Biomedical subjects

T Uchida

Publications and source records attributed to T Uchida.

At least 55 records · Page 3Linked to original sources

PubMed2001

Co-administration of adenovirus vector expressing CTLA4-Ig prolongs transgene expression in the brain of mice sensitized with adenovirus.

The duration of transgene expression in the brain is known to be shortened by previous sensitization to adenovirus. In order to prolong transgene expression, adenovirus vectors expressing CTLA4-Ig (AdCTLA), which blocks the B7-CD28 co-stimulatory signals required for T-cell activation, were used. Local administration of AdCTLA into the brain suppressed both the cellular and humoral immune responses to adenovirus vectors, and prolonged the duration of transgene expression. AdCTLA may be an effective tool for repeated gene transfer.

Abatacept↗

PubMed2001

Clinical significance of antibody against oxidized low density lipoprotein in patients with atherosclerotic coronary artery disease.

OBJECTIVES: This study was designed to establish the clinical significance of antibodies against oxidized low density lipoprotein (anti-Ox-LDL) titer in atherosclerotic coronary artery disease (CAD). BACKGROUND: Oxidative modification of LDL, which plays a key role in the development of atherosclerosis, induces immunogenic epitopes in the LDL molecule, and the presence of anti-Ox-LDL has been demonstrated in human sera. METHODS: Anti-Ox-LDL titer was measured by enzyme-linked immunosorbent assay in 108 patients who had angiographically verified CAD, and 31 patients who had chest pain but no significant CAD, as controls. RESULTS: The anti-Ox-LDL titer was higher (p < 0.01) in patients with multivessel CAD (19.4 +/- 10.1 AcU/ml, n = 68) than in the controls (9.8 +/- 4.1). However, no significant difference was shown between the single-vessel CAD group (15.1 +/- 6.4, n = 40) and the controls, or between the multivessel CAD group and the single-vessel CAD group. The titer was higher in patients with unstable angina (21.5 +/- 11.8 AcU/ml, n = 20, p < 0.01), or in patients with acute myocardial infarction (23.1 +/- 12.0, n = 20, p < 0.01) than in patients with stable-effort angina or old myocardial infarction (12.2 +/- 8.6, n = 68). Multiple logistic regression analysis indicated that the anti-Ox-LDL titer most powerfully discriminated CAD patients from controls (odds ratio [OR]: 1.20, 95% confidence interval [CI]: 1.07-1.33, p = 0.0006) and acute coronary syndrome from chronic CAD (OR: 1.09, 95% CI: 1.04-1.14, p = 0.0008). CONCLUSIONS: Serum anti-Ox-LDL titer not only can predict a presence of atherosclerotic CAD but also may be a marker of plaque instability. Low density lipoprotein oxidation may play an important role in the development of plaque instability.

Aged↗

PubMed2001

Solution structure of the human parvulin-like peptidyl prolyl cis/trans isomerase, hPar14.

The hPar14 protein is a peptidyl prolyl cis/trans isomerase and is a human parvulin homologue. The hPar14 protein shows about 30 % sequence identity with the other human parvulin homologue, hPin1. Here, the solution structure of hPar14 was determined by nuclear magnetic resonance spectroscopy. The N-terminal 35 residues preceding the peptidyl prolyl isomerase domain of hPar14 are unstructured, whereas hPin1 possesses the WW domain at its N terminus. The fold of residues 36-131 of hPar14, which comprises a four-stranded beta-sheet and three alpha-helices, is superimposable onto that of the peptidyl prolyl isomerase domain of hPin1. To investigate the interaction of hPar14 with a substrate, the backbone chemical-shift changes of hPar14 were monitored during titration with a tetra peptide. Met90, Val91, and Phe94 around the N terminus of alpha3 showed large chemical-shift changes. These residues form a hydrophobic patch on the molecular surface of hPar14. Two of these residues are conserved and have been shown to interact with the proline residue of the substrate in hPin1. On the other hand, hPar14 lacks the hPin1 positively charged residues (Lys63, Arg68, and Arg69), which determine the substrate specificity of hPin1 by interacting with phosphorylated Ser or Thr preceding the substrate Pro, and exhibits a different structure in the corresponding region. Therefore, the mechanism determining the substrate specificity seems to be different between hPar14 and hPin1.

Amino Acid Sequence↗

PubMed2001

Chrysotile asbestos fibers detected in the newborn pups following gavage feeding of pregnant mice.

Female pregnant mice were fed chrysotile asbestos suspension by gavage to determine whether there is transfer of fibers to the fetuses. Groups of mice were given 2 doses of either 50 microg chrysotile suspension in 0.2 ml sterile normal saline (treated), or 0.2 ml saline (control), and were allowed to mate 2 d later. After pregnancy was confirmed, the treated and control groups received 2 additional doses of chrysotile asbestos or saline on gestational d 7 and 12. Both groups were allowed to deliver naturally, and the pups were sacrificed at 8, 1, 19, or 20 d after birth. The lungs and liver of two pups from each mother were processed for fiber counts using electron microscopy and energy-dispersive x-ray analysis (EDXA). All pups of the treated group had chrysotile fibers, while none were present in pups from controls. The mean fiber count of the lungs of treated group of pups was 780 fibers/g, and the mean fiber count of the liver was 214 fibers/g. Mean length of the fibers in the lung and liver was 18.48 microm and 18.30 microm, respectively. The fibers were thin, measuring 0.42 microm and 0.33 microm in the lung and liver, respectively. There was no significant difference in the weight gain between the treated and control group of pups. The postnatal fetal mortality of the 2 groups, 8.2% for the treated and 4.5% for the control group, were not statistically significant. To our knowledge, this is the first animal study to demonstrate that oral ingestion of chrysotile asbestos during pregnancy results in transfer of asbestos fibers to the fetuses.

Administration, Oral↗

PubMed2001

Comprehensive allelotype study of ovarian tumors of low malignant potential: potential differences in pathways between tumors with and without genetic predisposition to invasive carcinoma.

Ovarian tumors of low malignant potential (LMP) are intermediate between adenomas and ovarian carcinomas (OC); however, the relevance of LMP to ovarian carcinogenesis is not clear. We performed a comparative analysis of allelotypes in 50 cases of LMP (42 mucinous and 8 serous) and 23 cases of OC (15 mucinous and 8 serous) to investigate any differences in genetic changes. Analysis of loss of heterozygosity (LOH) using 25 microsatellite markers reportedly associated with OC revealed that the total LOH frequency at each marker was significantly lower in LMP than in OC (p < 0.01). However, 9 (36%) loci showed higher LOH frequency in mucinous LMP than in mucinous OC. A genome-wide scan for LOH using 91 microsatellite markers and fine mapping revealed that LOH at D7S1805 (7q35) is characteristic of mucinous LMP (19.4% in mucinous LMP, 8.3% in mucinous OC). We further studied LOH in 3 cases of mucinous OC that were accompanied by mucinous LMP lesions. In 2 cases, LOH frequency was higher in the carcinoma portion than in the morphologically LMP portion. The other case showed microsatellite instability in the morphologically LMP portion and LOH in the carcinoma portion. Our results suggest the presence of an LMP-to-OC developmental sequence and the existence of a subset of LMP that does not develop into OC in the mucinous subtype of ovarian tumors.

Adenoma↗

PubMed2001

Histopathologic impact of TT virus infection on the liver of type C chronic hepatitis and liver cirrhosis in Japan.

The present investigation compared the histological findings in the liver of chronic hepatitis C patients who were or were not co-infected with TT virus (TTV) to determine the histological and clinical characteristics of TTV infection. One hundred eighty patients with chronic hepatitis or liver cirrhosis type C were included in this study. Serum samples were tested for the presence of TTV DNA by a nested polymerase chain reaction. The liver biopsy specimen of each patient was examined, and scores were assigned to indicate the severity of each of the following features: inflammatory cell infiltration in the periportal, parenchymal, and portal areas; fibrous stage; lymphoid reaction in the portal area; portal sclerotic change; perivenular fibrosis; pericellular fibrosis; damage of bile duct; and irregular regeneration of hepatocytes. Sixty-four (34.4%) of the 180 patients were positive for TTV DNA. The histological features of the liver and the blood biochemical parameters of the TTV DNA-positive and TTV DNA-negative patients, did not differ significantly except for the score of irregular regeneration (IR) of hepatocytes. Among those in the F4 stage of fibrosis, the score of IR of the TTV DNA-positive patients was significantly higher than that of the TTV DNA-negative patients. In conclusion, chronic TTV infection does not modify the biochemical features of chronic hepatitis type C patients. TTV may be a risk factor, however, for the development of hepatocellular carcinoma in patients with type C liver disease in the F4 stage.

Adolescent↗

PubMed2001

Gap junction remodeling in hypertrophied left ventricles of aortic-banded rats: prevention by angiotensin II type 1 receptor blockade.

Remodeling of gap-junctional organization in hypertrophied left ventricle (LV) in response to pressure overload in rats induced by abdominal aorta banding was investigated by immunoconfocal and electron microscopy. Eight to 12 weeks after banding, rats developed significant LV hypertrophy. In contrast to control LV myocytes, which showed connexin43 (Cx43) labeling largely confined to the intercalated disks, LV myocytes from aortic-banded rats showed dispersion of punctate Cx43 labeling over the entire cell surface. In LV tissues sectioned longitudinally, the proportion of Cx43 label at the intercalated disk decreased significantly (control, 0.87 v aortic-banded, 0.62). En-face views of intercalated disks of hypertrophied myocardium revealed a reduction of Cx43 gap junctions in the disk center, giving rise to a significant decrease in the proportion of the disk occupied by gap-junctional membrane (control, 0.32 v aortic-banded, 0.24). Electron microscopy of hypertrophied LV tissue revealed that Cx43-containing gap junctions were frequently displaced from their usual locations to form side-to-side contacts distant from the disk, and also appeared as annular profiles. In aortic-banded rats treated with the angiotensin II (AII) type 1 receptor (AT1) antagonist, losartan (10 mg/kg/day, 11 weeks) not only LV hypertrophy, but also the gap junction disorganization was markedly reduced. These results suggest that LV hypertrophy induced by pressure overload is associated with Cx43 gap junction disorganization and that AII may play an important role either directly or indirectly in gap-junctional remodeling.

Angiotensin Receptor Antagonists↗

PubMed2001

Concomitant aortic arch and root replacement using a stentless xenograft for acute type A dissection.

A 78-year-old woman with an aortic root aneurysm and aortic regurgitation developing acute type A dissection successfully underwent aortic root replacement using a stentless xenograft during core cooling, followed by total aortic arch replacement under selective cerebral perfusion with deep hypothermia. This bioprosthesis can be used in the same way as a free-hand homograft and potentially provides an aggressive, safe option for acute aortic dissection requiring aortic root reconstruction in elderly patients.

Acute Disease↗

PubMed2001

Congenital diverticulum of the left ventricle.

We present a case of a congenital left ventricular diverticulum of fibrous type that was surgically repaired. Considering the potential risks such as rupture, systemic thromboembolism, and arrhythmia, an early surgical intervention should be employed for this rare abnormality even in a child without clinical symptoms.

Child↗

PubMed2001

Partial pressure of oxygen and partial pressure of carbon dioxide of perfluorocarbon liquid during partial liquid ventilation: their regional difference and their dependence on tidal volume and positive end-expiratory pressure level.

OBJECTIVE: To investigate the regional partial pressure of oxygen (PO2) and partial pressure of carbon dioxide (PCO2) of the perfluorocarbon liquid (PpfcO2, PpfcCO2) during partial liquid ventilation (PLV). DESIGN: Prospective, controlled study. SETTING: A research laboratory at a university medical center. SUBJECTS: Thirteen Japanese white rabbits. INTERVENTIONS: After the tracheostomy, PLV was started with perflubron (15 ml/kg) following saline lung lavage. Fractional inspired oxygen (FIO2) was 1.0, respiratory rate was 30 bpm and tidal volume (VT) was 30 ml. Two epidural catheters (18 gauge) were inserted from the rubber diaphragm interposed in the respiratory circuit to sample perflubron. One catheter was inserted into the left lower lobe bronchus and placed at 5-6 cm distal from the carina (DISTAL). The other one was inserted at the tip of the endotracheal tube (PROXIMAL). Then the effect of the larger VT (50 ml) or positive end-expiratory pressure (PEEP; 10 cmH2O) to the gas tension in perflubron was examined. MEASUREMENTS AND MAIN RESULTS: (1) In the lower VT (30 ml) with 0 cmH20 PEEP, DISTAL PpfcO2 was significantly lower than PROXIMAL PpfcO2 (265 72 vs 386 +/- 47 mmHg, p < 0.0001), and DISTAL PpfcCO2 was significantly higher than PROXIMAL PpfcCO2 (51.1 +/- 14.4 vs 42.4 +/- 11.8 mmHg (p = 0.0007)), (2) the higher VT setting increased PpfcO2 (p = 0.0001) and decreased PpfcCO2 (p < 0.0001), although the gas tension gradient was significant, (3) 10 cmH2O PEEP increased PpfcO2 (p = 0.0004) and decreased PpfcCO2 (p = 0.0089) in the DISTAL sample. CONCLUSION: There was a difference in gas tension in perflubron between the central airway and the peripheral dependent lung region, and gas tension in perflubron was affected by the VT and the PEEP level.

Analysis of Variance↗

PubMed2001

Chronic rejection in H-2 matched cardiac allografts: early emergence of vasculopathy, alloantibody, and accumulation of IFN-gamma and IL-10 mRNA.

Cardiac allograft vasculopathy (CAV) is one of the crucial problems of clinical heart transplantation. We have developed a novel model of murine cardiac allograft rejection, in which chronic rejection associated with CAV occurs in its natural course. In this study we analyzed the pathogenesis of chronic cardiac allograft rejection using an H-2 matched multiple minor histocompatibility antigen-mismatched combination, AKR (H-2k) to C3H (H-2k) recipient mice. All the cardiac allografts survived for more than 100 days but were rejected within 260 days post-transplant (n = 13; mean survival times +/- standard deviation = 189.0+/-72.0; median = 210). The heartbeats of the graft became gradually weaker throughout the duration of the rejection process. Serial histological analyses with hematoxylin and eosin, elastica van Gieson or Masson trichrome staining revealed mononuclear cell infiltration and intimal thickening (i.e. CAV) which started in most grafts at 2 weeks post-transplant. These pathological changes eventually developed to severe graft fibrosis, and the severity of these changes correlated with the deterioration of the heartbeats. Production of anti-donor antibodies in most recipients was detectable by 2 weeks post-transplant, it peaked before day 100, and subsided before rejection was complete in most grafts. Intragraft expression of IFN-gamma and IL-10 mRNA was demonstrated by reverse transcriptase-polymerase chain reaction during early periods post-transplant. In this study, we demonstrate a novel model feasible for analysis of chronic cardiac allograft rejection, in which the vascular rejection processes, including fibrosis and alloantibody production, can be tested from an early stage on, after transplantation.

Animals↗

PubMed2001

Perioperative management protocols for children with moyamoya disease.

Protocols for prevention of cerebral ischemic attacks caused by hyperventilation resulting from crying, as observed in perioperative pediatric moyamoya patients, were evaluated. The first protocol involved the use of sedation when staff were setting up the intravenous lines, performing neuroimaging studies, and controlling postoperative pain. The second involved the use of wound-handling techniques designed to ease postoperative wound care; these included steristrip closure, use of paraffin gauze and not using adhesive tapes. We compared 14 and 11 surgical cases handled before and after the protocols were introduced, respectively. The number of patients with perioperative cerebral infarction decreased from 2 to 0. Appropriate sedation reduced the incidence of transient ischemic attacks from 28.6% to 3.7%. The average postoperative hospital stay was similarly reduced, from 21.3 days to 16.1 days, as a consequence of the reduced incidence of complications. It is concluded that the perioperative risks can be minimized when invasive procedures are managed according to our protocols.

Administration, Oral↗

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↗