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Biomedical subjects

Y Sudo

Publications and source records attributed to Y Sudo.

At least 145 records · Page 8Linked to original sources

A benzophenazine derivative, N-beta-dimethylaminoethyl 9-carboxy-5-hydroxy-10-methoxy-benzo[a]phenazine-6-carboxamide, as a new antitumor agent against multidrug-resistant and sensitive tumors.

NC-190, a benzophenazine derivative (N-beta-dimethylaminoethyl 9-carboxy-5-hydroxy-10-methoxy-benzo[a]phenazine-6-carboxamide), was effective against multidrug-resistant human and mouse tumor cells in vitro and in vivo. When vincristine (VCR)-resistant P388 leukemia-bearing mice were treated with an optimal dose of NC-190, four of six mice were cured, whereas treatment of mice with VCR resulted in only a marginal increase in life span. The compound also showed chemotherapeutic effect against Adriamycin-resistant P388 leukemia-bearing mice and was effective against various multidrug-resistant human and murine tumor cells in vitro. Its cytotoxicity to multidrug-resistant K562 cells was not enhanced by the addition of verapamil. The accumulation of NC-190 in multidrug-resistant K562 cells was slightly lower than that observed in sensitive K562 cells; the compound did not efficiently inhibit the binding of VCR to the plasma membrane of resistant cells, indicating that NC-190 has little affinity for P-glycoprotein. NC-190 inhibited the activity of DNA topoisomerase II. These observations suggest that NC-190 (1) is not transported out of resistant cells by P-glycoprotein and (2) inhibits DNA topoisomerase II activity in the cells, resulting in its likely effectiveness against various multidrug-resistant tumor cells.

Animals↗

Comparison of coronary hemodynamics in patients with internal mammary artery and saphenous vein coronary artery bypass grafts: a noninvasive approach using combined two-dimensional and Doppler echocardiography.

Blood flow in bypass grafts and recipient left anterior descending coronary arteries was evaluated with combined two-dimensional and Doppler echocardiography in 15 patients with an internal mammary artery graft and in 24 patients with a saphenous vein graft. Comparative studies of coronary hemodynamics were also performed regarding these two different grafting techniques. The graft vessel was detected in 11 (79%) of 14 patients with an internal mammary artery graft and in 20 (87%) of 23 with a saphenous vein graft. The recipient left anterior descending coronary artery was detected in 10 (67%) of the former group and 17 (71%) of the latter. The blood flow patterns obtained were generally biphasic, consisting of systolic and diastolic phases with higher velocity during diastole. The maximal diastolic flow velocity in internal mammary artery grafts was much higher than that in saphenous vein grafts. In patients with an internal mammary artery graft, the flow pattern characteristics within the recipient coronary artery were quite similar to those within the arterial graft, and flow velocities within the recipient coronary artery and the arterial graft were quantitatively almost identical. This outcome may contribute to the long-term patency seen in internal mammary artery grafts. On the other hand, the flow velocity in saphenous vein grafts was fairly low throughout the cardiac cycle. Flow velocity in the recipient coronary artery in patients with a saphenous vein graft was accelerated only in early diastole. As a result, the recipient coronary artery flow pattern and velocity differed substantially from those in the saphenous vein graft.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Flow Velocity↗

[A case of progressive systemic sclerosis with Sjögren's syndrome complicated by nephrotic syndrome caused by bucillamine].

A 53-year-old woman was admitted with complaints of edema in the lower legs. The patient had developed polyarthralgia in 1982 and had been treated with D-penicillamine and prednisolone under the diagnosis of rheumatoid arthritis. She then had developed sclerosis of skin as well as dry eyes and dry mouth. In November 1987, bucillamine treatment had started and proteinuria had appeared in February 1988. Her blood showed hypoproteinemia and was positive for anti-Scl-70 antibody test and for anti-SS-A antibody test. The skin biopsy and labial salivary gland biopsy revealed the increased collagen fibers in the subcutaneous tissue and the round cell infiltration around the salivary ducts. We diagnosed her as progressive systemic sclerosis (PSS) with Sjögren's syndrome (SjS) complicated by nephrotic syndrome. Subsequently a renal biopsy was performed. There were the granular deposition of IgG and complements in the glomerular capillary wall and electron dense deposits in the subepithelial region. These findings suggested that she had membranous nephropathy. Since such a renal lesion was rarely observed in PSS and SjS, it was highly probable that bucillamine induced the nephropathy. The bucillamine treatment was discontinued about 2 months after the nephrotic syndrome had developed. However, the nephrotic syndrome has continued for additional 8 months. Thus it is concluded that the renal damage is one of the important side effect caused by bucillamine.

Anti-Inflammatory Agents, Non-Steroidal↗

[Surgical therapy for WPW syndrome combined with paroxysmal atrial tachycardia].

A 47-years old man presented with life-threatening paroxysmal supraventricular tachycardia. Electrophysiological study revealed both paroxysmal atrial tachycardia and atrioventricular reentrant tachycardia. The earliest site of activation during paroxysmal atrial tachycardia was located on the cranial portion of the left atrium and just behind the aorta. The atrioventricular accessory passway was located at the posterolateral wall of the left ventricle. Cryosurgical ablation was performed to the cranial portion of the left atrium and the accessory passway was interrupted from inside of the left atrium under the cardiopulmonary bypass. In the postoperative electrophysiological study, neither atrial tachycardia nor atrioventricular reentrant tachycardias was inducible. Since then he has never experienced tachycardia attack for one year.

Cryosurgery↗

[Surgical treatment of inflammatory abdominal aortic aneurysm].

A 53-year-old man was hospitalized with chronic abdominal pain. A CT scan was performed and demonstrated an aortic aneurysm surrounded by a soft tissue mantle. In the laparotomy, extensive fibrotic adhesions between the aneurysm and the duodenum were discovered. This made mobilization of the duodenum and the left renal vein difficult. The aortic wall was white, thickened, and surrounded with dense fibrous tissue. The aneurysm was replaced by a Dacron graft. Histology of the fibrous tissue showed the features of chronic inflammation. He had no abdominal pain after the operation, and he was discharged in good health. In the preoperative diagnosis of inflammatory aneurysms, the CT scan is useful. We are of the opinion that the preferred treatment for inflammatory aneurysm is aneurysmectomy (or aneurysmorrhaphy) plus grafting.

Aorta, Abdominal↗

A fluorine-containing anthracycline (ME2303) as a new antitumor agent against murine and human tumors and their multidrug-resistant sublines.

A new fluorine-containing anthracycline derivative, ME2303, showed excellent antitumor activity against various experimental tumor models. The i.p. or i.v. administrations of ME2303 on Day 1 or on Days 1, 5, and 9 against i.p.-implanted L1210 leukemia cells rendered more than 50% of mice tumor free at wide ranges of nontoxic doses, whereas the incidence of cure obtained with Adriamycin (ADM) was less than that obtained with ME2303. ME2303 given i.p. or i.v. on Day 1 or Days 1, 5, and 9 was also effective against i.p.-implanted P388 leukemia cells, and higher incidences of cure were obtained than with ADM. ME2303 administered i.v. on Days 1, 8, 15, and 22 showed prominent antitumor activity against s.c.-implanted colon adenocarcinomas 26 and 38, Lewis lung carcinoma, B16 melanoma, and M5076 sarcoma. Against colon adenocarcinoma 26, ME2303 induced cure in 16 of 20 mice at doses of 35 to 71 mumol/kg, whereas no cure was observed with ADM. Significant growth inhibition of colon adenocarcinoma 38, Lewis lung carcinoma, B16 melanoma, and M5076 sarcoma cell lines was also observed at a dose of 18 to 106 mumol/kg. ME2303 was effective against human and murine multidrug-resistant cells in vitro. For example, human myelogenous leukemia K562 resistant to ADM (K562/ADM) was only 2.8-fold more resistant to ME2303, while the cells were 200-fold more resistant to ADM when the values for the concentration of drug required for 50% inhibition of cell growth were compared. ME2303 was also more effective than ADM against human leukemia CCRF-CEM resistant to vinblastine, human ovarian carcinoma A2780 resistant to ADM, human epidermoid carcinoma KB cells resistant to colchicine, and mouse leukemia P388 resistant to ADM and vincristine. Therapeutic effects were obtained in vivo against ADM- and, especially, vincristine-resistant P388 leukemia. ME2303 is one of the most interesting potential antitumor agents to be studied further.

Animals↗

Electrophysiological effects of FK664, a new cardiotonic agent, on preparations from guinea pig ventricle and from rabbit sino-atrial node.

Effects of the cardiotonic agent FK664, 6-(3, 4-dimethoxy-phenyl)-1-ethyl-4-mesitylimino-3-methyl-3,4-dihydro-2 (1H)-pyrimidone, on isolated guinea pig ventricular muscles and rabbit sinus node pacemaker cells were studied using micro-electrode techniques. In ventricular muscles driven at 0.5-1.0 Hz, FK664 above 3 mumol.litre-1 caused an increase in contractile force and a shortening of time to peak tension. This positive inotropic effect of FK664 was accompanied by a slight elevation of the early plateau phase of the action potential, while other action potential variables were unaffected. The change in contractile force induced by FK664 was abolished in a low Ca2+ medium (0.12 mmol.litre-1) or by treatment with ryanodine (2 mumol.litre-1), whereas it was relatively well preserved in the preparations pretreated with nefedipine (1 mumol.litre-1). The slow action potentials induced by isoprenaline (0.3 mumol.litre-1) in high K+ medium (30 mmol.litre-1) and the slow inward current measured by single sucrose gap voltage clamp at a holding potential of -40 mV were unaffected by FK664. In sinus node pacemaker cells, FK664 (1-10 mumol.litre-1) caused a dose dependent acceleration of phase 4 depolarisation and a shortening of spontaneous firing cycle length. This positive chronotropic effect of FK664 was markedly inhibited in a low Ca2+ medium (0.3 mmol.litre-1). These findings suggest that FK664 has positive inotropic and chronotropic effects on the heart, due to an enhancement of transsarcolemmal calcium influx through the low threshold, dihydropyridine insensitive Ca2+ channel population.

Action Potentials↗

Radioreceptor assay of clonazepam and diazepam in blood for therapeutic drug monitoring.

Rat cerebral cortex was used to prepare a suspension of benzodiazepine receptors. The suspension was mixed with an extract of specimen and [3H]flunitrazepam. The mixture was filtered through a membrane, and radioactivity on the membrane was measured. Clonazepam concentrations in patient plasma specimens determined by radioreceptor assay and gas-liquid chromatography agreed well. However, diazepam equivalent concentrations determined by radioreceptor assay were close to the sum of diazepam and desmethyldiazepam concentrations determined by high-performance liquid chromatography, as desmethyldiazepam had binding activity for the receptor. This receptor assay method is accurate, simple, requires less than 0.5 ml of plasma, and is therefore suitable for analyzing numerous samples in a short time.

Adolescent↗

[A case of tetralogy of Fallot with pulmonary aneurysm].

A case of pulmonary artery aneurysm associated with tetralogy of Fallot is presented. A 28-year-old man was admitted for evaluation of cyanosis and cardiac murmur. Preoperative angiography revealed tetralogy of Fallot and an aneurysm of the main pulmonary artery aneurysm. Operation consisted of pulmonary artery aneurysmectomy and total correction of the tetralogy of Fallot. Microscopic examination of the resected aneurysm showed the thickening of intima and fragmented elastic fibers of media. A brief review of the literature emphasizes the necessity of the surgical intervention.

Adult↗

Regulated expression of a gene encoding a nuclear factor, IRF-1, that specifically binds to IFN-beta gene regulatory elements.

Expression of the interferon-beta (IFN-beta) gene is induced by a variety of agents, including viruses. Evidence has been provided that a mouse nuclear factor, termed interferon regulatory factor-1 (IRF-1), specifically binds to the upstream regulatory region of the human IFN-beta gene and mediates virus-induced transcription of the gene. In this study, we describe the molecular cloning and characterization of the mouse and human cDNAs encoding IRF-1. Our results suggest that IRF-1 is also involved in the regulation of other genes such as IFN-alpha and MHC class I genes. Surprisingly, IRF-1 gene expression is dramatically induced by Newcastle disease virus in mouse L929 cells and by Concanavalin A in spleen cells. We show here that the IRF-1 gene possesses virus-inducible promoter.

Amino Acid Sequence↗

Type II collagen-induced murine arthritis. I. Induction and perpetuation of arthritis require synergy between humoral and cell-mediated immunity.

Immunization of DBA/1 mice with type II collagen resulted in typical and progressive arthritis, which is associated with the production of high titer of anti-collagen antibody and the induction of cell-mediated immunity as exemplified by delayed type hypersensitivity response as well as lymphokine production. In contrast, administration of heat-denatured collagen into DBA/1 mice failed to induce the arthritis. These mice produced only marginal antibody, whereas they developed comparable cell-mediated immunity to that induced by immunization with native collagen, and therefore the inoculation of heat-denatured collagen provided the regimen capable of inducing preferentially cell-mediated immunity without the generation of high level of antibody. Inasmuch as administration of antibody induced only marginal and transient joint swelling not associated with typical histologic lesion, the synergistic effect of humoral and cell-mediated immunities was investigated using antibody preparation and the regimen to induce selectively cell-mediated immunity. The results demonstrate that administration of antibody into DBA/1 mice pre-sensitized with heat-denatured collagen resulted in potent and progressive arthritis. Such synergy was further confirmed by the induction of arthritis in T cell-depleted DBA/1 mice that had been adoptively transferred with antibody and lymphoid cells from heat-denatured collagen-sensitized mice. Moreover, it was revealed that the nature of cells capable of transferring cell-mediated immunity was of Thy-1+ and L3T4+ Lyt-2-. These results indicate that anti-collagen antibody and L3T4+ T cell-mediated cellular immunity are crucially required for the perpetuated development of type II collagen-induced arthritis.

Animals↗

Evidence for a nuclear factor(s), IRF-1, mediating induction and silencing properties to human IFN-beta gene regulatory elements.

Transcription of the human interferon-beta (IFN-beta) gene is induced by a variety of agents such as viruses, dsRNA and some cytokines. In this study, we describe a nuclear factor, termed interferon regulatory factor-1 (IRF-1), that is involved in the transcription of IFN-beta and possibly other genes. We demonstrate that IRF-1 functions in virus-induced transcription by interacting with previously identified, IFN-beta regulatory DNA elements. Our data suggest that IRF-1 participates in the transient formation of an induction-specific complex(es) with the regulatory elements. IRF-1 may also be involved in silencing the function of the SV40 enhancer juxtaposed to the regulatory elements in uninduced cells.

Animals↗

Fluorescence and chemiluminescence enzyme immunoassays of 17 alpha-hydroxyprogesterone in dried blood spotted on filter paper.

Enzyme immunoassays for 17 alpha-hydroxyprogesterone (17-OHP) were developed. Horseradish peroxidase (HRP), glucose oxidase (GOD), invertase (INV) and glucose-6-phosphate dehydrogenase (G6PDH) were used as label enzymes. Double antibody coated beads or tubes were used for separating the bound and free fractions. Antisera used were prepared by using 4-carboxyethylthio-17-OHP and 3-carboxymethyl oxime-17-OHP-bovine serum albumin as immunogens. The bridge heterologous system was more sensitive than other site heterologous and homologous systems. The minimum amounts of 17-OHP detected were 0.25 and 1.0 pg/tube for fluorescence EIAs using HRP and GOD, and 0.1, 10 and 0.1 pg/tube for chemiluminescence EIAs using GOD, INV and G6PDH, respectively. The reproducibility and correlation with RIA were also studied. The present study demonstrates the feasibility of a neonatal screening for congenital adrenal hyperplasia.

17-alpha-Hydroxyprogesterone↗

[Immunohistochemical localization of hCG alpha, hCG beta CTP, hPL and SP1 on villous and extravillous trophoblasts in normal human pregnancy].

Trophoblasts are divided into villous trophoblasts and extravillous trophoblasts, depending on whether they constitute a villous structure, and cell columns intervene between them. We conducted an immunohistochemical localization of human chorionic gonadotropin (hCG) alpha, hCG beta C-terminal peptide (CTP), human placental lactogen (hPL) and pregnancy-specific beta 1-glycoprotein (SP1) on the trophoblasts of normal human pregnancy, using forty-one hysterectomized pregnant uteri (6-22 weeks). In villous trophoblasts, the capacity to synthesize hCG alpha, hCG beta CTP, hPL and SP1 seemed to develop according to the morphological change from mononuclear cells to multinuclear cells. In contrast, the synthetic capacity of these proteins seemed not to correspond with the morphological change in extravillous trophoblasts: The location of hCG alpha, hCG beta CTP and SP1 was restricted to the mononuclear trophoblasts in the superficial decidua, while hPL was present extensively in extravillous trophoblasts, including multinuclear trophoblasts in the deciduomuscular junction. Therefore, it may be reasonably said that extravillous trophoblasts have many biological features distinct from villous trophoblasts and differentiate in an independent manner. Mononuclear trophoblasts in the cell column were negative for these proteins, which, together with morphological observations, strongly suggest the germinative nature of these cells.

C-Peptide↗