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Biomedical subjects

Y Ueda

Publications and source records attributed to Y Ueda.

At least 37 records · Page 2Linked to original sources
PubMed1996

[Analysis of HCV infection in patients with hemophilia].

Second generation antibodies of HCV, HCV-RNA, genotype and data of liver function were investigated with the purpose of better understanding the condition of the 32 hemophiliac patients currently in our hospital. The results being: 1) The positivity ratio of second generation antibodies was 96.9% and a negative example occurred in only one infant born in 1990. 2) In the positive example of second generation antibodies, HCV-RNA positivity was 77.4%, which is extremely high result. 3) There are several kinds of genotypes, such as type I, type II, type II + III and type III. Type I is most commonly found in the younger generation. The possibly for this presence was suggested to be from imported blood products. 4) There were few findings of liver disorder in cases of HCV-RNA negative patients. Meanwhile, the presence of liver disorder was found in about 70% HCV-RNA patients. There is evidence of correlation between the level disorder and age of the patient. In general, initial infection for hemophiliac patients takes place early in life. Compared to non-hemophilia hepatitis C patients, the liver disorder occurs at all ages but is becoming more prevalent younger patients. Although not common, there were occasionally a few cases of liver disorder turning into cirrhosis of the liver in patients in their 30's.

Adolescent↗
PubMed1996

Decrease in oxygen cost of contractility during hypocapnic alkalosis in canine hearts.

Ca2+ sensitization of contractile machinery could theoretically enhance the mechanoenergetics of the heart. We studied the effects of alkalosis with Ca2+ sensitization on mechanoenergetics within the framework of the relationships of left ventricular pressure-volume area (PVA; a measure of the total mechanical energy), myocardial oxygen consumption per beat (VO2), and the contractility index [E(max) (slope of end-systolic pressure-volume relation)] in 10 excised, cross-circulated canine hearts. Alkalosis was stably maintained without hypoxia (mean pH 7.66). Alkalosis increased E(max) without changing the slope of the VO2-PVA relation, a reflected contractile efficiency. The incremental ratio of unloaded VO2 to E(max) in alkalosis was significantly lower than that in Ca2+ sensitization (0.0012 +/- 0.0010 vs. 0.0062 +/- 0.0030 ml O2 . mmHg-1 . ml . beat-1 . 100 g LV-2; P < 0.01). Basal metabolism under KCl arrest was unchanged by alkalosis, indicating the decreased energy cost of the excitation-contraction coupling by alkalosis. Compared with the control, alkalosis increased E(max) during the Ca2+ infusion of various concentrations without any further increase in unloaded VO2. Thus we demonstrated a decreased oxygen cost of contractility during alkalosis, presumably due to Ca2+ sensitization.

Alkalosis, Respiratory↗
PubMed1996

Pharmacokinetics of indomethacin ester prodrugs: gastrointestinal and hepatic toxicity and the hydrolytic capacity of various tissues in rats.

In order to develop a potential prodrug of indomethacin (IM) which causes less irritation to the gastrointestinal mucosa, the ester prodrugs [butyl ester (IM-BE) and octyl ester (IM-OE)] of IM were synthesized and evaluated for their ulcerogenic activity and hepatic injury after oral administration in rats. Additionally, the kinetics of hydrolysis of the prodrugs were examined to characterize the tissues or organs capable of hydrolyzing the ester bonds. The plasma levels of IM after the oral administration of IM-OE and IM-BE were comparatively low compared with those after IM, with a small bioavailability (2.1 and 15.0%, respectively). Ulcerogenic activity and hepatic injury, expressed by decreased hepatic microsomal enzyme activities, were hardly seen after repeated oral administration of the prodrugs, in contrast with the severely irritating effects of IM alone. Hydrolysis of the prodrugs was adequately described by first-order kinetics. IM-BE was relatively rapidly hydrolyzed in plasma, skin and whole blood, but the hydrolysis in the intestinal mucosa and liver was very slow. The hydrolytic rates for IM-OE were exceedingly small or negligible. These results indicate that the main part of IM-BE and IM-OE administered orally might not be hydrolyzed to IM in the gastrointestinal tract, and that the ester prodrugs themselves were absorbed through the mucosa; also, that the hydrolysis of ester bonds would be carried out mainly in the circulatory system. Consequently, IM-BE seems to be an ideal prodrug of IM.

Administration, Oral↗
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

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

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↗
PubMed1995

Urinary C4 excretion in systemic lupus erythematosus.

The fourth component of complement (C4) in urine was measured in 19 patients with systemic lupus erythematosus (SLE). Urinary C4 was detectable in all SLE patients using an enzyme linked immunosorbent assay. In 11 of 13 patients whose urinary C4 was serially measured, a decrease of urinary C4 was found in parallel with a decrease of disease activity of SLE. In the remaining 2 patients, the amount of C4 increased preceding a flare-up of the disease. The measurement of urinary C4 may be useful in evaluating the disease activity of SLE in individual patients and sometimes in predicting the flare-up of the disease. The specific hemolytic activity of excreted C4 and Western blotting analysis showed that urinary C4 consisted mainly of degraded fragments of C4. In two cases, camostat, a serine protease inhibitor, rapidly decreased the urinary C4 excretion, suggesting that the complement activation occurred in the glomerulus in lupus nephritis.

Adolescent↗
PubMed1995

Serial lectin affinity chromatography demonstrates altered asparagine-linked sugar chain structures of gamma-glutamyltransferase in human renal cell carcinoma.

Differences between human renal cortex and human renal cell carcinoma (RCC) in asparagine (Asn)-linked sugar chain structures of gamma-glutamyltransferase (GGT) were investigated by using a serial lectin affinity chromatographic technique. The relative amounts of GGT which passed through the concanavalin A (Con A) column but bound to the phytohaemagglutinin E column, were significantly decreased in RCC, but there were significant increases in the relative amounts of GGT which bound weakly to the Con A column and passed through the pea lectin (PSA) column, and bound strongly to the Con A column and bound to the wheat germ agglutinin column in RCC compared with those of the normal renal cortex. A significant correlation was observed in RCC between nuclear grade and relative amount of GGT which bound weakly to the Con A column and passed through the PSA column. The findings indicate that Asn-linked sugar chain structures are altered in RCC and suggest that studies of qualitative differences of sugar chain structures of GGT might lead to a useful diagnostic tool for human RCC.

Adult↗