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Biomedical subjects

Y Wada

Publications and source records attributed to Y Wada.

At least 109 records · Page 6Linked to original sources
PubMed2001

In vivo complex formation of oxidized alpha(1)-antitrypsin and LDL.

An inactivated form of alpha(1)-antitrypsin (AT) and LDL coelutes in gel permeation chromatography. To characterize and to quantify the amount of this fraction of AT, a monoclonal antibody was established against chloramine T-oxidized AT and named OxAT-4. OxAT-4 recognized the oxidatively modified AT, including hexylaldehyde- or 4-hydroxy-2-nonenal-modified AT, but neither normal active AT nor trypsin/AT complex. Comigration of apoB and oxidized AT was demonstrated by Western blotting analysis of AT-LDL by means of anti-apoB monoclonal antibody and OxAT-4. A complex of oxidized AT and LDL (AT-LDL) was isolated from human plasma LDL by affinity column with an OxAT-4 antibody-coated carrier. AT-LDL was degraded 4 times more effectively by mouse peritoneal macrophages, but this was not mediated by scavenger receptor class A type I. Localization of AT-LDL was detected in human atherosclerotic lesions of the coronary artery, but distribution of it was not completely identical to that of macrophages. In situ hybridization revealed AT expression by macrophages, which were present in intimal layers of the coronary artery. From these findings, we concluded that AT is produced and oxidized by macrophages, then attached to LDL in the intimal layer of the arterial wall. Although AT-LDL that escapes into the blood stream can be cleared by hepatocytes, the remaining AT-LDL may be taken up by macrophages and contribute to the lipid accumulation in arterial wall cells as the early stage of atherogenesis.

Animals↗
PubMed2001

Suppression of fatty acid metabolism after exercise stress in patients with no electrocardiographic ST segment shift during balloon angioplasty.

Although ST segment shift is a marker of myocardial ischemia, some patients have no ST segment shift during percutaneous transluminal coronary angioplasty (PTCA). The aim of this study is to investigate myocardial perfusion and metabolism in adaptation for ischemia using 201TI and 123I-BMIPP dual exercise stress myocardial single photon emission computed tomography (SPECT) (dual stress SPECT). In 28 patients with coronary artery disease, dual stress SPECT was performed 3 weeks before PTCA. Early and delayed images were obtained at 5 minutes and at 3 hours after termination of ergometer stress, respectively. During PTCA, 12-lead ECG was recorded, and a significant ST segment shift was defined as more than 1 mm elevation or a depression of the J-point at the first ballooning. No collateral circulation on the coronary angiogram or 201TI filling on the delayed images were observed on any of the target regions of PTCA. Patients were divided into 2 groups: with (Group A: n = 15) and without (Group B: n = 13) significant ST segment shift during PTCA. A redistribution of TI was observed in 14 (93%) of Group A and 10 (77%) of Group B patients. Incidence of BMIPP redistribution was significantly higher in Group B (11 [85%]) than in Group A (3 [20%]) (p < 0.05). Redistribution of BMIPP means suppression of fatty acid metabolism during exercise stress. Augmentation of glucose metabolism is speculated to be an energy source in ischemic preconditioning.

Angioplasty, Balloon, Coronary↗
PubMed2001

Human sleep EEG analysis using the correlation dimension.

Sleep electroencephalograms (EEG) were analyzed by non-linear analysis. Polysomnography (PSG) of nine healthy male subjects was analyzed and the correlation dimension (D2) was calculated. The D2 characterizes the dynamics of the sleep EEG, estimates the degrees of freedom, and describes the complexity of the signal. The mean D2 decreased from the awake stage to stages 1, 2, 3 and 4 increased during rapid eye movement (REM) sleep. The D2 during each REM sleep stage were high and those during each slow wave sleep stage were low, respectively, for each sleep cycle. The mean D2 of the sleep EEG in the second half of the night was significantly higher than those in the first half of the night. Significant changes were also observed during sleep stage 2, but were not seen during REM sleep and sleep stages 3 and 4. The D2 may be a useful method in the analysis of the entire sleep EEG.

Adult↗
PubMed2001

Effects of a new antiallergic drug, VUF-K-8788, on infiltration of lung parenchyma by eosinophils in guinea pigs and eosinophil-adhesion to human umbilical vein endothelial cells (HUVEC).

Airway inflammation and reversible airway obstruction are hallmarks of bronchial asthma. In this study, we investigated the effects of a new antiallergic drug, 7-[3-[4-(2-quinolinylmethyl)-1-piperazinyl]-propoxy]-2,3-dihydro-4H-1,4-benzothiazin-3-one (VUF-K-8788), on histopathological changes in lung parenchyma of guinea pigs during late-phase asthmatic reaction (LAR), and on eosinophil-adhesion to human umbilical vein endothelial cells (HUVEC). Repeated exposure to ovalbumin of sensitized guinea pigs induced inflammatory phenomena such as hyperplasia of airway epithelial cells, perivascular edema and infiltration of lung parenchyma by eosinophils. VUF-K-8788 inhibited these histopathological phenomena at 10 mg/kg p.o. Moreover, the eosinophil-adherence to HUVEC was inhibited by VUF-K-8788 at the concentration of 10-30 microM. In conclusion, this inhibitory effect of VUF-K-8788 on eosinophil-adherence might contribute to the prevention of LAR and infiltration by eosinophils in the experimental asthmatic model in guinea pigs.

Animals↗
PubMed2001

Structure-activity relationships of N-(3,5-dimethoxy-4-n-octyloxycinnamoyl)-N'-(3,4-dimethylphenyl)piperazine and analogues as inhibitors of acyl-CoA: cholesterol O-acyltransferase.

A novel series of acyl-CoA: cholesterol O-acyltransferase (ACAT) inhibitors were synthesized from a lead compound, 1-(4-hydroxy-3-methoxyphenyl)-7-phenylhept-1-en-3-one (1, Yakuchinone B) through a modification of three regions (A, B, C) in the molecule. In this study, the compounds prepared were tested for in vitro inhibitory activity on microsomal ACAT from the liver of rats and for in vivo hypocholesterolemic activity in rats given a high cholesterol diet. N-(3,5-Dimethoxy-4-n-octyloxycinnamoyl)-N'-(3,4-dimethylphenyl)piperazine (45), which belongs to the amide compounds, has finally been discovered. Compound 45 inhibited rat hepatic ACAT in a more striking manner than CI-976, an amide compound ACAT inhibitor, and it exhibited a high level of hypocholesterolemic activity in vivo. Since 45 strongly inhibited both microsomal ACAT prepared from HepG2 (a cell line derived from human hepatocarcinoma) and Caco2 (a cell line derived from human colon adenocarcinoma), there is speculation that 45 might have the ability to inhibit ACAT in both the human intestine and liver independent of the difference in the distribution of ACAT isozymes. On the other hand, 45 did not induce adrenotoxicity in subacute toxicity studies in rats. These results suggest that it has promise for development as a new therapeutic agent for hypercholesterolemia and atherosclerosis.

Animals↗
PubMed2001

Fulminant myocarditis in polymyositis.

Cardiac involvement in patients with polymyositis is usually asymptomatic and associated with a mild clinical course. A female patient with muscle weakness and cardiogenic shock, who was diagnosed with polymyositis and fulminant myocarditis, is described. A large amount of methylprednisolone, in addition to intra-aortic balloon pumping and percutaneous cardiopulmonary support, led to the recovery of her cardiac function. However, a massive cerebral embolism occurred and she died. Postmortem histopathological examination showed necroses of muscles and diffuse invasion of mononuclear cells in both the myocardium and the biceps muscle of her arm. Although the mechanism of cardiac dysfunction is not clear, immunosuppressive therapy was effective for fulminant myocarditis in the present case.

Acute Disease↗
PubMed2001

VUF-K-8788, a periphery-selective histamine H1 antagonist with anti-pruritic activities.

The pharmacological properties of 7-[3-[4-(2-quinolinylmethyl)-1-piperazinyl]-propoxy]-2,3-dihydro-4H-1,4-benzothiazin-3-one (VUF-K-8788) were investigated in vitro and in vivo. VUF-K-8788 inhibited [3H]-mepyramine from binding to the cell membrane of lung parenchyma (Ki value: 5.0 nM) and the histamine-induced contraction of isolated guinea pig ileum (pA2: 9.71) without affecting ileal contractions induced by acetylcholine, serotonin, KCl and BaCl2. The increase of vascular permeabilities induced by histamine and passive cutaneous anaphylaxis (PCA) in guinea pigs were inhibited by VUF-K-8788 in a dose-dependent fashion (ED50: 0.24 and 0.26 mg/kg, p.o., respectively). Moreover, the anti-histaminic effect of VUF-K-8788 was also observed in rats. In experiments on the effects on the central nervous system, VUF-K-8788 at 1 mg/kg, p.o. hardly antagonized the H1 receptor at all in the cerebral cortex of guinea pigs. VUF-K-8788 inhibited the PCA-induced scratching behavior completely without affecting thiopental-induced sleep in mice. These results suggested that VUF-K-8788 would be useful in the treatment of allergic disorders such as atopic dermatitis and eczema.

Animals↗
PubMed2001

A case of influenza subtype A virus-induced fulminant myocarditis: an experience of percutaneous cardio-pulmonary support (PCPS) treatment and immunohistochemical analysis.

A 64-year-old man was admitted to the emergency center of Furukawa City Hospital because of common cold-like symptoms and hypotension. He was diagnosed as fulminant myocarditis with cardiogenic shock and arrhythmia elicited by influenza virus subtype A. Cardiac angiography, echocardiography and biopsy also showed myocarditis, and serum antibody titer to influenza virus subtype A was increased to 4-fold in paired serums. Treatments of both percutaneous cardio-pulmonary support (PCPS) and intra-aortic balloon pumping (IABP) were carried out to sustain the general circulation. PCPS treatment was discontinued on the 25th day of the admission, but IABP was continued. Finally, he died of multiple organ failure. The autopsy revealed myocardial necrosis with a slight fibrosis and a small amount of lymphocytic infiltration into the ventricular wall, which were compatible with restrictive myocarditis. Moreover, immunohistochemical analysis also showed the presence of viral antigens in cardiac myocytes. This case clearly showed that PCPS and IABP can be beneficial to sustain the general circulation in fulminant myocarditis, but cardiac pumping function failed completely to recover from myocardial damage.

Cardiopulmonary Resuscitation↗
PubMed2001

Regulatory effect of experimental diabetes on the expression of endothelin receptor subtypes and their gene transcripts in the rat adrenal gland.

Endothelins (ETs) mediate paracrine control of vascular tone and secretion of steroids and catecholamines in the adrenal gland through two ET receptor subtypes, ETA and ETB. The differential distribution and function of these subtypes are responsible for the multiplicity of endothelin actions in this tissue. This study examines the regulatory effects of experimental diabetes on the gene expression, subtype specificity and localization of ET receptor subtypes, ET isopeptides, and endothelin-converting enzyme-1 (ECE-1) in the rat adrenal gland. The densities, pharmacological properties and distribution of ET receptor subtypes ETA and ETB in adrenal glands from streptozotocin-induced diabetic, insulin-treated diabetic and age-matched control rats were investigated, using radioligand receptor binding and autoradiographic techniques. The gene expression of ETA and ETB receptors ET-1, ET-3 and ECE-1 was evaluated using relative multiplex reverse transcription/PCR. The induction of diabetes caused a marked reduction in body weight but no significant change in adrenal gland size. The density of ET receptors was significantly increased in the diabetic rat adrenal gland, mainly because of an increase in the expression of ETB receptors. Insulin treatment normalized the diabetes-induced changes in the expression levels of ET receptor subtypes to control levels. The expression level of ET-1 mRNA was up-regulated, whereas ET-3 mRNA was down-regulated in the diabetic adrenal gland compared with the controls. The ECE-1 mRNA level in the adrenal gland was not altered by the induction of diabetes. Autoradiographic studies showed that ETA and ETB are the predominant receptor subtypes in the adrenal medulla and cortex respectively. These results suggest that ETA and ETB receptors are differentially distributed and regulated in the diabetic rat adrenal gland.

Adrenal Glands↗
PubMed2001

Malignant fibrous histiocytoma of the heart: case report and review of 46 cases in the literature.

A rare case of cardiac malignant fibrous histiocytoma (MFH) is reported. A 55-year-old woman complained of palpitation due to atrial fibrillation. Echocardiography, magnetic resonance imaging, and angiography demonstrated a tumor arising from the posterior wall of the left atrium. At surgery, the tumor was almost entirely resected and histologically defined as MFH. Neither chemotherapy nor irradiation was administered. Echocardiography revealed a local recurrence two months after the surgery and the patient died of advanced cachexy and heart failure 2 years later. The details of this case are presented with a review of the literature.

Age Factors↗
PubMed2001

[A boy diagnosed SLE after Staphylococcus aureus infection over a long period].

We encountered a 13-year-old boy with SLE who showed specific pathophysiology. The affected child was hospitalized because of long-standing cutaneous empyesis considered to be Staphylococcus aureus infection, followed by manifestation of meningoencephalitis-like symptoms. On a close check up, the patient was diagnosed as having SLE complicated with interstitial lupus nephritis and verrucosis of the left ventricle. Besides the findings, the blastogenesis of the patient's lymphocyte was low against stimulation of sac-1 which connects with the Fc portion of lgG, one of the constituent proteins of Staphylococcus. Moreover, anti-phospholipid antibodies turned positive during immunosuppressive therapy and subcutaneous abscess due to Pseudomonas aeruginosae developed concurrently at about the same time, which posed difficulties in the treatment. The affected child had had Staphylococcus aureus infections over a long period of time before diagnosis of SLE and was susceptible to bacterial infections due to Pseudomonas aeruginosae during the treatment. The clinical course of this case was considered important in presuming the complex immunologically abnormal condition of SLE in childhood.

Adolescent↗
PubMed2001

Diltiazem, a calcium antagonist, inhibits matrix metalloproteinase-1 (tissue collagenase) production and collagenolytic activity in human vascular smooth muscle cells.

Calcium antagonists (CAs) are widely prescribed for patients with cardiovascular diseases. CAs have been reported to inhibit smooth muscle cell (SMC) proliferation in addition to their effects on vascular tone. To determine whether CAs potentially affect vascular remodeling, we measured the expression of matrix-degrading enzymes in growth factor-stimulated SMC. Human cultured SMC were stimulated with 10 ng/ml of platelet-derived growth factor (PDGF)-BB with or without a calcium antagonist, diltiazem. In the cell counting assay, diltiazem (10-5 M) alone had no effect on the proliferation of quiescent SMC, however 10-6-10-5 M of diltiazem dose-dependently inhibited PDGF-stimulated SMC proliferation. The inhibitory effects of diltiazem on SMC proliferation were further confirmed by a 5-bromo-2'-deoxyuridine (BrdU) incorporation assay and flow cytometry. In Western blotting, matrix metalloproteinase (MMP)-1 (tissue collagenase) but not MMP-2 (72-kDa gelatinase) expression was upregulated by PDGF and phorbol ester (TPA), which were reduced by diltiazem in a dose-dependent manner. The downregulation of MMP-1 expression was consistent with the reduction of collagenolytic activity measured by a FITC-conjugated type I collagen breakdown assay. PDGF-stimulated c-Jun/AP-1 expression, a major transcriptional factor for MMP-1, was not affected by diltiazem. In contrast, intracellular calcium ions measured with a fluorometric assay of Fluo-3AM-loaded cells revealed that the PDGF-stimulated increase in the intracellular calcium content was dose-dependently reduced by diltiazem. Our data suggest that diltiazem inhibits not only proliferation but also MMP-1 expression and collagenolytic activity in PDGF-stimulated SMC. The administration of CAs potentially influences the process of vascular remodeling, and this possibility should be further verified in vivo.

Blotting, Western↗
PubMed2001

[Functional hemispheric asymmetry in sustained attention].

This study examined the existence of functional hemispheric asymmetry in visual sustained attention in a dual-task setting. In the experiments, a circular arrangement of Gabor patches (GPs) was successively presented in the periphery during a 40-min vigil. The primary task was successive discrimination of digit type (Experiment 1) or tone frequency (Experiment 2). The secondary task was oddball orientation detection, requiring subjects to determine whether all of GPs were same or whether there was an odd one in the upper left, upper right, lower left, or lower right visual fields. Overall, results indicated that the perceptual sensitivity (A') for the detection task was higher in the left visual field than in the right visual field. Visual field differences in the vigilance decrement (the decline in A' over time) were observed when the primary task involved auditory discrimination. The implications for the functional lateral asymmetry in human sustained attention are discussed.

Adult↗
PubMed2001

[Laparoscopic radical prostatectomy: initial 17 case report].

PURPOSE: We report our early experience of laparoscopic radical prostatectomy for clinically localized prostatic cancer. MATERIAL AND METHOD: Between April and December 2000, 17 patients with clinical stage T1c to T2b prostatic cancer underwent laparoscopic radical prostatectomy. The median age was 70.9 year old, the median preoperative PSA and the median Gleason score of biopsy specimens was 7.1 ng/ml, 6, respectively. We followed the operation technique from the "Montsouris technique". Briefly, we used five trocars (two 10-mm and three 5-mm trocars) and the operation was performed transperitoneally. Pelvic lymph node dissection was performed in only one patient (case 3). Urethrovesical anastomosis was performed with 6 to 9 interrupted 3-0 absorbable sutures. RESULTS: No conversion to open surgery or reoperation was required in all cases. Median operation time was 450 minutes (range 290 to 750) and median intraoperative bleeding (including urine) was 600 ml (range 100 to 3,135). Only one case (case 3) needed homologous blood transfusion. Median postoperative Foley catheterization period was 9 days (range 5 to 19). Intraoperative complications related to operation procedure were one rectal injury and three vesical injuries, which were treated by absorbable suturing laparoscopically. Major complication was one complete A-V block (case 3) who was required a transient discontinuance of the procedure. Surgical margins were negative in 13 cases. Postoperative pathological evaluation was one pT0, five pT2a, seven pT2b and four pT3a. PSA value decreased less than 0.2 ng/ml after surgery in all patients. Although six months have passed after the surgery in only 4 patients, all of them were fully continent. CONCLUSION: Although the operation time is still longer than that of conventional open procedures, intraoperative magnified vision allows a more precise and safer dissection, especially for apical dissection. We believe that operative time will decrease with more experience. These results show that laparoscopic radical prostatectomy can be an acceptable treatment option for localized prostatic cancer.

Aged↗
PubMed2001

[A case of advanced gastric cancer with Virchow's and paraaortic lymph node metastases successfully resected after combined chemotherapy of low-dose CDDP and 5-FU].

The patient was a 61-year-old woman who had Stage IV advanced gastric cancer with Virchow's and paraaortic lymph node metastases. The lesions were considered surgically incurable, so she was placed on neoadjuvant chemotherapy consisting of low-dose CDDP and 5-FU. After 3 courses of chemotherapy, the tumor had decreased remarkably in size and Virchow's metastasis had disappeared. She was considered to have a partial response (PR) and underwent distal gastrectomy. Histopathological examination of the primary tumor revealed that almost all cancer cells existed in the mucosal and submucosal layers; few had infiltrated the serosa. A few paraaortic lymph nodes were positive for metastasis, but a curative resection (Cur B) was performed. The patient received another course of chemotherapy after the operation. Low-dose CDDP and 5-FU therapy was associated with few adverse events in this case, and thought to be effective against advanced gastric cancer.

Adenocarcinoma↗
PubMed2001

Change of hypervariable region proteins of hepatitis C virus E2 in two infants.

Two infants vertically infected with hepatitis C virus (HCV) were followed-up from 3 or 4 months to 2.5 years of age. We analyzed five complementary DNA (cDNA) clones from each patient and compared the genetic drift of the HCV E2 gene hypervariable region (HVR) between the two infants and between the infants and their mothers within the two families. The HCV strains initially detected in infant 1 were identical to those found in her mother, while the HCV strains initially detected in infant 2 were very different from those of her mother. The mutation rate of HVR-1 proteins was higher in mother 1 than in mother 2, but was 1.6 to 2-fold higher in infant 2 than in infant 1 during the follow-up period. Serum ALT levels or serum HCV-core protein activity did not correlate with the mutation rates of HVR-1 proteins in either infant. However, the mutation rate of HVR-1 proteins significantly increased from 6 months of age in both infants, with concomitantly increased serum HCV antibody (anti-HCV) levels.

Adult↗