PubMed Health⌕ Search

Biomedical subjects

H Kitamura

Publications and source records attributed to H Kitamura.

At least 19 recordsLinked to original sources
PubMed2006

The intercomparison of cosmic rays with heavy ion beams at NIRS (ICCHIBAN) project.

The ICCHIBAN-2 experiment, the first dedicated to the ground-based intercomparison of passive space dosemeters, was carried out between 23 May and 28 May 2002 at the National Institute of Radiological Sciences in Chiba, Japan. The primary objective of the ICCHIBAN-2 experiment was to intercompare the response of passive dosemeters used in space crew dosimetry to monoenergetic heavy ions of charge and energy spanning a significant portion of the galactic cosmic ray (GCR) spectrum. During the ICCHIBAN-2 experiment, dosemeters from 12 different laboratories in 9 countries were irradiated under identical conditions to heavy ion beams of 150 MeV n(-1) (4)He, 400 MeV n(-1) (12)C, 490 MeV n(-1) (28)Si and 500 MeV n(-1) (56)Fe at the NIRS Heavy Ion Medical Accelerator.

Cosmic Radiation↗
PubMed2006

X-ray diffractometer combining synchrotron radiation and pulsed magnetic fields up to 40 T.

A synchrotron X-ray diffractometer incorporating a pulsed field magnet for high fields up to 40 T has been developed and a detailed description of this instrument is reported. The pulsed field magnet is composed of two coaxial coils with a gap of 3 mm at the mid-plane for passage of the X-rays. The pixel detector PILATUS 100K is used to store the diffracted X-rays. As a test of this instrument, X-ray diffraction by a powder sample of the antiferromagnet CoO is measured below the Néel temperature. A field-dependent lattice distortion of CoO due to magnetostriction is observed up to 38 T.

Journal Article↗
PubMed2006

Cytosolic overexpression of p62 sequestosome 1 in neoplastic prostate tissue.

AIMS: To investigate the expression of p62 in various prostatic tissues, and to demonstrate different immunohistochemical patterns of p62 expression in distinct pathological entities of the prostate. The p62 sequestosome 1 (SQSTM1) gene product is a multifunctional protein with ubiquitous expression in normal adult tissue. METHODS AND RESULTS: Overexpression of p62 was detected in prostate cancer cell lines and tissues by reverse transcriptase-polymerase chain reaction. Immunohistochemical staining for p62 was performed on 73 cases of paraffin-embedded prostatic tissue. p62 was negative or weakly positive only in the nucleus (pattern N) of prostatic gland epithelium in nine normal and hyperplastic prostate specimens, whilst most cancerous tissue showed intense, uniform staining for p62 in the cytoplasm (pattern C). Of the prostate cancer specimens, 91% showed positive pattern C immunoreactivity. Of the cases with high-grade prostatic intraepithelial neoplasia (PIN) around cancer, 77% showed pattern C. However, in specimens from the patients without prostate cancer PIN displayed pattern C in only 32% of cases. Western blot analysis showed that all cancer cell lines expressed p62 in the cytoplasm but there was little nuclear expression. CONCLUSION: Cytosolic overexpression of p62 is a novel immunohistochemical characteristic in prostatic adenocarcinoma and high-grade PIN, suggesting that p62 might be a novel marker for prostatic malignancy.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Parietal white matter abnormalities in obsessive-compulsive disorder: a magnetic resonance spectroscopy study at 3-Tesla.

OBJECTIVE: To identify a neurochemical basis for the hypothesis that an aberrant cortico-subcortical circuit underlies obsessive-compulsive disorder (OCD). The white matter was also investigated because of recent research which suggests the altered connectivity of axons. METHOD: Using 3-Tesla magnetic resonance spectroscopy, the relative concentrations of N-acetylaspartate (NAA) and choline-containing compounds (Cho) to creatine/phosphocreatine (Cr) were measured in the anterior cingulate, basal ganglia, thalamus, frontal and parietal white matter of 12 OCD patients, and 32 control subjects. RESULTS: The mean concentration of Cho/Cr was significantly higher in the patients than in the controls, but only in the parietal white matter, while no significant group differences in NAA/Cr were observed in any of the brain regions. Parietal Cho/Cr correlated positively with the severity of OCD symptoms. CONCLUSION: This finding provides indirect evidence for the parietal white matter involvement in OCD, thus suggesting a change in the phospholipids of myelinated axons and/or glia cells.

Adolescent↗
PubMed2005

Gastric mucosal hyperplasia via upregulation of gastrin induced by persistent activation of gastric innate immunity in major histocompatibility complex class II deficient mice.

BACKGROUND AND AIMS: Major histocompatibility complex class II deficient (Aalpha0/0) mice have decreased CD4+ T cells, making them immunologically similar to patients with acquired immunodeficiency syndrome (AIDS). Both patients with AIDS and Aalpha0/0 mice have hypertrophic gastric folds. To clarify the mechanism of gastric mucosal hyperplasia, we investigated the pathophysiology and the role of the innate immunity in the stomach of Aalpha0/0 mice. METHODS: Stomachs from 1-6 month old Aalpha0/0 mice, kept under specific pathogen free conditions, were examined at 1 month intervals histologically and immunohistochemically. Gene expression of proinflammatory cytokines, Toll-like receptors (TLRs), cyclooxygenase (COX)-2, and myeloperoxidase (MPO) activity in the gastric mucosa was investigated. Serum gastrin levels and gastric acidity were measured. Bacterial culture of the stomach was performed. To clarify the roles of hypergastrinaemia in the gastric mucosa, a gastrin receptor antagonist (AG041R) was administered. RESULTS: Aalpha0/0 mice had a diffusely thick corpus mucosa with infiltration of CD11b+ granulocytes and macrophages. Anti-Ki67 staining demonstrated expansion of the proliferating neck zone. Gene expression of interleukin 1beta, interferon gamma, TLR-2, TLR-4, and COX-2 were upregulated, and MPO activity was increased. Only a small amount of non-pathogenic bacteria was detected in the stomach. Serum gastrin levels and Reg-Ialpha positive cells in the gastric mucosa increased, despite normal gastric acidity. After treatment with AG041R, gastric mucosal thickness was significantly reduced. CONCLUSION: Persistent activation of innate immunity in the stomach induced gastric mucosal hyperplasia through upregulation of gastrin synthesis in Aalpha0/0 mice, suggesting a pathophysiology similar to the gastric changes in patients with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed2005

The transcriptional landscape of the mammalian genome.

This study describes comprehensive polling of transcription start and termination sites and analysis of previously unidentified full-length complementary DNAs derived from the mouse genome. We identify the 5' and 3' boundaries of 181,047 transcripts with extensive variation in transcripts arising from alternative promoter usage, splicing, and polyadenylation. There are 16,247 new mouse protein-coding transcripts, including 5154 encoding previously unidentified proteins. Genomic mapping of the transcriptome reveals transcriptional forests, with overlapping transcription on both strands, separated by deserts in which few transcripts are observed. The data provide a comprehensive platform for the comparative analysis of mammalian transcriptional regulation in differentiation and development.

3' Untranslated Regions↗
PubMed2005

Experimental microdosimetric distributions of protons, from 19 to 65 MeV, using an A150-walled Low Pressure Proportional Counter.

Microdosimetric distributions of protons, from 19 to 65 MeV, were measured using an A150-walled Low Pressure Proportional Counter at the cyclotron facility in the National Institute of Radiological Sciences. The measured distributions were found to be very different from the spectra assumed by the Continuous Slowing Down Approximation. The measurements consisted of determining the energy deposition by direct incident protons, by secondary electrons produced in the wall of the detector and by scattered protons at the wall. The secondary electron and the scattered proton distributions were studied using analytical functions and the MCNPX Monte Carlo code, respectively.

Electrons↗
PubMed2005

Expression of thymidylate synthase, dihydropyrimidine dehydrogenase, thymidine phosphorylase, and orotate phosphoribosyl transferase in prostate cancer.

The enzymes thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP), and orotate phosphoribosyl transferase (OPRT) are involved in the metabolism of the anticancer drug 5-fluorouracil. No reports have examined the expression of these enzymes in prostate cancer (CaP). A total of 25 previously untreated, hormone-sensitive CaP tissue samples and 11 benign prostatic hyperplasia (BPH) specimens were examined. Tissue of CaP and BPH tissue samples were obtained from formalin-fixed, paraffin-embedded sections by laser-captured microdissection, and then RNA was extracted. mRNA expression of TS, DPD, TP, and OPRT was analyzed by quantitative reverse transcriptase-polymerase chain reaction. TS and OPRT expression levels were significantly higher in CaP samples than in BPH. DPD expression level in poorly differentiated CaP was significantly lower than that in CaP with more favorable--well or moderately differentiated--histopathology.

Cell Differentiation↗
PubMed2005

[Early and late results and problems of coronary artery bypass grafting in patients over 80-year-old].

This study evaluated the validity of coronary artery bypass grafting (CABG) in patients over 80-year-old investigating the early and late result, patient's opinion to the surgery, and change of activities of daily living scale. From July 1993 to September 2002, consecutive 94 patients over 80-year-old were performed CABG in our institution. The group consisted of 43 female patients, and mean age of 82.6 years. Of these patients, 36 were operated conventional CABG (CABG group) and 58 patients were operated with off-pump CABG (OPCAB) group. There were no significant differences between 2 groups in preoperative characteristics except for anemia and hypertension. Operative results, including mortality, number of distal anastomoses, operative time had no significant differences between 2 groups. But maximum CK-MB fraction was higher in CABG group. There were 4 operative deaths, indicating operative mortality was 4.3%. Late results showed overall survival rate at 3 years was 81.1% and cardiac event free survival rate at 3 years was 88.8%. Questionnaire revealed over 80% patients were satisfied with the surgery but less than 40% patients felt activities of daily living (ADL) scale was improved. Operative results of CABG in octogenarians were satisfied, but more efforts to remain patient's high ADL were mandatory.

Activities of Daily Living↗
PubMed2005

Reduplicated basal lamina of the peritubular capillaries in renal biopsy specimens.

Reduplicated basal lamina of the peritubular capillaries (PTC) is usually found in kidney allografts in association with chronic transplant nephropathy and sometimes in native renal biopsies. In order to assess the incidence of this phenomenon in native renal biopsy specimens, we have carried out a retrospective review of the diagnostic ultrastructural pathology records of 80 consecutive renal biopsies excluding renal allografts and children with clinical signs of heavy proteinuria. Reduplicated basal lamina of the PTC was found in 19 out of the 80 cases (23.8%) with renal diseases. It was frequently seen in lupus nephritis, IgA nephropathy, and membranoproliferative glomerulonephropathy, being the subtypes of mesangial proliferative lesions. In a few cases it was also found in anti-neutrophil cytoplasmic autoantibody (ANCA) associated glomerulonephritis and benign nephrosclerosis renal biopsies. Reduplicated basal lamina of the PTC was strongly associated with glomerular and peritubular inflammation, and tubular necrosis. Peritubular interstitial edema, slight to moderately increased collagen fibrils, many spiraled collagen fibrils (indicative of degeneration), and collagen fibrils drawing from basal lamina were found around the reduplicated basal lamina of the PTC but not in normal basal lamina. These results indicate that in native renal biopsy specimens, reduplication of the basal lamina of the PTC is associated with endothelial cell injury and capillary permeability abnormality.

Adult↗
PubMed2004

PI3K-AKT pathway mediates growth and survival signals during development of fetal mouse lung.

We examined the roles of the PI3K-AKT signalling pathway in fetal lung development. By Western blotting, phosphorylated AKT (pAKT) was highly expressed in fetal days 12 and 14 with decreased expression thereafter. By immunohistochemistry, pAKT was expressed mainly in the respiratory epithelium of early fetal days. We examined the effects of fibroblast growth factor 1 (FGF1), PI3K inhibitors (LY294002 and wortmannin), MAPK inhibitor (PD98059) and both of FGF1 and each inhibitor on lung morphogenesis, BrdU incorporation and apoptosis. In the FGF1-treated explants, the number of terminal buds and BrdU-labelled cells increased significantly, while the LY294002-, wortmannin-, PD98059-treated explants demonstrated obvious decreases. The effects by FGF1 were inhibited by LY294002, wortmannin and PD98059. Regardless of the presence of FGF1, the LY294002-, wortmannin- and PD98059-treated explants increased apoptosis revealed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling assay in the mesenchyme of the explants. At the same time, the effect of LY294002, wortmannin, PD98059 on expression of surfactant apoprotein C (SPC) were also studied. The LY294002 and wortmannin treatments showed decreased expression of SPC. These findings suggest that the PI3K-AKT signalling pathway plays a pivotal role in mouse lung development through various biological processes.

Androstadienes↗
PubMed2004

Effects of p27Kip1 on cell cycle status and viability in A549 lung adenocarcinoma cells.

p27Kip1 is a cyclin-dependent kinase inhibitor, it negatively regulates G1 progression and is reported to modulate apoptosis. Phosphorylation of this protein is thought to regulate its intracellular localisation and affect its stability. The aim of this study was to regulate p27Kip1 expression levels, and to examine how this protein affects cell cycle status and modulates viability in A549 lung adenocarcinoma cells. In addition, the association between phosphorylation status of p27Kip1 and its intracellular localisation was investigated, using expression vectors with cDNA of p27Kip1 or mutants in which the phosphorylation sites had been mutated. Although overexpression of p27Kip1 reduced cell cycle progression, its removal did not change cell cycle status. Modest induction of p27Kip1 rescued adenovector-induced apoptosis and its removal with short interfering RNA increased spontaneous cell death. It was also observed that p27Kip1 localised mainly in the cytoplasm, and forced expression of p27Kip1 cDNA with the substitution of serine (S) 10, threonine (T) 157 and T198 to glutamate (phosphor-mimetic) induced its cytoplasmic localisation. In conclusion, p27Kip1, when expressed physiologically, exists mainly in the cytoplasm, has little effect on cell cycle status and contributes viability in A549 lung adenocarcinoma cells. It was also surmised that intracellular localisation of p27Kip1 dominates its function and that its localisation was partly determined by its phosphorylation.

Adenocarcinoma↗
PubMed2003

Meningioma showing VHL gene inactivation in a patient with von Hippel-Lindau disease.

The genetic mechanism of the tumorigenesis of meningioma in conjunction with von Hippel-Lindau (VHL) disease is unclear. The authors present a case of VHL disease associated with a posterior fossa meningioma and with multiple cerebellar hemangioblastomas. A germline mutation of the VHL gene and loss of heterozygosity on the VHL gene locus in 3p were detected in the meningioma. Tumorigenesis of a meningioma associated with VHL disease could be caused by inactivation of both alleles of the VHL gene.

Aged↗
PubMed2003

AG-041R stimulates cartilage matrix synthesis without promoting terminal differentiation in rat articular chondrocytes.

OBJECTIVE: AG-041R, a novel indolin-2-one derivative, has recently been demonstrated to induce systemic hyaline cartilage hyperplasia in rats. The aim of this study was to characterize its anabolic actions on chondrocytes. DESIGN: Chondrocytes were isolated from knee joints of 5-week-old SD rats. Effects of AG-041R on cartilage matrix synthesis were examined by measuring [(35)S]sulfate incorporation into proteoglycans, Alcian blue staining, and Northern blotting of cartilage matrix genes. ALP activity, mineral deposition and the expression of markers for hypertrophic chondrocytes, were assessed for terminal differentiation of chondrocytes. Roles of endogenous TGF-beta/BMPs and MEK1/Erk signaling in the action of AG-041R were investigated using the neutralizing soluble receptors and the MEK1 inhibitor. RESULTS: AG-041R accelerated proteoglycan synthesis assessed by both [(35)S]sulfate incorporation and Alcian blue stainable extracellular matrix accumulation. It also up-regulated the gene expression of type II collagen and aggrecan, as well as tenascin, a marker for articular cartilage. In contrast, AG-041R suppressed ALP activity, mineralization, and the gene expression of type X collagen and Cbfa1, indicating that AG-041R prevents chondrocyte terminal differentiation. AG-041R increased in BMP-2 mRNA, and the neutralizing soluble receptor for BMPs reversed the stimulatory effects of AG-041R on cartilage matrix synthesis. Moreover, AG-041R activated MEK1/Erk pathway, which was revealed to prevent chondrocyte terminal differentiation. CONCLUSION: AG-041R stimulates cartilage matrix synthesis without promoting terminal differentiation in rat articular chondrocytes, which is mediated at least in part by endogenous BMPs and Erk. The data demonstrates that AG-041R has a potential to be a useful therapeutic agent for articular cartilage disorders.

Alkaline Phosphatase↗
PubMed2003

Percutaneous calcitriol injection therapy (PCIT) for secondary hyperparathyroidism: multicentre trial.

A multicentre trial of percutaneous calcitriol injection therapy (PCIT) was designed to evaluate its clinical usefulness. During a 12-week period, measurement of intact PTH concentration, and other parameters, and ultrasonography were carried out in conjunction with PCIT in 19 haemodialysis patients with secondary hyperparathyroidism and enlarged parathyroid glands (PTGs) that were resistant to vitamin D pulse therapy. Calcijex was injected directly into the PTG three times per week on the patient's non-dialysis days: eight patients received a 2 microg/ml preparation (group A) and 12 received 1 microg/ml (group B). A strong clinical effect was observed in group A compared with group B, which suggests that the effect of calcitriol by direct injection is stronger when there is a higher concentration of calcitriol in the PTG. In group B, the cases with an initial intact PTH concentration <1000 pg/ml and a single enlarged PTG had a good response to the treatment. Concentrations of calcium and phosphate were not significantly changed in either group. All cases had decreased blood flow in the PTG after three episodes of PCIT and, although the size of the PTG was unchanged, or even a little increased, immediately after the treatment, it decreased gradually over 2-6 weeks. PCIT may be effective for comparatively slight secondary hyperparathyroidism, but further investigation is necessary because there were comparatively few cases.

Aged↗
PubMed2002

Inhibitory effect on expression of angiogenic factors by antiangiogenic agents in renal cell carcinoma.

Since it has been widely recognised that renal cell carcinoma is refractory to standard therapies such as chemotherapy and radiotherapy, a new modality of treatment is needed. One of the potential alternative therapies for renal cell carcinoma may be inhibition of angiogenesis. In this study, we analysed the inhibitory effects of several potential agents on expression of angiogenic factors such as vascular endothelial growth factor and basic fibroblast growth factor, which are the main mediators in angiogenesis of renal cell carcinoma. We used medroxyprogesterone acetate, interferon-alpha, interferon-gamma, minocycline hydrochrolide and genistein, which are known to be antiangiogeneic. Northern blot analyses revealed that, among the five agents examined, genistein had a strong inhibitory effect on expression of vascular endothelial growth factor mRNA and basic fibroblast growth factor mRNA. Medroxyprogesterone acetate and interferon-alpha did not significantly decrease the level of either vascular endothelial growth factor mRNA or basic fibroblast growth factor mRNA. Interferon-gamma and minocycline had mild inhibitory effects on vascular endothelial growth factor mRNA and basic fibroblast growth factor mRNA expression. Genistein also inhibited both vascular endothelial growth factor mRNA and basic fibroblast growth factor mRNA expression after treatment with epidermal growth factor and hypoxia. These findings suggest that one of the mechanisms of the inhibition of angiogenesis by genistein is suppression of the expression of the angiogenic factors vascular endothelial growth factor and basic fibroblast growth factor in renal cell carcinoma.

Angiogenesis Inhibitors↗
PubMed2002

Development of port-site metastasis after pneumoperitoneum.

BACKGROUND: Port-site metastasis is a critical problem in laparoscopic cancer surgery; the pathogenesis and means of prevention are still unclear. The aim of this study was to clarify by scanning electron microscopy the initial morphologic changes in the development of port-site metastasis. METHODS: Fifteen nude mice were injected with human gastric cancer (MKN 45) cells. Mice were killed on days 0, 3, and 8 (n = 5 each day) after intraperitoneal injection of 5 x 105 cancer cells and carbon dioxide (CO2) pneumoperitoneum at 4-6 mmHg for 20 min. The abdominal wall with the port sites was harvested and examined under both light and scanning electron microscopy. RESULTS: Immediately after CO2 pneumoperitoneum (day 0), the abdominal peritoneum was peeled away and the muscular layer was destroyed at the port site in all mice. Several cancer cells were attached to the injured port sites. On day 3, the subperitoneal tissue and muscular layer defects were replaced by granulation tissue, and several cancer cells were observed in the subperitoneal tissue. On day 8, a small nodule was macroscopically visible at the port site; it was completely covered by mesothelial cells and consisted of numerous cancer cells. CONCLUSIONS: Free cancer cells appear to attach to the injured port sites immediately after CO2 pneumoperitoneum, and these are associated with the development of port-site metastasis after laparoscopic cancer surgery.

Animals↗