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Biomedical subjects

M Fukuda

Publications and source records attributed to M Fukuda.

At least 19 recordsLinked to original sources

Induction of apoptosis and cellular senescence in mice lacking transcription elongation factor, Elongin A.

Elongin A is a transcription elongation factor that increases the overall rate of mRNA chain elongation by RNA polymerase II. To gain more insight into the physiological functions of Elongin A, we generated Elongin A-deficient mice. Elongin A homozygous mutant (Elongin A(-/-)) embryos demonstrated a severely retarded development and died at between days 10.5 and 12.5 of gestation, most likely due to extensive apoptosis. Moreover, mouse embryonic fibroblasts (MEFs) derived from Elongin A(-/-) embryos exhibited not only increased apoptosis but also senescence-like growth defects accompanied by the activation of p38 MAPK and p53. Knockdown of Elongin A in MEFs by RNA interference also dramatically induced the senescent phenotype. A study using inhibitors of p38 MAPK and p53 and the generation of Elongin A-deficient mice with p53-null background suggests that both the p38 MAPK and p53 pathways are responsible for the induction of senescence-like phenotypes, whereas additional signaling pathways appear to be involved in the mediation of apoptosis in Elongin A(-/-) cells. Taken together, our results suggest that Elongin A is required for the transcription of genes essential for early embryonic development and downregulation of its activity is tightly associated with cellular senescence.

Animals↗

No significant difference in neutrophil activation found among three H2RAs.

BACKGROUND: Even with the most effective treatment, Helicobacter pylori eradication is difficult in some patients. Therefore, patients sometimes require acid-suppressive therapy without H. pylori eradication. It has been reported that ranitidine inhibits neutrophil activation, whereas famotidine does not. However, few studies have been published concerning the activation of neutrophils before and after treatment using clinical doses of histamine-2 receptor antagonists in patients with H. pylori infection. AIM: To examine the effects of neutrophil activation after treatment with three different histamine-2 receptor antagonists. PATIENTS: This prospective, open-label, randomised, parallel-group study was conducted. Thirty patients with H. pylori infection were enrolled. These subjects were randomly assigned to receive one of the following treatments: (a) 150 mg ranitidine, (b) 20mg famotidine, or (c) 10 mg lafutidine b.d., for 4 weeks. Before and after histamine-2 receptor antagonist treatment, histological findings, myeloperoxidase activity, and interleukin-8 in the gastric mucosa were evaluated. RESULTS: On the basis of the histological findings between before and after histamine-2 receptor antagonist treatment, no significant differences were found in any groups. Similarly, there were no significant differences in myeloperoxidase activity or interleukin-8 levels. CONCLUSION: In patients with H. pylori, when used at clinical doses, any histamine-2 receptor antagonists can be used without concerning about inhibition of neutrophil activation.

Acetamides↗

Study on the vibrational energy relaxation of p-nitroaniline, N,N-dimethyl-p-nitroaniline, and azulene by the transient grating method.

The vibrational energy dissipation processes of the electronic ground states of p-nitroaniline and N,N-dimethyl-p-nitroaniline have been studied by transient grating spectroscopy with subpicosecond laser pulses. The rise time of the acoustic signal produced by the energy dissipation process of the hot ground state molecule was monitored. The acoustic signal was analyzed by an equation including the acoustic damping. The solvent temperature rise times in various solvents have been determined. The acoustic signals of azulene in previous papers [Y. Kimura et al., J. Chem. Phys. 123, 054512 (2005); 123, 054513 (2005)] were also reanalyzed using this equation. The temperature rise times in all cases are longer than the vibrational energy relaxation times of the solutes determined by the transient absorption measurements. The difference is discussed in terms of the energy transfer pathways from the solute to the solvent. We concluded that both the hydrogen bonding between the solute and the solvent and the lower frequency modes of the solutes play important roles in determining the energy transfer pathway from the solute to the solvent.

Journal Article↗

Ruptured intracranial aneurysm following gamma knife surgery for acoustic neuroma.

A-63-year-old woman underwent gamma knife surgery (GKS) for acoustic neuroma. Six years later, she suffered sudden onset of severe headache followed by a disturbance of consciousness and subarachnoid haemorrhage due to a ruptured aneurysm originating from the distal anterior inferior cerebellar artery. The aneurysm was not located at a branching site and was included within the radiation field. The aneurysm was treated by endovascular embolization, and now, 15 months later, the patient has recovered satisfactorily. This is the first report of aneurysm formation following GKS for acoustic neuroma.

Basilar Artery↗

Phase II study of irinotecan combined with carboplatin in previously untreated small-cell lung cancer.

To determine the efficacy and toxicity of irinotecan combined with carboplatin, we conducted a phase II trial. Eligibility criteria were: chemotherapy-naïve, small-cell lung cancer (SCLC), good performance status (PS: 0-2), age<or=75 years, and adequate organ function. The patients' characteristics were: male/female=56/5; PS 0/1/2=19/38/4; median age (range)=68 years(51-75 years); limited disease (LD)/extensive disease (ED)=27/34. The patients received irinotecan (50 mg m-2) on days 1, 8, and 15, and carboplatin (AUC 5, Chatelut formula) on day 1 every 4 weeks. In total, 61 patients were eligible and all were evaluated. In all, 31 patients were treated with four or more courses of chemotherapy. Of the patients, 17 showed a complete response (CR), 34 showed a partial response (PR), nine had stable disease (SD), and one had progressive disease (PD). The overall response rate was 84% (95% confidence interval (CI), 72-91%; LD 89%, ED 79%) and the CR rate was 28% (95%CI, 17-41%; LD 37%, ED 21%). The median time to tumour progression was 6.1 (LD 6.4, ED 5.4) months. The medial survival time was 15.0 (LD 20.0, ED 9.7) months, and the 2-year and 5-year survival rates were 31.1% (LD 48.1%, ED 17.7%) and 9.5% (LD 11.1%, ED 5.9%), respectively. Grade 3 or 4 leucopenia, neutropenia, thrombocytopenia, anaemia, and diarrhoea occurred in 33, 74, 41, 39, and 13% of cases, respectively. In conclusion, the combination of irinotecan and carboplatin is an active and well-tolerated regimen in cases of SCLC.

Aged↗

Efficient propagation of polarization from laser photons to positrons through compton scattering and electron-positron pair creation.

We have demonstrated for the first time the production of highly polarized short-pulse positrons with a finite energy spread in accordance with a new scheme that consists of two-quantum processes, such as inverse Compton scattering and electron-positron pair creation. Using a circularly polarized laser beam of 532 nm scattered off a high-quality, 1.28 GeV electron beam, we have obtained polarized positrons with an intensity of 2 x 10(4) e+ /bunch. The magnitude of positron polarization has been determined to be 73 +/- 15(stat) +/- 19(syst)% by means of a newly designed positron polarimeter.

Journal Article↗

Rab27 and its effectors in secretory granule exocytosis: a novel docking machinery composed of a Rab27.effector complex.

A small GTPase Rab27 is present on secretory granules in a wide variety of secretory cells and on melanosomes in melanocytes, and it is involved in controlling the trafficking of these organelles through interaction with a cell-type- or tissue-specific Rab27 effector(s). Slps (synaptotagmin-like proteins) and rabphilin contain an N-terminal Rab27-binding domain and C-terminal tandem C2 domains, and some of the Rab27-binding proteins have recently been shown to promote docking of Rab27-bound organelles to the plasma membrane. This mini-review presents a model for how the Rab27.effector complex controls the docking step in the trafficking of Rab27-bound organelles. Our results indicate that Slp2-a, Slp4-a/granuphilin-a and rabphilin are capable of interacting with the plasma membrane directly or indirectly, and thus that these Rab27 effectors form a bridge between Rab27-bound organelles and the plasma membrane.

Animals↗

Isolation and characterization of synovial cells from the human temporomandibular joint.

BACKGROUND: The synovial tissues with temporomandibular disorders (TMDs) often show chronic inflammatory changes and the synovial cells participate in the pathogenic processes of TMDs. The synovial membrane is composed of a synovial lining layer and a connective sublining layer. The synovial lining layer is made up of two kinds of cells: macrophage-like type A and fibroblastic type B cells. The aim of this study was to isolate and characterize synovial cells from the human temporomandibular joint (TMJ). METHODS: Synovial cells were isolated using an explant culture method. Then, we characterized the cultured synovial cells (SGA2 cells) using immunocytochemistry. RESULTS: SGA2 cells expressed the fibroblastic markers vimentin and prolyl 4-hydroxylase; they also expressed laminin and heat shock protein 27, all of which are markers of type B cells. However, some cells expressed the macrophage marker CD68. These CD68-positive cells simultaneously expressed laminin. CONCLUSIONS: We isolated and cultured synovial type B cells from the human TMJ, and identified the presence of intermediate type synovial lining cells, having the phenotypic properties of both type A and type B cells, among the synovial lining cells.

Antigens, CD↗

Evaluation of the position, mobility, and morphology of the disc by MRI before and after four different treatments for temporomandibular joint disorders.

OBJECTIVES: The purpose of this study was to evaluate changes in disc position, mobility, and morphology in patients with temporomandibular joint disorders (TMD) in response to four different treatments, splint therapy, pumping manipulation, arthrocentesis, and arthroscopic surgery, using magnetic resonance imaging (MRI). METHODS: Eighty-five joints (85 patients) with unilateral internal derangement or osteoarthritis that were successfully treated were included in this study. The patients were divided into four groups as follows: splint therapy group, pumping manipulation group, arthrocentesis group, and arthroscopic surgery group. Changes in the disc position, mobility, and morphology before and after treatment were compared among the four groups using MRI. RESULTS: All discs showed anterior disc displacement (ADD) without reduction before treatment. Only 10% of the joints became ADD with reduction after treatment, and the other joints remained ADD without reduction in spite of treatment. Discs treated by arthroscopic surgery were located more anteriorly compared with pre-treatment. In pre-treatment MRI, the rate of stuck disc increased as the stage of the treatment advanced. In post-treatment MRI, all temporomandibular joints (TMJs) had mobile discs. The disc deformity advanced after arthrocentesis and arthroscopic surgery. CONCLUSIONS: Even though clinical signs and symptoms were alleviated by treatment, most discs remained ADD without reduction on MRI in spite of treatment. This suggests that the four treatments do not necessarily improve the position and deformity of the disc, and that arthroscopic surgery advances the deformity and anterior displacement of the disc. Disc mobility is important for improving clinical signs and symptoms.

Adolescent↗

PR3-ANCA-positive crescentic necrotizing glomerulonephritis accompanied by isolated pulmonic valve infective endocarditis, with reference to previous reports of renal pathology.

Patients with infective endocarditis (IE) often have renal complications which may include infarcts, abscesses and glomerulonephritis (GN). Furthermore, it is generally accepted that there is an association between IE and anti-neutrophil cytoplasmic antibody (ANCA). Here, we report the case of a 24-year-old man who developed rapidly progressive GN in the course of IE due to infection with alpha-streptococcus. The initial clinical manifestation of the condition was severe sacroiliitis without fever. Sandwich ELISA showed that the patient was positive for PR3-ANCA at low titer, and the classical complement pathway was also activated. Renal biopsy demonstrated several lesions: focal embolic GN, GN with immune deposits and focal and segmental crescentic necrotizing GN. Treatment with antibiotics and steroids led to eradication of the infection, and resolution of the renal disease was accompanied by immediate disappearance of PR3-ANCA and hypocomplementemia. During a 4-year follow-up period, no recurrence was observed. There have only been 7 case reports of GN associated with IE and PR3-ANCA in which the renal pathology has been described, and the current report is the first to document renal pathology in a patient with isolated pulmonic valve IE and PR3-ANCA. Moreover, this report is the first to show a change in renal biopsy findings in response to treatment. A review of the 7 literature cases and that of our patient showed that none involved pauci-immune GN. Hence, further studies are needed to clarify the prevalence of pauci-immune GN in ANCA-positive IE patients.

Adult↗

Abnormal muscle response monitoring during microvascular decompression for hemifacial spasm.

BACKGROUND: Several studies have investigated the relation between intraoperative abnormal muscle response (AMR) findings and postoperative results in patients undergoing microvascular decompression (MVD) for hemifacial spasm (HFS). However, there is some debate over the reliability of AMR as an indicator of postoperative outcome. We investigated whether AMR findings obtained during MVD reflect postoperative outcome in patients with HFS. METHOD: Subjects were 60 HFS patients who underwent AMR monitoring during MVD. AMR recordings were obtained from the mentalis muscle by electrical stimulation of the temporal branch of the facial nerve and from the orbicularis oculi muscles by stimulation of the marginal mandibular branch. Surgical outcome was compared with AMR findings at the completion of MVD. Mean follow-up was 61 months. FINDINGS: HFS resolved completely in 50 patients in whom AMR disappeared intraoperatively and in 5 patients in whom the AMR amplitude was decreased at the end of MVD. Four patients showed HFS at the final follow-up examination despite cessation or decrease of AMR during surgery. In 1 patient, preoperative AMR waveforms persisted throughout MVD, but the postoperative outcome was excellent. CONCLUSIONS: Our findings suggest that intraoperative cessation or decreased amplitude of AMR at the end of surgery indicates a high likelihood of postoperative relief of HFS. We believe that intraoperative AMR monitoring is useful in MVD surgery for HFS.

Adult↗

The transport mechanisms of (222)Rn in soil at Tateishi as an anomaly spot in Japan.

The (222)Rn concentration profiles in soil have been measured at an anomaly spot in Tateishi, Japan. In winter, the concentrations were low and showed a negative gradient with depth, but in other seasons, the concentration had both positive and negative gradients with depth, and dramatically changed by time. On the assumption that there was ventilation in deep layers and with driving forces of wind and temperatures, these phenomena were successfully explained. This finding would contribute to a numerical model for (222)Rn transport in soil.

Computer Simulation↗

Odor-concentration coding in the guinea-pig piriform cortex.

By optical imaging of intrinsic signals, we demonstrated a possible code for odor concentration in the anterior piriform cortex of the guinea-pig. Odor-induced cortical activation, which primarily originated in layer II, appeared in a narrow band beneath the rhinal sulcus over the lateral olfactory tract, corresponding to the dorsal part of the anterior piriform cortex. Lower concentrations activated the rostral region of the band, whereas higher ones generated caudally spreading activation, and the site at which neural activation reached its maximum extent depended upon odor concentration. Different odors with low concentrations generated distinct but somewhat overlapping patterns in the rostral region of the band; the limited extent of cortical activity may be one focal domain for each odor. It was hard to judge, however, that odor-specific domains appeared in the anterior piriform cortex, because the strong stimuli induced largely overlapping patterns. Furthermore, the total area activated increased in proportion to concentrations raised to a power of 0.5-0.9. Importantly, these imaging results were confirmed with unit recordings which indicated a rostro-caudal gradient in odor-sensitivity among cortical neurons. Our results suggest that the dorsal part of the anterior piriform cortex may be associated with odor concentration. Therefore, in addition to recruitment of more olfactory sensory cells and glomeruli in response to stronger stimuli, a rostro-caudal gradient in axonal projections from mitral/tufted cells and/or in association fibers may play an important role in odor-concentration coding in the anterior piriform cortex.

Animals↗

HPA axis normalization, estimated by DEX/CRH test, but less alteration on cerebral glucose metabolism in depressed patients receiving ECT after medication treatment failures.

OBJECTIVE: To examine the clinical effects of electroconvulsive therapy (ECT) on depressed patients with medication treatment failures, we investigated the alterations in hypothalamic-pituitary-adrenocortical (HPA) function and regional cerebral metabolism rate of glucose (rCMRGlu) after ECT in these patients. METHOD: Before and after ECT, the combined dexamethasone/corticotrophin-releasing hormone (DEX/CRH) test was administered to seven patients who were referred for ECT. In the same patients, (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) was also assessed. RESULTS: Cortisol response in the DEX/CRH test significantly decreased after a successful ECT. A significant hypometabolism in various frontal regions and hypermetabolism in the parietal regions of these patients when compared with controls remained after ECT. CONCLUSION: Depressed patients who failed trials of antidepressant medication showed a remission with ECT that was accompanied by resolution of HPA dysregulation. However, measures of cerebral brain metabolism did not resolve.

Anti-Inflammatory Agents↗

Immunotactoid glomerulopathy with microtubular deposits, with reference to the characteristics of Japanese cases.

We present the case of a 69-year-old man with nephrotic syndrome and renal insufficiency, who developed lobular glomerulonephritis. An electron microscopy examination of a renal biopsy showed microtubular structures of 24 nm in diameter in the subendothelial space and the paramesangial area. These deposits were PAS-positive and Congo red-negative, and revealed predominantly positive staining for kappa light chain. There was no evidence of diseases with highly organized glomerular deposits, such as amyloidosis, cryoglobulinemia, systemic lupus erythematosus or paraproteinemia. Therefore, the patient was diagnosed to have immunotactoid glomerulopathy (ITG). During a seven-year course he has not developed any disease known to be associated with organized glomerular immune deposits. Hence, we believe ITG occurred as a primary glomerular disease in this case. We also highlight cases of ITG with microtubular deposits that have been reported in Japan, compare these cases to previous reports, and show that the characteristics of the Japanese cases are male predominance; a high incidence of membranoproliferative glomerulonephritis (MPGN); a low incidence of monoclonal gammopathy and hematological malignancies and a higher incidence of hypocomplementemia.

Aged↗

Achievement of ultralow emittance beam in the accelerator test facility damping ring.

For high luminosity in electron-positron linear colliders, it is essential to generate low vertical emittance beams. We report on the smallest vertical emittance achieved in single-bunch-mode operation of the Accelerator Test Facility, which satisfies the requirement of the x-band linear collider. The emittances were measured with a laser-wire beam-profile monitor installed in the damping ring. The bunch length and the momentum spread of the beam were also recorded under the same conditions. The smallest vertical rms emittance measured at low intensity is 4 pm at a beam energy of 1.3 GeV, which corresponds to the normalized emittance of 1.0x1.0(-8) m. It increases by a factor of 1.5 for a bunch intensity of 10(10) electrons. The measured data agreed to the calculation of intrabeam scattering within much better than a factor of 2.

Journal Article↗

Immunohistochemical localization of cyclooxygenase-1 and -2 in synovial tissues from patients with internal derangement or osteoarthritis of the temporomandibular joint.

This study examined the immunohistochemical expression and localization of cyclooxygenase-1 and -2 (COX-1 and COX-2) in synovial tissues from patients with internal derangement (ID) or osteoarthritis (OA) of the temporomandibular joint (TMJ). Synovial tissues from patients with condylar fractures of the mandible were studied as control. Synovial tissues from 13 TMJs of 10 patients with ID or OA and from 5 TMJs of 4 patients with fractures were examined for COX-1 and COX-2 expression by immunohistochemical staining using two monoclonal antibodies. In addition, whether the COX-2 expression grade correlated with the synovitis score and clinical findings was assessed. COX-2 was expressed in the synovial lining, infiltrating mononuclear cells, fibroblast-like cells, and blood vessels, including CD31-positive endothelial cells, in the synovium of patients with ID or OA. Expression levels of COX-1 in synovial lining cells and endothelial cells were similar in the specimens obtained from the patients with ID or OA and those obtained from the controls. The expression of COX-2 positively correlated with arthroscopic findings of synovitis (p = 0.55, P = 0.023) and with joint pain (p = 0.56, P = 0.021). These results suggest that up-regulation of COX-2 in synovium may play a part in the pathogenesis of synovitis in patients with ID or OA of the TMJ.

Adult↗