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Biomedical subjects

S Imai

Publications and source records attributed to S Imai.

At least 253 records · Page 14Linked to original sources

Effect of losartan, an AT1 selective angiotensin II receptor antagonist, on isoproterenol-induced cardiac ornithine decarboxylase activity.

Ornithine decarboxylase (ODC,EC 4.1.1.7), a rate-limiting enzyme in polyamine biosynthesis, is known to be induced by a beta-adrenoceptor agonist, isoproterenol (ISO). ODC activity and cardiac polyamine content are considered to be correlated with ISO-induced cardiac hypertrophy in rat hearts. To determine whether ISO-induced cardiac ODC activity is mediated through the renin-angiotensin system, especially at the AT1-receptor, we used a nonpeptide AT1 receptor antagonist, losartan, in this study. Losartan (10 mg/kg) suppressed both heart ODC and polyamine contents in ISO-treated rats. Although metoprolol (a selective beta-adrenoceptor antagonist) totally suppressed ODC activity, these results suggest that ISO-stimulated cardiac ODC activity may be regulated through beta 2-adrenoceptors coupled with AT1 receptors in rats.

Angiotensin II↗

[Usefulness of 123I-MIBG and 123I-BMIPP myocardial scintigraphy for detecting coronary artery disease and for evaluating left ventricular function].

We evaluated the diagnostic value of 123I-metaiodobenzylguanidine (MIBG) and 123I-labeled beta-methyliodophenyl pentadecanoic acid (BMIPP) myocardial SPECTs for evaluating coronary artery disease and left ventricular function, in comparison with the diagnostic value of 201Tl (Tl) SPECT. For forty-nine patients with coronary artery disease, resting MIBG and BMIPP SPECTs were performed to detect coronary artery stenosis, compared with the diagnostic value of exercise Tl. Left ventricular ejection fraction and regional wall motion were compared with the total US (TUS) and regional US (RUS) of resting MIBG and BMIPP SPECTs, and in turn, compared with resting Tl SPECT. The sensitivity of resting BMIPP SPECT for detecting coronary artery stenosis was lower, and the specificity of resting MIBG SPECT was lower than the other two methods. The accuracy of resting MIBG SPECT for evaluating coronary lesions was nearly the same as the accuracy of exercise Tl, but higher than that of BMIPP SPECT. Left ventricular ejection fraction was well correlated with TUS of resting MIBG SPECT (r = 0.80), resting BMIPP SPECT (r = 0.77), and resting Tl SPECT (r = 0.68). Regional wall motion was most correlated with RUS of resting BMIPP SPECT, compared with that of resting Tl and MIBG SPECTs. These data suggest that resting MIBG SPECT is useful for detecting coronary artery disease and that resting BMIPP SPECT is valuable in evaluating regional left ventricular function.

3-Iodobenzylguanidine↗

[Pharmacokinetic, bacteriological and clinical studies of SY5555 in the pediatric field].

Pharmacokinetic, bacteriological and clinical studies on SY5555, a new oral penem, were carried out, and the following results were obtained. 1. MICs were determined for 6 drugs, SY5555, clavulanic acid/amoxicillin (CVA/AMPC), cefaclor (CCL), cefotiam (CTM), cefpodoxime (CPDX), cefdinir (CFDN) against 20 strains of bacteria isolated from patients who were subsequently treated with SY5555. MICs of SY5555 for Gram-positive cocci ranged from 0.05 to 0.10 microgram/ml against 10 strains of Staphylococcus aureus. The MIC was < or = 0.025 microgram/ml against one strain of Streptococcus pyogenes, and MICs were from < or = 0.025 to 0.39 microgram/ml against Streptococcus pneumoniae. These MIC values were equivalent or superior to those of the other 5 drugs. MICs of SY5555 for Gram-negative bacilli were 0.39 and 6.25 micrograms/ml against Haemophilus influenzae, and these values were equivalent to those of the other drugs, except CPDX. The MIC of SY5555 was 0.39 microgram/ml against 2 strains of Escherichia coli, and this value was equivalent or superior to those of CVA/AMPC and CCL, similar or inferior to those of CPDX and CFDN, and inferior to that of CTM. The MICs of several drugs were determined for 10 strains of Bordetella pertussis and 30 strains of Campylobacter jejuni isolated from patients before this clinical study. The MICs of SY5555 against the 10 strains of B. pertussis were compared with those of 7 drugs, CCL, CTM, CPDX, ampicillin (ABPC), piperacillin (PIPC), imipenem (IPM) and erythromycin (EM). The MIC of SY5555 was 0.78 microgram/ml against all of the strains. This value was superior to those of CCL, CTM and CPDX, similar or inferior to that of IPM and inferior to those of PIPC and EM. The MICs of SY5555 against the 30 strains of C. jejuni were compared with those of 7 drugs. CCL, CTM, CPDX, CFDN, ABPC, IPM and EM, and the MIC of SY5555 was < or = 0.025 microgram/ml or 0.05 microgram/ml and these values were equivalent or superior to those of the 7 reference drugs. 2. SY5555 dry syrup was administered orally at 30 min. after meals, to a total of 5 patients, at doses of 5.0 and 10.0 mg/kg to 2 patients each and at a dose of 15.0 mg/kg to one patient and the plasma concentrations were determined. Peak concentrations were detected 1 to 3 hours after administration in all patients and the peak concentrations were 0.93 and 1.21 micrograms/ml at the 5.0 mg/kg dose, 2.85 and 5.49 micrograms/ml at the 10.0 mg/kg dose and 5.79 micrograms/ml at the 15.0 mg/kg dose.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗

Chronic effect of losartan in a murine model of dilated cardiomyopathy: comparison with captopril.

The long-term effects of losartan, an angiotensin II subtype-I receptor antagonist, were compared with those of captopril in a murine model of dilated cardiomyopathy caused by encephalomyocarditis virus. Four weeks after viral inoculation, 42 DBA/2 mice were given oral losartan 1.2 mg/kg/day (n = 8), 12 mg/kg/day (n = 8) or 60 mg/kg/day (n = 8) or captopril 7.5 mg/kg/day (n = 8) in drinking water or distilled water (n = 10). Mice were killed at the end of the 12-wk treatment period. Heart weight, left ventricular thickness, left ventricular cavity dimension and myocardial fiber diameter were significantly lower in mice given losartan 60 mg/kg as compared with the infected untreated group. Captopril had a similar effect on all parameters. The pathologic score of cardiac fibrosis was significantly lower in the mice treated with captopril but was not reduced in the mice treated with losartan. Moreover, as compared with the age- and sex-matched normal mice, cardiac mass and myocardial fiber diameter were significantly lower in normal mice treated with losartan 60 mg/kg. This study suggests that long-term treatment with losartan may prevent thickening of left ventricular wall and cavity dimension in dilated cardiomyopathy caused by encephalomyocarditis virus. The potency, and perhaps the efficacy, of losartan appear to be less than those of captopril.

Angiotensin Receptor Antagonists↗

[Mechanism of overshoot elevation of left ventricular ejection fraction during recovery after exercise in normal subjects and patients with coronary artery disease, assessed by 99mTc exercise radionuclide ventriculography].

An "overshoot" (OS) elevation of ejection fraction above resting levels has been demonstrated during recovery after exercise. To characterize the hemodynamic changes during recovery after bicycle exercise, we used radionuclide ventriculography under the Swan-Ganz catheter insertion in 16 normal subjects and 15 patients with coronary artery disease (CAD) at rest, during bicycle exercise and after exercise periods. In normal subjects, the ejection fraction increased from resting value during peak exercise, and showed overshoot elevation in the early recovery period. In patients with CAD, the ejection fraction decreased from resting value during peak exercise, then showed overshoot elevation in the early recovery period. In normal subjects, the end-diastolic volume (EDV) and the end-systolic volume (ESV) decreased from resting value during OS. In patients with CAD, the EDV at OS was not different from that at rest, the ESV decreased from resting value during OS. The systemic vascular resistance increased from resting value during OS. The systolic blood pressure/ESV, index for ventricular contractility, increased from resting value during OS in both groups. Thus, the decreased systemic vascular resistance does not playing a major role during recovery after exercise, whereas enhanced contractility is evident in both normal subjects and patients with CAD.

Coronary Disease↗

[Prognostic significance of 123I-metaiodobenzylguanidine scintigraphy in dilated cardiomyopathy].

The prognostic factor was identified by performing 123I-Metaiodobenzylguanidine (MIBG) myocardial scintigraphy on 17 patients with dilated cardiomyopathy (DCM). During 5 years period, 9 patients had cardiac events, four of whom died, six were admitted due to heart failure and five had ventricular tachycardiac events. At the starting point, we collected rest early and 3-hr-delayed MIBG SPECT along with rest 201T1 (T1) SPECT. In the SPECT, regional tracer uptake was scored using 4-grades defect score (0 = normal to 3 = uptake-defect), and summed up to total defect score (TDS). At the same time, we estimated left ventricular end-diastolic dimension/body surface area (LVDd/BSA), end-systolic dimension/body surface area (LVDs/BSA) and left ventricular ejection fraction (LVEF) by echo-cardiography, pulmonary arterial wedge pressure (PAWP) and New York Heart Association (NYHA) symptom class. We compared the clinical and hemodynamic parameters between the patients with cardiac events (group A) and the other patients (group B). TDS of delayed MIBG SPECT (p < 0.001), TDS of early MIBG SPECT (p < 0.05), TDS of T1 SPECT (p < 0.01), LVDd/BSA (p < 0.01), LVDs/BSA (p < 0.001) and NYHA class (p < 0.05) of group A were significantly larger than those of group B. But, LVEF of group A was significantly less than that of group B (p < 0.01). On multivariate analysis, the following parameters were independent predictors of cardiac events: TDS of delayed MIBG SPECT (p < 0.001), PAWP (p = 0.0124) and LVDd/BSA (p = 0.0026). These data suggest that delayed MIBG scintigraphy is thought to be important to predict cardiac events in patients with DCM.

3-Iodobenzylguanidine↗

[A case of desmoplastic malignant mesothelioma].

A 43-year-old man was admitted to Nara Medical University Hospital because of right-sided chest pain. Computed tomographic examination revealed a right pleural effusion and diffuse pleural thickening. Malignant mesothelioma was diagnosed from the results of a percutaneous pleural biopsy, and the patient then underwent right pleuro-pneumonectomy. The resected specimen was examined by light and electron microscopy, which revealed scattered sarcoma-like malignant cells with some epithelial differentiation, in abundant extracellular collagen with storiform derangement. Therefore, desmoplastic malignant mesothelioma (mixed type) was diagnosed. This is a rare histological subgroup of malignant mesotheliomas. The patient died 2 months after the operation, due to multiple and rapidly growing metastases. After lung tissue was dissolved, ferruginous (asbestos) bodies were counted, and the results were consistent with occupational exposure to asbestos (413 asbestos bodies per 5 g of lung tissue).

Adult↗

[A case of chondrosarcoma of the low grade malignancy originated in rib].

A case with chondrosarcoma of rib, which is relatively uncommon in Japan, in a 61-year-old man is reported. Chest X-ray examination revealed an abnormal shadow in the right of the chest wall. Chest CT scan and MRI disclosed the tumor to have been arosen from the right 5th rib protruding into the thoracic cavity. Surgical resections of the tumor with parts of the 4th and 5th ribs and parietal pleura were performed. The defect of the chest wall was repaired with muscle. The tumor measured 3.0 x 3.0 x 3.5 cm in size and was a chondrosarcoma of the low grade malignancy, histologically. Post operative course was uneventful with no adjuvant therapy.

Bone Neoplasms↗

[Role of pharmacist in cancer pain management].

It is essential for patients to have understanding of the significance of morphine administration and to cope well with its side effects, as it leads to enhancement of the analgesic effects of morphine in the treatment of cancer pain. Since August 1993 we have used the booklet "Relieving Pain Effectively--Manual for Patients" and have consulted up to date approximately 670 patients about taking narcotics. The initial information eliminates the anxiety before taking morphine--we set up the time that each patient should take medicine to fit their life-style and explain about the the medicine and its side-effects. For this reason, the above information takes approximately 30 to 60 minutes per patient. We guide the patient over to over till the pain and side-effects have disappeared and file a "Morphine Education Record" with the details. We also prepare a "Pain and Side-Effect Control Sheet" that consists of 6 items and a pain scale where 0 equals no pain and no side-effect and 5 equals most pain and side-effects. Patients select the scale themselves every day. Pharmacists provide the information to a doctor and advise him on steps against side-effects, selection of dose, interval and rescue-dose. This is a report on the role of the pharmacist in patient narcotics guideline for cancer pain management.

Humans↗

Complete Nucleotide Sequence of Mouse Mammary Tumor Virus from JYG Chinese Wild Mice: Absence of Bacterial Insertion Sequences in the Cloned Viral gag Gene.

Mammary tumors of a newly isolated strain of Chinese wild mouse (JYG mouse) harbor exogenous mouse mammary tumor virus (MMTV). The complete nucleotide sequence of exogenous JYG-MMTV was determined on the proviral 5' long terminal repeat (LTR)(partial)-gag-pol-env-3' LTR (partial) fragment cloned into a plasmid vector and the cDNA sequence from JYG-MMTV producing cells. Similarly to the other MMTV species the LTR of JYG-MMTV contains an open reading frame (ORF). The amino acid sequence of the JYG-MMTV ORF resembles that of SW-MMTV (92% identity) and endogenous Mtv-7 (93% identity) especially at the C-terminal region. Thus, a functional similarity in T-cell receptor V beta recognition as a superantigen is implicated among these MMTV species. Analysis of the viral gag nucleotide sequence revealed that this gene is not disrupted by the bacterial insertion sequence IS1 or IS2, which have been reported to be present in the majority of the plasmids containing the gag region. Comparison of amino acid sequences of JYG-MMTV with those of BR6-MMTV showed that over 96% of the amino acids of gag, pol, protease and env products are identical. These results suggest the intact nature of the nucleotide sequence of the near full-length MMTV genome cloned in the plasmid.

Journal Article↗

Gastric carcinoma: monoclonal epithelial malignant cells expressing Epstein-Barr virus latent infection protein.

In 1000 primary gastric carcinomas, 70 (7.0%) contained Epstein-Barr virus (EBV) genomic sequences detected by PCR and Southern blots. The positive tumors comprised 8 of 9 (89%) undifferentiated lymphoepithelioma-like carcinomas, 27 of 476 (5.7%) poorly differentiated adenocarcinomas, and 35 of 515 (6.8%) moderately to well-differentiated adenocarcinomas. In situ EBV-encoded small RNA 1 hybridization and hematoxylin/eosin staining in adjacent sections showed that the EBV was present in every carcinoma cell but was not significantly present in lymphoid stroma and in normal mucosa. Two-color immunofluorescence and hematoxylin/eosin staining in parallel sections revealed that every keratin-positive epithelial malignant cell expressed EBV-determined nuclear antigen 1 (EBNA1) but did not significantly express CD45+ infiltrating leukocytes. A single fused terminal fragment was detected in each of the EBNA1-expressing tumors, thereby suggesting that the EBV-carrying gastric carcinomas represent clonal proliferation of cells infected with EBV. The carcinoma cells had exclusively EBNA1 but not EBNA2, -3A, -3B, and -3C; leader protein; and latent membrane protein 1 because of methylation. The patients with EBV-carrying gastric carcinoma had elevated serum EBV-specific antibodies. The EBV-specific cellular immunity was not significantly reduced; however, the cytotoxic T-cell target antigens were not expressed. These findings strongly suggest a causal relation between a significant proportion of gastric carcinoma and EBV, and the virus-carrying carcinoma cells may evade immune surveillance.

Antibodies, Viral↗

[Cerebral digital tomosynthetic angiography for planning stereotactic biopsy of brain tumor].

We used cerebral digital tomosynthetic angiography for planning the probe trajectory of stereotactic biopsy of brain tumors in four patients. The probe trajectory was basically planned by MRI examinations. However, cerebral digital tomosynthetic angiography demonstrated detailed three-dimensional vascular anatomy around the brain tumors, and therefore was very helpful in revising the planned trajectory when there was a fairly large vessel likely to cross with it.

Adult↗

Insertional mutation of int protooncogenes in the mammary tumors of a new strain of mice derived from the wild in China: normal- and tumor-tissue-specific expression of int-3 transcripts.

A new mouse strain, Mus musculus Jyg, has been isolated from the wild in China. After several generations of inbreeding, Jyg mice have been found to develop mammary adenocarcinomas at a high incidence (70-80%). In order to understand the mechanism by which mammary tumors are induced in these mice, we analyzed 23 available mammary tumors and liver tissues with regard to mouse mammary tumor virus (MMTV) proviral integrations and the pattern of int oncogene (Wnt-1, int-2/Fgf-3, and int-3) rearrangements and expression. We found that (1) Jyg mice do not carry endogenous MMTV; (2) all tumors showed multiple MMTV proviral integrations and expressed high levels of MMTV; (3) Jyg MMTV is distinguishable from other MMTV strains; (4) a high percentage of the tumors (70%) had insertional mutations in int loci (Wnt-1, 26%; int-2, 13%; and int3, 43%); and (5) unlike Wnt-1 and int-2, a 5.9-kb int-3-related transcript is expressed in developing mouse embryos of all stages and adult mouse tissues including mammary tumors, whereas a 2.4- to 3.6-kb transcript is expressed only in Jyg mammary tumors with int-3 mutations. Taken together, this newly developed mouse strain and the milk-borne MMTV that it carries constitute a novel system for studies of the host and viral specificity of insertional mutagenesis of multiple int protooncogenes by MMTV and the role of these genes in the pathogenesis of mouse mammary carcinomas and tumor cell heterogeneity.

Animals↗

Mouse Mammary Tumor Virus Proviral Integration in the DD/Tbr Mice.

The patterns of mouse mammary tumor virus (MMTV) integration in the DNA of spontaneous-mammary tumors, salivary glands and livers of DD/Tbr mice were examined using MMTV env, int -1c and int-2c probes. The MMTV env probe revealed 1 to 7 new proviral insertions in all mammary tumors. MMTV integration into int-1 was observed in 10 of 18 mammary tumors, whereas that into int-2 was seen in only 2 of 18 tumors. Of the 13 salivary glands examined, only 3 showed new MMTV proviral integrations, but rearrangement in int-1 or int-2 loci by MMTV was not observed. Immuno-collidal gold electron microscopy revealed the presence of MMTV particles both in mammary tumors and in salivary glands, but no tumors were found to be developed in salivary glands. Taken together these results suggest that salivary glands support MMTV replication, but the virions thus produced may not lead to salivary gland tumorigenesis. It is suggested that the salivary gland is the source of horizontally transmitted MMTV in DD/Tbr mice.

Journal Article↗

Molecular cloning of a diacylglycerol kinase isozyme predominantly expressed in human retina with a truncated and inactive enzyme expression in most other human cells.

In order to clone novel diacylglycerol kinase (DGK) isozymes, we first obtained a DGK-related cDNA fragment by polymerase chain reaction using the human hepatoma cell line HepG2 mRNA and degenerated primers. The amplified fragment was subsequently used as a probe for screening the cDNA library from HepG2 cells. We obtained a cDNA clone coding for a novel DGK isozyme (designated DGK gamma) comprised of 791 amino acid residues. The amino acid sequence of DGK gamma was 52 and 62% identical to those of previously sequenced porcine 80-kDa and rat 90-kDa enzymes, respectively. DGK gamma, although initially cloned from the HepG2 cDNA libraries, was unexpectedly expressed in the human retina abundantly and to a much lesser extent in the brain. Other human tissues, including the liver and HepG2 cells, contained extremely low levels of DGK gamma mRNA. Furthermore, HepG2 cells and most of the human tissues except for the retina and brain expressed a truncated DGK gamma with an internal deletion of 25 amino acid residues (Ile451-Gly475). When transfected into COS-7 cells, the nontruncated cDNA gave phosphatidylserine-dependent DGK activity with no apparent specificity with regard to the acyl compositions of diacylglycerol. In contrast the truncated cDNA failed to give DGK activity in spite of the expression of its mRNA and enzyme protein in COS cells, thus demonstrating that the truncated DGK gamma is catalytically inactive. The sequence comparison of the three cloned DGKs revealed the presence of four highly conserved regions including the two sets each of EF-hand and zinc finger structures. Although the implication of the catalytically inactive form of DGK gamma remains unknown, this work further demonstrates the occurrence of multiple animal DGK isozymes with a conserved basic structure but with markedly different expression patterns depending on the cell types.

Amino Acid Sequence↗

Involvement of a Ca2+/calmodulin-dependent protein kinase II-associated mechanism in the induction of an outward potassium current by quisqualate.

The inhibitory action of a glutamate agonist, quisqualate, in association with the intracellular signal transduction, was electrophysiologically examined in identified Euhadra neurons. Quisqualate dose-dependently induced a slow outward current (Quis current) which was blocked by tetraethylammonium. This current was suppressed by intracellular injection of Ca2+/calmodulin-dependent protein kinase II (CaMKII), and was enhanced by a CaMKII inhibitor, KN-62. However, no significant changes in the Quis current were observed when the catalytic subunit of protein kinase A (PKA) or the protein kinase C (PKC) fragment (530-558) was intracellularly applied; or using a PKA inhibitor, H-8, or a PKC inhibitor, staurosporine. These results suggest a novel mechanism linked to CaMKII, by which quisqualate induces an outward potassium current.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Modulation of associated ovarian carcinoma antigens by 5 cytokines used as single agents or in combination.

Optimization of intraperitoneal radioimmunotherapy of ovarian cancer depends on increasing the antigenic expression of tumor cells. For this purpose, we studied the effect of 5 cytokines (IFN-alpha, IFN-beta, IFN-gamma, TNF-alpha and TGF-beta), used as single agents or in combination, on 4 ovarian cancer cell lines which present different antigenic profiles with the monoclonal antibodies (MAbs) tested (OC125, OVTL-3, MOv 18 and MOv 19). Analyses were performed by flow cytometry and the Scatchard technique in order to study antigenic modulation. The effect on proliferation was determined by cell counting. Expression of O3 antigen, recognized by the OVTL3 MAb, was increased up to 2.5 times after IFNs and TNF-alpha (used as single agent) on the 2 lines presenting low basal expression (SHIN-3 and IGROVI). The expression of CA125 antigen and the antigens recognized by MOv 18 and MOv 19 MAbs was not increased by any of the cytokines tested. The combination IFN-gamma+TNF-alpha was synergistic on cytotoxicity and enhanced O3 expression, providing 10 times as many sites per cell on the SHIN-3 line. For 3 other associations (IFN-alpha+IFN-gamma, IFN-beta+IFN-gamma and IFN-alpha+TNF-alpha), there was an additive effect on O3 expression and on cell cytotoxicity.

Antigens, Neoplasm↗