Biomedical subjects

Y Hirota

Publications and source records attributed to Y Hirota.

At least 19 recordsLinked to original sources

PubMed1995

Adjacent upstream superhelical writhe influences an Escherichia coli promoter as measured by in vivo strength and in vitro open complex formation.

This work investigates the effect on transcription of superhelical writhe located in the region immediately upstream of the -35 consensus sequence of Escherichia coli promoters. A set of double-stranded oligonucleotides, each with an unique DNA configuration, were designed, synthesized and substituted into an area of naturally occurring right-handed superhelical curvature immediately upstream of the beta-lactamase promoter in plasmid pUC19. All the mutants showed reduced promoter activities in E. coli cells. However, rightward superhelical writhe clearly facilitated transcription when compared with the effect produced by a straight DNA segment. Leftward writhe greatly repressed transcription. A plane curve showed an intermediate effect. This phenomenon was due not only to the difference in the ability of the segment to drive an open complex formation, but also to the difference in the binding affinity of RNA polymerase to the promoter. The positive effect of rightward writhe was also observed in vivo for the promoter of the tetracycline resistance gene of pBR322. The sense and extent of superhelical writhe of a DNA curvature seem to determine its influence on promoter activity.

Ampicillin↗

PubMed1995

Long-term denopamine therapy for hemodialysis patients with chronic heart failure.

Denopamine was orally administered for more than 12 months to patients with chronic heart failure on maintenance hemodialysis. The plasma level in subjects treated with denopamine at 30 mg/day tended to be higher than that in subjects on 15 mg/day. There was no gradual increase in plasma level as the duration of therapy prolonged. Left ventricular end-diastolic and end-systolic diameters as well as ejection fraction on echocardiography showed a tendency to be improved by denopamine. Similarly, the cardiothoracic ratio was improved temporarily. No adverse effects were detected by electrocardiography and laboratory tests. These observations suggest that denopamine is safe and effective for hemodialysis patients with chronic heart failure.

Administration, Oral↗

PubMed1995

A new water-soluble camptothecin derivative, DX-8951f, exhibits potent antitumor activity against human tumors in vitro and in vivo.

CPT-11, a semisynthetic derivative of camptothecin, exhibited strong antitumor activity against lymphoma, lung cancer, colorectal cancer, gastric cancer, ovarian cancer, and cervical cancer. CPT-11 is a pro-drug that is converted to an active metabolite, SN-38, in vivo by enzymes such as carboxylesterase. We synthesized a water-soluble and non-pro-drug analog of camptothecin, DX-8951f. It showed both high in vitro potency against a series of 32 malignant cell lines and significant topoisomerase I inhibition. The anti-proliferative activity of DX-8951f, as indicated by the mean GI50 value, was about 6 and 28 times greater than that of SN-38 or SK&F 10486-A (Topotecan), respectively. These three derivatives of camptothecin showed similar patterns of differential response among 32 cell lines, that is, their spectra of in vitro cytotoxicity were almost the same. The antitumor activity of three doses of DX-8951f administered i.v. at 4-day intervals against human gastric adenocarcinoma SC-6 xenografts was greater than that of CPT-11 or SK&F 10486-A. Moreover, it overcame P-glycoprotein-mediated multi-drug resistance. These data suggest that DX-8951f has a high antitumor activity and is a potential therapeutic agent.

Animals↗

PubMed1995

Effects of nicorandil on left ventricular systolic and diastolic function in patients with hypertrophic cardiomyopathy.

Various evidence suggest that myocardial ischemia is a major factor in the progression of hypertrophic cardiomyopathy (HCM). In this study, we investigated the effects of nicorandil on left ventricular (LV) systolic and diastolic function in 12 symptomatic patients with HCM using echocardiography and radionuclide angiography. Nicorandil (6 mg), when administered intravenously, produced no significant changes in any parameter, including LV filling dynamics. However, accelerated LV peak early filling velocity (0.51 +/- 0.13 to 0.59 +/- 0.14 m/sec, p < 0.01), and reduced peak velocity in atrial contraction (0.54 +/- 0.17 to 0.50 +/- 0.15 m/sec, p < 0.05) were observed by Doppler echocardiography after 4 weeks of oral administration of 10 mg nicorandil 3 times daily. This oral administration did not affect heart rate, blood pressure, LV outflow gradient, or LV systolic function. The same favorable results were observed in a wall motion analysis with radionuclide angiography: peak filling rate (PFR) in global LV (3.21 +/- 0.76 to 3.52 +/- 0.87 end-diastolic volume (EDV)/sec, p < 0.02), and apical (4.73 +/- 1.18 to 5.42 +/- 1.55 EDV/sec, p < 0.01) and lateral (4.78 +/- 1.60 to 5.52 +/- 1.51 EDV/sec, p < 0.05) segments was increased, and the time to peak filling rate (TPF) in septal (245 +/- 31 to 203 +/- 40 msec, p < 0.01) and lateral (222 +/- 54 to 193 +/- 34 msec, p < 0.05) segments was reduced. These findings indicate that nicorandil has beneficial effects on LV diastolic function in HCM. These favorable effects may be due to the improvement of subendocardial ischemia.

Adult↗

PubMed1995

Flow cytometric analysis and immunohistochemistry of delayed-type hypersensitivity responses in mice immunized with rat hepatocytes.

Delayed-type hypersensitivity (DTH) responses to rat hepatocytes (HCs) in mice were investigated by flow cytometric analysis and immunohistochemistry with monoclonal antibodies directed against murine class II, CD4, and CD8 antigens. Mice were immunized subcutaneously (s.c.) with 10(6) rat HCs (referred to as s.c.-immunized mice), and control mice were injected s.c. with sterile Hanks' solution (non-immunized mice). Four days later, 10(5) rat HCs were injected into the footpad of s.c.-immunized mice and non-immunized mice. The DTH response in s.c.-immunized mice significantly increased after challenge when compared to that in non-immunized mice. The numbers of class II+, CD4+, and CD8+ cells in the footpad, and CD4+ and CD8+ cells in the inguinal lymph node of s.c.-immunized mice significantly increased during the DTH response. An increase in the number of CD4+ cells in the footpad of s.c.-immunized mice after challenge was more significant than that of non-immunized mice. The number of CD4+ cells increased more markedly in the footpad of s.c.-immunized mice as compared to that of CD8+ cells. Furthermore, immunohistochemical studies of the footpad of s.c.-immunized mice showed more severe infiltration of CD4+ cells rather than CD8+ cells at the injection site of rat HCs. These results suggest that the DTH response in the footpad of mice immunized with rat HCs is associated with severe infiltration of CD4+ cells.

Animals↗

PubMed1995

[Characterization of intraoperative rupture of epithelial ovarian cancer at early stage].

OBJECTIVE: To investigate whether intraoperative rupture of epithelial ovarian cancer. influences the prognosis. METHODS: Between 1984 and 1994, 46 patients with stage Ia and Ic epithelial ovarian cancer were treated at Oita Medical University Hospital. Of 46 patients, 20 had stage Ia tumors, 16 stage Ic secondary to capsular invasion-serosal disease or positive ascites or washings (stage Ic-ascites), and 10 stage Ic secondary to intraoperative rupture (Ic-rupture). Survival analysis was performed to compare the three groups of patients. RESULTS: The ages (mean +/- SD) of patients with stage Ia, Ic-ascites and Ic-rupture at the first diagnosis were 40.1 +/- 17.0, 47.6 +/- 13.4 and 52.8 +/- 15.7, respectively. The age of the stage Ia group tended to be lower than those of the Ic-ascites and Ic-rupture groups. At operation, ovarian tumors of all patients in the Ic-rupture group were firmly adhered to surrounding organs, had markedly thin weak cyst walls and were easily ruptured during operation. Fourteen of 20 patients in the Ia group (70%), 5 of 16 patients in the Ic-ascites group (31.3%) and 3 of 10 patients in the Ic-rupture group (30%) showed signs of mucinous cystadenocarcinoma. The incidence of mucinous cystadenocarcinoma in Ia group was significantly lower than in the Ic-ascites (p < 0.025, chi 2-test) and Ic-rupture (p < 0.05, chi 2-test) groups. The Kaplan-Meier survival plot for stage Ia, Ic-ascites and Ic-rupture patients revealed a probability of 5-year survival of 100%, 87.5% and 63.5%, respectively. The probability of 5-year survival in the Ic-rupture group tended to be lower than that in other groups. CONCLUSIONS: The results of our study suggest that intraoperative rupture of a malignant ovarian cystic tumor may worsen the prognosis of patients with the FIGO stage I epithelial ovarian cancer.

Adolescent↗

PubMed1995

[Clinical features of epithelial ovarian cancer in young reproductive women].

A 10-year retrospective review of epithelial carcinoma of the ovary was performed about 95 patients which were diagnosed and treated at the Oita Medical University Hospital. The patients' ages at the first diagnosis ranged from 15 to 85 years with a mean of 51.6 years. Twenty-two of 95 patients (23.2%) were below the age of 40. Most patients analysed in this study complained of lower abdominal pain, lower abdominal mass, and/or lower abdominal fullness. Sixteen of 22 patients under the age of 40 (72.7%) and 27 of 73 patients over the age of 40 (37.0%) were diagnosed as having mucinous cystadenocarcinoma. The incidence of mucinous cystadenocarcinoma below the age of 40 was significantly higher than that over the age of 40 (p < 0.005, chi 2-test). Eleven patients below the age of 40 had FIGO stage Ia grade 1 disease and 2 of these patients were pregnant. The incidence of stage Ia disease under the age of 40 was significantly higher than that over the age of 40 (p < 0.005, chi 2-test). Both pregnant patients and 5 other patients with stage Ia disease were treated with only unilateral salpingo-oophorectomy. All patient with stage Ia disease had no evidence of recurrence within 5 years. This suggests that conservative surgery may be considered as the treatment for the FIGO stage Ia grade 1 ovarian cancer.

Adolescent↗

PubMed1995

Blood polychlorinated biphenyls and manifestation of symptoms in chronic "Yusho" patients.

The correlation between blood PCB concentration and clinical manifestation of symptoms was investigated in 259 chronic "Yusho" patients, using the information obtained from the nationwide health examination conducted in 1988, twenty years after the outbreak. Concentrations of blood PCBs ranged 0.6-32.0 ppb (mean; 4.78), and they were categorized into approximate quartile for analysis. For general fatigue, odds ratios at 2.7+, 4.1+, and 6.1+ ppb were 2.4, 3.6, and 3.1, respectively, with a reference category of < 2.7 ppb (test for trend; p < 0.005). For numbness in extremities, the corresponding odds ratios were 2.8, 2.8, and 2.9(p < 0.005). For comedone, they were 1.4, 1.0, and 4.0 on face (p < 0.025); and 3.6, 4.6, and 9.5 on trunk (p < 0.005), respectively. A distinctive increase in odds ratio was observed at 2.7 ppb for these two subjective symptoms; and at 6.1 ppb for skin symptoms. The blood PCB concentrations among patients were relatively close to the normal subjects. Therefore, the observed correlations may be due to the effects of PCBs with a peculiar pattern in components, PCQs or PCDFs, taken and retained in the patients. Association with blood PCBs was also suggested for headaches; abnormal breath sounds; and acneiform eruptions in the genital region, but were statistically insignificant. None of the eye symptoms showed significant association with blood PCBs.

Adult↗

PubMed1994

Isolation of a cDNA encoding the chicken p50B/p97 (Lyt-10) transcription factor.

NF-kappa B is a transcription factor composed of the p50 and p65 subunits. Recent works identified another human gene which encodes a molecule related to the p50 subunit, termed p50B, p49 or lyt-10. Here, we isolated the cDNA clones encoding chicken p50B/p97 (Lyt-10). The deduced amino acid sequence of the precursor protein, p97, shows conservation of the overall structure, and 86% identity in the Rel homology domain (RHD) and 56% identity in the ankyrin repeat domain (ARD) to human p50B/p97. Expression of this gene is highest in the chicken spleen.

Amino Acid Sequence↗

PubMed1994

Identification and carbohydrate specificity of a chicken serum mannan-binding protein reactive with a Ra chemotype strain of Salmonella typhimurium.

To compare a chicken serum mannan-binding protein (MBP) with a chicken Ra-reactive factor (RaRF), both serum proteins were isolated by combination of different chromatography. In SDS-PAGE, both purified proteins were resolved into a major protein band with a molecular weight of 34,000 and a few minor protein bands. In Western blotting with both purified proteins, only a single band with a molecular weight of 34,000 was detected with anti-chicken serum MBP antibody, indicating that the major protein band of chicken serum MBP and RaRF are antigenically identical. The combining sites of these two proteins were most reactive with N-acetylmannosamine followed by mannose, N-acetylglucosamine, and L-fucose. These findings suggest that chicken serum MBP may be identical to its corresponding bactericidal factor RaFR in terms of antigenicity and monosaccharide specificity.

Acute-Phase Proteins↗

PubMed1994

Serum concentration of a bovine mannan-binding protein reactive with a Ra chemotype strain of Salmonella typhimurium: no significant changes associated with mastitis.

The serum concentration of a bovine mannan-binding protein reactive with a Ra chemotype strain of Salmonella Typhimurium in sera from cows with or without mastitis were determined by sandwich enzyme-linked immunosorbent assay. From the results obtained for 10 healthy cows aged 2 to 7 years, mean +/- SD serum concentrations of MBP in bovine sera were 77.5 +/- 33.1 micrograms/ml. Concentrations in 7 healthy heifer calves aged 6 months were 52.2 +/- 10.2 micrograms/ml, whereas those in 7 healthy bullocks 65.8 +/- 21.8 micrograms/ml. Concentrations in 4 cows aged 4 to 7 years with mastitis were slightly lower (34 to 72 micrograms/ml). After recovery, the serum concentrations rose to the normal concentrations in healthy cows. These findings indicate that the serum concentrations of bovine MBP decrease during mastitis, suggesting that bovine MBP may not be an acute phase reactant.

Acute-Phase Proteins↗

PubMed1993

Analysis of chicken CD4 by monoclonal antibodies indicates evolutionary conservation between avian and mammalian species.

We have created a panel of mouse monoclonal antibodies detecting different epitopes on avian CD4 molecule. Two-color immunofluorescence analysis shows that chicken peripheral alpha beta T cells are either CD4 or CD8 single positive whereas most gamma delta T cells are CD4-negative both in the thymus and peripheral tissues. Unlabeled antibody competition analysis by flow cytometry demonstrates that several different epitopes on chicken CD4 are recognized by these antibodies. Antibodies precipitate a monomeric glycoprotein from surface-labeled chicken thymocytes and T cells with relative molecular mass (M(r) of 64 kd as analyzed by SDS gel electrophoresis. Removal of N-linked carbohydrates by endoglycosidase-F increases the electrophoretic mobility and reveals the core protein size with M(r) of 45 kd. The anti-CD4 antibodies inhibit antigen-induced cellular proliferation of a keyhole limpet hemocyanin (KLH) -specific T cell line. They synergize in the blocking of T cell proliferation with anti-class II major histocompatibility complex (MHC)-specific antibodies indicating that chicken CD4 is involved in antigen recognition process by CD4+ T cells. We also show that chicken CD4 is down-modulated in a similar manner as its mammalian equivalent when thymocytes are stimulated in vitro with phorbol esters. Altogether these findings suggest functional and biochemical conservation of the CD4 molecule in evolution.

Animals↗

PubMed1992

Noninvasive detection of left ventricular diastolic dysfunction using M-mode echocardiography to assess left ventricular posterior wall kinetics in hypertrophic cardiomyopathy.

In patients with hypertrophic cardiomyopathy (HC), it is difficult to determine the severity of left ventricular (LV) diastolic dysfunction. Three different patterns of LV posterior wall motion were found by M-mode echocardiography in patients with HC, and the use of these patterns is proposed as a new noninvasive index of the severity of LV diastolic dysfunction. M-mode echocardiograms were recorded prospectively from 35 patients with HC, and the posterior wall motion pattern in late systole and early diastole was classified into the following 3 types: (1) normal motion (n = 9); (2) flat motion--flat motion from late systole to early diastole, followed by rapid backward movement (n = 13); and (3) downward motion--slow backward movement from late systole (n = 13). There were no differences in the severity or type of hypertrophy, LV systolic function and pulsed Doppler indexes of LV filling among these 3 groups. However, LV end-diastolic pressure was increased in the groups with flat (15 +/- 6 mm Hg) and downward (16 +/- 9 mm Hg) motion. Furthermore, the maximal rate of decrease in LV pressure (normal 1,450 +/- 300, flat 1,250 +/- 300 and downward 860 +/- 80 mm Hg/s) and the time constant of LV pressure reduction (normal 60 +/- 15, flat 70 +/- 25 and downward 101 +/- 34 ms) showed a stepwise deterioration from the normal to the flat and then to the downward motion groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

PubMed1992

Structures of grain boundaries in long-chain Te crystals observed by high-resolution transmission electron microscopy.

Vacuum-deposited Te crystals, composed of endless chains of the right-handed or left-handed spiral, have been investigated by high-resolution electron microscopy with the aid of image simulation. A (010) grain boundary, which accompanies edge dislocations having an extra layer of the width of one Te chain, has been observed. A through-focal series of images reveal that it is not a reflectional nor a rotational twin boundary but a small angle grain boundary in a single crystal or an inversion twin. The lattice on one side of the boundary is shifted from that on the other side by [001]c/3 + [120]a/8, and inclined at 1.1 degrees around the c-axis of the other side. Also found between crystallites of [100] and [011] orientation is a grain boundary which is built with the (011) facets on one side of the boundary and the (211) or (0,1,10) facets on another side.

Crystallization↗

PubMed1992

Alteration of the curved helical structure located in the upstream region of the beta-lactamase promoter of plasmid pUC19 and its effect on transcription.

The region preceding the beta-lactamase promoter of Escherichia coli plasmid pUC19 has a curved DNA (bent DNA) structure. The center of the curvature was revealed to exist around nucleotide position 2580 of the plasmid, which is just beside RNA polymerase binding region. It was indicated that the identified region is curved even at 60 degrees C. The gross geometry of the curvature was altered by inserting synthetic double-stranded oligonucleotides between positions 2585 and 2586. Effect of the alteration on strength of the promoter was not detected in vitro. However, in vivo analyses showed that the promoter strength is apparently dependent, in part, on the gross geometry of the curvature. Insertions of 4 and 16 bp, both of which altered the gross geometry of the curvature greatly, caused considerable reductions of in vivo level of beta-lactamase mRNA. In vivo, overall three-dimensional structure of the region covering the promoter and the curvature seems to play some significant role in transcription of the gene.

Base Sequence↗

PubMed1992

Differentiation profiles of normal blast cell colonies derived from mononucleated cells, T cell depleted nonadherent cells and CD33-negative, CD34-positive normal human bone marrow cells.

Blast cell colonies can be grown reproducibly in methylcellulose from normal human mononuclear bone marrow cells (MNC) in the presence of 30% human plasma, 1 U human recombinant erythropoietin and 10% of medium conditioned by phytohemagglutinin stimulated leukocytes as a source of growth factors. The colonies can be recognized by inverted microscopy by their display of highly refractile cytoplasmic structures that resemble small vacuoles. A proportion of cells within these colonies remains CD34-positive (CD34+). The blast-like morphology of these cells was sustained for at least 14 to 21 days. The frequency of blast cell colony forming units (CFU-BL) can be increased by a series of separation procedures to produce E-rosette depleted, nonadherent cells (E-NAC), CD34+ cells and CD33-CD34+ cells. The mean number of CFU-BL per 10(5) cells was 1.9 +/- 1.6 in MNC, 5.7 +/- 2.7 in E-NAC, 108 +/- 51 in CD34+ cells and 112 +/- 109 in CD33-CD34+ cells. The enrichment procedures were not specific for CFU-BL but also resulted in a similar increase of multilineage and single lineage progenitors. The relative proportions of CFU-BL and other progenitors remained unchanged among these subpopulations. The size of individual blast cell colonies on day 16 varied from 20 to 1,600 cells. After 14 to 21 days, cells within blast cell colonies acquired mature morphological features. The majority of blast cell colonies developed into multilineage colonies (62%); some (38%) were restricted to a single hemopoietic lineage. Larger blast cell colonies had a higher probability of developing into multilineage colonies than smaller blast cell colonies.

Antigens, CD↗

PubMed1992

Various factors associated with the manifestation of influenza-like illness.

A survey enrolling 814 schoolchildren was conducted immediately after a peak epidemic in the 1988-1989 influenza season and then a case-control study for influenza-like illness (ILI) was carried out using information concerning illness onset and usual lifestyle. Based on the analysis of the correlations among symptoms and actions taken due to symptoms, cases were defined as those with fever greater than or equal to 38 degrees C and subsequent absenteeism and medical consultation during peak epidemic; within this, mild-ILI (MILI) was defined as fever greater than or equal to 38 degrees C and less than 39 degrees C, and severe-ILI (SILI) as fever greater than or equal to 39 degrees C. Controls were defined as those with no symptoms (NS) during that period. Adjusted odds ratios (OR) were obtained through an unconditional logistic regression model between the MILI (80) or SILI (48) and NS (196) groups from among respondents (803). For MILI, increased risks were observed for easily-inflamed tonsils (OR = 3.0, 95% CI: 1.7-5.4); and larger family size (1.9, 1.1-3.4); with decreased risks for higher school grades (0.4, 0.2-0.9); frequent intake of vegetables or fruits other than green/yellow vegetables (0.5, 0.3-1.0); and larger room space per capita (0.4, 0.2-0.9). For SILI, there were increased risks for easily-inflamed tonsils (3.8, 1.8-8.1) and history of doctor-diagnosed asthma (2.9, 1.2-6.7); and decreased risks for higher grades (0.2, 0.1-0.6), frequent intake of milk or dairy products (0.3, 0.1-0.6) and vaccination (0.3, 0.1-0.8).

Case-Control Studies↗

PubMed1992

Imbalance of deoxyribonucleoside triphosphates and DNA double-strand breaks in mouse mammary tumor FM3A cells treated in vitro with an antineoplastic tropolone derivative.

The mechanism by which alpha,alpha-bis(2-hydroxy-6-isopropyltropon-3-yl)-4-methoxytolu ene (JCI-3661) kills mouse mammary tumor FM3A (F28-7) cells was studied. When the cells were exposed to the drug at 3.7 microM, the intracellular dNTP pool became imbalanced because of decreases in dGTP and dATP and an increase in dTTP. The pattern of the dNTP imbalance was the same as that caused by hydroxyurea. When JCI-3661 was added to the culture medium, mature DNA strands broke, giving fragments of 100-200 kilobase pairs long as found by orthogonal-field-alternation gel electrophoresis. DNA strand breaks, detected by this technique, were observed in the cells at 12 h after the addition. The beginning of cell death was observed at about 14 h (trypan blue staining) or at about 12 h (colony-forming ability) after cultivation Breaks in the single and double strands of DNA, as measured by alkaline and neutral filter elution assay, became evident 24 h after treatment with 3.7 microM JCI-3661. Comparison of the ratio of single- and double-strand breaks caused by JCI-3661 to that following radiation suggested that JCI-3661 broke only double strands. Cycloheximide inhibited both the breakage of double strands and the cell death caused by JCI-3661. JCI-3661 decreased DNA synthesis more than RNA or protein synthesis. The breaks in double strands of DNA were probably important in the cell death caused by JCI-3661.

Animals↗