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Biomedical subjects

Y Inagaki

Publications and source records attributed to Y Inagaki.

At least 145 records · Page 8Linked to original sources

The efficacy of monatepil, a new calcium antagonist, in the treatment of essential hypertension.

A multicenter, open-label trial in Japan examined the efficacy, safety, and optimal dose of monatepil (AJ-2615) as monotherapy and in combination therapy with angiotensin-converting enzyme (ACE) inhibitors or beta-blockers. Patients with essential hypertension who had never been treated or had been refractory to conventional antihypertensive agents were enrolled in the trial. During a 4-week control period patients assigned to monotherapy received placebo and those assigned to combination therapy received an ACE inhibitor or beta-blocker and placebo. Patients with systolic blood pressure (BP) > or = 160 mm Hg and diastolic BP > or = 95 mm Hg at the end of the control period were enrolled in the study. The initial dose of monatepil was 30 mg/day in monotherapy and 15 mg/day in combination therapy; the daily dose was titrated to 60 mg/day according to the antihypertensive response. The treatment period was 8 to 12 weeks. Blood pressure decreased from 168 +/- 8/100 +/- 6 to 142 +/- 9/85 +/- 7 mm Hg (SD) with monatepil monotherapy, from 171 +/- 11/102 +/- 6 to 141 +/- 9/84 +/- 6 mm Hg in combination with ACE inhibitors, and from 175 +/- 13/102 +/- 7 to 153 +/- 21/91 +/- 9 mm Hg in combination with beta-blockers (P < .001). When patients in whom mean BP decreased by > or = 13 mm Hg were defined as responders, the response rate was 80.4%, 78.1%, and 51.6% in the respective groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗

Efficiency of oxetanocin-G, a novel nucleoside against the woodchuck hepatitis virus.

Oxetanocin-G (OXT-G), a potent antiviral agent, is a novel nucleoside isolated from the culture filtrate of Bacillus megaterium. We investigated the antiviral effect of oral administration of OXT-G for five days on woodchuck hepatitis virus (WHV), in vivo, using 12 woodchucks. Woodchucks were randomized into each of four treatment groups according to the dose of OXT-G. Two out of six woodchucks treated with 1.0 or 2.0 mg/kg/day of OXT-G died. After treatment with OXT-G, serum levels of WHV-DNA significantly decreased in all woodchucks. However, the antiviral effect was only partial and levels of serum WHV-DNA returned after the cessation of treatment. The amount of viral replicative intermediates was decreased in livers of woodchucks treated with OXT-G. Although further study of the toxicity of this compound would be essential before studies in man can be carried out, OXT-G has potent antiviral activity against WHV and may deserve evaluation as an antiviral agent in the treatment of chronic hepatitis B infections in humans.

Animals↗

Isolation of a Suppressor-mutator/Enhancer-like transposable element, Tpn1, from Japanese morning glory bearing variegated flowers.

The Japanese morning glory has an extensive history of genetic studies. Many mutants in the colors and shapes of its flowers and leaves have been isolated since the 17th century, and more than 200 genetic loci have been localized for the 10 linkage groups. They include over 20 mutable loci, several with variegated flower phenotypes. In a line of Japanese morning glory bearing variegated flowers called flecked, a transposable element of 6.4 kb, termed Tpn1, was found within one of the anthocyanin biosynthesis genes encoding dihydroflavonol-4-reductase (DFR). The 6.4-kb element carries 28-bp perfect terminal inverted repeats, the outer 13 bp being identical to those of the maize transposable element Suppressor-mutator/Enhancer. It is flanked by 3-bp direct repeats within the second intron of the DFR gene, 9 bp upstream of the third exon. When somatic and germinal excision occurs, it produces excision sequences characteristic of plant transposable elements. Cosegregation data of the variegated flower phenotype and the DFR gene carrying Tpn1 indicated that the mutable phenotype is due to excision of Tpn1 from the DFR gene. Sequences homologous to Tpn1 are present in multiple copies in the genome of Japanese morning glory.

Alcohol Oxidoreductases↗

Low plasma lidocaine concentration does not affect oxygen uptake at awakening from isoflurane anesthesia.

To clarify the effects of lidocaine in plasma after epidural administration on oxygen uptake (VO2) at awakening from isoflurane anesthesia, we measured VO2 in 45 patients undergoing abdominal hysterectomy under four conditions: control group, intravenous normal saline; epidural group, 3 mg/kg of 1.5% lidocaine epidurally as a bolus; and groups CIV-A and CIV-B, continuous intravenous infusion of 2% lidocaine, 0.5 and 1 mg/kg, respectively, for 5 min followed by 30 micrograms.kg-1 x min-1. VO2 at both periods of steady state during anesthesia before lidocaine administration and awakening from anesthesia were measured using a mass spectrometer system during spontaneous breathing. At awakening, VO2 in the control, CIV-A, and CIV-B groups increased significantly (P < 0.02) from 142 to 262-328 mL.min-1 x m-2 which as more (P < 0.01) than that in the epidural group which increased from 166 to 159 mL.min-1 x m-2. These results indicate that epidural lidocaine prevents the increase in VO2 associated with arousal from isoflurane anesthesia. This effect is not due to the absorbed plasma lidocaine but due to the epidural neural block.

Adult↗

Epidural lidocaine delays arousal from isoflurane anesthesia.

To clarify the effect of epidural lidocaine on arousal from inhaled anesthesia, we investigated the minimum alveolar anesthetic concentration at awakening (MAC-Awake) of isoflurane and the duration between discontinuance of isoflurane inhalation and arousal from anesthesia in 60 female abdominal hysterectomy patients. All patients received epidural catheterization and were randomly assigned to one of five groups. The control group, A, was given normal saline intravenously (IV) and epidurally. Group B was given 1 mg/kg of 2% lidocaine IV as a bolus. Groups C and D were given 0.5 and 1 mg/kg, respectively, of 2% lidocaine IV for 5 min, followed by 30 micrograms.kg-1.min-1. Group E was given 3 mg/kg of 1.5% lidocaine epidurally as a bolus. These doses of lidocaine or control saline were administered 15 min before the end of the surgical procedure. MAC-Awake values in Groups A, B, C, D, and E were 0.30% +/- 0.05%, 0.28% +/- 0.04%, 0.29% +/- 0.04%, 0.31% +/- 0.04%, and 0.18% +/- 0.05% (mean +/- SD), respectively. MAC-Awake in Group E was lower than in the other groups (P < 0.001). The duration until arousal in Group E (21.0 +/- 2.0 min) was longer than in Groups A, B, C, and D (12.6 +/- 1.8 min, 12 +/- 2.3 min, 13.3 +/- 2.5 min, and 14.3 +/- 2.7 min, respectively) (P < 0.001). Plasma lidocaine levels in Groups B, C, D, and E were 0.95 +/- 0.17 microgram/mL, 1.07 +/- 0.16 microgram/mL, 2.09 +/- 0.31 micrograms/mL, and 1.02 +/- 0.16 micrograms/mL, respectively. We conclude that analgesia produced by epidural lidocaine delays arousal from isoflurane anesthesia. Furthermore, lidocaine plasma levels are shown to be too low to cause any sedative effect, thus suggesting that postoperative pain may cause significantly faster arousal from anesthesia.

Adult↗

An autopsy case of hypertrophic cardiomyopathy with pathological findings suggesting chronic myocarditis.

Myocardial fibrosis in patients with hypertrophic cardiomyopathy (HCM) may play an important role in the function and/or dimensions of the left ventricle. We present an autopsied case of HCM followed for 10 years. A 68-year-woman with HCM underwent trans-aortic myectomy of the interventricular septum in 1979. A significant amount of round cell infiltration, myocardial fibrosis and disarray were observed in the resected specimen. She experienced repeated admissions due to diabetes mellitus and congestive heart failure, and died of renal failure in 1989. An autopsy revealed extensive myocardial fibrosis and significant cell infiltration in the ventricular myocardium. The infiltrating cells were almost all lymphocytes, and the ratio of CD4 to CD8 was 3.8. This ratio was different from that of typical viral myocarditis. This case suggests that there may be an undefined inflammatory process causing fibrosis in HCM, in addition to the ischemia due to intramural small coronary artery stenosis.

Aged↗

[Chemical iodination of hormonogenic tyrosine residues of human thyroglobulin is critical for the production of anti-thyroglobulin autoantibody and for the induction of experimental autoimmune thyroiditis in mice].

There is evidence from animal models that the iodine content of thyroglobulin (Tg) may influence its antigenicity in thyroid autoimmunity. To elucidate the effect of iodination of hormonogenic sites of human Tg (hTg) on its autoantigenicity, a synthetic peptide (TB: hTg 2546-2571), containing two hormonogenic tyrosine residues of hTg, and a chemically-iodinated peptide (TB-I) were prepared. We immunized C3H/He (H-2k) mice, a high responder strain to Tg, and BALB/c (H-2d), a low responder strain, with TB or TB-I plus lipopolysaccharide. Lymph node cells from the two strains immunized with TB or TB-I proliferated in response to both TB and TB-I. Anti-Tg autoantibodies were detected in both strains when immunized with TB-I, while immunization with TB failed to produce anti-Tg antibodies. Furthermore, one of the C3H/He mice immunized with TB-I developed diffuse thyroiditis, but BALB/c mice did not. These findings indicate that the iodination of the hormonogenic tyrosine residues of hTg, in other words, the synthesis of mono- and di-iodotyrosine (MIT and DIT) residues, is necessary for the production of anti-Tg autoantibodies in high and low responder mice and for the induction of autoimmune thyroiditis in high responder mice.

Amino Acid Sequence↗

[Immediate hypersensitive reactions to the ingestion of egg white and IgE binding to the egg white components].

IgE is considered to be involved in immediate hypersensitive reactions (IHR) following egg ingestion. IgE antibody levels to egg-white (EW) antigens in the IHR-positive group (n = 19, mean age +/- SD = 5.2 +/- 4.5 yr) were higher than those in the IHR-negative group (n = 13, mean of age +/- SD = 3.6 +/- 2.2 yr). However, even in the IHR-negative group, some patients showed high IgE to EW. RAST inhibition tests with heat-treated (100 degrees C, 5, 10, and 30 min) egg-white antigens were performed on 13 serum samples from subjects with IHR and 9 serum samples from subjects without IHR. Heat treatment decreased the IgE-binding activity of egg white and it was speculated that IgE from IHR-negative subjects bound to relatively heat-unstable sites of egg-white antigens. Furthermore, we selected IHR-negative subjects (n = 8, mean of age +/- SD = 3.0 +/- 1.7 yr) with higher IgE antibody levels than the lowest limit of IgE to EW of the IHR-positive group and compared IgE to ovomucoid (OM), ovalbumin (OA), conalbumin (CA), and lysozyme (Ly) between these IHR-negative and positive groups. IgE-binding activities to egg-white components, including OA, CA, and Ly but not OM, were significantly decreased with heat treatment. The IHR-negative group showed significantly lower IgE to OM (untreated, 5, 10, 30 min treatment) and 5 min treated OA alone than the IHR-positive group, while no difference was found in IgE to other components between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Evaluation of local treatment for unresectable primary liver tumor].

To ascertain the effect of local treatment for unresectable primary liver tumor, 59 patients were investigated retrospectively. Patients were classified into four groups; transcatheter arterial embolization (TAE) group, intermittent intra-arterial infusion chemotherapy group, combined therapy group (TAE+intermittent intra-arterial infusion chemotherapy) and a group without adjuvant therapy. The results revealed that TAE and intermittent intra-arterial infusion chemotherapy both prolonged the survival period. We found that the survival rate depends largely on the therapeutic method. No correlations were confirmed with the liver function nor stage grouping of the tumor. Therefore, we concluded that intermittent intra-arterial infusion chemotherapy is a beneficial treatment, considering its minimal adverse effect, broad indication and the fact that it does not require hospitalization.

Adult↗

[Two cases of rheumatoid arthritis presenting autoimmune hepatic diseases].

We report on two cases of rheumatoid arthritis (RA) presenting autoimmune hepatic diseases. The first patient, who had been diagnosed as RA at the age of 63, was hospitalized in order to undergo surgery for total left knee replacement at the age of 69. She acquired acute serum hepatitis as a result of blood transfusion she received during the operation. Five years later, she visited our clinic suffering from polyarthritis. She was found to have hyper-alkaline phosphatase (ALP) and hyper rGTP, but no AMA. The second patient, a 60-year-old female whose onset of RA was at the age of 45, complained of general fatigue, and was admitted to the hospital because of persistent liver dysfunction. When corticosteroid was administered to these patients, ALP and rGTP levels in the first case, and AST and ALT levels in the second case were reduced to values in the normal range. ANA in the first case continued to register negative, but ANA in the second case became positive after the patient developed acute hepatitis. Both patients were found to have anti-p25 triplet liver/kidney microsome antibody. We discuss the clinical significance of this antibody.

Aged↗

Processing of a fusion protein by endoprotease in COS-1 cells for secretion of mature peptide by using a chimeric expression vector.

The subtilisin-related proprotein convertase furin is expressed in various mammalian tissues. Expecting that COS-1 cells have a furin-like endoprotease, we constructed a fusion expression vector for production of a recombinant foreign protein having no signal peptide or a protein in truncated form into secreted mature protein. A cDNA fragment encoding N-terminal procalcitonin (pro-CT) of human calcitonin precursor was inserted into the mammalian expression vector pME18S. We used PCR techniques to generate four kinds of cDNAs encoding the C terminus of the pro-CT with Arg residues at P4 (Arg-Xaa-Lys-Arg), P6 (Arg-Xaa-Xaa-Xaa-Lys-Arg), or both (Arg-Xaa-Arg-Xaa-Lys-Arg), in addition to the Lys-Arg motif at the cleavage site, in order to determine the conditions for efficient processing in nonendocrine cells, such as COS-1 cells. The cDNA coding for the Fc fragment of human immunoglobulin G1 was fused in-frame to the cDNA encoding pro-CT at its C terminus. Upon transfection of the chimeric plasmids into COS-1 cells, almost all of the fusion protein with the Arg residues at both P4 and P6 were processed into secreted Fc product, even without cotransfection of furin. These results indicate that COS-1 cells have a furin-like endoprotease and suggest that pro-CT, with the Arg residues at both P4 and P6, can be used as a carrier peptide for expression of a foreign protein having no signal peptide or a protein in truncated form in COS-1 cells.

Amino Acid Sequence↗

Expression of intercellular adhesion molecule-1 on cardiac myocytes for myocarditis before and during immunosuppressive therapy.

Right ventricular endomyocardial biopsies were performed in 15 patients with unexplained cardiac dysfunction, and the expression of intercellular adhesion molecule-1 (ICAM-1) on the myocardium was examined using the streptavidin-biotin complex method. Three of 15 patients (20%) had histologic evidence of myocarditis, and 2 of 15 patients (13%) had borderline myocarditis. The patients with biopsy-proven myocarditis received immunosuppressive therapy (prednisolone 60 mg/day). Two of the 3 patients demonstrated a substantial increase (> 10%) in percent fractional shortening and left ventricular ejection fraction during therapy. Subsequent biopsies revealed ongoing myocarditis in 1 patient, and resolved myocarditis in the other. The remaining patient had persistent cardiac dysfunction, but the subsequent biopsy revealed resolving myocarditis. ICAM-1 immunoreactivity was observed on cardiac myocytes, vascular endothelial cells, and interstitial cells of the patients with myocarditis. However, in patients without myocarditis, ICAM-1 immunoreactivity was observed only on vascular endothelial cells and interstitial cells. ICAM-1 immunoreactivity was still observed on cardiac myocytes in the patients with ongoing or resolving myocarditis during immunosuppressive therapy, but was not detected in the patient with resolved myocarditis. This study demonstrates that ICAM-1 is expressed on cardiac myocytes of patients with myocarditis and persistent cardiac dysfunction despite immunosuppressive therapy. The persistent expression of ICAM-1 may cause chronic inflammation of the myocardium.

Adult↗

Structure and expression of novel protein-tyrosine kinases, Emb and Emt, in hematopoietic cells.

Two novel tyrosine kinase cDNAs were obtained from murine mast cells. These kinases, Emb and Emt, constitute a novel tyrosine kinase subfamily which may also include Tec, a kinase preferentially expressed in liver, and Dsrc28, a fruit fly kinase. Both lack hydrophobic stretches characteristic of the transmembrane domains found in growth factor receptor tyrosine kinases and carboxyl-terminal, negative regulatory tyrosine residue found in Src family kinases. In addition to the Src homology region 2 (SH2) and SH3 domains characteristic of the Src family kinases and other signaling molecules, Emb and Emt share a similar amino-terminal domain comprised mainly of two repeat segments. The emb 2.7-kb transcript was expressed in mast cells, myeloid cells and B lymphocytes while the emt 4.6-kb mRNA in mast cells, myeloid cells and T lymphocytes. The evidence for in vitro tyrosine kinase activity of Emb and Emt proteins is also provided.

Amino Acid Sequence↗

Lack of peptide-release activity responding to codon UGA in Mycoplasma capricolum.

In Mycoplasma capricolum, a relative of Gram-positive eubacteria with a high genomic AT-content (75%), codon UGA is assigned to tryptophan instead of termination signal. Thus, in this bacterium the release factor 2 (RF-2), that recognizes UAA and UGA termination codons in eubacteria such as Escherichia coli and Bacillus subtilis, would be either specific to UAA or deleted. To test this, we have constructed a cell-free translation system using synthetic mRNA including codon UAA [mRNA(UAA)], UAG [mRNA(UAG)] and UGA [mRNA(UGA)] in-frame. In the absence of tryptophan, the translation of mRNA(UGA) ceased at UGA sites without appreciable release of the synthesized peptides from the ribosomes, whereas with mRNA(UAA) or mRNA(UAG) the bulk of the peptides was released. Upon addition of the E.coli S-100 fraction or B.subtilis S-100 fraction to the translation system, the synthesized peptides with mRNA(UGA) were almost completely released from the ribosomes, presumably because of the presence of RF-2 active to UGA in the added S-100 fraction. These data suggest that RF-2 is deleted or its activity to UGA is strongly weakened in M.capricolum.

Base Sequence↗

Trans-activation and stable integration of the maize transposable element Ds cotransfected with the Ac transposase gene in transgenic rice plants.

To develop an efficient gene tagging system in rice, a plasmid was constructed carrying a non-autonomous maize Ds element in the untranslated leader sequence of a hygromycin B resistance gene fused with the 35S promoter of cauliflower mosaic virus. This plasmid was cotransfected by electroporation into rice protoplasts together with a plasmid containing the maize Ac transposase gene transcribed from the 35S promoter. Five lines of evidence obtained from the analyses of hygromycin B-resistant calli, regenerated plants and their progeny showed that the introduced Ds was trans-activated by the Ac transposase gene in rice. (1) Cotransfection of the two plasmids is necessary for generation of hygromycin B resistant transformants. (2) Ds excision sites are detected by Southern blot hybridization. (3) Characteristic sequence alterations are found at Ds excision sites. (4) Newly integrated Ds is detected in the rice genome. (5) Generation of 8 bp target duplications is observed at the Ds integration sites on the rice chromosomes. Our results also show that Ds can be trans-activated by the transiently expressed Ac transposase at early stages of protoplast culture and integrated stably into the rice genome, while the cotransfected Ac transposase gene is not integrated. Segregation data from such a transgenic rice plant carrying no Ac transposase gene showed that four Ds copies were stably integrated into three different chromosomes, one of which also contained the functional hph gene restored by Ds excision. The results indicate that a dispersed distribution of Ds throughout genomes not bearing the active Ac transposase gene can be achieved by simultaneous transfection with Ds and the Ac transposase gene.

Base Sequence↗

Immunohistochemical localization of plasminogen activator inhibitor-1 in human coronary atherosclerotic lesions involved in acute myocardial infarction.

Immunohistochemical localization of plasminogen activator inhibitor-1 (PAI-1) was studied using the streptavidin-biotin method in human atherosclerotic coronary arteries. The patients (one male and two females), whose ages ranged from 61 to 78 years, died of anteroseptal acute myocardial infarction without having received any thrombolytic therapy. PAI-1 immunoreactivities (IRs) were mainly detected in the endothelial cells, smooth muscle cells, and collagen fibers of the coronary arterial intima and not in thrombi. Remarkable immunohistochemical staining was seen in intimal collagen fibers. In one patient, intimal PAI-1 IRs partly bordered a thrombus and surrounded a large atheroma rich in cholesterol crystals. Our results suggest that PAI-1 is present in both cellular and extracellular components of human coronary atherosclerotic lesions.

Aged↗