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Biomedical subjects

T Yano

Publications and source records attributed to T Yano.

At least 433 records · Page 24Linked to original sources

Enhancing effect of high dietary iron on lung tumorigenesis in mice.

In our previous reports we indicated that oxidative stress on pulmonary nuclei caused by oxy radicals could be involved in glycerol-enhanced lung tumorigenesis in ddY mice treated with 4-nitroquinoline 1-oxide (4NQO). This study was undertaken to estimate if dietary iron could act as a stimulating factor on lung tumorigenesis in mice treated with 4NQO plus glycerol. Feeding excessive iron to mice treated with these agents significantly increased nuclear thiobarbituric acid reactive substances (TBARS) and DNA single strand breaks (DNA-SSB) in the lungs as compared with mice fed adequate iron 4 weeks after 4NQO injection. Nuclear non-haem iron level in mice fed excessive iron was also higher than the level in mice fed adequate iron. Twenty-three weeks after 4NQO injection (at the end of this experiment) the supply of excessive iron for 4 and 23 weeks after 4NQO injection stimulated the development of lung tumors in mice treated with 4NQO plus glycerol. These results suggest that a high dietary iron level acts as a stimulating factor on lung tumorigenesis in mice treated with 4NQO plus glycerol.

4-Nitroquinoline-1-oxide↗

Mediation of the physiological response of platelets by interactions of spectrin and protein 4.1 with the cytoskeleton.

Spectrin and protein 4.1 became associated with the Triton-insoluble cytoskeletons during platelet activation. Inhibition of platelet activation by a PGI2 analogue resulted in release of the proteins from the cytoskeletons. Changes in subcellular distributions of the proteins preceded changes in the state of platelet aggregation. These results suggest that interactions of spectrin and protein 4.1 with the cytoskeletons are involved in mediating the physiological response of the platelet.

Actins↗

Effect on insulin sensitivity of angiotensin converting enzyme inhibitors with or without a sulphydryl group: bradykinin may improve insulin resistance in dogs and humans.

The present study compared the effect on insulin sensitivity of ACE inhibitors with a sulphydryl group (captopril) or those without a sulphydryl group (delapril and enalapril) during the hyperinsulinaemic euglycaemic clamp test in both animal and clinical experiments. A possible contribution of bradykinin to the improvement of insulin sensitivity by ACE-inhibition was also studied. In healthy control and depancreatized dog experiments, administration of captopril either intravenously (3.0 mmol.kg-1) or orally (5.0 mmol.kg-1) increased insulin sensitivity indices and plasma bradykinin concentrations. In comparison, intravenous administration of an active metabolite of delapril (3.0 mmol.kg-1) and oral administration of either delapril or enalapril (5.0 mmol.kg-1) showed slight, but not significant increases in insulin sensitivity indices and plasma bradykinin concentrations. Infusion of a bradykinin antagonist (N-alpha-adamantane-acetyl-D-Arg-[Hyp3,Thi5,8,D-Phe7]-b bradykinin) (0.5 nmol.kg-1 x min-1) abolished the effect of captopril on insulin sensitivity. Furthermore, intravenous administration of bradykinin (0.1 nmol.kg-1 x min-1) increased insulin sensitivity indices. In clinical experiments, insulin sensitivity indices decreased in the following order: normotensive healthy subjects, hypertensive non-diabetic patients, normotensive NIDDM patients and hypertensive NIDDM patients. In these four groups, oral administration of captopril (2.0 mmol.kg-1) significantly increased insulin sensitivity indices, and a concomitant increase in plasma bradykinin concentrations was observed. By contrast, oral administration of enalapril or delapril showed slight, but not significant effects on insulin sensitivity indices and plasma bradykinin concentrations. From these studies, it is concluded that ACE inhibitors with a sulphydryl group have more potent action on the improvement in insulin sensitivity than those without a sulphydryl group.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗

MRI of pituitary adenomas: the position of the normal pituitary gland.

The position of the normal pituitary gland, assessed using gadolinium - enhanced MRI was compared with the position found at surgery for pituitary adenoma in 25 patients. The tumours were five microadenomas and 20 macroadenomas. Using T1-weighted imaging, the anterior lobe could be differentiated on the sagittal image in five patients (20%) and on the coronal image in four (16%). The high intensity of the posterior lobe could be differentiated using T1-weighted sagittal imaging in 13 patients (52%). The normal pituitary gland, which enhanced more strongly than tumour, could be differentiated using Gd-DTPA-enhanced MRI on the sagittal images in 22 cases (88%) and on the coronal image in 17 (68%). In seven patients, the normal pituitary gland surrounded the tumour; it was displaced superiorly in 14 cases and superioposterorly in two but in no case was it displaced anteriorly or downwards.

Adenoma↗

Embolisation of orbital varix.

A 34-year-old man with intermittent exophthalmos, found to have a large varix in the right orbit, was treated by endovascular surgery. Percutaneous transfemoral venous catheterisation and embolisation of the orbital varix was performed on two occasions. A Tracker 18 microcatheter was introduced through the right inferior petrosal sinus, cavernous sinus, superior ophthalmic vein and then into the varix, following a guidewire. Superselective venography of the right ophthalmic vein showed the varix. A total of 204 platinum microcoils was used to pack the varix. At the time of discharge, the exophthalmos had largely resolved. As this technique is much less invasive than surgical resection, we recommend an attempt at endovascular embolisation of orbital varices prior to surgical removal.

Adult↗

Ras oncogene enhances the production of a recombinant protein regulated by the cytomegalovirus promoter in BHK-21 cells.

In order to enhance recombinant protein productivity in animal cells, we developed the oncogene activated production (OAP) system. The OAP system is based on the premise that oncogenes are able to enhance promoter activity. To this end, we constructed reported plasmids by fusing various promoters to the human interleukin-6 (hIL-6) cDNA, and the effector plasmids by inserting individual oncogenes, for example c-myc, c-fos, v-jun, v-myb and c-Ha-ras, downstream from the human cytomegalovirus immediate early (CMV) promoter. Results of transient expression experiments with BHK-21 cells suggest that the CMV promoter is the most potent promoter examined and that the ras product is able to transactivate the beta-actin, CMV and SR alpha promoters. Recombinant BHK-21 cells producing hIL-6 under the control of the CMV promoter were contransfected with the ras oncogene and dihydrofolate reductase gene, then selected with 50 nM methotrexate to coamplify the ras oncogene. We were able to rapidly establish a stable and highly productive clone which exhibited a 35-times higher production rate as compared to the control value.

Actins↗

Comparative study on factors regulating the level of oxidative stress toward pulmonary nuclei in two different strains of mice.

1. The levels of active oxygen formed and thiobarbituric acid reactive substances (TBARS) in pulmonary nuclei of A/J strain were higher than those in the nuclei of ddY strain, while nuclear alpha-tocopherol level in the lungs of the former strain was lower than the the level in the latter strain. 2. Unsaturation index (UI) of nuclear fatty acids and oxidative damage to DNA in the lungs of A/J strain were higher than those in the lungs of ddY strain. 3. These results suggest that the capacity of nuclear active oxygen formation, nuclear alpha-tocopherol level and UI of nuclear fatty acids in the lungs can be main factors to regulate oxidative stress toward the pulmonary nuclei in the two strains of mice.

Animals↗

The metabolic fate of apolipoprotein A-I-containing lipoproteins internalized into HepG2 cells: resecreted lipoproteins as a potent inducer for cholesterol efflux.

In a chase study using double-radiolabeled apolipoprotein (apo) A-I-containing lipoproteins (14C-labeled cholesteryl ester and 125I-labeled apolipoprotein) with or without apo A-II (Lp A-I/A-II particle and Lp A-I particle), these lipoproteins internalized into HepG2 cells were demonstrated to be time-dependently released into the medium as trichloroacetic acid (TCA)-precipitable fraction. The molar ratio of 14C/125I-radioactivity of TCA-precipitable fraction in the medium was time-dependently decreased. In Sephacryl S-300 HR chromatography of both circulating mature and resecreted apo A-I-containing lipoproteins in the medium after the chase period, a single major protein peak corresponding to that of high density lipoproteins was detected by absorbance at 280 nm. The 14C-radioactivity in apo A-I-containing lipoproteins resecreted from HepG2 cells after 3-h chase was approximately one-fourth of that in circulating mature apo A-I-containing lipoproteins. Cholesterol mass in resecreted apo A-I-containing lipoproteins was three-tenths of that in circulating mature apo A-I-containing lipoproteins. In a cholesterol efflux experiment using macrophage foam cells labeled with [3H]cholesterol, apo A-I-containing lipoproteins resecreted significantly decreased cholesteryl ester radioactivity in macrophage foam cells, as compared with circulating mature apo A-I-containing lipoproteins. There were no remarkable differences in the metabolic fates and cholesterol efflux from macrophage foam cells between Lp A-I and Lp A-I/A-II particles. These results suggest that a part of apo A-I-containing lipoproteins internalized into HepG2 cells may be resecreted in the form of intact lipoproteins with lower cholesterol content, and apo A-I-containing lipoproteins resecreted may be a potent inducer for cholesterol efflux through the processes of reverse cholesterol transport.

Animals↗

Isolation of a carp complement protein homologous to mammalian factor D.

Factor D of carp (Cyprinus carpio) complement was purified to apparent homogeneity by a 4-step chromatographic procedure and examined for physicochemical and functional properties. Carp factor D proved to be an alpha-globulin with a molecular mass of 29 kDa and the serum concentration was estimated to be 6 micrograms/ml. The NH2-terminal amino acid sequence (30 residues including five unidentified positions) of carp factor D showed high homologies (57-60%) to those of mammalian factor D. Neither functional compatibility nor common antigenicity was observed between carp and human factor D. This report is apparently the first description on the factor D molecule in a non-mammalian species.

Amino Acid Sequence↗

Genes coding for Shiga-like toxins in bovine verotoxin-producing Escherichia coli (VTEC) strains belonging to different O:K:H serotypes.

Forty-six verotoxin-producing Escherichia coli (VTEC) strains isolated from diarrhoeic and healthy calves in Spain were examined for DNA sequences homologous to genes for verotoxins (VT1 and VT2) and enterotoxins (LT-I, LT-II, STaH, STaP and STb). Hybridisation showed that 26 (57%) of VTEC strains carried VT1 genes, 13 (28%) possessed VT2 genes, and 7 (15%) carried both VT1 and VT2 genes. No VTEC strains hybridised with DNA probes for enterotoxins. A correlation was found between the serotype and type of VT produced. Thus, all strains of serotypes O26:K-:H11 (13 strains), O103:K-:H2 (3 strains) and O128:K?:H- (4 strains) hybridised with the VT1 probe only, whereas all strains of serotypes O4:K-:H4 (3 strains) and O113:K-:H21 (4 strains) were positive with the VT2 probe only. By contrast, O81:K?:H28 (2 strains) and O157:K-:H- (2 strains) strains hybridised with both VT1 and VT2 probes. One strain of serotype O157:K-:H7 was VT2 positive.

Animals↗

Impaired follicular growth and abnormal luteinizing hormone surge in luteal phase defect.

OBJECTIVE: To determine whether luteal phase defect (LPD) is associated with follicular growth or LH surge. DESIGN: The length of luteal phase was determined by the date of ovulation assessed by serial ultrasound measurements of follicle growth on a daily basis. Luteal phase defect was defined when the length of the luteal phase was < 11 days and/or the midluteal serum P level was < 10 ng/mL (31.8 nmol/L). Preovulatory follicular growth was examined by transvaginal ultrasonography. Blood samples taken at midluteal phase were assayed for P. Urine LH levels were determined in samples collected twice a day during periovulatory cycles using rapid urinary assay kits. SETTING: Infertility outpatient clinic, Tokyo University Hospital. PATIENTS: Eighty-one menstrual cycles from 63 normally cycling infertile women who were not administered any medications. RESULTS: Thirty-six of 81 cycles showed LPD. The mean +/- SD maximal preovulatory follicular diameter was significantly smaller in LPD cycles than in non-LPD cycles (16.5 +/- 2.7 versus 19.0 +/- 2.8 mm). The mean +/- SD peak level of urinary LH surge was significantly lower in LPD cycles compared with non-LPD cycles (50 +/- 25 versus 65 +/- 21 IU/L). Luteal phase defect cycles showed a relatively high incidence of abnormal LH surges, namely, lower peak levels or prolonged duration. CONCLUSIONS: Luteal phase defect was associated with impaired follicular growth and/or abnormal LH surge. These factors may be involved in the pathogenesis of LPD.

Estradiol↗

Application of in vivo microdialysis to transdermal absorption of methotrexate in rats.

Microdialysis was applied to determine the in vivo transdermal absorption of methotrexate (MTX) in rats with or without a new penetration enhancer, 1-[2-(decylthio)ethyl]azacyclopentan-2-one (HPE-101). A solution composed of 2.5 mM MTX and 3% (w/v) HPE-101 was applied to the shaved abdomen, in which a semipermeable membrane cannula of 10-mm length was inserted intracutaneously with the use of an L-shaped needle. Intradermal microdialysis was performed at a flow rate of 1.0 microL/min for 12 hr. The concentration of MTX in the dialysate was measured by fluorescence polarization immunoassay (FPIA). HPE-101 (3%, w/v) significantly increased the dermal MTX concentration from 0.06 +/- 0.04 microM in the control to 56 +/- 26 microM in the dialysate from 8 to 12 hr. HPE-101 at concentrations of 0.75, 1.5, 2.25, and 3% (w/v) enhanced the total recovery of MTX in dermal dialysate from 0 to 10 hr by approximately 5, 18, 42, and 500 times compared with the control, respectively. The microdialysis system is useful for assessing in vivo transdermal drug absorption.

Administration, Cutaneous↗

Phylogenetic place of guinea pigs: no support of the rodent-polyphyly hypothesis from maximum-likelihood analyses of multiple protein sequences.

Graur et al.'s (1991) hypothesis that the guinea pig-like rodents have an evolutionary origin within mammals that is separate from that of other rodents (the rodent-polyphyly hypothesis) was reexamined by the maximum-likelihood method for protein phylogeny, as well as by the maximum-parsimony and neighbor-joining methods. The overall evidence does not support Graur et al.'s hypothesis, which radically contradicts the traditional view of rodent monophyly. This work demonstrates that we must be careful in choosing a proper method for phylogenetic inference and that an argument based on a small data set (with respect to the length of the sequence and especially the number of species) may be unstable.

Animals↗

Phosphofructokinase activity as a measure of maturation of rat oocytes developed in vivo and in vitro.

We determined the activity of phosphofructokinase (PFK), a rate-limiting enzyme of glycolysis, in the rat oocyte during maturation either by luteinizing hormone stimulation in vivo or by cultivation under various conditions. In vivo, the activity of PFK in the maturing oocyte increased significantly, suggesting that the glycolytic pathway developed as the first meiotic division proceeded. A breakdown of the germinal vesicle and an increased activity of PFK were observed when denuded oocytes were cultured. Treatment of the oocytes with dibutyryl cAMP and 3-isobutyl-1-methyl xanthine almost completely inhibited germinal breakdown, whereas the activity of PFK increased significantly. The data suggest that regulation of PFK activity is not directly dependent on cAMP or cAMP-dependent protein kinase, and is not necessarily dependent on meiotic maturation. Our study also revealed that epidermal growth factor (EGF) significantly increased PFK activity, showing that EGF may be a potent inducer of oocyte maturation.

1-Methyl-3-isobutylxanthine↗

Association of Mycoplasma pneumoniae antigen with initial onset of bronchial asthma.

Although mycoplasmal airway infection frequently exacerbates bronchial asthma, the cause of the initial onset of asthma remains unclear at present. In this report, we describe a patient in whom a previous acute mycoplasmal respiratory infection led to an initial onset of bronchial asthma. One month after the onset of the illness, cough and wheezing appeared. Pulmonary function studies revealed an airway obstructive dysfunction. Oral administration of bronchodilators resulted in a marked improvement of the asthmatic symptoms. An airway hyperresponsiveness to methacholine was demonstrated even 2 yrs after the initial onset of the illness, and IgE antibody specific to Mycoplasma pneumoniae was detected in the serum by use of enzyme-linked immunosorbent assay. An immediate skin test for M. pneumoniae was positive in addition to multiple positive skin tests. A bronchial inhalation challenge test with M. pneumoniae antigen also yielded a positive result. We conclude that the effects of mycoplasmal respiratory infections on the airway are multifactorial and involve a complex interplay of airway inflammation and IgE-mediated hypersensitivity.

Adult↗

Electrophoretic analysis of a gastric cancer-associated acid proteinase using a highly sensitive detection system.

A highly sensitive detection system for acid proteinase separated on polyacrylamide gel was established. This system consisted of two-dimensional electrophoresis, combined with isoelectric focusing and polyacrylamide gel electrophoresis, and casein clotting (caseogram). Human urine, serum and gastric tissues obtained from normal individuals and gastric cancer patients were analyzed using this system. The previous electrophoretic method was not sufficiently sensitive to detected small amounts of pepsinogen (PG) C in normal urine. However, the new rapid and sensitive method clearly revealed its presence. In gastric tissue containing cancer cells, an additional proteinase, which was not present in normal tissue, was detected and named medium moving proteinase (MMP). MMP resembled PGs in alkaline stability rather than the non-PG proteinase, slow moving proteinase (SMP).

Adult↗

In vivo microdialysis for the transdermal absorption of valproate in rats.

The suitability of sampling via microdialysis for a lipophilic drug, valproate (VPA), was evaluated by the elimination rate constant of VPA solution in an in vitro experimental first-order elimination system. The elimination rate constant of VPA in dialysate was found to be 0.43 +/- 0.05h-1, which was in good agreement with the real elimination rate constant (0.46 +/- 0.02h-1). A change in VPA concentration in the solution surrounding a microdialysis probe was well maintained by the microdialysis method, suggesting no adsorption between the membrane of the microdialysis probe and VPA. On the basis of the in vitro experiment, the effect of a penetration enhancer, 1-[2-(decylthio)ethyl]azacyclopentan-2-one (HPE-101), on the transdermal absorption of VPA was examined in rats by the use of microdialysis in vivo. An intradermal microdialysis was performed at a flow rate of 1.0 microliter/min for 7h after the dermal application of 50 mM VPA solution with or without 3% (w/v) HPE-101. HPE-101 increased the transdermal absorption rate of VPA by 80 times compared with the control. The microdialysis system was found to be quite useful for assessing the in vivo transdermal absorption of a lipophilic VPA.

Animals↗

Modulatory role of epidermal growth factor in follicle-stimulating hormone-induced DNA synthesis in cultured rat granulosa cells.

Epidermal growth factor (EGF) modestly increased DNA synthesis by cultured rat granulosa cells. FSH also stimulated DNA synthesis dose-relatedly with the maximal effect occurring at FSH 100 ng/ml. The stimulatory effect of FSH was still greater than that of EGF. However, in the presence of EGF, the stimulatory effect of FSH at any concentration was regulated to the level as high as when EGF alone stimulates. In addition, EGF inhibited DNA synthesis induced by forskolin, but enhanced the action of (Bu)2cAMP additively, which indicates that EGF attenuates DNA synthesis of granulosa cells by suppressing the activity of adenylate cyclase or cAMP production. As it is suggested that cAMP is the most likely intracellular second messenger for FSH, the regulatory effect of EGF on FSH-induced DNA synthesis could be, in part, due to suppression of cAMP production. These results suggest that EGF is involved in granulosa cell proliferation, irrespective of the presence of FSH, in a different pathway from FSH and additionally modulates the FSH growth-promoting effect as a local regulator. The interaction between EGF and FSH may be important in the control of follicular development.

Animals↗