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Biomedical subjects

M Ito

Publications and source records attributed to M Ito.

At least 19 recordsLinked to original sources
PubMed2006

Homing, proliferation and survival sites of human leukemia cells in vivo in immunodeficient mice.

The cellular components of the hematopoietic stem cell niche have been gradually identified. However, the niche for malignant hematopoiesis remains to be elucidated. Here, using human leukemia cells, which could be transplanted to immunodeficient mice, we studied the in vivo homing, proliferation and survival sites by immunohistopathology, compared with the corresponding sites for cord blood CD34(+) (CBCD34(+)) cells. The human leukemia cells initially localized on the surface of osteoblasts in the epiphysial region, and expanded to the inner vascular and diaphysial regions within 4 weeks. The percentage of CD34(+) leukemia cells in the bone marrow was transiently increased up to 50%. In vivo 5-bromo-2'-deoxyuridine labeling revealed that the epiphysis was the most active site for leukemia cell proliferation. CBCD34(+) cells showed the similar pattern of homing and proliferation to leukemia cells. After high-dose administration of cytosine-1-beta-D-arabinofuranoside, residual leukemia cells were localized in the perivascular endothelium as well as in contact with the trabecular endosteum. These findings suggest that xenotransplantation into immunodeficient mice provides a useful model to study the leukemia niche.

Animals↗
PubMed2006

Nonmyeloablative stem cell transplantation for nonmalignant diseases in children with severe organ dysfunction.

Allogeneic stem cell transplantation (SCT) can cure several nonmalignant diseases in children. However, patients frequently have significant morbidity before transplantation and there is a high transplant-related mortality. Nonmyeloablative SCT might achieve the same goals but with less toxicity. Six pediatric patients with nonmalignant diseases underwent nonmyeloablative SCT from different stem cell sources. All patients were conditioned with fludarabine/melphalan with additional anti-thymocyte globulin for haploidentical grafts and prophylaxis for graft-versus-host disease (GVHD) consisting of tacrolimus and methotrexate with additional prednisolone for haploidentical grafts. Hematopoietic stem cells were neither T-cell depleted nor purged. All patients had severe organ dysfunction that precluded transplantation with conventional conditioning. Five of the six are alive and in complete disease resolution at a median of 19 months (range, 7-53 months) after SCT. One patient died of bacteremia before engraftment. Three patients achieved complete donor chimerism. Two patients remained stable mixed chimerism. Short-term toxicities were minimal. Acute and chronic GVHD were not seen. In summary, the fludarabine-based nonmyeloablative regimen followed by SCT provides a good approach for children with nonmalignant diseases. Even patients with severe organ dysfunctions had adequate engraftment with acceptable toxicities.

Adolescent↗
PubMed2006

Phenotypes and genotypes in epilepsy with febrile seizures plus.

In the last several years, mutations of sodium channel genes, SCN1A, SCN2A, and SCN1B, and GABA(A) receptor gene, GABRG2 were identified as causes of some febrile seizures related epilepsies. In 19 unrelated Japanese families whose probands had febrile seizures plus or epilepsy following febrile seizures plus, we identified 2 missense mutations of SCN1A to be responsible for the seizure phenotypes in two FS+ families and another mutation of SCN2A in one family. The combined frequency of SCN1A, SCN2A, SCN1B, SCN2B, and GABRG2 mutations in Japanese patients with FS+ was 15.8%. One family, which had R188W mutation in SCN2A, showed digenic inheritance, and another modifier gene was thought to take part in the seizure phenotype. The phenotypes of probands were FS+ in 5, FS+ and partial epilepsy in 10, FS+ and generalized epilepsy in 3, and FS+ and unclassified epilepsy in 1. We proposed the term epilepsy with febrile seizures plus (EFS+), because autosomal-dominant inheritance in EFS+ might be rare, and most of EFS+ display a complex pattern of inheritance, even when it appears to be an autosomal-dominant inheritance. There is a possibility of simultaneous involvement of multiple genes for seizure phenotypes.

Adolescent↗
PubMed2006

Electron-phonon coupling reflecting dynamic charge inhomogeneity in copper oxide superconductors.

The attempt to understand copper oxide superconductors is complicated by the presence of multiple strong interactions in these systems. Many believe that antiferromagnetism is important for superconductivity, but there has been renewed interest in the possible role of electron-lattice coupling. The conventional superconductor MgB2 has a very strong electron-lattice coupling, involving a particular vibrational mode (phonon) that was predicted by standard theory and confirmed quantitatively by experiment. Here we present inelastic scattering measurements that show a similarly strong anomaly in the Cu-O bond-stretching phonon in the copper oxide superconductors La(2-x)Sr(x)CuO4 (with x = 0.07, 0.15). Conventional theory does not predict such behaviour. The anomaly is strongest in La(1.875)Ba(0.125)CuO4 and La(1.48)Nd(0.4)Sr(0.12)CuO4, compounds that exhibit spatially modulated charge and magnetic order, often called stripe order; it occurs at a wave vector corresponding to the charge order. These results suggest that this giant electron-phonon anomaly, which is absent in undoped and over-doped non-superconductors, is associated with charge inhomogeneity. It follows that electron-phonon coupling may be important to our understanding of superconductivity, although its contribution is likely to be indirect.

Journal Article↗
PubMed2006

Dicoumarol potentiates cisplatin-induced apoptosis mediated by c-Jun N-terminal kinase in p53 wild-type urogenital cancer cell lines.

3-3'-Methylene-bis [4-hydroxycoumarin] (dicoumarol), an inhibitor of NADPH:quinone oxidoreductase 1, has been reported to possess potential antineoplastic effects and the ability to abrogate p53 protein. In the present study, we investigated the cytotoxic effects of dicoumarol in combination with cisplatin (CDDP), using four bladder (RT112, 253J, J82 and UMUC3) and two prostate (LNCap and PC3) cancer cell lines. Single treatment with 100 microM dicoumarol suppressed cell proliferation but did not induce apoptosis at 24 h in all cell lines examined. On the other hand, pretreatment with dicoumarol enhanced cytotoxicity of CDDP in three cell lines with wild type of p53 (RT112, 253J and LNCap), but not in three other cell lines with mutant p53 or in RT112 stable transfectants with a dominant-negative mutant of p53. In RT112 and LNCap, CDDP induced p53 and p21 expression, while pretreatment of dicoumarol suppressed induction of p53/p21 and resulted in sequential activation of c-Jun N-terminal kinase (JNK) in a time-dependent manner. Furthermore, inhibition of JNK, using SP600125, completely suppressed activity of caspases and poly-(ADP-ribose) polymerase cleavage, leading to suppression of enhancement of CDDP-mediated apoptosis by dicoumarol. These results suggested that dicoumarol could enhance cytotoxicity of CDDP in urogenital cancer cells with wild-type p53 through the p53/p21/JNK pathways.

Antineoplastic Agents↗
PubMed2006

Multicentre prospective study of perinatal depression in Japan: incidence and correlates of antenatal and postnatal depression.

A multicentre study on the epidemiology of perinatal depression was conducted among Japanese women expecting the first baby (N = 290). The incidence rate of the onset of the DSM-III-R Major Depressive Episode during pregnancy (antenatal depression) and within 3 months after delivery (postnatal depression) were 5.6% and 5.0%, respectively. Women with antenatal depression were characterised by young age and negative attitude towards the current pregnancy, whereas women with postnatal depression were characterised by poor accommodation, dissatisfaction with sex of the newborn baby and with the emotional undermining. Antenatal depression was a major risk factor for postnatal depression.

Adult↗
PubMed2006

Anti-parietal cell antibody and serum pepsinogen assessment in screening for gastric carcinoma.

BACKGROUND: Anti-parietal cell antibody is found in patients with Helicobacter pylori-positive gastritis and is related to atrophic gastritis and gastric carcinoma. AIM: To identify the characteristics of patients at high-risk for gastric carcinoma in terms of anti-parietal cell antibody and serum pepsinogen. PATIENTS AND METHODS: Subjects were 92 H. pylori-positive patients (54 men, 38 women; mean age, 57.9 years; range, 15-88 years). The serum concentrations of pepsinogen I and II were determined by radioimmunoassay, and the presence of anti-parietal cell antibody was assessed by enzyme-linked immunosorbent assay. Degrees of inflammation and atrophy in the corpus of the stomach were evaluated histologically. RESULTS: Patients were classified into four groups according to anti-parietal cell antibody status and pepsinogen I/II ratio. Anti-parietal cell antibody-negative/pepsinogen I/II-low patients had the highest risk for gastric carcinoma (prevalence of gastric carcinoma: 7/13=53.8%, odds ratio=7.6, 95% confidence interval, 1.2-48.0). Anti-parietal cell antibody titre was high when inflammation in the corpus was severe (p=0.06) and significantly low when atrophy in the corpus was severe (p=0.01). CONCLUSION: Our results showed that patients with a negative anti-parietal cell antibody titre and low pepsinogen I/II ratio are at high-risk for gastric carcinoma.

Adolescent↗
PubMed2006

Inhibition of NADPH oxidase 4 activates apoptosis via the AKT/apoptosis signal-regulating kinase 1 pathway in pancreatic cancer PANC-1 cells.

Pancreatic adenocarcinoma is an aggressive human malignancy and is characterized by resistance to apoptosis. Recently, NADPH oxidase (Nox) 4-mediated generation of intracellular reactive oxygen species (ROS) was proposed to confer antiapoptotic activity and thus a growth advantage to pancreatic cancer cells. The signaling mechanism by which Nox4 transmits cell survival signals remains unclear. Here, we show that both a flavoprotein inhibitor, diphenylene iodonium (DPI), and small interfering RNAs designed to target Nox4 mRNA (siNox4RNAs) inhibited superoxide production in PANC-1 pancreatic cancer cells, and depletion of ROS by DPI or siNox4RNAs induced apoptosis. Parallely, DPI treatment and siNox4RNA transfection blocked activation of the cell survival kinase AKT by attenuating phosphorylation of AKT. Furthermore, AKT phosphorylation of apoptosis signal-regulating kinase 1 (ASK1) on Ser-83 was reduced by DPI and siNox4RNAs. When ASK1Ser83Ala (an AKT phosphorylation-defective ASK1 mutant) was introduced into PANC-1 cells, this mutant alone induced apoptosis. But, addition of DPI or co-transfection of siNox4RNA had no additive effect, indicating that the mutant can substitute for these reagents in apoptosis induction. Taken together, these findings suggest that ROS generated by Nox4, at least in part, transmit cell survival signals through the AKT-ASK1 pathway in pancreatic cancer cells and their depletion leads to apoptosis.

Adenocarcinoma↗
PubMed2006

Calcium supplementation does not reproduce the pharmacological efficacy of alfacalcidol for the treatment of osteoporosis in rats.

The purpose of this study was to assess whether a nutritional supply of calcium (Ca) could be substituted for alfacalcidol (ALF) administration in preventing bone loss due to estrogen deficiency. Female Wistar-Imamichi rats (8 months old) were ovariectomized (OVX) or sham-operated. OVX rats received ALF administration (0.025, 0.5, or 0.1 microg/kg, p.o., 5 times a week) with standard rodent chow [Ca 1.2%, phosphorus (P) 1.04%], a Ca-enriched diet containing 2%, 4%, or 6% Ca (Ca/P ratio of 2, 4, and 6, respectively), or a Ca/P-enriched diet (Ca/P ratio of 1.2). After 12 weeks of treatment, all rats were killed to harvest the spine, serum, and urine samples. Neither the ALF treatment nor the Ca supplement caused hypercalcemia. In the spine, ALF prevented decreases in bone mineral density (BMD) and compressive strength of lumbar spine induced by OVX. Micro-computed tomographic analysis confirmed that ALF significantly improved the trabecular bone pattern factor and the structure model index and suppressed bone destruction. In contrast, of particular interest, high-dose Ca administration did not have marked effects on bone fragility. Also, when both Ca and P were administered in high doses, BMD and mechanical strength decreased dose-dependently, urinary P excretion significantly increased, and serum parathyroid hormone level increased. Together, it is difficult to adjust the Ca supply through diet alone without disrupting the balance between serum Ca and P levels. Consequently, we conclude that ALF is beneficial for the treatment of osteoporosis, which is not achieved by the use of a Ca supplement.

Amino Acids↗
PubMed2006

Regulation of human lung epithelial cell numbers by diesel exhaust particles.

Particulate air pollution is associated with respiratory morbidity and has cytotoxic and pro-inflammatory effects. The effects of diesel exhaust particles (DEP) on proliferation and apoptosis of A549 lung epithelial cells were examined. When deprived of serum (serum starvation), epithelial cell numbers fell, but DEP (5-200 microg.mL-1) prevented this. Using flow cytometric analysis of propidium iodide (PI) staining, DEP (10 microg.mL-1) increased cells in the S phase of cell cycle from 12.85 to 18.75% after 48 h, reversing serum starvation-induced G0/1 arrest. DEP also reduced the increase in apoptotic cells, as defined by double expression of annexin V/PI, observed after serum starvation (from 28.35 to 15.46%). The antioxidants, N-acetylcysteine (NAC; 33 mM) and AEOL10113 (10-100 microM), the N-terminal c-jun kinase inhibitor, SP600125 (33 microM), and nuclear factor-kappaB inhibitor, SN50 (33 microM), inhibited DEP-induced cell number increase. NAC inhibited DEP-induced reduction of G0/1 and increase in cells in the S and G2/M phases. Expression of p21CIP1/WAF1 mRNA and protein seen with serum starvation was reduced by DEP. In conclusion, diesel exhaust particles prevented serum starvation-led decreases in A549 epithelial cells by inducing cell cycle progression and preventing apoptosis, processes involving oxidative stress, inhibition of p21CIP1/WAF1 expression and stimulation of N-terminal c-jun kinase and nuclear factor-kappaB. Therefore, low-dose diesel exhaust particle exposure may lead to lung epithelial cell hyperplasia.

Apoptosis↗
PubMed2006

Impaired bone anabolic response to parathyroid hormone in Fgf2-/- and Fgf2+/- mice.

Since parathyroid hormone (PTH) increased FGF2 mRNA and protein expression in osteoblasts, and serum FGF-2 was increased in osteoporotic patients treated with PTH, we assessed whether the anabolic effect of PTH was impaired in Fgf2-/- mice. Eight-week-old Fgf2+/+ and Fgf2-/- male mice were treated with rhPTH 1-34 (80mug/kg) for 4 weeks. Micro-CT and histomorphometry demonstrated that PTH significantly increased parameters of bone formation in femurs from Fgf2+/+ mice but the changes were smaller and not significant in Fgf2-/- mice. IGF-1 was significantly reduced in serum from PTH-treated Fgf2-/- mice. DEXA analysis of femurs from Fgf2+/+, Fgf2+/-, and Fgf2-/- mice treated with rhPTH (160mug/kg) for 10 days showed that PTH significantly increased femoral BMD in Fgf2+/+ by 18%; by only 3% in Fgf2+/- mice and reduced by 3% in Fgf2-/- mice. We conclude that endogenous Fgf2 is important for maximum bone anabolic effect of PTH in mice.

Animals↗
PubMed2006

Restriction of dietary Iodine does not ameliorate the early effect of anti-thyroid drug therapy for Graves' disease in an area of excessive iodine intake.

The close relationship between iodine intake and the effects of anti-thyroid drugs (ATD) for Graves' disease (GD) has been well established. However, it remains unknown whether restriction of dietary iodine improves the effect of ATD. This study aimed to clarify this issue in Japanese patients with GD who routinely ingest large amounts of dietary iodine. We performed a prospective clinical study in 81 patients with newly diagnosed GD who were divided into an iodine restricted group and a control group. Urinary iodine, thyroid hormones and TSH receptor antibody were measured during the first 8 weeks of ATD therapy. Urinary iodine concentrations in the iodine restricted group were significantly lower than in the control group (p=0.043). However, there were no significant differences in the decrease of thyroid hormones and TSH receptor antibody between the two groups. Restriction of dietary iodine does not ameliorate the effect of ATD therapy for GD in an area of excessive iodine intake.

Adult↗
PubMed2006

Two cases of subacute thyroiditis presenting in pregnancy.

Subacute thyroiditis (SAT) is an extremely rare cause of thyrotoxicosis in pregnant women. Untreated, thyrotoxicosis may result in complications, such as prematurity and congenital malformations in the fetus. We report two cases of first trimester subacute thyroiditis, one mild and one severe. The severe case, as demonstrated by laboratory and ultrasound findings, was successfully treated with prednisolone. In this case, it was thought that the benefits of pharmacological therapy outweighed the risk of potential teratogenesis by the medication. In contrast, the milder case was managed conservatively and resolved without treatment. These cases illustrate how laboratory and ultrasound findings can be used to determine whether treatment should be initiated and, once begun, if medication levels need to be adjusted. In both cases, the pregnancies resulted in healthy full-term infants.

Adult↗
PubMed2006

Electron microscopic investigation on the osteogenesis at titanium implant/bone marrow interface under masticatory loading.

Electron microscopic investigation on osteogenetic process at the implant surface of threadless rod-type titanium implants with different surface roughness of Ra 0.4 +/- 0.01 microm, Sm 2.6 +/- 0.3 microm and Ra 2.0 +/- 0.12 microm, Sm 36 +/- 9.1 microm was performed at the early stage of 21 and 42 days post implantation into the jawbones of four beagles under the load bearing condition of functional mastication. The implant surfaces were covered with a blood clot and haematopoietic stem cells (HSC) including phagocytic monocytes immediately after the implantation. Successively, osteogenic stem cells (OSC) migrated from cortical and/or trabecular endosteum to the HSC-layer on the implant surface. The new bone formation at the implant/bone marrow interface was developed by collaboration of osteomediator cells (OMC) differentiated from monocytes of HSC and osteoblast phenotype cells of OSC derived from endosteum of cortical bone and/or trabecular. The new bone layer at the implant surface consisted of two layers, solution-mediated calcification layer of pseudo bone and cell (osteoblast) -mediated calcification layer of true bone. The pseudo bone was produced by solution-mediated calcification of OMC- and HSC-remnants near by the implant surface. The bone healing process at the implant/bone marrow interface depended upon two factors; the migration of OSC from cortical and/or trabecular endosteum to the implant surface and the healing potentiality. Topographic dependency upon the bone healing potential at implant/bone marrow interface was not confirmed in this experiment under the load bearing condition of functional mastication.

Animals↗
PubMed2006

Pulse-spray pharmacomechanical thrombolysis for proximal deep vein thrombosis.

OBJECTIVE: The aim of this study was to evaluate the efficacy, safety, and feasibility of pulse-spray pharmacomechanical thrombolysis to treat proximal deep vein thrombosis (DVT) in conjunction with the placement of a non-permanent IVC filter. METHODS: We studied 31 consecutive patients with acute proximal DVT defined as the inferior vena cava (IVC), iliac vein and/or femoral vein, who were diagnosed using duplex ultrasonography and/or contrast venography. All were treated with pulse-spray urokinase. Early success was assessed by comparing the pre- and post-treatment venographic severity score. Non-permanent IVC filters were used to reduce the risk of pulmonary thromboembolism. RESULTS: The average total urokinase dose was 1.71 million IU (range: 0.72-3.6 million IU) and the average duration of therapy was 2.4 days. The average percentage of thrombus lysed was 85% (range: 22-100%). A large thrombus trapped by the filter was detected using cavography before extraction of the filter in one patient. There was no major treatment-related adverse event. CONCLUSION: The combination of pulse-spray pharmacomechanical thrombolysis and the prophylactic use of a non-permanent IVC filter was a safe and effective approach for treating acute proximal DVT.

Adult↗
PubMed2006

Male New Zealand Black/KN mice: a novel model for autoimmune-induced permanent alopecia?

BACKGROUND: Irreversible, permanent and scarring alopecia is associated with several autoimmune diseases, including all autoimmune connective tissue disorders. The pathogenesis of autoimmune-induced permanent alopecia (APA) is still poorly understood, and instructive, simple mouse models for the study of APA are needed urgently. During the course of our studies in a well-established mouse model for chronic rheumatoid arthritis, the New Zealand Black/KN (NZB/KN) mouse, we noticed that ageing male NZB/KN mice developed spontaneous APA. OBJECTIVES: To study whether alopecia seen in ageing male NZB/KN mice displays key features of human APA and may, thus, be a useful new mouse model for clinically relevant APA research. METHODS: NZB/KN, the F1 hybrid of NZW/N Slc x NZB/KN (W/BKN F1), the F1 hybrid of NZB/KN x NZW/N Slc (BKN/W F1), and the F2 hybrid of W/BKN F1 x W/BKN F1 mice were employed in this study, in order to check which strain carries the highest risk of alopecia development. Besides routine histology, CD3, CD4 and CD8 expression as well as immunoglobulin (Ig) G and IgM deposition in hair follicles were investigated by immunohistology/immunofluorescence. Mast cell distribution/degranulation and Ki-67 (proliferation)/TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling) (apoptosis) positive cells were also analysed. RESULTS: Only F2 male NZB/KN mice were prone to develop alopecia, suggesting that Y chromosome-associated gene(s) are involved in the pathogenesis of APA, which incidence rises with increasing age. The lesional alopecia skin in 12-month-old male NZB/KN mice showed a sharp decline in hair follicle density, thus meeting a key criterion of permanent alopecia. Both macroscopically and histologically, the alopecia seen in these mice resembled in many respects different stages of clinical APA, such as alopecia associated with chronic discoid lupus erythematosus (DLE) in humans. Lesional APA hair follicles in mice displayed intrafollicular and perifollicular mononuclear cell infiltrates, as well as an increased number of activated (degranulated) perifollicular mast cells. In the fully developed lesion, many CD4+ cells were seen in perifollicular locations, including the epithelial stem cell region (bulge), and also contained a few CD8+ T cells. IgM deposits were found in the follicular basement membrane zone (BMZ). Both in the bulge and the hair matrix region of the affected anagen hair follicles, there were signs of massive keratinocyte apoptosis. CONCLUSIONS: Our currently available data suggest that male but not female NZB/KN mice may indeed represent a suitable mouse model for APA, with some similarities to the permanent alopecia seen in human DLE patients, although additional and confirmatory investigations are needed before this mouse strain can be accepted as a murine equivalent of APA in humans.

Aging↗