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Biomedical subjects

H Ito

Publications and source records attributed to H Ito.

At least 379 records · Page 21Linked to original sources

Reduction of polyethylene wear by concave dimples on the frictional surface in artificial hip joints.

For the purpose of reduction of polyethylene wear generated in artificial hip joints, concave dimples were formed on the surface of the metal femoral head by electrical discharge etching with the constant diameter of 0.5 mm, pitch of 1.2 mm, and depth of 0.1 mm. Using a hip joint simulator, the total amount of polyethylene wear was 7.2 mg in the concave-patterned condition and 23.1 mg in the nonpatterned condition. The reasons for the reduction of polyethylene wear by the concave pattern may be i) a reduction of abrasive wear by providing escape dimples for wear particles and ii) an improvement in the lubricity on the frictional surface by the supply of lubricant that is stored in dimples.

Friction↗

Effects of the AT1 receptor antagonist on adhesion molecule expression in leukocytes and brain microvessels of stroke-prone spontaneously hypertensive rats.

To elucidate the possible involvement of angiotensin II (AII) in the pathogenesis of microvascular changes in severe hypertension, we investigated the effects of angiotensin II type 1 (AT1) receptor antagonist and angiotensin-converting enzyme inhibitor (ACEI) on the expression of adhesion molecules of leukocytes and brain microvessels. Male stroke-prone spontaneously hypertensive rats (SHRSP) at 19 weeks of age were divided into three groups and age-matched Wistar-Kyoto rats (WKY) were used as the control group. AT1 receptor antagonist (TCV-116, 0.5 mg/kg/day) and ACEI (captopril, 20 mg/kg/day) were administered to SHRSP for 4 weeks. Mac-1 expression in leukocytes was investigated by flow cytometric analysis. For endothelial cells, we examined the expression of intercellular adhesion molecule-1 (ICAM-1), the AT1 receptor, and glucose transporter-1 (GLUT-1, a marker of the blood-brain barrier) using reverse transcription-polymerase chain reaction (RT-PCR). The blood pressure of AT1 receptor antagonist and ACEI-treated groups was slightly lower than that of the control, but was still greater than 220 mm Hg. Mac-1 expression, as well as ICAM-1 expression, was higher in control SHRSP than in WKY. Such enhanced expression of adhesion molecules in SHRSP was ameliorated by the administration of AT1 receptor antagonist or ACEI, the former being more effective. AT1 receptor expression was higher in control SHRSP than in WKY, and was lower in the AT1 receptor antagonist group, whereas no difference was found in the ACEI group. No significant differences were found in GLUT-1 expression among all groups. In the case of hypertensive cerebral injuries in SHRSP, leukocytes may have an important role for initiation via adhesion to endothelial cells. AT1 receptor antagonist showed a beneficial effect for the amelioration of enhanced expression of adhesion molecule in both leukocytes and endothelial cells. Thus, AII seems to be an important mediator for the hypertensive microvascular injuries.

Angiotensin II↗

Cytotoxic activity of hydrolyzable tannins against human oral tumor cell lines--a possible mechanism.

Hydrolyzable tannins showed higher cytotoxic activity against human oral squamous cell carcinoma and salivary gland tumor cell lines than against normal human gingival fibroblasts, whereas gallic acid, a component unit of tannins, showed much weaker selective cytotoxicity. The cytotoxic activity of dimeric compounds was generally higher than that of monomeric compounds. Macrocyclic ellagitannin oligomers, such as oenothein B, woodfordin C and woodfordin D showed the greatest cytotoxic activity, and their activity (per given number of molecules) was one order higher than those of gallic acid and epigallocatechin gallate, a major component of green tea. These compounds induced apoptotic cell death characterized by DNA fragmentation (as demonstrated by the TUNEL method) and cleavage of cytokeratin 18 by activated caspase(s) (as demonstrated by M30 monoclonal antibody). ESR spectroscopy revealed that these macrocyclic compounds at higher concentrations produced their own radicals and significantly enhanced the radical intensity of sodium ascorbate, possibly by their prooxidant actions. Catalase failed to eliminate their apoptosis-inducing activity, reducing the possibility of the involvement of hydrogen peroxide production in the extracellular fraction. These observations suggested that the antitumor activity of macrocyclic ellagitannin oligomers reported previously might be explained by their apoptosis-inducing activity.

Antineoplastic Agents↗

Effects of tannins and related polyphenols on superoxide-induced histamine release from rat peritoneal mast cells.

The effects of tannins and related polyphenols on KO2- and compound 48/80-induced histamine release from rat peritoneal mast cells were examined. Pretreatment with hydrolyzable tannins (1-100 microM) significantly inhibited KO2-induced histamine release. Dimeric ellagitannins, which have hexahydroxydiphenoyl (HHDP) and valoneoyl residues and/or a valoneoyl-related acyl unit in the molecule, showed more potent inhibitory effects than monomeric hydrolyzable tannins. The most effective inhibition was exhibited by agrimoniin and euphorbin C (IC50 0.68 and 0.80 microM), which have dehydrodigalloyl and euphorbinoyl groups, respectively, as well as the HHDP group. However, procyanidins, flavonoids and related polyphenols with small molecular weights, except for epigallocatechin gallate, exhibited negligible effects. Although clinically used antiallergic drugs, azelastine, astemizole, ketotifen and epinastine have been shown to prevent KO2-induced histamine release, their potencies were all less than those of ellagitannins. An inhibitory effect on compound 48/80-induced histamine release was also exhibited by higher molecular weight tannins. The inhibitory effect on histamine release caused by different stimulants suggested that ellagitannins act as cell membrane stabilizers as well as radical scavengers.

Animals↗

Absorption of chlorogenic acid and caffeic acid in rats after oral administration.

Absorption of orally administered chlorogenic acid (5-caffeoylquinic acid) and caffeic acid in rats was studied to obtain plasma pharmacokinetic profiles of their metabolites. Rats were administered 700 micromol/kg body weight of chlorogenic or caffeic acid, and blood was collected from the tail for 6 h after administration. Ingested caffeic acid was absorbed from the alimentary tract and was present in the rat blood circulation in the form of various metabolites. On the other hand, only traces of metabolites, supposedly caffeic and ferulic acids conjugates, were detected in rat plasma for 6 h after chlorogenic acid administration. Chlorogenic acid and small amounts of caffeic acid were found in the small intestine for 6 h after chlorogenic acid administration. These results suggest that chlorogenic acid is not well absorbed from the digestive tract, unlike caffeic acid, and subject to almost no structural changes to the easily absorbed forms.

Administration, Oral↗

Cypellocarpins A-C, phenol glycosides esterified with oleuropeic acid, from Eucalyptus cypellocarpa.

Three new phenol glycosides acylated with (+)-oleuropeic acid, cypellocarpins A (1), B (2), and C (3), along with seven known compounds, were isolated from the dried leaves of Eucalyptus cypellocarpa. Structures of the new compounds were determined on the basis of spectroscopic methods, including 2D NMR experiments and chemical degradation. These new compounds and a known related glucoside (7) showed potent in vitro antitumor-promoting activity in a short-term bioassay evaluating the inhibitory effect on Epstein-Barr virus early antigen activation induced by 12-O-tetradecanoyl phorbol 13-acetate (TPA). These compounds also suppressed an in vivo two-stage carcinogenesis induced with nitric oxide and TPA on mouse skin.

Animals↗

Circulating p53 antibody in patients with colorectal cancer: relation to clinicopathologic features and survival.

The presence of serum anti-p53 antibody has been reported to be associated with survival of patients with breast cancer, ovarian cancer, and hepatocellular carcinoma. To clarify prognostic significance of p53 antibody in colorectal cancer, serum p53 antibody was measured in patients with colorectal cancer. The 89 patients included 71 with colorectal cancer and 18 with colon polyp. An enzyme-linked immunosorbent assay was used to detect p53 antibodies in serum. Clinicopathological parameters such as age, sex, degree of differentiation of cancer, location of tumor, liver metastasis, stage classification, Dukes classification, CEA, CA19-9, and immunostaining of p53 and anti-p53 antibody were evaluated as prognostic factors of colorectal cancer. p53 antibody was positive in 18 of 71 (25%) with colorectal cancer, whereas it was positive in only 1 of 18 (6%) with colon polyp. The patients with p53 antibody had higher CEA and CA19-9 levels, higher positive rates of p53 protein expression in cancer cells, and higher liver metastasis rates. The p53 antibody positivity at stage classification I-IIIb/ Dukes classification A-C was significantly lower than that at stage classification IV/Dukes classification D. Overall survival in colorectal cancer patients with p53 antibody was significantly shorter than in those without p53 antibody. A Cox regression analysis showed that liver metastasis, stage classification, Dukes classification, CA19-9, and p53 antibody were significant prognostic factors in colorectal cancer. Serum anti-p53 antibody could serve as one of the prognostic factors in patients with colorectal cancer.

Aged↗

Postoperative radiation therapy for pituitary adenoma.

BACKGROUND: We evaluated the efficacy of postoperative radiation therapy (RT), prognostic factors for local control probability, dose response relationship and treatment sequelae in 75 patients with pituitary adenoma. MATERIALS AND METHODS: A total dose of 48-60 Gy (median: 50 Gy) was delivered with a conventional fractionation schedule after surgery. Of 75 patients, 55 (73%) were followed for more than 5 years and 27 (36%) were followed for more than 10 years with a median of 95 months. RESULTS: Five- and 10-year local control probabilities were 87.1% and 85.0%, respectively. Univariate analysis revealed that age (p = 0.007), tumor volume smaller than 30 cm3 (p = 0.018) and the absence of prolactin secretion (p = 0.003) were significantly favorable prognostic factors for local control probability. After multivariate analysis combining these 3 factors, tumor volume smaller than 30 cm3 (p = 0.017) and age (p = 0.039) were statistically significant. Patients with prolactinoma greater than 30 cm3 showed particularly poor local control rates. No significant improvement of the local control rate was detected with increasing total irradiation doses between 48 and 60 Gy (p = 0.29). The most common side effect was hypopituitarism, and there were no severe sequelae such as optic neuropathy or brain necrosis. CONCLUSION: Except with prolactinoma, the dose of postoperative RT for pituitary adenoma should not exceed 50 Gy. Large prolactinoma, however, was very difficult to control with the irradiation doses between 50 and 60 Gy, and would be good candidates for stereotactic radiosurgery or stereotactic radiation therapy.

Adenoma↗

Histopathology of a human allografted kidney with clinically sufficient function.

To clarify the clinico-pathological significance of protocol biopsy and clinically silent rejection in the management of renal graft recipients, we selected a total of 139 (23%) from 604 biopsy specimens according to the following criteria: 1) less than 1.4 mg/dL of serum creatinine and 2) more than 1,500 mL/d of urine volume at time of biopsy. Clinical indications for the biopsy were classified into five categories: i) protocol biopsy (73 specimens), including 69 cases at discharge post-transplantation; ii) slight increase in serum creatinine (32); iii) proteinuria (20); iv) evaluation of pulse-therapy (13); and v) fever elevation (1). Except for the last category, the specimens were histopathologically diagnosed as being normal in 50 (68%), 6 (17%), 1 (5%), and 5 (38%) specimens, respectively. Even borderline changes, and mild acute rejection, as well as drug-induced nephropathy were included, implying the existence of clinically silent rejection or drug-induced nephropathy. Obvious diversity in the histopathological diagnosis was noted in category iii) showing proteinuria, which was mainly caused by chronic rejection, drug-induced nephropathy and glomerulonephritis. The graft survival rate was no different among the four categories, except for category v). These results indicate that biopsies obtained from functionally sufficient renal grafts could provide useful information in the management of the recipients. The clinical significance of protocol biopsy awaits further clarification by the analysis of a large number of cases.

Biopsy↗

Both the HLA-CPB1 and -DRB1 alleles correlate with risk for multiple sclerosis in Japanese: clinical phenotypes and gender as important factors.

The purpose of this study was to clarify the association of HLA-DRB1 and -DPB1 alleles with multiple sclerosis (MS) in Japanese, to determine whether optico-spinal MS (OS-MS) and conventional MS are immunogenetically distinct, and to verify the role of gender difference in HLA associations of MS. We studied HLA-DRB1 and -DPB1 polymorphisms in 166 Japanese patients with MS. Forty-seven patients were classified as having the optico-spinal MS (OS-MS) and 119 as having conventional MS. A lack of DPB1*0301 and a higher frequency of DPB1*0501 compared with controls (corrected P<0.0074; odds ratio=9.48) were found in OS-MS. By contrast, we found for the first time an association of DPB1*0301 with conventional MS in Japanese (corrected P=0.0444; odds ratio=3.28). Logistic analysis, adjusted for sex and age, revealed independent associations of DPB1*0301 (P=0.0004, adjusted odds ratio (aOR)=4.70), DPB1*0501 (P=0.0081, aOR= 2.50) and DRB1*1501 (P=0.0252, aOR=2.21) with conventional MS. However, the frequencies of DRB1*1501 and DPB1*0501 in male patients with conventional MS were equal to those in male controls while the DPB1*0301 frequency was increased in both male and female patients. We did not find any association of these HLA alleles with disease course and severity. In conclusion, OS-MS is a DPB1*0501-associated distinct subtype of MS, and DPB1*0301 is the most strongly associated allele with conventional MS in Japanese. In addition, gender plays an important role in HLA association with MS.

Alleles↗

Formation of the male-specific muscle in female Drosophila by ectopic fruitless expression.

The Drosophila fruitless (fru) gene product Fru has been postulated to be a neural sex-determination factor that directs the development of at least two male-specific characteristics, namely courtship behaviour and formation of the muscle of Lawrence (MOL). The fru gene encodes a putative transcription factor with a BTB domain and two zinc-finger motifs, and with consensus Tra-binding sequences. The binding of Tra to these sequences results in sex-specific alternative splicing of the fru mRNA, leading to production of the 'male-type' or 'female-type' Fru protein. We show here that the Fru protein is not detected in the female central nervous system (CNS), despite the similar level of expression of fru mRNA in both male and female CNS. As ectopic expression of both the 'male-type' (with the sequence for the amino-terminal extension) and 'female-type' (without the sequence for the amino-terminal extension) fru cDNA can induce formation of the MOL in females, the presence or absence of the Fru protein, and not its sex-specific structure, seems to be responsible for the sexually dimorphic actions of the fru gene.

Alleles↗

Allogeneic bone marrow transplantation with co-stimulatory blockade induces macrochimerism and tolerance without cytoreductive host treatment.

Allogeneic bone marrow transplantation (in immunocompetent adults) has always required cytoreductive treatment of recipients with irradiation or cytotoxic drugs to achieve lasting engraftment at levels detectable by non-PCR-based techniques ('macrochimerism' or 'mixed chimerism'). Only syngeneic marrow engraftment at such levels has been achieved in unconditioned hosts. This requirement for potentially toxic myelosuppressive host pre-conditioning has precluded the clinical use of allogeneic bone marrow transplantation for many indications other than malignancies, including tolerance induction. We demonstrate here that treatment of naive mice with a high dose of fully major histocompatibility complex-mismatched allogeneic bone marrow, followed by one injection each of monoclonal antibody against CD154 and cytotoxic T-lymphocyte antigen 4 immunoglobulin, resulted in multi-lineage hematopoietic macrochimerism (of about 15%) that persisted for up to 34 weeks. Long-term chimeras developed donor-specific tolerance (donor skin graft survival of more than 145 days) and demonstrated ongoing intrathymic deletion of donor-reactive T cells. A protocol of high-dose bone marrow transplantation and co-stimulatory blockade can thus achieve allogeneic bone marrow engraftment without cytoreduction or T-cell depletion of the host, and eliminates a principal barrier to the more widespread use of allogeneic bone marrow transplantation. Although efforts have been made to minimize host pre-treatment for allogeneic bone marrow transplantation for tolerance induction, so far none have succeeded in eliminating pre-treatment completely. Our demonstration that this can be achieved provides the rationale for a safe approach for inducing robust transplantation tolerance in large animals and humans.

Abatacept↗

Blockade of interleukin 6 trans signaling suppresses T-cell resistance against apoptosis in chronic intestinal inflammation: evidence in crohn disease and experimental colitis in vivo.

The pro-inflammatory cytokine interleukin (IL)-6 (refs. 1-5) can bind to cells lacking the IL-6 receptor (IL-6R) when it forms a complex with the soluble IL-6R (sIL-6R) (trans signaling). Here, we have assessed the contribution of this system to the increased resistance of mucosal T cells against apoptosis in Crohn disease (CD), a chronic inflammatory disease of the gastrointestinal tract. A neutralizing antibody against IL-6R suppressed established experimental colitis in various animal models of CD mediated by type 1 T-helper cells, by inducing apoptosis of lamina propria T cells. Similarly, specific neutralization of sIL-6R in vivo by a newly designed gp130-Fc fusion protein caused suppression of colitis activity and induction of apoptosis, indicating that sIL-6R prevents mucosal T-cell apoptosis. In patients with CD, mucosal T cells showed strong evidence for IL-6 trans signaling, with activation of signal transducer and activator of transcription 3, bcl-2 and bcl-xl. Blockade of IL-6 trans signaling caused T-cell apoptosis, indicating that the IL-6-sIL-6R system mediates the resistance of T cells to apoptosis in CD. These data indicate that a pathway of T-cell activation driven by IL-6-sIL-6R contributes to the perpetuation of chronic intestinal inflammation. Specific targeting of this pathway may be a promising new approach for the treatment of CD.

Adult↗

Roles and relationship of macrophages and monocyte chemotactic and activating factor/monocyte chemoattractant protein-1 in the ischemic and reperfused rat heart.

Reperfusion injury is a troublesome and unresolved problem in acute myocardial infarction and is believed to be associated with inflammatory reactions in which various types of cells and cytokines participate, in particular, macrophages and monocyte chemoattractant protein-1 (MCP-1). We designed this study to clarify the role and relationship of macrophages and MCP-1 in ischemic and reperfused heart. The number and distribution of macrophages and MCP-1 messenger RNA (mRNA) in the ischemic and reperfused rat heart were examined with in situ hybridization and immunohistochemistry. Myocardial samples were obtained at several times. In situ hybridization was performed with digoxigenin-labeled antisense RNA probe for rat MCP-1 mRNA, and immunohistochemistry was performed with antimacrophage antibody. Double staining with in situ hybridization and immunohistochemistry was also performed. The number of MCP-1 mRNA-positive cells increased after reperfusion and peaked at 3 hours after reperfusion. Early infiltration of ischemic tissues by macrophages was also observed at the time of the absence of an increase of MCP-1 mRNA-positive cells, and this infiltration was not significantly accelerated by reperfusion, but by ischemia itself. The numbers of both MCP-1 mRNA-positive cells and macrophages increased in the ischemic marginal region over time. From the result of double staining, and based on the cellular morphology and the distribution, the majority of MCP-1 mRNA-positive cells appeared to be activated macrophages. This suggests that macrophages may not be attracted to cardiac tissue only by MCP-1 and that MCP-1 may have some roles other than attracting macrophages into ischemic heart. It also suggests that macrophages and MCP-1 may play an important role in reperfusion injury and that MCP-1 may be one of the key molecules of reperfusion injury. These observations may contribute to the development of a new therapeutic approach to the prevention of reperfusion injury.

Animals↗

Epigenetic regulation of androgen receptor gene expression in human prostate cancers.

Epigenetic mechanisms including DNA methylation and histone deacetylation are thought to play important roles in gene transcriptional inactivation. Heterogenous expression of androgen receptor (AR), which appears to be related to variable responses to endocrine therapy in prostate cancer (PCa) may also be due to epigenetic factors. The methylation status of the 5' CpG island of the AR in 3 prostate cancer cell lines and 10 primary and 14 hormone-refractory PCa samples was determined using the bisulfite PCR methods. In DU145, CpG-rich regions of the AR were hypermethylated. By an immunohistochemical analysis, only one PCa sample had no AR expression, the others being heterogenous. Bisulfite sequencing and methylation-specific PCR analysis showed aberrant methylation of AR 5'-regulatory region in 20% of 10 primary and 28% of 14 hormone-refractory PCa samples. To clarify the effect of epigenetic regulation on AR expression, we treated three prostate cancer cell lines with a demethylating agent, 5-aza-2'-deoxycytidine (azaC), and a histone deacetylase inhibitor, Trichostatin A (TSA). In DU145, re-expression of AR mRNA was detected after treatment with azaC and/or TSA. Our results suggest that epigenetic regulations including CpG methylation and histone acetylation may play important roles in the regulation of the AR.

Antimetabolites, Antineoplastic↗

Beneficial effects of arterialization of the portal vein on extended hepatectomy.

BACKGROUND: Extended hepatectomy may result in postoperative liver failure. The aim of this study was to evaluate the effects of arterialization of the portal vein on oxygen supply, hepatic energy metabolism and liver regeneration after extended hepatectomy. METHODS: Portal haemodynamics were evaluated 0 or 10 days after arterialization of the portal vein in three experimental groups: 85 per cent partial hepatectomy, 85 per cent partial hepatectomy 10 days after arterialization of the portal vein and 85 per cent partial hepatectomy 10 days after ligation of the hepatic artery. Survival rates, weight of the regenerating liver, levels of adenine nucleotides and hepatic energy charge were assessed. RESULTS: Arterialization of the portal vein caused a significant increase in partial pressure of oxygen and oxygen saturation. Portal blood flow 10 days after arterialization was significantly increased. Survival rate and weight of the regenerating liver in the group with arterialization of the portal vein were significantly higher than those in the other two groups. The group with arterialization of the portal vein showed the highest levels of adenosine 5'-triphosphate. CONCLUSION: The increase in portal blood flow and oxygen supply produced by arterialization of the portal vein has beneficial effects on hepatic energy metabolism and liver regeneration, and leads to improved survival after experimental extended hepatectomy.

Animals↗

Molecular structure of bacterial endotoxin (Escherichia coli Re lipopolysaccharide): implications for formation of a novel heterogeneous lattice structure.

Analyses of crystals of Escherichia coli Re lipopolysaccharide (LPS) formed after storage in 1% triethylamine indicate that the LPS molecules are assembled to form a monolayered structure consisting of a novel heterogeneous lattice structure, the greater part of which is occupied by one kind of lattice (lattice I), corresponding to the acyl chain portion of lipid A, and the remainder is occupied by the other kind of lattice (lattice II), corresponding to the 3-deoxy-Dmanno-octulosonic acid (dOclA) dimer and the N-acetylglucosamine disaccharide of lipid A. X-ray diffraction reveals that the type of cell is monoclinic (a = 5.53 A, b = 27.2 A, c = 6.47 A, alpha = 90 degrees, beta = 125.8 degrees, gamma = 90 degrees ). Atomic force microscopy shows that crystals consist of multiple layers; the thickness of a layer corresponds to the b-axis value, and two types of surface topographies are visualized. One, regarded as the view onto the acyl chain ends, is two-dimensional arrays of oval bodies that constitute the lattice, with the lattice constants corresponding to the a- and c-axes and the angle of beta (lattice I). The other, regarded as the view onto the dOclA dimers, is two-dimensional arrays of dromedary-back-like bodies that constitute the lattice with axes of 9.0 and 10.7 A and the angle of 65 degrees formed by both axes (lattice II). Based on these results, we present the molecular model of E. coli Re LPS.

Carbohydrate Conformation↗

Role of neutrophils in sinusoidal endothelial cell injury after extensive hepatectomy in cholestatic rats.

BACKGROUND AND AIMS: The authors have shown previously that sinusoidal endothelial cell injury developed concomitantly with the accumulation of neutrophils in the hepatic sinusoidal space in cholestatic rats after extensive hepatectomy. The aim of the present study was to investigate the role of neutrophils in the development of this kind of endothelial cell injury. METHODS: Rats underwent 78% partial hepatectomy after 2 weeks of cholestasis, and subsequent external biliary drainage for 5 days. To decrease the number of neutrophils, antirat neutrophil serum was administered intraperitoneally. Some serum parameters and histological specimens were examined 48 h after partial hepatectomy. RESULTS: Anti-neutrophil serum significantly reduced the number of accumulated neutrophils in the hepatic sinusoids. Although the purine nucleoside phosphorylase: alanine aminotransferase ratio, a marker of non-parenchymal cell injury, was increased in cholestatic-hepatectomized rats, this abnormality was significantly attenuated by the treatment with antineutrophil serum. Electron microscopically, focal detachment of cytoplasms of sinusoidal endothelial cells was observed occasionally in cholestatic-hepatectomized rats, but was not found in the antirat neutrophil serum-treated rats. CONCLUSION: These results indicate that accumulated neutrophils might be important effector cells in the pathogenesis of sinusoidal endothelial cell injury after extensive hepatectomy in cholestatic rats, even after appropriate external biliary drainage.

Alanine Transaminase↗