Search PubMed⌕ Search

Biomedical subjects

H Ito

Publications and source records attributed to H Ito.

At least 343 records · Page 19Linked to original sources

Chemistry and function of vegetable polyphenols with high molecular weights.

Structure and function of polypehnols with high molecular weights (tannins) were briefly reviewed to better understand the significance of polyphenol-rich foods and beverages. In a survey of bioactive ellagiannins with a macrocyclic structure and/or a gluconic acid core, some new oligomeric ellagitannins (eucarpanins and elaeagnatins) have been found in species of Myrtaceae and Elaeagnaceae, and their structures were elucidated by spectroscopic and chemical methods. Cytotoxic activity against human oral tumor cell lines and antibacterial activity against Helicobacter pylori have been evaluated for the ellagitannins obtained from both plants, and related compounds. The macrocyclic dimers, oentothein B, camelliin B and woodfordin C showed a remarkable cytotoxicity against human oral squamous cell carcinoma, but not against normal cells. These active tannins induced apoptosis of tumor cells. A potent antibacterial activity against Helicobacter pylori was exhibited by monomeric ellagitannins such as tellimagrandin I and stricitinin.

Anti-Bacterial Agents↗

Tumour necrosis factor-alpha up-regulates the expression of BMP-4 mRNA but inhibits chondrogenesis in mouse clonal chondrogenic EC cells, ATDC5.

Tumour necrosis factor (TNF)-alpha causes the degradation of articular cartilage in arthritis via direct actions on chondrocytes. However, it remains unknown whether TNF-alpha affects chondrogenesis in chondroprogenitors. In the present study, we assessed the effects of TNF-alpha in vitro on chondrogenesis using mouse clonal chondrogenic EC cells, ATDC5. TNF-alpha (10 ng/ml) stimulated [3H] thymidine incorporation in undifferentiated ATDC5 cells, and suppressed cartilaginous nodule formation and the accumulation of cartilage-specific proteoglycan. We recently showed that undifferentiated ATDC5 cells express BMP-4 and that exogenously administered BMP-4 promotes chondrogenesis in these cells. Interestingly, TNF-alpha up-regulated the expression of BMP-4 mRNA in undifferentiated ATDC5 cells in time- and dose-dependent manners. However, exogenously administered BMP-4 was not capable of reversing the inhibitory action of TNF-alpha on chondrogenesis in ATDC5 cells. These results indicate that TNF-alpha stimulates both cell proliferation and BMP-4 expression but inhibits chondrogenesis in chondroprogenitor-like ATDC5 cells.

Animals↗

Graft vasculopathy and tolerance: does the balance of Th cells contribute to graft vasculopathy?

BACKGROUND: Cardiac allograft vasculopathy (CAV) is sometimes observed even though the allograft may survive indefinitely. In this study, we examined whether or not the preferential activation of Th2-type cells prevents the development of CAV. METHODS: Hearts from C57BL/10 mice were transplanted heterotopically into the abdominal cavities of C3H.He recipient mice, and monoclonal antibodies (mAbs) to T-cell receptor (TCR) alphabeta or CD80/CD86 were administered after transplantation. The incidence of CAV was then examined histologically. To investigate the relative Th1/Th2 balance, the levels of IFNgamma and IL4 in the transplanted hearts were measured. RESULTS: Indefinite heart graft survival was observed in mice treated with either the anti-TCRalphabeta or anti-CD80/CD86 mAbs and these mice accepted donor-type (C57BL/10) skin grafts but rejected those from a third party (BALB/c). Evidence of CAV was found in the mice treated with the anti-TCRalphabeta mAb, but CAV did not develop in the mice treated with anti-CD80/CD86 mAbs. Preferential activation of Th2-type cells was dominant in the tolerant mice treated with anti-TCRalphabeta mAb, but it was not dominant in the tolerant mice treated with anti-CD80/CD86 mAbs. CONCLUSION: These findings suggest that the dominance of Th2-type cells does not prevent allograft vasculopathy.

Adoptive Transfer↗

AT1 receptor antagonist prevents brain edema without lowering blood pressure.

In order to investigate the role of Angiotensin II (AII) for the vasogenic cerebral edema, the AT1 receptor antagonist (TCV-116) was administered to 19-week-old stroke-prone spontaneously hypertensive rats (SHRSP) for 2 weeks at a dosage which did not decrease the blood pressure. Although no remarkable changes were found in blood pressure after treatment, the average brain weight of the treated group was relatively lower as compared to that of control SHRSP and no edematous changes were found in any brains. The immunohistochemical expression of intercellular adhesion molecule-1 (ICAM-1) was less and the glucose transporter-1 (GLUT-1) expression was much more intense in the endothelial cells of the micro vessels in the cerebral cortex of the treated group. Fibrinogen expression around micro-vessels was also remarkably reduced in the treated group. A decreased expression of ICAM-1 in the treated group was confirmed by RT-PCR analysis. These results indicate that the AT1 receptor blockade ameliorates hypertensive cerebral injury in a blood pressure-independent manner and suggest that AII may have an important role for endothelial injury in severe hypertension.

Angiotensin II↗

Effects of inducible nitric oxide synthase inhibition on cerebral edema in severe hypertension.

In order to clarify the causative role of cytotoxic nitric oxide (NO) in hypertensive cerebral injury, the effects of inducible nitric oxide synthase (iNOS) inhibition on leukocytes and endothelial function were examined using stroke-prone spontaneously hypertensive rats (SHRSP). For the iNOS inhibition, S-methylisothiourea (SMT) was administered to 12-week-old male SHRSP for 3 weeks. Immunohistochemical examination were carried out for the expression of intercellular adhesion molecule-1 (ICAM-1), glucose transporter-1 (GLUT-1), fibrinogen and glial fibrillary acidic protein (GFAP) in cerebral cortex. The effects of iNOS inhibition was also examined for Mac-1 expression by flow cytometric analysis. Plasma NO metabolites level was significantly lower in the SMT group than in the control group. Mac-1 expression was inhibited by SMT. In the SMT group, brain weight was significantly lower than in the control. By SMT administration, ICAM-1 expression was suppressed, GLUT-1 was enhanced, fibrinogen was decreased and GFAP was decreased as compared to those in control group. In hypertensive cerebral injury in SHRSP, iNOS-derived NO, mainly in activated leukocytes, could be an important causative factor for endothelial injury.

Animals↗

Relationship between striatal [123I]beta-CIT binding and four major clinical signs in Parkinson's disease.

We investigated the correlation between clinical severity and striatal [123I]-CIT binding in 12 patients with Parkinson's Disease (PD: 6 men and 6 women, age: 65 +/- 7 years, Hoehn & Yahr stage: 1 to 3). The clinical severity of PD patients was measured with the Unified Parkinson's Disease Rating Scale (UPDRS) after withdrawal of antiparkinsonian medication at least 12 hours before assessment. [123I]beta-CIT binding in the caudate and putamen was measured at 3 hours [V''3 (day 1)], and at 24 hours [V''3 (day 2)) after tracer injection with small square ROIs. The specific striatal uptake index (day 2) was calculated with large square ROIs that encompassed the whole striatum. The best correlation (r = -0.82, p < 0.0012) was between putamenal V''3 (day 2) and the motor UPDRS scores. When the motor UPDRS scores were divided into four subscales, bradykinesia was the only sign that correlated significantly with putamenal V''3 (day 2) (r = -0.81, p < 0.002). [123I]beta-CIT SPECT is a useful marker of disease severity in PD with potential utility in the serial monitoring of disease progression.

Aged↗

Efficacy of HSP72 induction in rat liver by orally administered geranylgeranylacetone.

It is well known that heat-shock proteins (HSPs) have a cytoprotective function as "molecular chaperones" when cells are exposed to several stress conditions. Geranylgeranylacetone (GGA) is an antiulcer drug that was developed in Japan and it has recently been reported to induce HSP72 in rat gastric mucosa. In this experiment, we investigated the induction of HSP72 in rat liver in response to oral administration of GGA and assessed its ability to induce tolerance to warm ischemic injury by this approach. We prepared donor rats by orally administering GGA to them and compared HSP72 expression in graft liver, survival rates, and serum TNF-alpha concentrations after liver transplantation with the findings in controls. The survival rates were significantly increased when the livers were obtained from donor rats given GGA. Western blotting revealed expression of HSP72 in graft livers given GGA, and the serum TNF-alpha levels were significantly suppressed in the rats given GGA. Oral administration of GGA induced HSP72 in graft livers, and they were better able to tolerate warm ischemic injury. Oral administration of GGA appears to provide a promising new strategy for preventing ischemia-reperfusion injury.

Administration, Oral↗

Effect of soy protein on bone metabolism in postmenopausal Japanese women.

We conducted a cross-sectional study of the effects of soybean protein intake on bone mineral density and biochemical markers in 85 postmenopausal Japanese women. Nutrients in the diet of postmenopausal Japanese women visiting the osteoporosis unit, including subjects with normal lumbar spine bone mineral density (L2-4 BMD), were investigated by questionnaire, and the calculated daily energy, protein, soy protein and calcium intake were obtained. L2-4 BMD was measured with dual-energy X-ray absorptiometry, and assays done of serum alkaline phosphatase (ALP) and serum intact osteocalcin (IOC) as bone formation markers and urinary pyridinoline (UPYR) and urinary deoxypyridinoline (UDPYR) as bone resorption markers. Soy protein intake was significantly associated with the Z-score for L2-4 BMD (r = 0.23,p = 0.038) and UDPYR (r = -0.23, p = 0.034). Stepwise multiple regression analyses showed that soy protein intake is significantly associated with the Z-score for L2-4 BMD (beta = 0.225, p = 0.04) and UDPYR (beta = -0.08, p = 0.03) among four nutritional factors. These results suggest that high soy protein intake is associated with a higher bone mineral density and a lower level of bone resorption, but further studies are needed to confirm the causal dynamic mechanisms.

Absorptiometry, Photon↗

High 5HT2A receptor occupancy in M100907-treated schizophrenic patients.

RATIONALE: Selective drugs are required to test the hypothesis whether antipsychotic effects may be induced or modulated by 5HT(2A) receptor antagonism. M100907 (previously known as MDL 100,907) is a highly selective 5HT(2A) antagonist in clinical development. OBJECTIVE: To test if the suggested clinical dose of 20 mg M100907 daily induces high 5HT(2A) receptor occupancy in patients with schizophrenia. METHODS: The 5HT(2A) receptor occupancy was determined in two patients with schizophrenia treated with M100907, 20 mg once a day. Positron emission tomography (PET) with (11)C-labeled M100907, was performed prestudy and under steady state conditions. Clinical ratings were performed weekly. RESULTS: Clinical treatment with M100907, 20 mg daily induced a very high 5HT(2A) receptor occupancy in the frontal cortex of both patients (>90%). M100907 was well tolerated. One patient improved minimally and one patient became minimally worse during treatment. CONCLUSIONS: The results confirm that an oral dose of 20 mg per day ensures adequate 5HT(2A) receptor occupancy for clinical proof of concept. The sample is too small to allow conclusions about the clinical effect.

Adult↗

Immune gene therapy of experimental mouse brain tumor with adenovirus-mediated gene transfer of murine interleukin-4.

We examined the antitumor activity of replication-deficient adenoviral vectors carrying the murine interleukin-4 (IL-4) gene (AdCIL4) using a syngeneic brain tumor model in mice. Mice implanted with malignant astrocytoma cells infected with AdCIL4 survived significantly longer than those in the control groups. Immunocytochemical analysis of the tumors showed that AdCIL4 caused the strong up-regulation of MHC class II antigen expression by the tumor cells and macrophages, and consequent infiltration by CD8+ T lymphocytes. This study demonstrates the efficacy of IL-4 gene transfection mediated by adenoviral vectors for intracerebral tumor and characterizes the immunoreaction caused by AdCIL4.

Adenoviridae↗

Pediatric acoustic schwannoma showing rapid regrowth with high proliferative activity.

Acoustic schwannoma is a slow-growing tumor and usually occurs in adult patients. We report a rare pediatric case of acoustic schwannoma with high proliferative potential. A 10-year-old boy was diagnosed as having a right cerebellopontine angle tumor. The tumor was subtotally resected. Histological examination revealed a typical acoustic schwannoma with a few mitotic figures. Chromosomal analysis showed no abnormality on the long arm of chromosome 22 associated with neurofibromatosis type 2. The lesion re-grew rapidly as an acoustic schwannoma, necessitating subtotal resection on three occasions and CyberKnife radiosurgery. The immunohistochemical MIB-1 staining indices of the specimens obtained at the first, second, and third operations were 2.3%, 4.6% and 14.7%, respectively. The immunohistochemical proliferative potential of acoustic schwannoma is discussed.

Biomarkers, Tumor↗

Congenital balloon digits in two neonates caused by constriction rings.

Balloon digits were found in two neonates with congenital constriction ring syndrome. The affected digits were the right long finger and right great toe. They were surgically treated at the age of 10 and 9 days, respectively. Morphologic improvement was dramatic after surgery. In cases with extensive enlargement, severe cyanosis, redness, and no subsidence of edema within several days after birth, early operative treatment may be necessary to maintain digit viability and prevent autoamputation due to circulatory embarrassment. It can also be helpful to prevent fibrosis of the subcutaneous tissue. Pathologic examination revealed marked proliferation of fibrous tissue and lymphatic vessels.

Constriction, Pathologic↗

Thymidine phosphorylase expression results in a decrease in apoptosis and increase in intratumoral microvessel density in human gastric carcinomas.

Thymidine phosphorylase (dThdPase)/platelet-derived endothelial cell growth factor (PD-ECGF) is expressed at higher levels in a variety of human carcinomas than in adjacent normal tissue. The higher expression is associated with an increase in intratumoral microvessel density (IMVD) and an unfavorable patient prognosis. This study examined the role of dThdPase in apoptosis, IMVD and p53 expression in human gastric carcinomas, dThdPase expression was noted in 12 (35.3%) of 34 early carcinomas, and in 20 (55.6%) of 36 advanced carcinomas. At least 10 areas consisting of carcinoma cells with diffuse dThdPase expression from the 32 dThdPase-positive tumors (category I), and 10 areas without dThdPase expression from the 38 negative tumors (category II) were selected from each case. For early gastric carcinoma, the mean IMVD was 88.8+/-19.4 in category I and 61.4+/-17.3 in category II carcinomas, while for advanced gastric carcinoma, the mean IMVD was 98.8+/-21.0 in category I and 76.0+/-27.1 in category II carcinomas. The mean IMVD was significantly higher in category I than in category II tumors (P<0.05). The mean apoptotic index (AI: percentage of apoptotic cells) was 1.95+/-1.30 in category I, and 3.76+/-1.49 in category II carcinomas for early gastric carcinoma, and 1.51+/-0.98 in category I and 2.14+/-0.66 in category II carcinomas for advanced gastric carcinoma, the value of the mean AI being significantly (P<0.05) higher in dThdPase-negative tumors (category II) than in the positive tumors (category I), regardless of tumor stage or histological type. There was a significant inverse correlation (P<0.001) between AI and IMVD. These results indicate that dThdPase expression is associated with both an increase in intratumoral microvessels and a decrease in apoptosis in human gastric carcinomas.

Adenocarcinoma↗

Monosynaptic inputs from the nucleus tractus solitarii to the laryngeal motoneurons in the nucleus ambiguus of the rat.

The cricothyroid (CT) and the posterior cricoarytenoid (PCA) muscles in the larynx are activated by the laryngeal motoneurons located within the nucleus ambiguus; these motoneurons receive the laryngeal sensory information from the nucleus tractus solitarii (NTS) during respiration and swallowing. We investigated whether the neurons in the NTS projected directly to the laryngeal motoneurons, and what is the synaptic organization of their nerve terminals on the laryngeal motoneurons using the electron microscope. When wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) was injected into the NTS after cholera toxin subunit B-conjugated HRP (CT-HRP) was injected into the CT muscle or the PCA muscle, the anterogradely WGA-HRP-labeled terminals from the NTS were found to directly contact the retrogradely CT-HRP-labeled dendrites and soma of both the CT and the PCA motoneurons. The labeled NTS terminals comprised about 4% of the axosomatic terminals in a section through the CT motoneurons, and about 9% on both the small (PCA-A) and the large (PCA-B) PCA motoneurons. The number of labeled axosomatic terminals containing round vesicles and making asymmetric synaptic contacts (Gray's type I) was almost equal to that of the labeled terminals containing pleomorphic vesicles and making symmetric synaptic contacts (Gray's type II) on the CT motoneurons. The labeled axosomatic terminals were mostly Gray's type II on the PCA-A motoneurons, while the majority of them were Gray's type I on the PCA-B motoneurons. These results indicate that the laryngeal CT and PCA motoneurons receive a few direct excitatory and inhibitory inputs from the neurons in the NTS.

Animals↗

Primary intracranial malignant schwannoma of trigeminal nerve. A case report with review of the literature.

The authors report a rare case of primary intracranial malignant schwannoma of the trigeminal nerve occuring in a 30-year-old woman without von Recklinghausen's neurofibromatosis (VRNF). The tumour arose from the intracranial part of the left trigeminal nerve, without skull base destruction. The tumour was partially removed operatively, followed by focal 50 Gy irradiation, but unfortunately the tumour showed rapid regrowth. A second operation was attempted, but she died of cerebral infarction soon after operation. Histologically, the original tumour was characterized by the presence of foci of extremely high cellularity, pleomorphism and mitosis in an otherwise typical benign schwannoma. Immunohistochemically, the tumour cells were positive for S-100 protein even in the atypical areas, suggesting the tumour to be of Schwann cell origin. However, the recurrent tumour was composed of undifferentiated spindle cells, which were negative for S-100 protein. Thus, it is possible to consider that the S-100 protein expression could reflect the degree of differentiation of Schwann cells. Furthermore, the postoperative irradiation might have exacerbated the malignant progression in the present case.

Adult↗

Cox-2 expression in retinoblastoma.

PURPOSE: Cox-2, a prostaglandin synthase, is overexpressed in colorectal cancers and is involved in angiogenesis as well as in tumorigenesis. In this study, we investigate the expression of Cox-2 in retinoblastoma. METHODS: Twenty-nine formalin-fixed retinoblastoma specimens were examined by the labeled-streptavidin-biotin method using anti-Cox-2 antibody. RESULTS: Cox-2 positive immunoreactions were observed in 28 (96%) of 29 retinoblastomas specimens. CONCLUSION: This preliminary study suggests the overexpression of Cox-2 in both differentiated and undifferentiated retinoblastoma and its possible role in tumorigenesis.

Child, Preschool↗

Biological features and preoperative evaluation of mediastinal nodal status in non-small cell lung cancer.

BACKGROUND: To examine whether biological features of primary tumor can help preoperative evaluation of mediastinal nodal status in non-small cell lung cancer. METHODS: A total of 450 patients who underwent tumor resection and mediastinal dissection were reviewed. p53 status and proliferative fraction (PI) were evaluated immunohistochemically. RESULTS: The accuracy of preoperative evaluation of mediastinal nodal status with computed tomography (CT) was 72.2%; mediastinal nodal metastases had not been revealed until operation in 59 patients (13.1%) (false-negative), and no metastasis was revealed in 66 patients (14.7%) although mediastinal nodal enlargement had been demonstrated by CT (false-positive). The number of false-negative patients was significantly larger when p53 aberrant expression was positive or when PI was higher. Combined with p53 status and PI, there were 27 false-negatives (24.1%) among patients with aberrant p53 expression and higher PI, whereas only two false-negatives (1.5%) among those with negative p53 expression and lower PI. CONCLUSIONS: Mediastinoscopy may be recommended for tumor showing aberrant p53 expression and higher PI, even when CT demonstrates no mediastinal nodal enlargement.

Aged↗

Flavonoid and benzophenone glycosides from Coleogyne ramosissima.

A benzophenone glucoside and two flavonol glycosides were isolated together with 27 known polyphenols from the aerial parts of Coleogyne ramosissima, and their structures were elucidated by spectroscopic and chemical methods as iriflophenone 2-O-beta-glucopyranoside, isorhamnetin 3-O-2G-rhamnopyranosylrutinoside-7-O-alpha-rhamnopyranoside and limocitrin 3-O-rutinoside-7-O-beta-glucopyranoside, respectively.

Carbohydrate Conformation↗