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Biomedical subjects

H Itoh

Publications and source records attributed to H Itoh.

At least 19 recordsLinked to original sources

Changes in HRCT findings in patients with respiratory bronchiolitis-associated interstitial lung disease after smoking cessation.

High-resolution computed tomography (HRCT) findings in patients with respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) are varied and nonspecific. There is no known report of changes in HRCT findings and respiratory function test results for RB-ILD patients following the cessation of smoking. Five patients with RB-ILD, confirmed by surgical lung biopsy, were retrospectively studied. Each stopped cigarette smoking and did not receive corticosteroid therapy after diagnosis. The clinical symptoms, respiratory function test results and HRCT findings obtained at the final observation were compared with those from the time of diagnosis. Ground-glass opacity and centrilobular nodules corresponding to pathological respiratory bronchiolitis, as well as intralobular fine linear-reticular opacity corresponding to fibrosis involving the subpleural alveolar septa, showed computed tomography-pathological correlations. Both clinical symptoms and the diffusing capacity of the lungs for carbon monoxide improved significantly following smoking cessation, as did ground-glass opacity and centrilobular nodules seen during the initial HRCT examination. Centrilobular nodules and ground-glass opacity, which are the main features of high-resolution computed tomography of respiratory bronchiolitis-associated interstitial lung disease patients and represent pathological respiratory bronchiolitis, can be improved by smoking cessation. The diffusing capacity of the lung for carbon monoxide in respiratory function tests can be also improved.

Adult↗

Human oviductal epithelial cells express Toll-like receptor 3 and respond to double-stranded RNA: Fallopian tube-specific mucosal immunity against viral infection.

BACKGROUND: The aim of this study was to evaluate the site-specific immunoregulatory mechanisms against viral infection in human Fallopian tubes. METHODS: We therefore investigated the effects of double-stranded RNA (dsRNA) on the production of interleukin (IL)-6, IL-8 and granulocyte chemotactic protein-2 (GCP-2) by cultured oviductal epithelial cells (OECs) using enzyme-linked immunosorbent assays. Phosphorylation of inhibitor kappaB-alpha (IkappaB-alpha) protein after dsRNA stimulation and the expression of Toll-like receptor (TLR) 3 in these cells were also evaluated by western blot analysis. RESULTS: Polyriboinosinic:polyribocytidylic acid (poly I:C), a synthetic dsRNA that antagonizes TLR3, stimulated the secretion of IL-6, IL-8 and GCP-2 by OECs. Poly I:C-induced production of these cytokines by OECs was inhibited by the pretreatment of these cells with anti-TLR3 antibody. The phosphorylation of IkappaB-alpha protein was detected in OECs after stimulation by poly I:C. The expression of TLR3 was also detected in OECs. CONCLUSION: These results suggest that the epithelial cells of the human Fallopian tube have evolved a unique, site-specific mechanism for recognizing viral infection. TLR3-mediated production of proinflammatory cytokines and chemokines in OECs in response to viral dsRNA may be important for antiviral immunity in the human female reproductive tract.

Adult↗

Enhanced expression of hepatocyte growth factor activator inhibitor type 2-related small peptide at the invasive front of colon cancers.

BACKGROUND: Hepatocyte growth factor activator inhibitor type 2-related small peptide (H2RSP) is a small nuclear protein abundantly expressed in the gastrointestinal epithelium. However, its functions remain unknown. AIMS: To investigate the expression and localisation of H2RSP in normal, injured and neoplastic human intestinal tissue. METHODS: Immunohistochemical examination and in situ hybridisation for H2RSP were performed using normal and diseased intestinal specimens. Its subcellular localisation and effects on the cellular proliferation and invasiveness were examined using cultured cells. RESULTS: In the normal intestine, H2RSP was observed in the nuclei of surface epithelial cells and this nuclear localisation was impaired in regenerating epithelium. In vitro, the nuclear translocation of H2RSP was observed along with increasing cellular density, and an overexpression of H2RSP resulted in a reduced growth rate and enhanced invasiveness. H2RSP expression was down regulated in well-differentiated colorectal adenocarcinomas. However, a marked up regulation of the cytoplasmic H2RSP immunoreactivity was observed in cancer cells at the invasive front. These cells showed low MIB-1 labelling, an enhanced p16 expression and nuclear beta-catenin. The number of H2RSP-positive cells in the invasive front of well-differentiated adenocarcinomas was considerably higher in the cases with lymph node metastases than in node-negative ones. CONCLUSION: In the normal intestine, the nuclear accumulation of H2RSP is a marker of differentiated epithelial cells. Although H2RSP was down regulated in colorectal adenocarcinomas, a paradoxical up regulation was observed in actively invading carcinoma cells. H2RSP immunoreactivity at the invasive front may serve as a marker of invasive phenotype of well-differentiated colon cancers.

Adenocarcinoma↗

Identification of the carbon antisite-vacancy pair in 4H-SiC.

The metastability of vacancies was theoretically predicted for several compound semiconductors alongside their transformation into the antisite-vacancy pair counterpart; however, no experiment to date has unambiguously confirmed the existence of antisite-vacancy pairs. Using electron paramagnetic resonance and first principles calculations we identify the S15 center as the carbon antisite-vacancy pair in the negative charge state (C(Si)V-(C)) in 4H-SiC. We suggest that this defect is a strong carrier-compensating center in n-type or high-purity semi-insulating SiC.

Journal Article↗

Divacancy in 4H-SiC.

Electron paramagnetic resonance and ab initio supercell calculations suggest that the P6/P7 centers, which were previously assigned to the photoexcited triplet states of the carbon vacancy-antisite pairs in the double positive charge state, are related to the triplet ground states of the neutral divacancy. The spin density is found to be located mainly on three nearest C neighbors of the silicon vacancy, whereas it is negligible on the nearest Si neighbors of the carbon vacancy.

Journal Article↗

The anatomical basis of complete atrioventricular block in cats with hypertrophic cardiomyopathy.

The cardiac conduction system was examined histologically in 13 feline cases of hypertrophic cardiomyopathy (HCM) with complete atrioventricular (AV) block. Marked degeneration and fibrous replacement of the AV conduction system were consistently observed in the combined regions of the branching portion of the AV bundle and the upper portion of the left bundle branch. These changes were associated with extensive fibrosis of the central fibrous body and endocardial and myocardial fibrosis in the upper border of the ventricular septum. Chondrometaplastic lesions or osseous lesions, or both, present in the base of the central fibrous body, compressed the underlying penetrating or branching (or both) portions of the AV bundle, causing apparent reduction of the conduction fibres. The pathological process and the nature and predilection sites of the lesions resembled those associated with ageing in human patients with complete AV block. It is possible that the pathological process in the cats was fundamentally related to the normal ageing phenomenon and may have been exacerbated by mechanical forces created by the cardiac hypertrophy associated with HCM.

Animals↗

Perfusion imaging of meningioma by using continuous arterial spin-labeling: comparison with dynamic susceptibility-weighted contrast-enhanced MR images and histopathologic features.

PURPOSE: The goal of the present study was to determine the utility of continuous arterial spin labeling (CASL) for characterization of meningioma by MR perfusion imaging and to compare these results with those obtained from the T2 dynamic susceptibility contrast (T2DSC) method and from histopathologic examination. METHODS: Twenty-one cases of meningiomas were examined at 1.5T. CASL perfusion imaging was implemented on the basis of multisection single-shot echo-planar imaging with velocity-driven adiabatic spin-inversion preparation. T2DSC perfusion imaging was also performed by using a double-echo spoiled gradient echo sequence in a section containing the tumor. By focusing on the regions of interest, maps of % signal intensity change and cerebral blood flow (CBF) were determined from CASL and cerebral blood volume (CBV). CBF and mean transit time (MTT) were obtained from T2DSC. The microvessel area (MVA) was determined from specimens immunostained with anti-CD31 in 14 cases by measuring the total amount of staining in each histologic section. Linear regression analysis was performed for rCBF values from both perfusion methods and for % signal intensity change and MVA. RESULTS: There was a significant correlation between CBF values determined from both perfusion methods (r(2) = 0.73; P < .001); however, the slope from T2DSC to CASL was less than unity, likely because of the different vascular weighting used for each method. There was also a significant correlation between CASL-% signal intensity change and MVA determined by histopathology (r(2) = 0.91; P < .00001). Perfusion values were the greatest for angiomatous meningioma and lowest for fibrous meningioma when using either perfusion method. CONCLUSIONS: CASL and T2DSC perfusion methods are comparable in the characterization of meningiomas. Further, CASL is of use in assessing tumor microcirculation.

Adult↗

Increased expression and activation of matrix metalloproteinase-2 (MMP-2) in O-1N: hamster oral squamous cell carcinoma with high potential lymph node metastasis.

Oral squamous cell carcinoma (OSCC) is one of the most common head and neck cancers with poor clinical outcome. MMP-2 was implied to contribute to the invasiveness and metastatization of various malignancies because of the degradation of type IV collagen. In this experiment, ELISA, Western blot and Q-RT-PCR was performed to investigate the expression and activation of MMP-2 in serum and tumor from hamster oral cancer model with high lymph node metastasis based on the various stages of OSCC development. Active MMP-2 in the serum was found elevated during oral cancer progression. In the metastatic stage, total MMP-2 level was 46% higher than it in the expansive stage, while active MMP-2 level increased 6-fold than it in the expansive stage. MMP-2 serum activation ratio was significantly enhanced in the metastatic stage than before tumor transplantation and that in the expansive stage. MMP-2 protein and MMP-2 mRNA was found to be increased during oral cancer development in hamster models. The increase of MMP-2 expression and activation starts prior to the metastasis occurrence, indicating the important role of MMP-2 in the early phase of oral cancer progression. Active MMP-2 level in serum may be a useful indicator for monitoring oral cancer progression.

Animals↗

Effects of barbiturates on ATP-sensitive K channels in rat substantia nigra.

ATP-sensitive K channels are widely expressed in cytoplasmic membranes of neurons, and they couple cell metabolism to excitability. They are thought to be involved in neuroprotection against cell damage during hypoxia, ischemia and excitotoxicity by hyperpolarizing neurons and reducing excitability. Although barbiturates are often used in patients with brain ischemia, the effects of these agents on neuronal ATP-sensitive K channels have not been clarified. We studied the effects of thiopental and pentobarbital on surface ATP-sensitive K channels in principal neurons of rat substantia nigra pars compacta. Whole cell voltage- and current-clamp recordings were made using rat midbrain slices. ATP-sensitive K channels were activated by intracellular dialysis with an ATP-free pipette solution during perfusion with a glucose-free solution. When the pipette solution contained 4mM ATP and the perfusing solution contained 25 mM glucose, the membrane current at -60 mV remained stable. When intracellular ATP was depleted, hyperpolarization and an outward current developed slowly. Although thiopental did not affect the membrane current in the presence of ATP and glucose, it reversibly inhibited the hyperpolarization and outward current induced by intracellular ATP depletion at 100 and 300 microM. Thiopental reduced the ATP depletion-induced outward current by 4.7%, 36.7% and 87% at 30, 100 and 300 microM, respectively. The high dose of pentobarbital also exhibited similar effects on ATP-sensitive K channels. These results suggest that barbiturates at high concentrations but not at clinically relevant concentrations inhibit ATP-sensitive K channels activated by intracellular ATP depletion in rat substantia nigra.

Adenosine Triphosphate↗

Effect of the adenovirus E1A gene on nitric oxide production in alveolar epithelial cells.

This study determined the effect of the adenovirus E1A gene on nitric oxide (NO) production in alveolar epithelial (A549) cells. E1A-positive A549 cells (E1A transfectants), E1A-negative A549 cells (control transfectants) and untransfected A549 cells were placed in 96-well tissue culture plates. After stimulation with lipopolysaccharide (LPS) or cytokine mixture (CM), the biochemical reaction products of NO (nitrite and nitrate) in the culture medium were measured by chemiluminescence. The inducible (iNOS) and the endothelial (eNOS) isoforms of nitric oxide synthase (NOS) protein expression were examined by Western blotting. iNOS mRNA expression was examined by Northern blotting and RT-PCR. CM-induced NO production by E1A-positive A549 cells was significantly lower than that of E1A-negative cells (p < 0.0001). LPS stimulation failed to enhance NO production in both cell types. CM induced iNOS protein expression in E1A-negative A549 cells, but not in E1A-positive cells. eNOS protein expression was constitutive and was not affected by CM stimulation, LPS stimulation or E1A. CM induced iNOS mRNA expression in E1A-negative A549 cells, but not in E1A-positive cells. In conclusion, the adenovirus E1A gene suppressed NO production through transcriptional control of the iNOS gene in A549 cells. This inhibition of NO production may enable the virus to persist in human tissue, since NO is an antiviral effector of the innate immune system.

Adenovirus E1A Proteins↗

Increased serum concentrations of tissue inhibitor of metalloproteinase-1 in COPD patients.

Matrix metalloproteinase (MMP)-9 and tissue inhibitors of metalloproteinase (TIMP)-1 concentrations are increased in the sputum of asthma and chronic bronchitis patients, and are thought to be related to airflow obstruction. However, serum concentrations of these enzymes have not been clearly evaluated in patients with chronic obstructive pulmonary disease (COPD). The aim of this study was to examine the serum concentrations of these enzymes in COPD and asthmatic patients in order to determine their relationship with airway obstruction. Serum samples were obtained from 72 patients with COPD: 66 control subjects and 26 patients with asthma. Smoking histories of control subjects were matched with those of COPD patients. Serum concentrations of TIMP-1 and MMP-9 were determined by ELISA. The circulating TIMP-1 concentration was significantly higher in stable COPD patients than in control and asthmatic subjects, and was significantly negatively correlated with forced expiratory volume in one second/forced vital capacity in COPD patients. The molar ratio between MMP-9 and TIMP-1 was significantly lower in COPD patients than in control subjects. In patients with COPD, the serum TIMP-1 concentration was significantly increased during disease exacerbation. In conclusion, the current findings suggest that serum tissue inhibitors of metalloproteinase-1 concentration can be used as a serum marker of airway obstruction and exacerbation in chronic obstructive pulmonary disease patients.

Adrenal Cortex Hormones↗

[Strategy for thrombosed type A acute aortic dissection].

The surgical treatment for thrombosed type A aortic dissection is controversial. We treated 15 cases (28.8%) with thrombosed type A acute aortic dissection among 52 cases of all type A acute aortic dissection during past 7 years and 8 months. Nine cases was treated conservatively and 6 cases received emergent operation due to cardiac tamponade, shock, and ulcer-like projection (ULP) in the ascending aorta (> 50 mm). In the group of conservative therapy, 2 cases in which the ascending aorta was enlarged (54, 60 mm), was converted to operation in the acute phase because of further enlargement of ascending aorta and increase of cardiac effusion. The other patients (aortic diameter: 40-46 mm) who received conservative therapy were well controlled by medical therapy in the early and late phase except 1 who died suddenly in the follow-up. There was no mortality and late death in the operated patients. From these results, we conclude that thrombosed type A aortic dissection in which the diameter of ascending aortic aorta is larger than 50 mm, have cardiac tamponade and ULP in the ascending aorta might needs operation.

Aged↗

[Left coronary ostial stenosis caused by syphilitic aortitis].

We report 2 cases of cardiovascular disease related to end-stage syphilitic infection, which is now relatively rare. A 49-year-old man (case 1), and a 45-year-old man (case 2) were admitted to our hospital for angina pectoris. Cardiac catheterization showed severe aortic regurgitation and left coronary ostial stenosis. Active syphilis was detected in both cases by routine blood examination on admission. Oral ampicillin was started immediately to treat the syphilis; however, during the course of treatment, acute heart failure developed in both patients. We performed emergency aortic valve replacement and coronary artery bypass grafting. Intraoperatively, the orifice of the left coronary artery was almost occluded, and retrograde perfusion of cardioplegia was needed to induce cardiac arrest. Both patients recovered uneventfully. When treating patients with antibiotics for syphilitic disease, it is important to prepare for the possibility of urgent surgery.

Coronary Stenosis↗

[Ruptured infected descending aortic aneurysm successfully treated by omentopexy and a rifampicin-soaked vascular prosthesis; report of a case].

A 73-year-old man was admitted for investigation of back pain, blood-stained sputum, and a high fever. Computed tomography (CT) showed a pseudoaneurysm in the descending aorta and intravenous antibiotic therapy was begun immediately after blood had been taken for culture. However, his temperature continued to spike daily, up to 38 degrees C, and his CRP was also elevated. The blood cultures were negative. The aneurysm ruptured and we replaced the descending aorta with a rifampicin (RFP)-soaked vascular prosthesis, and wrapped it with greater omentum. Postoperative antibiotic therapy with vancomycin hydrochloride, RFP, and amikacin sulfate was continued for 8 weeks. The patient recovered uneventfully. Thus, an infected aneurysm was effectively treated with a RFP-soaked vascular prosthesis and omentopexy.

Aged↗

Experimental transplantation study for possible transformation of bone marrow cells in the mouse placenta.

The aim of the present study is to establish a mouse model of the transplantation of bone marrow cells into the placenta in mid-gestation. The mononuclear fraction of bone marrow cells was isolated by Ficoll gradient centrifugation from the femur bones of C57BL/6 green fluorescent protein (GFP) gene transgenic (Tg) mice. After intraperitoneal injection of pentobarbital sodium, the abdominal cavities of pregnant non-Tg (C57BL/6 or ICR) mice were opened at 9.5 days postcoitum (dpc). The mononuclear fraction of bone marrow cells from Tg mice (3-5 x 10(5)cells/3 microl) was directly injected into the placental portion of the pregnant uterus, at a depth of approximately 3 mm, using a 31-gauge injector. The placenta was sampled at 14.5 dpc. Confocal laser scanning microscopic analysis of the serial sections of the sampled placenta (150-250 sections/placenta) was carried out to detect GFP-positive cells and to assess immunostaining for cytokeratin, CD34, p57(Kip2) and prolactin. Most pregnant mice survived until sampling of the placenta at 14.5-18.5 dpc (88.9% for C57BL6 and 100% for ICR). The survival rate of fetuses from mice in which the placenta was transplanted with GFP-positive bone marrow cells was approximately 50%. A small population (0.154%) of injected bone marrow cells was retained in the placental tissue. Immunohistochemically, cytokeratin, CD34 and p57(Kip2) were positively stained in 0.062%, 4.5% and 2.1% of GFP-positive cells, respectively, while prolactin was not positive in any of the cells examined. GFP-positive bone marrow cells were successfully transplanted to the murine placenta. Future investigations of the specific antigens in bone marrow cells retained in the placenta may enable a better understanding of the local regulation of placental development.

Animals↗

Cyclic mechanical stretching and interleukin-1alpha synergistically up-regulate prostacyclin secretion in cultured human uterine myometrial cells.

Prostacyclin (PGI2), a potent uterine smooth muscle relaxant, is postulated to be a major prostaglandin (PG) secreted from the human myometrium. PGI2 metabolite concentrations in the maternal plasma were reported to be elevated during pregnancy, especially during labor. Recently, we developed cultured human myometrial cells from pregnant women and reported that cyclic mechanical stretching mimicking labor increased PGI2 secretion from these cells by up-regulating PGI2 synthase promoter activities. Since elevation of cervical/vaginal interleukin-1alpha (IL-1alpha) concentrations is also a characteristic feature of delivery, and IL-1alpha is a known stimulator of PG synthesis, we investigated a possible synergistic effect of cyclic mechanical stretching and IL-1alpha on PGI2 production in cultured human myometrial cells. Treatment with IL-1alpha (10 ng/ml) significantly augmented (4- to 60-fold) the secretion of PGI2, prostaglandin E2 (PGE2), prostaglandin F2alpha (PGF2alpha) and thromboxane A2 (TXA2) from cultured human myometrial cells obtained from non-pregnant and pregnant women as well as in cultured human umbilical artery and cultured human coronary artery smooth muscle cells (p < 0.05 for all comparisons). However, labor-like cyclic mechanical stretching up-regulated IL-1alpha-augmented PGI2 secretion from myometrial cells obtained from non-pregnant and pregnant women 2.1- to 2.8-fold (p < 0.05 for all comparisons), but not PGE2, PGF2alpha nor TXA2. Moreover, such an augumentation of PGI2 secretion by cyclic mechanical stretching was not observed in cultured human umbilical artery nor in cultured human coronary artery smooth muscle cells. These results suggest that cyclic mechanical stretching by labor, in concert with IL-1alpha stimulation, contributes to the increase in myometrial PGI2 secretion during delivery.

6-Ketoprostaglandin F1 alpha↗

Effects of neuromuscular-blocking drugs in rats in vivo: direct measurements in the diaphragm and tibialis anterior muscle.

BACKGROUND: Effects of neuromuscular-blocking drugs are often investigated in rodents using both the diaphragm in vitro and the tibialis anterior muscle in vivo. Differences in the properties of these muscles cannot be neglected. We evaluated the neuromuscular effects of drugs on the rat diaphragm in vivo in comparison with the tibialis anterior muscle, directly measuring twitch tension with a force transducer. METHODS: Respectively using sternotomy and an approach via the gluteal space, transducers were attached to the diaphragm and the tibialis anterior muscle. Phrenic and sciatic nerves were stimulated supramaximally by single square pulses to record isometric contraction of muscles. Pancuronium, vecuronium, or rocuronium was infused continuously at a rate adjusted repeatedly until stable tension was obtained. Effective doses for 50% (ED 50) and 90% (ED 90) depression of tension were calculated, using a cumulative infusion dosing method. RESULTS: Isometric contraction of the diaphragm could be recorded despite movements of the heart and lungs. For all three drugs, both mean ED 50 and ED 90 were more than twice as large for the diaphragm as for the tibialis anterior (P<0.05). In addition, slopes of dose-response curves for the diaphragm were significantly less steep than those of the tibialis anterior for the three drugs. CONCLUSION: Neuromuscular-blocking effects on the diaphragm can be recorded in vivo. According to direct contractile force measurement, the diaphragm is more resistant to non-depolarizing neuromuscular-blocking drugs than the tibialis anterior muscle.

Animals↗