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Biomedical subjects

Akira Ito

Publications and source records attributed to Akira Ito.

At least 55 records · Page 3Linked to original sources
PubMed2005

Small bowel bacterial overgrowth may not affect bone mineral density in older people.

BACKGROUND & AIMS: Small bowel bacterial overgrowth (SBBO) may be associated with malnutrition, diarrhea, and weight loss. Recently, bone mineral density (BMD) in patients with SBBO was reported to be lower, and SBBO may be an important factor in the development of metabolic bone disease. However, the subjects in these studies were relatively young patients with intestinal diseases. There is no information on the effect of SBBO on BMD in older people. METHOD: Seventeen relatively active and 33 disabled older people participated in this study. SBBO was determined by a breath hydrogen (H2) test after ingestion of a glucose solution. BMD of the lumbar spine and femur were measured using a dual energy X-ray absorptiometry scan (DEXA). RESULTS: One healthy control and 11 disabled subjects were SBBO-positive. The Z-scores of the lumbar spine were not statistically different between groups, and a high incidence of disorders, >70%, was seen in all groups. On the other hand, there were significant differences in the femoral BMD between the healthy controls and the SBBO-negative (P<0.001) and SBBO-positive (P<0.05) groups. No significant difference was seen in femoral BMD between SBBO-positive and SBBO-negative institutionalized people. CONCLUSION: SBBO seems to have little effect on BMD in people approximately 80 years old.

Absorptiometry, Photon↗
PubMed2005

Triptolide, a diterpenoid triepoxide, induces antitumor proliferation via activation of c-Jun NH2-terminal kinase 1 by decreasing phosphatidylinositol 3-kinase activity in human tumor cells.

Triptolide, a diterpenoid triepoxide extracted from the Chinese herb Tripterygium wilfordii Hook f., exerts antitumorigenic actions against several tumor cells, but the intracellular target signal molecule(s) for this antitumorigenesis activity of triptolide remains to be identified. In the present study, we demonstrated that triptolide, in a dose-dependent manner, inhibited the proliferation of human fibrosarcoma HT-1080, human squamous carcinoma SAS, and human uterine cervical carcinoma SKG-II cells. In addition, triptolide was found to decrease phosphatidylinositol 3-kinase (PI3K) activity. A PI3K inhibitor, LY-294002, mimicked the triptolide-induced antiproliferative activity in HT-1080, SAS, and SKG-II cells. There was no change in the activity of Akt or protein kinase C (PKC), both of which are downstream effectors in the PI3K pathway. Furthermore, the phosphorylation of Ras, Raf, and mitogen-activated protein/extracellular signal-regulated kinase 1/2 was not modified in HT-1080 cells treated with triptolide. However, the phosphorylation of c-Jun NH(2)-terminal kinase 1 (JNK1) was found to increase in both triptolide- and LY-294002-treated cells. Furthermore, the triptolide-induced inhibition of HT-1080 cell proliferation was not observed by JNK1 siRNA-treatment. These results provide novel evidence that PI3K is a crucial target molecule in the antitumorigenic action of triptolide. They further suggest a possible triptolide-induced inhibitory signal for tumor cell proliferation that is initiated by the decrease in PI3K activity, which in turn leads to the augmentation of JNK1 phosphorylation via the Akt and/or PKC-independent pathway(s). Moreover, it is likely that the activation of JNK1 is required for the triptolide-induced inhibition of tumor proliferation.

Antineoplastic Agents↗
PubMed2005

A unique gene expression signature discriminates familial Alzheimer's disease mutation carriers from their wild-type siblings.

Alzheimer's disease (AD) is a neurodegenerative disease with an insidious onset and progressive course that inevitably leads to death. The current diagnostic tools do not allow for diagnosis until the disease has lead to irreversible brain damage. Genetic studies of autosomal dominant early onset familial AD has identified three causative genes: amyloid precursor protein (APP), presenilin 1 and 2 (PSEN1 and PSEN2). We performed a global gene expression analysis on fibroblasts from 33 individuals (both healthy and demented mutation carriers as well as wild-type siblings) from three families segregating the APP(SWE), APP(ARC) and PSEN1 H163Y mutations, respectively. The mutations cause hereditary progressive cognitive disorder, including typical autosomal dominant AD. Our data show that the mutation carriers share a common gene expression profile significantly different from that of their wild-type siblings. The results indicate that the disease process starts several decades before the onset of cognitive decline, suggesting that presymptomatic diagnosis of AD and other progressive cognitive disorders may be feasible in the near future.

Alzheimer Disease↗
PubMed2005

Intratumoral injection of immature dendritic cells enhances antitumor effect of hyperthermia using magnetic nanoparticles.

Dendritic cells (DCs) are potent antigen-presenting cells that play a pivotal role in regulating immune responses in cancer and have recently been shown to be activated by heat shock proteins (HSPs). We previously reported that HSP70 expression after hyperthermia induces antitumor immunity. Our hyperthermia system using magnetite cationic liposomes (MCLs) induced necrotic cell death that was correlated with HSP70 release. In the present study, we investigated the therapeutic effects of DC therapy combined with MCL-induced hyperthermia on mouse melanoma. In an in vitro study, when immature DCs were pulsed with mouse B16 melanoma cells heated at 43 degrees C, major histocompatibility complex (MHC) class I/II, costimulatory molecules CD80/CD86 and CCR7 in the DCs were upregulated, thus resulting in DC maturation. C57BL/6 mice bearing a melanoma nodule were subjected to combination therapy using hyperthermia and DC immunotherapy in vivo by means of tumor-specific hyperthermia using MCLs and directly injected immature DCs. Mice were divided into 4 groups: group I (control), group II (hyperthermia), group III (DC therapy) and group IV (hyperthermia + DC therapy). Complete regression of tumors was observed in 60% of mice in group IV, while no tumor regression was seen among mice in the other groups. Increased cytotoxic T lymphocyte (CTL) and natural killer (NK) activity was observed on in vitro cytotoxicity assay using splenocytes in the cured mice treated with combination therapy, and the cured mice rejected a second challenge of B16 melanoma cells. This study has important implications for the application of MCL-induced hyperthermia plus DC therapy in patients with advanced malignancies as a novel cancer therapy.

Animals↗
PubMed2005

Anticancer effect of hyperthermia on prostate cancer mediated by magnetite cationic liposomes and immune-response induction in transplanted syngeneic rats.

BACKGROUND: The hyperthermic effect of magnetic particles was examined in rat prostate cancer in vivo. Magnetic cationic liposomes (MCLs) have a positive surface charge and generate heat in an alternating magnetic field (AMF) due to hysteresis losses. METHODS: Rat prostate cancer cells (PLS 10; androgen independent) were injected subcutaneously into the flank of F344 rats. MCLs were injected into rat prostate cancer nodules that had grown to 5-6 mm in diameter, and were then exposed to an AMF. Tumor growth rates were measured. To examine whether hyperthermia caused immune induction for PLS 10, cytotoxicity assays and immunohistochemical staining for CD3, CD4, CD8, and Heat Shock Protein (HSP) 70 were performed. RESULT: The tumor temperature increased to 45 degrees C whereas the body temperature remained at around 38 degrees C. Tumor regression was observed in the hyperthermic group. CD3, CD4, and CD8 immunocytes were present in the tumor tissues of the rats exposed to hyperthermia, but they were not detected in any of the tumor tissue of untreated rats. HSP70 also appeared in the viable area at its boundary with the necrotic area. The cytotoxic activity of tumor-transplanted rats for PLS 10 cells increased in hyperthermic-treatment rats. CONCLUSION: These results suggest that hyperthermia using MCLs is an effective therapy for prostate cancer, since this treatment appears to kill the prostate cancer cells not only directly by heating but also by inducing an immune response. This therapy may cure not only the primary lesion but also metastatic lesions.

Animals↗
PubMed2005

Cancer immunotherapy based on intracellular hyperthermia using magnetite nanoparticles: a novel concept of "heat-controlled necrosis" with heat shock protein expression.

Heat shock proteins (HSPs) are highly conserved proteins whose syntheses are induced by a variety of stresses, including heat stress. Since the expression of HSPs, including HSP70, protects cells from heat-induced apoptosis, HSP expression has been considered to be a complicating factor in hyperthermia. On the other hand, recent reports have shown the importance of HSPs, such as HSP70, HSP90 and glucose-regulated protein 96 (gp96), in immune reactions. If HSP expression induced by hyperthermia is involved in tumor immunity, novel cancer immunotherapy based on this novel concept can be developed. In such a strategy, a tumor-specific hyperthermia system, which can heat the local tumor region to the intended temperature without damaging normal tissue, would be highly advantageous. To achieve tumor-specific hyperthermia, we have developed an intracellular hyperthermia system using magnetite nanoparticles. This novel hyperthermia system can induce necrotic cell death via HSP expression, which induces antitumor immunity. In the present article, cancer immunology and immunotherapy based on hyperthermia, and HSP expression are reviewed and discussed.

Animals↗
PubMed2005

Isolation and identification of histone H3 protein enriched in microvesicles secreted from cultured sebocytes.

Secretion of microvesicles, defined as sebosomes, containing lipid particles were discovered for the first time in cultured sebocytes. After reaching confluency, hamster-cloned sebocytes released bubble-like microvesicles with a diameter range of 0.5-5.0 microm. They had a complex structure containing multiple Oil Red O-stainable particles. The lipid components of the microvesicles were large amounts of squalene both of hamster-cloned and rat primary cultured sebocytes. The microvesicles contained a concentrated 17-kDa cationic protein, which was soluble in sulfate buffer including Nonidet P-40 at pH 1.5. As the protein bound tightly to heparin-Sepharose and eluted with 1.5 M NaCl, it was further purified from a SDS-PAGE gel. Peptide sequencing identified the protein to be histone H3. Polyclonal antibodies against the purified protein detected the antigen in the microvesicles both in the hamster-cloned and rat primary cultured sebocytes. The antibodies demonstrated a distribution of the protein within the nucleus, cytoplasm, and precursor microvesicles. When a gene construct encoding histone H3-enhanced green fluorescent protein was transfected to the sebocytes, fluorescence of the fusion proteins was detected within both the nucleus and the precursor microvesicles of the cytoplasm. The distribution of heparan sulfate was evident in the microvesicles, and it suggested the possibility that the histone H3 protein was recruited and then condensed to the secreted microvesicles by the molecules. In addition, the 14-3-3 protein, which was detected in the microvesicles, also may help incorporate the histone H3 protein in the microvesicles because it can bind to both histone and lipid particles.

Animals↗
PubMed2005

Echinococcus shiquicus n. sp., a taeniid cestode from Tibetan fox and plateau pika in China.

The taeniid cestode Echinococcus shiquicus n. sp. was found from the Tibetan fox Vulpes ferrilata and the plateau pika Ochotona curzoniae in the Qinghai-Tibet plateau region of China. In the adult stage, E. shiquicus from the foxes is morphologically similar to Echinococcus multilocularis. However, the new species is differentiated by its smaller rostellar hooks, fewer segments, distinct position of genital pore in the mature segment and fewer eggs in the gravid segment. Hydatid cysts of E. shiquicus found in the livers from the pikas were essentially unilocular but an oligovesicular cyst was also found. The data of mitochondrial and nuclear DNA sequences proved E. shiquicus to be a valid taxon.

Amino Acid Sequence↗
PubMed2005

Magnetic force-based mesenchymal stem cell expansion using antibody-conjugated magnetoliposomes.

Recently, there has been an accumulation of evidence indicating that human mesenchymal stem cells (MSCs, multipotent cells resident in the bone marrow) are useful for autologous cell transplantation. However, only small numbers of MSCs have been obtained in bone marrow aspirates. We have developed a novel methodology for enriching and proliferating MSCs from bone marrow aspirates using antibody-conjugated magnetoliposomes (AMLs). The AMLs are liposomes conjugated to anti-CD105 antibody (immunoliposomes) and contain magnetite nanoparticles (diameter 10 nm). In the present study, the AMLs were added to a small volume (1 mL) of human bone marrow aspirate. After a 1-h incubation period, the bone marrow aspirates containing AMLs were seeded into 10-cm tissue culture dishes, and a disk-shaped magnet (diameter 2.2 cm; height 1 cm; 4000 Gauss) was positioned under the dish to enrich MSCs by magnetic force. The MSCs proliferated, forming colonies at the site where the magnet was positioned. In contrast, no colonies and very few viable cells were observed in ordinary culture based on plastic-adherent tendencies of cells without use of AMLs. These results suggest that this AML culture method can rapidly and efficiently expand a small number of MSCs into numbers suitable for clinical application.

Animals↗
PubMed2005

Usefulness of recombinant Em18-ELISA to evaluate efficacy of treatment in patients with alveolar echinococcosis.

Alveolar echinococcosis (AE) is a rare parasitic disease caused by Echinococcus multicularis and most commonly involves the liver. Early diagnosis is essential to improve the prognosis of patients with AE of the liver. Em18, an 18-kD diagnostic antigen from Echinococcus multilocularis, is highly specific and sensitive to detect AE. We previously reported that an enzyme-linked immunosorbent assay (ELISA) system using a recombinant Em18 antigen (RecEm18) was highly useful in the differential serodiagnosis of AE. In this report, we present seven AE patients who showed dynamic changes in RecEm18-ELISA values in the course of long-term follow up of albendazole (ABZ) chemotherapy, and/or resections of the liver or bone metastasis. All seven AE patients revealed positive values, over the cutoff level, of the RecEm18-ELISA before the treatments. The values in six patients fell below the cutoff level after the treatments, but the value in a patient with recurrence never fell below the cutoff level, and increased again. From these results, it seems that the RecEm18-ELISA is useful to evaluate the efficacy of treatment and predict recurrence in patients with AE. RecEm18-ELISA may be an important examination for: (a) the mass screening of AE in Japan, (b) the confirmative diagnosis of AE prior to surgical and/or chemotherapeutic treatments, (c) the follow up of AE patients after treatments, and (d) for deciding on the discontinuation of chemotherapy in patients with an appropriate response.

Administration, Oral↗
PubMed2005

The effect of RGD peptide-conjugated magnetite cationic liposomes on cell growth and cell sheet harvesting.

Tissue engineering requires novel technologies for establishing 3D constructs, and the layered method of culturing cell sheets (cell sheet engineering) is one potentially useful approach. In the present study, we investigated whether coating the culture surface with RGD (Arg-Gly-Asp) peptide-conjugated magnetite cationic liposomes (RGD-MCLs) was able to facilitate cell growth, cell sheet construction and cell sheet harvest using magnetic force without enzymatic treatment. To promote cell attachment, an RGD-motif-containing peptide was coupled to the phospholipid of our original magnetite cationic liposomes (MCLs). The RGD-MCLs were added to a commercially available 24-well ultra-low-attachment plate the surface of which comprised a covalently bound hydrogel layer that was hydrophilic and neutrally charged. A magnet was placed on the underside of the well in order to attract the RGD-MCLs to the surface of the well, and then NIH/3T3 cells were seeded into the well. Cells adhered to the bottom of the culture surface, which was coated with RGD-MCLs, and the cells spread and proliferated to confluency. After incubation, the magnet was removed and the cells were detached from the bottom of the plates, forming a contiguous cell sheet. Because the sheets contained magnetite nanoparticles, they could be harvested using a magnet inserted into the well. These results suggest that this novel methodology using RGD-MCLs and magnetic force, which we have termed 'magnetic force-based tissue engineering (Mag-TE)', is a promising approach for tissue engineering.

Adsorption↗
PubMed2005

A rapid assay for detecting antibody against leucocytozoonosis in chickens with a latex agglutination test using recombinant R7 antigen.

A method for detecting antibody against leucocytozoonosis in chickens by latex agglutination (LA) was developed using latex beads coated with recombinant R7 (rR7), an outer membrane antigen of second-generation schizonts of Leucocytozoon caulleryi. Compared with the agar gel precipitation test, which is widely used in Japan, LA could detect antibody induced by L. caulleryi infection with greater sensitivity. No agglutination was detected with sera from specific pathogen free or layer chickens that had not been vaccinated with oil-adjuvanted rR7 antigen, or infected with L. caulleryi, nor with sera from chickens inoculated with other pathogens, establishing the specificity of the assay. The LA test was also able to be used to quantify serum antibody induced by vaccination, which is not possible with the agar gel precipitation test. This study has shown that LA using the rR7 antigen is a simple, quick, and useful method for detecting antibody against L. caulleryi.

Animals↗
PubMed2005

Coronary microvascular dysfunction in patients with microvascular angina: analysis by TIMI frame count.

We have previously reported that angina pectoris persists in patients with coronary microvascular spasm (MVS) even on calcium channel blockers. Because measurement of myocardial lactate production in the coronary sinus is necessary to diagnose MVS, a more feasible diagnostic method needs to be developed. In this study, we examined the diagnostic significance of Thrombolysis in Myocardial Infarction (TIMI) frame count, a marker of coronary blood flow, in 131 consecutive patients who underwent provocation test for coronary spasm with acetylcholine (ACh). Epicardial coronary spasm (ES) was diagnosed as more than 75% of ACh-induced vasoconstriction noted by coronary angiography. MVS was diagnosed as ACh-induced myocardial ischemia (chest pain, ischemic ECG changes, and myocardial lactate production) without ES. TIMI frame count was significantly increased in patients with MVS alone (n = 35) and those with ES + MVS (n = 16) compared with those with ES alone (n = 53) or those with no myocardial ischemia (Normal, n = 27) either before and after intracoronary ACh and even after intracoronary isosorbide dinitrate (ISDN) in both the left anterior descending (LAD) and the left circumflex coronary artery (LCX). TIMI frame count in LAD correlated well to that in LCX in patients with MVS, suggesting diffuse impaired coronary microcirculation in the myocardium. These results suggest that increased TIMI frame count in response to ACh reflects microvascular dysfunction in MVS and that ISDN may not be enough to relieve MVS. Thus, TIMI frame count may be useful to diagnose MVS without requiring coronary sinus catheterization or myocardial lactate production measurement.

Acetylcholine↗
PubMed2005

Expression of perilipin A on the surface of lipid droplets increases along with the differentiation of hamster sebocytes in vivo and in vitro.

To clarify the involvement of perilipin, a lipid-droplet-surface protein associated with adipocytes and steroidogenic cells, in the differentiation of sebocytes, we investigated the expression of perilipin in sebaceous glands in vivo and in vitro. Perilipin was expressed in sebaceous glands of the hamster auricle in vivo and was localized at the surface of intracellular lipid droplets in differentiated hamster sebocytes in vitro. Western blot analysis showed that perilipin with a molecular weight of approximately 57 kDa, which was identical to that in differentiated mouse 3T3-L1 adipocytes, was detected in cultured sebocytes, indicating that sebaceous glands expressed perilipin A. In addition, the production of perilipin A in cultured sebocytes was transcriptionally augmented by sebocytic-lipogenesis stimulators, insulin, and 5alpha-dihydrotestosterone, whereas it was decreased by a suppressor of sebocytic differentiation, epidermal growth factor. Furthermore, hamster sebocytes were found to express peroxisome proliferation-activating receptor alpha and gamma1, the activation of which by WY14643 and troglitazone, respectively, caused the transcriptional augmentation of perilipin A expression along with an increase in levels of triacylglycerols in lipid droplets in sebocytes. Therefore, these results provide novel evidence that the expression of perilipin A increases on the surface of intracellular lipid droplets augmented along with the differentiation of hamster sebocytes.

3T3-L1 Cells↗
PubMed2005

Augmentation of lipogenesis by 15-deoxy-Delta12,14-prostaglandin J2 in hamster sebaceous glands: identification of cytochrome P-450-mediated 15-deoxy-Delta12,14-prostaglandin J2 production.

Prostaglandins (PGs) play important roles in the regulation of cutaneous cell functions under physiological and pathological conditions. In this study, we examined the involvement of PGs in sebocyte lipogenesis using non-steroidal anti-inflammatory drugs in vivo and in vitro. Hamster auricle sebocytes spontaneously differentiated to accumulate intracellular triacylglycerol (TG), under which the relative levels of 15-deoxy-Delta(12,14)-PGJ2 (15d-PGJ2) to PGF(2alpha) and PGE2 increased. 15d-PGJ2 was found to augment the formation of lipid droplets, which was because of an increase of TG synthesis by diacylglycerol acyltransferase (DGAT). Furthermore, sebocytes constitutively produced cyclooxygenase 2 (COX-2), but not COX-1, in vivo and in vitro. When sebocytes were treated with COX inhibitors such as indomethacin, diclofenac, or NS-398, the production of PGF(2alpha) and PGE2 decreased. The production of 15d-PGJ2, however, was increased in these inhibitor-treated sebocytes. In addition, indomethacin, diclofenac, and NS-398 augmented the synthesis of TG along with the increase in DGAT activity. Similarly, topical administration of indomethacin to hamster auricles caused the development of sebaceous glands with the augmentation of sebum deposition in vivo. Furthermore, indomethacin and NS-398-augmented 15d-PGJ2 production and TG synthesis were suppressed by a non-selective cytochrome P-450 (CYP) inhibitor, SKF-525A. A ligand activator of peroxisome proliferation activating receptor gamma (PPARgamma), troglitazone-induced synthesis of TG, however, was not altered even in the presence of SKF-525A. These results suggest that 15d-PGJ2 is a crucial stimulator of sebocyte lipogenesis by augmenting DGAT-mediated synthesis of TG. In addition to the COX-2-dependent pathway of PG synthesis, our findings suggest a sebocyte-specific pathway of 15d-PGJ2 production by CYP, the activity of which may be evoked by inhibiting COX-2.

Animals↗
PubMed2005

Collagenous Alzheimer amyloid plaque component assembles amyloid fibrils into protease resistant aggregates.

Recently, a novel plaque-associated protein, collagenous Alzheimer amyloid plaque component (CLAC), was identified in brains from patients with Alzheimer's disease. CLAC is derived from a type II transmembrane collagen precursor protein, termed CLAC-P (collagen XXV). The biological function and the contribution of CLAC to the pathogenesis of Alzheimer's disease and plaque formation are unknown. In vitro studies indicate that CLAC binds to fibrillar, but not to monomeric, amyloid beta-peptide (Abeta). Here, we examined the effects of CLAC on Abeta fibrils using assays based on turbidity, thioflavin T binding, sedimentation analysis, and electron microscopy. The incubation of CLAC with preformed Abeta fibrils led to increased turbidity, indicating that larger aggregates were formed. In support of this contention, more Abeta was sedimented in the presence of CLAC, as determined by gel electrophoresis. Moreover, electron microscopy revealed an increased amount of Abeta fibril bundles in samples incubated with CLAC. Importantly, the frequently used thioflavin T-binding assay failed to reveal these effects of CLAC. Digestion with proteinase K or trypsin showed that Abeta fibrils, incubated together with CLAC, were more resistant to proteolytic degradation. Therefore, CLAC assembles Abeta fibrils into fibril bundles that have an increased resistance to proteases. We suggest that CLAC may act in a similar way in vivo.

Alzheimer Disease↗
PubMed2005

Medical application of functionalized magnetic nanoparticles.

Since magnetic particles have unique features, the development of a variety of medical applications has been possible. The most unique feature of magnetic particles is their reaction to a magnetic force, and this feature has been utilized in applications such as drug targeting and bioseparation including cell sorting. Recently, magnetic nanoparticles have attracted attention because of their potential as contrast agents for magnetic resonance imaging (MRI) and heating mediators for cancer therapy (hyperthermia). Magnetite cationic liposomes (MCLs), one of the groups of cationic magnetic particles, can be used as carriers to introduce magnetite nanoparticles into target cells since their positively charged surface interacts with the negatively charged cell surface; furthermore, they find applications to hyperthermic treatments. Magnetite nanoparticles conjugated with antibodies (antibody-conjugated magnetoliposomes, AMLs) are also applied to hyperthermia and have enabled tumor-specific contrast enhancement in MRI via systemic administration. Since magnetic nanoparticles are attracted to a high magnetic flux density, it is possible to manipulate cells labeled with magnetic nanoparticles using magnets; this feature has been applied in tissue engineering. Magnetic force and MCLs were used to construct multilayered cell structures and a heterotypic layered 3D coculture system. Thus, the applications of these functionalized magnetic nanoparticles with their unique features will further improve medical techniques.

Animals↗