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Biomedical subjects

H Miwa

Publications and source records attributed to H Miwa.

At least 19 recordsLinked to original sources

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

Expression of the Wilms' tumor gene (WT1) in human leukemias.

Leukemic cells from seventy patients with various types of human leukemias were examined for expression of the WT1 gene, the Wilms' tumor gene located at chromosome 11p13. WT1 was expressed in 7 of 16 cases of acute lymphoblastic leukemia, 15 of 22 with acute myelogenous leukemia and 8 of 10 in blast crisis of chronic myelogenous leukemia. No detectable WT1 RNA was found in chronic leukemias, including chronic lymphocytic leukemia, plasma cell leukemia, hairy cell leukemia and chronic myelogenous leukemia in chronic phase. The expression pattern of WT1 in these human leukemia samples indicates the involvement of this gene in the early stage of hematological cell differentiation.

Adolescent

c-kit gene expression in CD7-positive acute lymphoblastic leukemia: close correlation with expression of myeloid-associated antigen CD13.

Expression of human c-kit proto-oncogene and interleukin-7 receptor (IL-7R) in acute lymphoblastic leukemia (ALL) cells expressing CD7 was examined by Northern-blot analysis and reversed transcription polymerase chain reaction (RT-PCR) assay in relation to the phenotypes. Leukemic cells from four out of 12 CD7+ ALL patients, all of which fulfilled the criteria of ALL in the FAB classification, expressed c-kit genes. Surface CD3 (sCD3) was absent in all of these cases, while cytoplasmic CD3 (cCD3) was found in the two sCD3- cases. CD3 epsilon transcripts were detected in one of the sCD3- cCD3- cases. IL-7R genes were transcribed in the three cases with c-kit gene expression. In addition, there was a good correlation between c-kit gene expression and myeloid associated antigen CD13 positivity of the leukemic cells. None of the patients with c-kit gene expression had mediastinal tumor. Our results show that leukemic cells in a proportion of CD7+ ALL express receptors for cytokines that are secreted by bone marrow stromal cells. Ligands for c-kit genes and IL-7 could play an important role for the regulation of proliferation and differentiation of T-cell progenitors in bone marrow.

Antigens, CD

[A case of aortic valve stenosis and regurgitation with idiopathic thrombocytopenic purpura].

A patient of aortic valvular disease with idiopathic thrombocytopenic purpura underwent aortic valvular replacement. We report a preventive measure against the intra and postoperative bleeding. The patient was a 67-year-old man. He was diagnosed as aortic valvular stenosis with regurgitation. There was no abnormal data about the coagulation test. Thrombocyte count was 8.2 x 10(4)/mm3, but thrombocytopenic life span had shortened 3.8 days. So, we used gamma-globulin 400 mg/kg/day for 5 days before the day of operation and infused blood platelets on the day of operation. There was no problem intra and postoperative period. On the 14th postoperative day thrombocyte count increased to 22.9 x 10(4)/mm3, and thrombocytopenic life span returned to normal range (7.6 days). But on the 45th day of postoperation, thrombocyte count decreased to 11.0 x 10(4)/mm3. We think that many gamma-globulin medication is a useful method to prevent intra and postoperative bleeding resulting from idiopathic thrombocytopenic purpura.

Aged

[The usefulness of the emergency hepatobiliary scintigraphy to rule out acute cholecystitis--43 patients report].

We studied emergency hepatobiliary scintigraphy in the 43 patients to rule out acute cholecystitis. After injection of 185-222 MBq (5-6 mCi) of 99mTc-EHIDA or 99mTc-HIDA, serial static scintigraphic images were obtained up to 7 hours in maximum. Of 43 patients in this study, 20 had a normal scan and finally in all of them cholecystitis was ruled out. Of the 43 patients, 14 had an abnormal scan (nonvisualized gall bladder). In 10 of them the diagnosis of acute cholecystitis was confirmed after emergency cholecystectomy. The other 9 patients of 43 had an incomplete scan mainly due to liver dysfunction. Four of them had acute cholecystitis in the cholecystectomy. These results indicate that acute cholecystitis can be excluded by the findings of gall bladder visualization in hepatobiliary scintigram. We concluded that emergency hepatobiliary scintigraphy is very useful to rule out acute cholecystitis.

Acute Disease

[The surgical treatment for the Stanford type A aortic dissection].

Twenty-nine patients who underwent operation at Shinshu University Hospital for the Stanford type A dissecting aneurysm were analysed. The patients were operated on in the acute stage within 2 weeks after onset. In 13 of these 26 acute cases, the graft replacement of the ascending and arch of the aorta was performed (group A). The patients were operated under a separate perfusion to the brain and the distal anastomosis to the proximal portion of the descending aorta was performed using the method of open distal anastomosis. In other 13 cases, the graft replacement of the ascending aorta was performed (group B). Operative mortality rate was 19% in this series (group A: 23%, group B: 15%). There was no significant difference in their operative mortality of acute stage. And there was also no significant difference in their post operative course of acute stage operations. We concluded that the graft replacement of the ascending and arch of the aorta was better than the graft replacement of the ascending aorta alone for the patients with Stanford type A acute aortic dissection.

Aged

[A new system of diagnosis and classification--malignant lymphoma].

Malignant lymphoma is usually divided into Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) according to biological characteristics. Malignant lymphoma in Japan has such the characteristics as few incidence of HD, which is usually favorable in prognosis, and high incidence of NHLs, which have further distinctive features of less incidence of favorable follicular B cell lymphoma and of higher incidence of unfavorable diffuse T cell lymphoma including adult T cell leukemia/lymphoma (ATLL) in comparison with those in western countries. As a recent trend of progress in lymphoma diagnosis an introduction of immunological and molecular biological techniques has given an impact to the previous classification of malignant lymphoma based mainly on morphological criteria. Nowadays, the classification of pathologic type in HD seems to be settled in Rye classification. On the other hand in NHL the LSG classification has been well fixed in Japan and Working Formulation originated in USA has been well used internationally after a historical confusion. In this article a present state of working classification in malignant lymphoma is briefly described and discussed.

Hodgkin Disease