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Biomedical subjects

M Inoue

Publications and source records attributed to M Inoue.

At least 73 records · Page 4Linked to original sources
PubMed2005

Epidemiology of gastric cancer in Japan.

Despite its decreasing trend in Japan, gastric cancer remains an important public health problem. Although the age standardised rates of gastric cancer have been declining for decades, the absolute numbers are increasing because of the rapid aging of the population. A large proportion of Japanese gastric cancers are detected at an early stage, with a better overall survival rate. As with Western developed countries, a change in the social environment such as reduced salt use and increased fresh vegetable and fruit intake as well as improvement of food storage may play an important part in the decline. Differences in Helicobacter pylori infection rates between generations presumably have contributed to the generation related variation in the declining trends. It is expected that most gastric cancers in Japan may be preventable by lifestyle modification such as salt reduction and increased fruit and vegetable intake, together with avoidance of smoking and countermeasures against H pylori infection so that the level now evident in Western developed countries can be reached.

Female↗
PubMed2005

Cytotoxic chemotherapy successfully induces durable complete remission in 2 patients with mosquito allergy resulting from Epstein-Barr virus-associated T-/natural killer cell lymphoproliferative disease.

Recent findings indicate that Epstein-Barr virus (EBV)-infected T-/natural killer (NK) cells play an important role in the pathogenesis of mosquito allergy, and most patients with mosquito allergy die early in life if not properly treated. Over the last 7 years, we have been using combination chemotherapy and allogeneic stem cell transplantation for the treatment of EBV-associated T-/NK cell lymphoproliferative disease (LPD) in which chronic active EBV infection and mosquito allergy were included. As of this writing, we have successfully treated 2 patients with mosquito allergy with chemotherapy in which EBV-infected T-/NK cells were eradicated. The findings suggest the possible role of chemotherapy in the treatment of EBV-associated T-/NK cell LPD.

Animals↗
PubMed2005

ADAMTS-1 is involved in normal follicular development, ovulatory process and organization of the medullary vascular network in the ovary.

To clarify the role of disintegrin-like and metalloproteinase with thrombospondin type I motifs-1 (ADAMTS-1) in ovarian function, we examined abnormalities in ovulatory processes, folliculogenesis and the vascular system of ADAMTS-1 null ovaries. First, when immature female mice were treated with pregnant mare serum gonadotropin (PMSG)/human chorionic gonadotropin (hCG), the number of ovulated oocytes was markedly decreased in ADAMTS-1 null mice in comparison to ADAMTS-1 (+/-) controls. The proportion of anovulated follicles to total mature follicles was significantly higher in ADAMTS-1 null females when compared with controls. The numbers of growing follicles at each stage were counted. The number of follicles at type 5b (late preantral) and later stages was markedly reduced in ADAMTS-1 null mice, irrespective of gonadotropin treatment (no gonadotropins, PMSG alone or PMSG/hCG). These data demonstrate that impairment of ovarian function to ovulate oocytes in ADAMTS-1 null mice occurs at two different levels: in the development of growing follicles and ovulatory processes. Furthermore, ADAMTS-1 null ovaries included a number of unusual atretic follicles that showed no sign of oocyte degeneration but lost the surrounding granulosa cell layers and were considered to be derived from type 4 or 5a follicles. These results suggest that ADAMTS-1 is important for follicular development beyond the type 4 and/or 5a and for maintaining normal granulosa cell layers in follicles. Finally, the number of large blood vessels in the medullar zone was significantly decreased in ADAMTS-1 null mice ovaries, suggesting that ADAMTS-1 is also involved in the organization of the medullary vascular network.

ADAM Proteins↗
PubMed2004

Osteoclastogenesis inhibitory factor/osteoprotegerin reduced bone loss induced by mechanical unloading.

Skeletal unloading resulting from space flight and prolonged immobilization causes bone loss. Such bone loss ostensibly results from a rapid increase in bone resorption and subsequent sustained reduction in bone formation, but this mechanism remains unclear. Osteoclastogenesis inhibitory factor/osteoprotegerin (OCIF/OPG) is a recently identified potent inhibitor of osteoclast formation. We studied effects of OPG administration on tail-suspended growing rats to explore the therapeutic potential of OPG in the treatment and prevention of bone loss during mechanical unloading, such as that which occurs during space flight. Treatment with OPG in tail suspension increased the total bone mineral content (BMC g) of the tibia and femur and the total bone mineral density (BMD g/cm2) of the tibia. Moreover, treatment with OPG prevented reduction not only of BMC and BMD, but also of bone strength occurring through femoral diaphysis. Treatment with OPG in tail-suspended rats improved BMC, BMD and bone strength to levels of normally loaded rats treated with vehicle. Treatment with OPG in normally loaded rats significantly decreased urinary excretion of deoxypyridinoline, but the effect of OPG in tail suspension was unclear. These results indicate that OPG may be useful in inhibiting bone loss-engendered mechanical unloading.

Amino Acids↗
PubMed2004

Effect of enamel matrix proteins on the phenotype expression of periodontal ligament cells cultured on dental materials.

Cells within the periodontal ligament have the potential to regenerate a periodontal connective tissue attachment on pathologically exposed root surfaces as well as on several material surfaces including titanium. However, rather than a periodontal connective tissue attachment, a fibrous encapsulation or chronic inflammatory response has been reported at the material connective tissue interface for most dental materials. Cementum is the first tissue of the periodontal connective tissue attachment to develop and the secretion of enamel matrix related proteins on the newly mineralized dentin surface precedes and is thought to induce cementum formation. Enamel matrix-related proteins may also function in the adult because the application of an acid extract of porcine enamel protein matrix (Emdogain(R), EMD) on pathologically exposed root surfaces has been shown to result in cementum regeneration. Therefore, the objective of the present study was to determine whether the application of EMD to materials that do not normally support cementogenesis in vivo would alter the in vitro phenotype of periodontal ligament (PDL) cells including the synthesis of cementum-associated extracellular matrix proteins. Primary PDL cells were established from 21-day-old Sprague-Dawley rats, and were cultured on four materials commonly encountered in dental practice (gutta percha, calcium hydroxide, amalgam, and super EBA cement) with and without the application of EMD. After 7 or 14 days of culture, total-DNA content, collagen synthesis, alkaline phosphatase activity, and the synthesis of a 42-kDa cementum-associated extracellular matrix protein were determined. PDL cells cultured on all materials had decreased total DNA content. The application of EMD further decreased total DNA content. PDL cells cultured on gutta percha and calcium hydroxide with the application of EMD had similar levels of collagen synthesis and alkaline phosphatase activity but also expressed a 42-kDa cementum extracellular matrix-associated protein when compared to the other groups. These results suggest that EMD can alter the phenotype of PDL cells when cultured on these dental materials.

Alkaline Phosphatase↗
PubMed2004

Effect of enamel matrix proteins on the periodontal connective tissue-material interface after wound healing.

The periodontal ligament has the potential to regenerate a complete periodontal connective tissue attachment, starting with the deposition of cementum, on pathologically exposed root surfaces as well as several materials including titanium oxide. However, most commonly used dental materials result in a fibrous encapsulation or a chronic inflammatory response after periodontal wound healing rather than the formation of a periodontal connective tissue attachment. Recently, an extract of porcine enamel matrix (Emdogain(R), EMD) has been reported inductive of cementum formation in both in vivo and in vitro studies. The aim of this study was to determine the effect of EMD, when applied to materials previously reported not supportive of periodontal connective tissue formation, on the periodontal connective tissue-material interface obtained with these materials in vivo. Bilateral osteotomies were performed on the mandible of a Yucatan minipig exposing the buccal root surface of four premolars. A series of four preparations were placed in each root surface that were subsequently filled with calcium hydroxide, gutta percha, mineral trioxide aggregate (MTA), or left unfilled. One side, in addition, received an application of EMD prior to surgical closure. A bioabsorbable surgical barrier membrane was placed over the osteotomy sites to exclude gingival connective tissue from the wound-healing environment. The mucoperiosteal flaps were then readapted and sutured in position. The animal was euthanized 10 weeks after the procedure, block sections obtained and prepared for light microscopy. Results demonstrated complete regeneration of alveolar bone and periodontal ligament in all four teeth from the EMD-treated side. Fibers from the periodontal ligament were observed to insert into a mineralized matrix consistent with cementum on all four root preparations. In contrast, massive root resorption without regeneration of alveolar bone was found on all teeth from the side not treated with EMD. The results of this pilot study suggest that the application of EMD to material surfaces that normally do not support periodontal connective tissue attachment formation can alter the type of periodontal connective tissue interface obtained with these materials.

Animals↗
PubMed2004

Decrease in cortical benzodiazepine receptors in symptomatic patients with leukoaraiosis: a positron emission tomography study.

BACKGROUND AND PURPOSE: [11C]flumazenil (FMZ), a ligand that selectively binds to the central benzodiazepine receptor in the neuronal membrane, is useful for evaluating neuronal viability in a positron emission tomography (PET) scan. Using this ligand, we investigated whether there was a correlation between neuronal integrity in various brain structures and dementia in patients with leukoaraiosis. METHODS: Twelve patients with extensive leukoaraiosis on magnetic resonance imaging were divided into groups of patients with or without dementia. Based on a 2-compartment, 2-parameter model that included metabolite-corrected arterial input and PET-measured cerebral radioactivity, the distribution volume of FMZ (FMZ-V(d)) was calculated in various regions of interest by nonlinear curve fitting. Additionally, tracer kinetic analysis was applied for voxel-by-voxel quantification of FMZ-V(d), and data analysis was performed by statistical parametric mapping. RESULTS: The presence of dementia was associated with a reduced FMZ-V(d) in widespread areas of the cerebral cortex, including the bilateral frontopolar and frontal/insular areas, the left temporo-occipital border areas, and the left marginal cortical areas. CONCLUSIONS: Differences in neuronal integrity in the cerebral cortex might determine whether patients with leukoaraiosis become symptomatic or not.

Aged↗
PubMed2004

Rabeprazole 10 mg twice daily is superior to 20 mg once daily for night-time gastric acid suppression.

BACKGROUND: Insufficient acid suppression is one of the main causes of proton pump inhibitor-refractory gastro-oesophageal reflux disease. AIM: To achieve more potent and long-lasting acid suppression, different dosage regimens of rabeprazole were compared in relation to the CYP2C19 genotype status. METHODS: In a cross-over study, 18 healthy Helicobacter pylori-negative males (six homozygous extensive metabolizers, six heterozygous extensive metabolizers and six poor metabolizers) were given rabeprazole 10 mg once daily, 20 mg once daily or 10 mg twice daily, or water only (baseline data), for 7 days each. On day 7 of each regimen, 24-h intragastric pH-metry was performed. RESULTS: No significant differences were observed in median pH values and pH>4 holding time ratios between rabeprazole 10 mg once daily and 20 mg once daily. However, with rabeprazole 10 mg twice daily, these parameters were significantly higher than those with 20 mg once daily. The potency of acid suppression by rabeprazole was influenced by the CYP2C19 genotype status. The differences were somewhat significant but not large. The incidence of nocturnal acid breakthrough was lowest with rabeprazole 10 mg twice daily. CONCLUSIONS: Rabeprazole 10 mg twice daily, not 20 mg once daily, should be administered to achieve more potent and long-lasting acid suppression.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2004

Hydroxyapatite particles as a controlled release carrier of protein.

This study examines the possibility of using hydroxyapatite (HAp) particles as a controlled release carrier of protein. In order to achieve effective protein release from HAp particles, it is necessary to regulate the conjugated amount of protein on HAp and the resorption of HAp. HAp particles were synthesized at different temperatures (40 degrees C, 60 degrees C, 80 degrees C) in wet condition and the physico-chemical properties of synthesized HAp particles were examined. HAp particles synthesized at low temperatures showed low crystallinity, high solubility and large specific surface area. The useful growth factors for bone regeneration, such as BMP, bFGF and TGF-beta, are basic proteins, so cytochrome c (pI=10.2) was used as a model protein and the adsorptive property of protein on HAp particles was investigated. The protein adsorption on HAp particles changed depending on its specific surface area and the chart of protein adsorption on HAp particles showed a typical Langmuir curve. These findings suggest that the adsorbed amount of protein on HAp particles could be regulated by HAp synthesizing temperature and the concentrations of protein solution. The release kinetics of protein from the HAp particles that adsorbed the protein (HAp-pro) was also evaluated in different pH solutions (pH 4.0 and 7.0). The released protein gradually increased time dependently when HAp-pro were immersed in pH 4.0 solution, but the released protein was significantly smaller when HAp-pro were immersed in pH 7.0 solution. Moreover, the release rate of protein from HAp-pro differed in each HAp that was synthesized at different temperatures, suggesting that the release of protein from HAp-pro depended on HAp resorption. These results suggest that HAp particles synthesized at different temperature are useful as a controlled release carrier of protein.

Adsorption↗
PubMed2004

Suppressive effects of a selective cyclooxygenase-2 inhibitor, etodolac, on 4-nitroquinoline 1-oxide-induced rat tongue carcinogenesis.

The present study was conducted to examine effects of a clinically available selective cyclooxygenase (COX)-2 inhibitor, etodolac, on the development of rat tongue squamous cell carcinomas (SCCs) induced by 4-nitroquinoline 1-oxide (4-NQO), and on the immunohistochemically demonstrable expression of COX-2. Fischer 344 rats, 6 weeks old at the commencement, were administered 4-NQO at the doses of 20-30 ppm in their drinking water for 12 weeks. Then, etodolac was supplemented into the diet at doses of 150 and 300ppm for 16 weeks. Rats were sacrificed at 28 weeks and tongue lesions were histologically examined. The incidence and the multiplicity of SCCs induced by 4-NQO were dose-dependently reduced by etodolac, with significance at the highest dose of 300 ppm. Etodolac did not significantly affect the immunohistochemical expression of COX-2 in the lesions which did develop. These results indicate that etodolac can inhibit the development of rat tongue SCCs, probably by inhibiting COX-2 activity rather than its expression. Thus, etodolac may be a promising candidate chemopreventive agent for individuals at high risk of oral cancer.

4-Nitroquinoline-1-oxide↗
PubMed2004

Urinary diversion in children with pelvic tumors.

PURPOSE: The aim of this study was to investigate children presenting with malignant pelvic tumors obstructing the upper urinary tract. METHODS: Seventeen children with upper urinary tract obstruction by a malignant tumor were reviewed. A nephrostomy tube or Double J (DJ) stent was inserted into each obstructed urinary system and removed after tumor shrinkage and/or hydronephrosis regression. RESULTS: There were 9 boys and 8 girls in the study; the mean age and median follow-up were 5.7 years and 2.5 years, respectively. The most common obstructing tumor was rhabdomyosarcoma. Twelve children underwent diversion by nephrostomy tubes and 3 by DJ stents; 2 patients underwent resection of the tumors with ureteroureterostomy. Complications after the insertion of the stents included febrile urinary tract infections (UTI) or pyelonephritis in 4 of the children with DJ stents. In the nephrostomy group, febrile UTI developed in 3 and the tube fell out in 1, and was blocked in another. Of the 17 children, 9 have no evidence of disease, 2 are currently under treatment, and 6 died of cancer. CONCLUSIONS: The prognosis of children with malignant pelvic tumor obstructing the upper urinary system justifies urgent and optimal upper tract diversion, enabling chemotherapy to be started immediately.

Child, Preschool↗
PubMed2004

Semiquantative analysis of expression of mucosal addressin cell adhesion molecule-1 during small bowel graft rejection in rats.

AIM: Mucosal addressin cell adhesion molecule-1 (MAdCAM-1) mediates the homing of lymphocytes to gut-associated lymphoid tissues (GALT). We performed a semiquantative analysis of MAdCAM-1 expression during small bowel graft rejection. METHODS: Orthotopic small bowel transplantations (SBT) were performed from BN rats to LEW rats. Isografted animals served as controls. Animals were sacrificed on days 3, 4, 5, 6, and 7 after SBT. Cryostat sections were prepared from grafts, including Peyer's patches (PPs). Indirect immunoperoxidase staining was performed using mAbs against MAdCAM-1. The degree of vascular endothelial staining on high endothelial venules (HEV) in the PPs was graded from 1 (low levels) to 5 (high levels), and in the vessels of the lamina propria from 1 (faint), 2 (low at the base of villi), 3 (low to the middle of villi), 4 (high to the middle of villi), to 5 (high to villus tip). RESULTS: MAdCAM-1 expression on HEVs in PPs was down-regulated during rejection. In contrast its expression on endothelial cells of vessels in the lamina propria was up-regulated during rejection. CONCLUSION: Alteration in MAdCAM-1 expression may be associated with the development of SB graft rejection. The vessels at the base of villi, which are associated with lymphocyte recruitment, may become sites of intense immune reactivity during the early phase of small bowel allograft rejection.

Animals↗
PubMed2004

Oxidative stress promotes the regression of fetal liver hemopoiesis.

Although apoptosis is believed to play an important role in the ontogenetic development of animals, the molecular mechanism that triggers the regression of liver hemopoiesis during the perinatal period is not known. Apoptosis is induced by many factors such as a decrease in growth factors and increased oxygen stress. Since hepatic gamma-glutamyl transferase (GT) levels change markedly during the perinatal period in rodents, the metabolism of glutathione (GSH), a naturally occurring major antioxidant, might change significantly in and around liver cells. Hemopoietic cells but not hepatocytes exhibit significant apoptosis in thiol-free medium and the hemopoietic apoptosis can be inhibited by various thiols, such as L-cysteine, N-acetyl-L-cysteine, and GSH. The contribution of GSH levels in and around fetal liver cells in the triggering of apoptosis in hemopoietic cells is discussed.

Animals↗
PubMed2004

Postischemic administration of Sendai virus vector carrying neurotrophic factor genes prevents delayed neuronal death in gerbils.

Sendai virus (SeV) vector-mediated gene delivery of glial cell line-derived neurotrophic factor (GDNF) and nerve growth factor (NGF) prevented the delayed neuronal death induced by transient global ischemia in gerbils, even when the vector was administered several hours after ischemia. Intraventricular administration of SeV vector directed high-level expression of the vector-encoded neurotrophic factor genes, which are potent candidates for the treatment of neurodegenerative diseases. After occlusion of the bilateral carotid arteries of gerbils, SeV vector carrying GDNF (SeV/GDNF), NGF (SeV/NGF), brain-derived neurotrophic factor (SeV/BDNF), insulin-like growth factor-1 (SeV/IGF-1) or vascular endothelial growth factor (SeV/VEGF) was injected into the lateral ventricle. Administration of SeV/GDNF, SeV/NGF or SeV/BDNF 30 min after the ischemic insult effectively prevented the delayed neuronal death of the hippocampal CA1 pyramidal neurons. Furthermore, the administration of SeV/GDNF or SeV/NGF as late as 4 or 6 h after the ischemic insult also prevented the death of these neurons. These results indicate that SeV vector-mediated gene transfer of neurotrophic factors has high therapeutic potency for preventing the delayed neuronal death induced by transient global ischemia, and provides an approach for gene therapy of stroke.

Animals↗
PubMed2004

Generation of a recombinant Sendai virus that is selectively activated and lyses human tumor cells expressing matrix metalloproteinases.

Malignant tumor cells often express matrix metalloproteinases (MMPs) at a high level to enable their dissemination and metastasis. Sendai virus (SeV), a nonsegmented negative strand RNA virus, spreads in the target tissues in vivo via cleavage activation of the viral fusion glycoprotein by a tissue-specific, trypsin-like enzyme. By deleting the viral matrix protein, we previously generated a recombinant SeV that does not bud to mature virions, but is highly fusogenic and spreads extensively from cell to cell in a trypsin-dependent manner. Here, we changed the tryptic cleavage site of the fusion glycoprotein of this virus to a site susceptible to MMPs. The resulting recombinant virus was no longer activated by trypsin but spread efficiently in cultured cells supplemented with MMP2 or MMP9 and in human tumor cell lines expressing these MMPs. Furthermore, the virus spread extensively in tumor cells xenotrasplanted to nude mice without disseminating to the surrounding normal cells, leading to the inhibition of the tumor growth in the mice. These results demonstrate the selective targeting and killing of human tumor cells by recombinant SeV technology and greatly advance the reemerging concept of oncolytic virotherapy, which currently appears to rely largely upon a natural preference of certain viruses for cancer cells.

Animals↗
PubMed2004

Platelet responses and anaphylaxis-like shock induced in mice by intravenous injection of whole cells of oral streptococci.

Intravenous injection of lyophilized whole cells of various oral streptococcal strains into muramyldipeptide (MDP)-primed C3H/HeN mice induces rapid anaphylactoid shock. Here we examined the mechanism underlying this shock. In non-primed mice, Streptococcus intermedius K-213K (SiK213) and Streptococcus constellatus T21 (ScT21) produced little or no sign of shock. In MDP-primed mice, SiK213 caused lethal shock, while ScT21 only had a weak effect. SiK213 induced decreases in blood platelets and 5-hydroxytryptamine (5HT) preceding the shock, while the effects of ScT21 were weak. The SiK213-induced 5HT decrease and shock were reduced by a complement-C5 inhibitor. These results suggest that (i). streptococcal bacterial cells can induce rapid platelet responses, (ii). complement-dependent degradation of platelets may be involved in streptococcus-induced shock, (iii). the streptococcus-induced platelet degradation or degranulation may occur largely in the systemic circulation, and (iv). platelets may play a role not only in infectious diseases caused by gram-negative bacteria, but also in diseases caused by gram-positive bacteria.

Acetylmuramyl-Alanyl-Isoglutamine↗