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Biomedical subjects

Y Ueda

Publications and source records attributed to Y Ueda.

At least 469 records · Page 26Linked to original sources
PubMed1996

Studies on cerebral protective agents. X. Synthesis and evaluation of anticonvulsant activities for novel 4,5,6,7-tetrahydrothieno[3,3-c]pyridines and related compounds.

Novel 4,5,6,7-tetrahydrothieno[3,2-c]pyridines, 1-thienyl-1,2,3,4-tetrahydroisoquinolines and related compounds, in which the benzene rings of (+)-1 (FR115427) were replaced with heteroaromatic rings such as thiophene, furan, benzothiophene and indole, were synthesized and evaluated for anticonvulsant activity against i.c.v. N-methyl-D-aspartate (NMDA)-induced seizures in mice. Among these compounds, (+)-4-methyl-4-phenyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridine hydrochloride ((+)-2a), (+)-4-methyl-4-(2-thienyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine hydrochloride ((+)-2g), and (-)1-methyl-2-(2-thienyl)-1,2,3,4-tetrahydroisoquinoline hydrochloride ((-)-3a) showed significant anticonvulsant activity. The structure-activity relationships with regard to the anticonvulsant activity of this series of compounds are discussed.

Animals↗
PubMed1996

Studies on cerebral protective agents. IX. Synthesis of novel 1,2,3,4-tetrahydroisoquinolines as N-methyl-D-aspartate antagonists.

A series of 1,2,3,4-tetrahydroisoquinoline derivatives were synthesized and evaluated for anticonvulsant activity against intracerebro-ventriculas (i.c.v.) N-methyl-D-aspartate (NMDA)-induced seizures in mice. Among these compounds, (+)-1-methyl-1-phenyl-1,2,3,4-tetrahydroisoquinoline hydrochloride ((+)-1a, FR115427) was the most effective anticonvulsant, and also protected CA1 hippocampal neurons from ischemia-induced neuronal degeneration in rats at 32 mg/kg i.p. In addition, (+)-1a showed anti-hypoxic activity in mice at 3.2-32 mg/kg i.p. The absolute configuration at the C-1 position of the isoquinoline ring was determined to be S by a single-crystal X-ray analysis of (+)-1a (+)-di-p-toluoyl-D-tartrate. Structure-activity relationships with regard to the anticonvulsant activity of this series of compounds are discussed, and the three-dimensional structures of (S)-(+)-1a and MK801 are compared.

Animals↗
PubMed1996

Purification and characterization of ferredoxin from Hydrogenobacter thermophilus strain TK-6.

Ferredoxin was purified from cells of Hydrogenobacter thermophilus strain TK-6. Purification was performed aerobically by the addition of octyl-beta-glucoside to the buffers. The purified ferredoxin had a molecular mass of 13,000 and contained a [4F3-4S] cluster. The protein had a long stretch at the N-terminal region; however, the sequence was not similar to the sequences of ferredoxins with a long stretch from Archaebacteria.

Amino Acid Sequence↗
PubMed1996

Accumulation of albumin-linked and free-form pentosidine in the circulation of uremic patients with end-stage renal failure: renal implications in the pathophysiology of pentosidine.

Pentosidine is an advanced glycation end product and its formation is shown to be closely related to oxidative processes. Recent studies have shown that pentosidine levels are increased not only in plasma and matrix proteins from diabetic patients, but also markedly in nondiabetic hemodialysis patients. Currently, the mechanism of accumulation and kinetics of pentosidine formation in hemodialysis patients remain unknown. Gel filtration of uremic plasma revealed that plasma pentosidine exists in the albumin fraction (approximately 90%) and, interestingly, in free form (approximately 5%) as well. Plasma free pentosidine was undetectable in subjects with normal renal function. There was a significant correlation between the plasma levels of albumin-linked and free pentosidine in hemodialysis patients. Kinetic studies indicated that dietary pentosidine was absorbed into the circulation and that, after either oral or intravenous administration of pentosidine to intact or nephrectomized rats, the plasma free pentosidine level was closely linked to the level of renal function. These findings demonstrate that: (1) Pentosidine accumulates as albumin-linked and in free form in the circulation of uremic patients; (2) dietary pentosidine can be absorbed into the circulation, thus being one possible origin of circulating free pentosidine; (3) free pentosidine may accumulate as a result of decreased glomerular filtration; and (4) the mechanism of accumulation of albumin-linked pentosidine is not related to high glucose levels. It suggests the simultaneous accumulation, during renal failure, of either unknown pentosidine precursor(s) or catalyst(s) of glycoxidation, independent of glucose.

Animals↗
PubMed1996

Glioblastoma multiforme in the left frontal lobe subsequent to malignant lymphoma in the right orbit.

A 62-year-old male presented with glioblastoma multiforme in the left frontal lobe manifesting as motor aphasia, subsequent to a malignant lymphoma in the right orbit. He underwent subtotal removal of the right orbital mass presenting as right exophthalmos which was shown by histological examination to be non-Hodgkin's lymphoma. He received 30 Gy Lineac irradiation to the right orbit. His post-operative course was satisfactory. Magnetic resonance (MR) imaging with gadolinium-diethylenetriaminepenta-acetic acid (Gd-DTPA) 7 months later demonstrated a small spotty enhanced lesion in the left frontal lobe. He developed motor aphasia 1 year after irradiation. MR imaging disclosed an enhanced mass in the left frontal lobe, which was totally removed. Histological examination revealed glioblastoma multiforme. Patients with malignant lymphoma may develop a subsequent second malignant tumor. MR imaging with Gd-DTPA is quite useful for early detection of a second brain tumor.

Brain Neoplasms↗
PubMed1996

Non-random chromosomal rearrangements and their implications in clinical features and outcome of multiple myeloma and plasma cell leukemia.

Rearrangements of bands 14q32.3 and 19p13.3 and preferential deletion of the short arm of chromosome 1 were nonrandom chromosomal abnormalities in MM and PCL, warranting further investigation at the molecular level. From the viewpoint of clinical relevance, chromosome 14q32 translocation seems to be associated with leukemic manifestation, level of LDH, and shorter survival period from the time of chromosomal analysis. However, these results were obtained from patients with advanced disease, most of whom had already been treated with alkylating agents prior to cytogenetic analysis. To investigate the karyotypes of MM in the early stage and to determine correlations with clinical features, non-dividing cells should be analyzed. For this purpose, interphase FISH and/or comparative genomic hybridization are promising procedures to detect genomic alterations in early multiple myeloma.

Adult↗
PubMed1996

High levels of Ca(2+)-independent endonuclease activity capable of producing nucleosomal-size DNA fragmentation in non-adherent marrow mononuclear cells from patients with myelodysplastic syndromes and acute myelogenous leukemia.

The endogenous endonucleases capable of producing nucleosomal-size DNA fragmentation are considered candidates of the key enzyme of apoptosis. We examined these activities in the nuclear fraction of non-adherent marrow mononuclear cells (NonAd-MNCs) from patients with myelodysplastic syndromes (MDS) and acute myelogenous leukemia (AML) using a nuclear autodigestion method. We detected Ca2+/Mg(2+)-dependent endonuclease activity in all samples examined. In contrast, Ca(2+)-independent activity with the ability to produce nucleosomal-size DNA fragmentation was found only in samples from a proportion of patients with MDS (12 of 26 consecutive cases) and all the patients with AML (n = 6), but not in the samples from control group patients (n = 10). This activity was correlated with the percentage of bone marrow (BM) blast cells to some extent. Although the levels of these endogenous endonuclease activities seem not to be correlated directly with the susceptibility of the cells to apoptosis, we postulate that the Ca(2+)-independent endonuclease activity may be associated with apoptosis and/or cell proliferation. Further follow-up study of these patients may be meaningful to clarify the prognostic significance of the Ca(2+)-independent endonuclease activity in patients with MDS.

Adult↗
PubMed1996

Matrix metalloproteinase 9 (gelatinase B) is expressed in multinucleated giant cells of human giant cell tumor of bone and is associated with vascular invasion.

Human giant cell tumor (GCT) consists of multinucleated giant cells and mononuclear stromal cells, and is characterized by frequent vascular invasion without distant metastases. To study the role of matrix metalloproteinases (MMPs) in the vascular invasion, we examined production of MMP-1 (tissue collagenase), -2 (gelatinase A), -3 (stromelysin-1), -9 (gelatinase B), and tissue inhibitors of metalloproteinases (TIMP-1 and -2) in GCT. MMP-9 was highly and predominantly expressed in giant cells by both immunohistochemistry and in situ hybridization. Expression of other MMPs was also observed in some cases but was inconstant. Sandwich enzyme immunoassays demonstrated that MMP-9 is the predominant MMP secreted by GCT. There was a definite imbalance between the amounts of MMP-9 and those of TIMPs in the culture media of GCT, leading to detectable gelatinolytic activity in an assay using 14C-gelatin. Gelatin zymography demonstrated the main activity at about 90 kd, which was identified as the zymogen of MMP-9 by immunoblotting. Immunohistochemistry for type IV collagen and laminin, major basement membrane components, showed that disappearance of the proteins is closely associated with MMP-9-positive giant cells. These results indicate the production of MMP-9 by multinucleated giant cells and suggest that the metalloproteinase may contribute to proteolysis associated with vascular invasion and local bone resorption in human GCT.

Adolescent↗
PubMed1996

[Surgical treatment of double-orifice mitral valve associated with incomplete-type endocardial cushion defect].

We report surgical treatment of double-orifice mitral valve (DOMV) associated with incomplete-type endocardial cushion defect. All three cases had "central type DOMV classified by Cascos" with bridging tissue between two mitral orifices. We closed mitral cleft in the two cases with moderate mitral regurgitation, although we left the bridging tissue. It is thought to be beneficial to leave the bridging tissue undivided to avoid postoperative mitral regurgitation in such cases.

Adult↗
PubMed1996

[Three cases of drug-induced hemolytic uremic syndrome].

We report three cases of drug-induced hemolytic uremic syndrome (HUS). Three patients with advanced gastrointestinal cancer underwent a curative operation and adjuvant chemotherapy with Mitomycin C (MMC), 5FU and Ara-C. Later, progressive anemia, thrombocytopenia, renal dysfunction and elevation of serum LDH were recognized. A diagnosis of HUS was made. As they had no symptoms of infectious diseases or relapse of cancer, the cause of HUS was thought to be MMC. Treatment with antiplatelet drugs and fresh frozen plasma was effective for two patients. However, one patient died of pulmonary edema.

Aged↗
PubMed1996

[Surgical treatment of infective endocarditis].

From 1981 to 1996, 48 consecutive patients, aged range 1 to 72 years, underwent surgical treatment for infective endocarditis. The infection was in the aortic valve in 10 patients, the mitral valve in 17, the aortic and mitral valves in 7, mixed aortic, mitral and tricuspid valves in one, the tricuspid valve in 9, the pulmonary valve in 3, and the other in 2, thirty-seven patients had native valve endocarditis (NVE) of which 22 cases were in the active stage. Seven cases had active prosthetic valve endocarditis (PVE) and 4 had VSD patch infection. The overall hospital mortality rate was 14.6% (7/48). The hospital mortality rate of NVE was 2.7% (1/37) and that of active NVE was 4.5% (1/22). That of PVE was 71.4% (5/7) and one of 4 cases with VSD patch infection was lost, so the mortality rate of the prosthetic material infection was 54.5% (6/11). Only 1 patient required reoperation for persistent infection. There were 2 late deaths caused by noncardiac disease. Thirty-nine of the total IE patients are now survived. These data demonstrate excellent results in patient with NVE undergoing the surgical treatment at the early phase, and support the premise that patients with active PVE should have also early surgical intervention.

Adolescent↗
PubMed1996

[Apoptosis in MDS].

We examined the endonuclease activity capable of inducing internucleosomal DNA fragmentation in hematopoietic cells. Mg(2+)-dependent nuclease activity was high in hematopoietic progenitor cells and the activity decreased with myeloid or erythroid differentiation. This was the case in MDS as well as in normal hematopoiesis. In contrast, Ca2+/Mg(2+)-dependent nuclease activity varied widely in the samples from MDS and the possibility was indicated that the activity of Glycophorin A+ cells was related to the degree of anemia. We also investigated DNA strand breaks in bone marrow samples from 16 patients with MDS and 10 with other diseases by an in situ end labeling (ISEL) technique. The reactivity in ISEL tended to increase parallel to disease progression of MDS. The high ISEL-positivity was also observed in some samples from patients with MPD and other diseases. Though ISEL is a useful technique for quantification of apoptosis, our results suggested that MDS cells with ISEL positive staining are not necessarily in the process of apoptosis.

Apoptosis↗
PubMed1996

Restoration of ischemic contractile failure of indo-1-loaded guinea pig heart by a calcium sensitizer, MCI-154.

We investigated the effect of a new Ca++ sensitizer, MCI-154, which is known to increase myofibrillar Ca++ sensitivity and maximal Ca(++)-activated force, on Ca++ transients and left ventricular (LV) function in indo-1-loaded Langendorff guinea plg hearts subjected to a reduction in coronary perfusion pressure from 80 to 40 mm Hg. During low-flow ischemia, LV contractility decreased by 50%, whereas systolic and diastolic indo-1 fluorescence ratios increased by 10%. The treatment with MCI-154 (10(-10) to 10(-6) M) 15 min after ischemia effectively restored the depressed LV function with little effect on indo-1 ratio. EMD 53998 (10(-9) to 10(-6) M), which also acts on maximal Ca(++)-activated force, restored LV function with a minimal impact on indo-1 ratio, but at 10(-5) M, EMD 53998 caused diastolic dysfunction, and its beneficial effect on systolic function disappeared. The relation between indo-1 ratio and LV contractility showed that MCI-154 and EMD 53998 restored ischemic contractile failure by Ca(++)-sensitizing action. It was noted that the restoration of LV dysfunction by MCI-154 or EMD 53998 was more pronounced than that by pimobendan, which acts primarily on Ca++ sensitivity. In contrast, the phosphodiesterase inhibitor milrinone restored LV function, but it doubled the increase in indo-1 ratio during ischemia. These findings suggest that a decrease in myofilament Ca++ responsiveness may be an important cause of ischemic contractile failure and that the restoration of depressed Ca++ responsiveness by intervention such as MCI-154 may be a promising approach for restoring the depressed function.

Animals↗
PubMed1996

[Effects of prostaglandin E1 on transient forebrain ischemia, especially in hippocampal CA 1 regions of the gerbil].

The effects of prostaglandin E1 (PGE1) on transient forebrain ischemia were studied in the gerbil. The animals were randomly divided into six groups of 6 each according to the method of administration as follows: group 1, no administration; group 2, subcutaneous administration with 5 ml.kg-1 of physiological saline, 30 min prior to ischemia; group 3, the same method with 3 mg.kg-1 of PGE1; group 4, 3 mg.kg-1 of PGE1, during 24 hours (12 hours prior to ischemia, and 12 hours following ischemia); group 5, 3 mg.kg-1 of PGE1, during 96 hours (12 hours prior to ischemia and 84 hours following ischemia); and group 6, sham operation. They were anesthetized with isoflurane and transient forebrain ischemia was induced by occluding bilateral common carotid arteries for 5 min. The extracranial electroencephalogram (EEG) was recorded from the electrodes placed at the vertex. During the experimental procedures, temperatures at tympanic membrane and rectum were maintained at 37.0 +/- 0.2 degrees C by means of a heating mat and control of the air temperature in all groups. After 6 days of survival, they were sacrificed, and the brain tissues were fixed for the immunohistochemical and histopathological analyses. The hippocampal CA 1 regions were stained for monoclonal anti microtubule-associated protein 2 (MAP 2), and hematoxylin and eosin. In the 4th group, EEG recovery was recognized earlier than the other groups. Immunoreactivities for MAP 2 and the number of surviving pyramidal cells after ischemia in the CA 1 regions were also well maintained. These results suggest the PGE1, has protective effects against degradation of cytoskeletal proteins and delayed neuronal death in the gerbil, and it might be due to direct protective action of cell membrane in addition to its microcirculatory improvement.

Alprostadil↗
PubMed1996

[Cheiro-oral syndrome following a cortical brain infarction in the precentral gyrus and at the base of the central sulcus. A case report].

We report a patient who manifested cheiro-oral syndrome following a cortical brain infarction without involvement of postcentral gyrus. A 67-year-old man was admitted to our hospital because of sudden paresthesia in his right face and right thumb and index finger. His cranial magnetic resonance imaging disclosed that the infarction was located in the left precentral sulcus and at the base of the central sulcus, while the left postcentral gyrus was not involved. His sensory symptom was attributed to the lesion of the Brodmann's area 3a, which is located at the base of the central sulcus. We postulate that the lesions responsible for cortical cheiro-oral syndrome are dispersed more widely than those for thalamic or pontine ones, since the somatotopy of face and hand in the cortex is distributed more extensively than that in the thalamus or pons.

Aged↗
PubMed1996

[Preclinical and clinical studies on the efficacy of bifonazole in patients with tinea pedis at 10 years after approval. Part 1. Susceptibility to bifonazole of clinical isolates of dermatophytes].

An investigation was carried out to determine whether or not here had been any changes in the susceptibility of clinically isolated strains of Trichophyton metagrophytes and Trichophyton rubrum (both leading causes of tinea) to bifonazole, an imidazole derivative and antifungal for topical use. Susceptibility was measured in 107 strains of these fungi isolated from clinical samples during a study on the treatment of tinea pedis with Mycospor cream in 1995, 42 strains isolated and stored in 1990, and 39 strains isolated and stored prior to development of the drug. The results are as follows: (1) There was no distinct difference in the susceptibility to bifonazole of T. mentagrophytes strains isolated before 1986 and those isolated in 1990 or 1995. (2) T. rubrum strains isolated before 1986 were slightly more susceptible to bifonazole than those isolated in 1995, while the 1990 strains were slightly less susceptible than the 1995 strains, but the difference was not significant. (3) The highest MICs of bifonazole for all the T. mentagrophytes and T. rubrum strains isolated from before 1986 and those in 1995 were relatively low, being 2.5 micrograms/ml and 1.25 micrograms/ml, respectively. These results suggest that no resistance or reduced susceptibility to bifonazole has emerged among clinical isolates of dermatophytes since the development of the drug.

Antifungal Agents↗
PubMed1996

[Fundamental and clinical studies on the efficacy of bifonazole in patients with tinea pedis at 10 years after approval. Part 2. Clinical evaluation].

The usefulness of bifonazole (Mycospor), a topical imidazole antifungal agent approved 10 years ago, was evaluated for the treatment of tinea pedis. Mycospor cream was applied by 141 patients with tinea pedis once daily for 4 233ks, and the clinical efficacy and adverse reactions (as well as any correlations with susceptibility of isolates and the mycological activity of the agent against these isolates) were studied. The results were then compared to those of a previous study. The following results were obtained. 1. Mycological activity Mycological examination results became negative in 63.2% (36/57) of the patients with plantar tinea pedis, in 94.1% (32/34) of those with interdigital tinea pedis, and in 74.7% (68/91) of all tinea pedis patients. 2. Mycological activity and MIC No correlation was found between the MICs of bifonazole against the pathogenic fungi and the rate of eradication on mycological examination. 3. Improvement of symptoms The improvement rates for local symptoms were 82.5% for plantar tinea pedis, 85.7% for interdigital tinea pedis, and 83.7% for all tinea pedis. 4. Clinical efficacy Good clinical efficacies were found in 61.4% of the patients with plantar tinea pedis, in 88.6% of those with interdigital tinea pedis, and in 71.7% of all patients. 5. Safety Regarding adverse reactions, what seemed to be contact dermatitis was reported in 5 out of 127 cases (3.9%). The reaction decreased or disappeared in all cases. 6. Usefulness Mycospor was found to be useful in 64.9% of patients with plantar tinea pedis, in 88.6% of those with interdigital tinea pedis, and in 73.9% of all tinea pedis patients. 7. Comparison with former results The results obtained in the present clinical study were comparable to those obtained in patients with tinea pedis treated in a double-blind comparative study conducted during the development of as a new topical antifungal agent. From the above results, Mycospor cream was confirmed to be still useful, although it has been used widely for the topical treatment of cutaneous mycoses in the past 10 years since its approval.

Adult↗