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Biomedical subjects

T Ueda

Publications and source records attributed to T Ueda.

At least 613 records · Page 34Linked to original sources

[The mechanism of apoptosis induced by anticancer agents in human leukemia HL-60 cells].

The present study was designed to investigate the contribution of proteases in anticancer agents-induced apoptosis of human leukemia HL-60 cells. A serine protease inhibitor TPCK and an ICE-like protease inhibitor VAD-FMK prevented etoposide, camptothecin and ara-C-induced internucleosomal DNA cleavage. Using a cell-free system, we have examined the inhibitory mechanism of these inhibitors on etoposide-induced internucleosomal DNA cleavage. We found that cell lysates prepared from etoposide-treated HL-60 cells undergoing apoptosis contain the significant activity to induce internucleosomal DNA fragmentation in isolated nuclei. On the other hand, we could not detect such activity in the cell lysates from untreated HL-60 cells. Treatment of the cell lysates with a serine protease inhibitor TPCK abrogated the DNA fragmenting activity. An ICE-like protease inhibitor VAD-FMK had no effect on this DNA fragmenting activity in vitro. However, the formation of TPCK-sensitive DNA fragmenting activity in etoposide-treated cells was blocked by the VAD-FMK. These data indicate that serine and ICE-like proteases may be involved in etoposide-induced apoptosis at the different stages, and especially a serine protease may be closely associated with the final step for induction of DNA fragmentation during apoptosis in HL-60 cells.

Antineoplastic Agents↗

[A successful surgical case of a dissecting aortic aneurysm with right-sided aortic arch and right-sided descending aorta].

The patient was a 70-year-old female whose aortogram and chest computer tomogram revealed DeBakey type IIIb dissecting aortic aneurysm in association with right-sided aortic arch, right-sided descending aorta and aberrant left subclavian artery arising from the Kommerell's diverticulum. Because she had cachexy with hoarseness and difficulty in swallowing caused by an aneurysm she received hypotensive therapy until recovery of her general condition before elective operation. The aneurysm was 7 cm in diameter and was replaced with vascular graft. Reconstruction of the aberrant left subclavian artery and closure of the false lumen via right thoracotomy were also performed under partial bypass installed between the right common femoral vein and artery using modified PCPS. Postoperative computer tomogram and aortogram showed properly replaced vascular graft and closure of false lumen. Dissecting aortic aneurysm complicated with a right-sided arch is quite rare. Including our case, 12 cases have been reported in the world and 9 cases were in Japan. This is one of the most successful surgical case for DeBakey type IIIb dissecting aortic aneurysm in association with right-sided aortic arch, right-sided descending aorta and aberrant left subclavian artery arising from the Kommerell's diverticulum.

Aged↗

[Surgical repair of a dissecting aortic aneurysm with entry at proximal descending aorta through left thoracotomy--a case report].

A 45-year-old man underwent a distal arch and descending aortic replacement through a left thoracotomy. His chronic type A dissecting aortic aneurysm had the entry at the proximal descending aorta. After 9 years of his first dissection, he suffered from a second dissection. In computerized tomogram (CT), the ascending and descending aorta enlarged to 6.0 cm and 7.0 cm in diameter, respectively and descending aorta showed a three channeled dissection. The open proximal anastomosis technique was used under the deep hypothermic circulatory arrest (HCA) followed by selective cerebral perfusion (SCP). Surgical repair included the obliteration of the proximal false lumen at the level between the left carotid and subclavian artery. A thrombosed retrograde dissection in the ascending aorta was revealed in postoperative evaluation, and decreased in size at follow up CT.

Aortic Dissection↗

[Intraperitoneal administration of carboplatin loaded alpha-tricalcium phosphate (alpha-TCP) particles in rats bearing abdominal carcinomatosis].

It is difficult to treat abdominal carcinomatosis with conventional chemotherapy, and many kinds of localized chemotherapy have been attempted. We used alpha-tricalcium phosphate (alpha-TCP) particles as a drug carrier in this study. alpha-TCP, which has chemically similar properties to human bone, has an excellent biocompatibility with human tissues and is biodegradable. The particles measured 50 to 100 microns in diameter, were round in shape and very porous. These particles have many open micro-pores of about 1 to 3 microns, which are beneficial for containing drugs. The compatibility and biodegradation of alpha-TCP particles were studied following intraperitoneal (ip) administration in normal rats. The following results were obtained: (1) alpha-TCP particles were intaken in the great omentum, and dissolved gradually. (2) The efficacy of ip administration of carboplatin-loaded alpha-TCP (alpha-TCP-CBDCA) was examined using a Donryu rat model with AH130 abdominal carcinomatosis. The alpha-TCP-CBDCA contained 200 mg alpha-TCP and 4 mg CBDCA. The pharmacokinetics of CBDCA following ip administration of alpha-TCP-CBDCA were studied. Pt levels in ascites and great omentum were higher in the alpha-TCP-CBDCA ip from 0.5 to 168 hours than those in the free-CBDCA ip and iv groups. These results suggest that the efficacy of CBDCA may be enhanced by utilizing alpha-TCP particles as a drug delivery carrier.

Animals↗

Superior cytotoxic potency of mitoxantrone in interaction with DNA: comparison with that of daunorubicin.

The mechanism of action of the anthraquinone antileukemic drug mitoxantrone (MIT) was investigated and compared with that of daunorubicin (DNR) with emphasis on the interaction with DNA to clarify the more potent cytotoxic activity of MIT than DNR in human leukemia cells. MIT showed similar characteristics to those of the anthracyclines such as DNR in that binding of MIT to DNA was associated with reduced template activity and cleavage of DNA in HL-60 human leukemia cells. However, as compared with DNR, MIT showed an increased number of binding sites on DNA, a lower inhibition constant for DNA polymerization, and a greater DNA cleavage activity. These properties may contribute to its greater potency than that of DNR, with which MIT inhibited the proliferation of HL-60 human leukemia cells.

Antineoplastic Agents↗

[Cyclic alteration in atheroma plaque morphology observed by intracoronary ultrasound: initiation mechanism of acute myocardial infarction].

Rupture of plaque is an important factor in the initiation of acute myocardial infarction. Plaque rupture is related to stress distribution in atheroma, but morphological alteration in coronary atheroma plaque in vivo is little understood. Atheroma plaque was observed during the cardiac cycle using 3.5 or 2.8 F, 30 MHz intracoronary ultrasound (ICUS) in seven patients with coronary artery disease. Coronary ostial pressure (P) measurements were simultaneously performed. Seven of the eccentric stenotic sites were analyzed. Intima-medial thickness (Th) and regional radius of curvature (R) at the middle and lateral portions of the atheroma were measured. Delta Th and % delta Th were calculated from change in thickness from end-diastole to peak systole. These parameters of the middle portion were compared with those of the lateral portion. The lateral % delta Th was 20.1 +/- 13.6% (delta Th 0.13 +/- 0.08 mm; 0.69 to 0.56 mm), and was significantly greater than the middle % delta Th [5.8 +/- 6.6% (delta Th 0.06 +/- 0.08 mm; 1.24 to 1.18 mm), p < 0.05]. Regional radius of curvature did not significantly differ. Wall stress calculated as P x R/Th was greater at the lateral portion (peak systole 3.7 x 10(5) dynes/cm2, end-diastole 1.9 x 10(5) dynes/cm2) than at the middle portion (peak systole 1.4 x 10(5) dynes/cm2, end-diastole 0.9 x 10(5) dynes/cm2). The change in stress from end-diastole to peak systole at the lateral portion was significantly greater (1.8 x 10(5) dynes/cm2) than that at the middle portion (0.5 x 10(5) dynes/cm2). The change in stress during the cardiac cycle, caused by the increase in intracoronary pressure, was greater at the lateral than at the middle of the plaque. This imbalanced distribution of stress may result in greater thinning of plaque at the lateral portion. Therefore, the distortion of plaque may be a mechanism for atheroma rupture at the lateral portion.

Aged↗

[Association between dental erosion and exposure to acids in a chemical factory].

An examination of dental erosion status and a semi-quantitative assessment of exposure to acids were carried out for 134 workers in a chemical factory in Osaka Prefecture, and an association between the dental erosion and the exposure to acids was discussed. 1) Percentage of workers with dental erosion of grade + or more among the subjects was 30.6%. 2) Most of the erosion was observed in the front teeth. There were more eroded teeth in the upper jaw than in the lower jaw. 3) The workers were divided into 4 groups according to job type at the time of the examination: production, research, clerical work and others. The production workers, those routinely handling a large amount of various kinds of acids, was the highest proportion of workers with eroded teeth. Because some of the clerical workers had previously handled acids, this group of workers included a larger number of those with dental erosion than the other two groups. 4) More than half of the workers who had been engaged in production had eroded teeth including those of grade +/- 5) The intensity of exposure to acids, as a semi-quantitative index for cumulative exposure to acids, was calculated in each worker from a score for the job type and its duration. A significant association was observed between the intensity and the manifestation of dental erosion.

Acids↗

Surfactant enhances adenovirus-mediated gene expression in rabbit lungs.

The efficiency and localization of gene transfer for gene therapy in the lung will depend on vector selection and technique used to deliver the vector. We hypothesized that surfactant might facilitate gene transfer because of its biophysical properties that enhance spreading of saline suspensions in the airways. We used a replication defective adenovirus directing the expression of the luciferase reporter gene at different virus doses and surfactant concentrations and instilled 4 ml suspensions into the lungs of adult rabbits. Transgene expression measured as luciferase-dependent light units in tissue homogenates 3 days after instillation had similar lobar distributions for surfactant-viral suspensions and for phosphate-buffered saline viral suspensions. However, total light units were four- to six-fold increased for viral doses of < 10(10) plaque forming units in 10 mg/ml or 25 mg/ml surfactant suspensions. The percentage of total transgene expression in the tracheacarina-bronchus decreased from over 50% to about 10% for virus instilled with surfactant concentrations of 2 mg/ml or greater, indicating preferential expression in airway epithelial cells located more distally in the lung. Surfactant did not enhance persistence of transgene expression 7 or 14 days after instillation. Surfactant facilitates adenovirally mediated gene transfer in the peripheral lung and enhances transgene expression.

Adenoviruses, Human↗

Expression of the KAI1 protein in benign prostatic hyperplasia and prostate cancer.

The KAI1 gene, recently identified as a metastatic suppressor gene for prostate cancer, was cloned and was revealed to be identical to the C33/IA4/ R2/4R9 gene. The expression of KAI1 protein was examined immunohistochemically in the tissues from 14 cases of benign prostatic hyperplasia and 46 cases of prostate cancer using mouse monoclonal anti-human C33 antibody. In benign prostatic hyperplasia tissues, KAI1 protein was uniformly expressed in the glandular cell membrane at cell-to-cell borders. The KAI1 protein in the tissues of untreated prostate cancer was also located at similar sites to those of benign prostatic hyperplasia, but the percentage of strongly positive cancer cells was correlated inversely to the Gleason pattern (P < 0.0001, one-way analysis of variance). There was also a statistically inverse correlation between the percentage of KAI1-positive cancer cells and the clinical stage (chi 2 = 9.6; P = 0.0081). In 4 cancer death cases relapsed from endocrine therapy, KAI1 protein was not stained in either primary or metastatic foci. These results indicate that the expression of KAI1 protein correlates to tumor characteristics in prostate cancer.

Adenocarcinoma↗

[Longitudinal study on association between care conditions and mortality among frail elderly living at home].

In order to elucidate the association between care conditions and mortality rate, a two year longitudinal study was performed on 115 frail elderly living at home. The main results were as follows; 1. Of the 115 frail elderly, 45 persons (39.1%) died during the two years. 2. A multiple logistic regression analysis revealed that the following factors were correlated to their death: age, activities of daily living (ADL), type of bedding. 3. Although ADL level was lower in the bed group than the Japanese style bed (futon) group at the first survey, survival rate was 69.8% in bed group and 47.5% in futon group. The relative risk of death with beds was 0.61 (95% confidence intervals 0.38-0.96) and was statistically significant.

Activities of Daily Living↗

[Operative results and long-term prognosis of aortic dissections].

We retrospectively analyzed the operative results and the long-term prognosis of aortic dissections. Between 1966 and 1996, we operated upon 137 patients with aortic dissection. According to the date of the first operation, they were classified into early (1966, 1985), middle (1985, 1992), and late (1992, 1996) cases. The hospital mortality rates of Stanford type. A patients were 40% (12/30) for early cases, 21 (6/28) for middle cases, and 13% (3/24) for late cases. Those of type-B patients were 10% (3/30) for early cases, 21% (3/11) for middle cases and 6% (1/16) for late cases. Actuarial survival rates for the all operative survivors of type-A patients (n = 60) were 77% at five year and 63% at 10 year. Those of type-B patients were 63% at five year and 20% at ten year. The difference of the two survival curves was significant (p < 0.01). In conclusion, the operative mortality rates for both type-A and type-B aortic dissection have reduced. But the more extended and rationale operation is recommended especially for type-B dissection in order to improve long-term prognosis.

Adult↗

[Dynamics of uric acid metabolism in hyperuricemia].

This paper is a review of the studies on urate metabolism of gouty patients with hyperuricemia and normal healthy subjects, performed mainly in our laboratory. The pathogenesis of hyperuricemia consisted of overproduction and underexcretion, which can be estimated using the urate clearance test. Overproduction was defined as urinary urate excretion (Uua) higher than [0.030 Cua + 0.325] mg/kg/hr and underexcretion as urate clearance (Cua) lower than 6.1 ml/min. According to those criteria, hyperuricemia was classified into the 4 types of overproduction (12%), underexcretion (60%), combined (25%) and normal type (3%). Patients with overproduction had a tendency of lower serum urate level (Sua) than those with underexcretion, higher Uua than those with the normal control and lower Cua and creatinine clearance (Ccr) than those with the normal control. Patients with underexcretion had a tendency of higher Sua and lower Cua, Ccr and Cua/Ccr ratio than those with overproduction or normal control. Patients with the combined type had the highest Sua among the 4 types, and those with the normal type had the lowest Sua. These findings indicate that each subtype of hyperuricemia has characteristic features in the urate metabolism, which are valuable for better understanding and treatment of hyperuricemia in gouty patients.

Blood Proteins↗

[Characteristic features of gouty patients].

Characteristic feature of pathogenesis, epidemiology and laboratory findings in hyperuricemia of gouty patients are studied and reasonable treatments of gout in clinical medicine are discussed. Gout is characterized by repeated arthritis attacks on the metacarpophalangeal joint of the first toe or other small joints, especially overworked joints or those exposed to cold. The arthritis attack lasts for 3.5 days and then diminishes gradually. The intervals are shortened in patients under poor hyperuricemic control but tophi formation is less frequent. Complications in combination with hyperlipidemia, diabetes mellitus, obesity and hypertension, which are compatible to syndrome X, are frequent in gouty patients and are suspected of rapidly progressing to arteriosclerosis, such as ischemic heart diseases. Hyperuricemia consists of over-production and underexcretion, which can be diagnosed by the urate clearance test. Classification is valuable for surveying the underlying diseases of secondary hyperuricemia and treating gouty patients. Underexcretion was observed in 85% of gouty patients with hyperuricemia and even the mean urate clearance in the overproduction type was significantly lower than that of normal controls, suggesting that underexcretion is a fundamental phenomenon in all gouty patients. Treatments of complications as well as those of hyperuricemia with uricosuric agents are required for clinical treatment of gouty patients.

Adolescent↗

Kinetically trapped structure in the renaturation of reduced oxindolealanine 62 lysozyme.

The refolded products of reduced native lysozyme and reduced OX62 lysozyme, in which Trp62 is converted to oxindolealanine (OX62) during the renaturation of sulfhydryl-disulfide interchange reactions at pH 8 and 37 degrees C, were investigated. On gel-chromatography eluted with 10% aqueous acetic acid containing 4 M urea, two peaks appeared in the refolded product of reduced OX62 lysozyme while a single peak appeared in the refolded product of reduced native lysozyme. From the analyses of the activity and primary and the tertiary structures of the derivative, the structure of the derivative from reduced native lysozyme was confirmed to be identical to that of the untreated one. On the other hand, the refolded product from reduced OX62 lysozyme had the same primary structure but a different tertiary structure compared to the untreated one. The tertiary structure of the refolded product from the reduced OX62 lysozyme was changed to that of the untreated one by the denaturation-renaturation treatment under nonreduced conditions. However, the refolded species was barely changed to that of the untreated one by incubation under physiological conditions. Therefore, the refolded product from reduced OX62 lysozyme was suggested to be a metastable and kinetically trapped product in the renaturation process of reduced OX62 lysozyme. In addition, an interaction involving the folding process of reduced lysozyme was discussed on the basis of the NMR analyses of the metastable structure.

Amino Acid Sequence↗

Determining surgical indications for acute type B dissection based on enlargement of aortic diameter during the chronic phase.

BACKGROUND: In patients with Stanford type B dissection who have been treated successfully with medical hypotensive therapy during the acute phase, a large number have incurred the risk of surgery during their chronic phases because of enlargement of the dissected aorta. The purpose of this study was to determine the indications for surgical treatment of acute type B dissection by studying chronic-phase enlargements of aortic dissections in patients treated successfully with medical hypotensive therapy during the acute phase. METHODS AND RESULTS: In 41 patients with type B dissection who had been treated medically during the acute phase, univariate and multivariate factor analyses were made to determine the predominant predictors for chronic-phase enlargement (> or = 60 mm) of the dissected aorta. Computed tomography was performed every 4 to 14 months to observe whether there was enlargement of the maximum aortic diameter. The predominant predictors for aortic enlargement in the chronic phase were the existence of a maximum aortic diameter of > or = 40 mm during the acute phase (P < .001) and a patent primary entry site in the thoracic aorta (P = .001). The values of actuarial freedom from aortic enlargement for the patients with a large aortic diameter (> or = 40 mm) during the acute phase and a patent primary entry site in the thorax at 1, 3, and 5 years were 70%, 29%, and 22%, respectively. No aortic enlargement was observed in the other patients throughout the entire follow-up period. CONCLUSIONS: These data suggest that patients with acute type B dissection who have a large aortic diameter (> or = 40 mm) and a patent primary entry site in the thorax should be treated surgically during the acute phase on the condition that the surgical risk in this phase is limited.

Acute Disease↗

Induction of apoptotic cell death by pancreatitis-associated ascitic fluid in Madin-Darby canine kidney cells.

We investigated the cytotoxicity on Madin-Darby canine kidney (MDCK) cells of pancreatitis-associated ascitic fluid (PAAF) collected from rats with experimental necrotizing pancreatitis. PAAF reduced viability of MDCK cells in a time- and dose-dependent manner. We detected DNA fragmentation on the PAAF-treated MDCK cells, indicating that the cytocidal action of PAAF is via apoptosis. From the results obtained, we conclude that PAAF contains factor(s) inducing apoptosis on MDCK cells, and we assume that apoptotic cell death is involved in the mechanism of organ failure in acute pancreatitis.

Acute Disease↗

Visible spectrophotometric assay, purification, and molecular properties of a lipoxygenase from eggplant (Solanum melongena Linne) fruits.

We purified a lipoxygenase to homogeneity from eggplant (Solanum melongena Linne) fruits employing the established visible spectrophotometric assay, in which the products of the lipoxygenase-catalyzed reaction, hydroperoxyfatty acids, oxidizes 2,2'-azino-di-[3-ethylbenzothiazoline-(6)-sulfonic acid] diammonium salt in the presence of a catalyst cytochrome c to yield chromophores in the visible region. This allowed for the rapid detection of the lipoxygenase activity and was helpful in accomplishing the efficient purification of the lipoxygenase. The purified lipoxygenase was a monomeric enzyme with a molecular weight of 95,000, s20,w of 5.3 S, and an isoelectric point of 4.4. The specific activity and Km value for the linoleate oxygenation were 7.8 mumol min-1 mg-1 and 0.8 mM, respectively, at 25 degrees C and pH 7.0. The enzyme contained 1.3 g-atom of nonheme iron per enzyme.

Chromatography, Gel↗