commonly express CD19 while preserving the stem cell-associated antigens, and differentiate into the granulocytic pathway with discordant maturation such as low CD33 expression.

Adult↗

RNA expression of the WT1 gene in Wilms' tumors in relation to histology.

BACKGROUND: On the basis of accumulating data, the recently isolated WT1 gene is a Wilms' tumor gene and a putative tumor suppressor gene. These findings include expression in developing fetal kidney, intragenic deletions in tumors, and germline mutations in predisposed individuals. Wilms' tumors, which exhibit a broad range of differentiation, are composed of three cell types: blastema, epithelium, and stroma. PURPOSE: The purpose of this study was to investigate the relationship between WT1 gene expression and histologic composition in Wilms' tumors in an effort to elucidate how the WT1 gene functions in proliferation of these histologic components. METHODS: We used Northern blot hybridization to study WT1 gene expression by messenger RNA (mRNA) accumulation in 20 tumors of varying histology and in adjacent uninvolved kidney tissue. In two patients, tumors were also compared before and after therapy. RESULTS: Tumors that were predominantly blastemal expressed high amounts of WT1 mRNA, whereas predominantly stromal tumors expressed either low or undetectable amounts. Blastemal tumors that were predominantly poorly differentiated expressed WT1 mRNA at higher levels than those that were more well differentiated. Although we expected that a putative tumor suppressor gene like WT1 would generally be expressed at lower levels in tumor than in normal kidney, this was true only in predominantly stromal cells. One of the two patients studied before and after therapy had a dramatic response to therapy accompanied by a decline in WT1 gene expression and disappearance of blastemal and epithelial elements. CONCLUSIONS: A correlation was observed between WT1 gene expression and histology of the tumors. Level of expression was inversely related to the degree of differentiation in blastemal tumors and in the patient with a dramatic response to therapy. These results, in conjunction with the observation that WT1 mRNA is abundant in normal fetal kidney, suggest that WT1 gene expression is related to kidney development, especially in differentiation of blastemal components. IMPLICATIONS: Further studies to search for alterations of the WT1 gene in tumors and to identify regulatory factors in gene expression will increase understanding of the role of this gene in normal development and tumorigenesis.

Gene Expression Regulation, Neoplastic↗

Maturational stage specific immunoglobulin heavy chain gene rearrangements, determined by D and D upstream region gene structures.

In 43 cases of various B-cell lineage tumors, precise gene structures of rearranged immunoglobulin heavy chain (IgH) were studied. By Southern-blot analysis of D upstream (5'D) gene of IgH, biallelic rearrangement structures, D-J or V-D-J, were determined and consequently maturational stage specific IgH rearrangement patterns were investigated. B-precursor ALL cases (especially stage IV of Nadler's criteria) have V-D-J rearranged IgH genes on both alleles. In contrast, most of the mature B-cell malignancies, excluding multiple myeloma, have IgH genotype of D-J/V-D-J. In addition, in case of D-J/V-D-J, the D gene used in D-J joining has been speculated by Southern-blot of D genes. So, these approaches for inquiring precise structures of rearranged IgH genes are supposed to provide new information of lymphocyte differentiation and leukemogenesis.

Antigenic Variation↗

Structural alterations of the p53 gene in human leukemias.

We have investigated alterations of the p53 gene in human leukemias by polymerase chain reaction-mediated restriction fragment length polymorphism analysis. This method detects the codon 72 polymorphism of the p53 gene, allowing identification of loss of heterozygosity (LOH) of the p53 gene. In this study, at least two specimens were obtained from each patient to compare the allele status at different points of clinical course. Of 21 cases examined 7 were heterozygous at this polymorphic site and were evaluable for LOH study. Only one patient of Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL) lost the heterozygosity in the specimen of her last relapse. Leukemic cells from her repeated relapses including the last one revealed to have the clonally rearranged immunoglobulin H chain gene of the same size, indicating that alteration of the p53 gene in this patient might account for the lethal relapse as a clonal evolution event. Northern-blot analysis of the p53 gene showed that one case of CD7(+) ALL had altered p53 mRNA. Overall, it is demonstrated that alterations of the p53 gene might be involved in the pathogenesis or progression of at least some human leukemias, although the alterations in leukemias seemed to be not as frequent as in solid tumors.

Base Sequence↗

Small eye (Sey): cloning and characterization of the murine homolog of the human aniridia gene.

Phenotypic parallels and genetic evidence from comparative mapping suggest that the murine Small eye (Sey) and human aniridia (AN) disorders are homologous. This report describes the isolation of a murine embryonic cDNA that is structurally homologous to the AN cDNA were recently cloned. The murine cDNA detects a 2.7-kb transcript in the adult mouse eye and cerebellum and in human glioblastomas, suggesting a neuroectodermal involvement in the etiology of Sey/AN. Sequence comparison between the murine and the human cDNAs revealed extensive homology in nucleotide sequence (greater than 92%) and virtual identity at the amino acid level. None of the differing amino acids was located within the paired box and homeobox DNA-binding domains. These results provide evidence for a common molecular basis underlying the two genetic disorders and suggest that the Sey system would be an authentic model for human AN.

Amino Acid Sequence↗

Incidence of Paneth cells in minute tubular adenomas and adenocarcinomas of the large bowel.

This study attempted to demonstrate the incidence of Paneth cells within large bowel tubular adenoma and adenocarcinoma according to location and macroscopic appearance using minute tumors (up to 5 mm in size). We have shown that Paneth cells were sometimes seen in the early stage of the development of large bowel epithelial neoplasia. According to the macroscopic appearance (elevated or depressed type), in large bowel epithelial neoplasia, there was a statistical difference between the depressed type (32.5%, 14 of 40 cases) and the elevated type (16.6%, 24 of 145 cases) (Chi square analysis, p < 0.05) in the incidence of Paneth cells. Paneth cells were seen more frequently in adenocarcinoma (45.8%, 11 of 24 cases) than in tubular adenoma (16.8%, 27 of 161 cases), with a significant statistical difference (Chi square analysis, p < 0.01). According to location, in both tubular adenoma and adenocarcinoma, Paneth cells were more frequently observed in the proximal colon (tubular adenoma: p < 0.01, adenocarcinoma: p < 0.05, Chi square analysis).

Adenocarcinoma↗

Effect of antacid on absorption of the quinolone lomefloxacin.

The effect of antacid on the absorption of lomefloxacin (LFLX) in humans was studied. When LFLX was orally administered concomitantly with aluminum- and magnesium-containing antacids under fasting conditions, its level in plasma decreased by one-half and its area under the concentration-time curve was reduced by 40% compared with the levels observed after treatment with LFLX alone. The urinary recovery value also decreased by 40%. No such effects were noted after coadministration of LFLX and a nonmetallic antacid. This study confirmed the existence of chelate complexes of LFLX with Al3+ and Mg2+ and examined the chelating strength. The stability constants of LFLX with Al3+ and Mg2+ were measured and compared with those of ofloxacin and norfloxacin; little difference was observed among them. LFLX was found to bind more strongly with Al3+ than with Mg2+. Further, the existence of chelate formation was proven by 13C-nuclear magnetic resonance spectroscopy. The decrease in the LFLX level in plasma in humans could be explained by a reduced absorption of the Al(3+)- and Mg(2+)-LFLX chelate complexes.

Adult↗

Isolation and characterization of new peptide antibiotics, plusbacins A1-A4 and B1-B4.

New antibiotics, plusbacins A1-A4 and B1-B4, were isolated from the culture broth of a strain of Pseudomonas sp. These antibiotics were isolated as a complex by column chromatographies on Diaion HP-20 and silica gel, and then separated by HPLC. They are amphoteric in nature. The hydrochlorides are obtained as colorless powders, soluble in methanol and alkaline water. From their physico-chemical properties, these antibiotics are presumed to be acyloctapeptides containing a lactone linkage, and their differences occur in amino acid and fatty acid residues. The antibiotics are active against Gram-positive bacteria in vitro and in vivo.

Amino Acids↗