Search PubMed⌕ Search

Biomedical subjects

H Nakamura

Publications and source records attributed to H Nakamura.

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

Differential apoptotic pathways in human keratinocyte HaCaT cells exposed to UVB and UVC.

The induction of apoptosis in keratinocytes by ultraviolet (UV)-irradiation is considered to be a protective function against skin cancer. UV-induced DNA damage is a crucial event in UVB- and UVC-mediated apoptosis. However, the differences between the UVB- and UVC-induced apoptotic pathways remain unclear. Here we examine the differential mechanisms by which UVB and UVC irradiations induce keratinocyte apoptosis using human keratinocyte HaCaT cells. Differences in the production of (6-4)photoproducts ((6-4)PPs) and cyclobutane pyrimidine dimers (CPDs) were measured following irradiation with UVB and UVC at doses causing the same extent of apoptotic cell death. In addition, main apoptotic features, such as caspase activation and its regulation, were compared between UVB- and UVC-induced apoptosis. Exposures of 500 J/m(2) UVB and 100 J/m(2) UVC resulted in apoptosis to almost the same extent. At these apoptotic doses, the amounts of both (6-4)PPs and CPDs were significantly larger in the case of UVC irradiation than UVB irradiation; in parallel, the release of cytochrome c and Smac/DIABLO and the activation of caspases-9 following UVC irradiation were greater than after UVB irradiation. Importantly, caspase-8 activation occurred only in UVB-irradiated cells. Furthermore, the activation of caspase-8 was not inhibited by caspases-9 and -3 specific tetrapeptide inhibitors, indicating that the caspase-8 cleavage is not due to feedback from activation of caspases-9 and -3. Thus, these results clearly suggest that the reason apoptosis is induced to the same extent by UVB irradiation as by UVC irradiation, despite the lower production of photoproducts in DNA by UVB irradiation, is attributable to the additional activation of the caspase-8 pathway. Thus, UVB irradiation induces apoptosis through both mitochondrial (intrinsic) and caspase-8 activation (extrinsic) pathways, while UVC induces apoptosis only via the intrinsic pathway.

Apoptosis↗
PubMed2005

Characteristics of peripheral microembolization during iliac stenting: Doppler ultrasound monitoring.

OBJECTIVE: To evaluate the characteristics of distal microembolic signals (MES) during iliac stenting using Doppler ultrasound monitoring. DESIGN: Prospective clinical study. METHODS: A 2-MHz probe was used to monitor continuously at the ipsilateral tibioperoneal trunks during technically and hemodynamically successful iliac stenting in 10 patients without infrainguinal occlusive lesion. MESs at guide-wire, balloon, or stent crossing (phase 1), predilatation (phase 2), stent deployment (phase 3), postdilatation (phase 4), and contrast medium or heparinized saline injection (at injection) were analyzed. Differentiation of gaseous emboli from particulate emboli was achieved by calculation of the sample volume length. RESULTS: No distal embolic complications were observed. Five hundred and forty-one MESs were detected. The MES incidence and intensity in phase 3 were significantly higher than those in phase 1, phase 2, and phase 4 (p<0.05). The MES intensity at injection was significantly higher than that in each of four phases (p<0.0001). CONCLUSIONS: Both the MES incidence and intensity were highest at stent deployment. Further study is required of microembolism during endovascular procedures in the lower extremities.

Aged↗
PubMed2005

The role of subchondral bone resorption pits in osteoarthritis: MMP production by cells derived from bone marrow.

OBJECTIVE: The vascular invasion of bone marrow tissue into the subchondral plate is often observed in articular cartilage and we named it the subchondral bone absorption pit; however, its implication in the pathogenesis of osteoarthritis (OA) has been poorly understood. The purpose of this study was to evaluate its characteristics and roles in osteoarthritic conditions. METHODS: Articular cartilage specimens from 11 patients with medial type knee OA and 7 non-arthritic cadavers were analyzed with HE staining. OA sections were stained with safranin-O, TRAP (tartrate resistant acid phosphatase) and immunostained with anti-MMP-1, MMP-3, MMP-13, vitronectin receptor (VNR)-alpha chain, vimentin and bone morphogenic protein (BMP) 2/4 antibodies. RESULTS: Subchondral bone resorption pits were classified according to the extent of invasion: pits with bone marrow tissue were located within uncalcified cartilage below the tidemark in grade I and invaded beyond the tidemark in grade II, while no invasion was seen in grade 0. Grade II pits were dominant in OA compared to non-arthritic joints, especially medial condyles. Proteoglycan detected with safranin-O staining was lost around the tip of grade II pits and the density of pits was related to the modified Mankin Score. Cells in pits expressed vimentin, MMP-1, MMP-3 and MMP-13. Some polynuclear cells co-expressed VNR-alpha chain and MMP-13, whereas pits showed reparative features expressing BMP. CONCLUSION: These results suggest that subchondral bone resorption pits contribute to cartilage degradation by expressing matrix metalloproteinases in OA.

Aged↗
PubMed2005

Initial distribution volume of glucose is correlated with intrathoracic blood volume in hypovolaemia and following volume loading in dogs.

BACKGROUND AND OBJECTIVE: Initial distribution volume of glucose (IDVG) reliably measures the central extracellular fluid volume in the presence of fluid gain or loss. We hypothesized that IDVG has a close relationship with intrathoracic blood volume (ITBV), which has recently been used as an indicator of cardiac preload. We therefore examined whether IDVG can correlate with ITBV in various fluid volume states. METHODS: Fourteen anaesthetized mongrel dogs were mechanically ventilated. ITBV and cardiac output were measured by single transpulmonary thermodilution technique. IDVG and indocyanine green derived plasma volume (PV-ICG) were determined by the administration of 100 mg kg(-1) glucose and 0.5 mg kg(-1) indocyanine green solutions, respectively, and calculated by applying a one-compartment model. Three sets of measurements were performed before and after haemorrhage (30 mL kg(-1) and subsequent fluid volume loading (90 mL kg(-1) of lactated Ringer's solution). RESULTS: A linear correlation was observed between IDVG and ITBV (r2 = 0.52, n = 42, P < 0.001) and between PV-ICG and ITBV (r2 = 0.44, n = 42, P < 0.001) throughout the procedures. A linear correlation was also observed between changes in IDVG and those in ITBV (r2 = 0.76, n = 28, P < 0.001). The ITBV/IDVG ratio during normovolaemia was 0.26 +/- 0.04, which remained unchanged during the procedure. CONCLUSION: Results showed that that IDVG has a linear correlation with ITBV, and support the concept that IDVG measurement has potential as a surrogate measure of ITBV in various fluid volume states.

Animals↗
PubMed2005

Radiation streaming experiment through a labyrinth of the 12 GeV proton accelerator facility at KEK(2)--TLD REM-counter method.

The doses of radiation streaming through a labyrinth were measured using thermoluminescence dosemeters (TLDs) and neutron moderators for TLDs at the neutrino beam line of the 12 GeV proton accelerator facility of High Energy Accelerator Research Organization (KEK). The calculated doses using the Monte Carlo code, MCNPX basically agreed with the experimental results. However, unexpectedly, the calculated neutron doses were smaller than the measured ones along the upstream side of the labyrinth.

Computer-Aided Design↗
PubMed2005

Detection of apoptosis-specific autoantibodies directed against granzyme B-induced cleavage fragments of the SS-B (La) autoantigen in sera from patients with primary Sjögren's syndrome.

The objective of this study was to detect autoantibodies against granzyme B cleavage products in sera from patients with primary Sjögren's syndrome (SS). Cell lysates derived from human salivary gland (HSG) cell lines were incubated with granzyme B. The susceptibility to the generation of cleavage fragments of SS autoantigens was assayed by immunoblotting using sera from 57 primary SS patients, 17 primary SS patients with malignant lymphoma (ML), 28 systemic lupus erythematosus (SLE) patients, and 20 healthy controls. A 27 kD protein was recognized by serum autoantibodies in 8 (14.0%) of 57 primary SS patients, 5 (29.4%) of 17 SS patients with ML, 2 (7.1%) of 28 SLE patients, but not in 20 normal subjects. This protein was recognized by anti-SSB (La) monoclonal antibodies. Granzyme B-treated recombinant La protein was also shown to migrate as a discrete 27 kD protein by SDS PAGE. Blocking studies demonstrated the existence of an apoptosis-specific B cell epitope present in sera from 2 of 8 primary SS patients and in 2 of 5 primary SS patients with ML which recognized the 27 kD protein. Granzyme B-induced La fragments are generated during cytotoxicity in vitro. This is the first report describing autoantibodies in sera from primary SS patients that specifically recognize fragments of the La protein that are produced by the granzyme B protease.

Adult↗
PubMed2005

Aggrecanase analysis of synovial fluid of temporomandibular joint disorders.

OBJECTIVES: To determine whether or not aggrecanase in synovial fluid can be used as a biochemical marker in the diagnosis of temporomandibular joint disorder (TMJD). MATERIALS AND METHODS: Forty-four samples of synovial fluid were obtained from 35 patients with internal derangement or osteoarthritis and 15 control samples from 10 asymptomatic volunteers. Aggrecanase in the synovial fluid was examined by immunoblotting. RESULT: The incidence of aggrecanase expression in TMJD group were significantly higher than that in the normal control group (P < 0.05). Those with severe OA and anterior disc displacement without reduction showed significantly high expression of aggrecanase compared with other disease subgroups (P < 0.05). CONCLUSION: These findings suggested that aggrecanase could be a potential biochemical marker for cartilage degeneration in the TMJD.

Adolescent↗
PubMed2005

RS3PE syndrome presenting as vascular endothelial growth factor associated disorder.

OBJECTIVES: To characterise serum concentrations of various cytokines and detection by magnetic resonance imaging (MRI) of synovial hypervascularity in patients with remitting seronegative symmetrical synovitis with pitting oedema (RS3PE) syndrome before and after corticosteroid treatment. METHODS: Vascular endothelial growth factor(165) (VEGF(165)), tumour necrosis factor alpha (TNFalpha), and interleukin 1beta (IL1beta) were measured by enzyme linked immunosorbent assay (ELISA) in serum samples from three patients with RS3PE syndrome. As controls, serum samples from 26 healthy volunteers, 12 patients with rheumatoid arthritis, 10 patients with systemic lupus erythematosus, 13 patients with polymyositis/dermatomyositis, 13 patients with vasculitis syndrome, and 6 patients with mixed connective tissue disease were also analysed. Synovial hypervascularity of patients with RS3PE syndrome was estimated by rate of enhancement (E-rate) in a dynamic MRI study. RESULTS: Serum concentrations of VEGF(165) (mean (SD) 2223.3 (156.3) pg/ml) were significantly higher in patients with active RS3PE syndrome than in controls before corticosteroid treatment. TNFalpha and IL1beta levels were similar in patients and controls. Synovial hypervascularity in affected joints and subcutaneous oedema decreased during corticosteroid treatment, in parallel with the fall in serum VEGF(165). CONCLUSIONS: VEGF promotes synovial inflammation and vascular permeability in patients with RS3PE syndrome, suggesting that RS3PE can be classified as a VEGF associated disorder.

Adrenal Cortex Hormones↗
PubMed2005

Histopathological and immunohistochemical studies of lenticules after epikeratoplasty for keratoconus.

AIMS: To examine histopathological and immunohistochemical changes in lenticules and host of corneal buttons from patients who previously underwent epikeratoplasty for keratoconus. METHODS: 12 penetrating keratoplasty specimens from patients with keratoconus who had previously undergone epikeratoplasty, eight keratoconus, and seven normal corneas were examined. Immunostaining for Sp1, alpha1-proteinase inhibitor (alpha1-PI), and alpha2-macroglobulin (alpha2M) were performed. RESULTS: In nine of the 12 lenticules, the keratoconus-like disruptions were found in Bowman's layer. Peripheral and posterior keratocyte repopulation of the lenticules was observed in all cases. Keratocyte repopulation in the anterior and mid-stromal regions of the lenticules appeared related to the time since epikeratoplasty. Sp1 nuclear staining of the basal and wing epithelial cells was more intense in lenticules and keratoconus corneas than in normal corneas. Lenticular, host, and keratoconus keratocytes showed positive Sp1 staining, whereas staining was absent in normal corneas. Compared to normal corneas, alpha1-PI and alpha2M immunostaining was lower in the lenticules, host, and keratoconus specimens. CONCLUSIONS: The epithelial cells and keratocytes repopulated in the lenticules retain keratoconus-like biochemical abnormalities such as upregulation of Sp1 and downregulation of alpha1-PI and alpha2M. The authors speculate that both keratocytes and the corneal epithelium may participate in the development of keratoconus.

Adolescent↗
PubMed2005

Ten year recurrence after first ever stroke in a Japanese community: the Hisayama study.

BACKGROUND: Very few population based cohort studies have focused on the long term recurrence of stroke. OBJECTIVE: To examine 10 year cumulative recurrence rates for stroke in a Japanese cohort according to pathological type and clinical subtype of brain infarction. METHODS: During a 32 year follow up of 1621 subjects >/=40 years of age, 410 developed first ever stroke. These were followed up prospectively for 10 years after stroke onset. RESULTS: During follow up, 108 (26%) experienced recurrent stroke. The cumulative recurrence rates were 35.3% at five years and 51.3% at 10 years. The 10 year recurrence rates of subarachnoid haemorrhage (SAH), brain haemorrhage, and brain infarction were 70.0%, 55.6%, and 49.7%, respectively; the difference between SAH and brain infarction was significant (p = 0.004). Most recurrent episodes after SAH or brain haemorrhage happened within a year after the index stroke, whereas recurrence of brain infarction increased consistently throughout the observation period. Cardioembolic stroke had a higher recurrence rate (75.2%) than lacunar infarction (46.8%) (p = 0.049). The 10 year risk of stroke recurrence increased with age after lacunar or atherothrombotic brain infarction, but not after the other types or subtypes. After atherothrombotic brain infarction, cardioembolic stroke, or SAH, the type and subtype of most recurrent strokes were the same as for the index stroke, but recurrence after lacunar infarction or brain haemorrhage showed divergent patterns. CONCLUSIONS: Japanese people have higher recurrence rates of stroke than other populations. Recurrence rate after a first brain infarct increases consistently through the next 10 years.

Adult↗
PubMed2005

Molecular and biomechanical characterization of mineralized tissue by dental pulp cells on titanium.

The application of implant therapy is still limited, because of various risk factors and the long healing time required for bone-titanium integration. This study explores the potential for osseointegration engineering with dental pulp cells (DPCs) by testing a hypothesis that DPCs generate mineralized tissue on titanium. DPCs extracted from rat incisors positive for CD44, alkaline phosphatase activity, and mineralizing capability were cultured on polystyrene and on machined and dual-acid-etched (DAE) titanium. Tissue cultured on titanium with a Ca/P ratio of 1.4 exhibited plate-like morphology, while that on the polystyrene exhibited fibrous and punctate structures. Tissues cultured on titanium were harder than those on polystyrene, 1.5 times on the machined and 3 times on the DAE. Collagen I, osteopontin, and osteocalcin genes were up-regulated on titanium, especially the DAE surface. In conclusion, DPCs showing some characteristics of the previously identified dental pulp stem cells can generate mineralized tissue on titanium via the osteoblastic phenotype, which can be enhanced by titanium surface roughness.

Acid Etching, Dental↗
PubMed2005

Growth kinetics and integrin expression of fibroblasts infiltrating devitalised patellar tendons are different from those of intrinsic fibroblasts.

We compared the biological characteristics of extrinsic fibroblasts infiltrating the patellar tendon with those of normal, intrinsic fibroblasts in the normal tendon in vitro. Infiltrative fibroblasts were isolated from the patellar tendons of rabbits six weeks after an in situ freeze-thaw treatment which killed the intrinsic fibroblasts. These intrinsic cells were also isolated from the patellar tendons of rabbits which had not been so treated. Proliferation and invasive migration into the patellar tendon was significantly slower for infiltrative fibroblasts than for normal tendon fibroblasts. Flow-cytometric analysis indicated that expression of alpha5beta1 integrin at the cell surface was significantly lower in infiltrative fibroblasts than in normal tendon fibroblasts. The findings suggest that cellular proliferation and invasive migration of fibroblasts into the patellar tendon after necrosis are inferior to those of the normal fibroblasts. The inferior intrinsic properties of infiltrative fibroblasts may contribute to a slow remodelling process in the grafted tendon after ligament reconstruction.

Animals↗
PubMed2005

CYP1A1 is a major enzyme responsible for the metabolism of granisetron in human liver microsomes.

Granisetron, a potent 5-HT3 receptor antagonist, has been reported to be mainly metabolized to 7-hydroxygranisetron and a lesser extent to 9'-desmethylgranisetron in humans. A previous study indicated that cytochrome P450 (CYP)3A4 is a major catalyst of 9'-demethylation, although the major CYP isoform(s) responsible for 7-hydroxylation are unknown. To clarify granisetron 7-hydroxylase, the in vitro metabolism of granisetron using expressed human CYPs and human liver microsomes was investigated. 7-Hydroxygranisetron was produced almost exclusively by CYP1A1, while, apparently, 9'-desmethylgranisetron was preferentially produced by CYP3A4. Marked inter-individual differences in the ratio of the formation of 7-hydroxygranisetron and 9'-desmethylgranisetron in human liver microsomes was observed. Granisetron 7-hydroxylase activity was strongly correlated with benzo[a]pyrene 3-hydroxylase activity (p<0.0001), but not with testosterone 6beta-hydroxylase activity in human liver microsomes. Furthermore, an anti-human CYP1A1 antibody completely inhibited 7-hydroxylation in human liver microsomes, however, the reaction was not inhibited at all by an anti-CYP3A4 antibody. On the other hand, granisetron 9'-demethylase activity correlated significantly not only with testosterone 6beta-hydroxylase activity (p<0.0001) but also with benzo[a]pyrene 3-hydroxylase activity (p<0.01). Consistent with this, both the anti-CYP1A1 and anti-human CYP3A4 antibodies inhibited the 9'-demethylase activity. These data indicate that CYP1A1 is a major enzyme responsible for the metabolism of granisetron via a main 7-hydroxylation pathway and an alternative 9'-demethylation route. This is the first report demonstrating the substantial contribution of CYP1A1 to the metabolism of a drug, although its role in the metabolism of environmental compounds is well established.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed2005

Pulmonary alveolar microlithiasis: CT and pathologic findings in 10 patients.

BACKGROUND AND AIM: To evaluate CT findings of pulmonary alveolar microlithiasis and correlate the CT with the pathologic findings. METHODS: The study included 10 patients with pathologically proven microlithiasis. Two independent observers evaluated the presence, extent and distribution of the CT findings. CT findings were compared with those at autopsy in two patients and with transbronchial biopsy in eight patients. RESULTS: All patients had a myriad of calcified nodules measuring approximately 1 mm in diameter. Close apposition of the nodules resulted in areas of ground-glass attenuation and consolidation, which were the predominant abnormality on CT in all 10 patients, involving 41% +/- 16.3 (mean +/- SD) and 30% +/- 4.8 of the lung parenchyma, respectively. Calcifications were also seen along interlobular septa, bronchovascular bundles and pleura. Other findings included interlobular septal thickening, thickening of bronchovascular bundles, nodules, and subpleural cysts. There was a solid agreement between the observers for the presence (kappa value; 0.77) and extent (Spearman rank correlation; r = 0.81 to 1.0 p < 0.01) of abnormalities. Autopsy specimens demonstrated microliths in alveolar airspaces and along interlobular septa, bronchovascular bundles and pleura. Subpleural small cysts were shown to represent dilated alveolar ducts. CONCLUSION: Pulmonary microlithiasis is characterised by the presence of numerous small, calcified nodules, calcifications along interlobular septa, bronchovascular bundles and pleura, ground-glass opacities, consolidation, and subpleural cysts. The cysts represent dilated alveolar ducts.

Adult↗
PubMed2005

Perineal-onset Fournier's gangrene in a patient undergoing hemodialysis--importance of perineal-onset manifestation.

We present a rare case of perineal-onset Fournier's gangrene in a patient undergoing hemodialysis. A 51-year-old Japanese man manifested an acute-onset perineal pain with perirectal abscess; subsequently, the pain extended to the abdomen, chest, and loin despite quick treatment. His consciousness deteriorated to delirium and he died of septic shock on the third day of admission. Computed tomography (CT) revealed soft-tissue air along the right rectal wall, moreover, the infection extended to the anterior wall of the bladder and the right peripsoas muscle. On the basis of the clinical course and CT findings, the patient was diagnosed as having the complications of Fournier's gangrene, however, no scrotal lesions were detected. Fournier's gangrene is considered to be easily diagnosed on the basis of skin lesions, such as scrotal erythema and swelling. However, in the early stage, the diagnosis of Fournier's gangrene is difficult in a patient with perineal pain before the detection of skin lesions. In conclusion, definitely the key to improving the prognosis of this fulminant infection is the prompt recognition of the pathological process. Therefore, Fournier's gangrene should always be considered when patients undergoing hemodialysis manifest perirectal disorders, even when no scrotal lesions are detected, because there is the possibility of intra-abdominal and intra-retroperitoneal infections resulting in septic shock.

Abscess↗
PubMed2005

Roles of and correlation between alpha-smooth muscle actin, CD44, hyaluronic acid and osteopontin in crescent formation in human glomerulonephritis.

BACKGROUND: alpha-Smooth muscle actin (SMA), CD44, hyaluronic acid (HA) and osteopontin (OPN) are involved in crescent formation; however, the correlation between these molecules during the formation and progression of the crescents in human glomerulonephritis (GN) has not been fully evaluated. METHODS: To investigate the expression of alpha-SMA, CD44, HA, OPN and CD68 renal biopsy specimens from 14 patients with crescentic GN were examined by immunohistochemistry. All crescents were separated into cellular, fibrocellular and fibrous. The extent of staining in each crescent was scored semiquantitatively. The change in the expression of each molecule and its correlation with other molecules during the formation and progression of the crescents were estimated statistically. RESULTS: The expression of alpha-SMA was significantly up-regulated in the fibrocellular crescents compared with that in the cellular and fibrous crescents. The expression of CD44, OPN and CD68 was significant in the cellular crescents compared with that in the fibrocellular and fibrous crescents. The deposition of HA in the three groups of crescents was high level. However, that of HA was not significant among three groups of crescent. The expression of CD44 in the cellular crescents correlated significantly with the expression of OPN and CD68, and the deposition of HA in the cellular crescents. The expression of OPN in the cellular crescents correlated with the deposition of HA and the expression of CD68 in the cellular crescents. The expression of alpha-SMA in the cellular and fibrocellular crescents correlated with the deposition of HA in the cellular and fibrocellular crescents. CONCLUSION: The expression of CD44, HA, OPN and CD68 was up-regulated at the early stage of the crescent formation in human crescentic GN. Moreover, myofibroblasts and cell-matrix interactions mediated by the CD44-OPN and CD44-HA receptor-ligand pairs may play important roles in the formation and progression of the crescents.

Actins↗
PubMed2004

Plasma devices to guide and collimate a high density of MeV electrons.

The development of ultra-intense lasers has facilitated new studies in laboratory astrophysics and high-density nuclear science, including laser fusion. Such research relies on the efficient generation of enormous numbers of high-energy charged particles. For example, laser-matter interactions at petawatt (10(15) W) power levels can create pulses of MeV electrons with current densities as large as 10(12) A cm(-2). However, the divergence of these particle beams usually reduces the current density to a few times 10(6) A cm(-2) at distances of the order of centimetres from the source. The invention of devices that can direct such intense, pulsed energetic beams will revolutionize their applications. Here we report high-conductivity devices consisting of transient plasmas that increase the energy density of MeV electrons generated in laser-matter interactions by more than one order of magnitude. A plasma fibre created on a hollow-cone target guides and collimates electrons in a manner akin to the control of light by an optical fibre and collimator. Such plasma devices hold promise for applications using high energy-density particles and should trigger growth in charged particle optics.

Journal Article↗