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Biomedical subjects

H Hirota

Publications and source records attributed to H Hirota.

At least 73 records · Page 4Linked to original sources
PubMed1993

Aphidicolin potentiates apoptosis induced by arabinosyl nucleosides in human myeloid leukemia cell lines.

We investigated the effect of aphidicolin, an inhibitor of DNA polymerase alpha and delta, on the induction of apoptosis by arabinosyl nucleosides in a human promyelocytic leukemia cell line, HL-60. Pretreatment of HL-60 cells with aphidicolin (2 microM) significantly increased the number of morphologically apoptotic cells induced by 1-beta-D arabinofuranosylcytosine (ara-C) during 4 hr of incubation. This is consistent with the appearance of DNA fragmentation as determined quantitatively by diphenylamine or by agarose gel electrophoresis. The inhibition of cell growth on day 3 after drug exposure was correlated with the degree of apoptosis: Such synergistic interaction between aphidicolin and ara-C has also been observed in other human myeloid leukemia cell lines, U937 and KG-1. In addition, the induction of apoptosis by 9-beta-D arabinofuranosyladenine or 9-beta-D arabinofuranosylguanine is augmented by aphidicolin.

Aphidicolin↗
PubMed1993

Analysis of hprt gene mutation following anti-cancer treatment in pediatric patients with acute leukemia.

We evaluated the genotoxic effect of cancer therapy on somatic cell mutation by isolating 6-thioguanine-resistant mutants in peripheral lymphocytes. The study population comprised 45 children with acute lymphoblastic leukemia (ALL), 13 children with acute myelogenous leukemia (AML) and 28 age-matched healthy controls. The geometric mean mutant frequency for ALL patients was 7.8 x 10(-6), which was significantly higher than that for AML patients (1.7 x 10(-6)) or for healthy controls (1.1 x 10(-6)). Fifteen patients with ALL showed a high mutant frequency above 10 x 10(-6), although 10 of them had completed their treatment at least 24 months earlier. Moreover, repeated measurements of mutant frequency at intervals of 12 or more months revealed that the values were very stable. Structural hypoxanthine-guanine phosphoribosyl transferase (hprt) gene alterations, as determined by Southern blot analysis, were seen in 23% (12/52) of mutant clones derived from ALL patients, but not in those from the controls. These results suggest that intensive anti-cancer therapy of children may produce persistent somatic mutations, which could be related to the appearance of second neoplasms.

Adolescent↗
PubMed1993

Radionuclide assessment of left ventricular performance on exercise after external conduit operation.

Only limited information is available concerning left ventricular (LV) response to exercise after an external conduit operation for cyanotic congenital heart disease. Sixteen patients who had undergone external conduit repair (EC group) were studied with multi-gated cardiac pool imaging using a supine bicycle ergometer on 20 occasions. Six patients with a history of Kawasaki disease without coronary artery stenosis served as controls (control group). Myocardial imaging and cardiac catheterization were also performed in the EC group. There was no significant difference in left ventricular ejection fraction (LVEF) at rest between the groups. However, on exercise, LVEF of the EC group was significantly lower than that of the control group. Nine patients in the EC group showed a perfusion defect (PD) on 12 occasions. LVEF on exercise of the patients with PD was significantly lower than that of the patients without PD. Furthermore, only the patients with PD showed a LVEF decrease of 5% or more in response to exercise. In the EC group, a significant inverse relationship was demonstrated between right ventricular systolic pressure (RVP) and LVEF response to exercise. However, two out of four patients who underwent external conduit replacement improved their LVEF response to exercise with successful reduction of RVP. These findings indicate that an impaired left ventricular response to exercise was common in patients after external conduit operations. Myocardial damage and right ventricular outflow tract obstruction could be the causes of this left ventricular dysfunction.

Adolescent↗
PubMed1993

Highly purified eicosapentaenoic acid attenuates tissue damage in experimental myocardial infarction.

We examined the effects of dietary supplementation with eicosapentaenoic acid (EPA) on experimental myocardial infarction in dogs. Twenty-five dogs were fed standard diets, 10 of which were supplemented with EPA-ester (100 mg/kg body weight/day) for 8 weeks, while 15 served as controls. After ingesting EPA for 8 weeks, the ratio of EPA to arachidonic acid (AA) in platelet cell membranes significantly increased (from 0.033 to 0.105; p < 0.01). The chemotactic response of neutrophils to leukotriene B4 (LTB4) was reduced in the EPA group (34% reduction at 10(-6) M LTB4, p < 0.01). Also in the EPA group, the amount of 12-hydroxyeicosatetraenoic acid, one of the chemotactic products of AA in infarcted myocardium, was reduced to 40% (p < 0.05). EPA treatment resulted in significant reduction in the ultimate size of the infarcted area. Contractile function of infarcted myocardium was well-preserved in the EPA group. Myeloperoxidase activity, an indication of the infiltration of neutrophils into the infarcted myocardium, was less in the EPA group than in the controls (0.68 +/- 0.25 U/0.1 gr. vs 1.22 +/- 0.55 U/0.1 gr., p < 0.05). Therefore, we conclude that dietary supplementation with EPA attenuates ischemic myocardial damage through inhibition of neutrophilic infiltration into the infarcted myocardium.

Animals↗
PubMed1993

[Acute mixed lineage leukemia showing resistance to AML and ALL therapy].

A 51-year-old female was who admitted complaining of cough and slight fever and lower limb petechia. The laboratory examinations revealed leukocytosis (49,400/microliters) with blasts (71%) in the peripheral blood. The NCC was 30 x 10(4)/microliters with 84.8% blasts in the bone marrow. Myeloperoxidase staining was positive for 6% of blasts. Auer rods were not seen in some blasts. Thus, acute myeloblastic leukemia (M1) was diagnosed according to FAB classification. In the peripheral blood, 43.3% of blasts expressed CD19, 10.3% of blasts expressed CD20 and 55.6% of blasts expressed CD33 on admission. Though she received two courses of DCMP according to the DCMP-85 protocol, and one combined course of mitoxantrone, etoposide, and Ara-C. The NCC was 20.0 x 10(4)/microliters with 70% blasts in the bone marrow. CD19 was expressed by 72.4% of blasts and 35.0% expressed CD20. The ALL-90 protocol was started, but remission was not achieved. Thus this case was considered to be acute mixed lineage leukemia.

Antigens, CD↗
PubMed1993

Mechanism of enhancement of neutrophil survival by granulocyte colony-stimulating factor and adenine.

An in vitro study was performed on the effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) and adenine on the survival of purified human neutrophils. The addition of rhG-CSF (1 to 100 ng/mL) or adenine (100 microM) enhanced the survival of neutrophils. The maintenance of O2- production in response to N-formylmethionyl-leucyl-phenyl-alanine (FMLP) suggested that these neutrophils were functionally alive. Neutrophils in cultures had shown two distinct biochemical changes during cell death: DNA fragmentation and depletion of cellular adenosine triphosphate (ATP) pools. Treatment with rhG-CSF (10 ng/mL) significantly delayed the appearance of DNA fragmentation as measured quantitatively by diphenylamine or by agarose gel electrophoresis. On the other hand, adenine had no effect on the generation of DNA fragmentation. The decrease of ATP during incubation for 12 hours was similar in control and rhG-CSF-treated neutrophils, while rhG-CSF prevented the further decline of ATP seen in control cultures. In contrast, adenine (100 microM) preserved ATP at levels significantly higher than in controls at both 12 hours and 24 hours of incubation. Our results suggest that rhG-CSF and adenine promote the survival of neutrophils in vitro by different mechanisms.

Adenine↗
PubMed1993

Role of protein kinase C in neutrophil survival enhanced by granulocyte colony-stimulating factor.

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) (10 ng/mL) prolonged human neutrophil survival in culture by at least 36 hours. The addition of H-series compounds at concentrations that are considered to inhibit both protein kinase C (PKC) and cyclic adenylate monophosphate (cAMP)-dependent protein kinase (PKA) counteracted the effect of rhG-CSF. Concomitantly, the inhibition of nucleosomal DNA fragmentation by rhG-CSF was canceled. At lower concentrations, presumably capable of inhibiting only PKA, however, the compounds exhibited marginal effects on rhG-CSF-mediated increase of cell survival. These PKC inhibitors did not influence the priming effect of rhG-CSF significantly, as determined by O2- production stimulated by N-formyl-L-methionyl-L-leucyl phenylalanine (fMLP). Our results suggest that PKC plays an important role in the mechanism by which rhG-CSF promotes neutrophil survival, in striking contrast with the priming effect elicited by rhG-CSF.

Adult↗
PubMed1993

Digital radiology and PACS.

Future hospital information systems should permit the systematic storage of all information generalized within the hospital, including medical diagnostic images. For such a system to be realized, implementation of a picture archiving and communication system (PACS) is needed. The development of computed radiography with an imaging plate (CR) has made it possible for digitalization of all kinds of projection radiographs, and thus for PACS to be realized. In this paper the clinical usefulness of CR and many factors required to realize PACS are described.

Data Display↗
PubMed1992

Identification of 7 alpha-hydroxy-3-oxo-4-cholestenoic acid in chronic subdural hematoma.

We detected a novel kind of bile acid in the content of chronic subdural hematoma. This substance was specifically found in chronic subdural hematoma, and not in subdural hygroma, which is pathologically similar except for the lack of capsular membrane. The compound was identified as 7 alpha-hydroxy-3-oxo-4-cholestenoic acid by high performance liquid chromatography, gas chromatography-mass spectrometry, and nuclear magnetic resonance spectrometry. The structure was confirmed by the comparison with the chemically synthesized compound. The average contents in chronic subdural hematoma were 658.09 +/- 137.53 ng/ml, while those in normal human plasma were 126.27 +/- 17.73 ng/ml. It was not detected in normal cerebrospinal fluid. The higher level in chronic subdural hematoma than human plasma strongly suggests the local, extrahepatic production of this type of C27 bile acids.

Bile Acids and Salts↗
PubMed1992

Incidence and natural course of trabecular ventricular septal defect: two-dimensional echocardiography and color Doppler flow imaging study.

This study was designed to determine the prevalence of trabecular ventricular septal defect (t-VSD) in neonates and to evaluate the effects of its location, morphologic features, and size on its natural course during infancy. One thousand twenty-eight term newborn infants were examined by color Doppler flow imaging with orthogonal ultrasonographic views. Ten girls and 11 boys (2.0%) were found to have t-VSD. The natural course of the defect was examined in 42 consecutive cases, consisting of this group of 21 neonates and another group of 21 neonates with t-VSD. The morphologic features of the defect within the trabecular septum were classified as one or two defects (36 cases) and as a mesh-like defect (six cases). Reduction in size began from the right ventricular side or from within the trabecular septum. Spontaneous closure occurred most commonly during the first 6 months of life and was observed in 32 cases (76%) by 12 months of age: the frequency of closure was not related to the morphologic features and the initial size of the defect, but apical defects tended to have higher persistent patency than did defects in other locations (p less than 0.05). We conclude that the frequency of t-VSD in neonates and the frequency of spontaneous closure during early infancy are higher than previously believed. This information is important for predicting the natural course of t-VSD and deciding on its proper management.

Blood Flow Velocity↗
PubMed1991

Choriocarcinoma of the septum pellucidum: case report.

A case of choriocarcinoma of the septum pellucidum is presented. The patient, a 6-year-old boy, demonstrated high levels of human chorionic gonadotropin in his urine, serum, and cerebrospinal fluid, and precocious puberty. The physical conditions and laboratory data returned to normal after surgical removal of the tumor, whole brain irradiation, and chemotherapy. Currently, there is no evidence of recurrence at 5 months after surgery.

Brain Neoplasms↗
PubMed1991

A huge intracranial xanthogranuloma in the middle cranial fossa: case report.

Xanthogranulomas of the dura presenting with clinical symptoms are rare. We report here a case of a huge dural xanthogranuloma in the middle cranial fossa, which caused hemiparesis through marked displacement and stenosis of the middle cerebral artery. Although such tumors usually arise in association with histiocytosis X or familial hyperlipoproteinemia, the present case was not associated with these diseases.

Aged↗
PubMed1991

WF-2421, a new aldose reductase inhibitor produced from a fungus, Humicola grisea.

WF-2421 is a novel aldose reductase inhibitor produced by Humicola grisea. WF-2421 was purified from the culture filtrate by successive ion exchange chromatography and the chemical structure was assigned to be alpha-formamido-5'-(2-formamido-1-hydroxyethyl)- beta,2',6-trihydroxy-3-biphenylpropanoic acid (1) on the basis of spectroscopic evidence. The IC50 value of WF-2421 was 3 x 10(-8) M against partially purified aldose reductase of rabbit lens.

Aldehyde Reductase↗
PubMed1991

YS-822A, a new polyene macrolide antibiotic. II. Planar structure of YS-822A.

The planar structure of a new polyene macrolide antibiotic, YS-822A, which was isolated from the culture filtrate of a mutant strain H-8 of Streptoverticillium eurocidicum var. asterocidicus S-822, was established as I on the basis of spectroscopic evidences and by comparison spectroscopic data with nystatin A1 (II) and amphotericin A (III), representative polyene macrolide antibiotics. Molecular formula of YS-822A was established as C37H59NO14 (MW 741) by elemental analysis, NMR, and FAB mass spectra. The UV spectrum of YS-822A was very similar to that of nystatin A1, suggesting that YS-822A also has a conjugated all-trans-tetraene moiety. 1H and 13C NMR spectra of YS-822A showed a number of broad and overlapped signals, but the 1H-1H and 13C-1H COSY spectra implied the existence of a mycosamine moiety and several other partial structures. The connectivity of these partial structures was established by extensive 2D NMR experiments, including homonuclear Hartmann-Hahn and heteronuclear multiple-bond connectivity measurements, which led to the determination of the gross planar structure of YS-822A as I.

Amphotericin B↗
PubMed1990

YS-822A, a new polyene macrolide antibiotic. I. Production, isolation, characterization and biological properties.

A new polyene macrolide antibiotic, YS-822A was isolated from the culture filtrate of a mutant strain H-8 of Streptoverticillium eurocidicum var. asterocidicus S-822. Whereas the original S-822 strain produced not only YS-822 substances but also teleocidin as by-product which is well-known as a strong carcinogenic promoter, the mutagenized H-8 strain produced the antibiotic with only a trace amount of teleocidin. Chemical and biological characterizations of the antibiotic revealed that YS-822A (molecular formula: C37H59NO14) is a new polyene macrolide with a wide antifungal spectrum and a low acute toxicity.

Animals↗
PubMed1989

Newcastle disease virus evolution. II. Lack of gene recombination in generating virulent and avirulent strains.

Sequence analysis and comparison of the fusion glycoprotein genes of 11 Newcastle disease virus (NDV) isolates indicated a high degree of functional and structural constraint exerted on the change of the glycoprotein. However, synonymous nucleotide substitutions occurred frequently throughout the coding region. Facilitated by an analysis of synonymous difference (Ks) in pairwise strain comparison, we defined the branching orders of the strains and identified three distinct evolutionary lineages correlating with the virulence as expressed by mean death time (MDT) for chick embryo. The typically virulent strains with MDT of about 50 hr were associated with one lineage, while the typically nonvirulent strains with MDT of infinity were of another lineage. The third lineage consisted of both virulent and avirulent strains whose MDTs lay on a continuum from 50 to 120 hr. Synonymous substitutions were found to occur with almost the same rates in the adjacent hemagglutinin-neuraminidase and membrane protein genes as in the fusion protein gene, and the branching orders based upon the Ks for these genes were essentially identical to those derived from the fusion protein gene. Therefore, no gene exchange by recombination seems to have occurred to generate the strains of distinct lineages. Rather, the different strains appear to have evolved through various degrees of accumulation of point mutations. Besides these evolutionary features, the present study strongly supports the importance of the previously identified signals for gene expression and for the proteolytic activation of the gene product.

Animals↗
PubMed1989

Insulin secretion in childhood obesity.

In 132 severely obese children (72 boys and 60 girls) who underwent institutional therapy, oral glucose tolerance tests were carried out on admission, and these children were divided into groups with normal and high insulin levels, in terms of the sigma IRI values obtained, on the basis of the reference value + 2SD calculated by Maruhama et al. From these children, those who had diabetes mellitus (DM) and those in whom DM was suspected were distinguished according to the diagnostic criteria of USPHS (Drash et al). The insulin levels were normal in 58 children and high in 64. Ten children were found to have DM, and 19 were suspected to have DM. Metabolism of the glucose load occurred at both normal and high insulin levels in some children. There was also a group of children in whom glucose metabolism was incomplete at high insulin levels and a group of children in whom glucose metabolism was not possible even at high insulin levels, showing an obvious DM reaction. These findings suggest that there is a difference in the sensitivity of the insulin receptors in these children. Age, severe obesity and a family history of DM were considered to be risk factors for DM. Although there was a moderate, positive correlation between sigma IRI and the obesity index and between sigma IRI and age, it seems that the level of insulin secretion varies considerably in obese children.

Adolescent↗