Effect of ubenimex on a CD5-CD13+ CLL patient with an aggressive clinical course.
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Aged↗
Biomedical subjects
S Sawada
Publications and source records attributed to S Sawada.
[Two cases of nephrogenic adenoma in the bladder diverticulum].
We report two cases of a nephrogenic adenoma in the bladder diverticulum. The first patient was an 81-year-old man with gross hematuria. Cystoscopy revealed bladder diverticulum and a papillary tumor within. Bladder diverticulectomy was performed and the histopathological diagnosis was a nephrogenic adenoma. The second patient was a 50-year-old man with gross hematuria and dysuria. Transabdominal ultrasound revealed bladder diverticulum. Transurethral coagulation of the bladder diverticulum was performed. Then three papillary tumors were detected, and were resected transurethrally. The histopathological diagnosis was a nephrogenic adenoma. These are the first and second cases of a nephrogenic adenoma in the bladder diverticulum reported in Japan.
Adenoma↗
[Radiation exposure to patient and radiologist during transcatheter arterial embolization for hepatocellular carcinoma].
PURPOSE: To evaluate radiation exposure to patients and radiologists during transcatheter arterial embolization(TAE) for hepatocellular carcinoma. MATERIALS AND METHODS: In 39 TAE procedures performed at eight institutes, skin doses were evaluated with thermoluminescence dosimeters at the patient's back(entrance surface) and lower abdomen, and at the radiologist's forehead and abdomen. Real-time dosimeters were also used to evaluate patient skin dose. RESULTS: The patients' mean entrance surface dose was 973 +/- 681 mGy(range, 185 to 3543 mGy) with the mean fluoroscopic time of 21 minutes and 6 digital subtraction angiography(DSA) acquisitions. The dose at the patients' lower abdomen was 0.98 +/- 0.77 mGy. Doses for the radiologists were 0.04 +/- 0.04 mGy at the forehead and 0.15 +/- 0.19 mGy and 0.005 +/- 0.01 mGy at the abdomen over and under the apron, respectively. Fifty-six percent of the patients' skin dose was from DSA and 44% from fluoroscopy. CONCLUSIONS: Patient skin dose may occasionally exceed the dose for transient erythema. Because a patient may have repeated TAEs, skin doses or X-ray conditions should be recorded. The exposed doses of radiologists were considered to be acceptable with proper techniques. Further efforts to reduce radiation should be directed toward both DSA and fluoroscopy.
Aged↗
Inhibitory effect of tea flavonoids on the ability of cells to oxidize low density lipoprotein.
Dietary flavonoid intake has been reported to be inversely related to mortality from coronary heart disease, and the anti-atherosclerotic effect of flavonoids is considered to be due probably to their antioxidant properties. Oxidation of low density lipoprotein (LDL) has been reported to be induced by the constituent cells of the arterial wall. Accordingly, we examined the effect of pretreatment with tea flavonoids, such as theaflavin digallate, on the ability of cells to oxidize LDL. Theaflavin digallate pretreatment of macrophages or endothelial cells reduced cell-mediated LDL oxidation in a concentration- (0-400 microM) and time- (0-4 hr) dependent manner. This inhibitory effect of flavonoids on cell-mediated LDL oxidation was in the order of theaflavin digallate > theaflavin > or = epigallocatechin gallate > epigallocatechin > gallic acid. Further, we investigated the mechanisms by which flavonoids inhibited cell-mediated LDL oxidation using macrophages and theaflavin digallate. Theaflavin digallate pretreatment decreased superoxide production of macrophages and chelated iron ions significantly. These results suggest that tea flavonoids attenuate the ability of the cell to oxidize LDL, probably by reducing superoxide production in cells and chelating iron ions.
Animals↗
Tumor diameter/volume and pelvic node status assessed by magnetic resonance imaging (MRI) for uterine cervical cancer treated with irradiation.
PURPOSE: To evaluate the prognostic value of tumor diameter/volume and pelvic node status assessed by magnetic resonance imaging (MRI) in patients with uterine cervical cancer treated with radiation therapy. METHODS AND MATERIALS: Forty-four patients with intact uterine cervical squamous carcinoma treated with a combination of external irradiation and high-dose-rate intracavitary therapy were analyzed. Actuarial disease-free survival (DFS), pelvic control rate (PC), and distant metastasis-free rate (DMF) were analyzed by tumor diameter, volume, and pelvic node status assessed by pretreatment MRI. RESULTS: Anteroposterior (AP) and lateral (RL) tumor diameter significantly affected DFS. The 2-year DFS was 74% for patients with < 40 mm in AP diameter tumor, and 24% for > or = 40 mm tumor (p = 0.02). Whereas PC was not influenced, DMF was significantly affected by AP tumor diameter. Tumor volume did not significantly affect any endpoints. Patients with enlarged pelvic nodes had significantly poorer outcome compared to those with none on PC, DMF, and DFS. The 2-year DFS was 78% for node-negative, and 10% for node-positive patients (p = 0.0001). CONCLUSION: AP tumor diameter and pelvic lymph node status assessed by MRI were the significant prognostic factors in uterine cervical cancer treated with irradiation. Prognostic value of tumor volume should be reassessed prospectively with an appropriate imaging technique. AP tumor diameter predominantly affected the incidence of distant metastasis, and lymph node status affected both pelvic control and distant metastasis.
Adult↗
A role of protein kinase C in the regulation of cytosolic phospholipase A(2) in bradykinin-induced PGI(2) synthesis by human vascular endothelial cells.
The purpose of this study was to elucidate the mechanism by which bradykinin (BK) enhances prostacyclin (PGI(2)) production in human umbilical vein endothelial cells (HUVEC). BK-induced enhancement of PGI(2) synthesis was observed in a dose- and time-dependent manner, and it also increased [Ca(2+)](i) followed by enhancement of cytosolic phospholipase A(2) (cPLA(2)) activity. The PKC inhibitors GF109203X and H7 attenuated the BK-induced increase in [Ca(2+)](i) and inhibited the BK-induced PGI(2) synthesis. Phorbol 12-myristate 13-acetate increased cPLA(2) activity and PGI(2) synthesis but failed to alter [Ca(2+)](i). BK increased cPLA(2) mRNA eightfold by 15 min, and this increase was inhibited by pretreatment with the PKC inhibitors. In response to cycloheximide pretreatment, cPLA(2) mRNA was superinduced. These results suggest that BK stimulates PGI(2) synthesis in HUVEC by activation of cPLA(2) by dual mechanisms: an elevation of [Ca(2+)](i) and a PKC-dependent pathway. Moreover, changes in calcium kinetics and expression of cPLA(2) mRNA may underlie the BK-induced PGI(2) enhancement in these cells.
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
Interhospital network system using the worldwide web and the common gateway interface.
We constructed an interhospital network system using the worldwide web (WWW) and the Common Gateway Interface (CGI). Original clinical images are digitized and stored as a database for educational and research purposes. Personal computers (PCs) are available for data treatment and browsing. Our system is simple, as digitized images are stored into a Unix server machine. Images of important and interesting clinical cases are selected and registered into the image database using CGI. The main image format is 8- or 12-bit Joint Photographic Experts Group (JPEG) image. Original clinical images are finally stored in CD-ROM using a CD recorder. The image viewer can browse all of the images for one case at once as thumbnail pictures; image quality can be selected depending on the user's purpose. Using the network system, clinical images of interesting cases can be rapidly transmitted and discussed with other related hospitals. Data transmission from relational hospitals takes 1 to 2 minutes per 500 Kbyte of data. More distant hospitals (e.g., Rakusai Hospital, Kyoto) takes 1 minute more. The mean number of accesses our image database in a recent 3-month period was 470. There is a total about 200 cases in our image database, acquired over the past 2 years. Our system is useful for communication and image treatment between hospitals and we will describe the elements of our system and image database.
CD-ROM↗
Chronic antisense therapy for angiotensinogen on cardiac hypertrophy in spontaneously hypertensive rats.
OBJECTIVE: We examined the effect of the suppression of plasma angiotensinogen (AGT) by the intravenous injection of antisense oligodeoxynucleotides (ODNs) against AGT targeted to the liver on cardiac remodeling in spontaneously hypertensive rats (SHR). The ODNs against rat AGT were coupled to asialoglycoprotein (ASOR) carrier molecules, which serve as an important method for regulating liver gene expression. METHODS: Male SHR (n = 18), and age-matched male Wistar-Kyoto rats (WKY, n = 6) were used for this study. At 10 weeks of age, the SHR were divided into three groups (each group n = 6), and the systolic blood pressure (SBP) did not significantly change among them. The control SHR and WKY groups received saline, the sense SHR group was injected with the sense ODNs complex and the antisense SHR group was injected with the antisense ODNs complex, from 10 to 20 weeks of age. ASOR-poly(L)lysine-ODNs complex was injected via the tail veins twice a week. RESULTS: At the end of the treatment, a reduction of hepatic AGT mRNA, cardiac angiotensin II type 1 receptor mRNA and the plasma AGT concentration was only observed in the antisense-injected SHR but not in the other groups of SHR and WKY. This antisense therapy did not significantly change the mRNA expression for angiotensin converting enzyme, angiotensin II type 2 receptor and AGT in the left ventricle (LV) among all three groups. Although the plasma angiotensin II (Ang II) concentration significantly decreased to the level of WKY after the antisense therapy, the SBP, LV to body weight ratio and % collagen volume fraction also showed a reduction, however, these findings were still larger than in the WKY than in either the sense-injected SHR or control SHR. CONCLUSION: The plasma AGT is considered to play a role in the development of cardiac hypertrophy in SHR, but it has not a complete effects on cardiac remodeling even if the plasma Ang II levels are inhibited because of an insufficient suppression of hypertension.
Analysis of Variance↗
Secretion of prebeta HDL increases with the suppression of cholesteryl ester transfer protein in Hep G2 cells.
Prebeta HDL are small, protein rich lipoproteins that are predominantly composed of apo A-I, without apo A-II. Prebeta HDL are secreted from the liver as nascent HDL and/or are produced in the incubated plasma by cholesteryl ester transfer protein (CETP). However, the role of CETP in the secretion of HDL from the liver has yet to be determined. In the present study, we examined the effect of the suppression of hepatic CETP by antisense oligodeoxynucleotides (ODNs) against CETP targeted to the liver on the secretion of apo A-I using a Hep G2 cell culture. The ODNs against CETP were coupled to asialoglycoprotein (ASOR) carrier molecules, which serve as an important method for the regulation of liver gene expression. Hep G2 cells were cultured in DMEM supplemented with 10 FBS. After 2 days, the medium was changed to DMEM with EGF and the cells were divided into three groups. The control group received saline, while the sense group was mixed with the sense ODNs complex and the antisense group was mixed with the antisense ODNs complex, respectively, for 2 days. Both the hepatic CETP mRNA and the CETP mass in the medium in the antisense group decreased significantly more than in the sense and the control groups (CETP mass: 1.697 + /- 0.410 ng/mg cell protein vs. 2.367 + /- 0.22 and 2.360 + /- 0.139, n = 3 in each determination). In contrast, both the hepatic apo A-I mRNA and the apo A-I mass in the medium in the antisense group were significantly higher than those in the sense and the control groups (apo A-I mass; 1.877 + /- 0.215 micro/mg cell protein vs. 1.213 + /- 0.282 and 1.097 + /- 0.144, n = 3 in each determination). The increase in apo A-I was mainly due to the increase in prebeta apo A-I. These findings may partly explain why HDL and apo A-I increase in patients with CETP deficiency, while also indicating the possibility that the original level of prebeta HDL is sufficient in such patients.
Apolipoprotein A-I↗
The effect of the chemical structure of the phospholipid polymer on fibronectin adsorption and fibroblast adhesion on the gradient phospholipid surface.
The interaction between biocomponents and the polyethylene (PE) surface modified with poly[omega-methacryloyloxyalkyl phosphorylcholine (MAPC)] was considered taking into account the surface characteristics, i.e., density, mobility, and orientation of the poly(MAPC). The PE surface, grafted gradually with the poly(MAPC) was prepared by corona irradiation method. The amount of peroxide produced on the PE surface which was determined with 1,1-diphenyl-2-picryl-hydrazyl, increased with an increase in the energy of the corona. The surface density of the poly(MAPC) was increased with an increase in the amount of the peroxides produced by the corona irradiation. The orientation and mobility of the poly(MAPC) grafted on the PE surface was evaluated with 1,6-diphenyl-1,3,5-hexatriene. The orientation of the poly[6-methacryloyloxyhexyl phosphorylcholine (MHPC)] which has six methylene chains between the phospholipid polar group and the backbone was higher than that of other poly(MAPC)s. The mobility of the poly(MAPC) decreased with an increase in the methylene chain length in the MAPC unit. The fibronectin adsorption on the gradient PE sheet grafted with poly(MAPC) was determined with enzyme-labeled immunoassay. The amount of adsorbed fibronectin on the PE grafted with poly[2-methacryloyloxyethyl phospohorylcholine(MPC)] and poly(MHPC) decreased with an increase in their surface density. Especially, the PE sheet grafted with the poly(MHPC) was effectively reduced compared with other poly(MAPC)s. On the poly[10-methacryloyloxydecyl phosphorylcholine (MDPC)], there is a minimum amount of adsorbed fibronectin. The fibronectin adsorption pattern on the PE sheet grafted with poly(MAPC) was quite different from the chemical structure of the MAPC unit. The human normal diploid fibroblasts (WI-38 cells) were cultured on the gradient PE sheet grafted with poly(MAPC) changing the concentration of seeded WI-38 cells. The adhesion behavior of the WI-38 cells was different depending on the concentration of the seeded WI-38 cells. When the concentration was low, the number of the adherent WI-38 cells had the same tendency as fibronectin adsorption. The gradient PE sheet grafted with the poly(MHPC) effectively reduced WI-38 cells adhesion even when the concentration of the WI-38 cells was high. The biocompatibility of polymer surfaces can be improved by highly oriented phosphorylcholine group.
Adsorption↗
Effect of probucol on intracellular pH and proliferation of human vascular endothelial cells.
We investigated the effect of probucol on the intracellular pH ([pH]i) and proliferation of human umbilical vein endothelial cells (HUVEC), as well as their production of prostacyclin (PGI2). The addition of probucol produced a biphasic shift in [pH]i, with a brief initial acidification followed by a rapid alkaline shift. After pretreatment with EGTA, the initial decrease in [pH]i was abolished, and the subsequent increase was inhibited. After pretreatment with amiloride, only the increase of [pH]i was abolished. These results suggest that the probucol-induced increase of [pH]i was mainly dependent on Na+/H+ exchange and partly on extracellular Ca2+. In contrast, the addition of LDL produced a decrease of [pH]i. Under Ca2+-free condition, [pH]i was further decreased by LDL. In cells pretreated with amiloride, however, [pH]i was not further decreased by LDL. It was found that probucol promoted cell proliferation, and LDL inhibited cell proliferation. Addition of probucol also enhanced prostacyclin generation by HUVEC. This enhancement of PGI2 generation resulted from increased release of Ca2+ from the storage sites, due not only to increased production of inositol 1,4,5-triphosphate (IP3) but also to the increase of [pH]i. These findings may help to explain the antiatherosclerotic action of probucol.
Amiloride↗
The mechanism of thrombin-induced prostacyclin synthesis in human endothelial cells with reference to the gene transcription of prostacyclin-related enzymes and Ca2+ kinetics.
This study was designed to evaluate the effect of thrombin on prostacyclin (PGI2) production in cultured human vascular endothelial cells in association with intracellular Ca2+ and with the gene expression of prostaglandin H2 synthase (PGHS) and phospholipase A2 (PLA2) using competitive polymerase chain reaction. Thrombin enhanced the PGI2 synthesis dependent with time. Additionally, thrombin increased the intracellular Ca2+, which stimulates PLA2, resulting in arachidonic acid cleavage from membrane phospholipids and its subsequent conversion into PGI2 through the PGHS pathway. The elevation of intracellular Ca2+ was a result of Ca2+ influx and Ca2+ release from its intracellular storage sites. In this study, PGHS-1 mRNA was constitutively expressed, whereas PGHS-2 mRNA was not. With the stimulation of thrombin, cytosolic PLA2 (cPLA2) mRNA increased 9-fold at 15 min, PGHS-1 mRNA increased 3.4-fold at 180 min, and PGHS-2 mRNA increased 38-fold at 60 min. These results suggest that the elevation of intracellular Ca2+ and the expression of cPLA2, PGHS-1, and PGHS-2 mRNA cause PGI2 generation.
Calcium↗
The rebound phenomenon of glycerol-induced changes in the endolymphatic space.
Volumetric changes of the scala media were histologically investigated in normal guinea pigs to see whether glycerol-induced volumetric change of the scala media followed a biphasic course similar to the auditory threshold in the glycerol test. Glycerol was administered orally in a 12 ml/kg dose. The volume of the scala media was assessed by examining the cross-sectional area of the scala media in the mid-modiolar sections of the cochlea. Histological study revealed that the time-course of the change in the volume of the scala media after glycerol intake showed biphasic changes. Specifically, the early phase of the glycerol effect is a decrease in endolymph volume. The volume of the scala media significantly decreased by 11.4+/-2.9% 2 h after glycerol intake. Thereafter, the volume began to increase, and reached its peak 6-12 h after intake. In addition, the volume of the scala media significantly increased by 17.6+/-1.1% after 6 h. The present study indicated that the secondary increase in the volume of the scala media following glycerol intake played an important role in the rebound phenomenon in the glycerol test, although the mechanism underlying the hearing loss with the endolymphatic hydrops remains to be elucidated.
Administration, Oral↗
Hyperfractionated radiotherapy followed by adjuvant chemotherapy for nasopharyngeal cancer: report of seven cases.
Cases of hyperfractionated radiotherapy and adjuvant chemotherapy for nasopharyngeal cancer are reported. Seven patients received hyperfractionated radiotherapy (76.8-81.6 Gy/64-68 fractions to primary tumor) and two cycles of cisplatin (80 mg/m2 i.v. on day 1) plus 5-FU (800 mg/m2 continuous infusion on days 2-6). Mucositis was the most frequent side effect in hyperfractionated radiotherapy. Moderate leukopenia was the major side effect of adjuvant chemotherapy. With a mean follow-up time of 34 months (range 25-48 months), five of the seven patients were locoregionally controlled. Two developed distant metastases. Two patients suffered late complications (posterior nasopharyngeal wall necrosis and brain necrosis). These results suggested that our regimen was almost well tolerated and might be of use in locoregional control of nasopharyngeal cancer. However, it carries some risk of late complications and might be inadequate for preventing distant metastases. A three-dimensional conformal boost irradiation technique and adequate dose intensity chemotherapy might be encouraged.
Adult↗
Detection of two novel mutations (nt2762, exon 2, CAG to TAG, and nt2483 or 2484, exon 2, +A) in individuals with congenital type I antithrombin deficiencies.
Genetic analyses were performed on two Japanese kindreds with congenital type I antithrombin deficiency causing recurrent thrombosis. The seven exons and flanking intron regions of the antithrombin gene were amplified by polymerase chain reaction followed by direct nucleotide sequencing. In case 1, one novel nonsense mutation, CAG to TAG at codon 100, nucleotide 2762, in exon 2, was detected. In case 2, one novel minor insertion, AT to AAT at codon 7, nucleotide 2483 or 2484, in exon 2, was detected, leading to a frameshift which resulted in a stop codon TGA at codon 32.
Adolescent↗
Prolonged partial liquid ventilation in spontaneously breathing awake animals.
OBJECTIVE: To date, studies of partial liquid ventilation (PLV) have examined its effects acutely in anesthetized and mechanically ventilated subjects. We set out to develop a model of prolonged PLV in awake, spontaneously breathing animals. DESIGN: Animal case series SETTING: Cardiopulmonary physiology laboratory. SUBJECTS: Fifteen New Zealand white rabbits (3.2+/-0.39 kg). INTERVENTIONS: Animals were anesthetized and instrumented with a novel technique allowing percutaneously assisted placement of an intratracheal catheter with a subcutaneously tunneled externalized free end. After anesthetic recovery, PLV was performed in spontaneously breathing unsedated animals. MEASUREMENTS AND MAIN RESULTS: Evaporative losses were determined using a single 10 mL/kg perflubron dose (n = 5); hourly radiographs were obtained until residual perflubron was minimal. For prolonged PLV (n = 10), a 10-mL/kg initial perflubron dose was followed every 4 hrs with 5-mL/kg supplements. Radiographs were obtained immediately before and after perflubron administration and were scored (0-5) by a radiologist blinded to dosing regimen and time interval. Data were analyzed with ANOVA and Student's t-test with correction for multiple comparisons. Initial filling was nearly complete (score = 4.8+/-0.42); lungs were maintained approximately half-filled through 4 hrs (score = 2.53+/-0.71). By 6 hrs, the majority of perflubron had evaporated (score = 1.75+/-0.53). Over 24 hrs, radiographs documented continuous perflubron exposure (postffill = 4.53+/-0.64, prefill = 3.40+/-0.71, average = 3.97+/-0.43); scores were comparatively higher after filling (after = 4.53+/-0.64, before = 3.4+/-0.71, p< .001). Left and right lung volumes were equivalent (left = 4.06+/-0.47, right = 3.89+/-0.39, p = .027). All animals survived the 24 hrs of PLV. CONCLUSIONS: Percutaneously assisted intratracheal cannulation with catheter exteriorization permits prolonged PLV in spontaneously breathing, unsedated animals. Continuous perfluorocarbon exposure with this method is reproducible, consistent, and well tolerated for 24 hrs in uninjured animals.
Analysis of Variance↗
Interleukin-1alpha stimulated prostacyclin release by increasing gene transcription of prostaglandin H synthase and phospholipase A2 in human vascular endothelial cells.
This study was conducted to evaluate the effects of interleukin-1alpha (IL-1alpha) on prostacyclin (PGI2) production in cultured human vascular endothelial cells in association with intracellular Ca2+, inositol 1,4,5-trisphosphate (IP3), and with prostaglandin H synthase (PGHS) and phospholipase A2 (PLA2) gene expression by using the competitive polymerase chain reaction (PCR) method. IL-1alpha did not increase PGI2 production for 15 min, but induced an increase of about three-fold relative to that in controls at 60 and 180 min. IL- 1alpha had no effect on intracellular Ca2+ levels throughout the experimental period. In this study, consistent with previous reports, PGHS-1 messenger RNA (mRNA) was constitutively expressed, whereas PLA2 mRNA was not. After stimulation with IL-1alpha, PLA2 mRNA level showed an eightfold increase within 15 min, and PGHS-2 mRNA level increased by 76-fold within 180 min. PGHS-1 mRNA level was increased 1.6-fold at 180 min. These results suggest the existence of regulatory mechanisms of IL-1alpha-induced PGI2 production, which involve PGHS and PLA2 gene transcription.
Base Sequence↗
Dosimetric characteristics of acrylic and stainless steel cones for electron beam therapy.
Dosimetric characteristics of acrylic and stainless steel cones for electron beam therapy were investigated. Acrylic and stainless steel cylindrical cones of 6, 7, and 8 cm in diameter and electron beams of energies 6, 9, 12, 15, 18, and 21 MeV were used for the measurements. Both acrylic and stainless steel cones showed high dose areas along the rim. The dose along the rim grew with increasing electron beam energy. The highest dose along the rim was 115% of the maximum dose on a central axis when a 6-cm-diameter acrylic cone and 21-MeV electrons were combined.
Acrylates↗