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Biomedical subjects

T Uchida

Publications and source records attributed to T Uchida.

At least 37 records · Page 2Linked to original sources
PubMed2001

Childhood subarachnoid hemorrhage associated with fibromuscular dysplasia.

A rare case of childhood subarachnoid hemorrhage (SAH) is reported. A 5-year-old boy presented with SAH. A cerebral angiogram showed obstruction of the first segment of the left anterior cerebral artery (A1). The A1 was surgically trapped to prevent rebleeding. Proliferation of myofibroblasts was revealed in the intima of the A1. Cerebral infarction appeared in the territory of the left middle cerebral artery (MCA) on day 2 after onset of SAH, and the patient suffered a second SAH on day 26. The second angiogram showed stenosis and a saccular aneurysm in the left MCA. A second surgery, neck clipping of the aneurysm, was needed. The multiple arterial lesions and histological findings indicated that the SAHs and the infarction were caused by the dissecting aneurysm affected with fibromuscular dysplasia (FMD). Intracranial FMD is mainly detected in children and causes cerebral ischemia and bleeding. Surgical treatment of childhood SAH should be discretely chosen with due consideration for FMD.

Aortic Dissection↗
PubMed2001

High-resolution scanning electron microscopic evaluation of cell-membrane porosity by ultrasound.

The effect of low-intensity ultrasound on HL-60 cells (human promyelocytic leukemia cells) in the presence of the photo sensitizing drug merocyanine 540 (MC 540) was evaluated morphologically, using a high-resolution scanning electron microscope and a transmission electron microscope. Exposure of HL-60 cells to ultrasound without MC 540 resulted in a decrease of finger-like processes in the cells. The cells showed many undulating ruffles on the surface. Distinct pits or holes in the membrane were not observed in these cells. The surface of HL-60 cells treated only with MC 540 was relatively smooth compared with that of control cells. HL-60 cells exposed to ultrasound in the presence of MC 540 showed apparent surface deformation. Numerous crater-like depressions of heterogeneous dimensions were observed in many cells. In addition, various-sized pores were noted in the cell membranes of more damaged cells. These results indicate that cell degeneration was induced by a rapid change in cell membrane porosity during sonication in the presence of MC540.

Apoptosis↗
PubMed2001

Pericardiectomy for constrictive pericarditis using the harmonic scalpel.

A 35-year-old man with constrictive pericarditis underwent pericardiectomy. The pericardium was dissected with a Harmonic Scalpel (Ethicon Endo-Surgery, Cincinnati, OH). This new device has many advantages including no muscular stimulation, low heat, a smokeless field, and easy hemostasis. The Harmonic Scalpel is beneficial for dissection of thickened pericardium.

Adult↗
PubMed2001

Ligand migration in human myoglobin: steric effects of isoleucine 107(G8) on O(2) and CO binding.

To investigate the ligand pathway in myoglobin, some mutant myoglobins, in which one of the amino acid residues constituting a putative ligand-docking site, Ile107, is replaced by Ala, Val, Leu, or Phe, were prepared and their structural and ligand binding properties were characterized. The kinetic barrier for the ligand entry to protein inside was lowered by decreasing the side-chain volume at position 107, indicating that the bulky side chain interferes with the formation of the activation state for the ligand migration and the free space near position 107 would be filled with the ligand in the activation state. Another prominent effect of the reduced side-chain volume at position 107 is to stabilize the ligand-binding intermediate state. Because the stabilization can be ascribed to decrease of the positive enthalpy, the enlarged free space near position 107 would relieve unfavorable steric interactions between the ligand and nearby amino acid residues. The side-chain volume at position 107, therefore, is crucial for the kinetic barrier for the ligand migration and free energy of the ligand-binding intermediate state, which allows us to propose that some photodissociated O(2) moves toward position 107 to be trapped and then expelled to the solvent.

Alanine↗
PubMed2001

Transient left ventricular apical ballooning without coronary artery stenosis: a novel heart syndrome mimicking acute myocardial infarction. Angina Pectoris-Myocardial Infarction Investigations in Japan.

OBJECTIVES: To determine the clinical features of a novel heart syndrome with transient left ventricular (LV) apical ballooning, but without coronary artery stenosis, that mimics acute myocardial infarction, we performed a multicenter retrospective enrollment study. BACKGROUND: Only several case presentations have been reported with regard to this syndrome. METHODS: We analyzed 88 patients (12 men and 76 women), aged 67 +/- 13 years, who fulfilled the following criteria: 1) transient LV apical ballooning, 2) no significant angiographic stenosis, and 3) no known cardiomyopathies. RESULTS: Thirt-eight (43%) patients had preceding aggravation of underlying disorders (cerebrovascular accident [n = 3], epilepsy [n = 3], exacerbated bronchial asthma [n = 3], acute abdomen [n = 7]) and noncardiac surgery or medical procedure (n = 11) at the onset. Twenty-four (27%) patients had emotional and physical problems (sudden accident [n = 2], death/funeral of a family member [n = 7], inexperience with exercise [n = 6], quarreling or excessive alcohol consumption [n = 5] and vigorous excitation [n = 4]). Chest symptoms (67%), electrocardiographic changes (ST elevation [90%], Q-wave formation [27%] and T-wave inversion [97%]) and elevated creatine kinase (56%) were found. After treatment of pulmonary edema (22%), cardiogenic shock (15%) and ventricular tachycardia/fibrillation (9%), 85 patients had class I New York Heart Association function on discharge. The LV ejection fraction improved from 41 +/- 11% to 64 +/- 10%. Transient intraventricular pressure gradient and provocative vasospasm were documented in 13/72 (18%) and 10/48 (21%) of the patients, respectively. During follow-up for 13 +/- 14 months, two patients showed recurrence, and one died suddenly. CONCLUSIONS: A novel cardiomyopathy with transient apical ballooning was reported. Emotional or physical stress might play a key role in this cardiomyopathy, but the precise etiologic basis still remains unclear.

Adolescent↗
PubMed2001

A technique of cervical aortic graft transplantation in mice.

A new method of mouse aortic graft transplantation into carotid artery was developed with cuff technique. By harvesting the descending aorta of the donor using a small Teflon cuff (external diameter 0.6 mm, internal diameter 0.4 mm) and super fine-tip forceps, and modifying the method of mouse heterotopic heart transplantation with cuff technique, donor descending aortic allografts could be interposed in the common carotid artery of recipient mice. Histological analysis demonstrated neither evidence of tissue damage nor intimal thickening in isograft implanted over 100 days. We strongly recommend that this new model of aortic transplantation in mice is a simple and useful technique for vascular transplantation research.

Animals↗
PubMed2001

Hypermethylation of p16INK4A gene promoter during the progression of plasma cell dyscrasia.

Recent studies have indicated a close relationship between inactivation of tumor suppressor genes (TSGs) and disease progression. The genes encoding the cyclin-dependent kinase inhibitors p16INK4A and p15INK4B are potent TSGs, and correlations between their inactivation and disease progression have also been reported in various malignancies. In this study, we analyzed the methylation status of p16INK4A and p15INK4B gene promoters in plasma cell dyscrasias (PCDs) by methylation-specific PCR (MSP). In analyses using DNAs extracted from bone marrow mononuclear cells (BM-MNCs), patients with multiple myeloma (MM) showed frequent hypermethylation of the p16INK4A gene (15/37, 41%), whereas p15INK4B gene methylation was not so frequent (5/37, 14%). Many patients whose BM-MNC showed dense methylation of the p16INK4A gene had extramedullary plasmacytoma (extra-PC), and all available extra-PC samples showed alterations of the p16INK4A gene (4; dense methylation, 1; homozygous deletion). In contrast to MM, hypermethylation of the p16INK4A gene was significantly infrequent in indolent PCDs (2/22, 9%, P= 0.0055). The infrequency in indolent PCDs was also confirmed by analyses using DNAs extracted from BM smears (1/29, 3%). It is possible that hypermethylation of the p16INK4A gene promoter contributes to progression to aggressive MM from indolent PCD, especially to extra-PC development.

Biomarkers↗
PubMed2001

A case of autoimmune hepatitis with a high titer of antimitochondrial antibody and normal gamma-globulinemia.

We report here a patient with chronic active hepatitis who had no markers for hepatitis viruses and no hyper-gamma-globulinemia, but had high titers of antimitochondrial antibody. Serum levels of alkaline phosphatase were normal, and antinuclear antibody, antismooth muscle antibody, and antiliver kidney microsome antibody tested negative. The titers of antimitochondrial antibody exceeded 1:640, and the positivity for anti-M2 was ascertained by using both ELISA and immunoblot with beef-heart mitochondria and a recombinant pyruvate dehydrogenase E2 subunit as antigens. This patient responded to ursodeoxycholic acid (UDCA) therapy in the beginning, but her hepatitis flared up during UDCA therapy. In contrast, she responded completely to corticosteroid therapy. The clinical course and histological findings of this patient strongly suggest that this patient has autoimmune hepatitis.

Aged↗
PubMed2001

Irregular regeneration of hepatocytes is an important factor in the hepatocarcinogenesis of liver disease.

The goal of this study was to assess the relationship between the degree of irregular regeneration of hepatocytes (IR) and the development of hepatocellular carcinoma (HCC). We examined the liver biopsy specimens from patients with chronic liver disease (CLD), and the noncancerous liver tissue in the surgically resected specimens from patients with HCC. Liver tissues were obtained from 18 patients with B-viral CLD, 38 with C-viral CLD, and 5 with nonB-nonC (NBNC)-CLD who underwent liver biopsy, and 24 patients with B-viral HCC, 67 with C-viral HCC, and 17 with NBNC-HCC who underwent surgical resection. The IR score of the noncancerous region of the liver of the HCC patients and that of the liver biopsy specimens of the CLD patients, were compared. Of the 108 samples of noncancerous liver tissue from the HCC patients, 70% showed an IR score of moderate or higher (IR = 3 or 4), and only 1.9% showed an IR score of none or minimal (IR = 0 or 1). The degree of IR of hepatocytes in the HCC patients was significantly more severe than that in the CLD patients in each etiological type of CLD. High IR may reflect the histologic expression of genetic instability, namely a carcinogenic state, although prospective studies are needed to determine its relationship to the risk for developing HCC.

Adult↗
PubMed2001

Relative importance of calcium-activated potassium channels in nipradilol-induced aortic relaxation in rats.

Nipradilol (CAS 81486-22-8), a vasodilatory beta-blocker, has been shown to dilate smaller vessels than nitroglycerin does, and the vasodilative effects of nipradilol have been reported to be less mediated by cyclic GMP (guanosine monophosphate) than those of nitroglycerin. To test the hypothesis that cyclic GMP-independent potassium channels have a larger role in nipradilol-induced aortic relaxation than cyclic GMP-dependent mechanisms, the effects of a potassium channel blocker, tetraethylammonium (TEA, CAS 56-34-8), and of a guanylate cyclase inhibitor, methylene blue (MB, CAS 61-73-4), on nipradilol-induced aortic relaxation were investigated and compared with those on nitroglycerin-induced aortic relaxation in isolated rat aortic rings. Relaxation response was expressed as percent relaxation, which is a percentage of the tension developed by 10(-7) mol/l norepinephrine. Nitroglycerin and nipradilol similarly relaxed the aortic ring in a concentration-dependent manner (10(-9)-10(-4) mol/l). In contrast, desnitronipradilol, a nipradilol analogue which has no nitroxy group, induced almost no aortic relaxation. TEA at 10(-3) mol/l, which is selective for calcium-activated potassium channels, inhibited the aortic relaxation induced by nipradilol (10(-5) mol/l) to a significantly greater extent than that induced by nitroglycerin (10(-5) mol/l) (% relaxation: 30.0 +/- 6.8 vs. 51.1 +/- 6.1%, p < 0.05). MB (10(-5) mol/l) suppressed the relaxation by nitroglycerin slightly but not significantly more than that by nipradilol. (% relaxation: 54.7 +/- 9.9 vs. 64.6 +/- 5.7%). The combination of TEA and MB almost completely eliminated the relaxation induced by nipradilol as well as by nitroglycerin. Thus, cyclic GMP-independent calcium activated potassium channels may be more involved in the aortic relaxation by nipradilol than that by nitroglycerin in rats.

Adrenergic beta-Antagonists↗
PubMed2001

Expression of tyrosine kinase receptors Tie-1 and Tie-2 in giant cell tumor of the tendon sheath: a possible role in synovial proliferation.

We have recently demonstrated that Tie-1 and Tie-2 are expressed in synovial cells from rheumatoid arthritis (RA). To elucidate the possible involvement of Tie receptors in synovial proliferation, we analyzed their expression by immunostaining in five cases of giant cell tumor of tendon sheath (GCTTS), which represents a proliferating lesion of synovial cells. Strong immunoreactivity for both Tie-1 and Tie-2, regardless of the individual patient's profile, was observed in all cases of GCTTS. Six sets of double immunohistochemical stainings for Tie-1/Tie-2 and fibronectin, CD68, or CD34 were carried out to determine the phenotype of Tie-1 and Tie-2-positive tumor components. In these studies, both Tie-1 and Tie-2 immunoreactivity were widely observed in the fibronectin-positive fibroblastic and the CD68-positive histiocytic mononuclear cells, as well as in the osteoclast-like giant cells. In tumor vasculature, Tie receptors were expressed in the CD34-positive endothelial cells possessing proliferating cell nuclear antigen (PCNA) immunoreactivity. We also evaluated the correlation of Tie-1/Tie-2 expression and proliferating cells in GCTTS by using double staining of Tie-1/Tie-2 together with PCNA. Overexpression of PCNA immunoreactivity was frequently found in Tie receptors-positive cells with no obvious differences in the expression pattern of Tie-1 and Tie-2. These findings suggest the possible involvement of Tie receptors in the pathogenesis of GCTTS other than solely via their involvement in angiogenesis and subsequent vascularization. It was demonstrated that Tie-2 immunoreactivity was restricted to the fibroblastic, but not histiocytic, phenotype in RA synovium, suggesting different regulatory control of Tie-2 expression in GCTTS and RA synovium. Overexpression of Tie receptors in GCTTS may imply a biological role for these receptors in synovial proliferation.

Adult↗
PubMed2001

Significance of platelet aggregability immediately after blood sampling and effect of cigarette smoking.

A novel type platelet aggregometer, a WBA Analyzer, has enabled us to obtain the platelet aggregability data immediately after blood sampling, which is considered to closely reflect in vivo platelet function. Using this analyzer, we measured the platelet aggregatory threshold index (PATI) 5 min after blood sampling and compared it with that 60 min after blood sampling in 20 healthy male volunteers (10 smokers and 10 non-smokers). In the non-smokers, PATI was 10.3+/-2.3 microM 5 min after blood sampling, and it decreased to 4.7+/-1.5 (P<0.001) 60 min after blood sampling. In the smokers, the PATI was 7.7+/-2.9 microM 5 min after blood sampling, and it decreased to 3.8+/-1.5 (P<0.001) at 60 min after blood sampling. In the smokers, the PATI 5 min after blood sampling increased after a 4-week cessation of smoking (10.4+/-2.9, P<0.01), although the PATI 60 min after blood sampling did not change (4.2+/-1.6 microM). The measurement of platelet aggregability immediately after blood sampling using a WBA Analyser may be useful to evaluate not only platelet function in various thrombotic disorders, but also the effects of various anti-platelet drugs. Cessation of smoking should also be encouraged in the light of the adverse effects on platelet function.

Adult↗
PubMed2001

p53 Mutation in bladder cancer patients in Japan and inhibition of growth by in vitro adenovirus-mediated wild-type p53 transduction in bladder cancer cells.

BACKGROUND: Altered expression of p53 has been described in nearly half of bladder cancers, and p53 mutations are presumed to play a role in the multistep progression of these tumors. MATERIALS AND METHODS: The incidence of mutation in the p53 gene and its correlation with histopathologic findings and patient survival were evaluated in 105 Japanese patients with bladder cancer. Laboratory experiments were also performed to confirm the infectivity and efficacy in tumor growth inhibition of an adenovirus expressing wild-type p53 in EJ bladder cancer cells. RESULTS: Mutations of p53 were observed in 38 bladder cancer specimens (36%), with a significantly higher incidence of mutation being seen in tumors of higher stage and grade. The overall survival was worse in patients with the p53 mutation. In laboratory experiments, adenoviral vectors infected bladder cancer cells in a dose- and cell density-dependent manner. The adenovirus-mediated transduction of wild-type p53 resulted in dose-dependent growth inhibition of bladder cancer cells in vitro. No significant cytotoxicity was observed after infection by a control adenovirus. CONCLUSION: Transduction of wild-type p53 might be a potential therapeutic option for bladder cancer.

Adenoviridae↗
PubMed2001

Antitumor effect of bcl-2 antisense phosphorothioate oligodeoxynucleotides on human renal-cell carcinoma cells in vitro and in mice.

BACKGROUND AND PURPOSE: Programmed cell death is a genetically regulated pathway that is altered in many cancers. This process is, in part, regulated by the bcl-2 oncogene. Antisense oligodeoxynucleotides (ODNs) targeted to specific oncogenes have been used with some therapeutic success in animal models of leukemia and melanoma cells and human Hodgkin's lymphoma. We evaluated the effects of antisense ODNs targeted to the bcl-2 oncogene on the proliferation of human renal-cell carcinoma (RCC) cells in vitro and on the growth of human RCC xenografts in BALBc nude (nu/nu) mice. MATERIALS AND METHODS: Expression bcl-2 mRNA in five RCC cell lines (ACHN, Caki-1, RCZ, RCW, and OS-RC-2) was analyzed by reverse transcriptase-polymerase chain reaction. The effects of phosphorothioated ODNs containing human bcl-2 sense and bcl-2 antisense sequences that were transfected with Lipofectin on the proliferation and viability of cultures of established human RCC cell lines were determined by MTS assay. The expression of Bcl-2 protein in ACHN tumor cells following antisense bcl-2 (AS2) ODN treatment was evaluated by Western blot analysis, and the extent of apoptosis in these cells was determined by fluorescence-activated cell sorter (FACS) analysis. The antitumor activity in ACHN xenografts in nu/nu mice was monitored by measuring differences in tumor weight in treated and control mice. RESULTS: Expression of bcl-2 mRNA was detected in all five RCC lines. Treatment with antisense bcl-2 ODNs inhibited the growth of all tested RCC cells and decreased Bcl-2 protein expression in ACHN cells. The AS2 antisense ODN complementary to the coding region of bcl-2 mRNA showed a superior antiproliferative effect compared with AS1 ODN complementary to the translation initiation region. Inhibition by antisense bcl-2 ODNs of ACHN cells was dose dependent. The FACS analysis revealed that growth inhibition was associated with the induction of programmed cell death. In vivo, AS2 ODN antitumor activity was noted in locally injected groups. CONCLUSIONS: Treatment of human RCC with antisense ODNs targeted to bcl-2 inhibits growth and is associated with the induction of programmed cell death. These results suggest therapeutic use of antisense bcl2 in the treatment of RCC.

Animals↗