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Biomedical subjects

T Inoue

Publications and source records attributed to T Inoue.

At least 19 recordsLinked to original sources

Prism adaptation to optical deviation alleviates pathologic pain.

BACKGROUND: The human visual and somatosensory systems are interdependent. Using a visual subjective body-midline (SM) judgment task, we previously confirmed that pathologic pain and deafferentation can modify visuospatial perception, indicating that altered somatosensory experience can modify visual perception. Conversely, in the present study we investigated whether a change in visual experience can modify perception of pathologic pain. METHODS: We used prism adaptation (PA) to modify subjects' visual experience. Five patients with complex regional pain syndrome (CRPS) adapted to wedge prisms, producing a 20-degree visual displacement toward the unaffected side. Further, we used several types of prisms in a longitudinal single-case study. Wearing prismatic goggles, the subjects performed a target-pointing task once a day for 2 weeks. We evaluated pain intensity and visual SM judgment to measure the adaptive aftereffects at three time points: before PA (pre-test), immediately after the first PA exposure (IA-test), and after a 14-day sequence of PA exposure (post-test). RESULTS: PA toward the unaffected side alleviated pathologic pain and other CRPS pathologic features, when measured at post-test. None of the IA-test results showed an analgesic effect. In the longitudinal study, sham PA and 5-degree PA did not produce any effects, and PA toward the affected side actually exacerbated the subjective pain. CONCLUSIONS: Our findings suggest that vision can influence pathologic pain, and preliminarily suggest that prism adaptation has a direction-specific and reproducible effect on not only pathologic pain but also other CRPS pathologic features. Thus, prism adaptation may be a viable cognitive treatment for CRPS.

Adaptation, Physiological↗

Pathologic pain distorts visuospatial perception.

Spatial perception is achieved by integrating multisensory information. Using visual subjective body midline (vSM) judgments in patients with unilateral limb pain (complex regional pain syndrome [CRPS]), we found that their vSM deviated toward the affected side; however, deafferentation of the affected limb caused a transient pain decrease and a transient shift of the vSM deviation toward the unaffected side. Our results indicate that the persistent pain state in CRPS distorts visuospatial perception.

Adaptation, Physiological↗

SIRT2, a tubulin deacetylase, acts to block the entry to chromosome condensation in response to mitotic stress.

We previously identified SIRT2, an nicotinamide adenine dinucleotide (NAD)-dependent tubulin deacetylase, as a protein downregulated in gliomas and glioma cell lines, which are characterized by aneuploidy. Other studies reported SIRT2 to be involved in mitotic progression in the normal cell cycle. We herein investigated whether SIRT2 functions in the mitotic checkpoint in response to mitotic stress caused by microtubule poisons. By monitoring chromosome condensation, the exogenously expressed SIRT2 was found to block the entry to chromosome condensation and subsequent hyperploid cell formation in glioma cell lines with a persistence of the cyclin B/cdc2 activity in response to mitotic stress. SIRT2 is thus a novel mitotic checkpoint protein that functions in the early metaphase to prevent chromosomal instability (CIN), characteristics previously reported for the CHFR protein. We further found that histone deacetylation, but not the aberrant DNA methylation of SIRT2 5'untranslated region is involved in the downregulation of SIRT2. Although SIRT2 is normally exclusively located in the cytoplasm, the rapid accumulation of SIRT2 in the nucleus was observed after treatment with a nuclear export inhibitor, leptomycin B and ionizing radiation in normal human fibroblasts, suggesting that nucleo-cytoplasmic shuttling regulates the SIRT2 function. Collectively, our results suggest that the further study of SIRT2 may thus provide new insights into the relationships among CIN, epigenetic regulation and tumorigenesis.

Cell Line, Tumor↗

Ischaemic stroke with malignancy may often be caused by paradoxical embolism.

BACKGROUND: Although ischaemic stroke with malignancy occasionally occurs, the mechanisms of stroke in such cases have not been investigated in detail. OBJECTIVE: To examine the mechanisms of ischaemic stroke with malignancy, particularly in relation to right-to-left shunt (RLS). METHODS: Consecutive patients with ischaemic stroke within 24 h of stroke onset were prospectively studied. Contrast saline transcranial Doppler examination was carried out for all patients, to investigate the presence of RLS. When patients with stroke had RLS, deep venous thrombosis (DVT) or pulmonary embolism was assessed to diagnose paradoxical brain embolism. RESULTS: Participants comprised 184 consecutive patients (115 men and 69 women) with a mean (standard deviation (SD)) age of 73 (11.8) years and mean (SD) National Institutes of Health Stroke Scale (NIHSS) score of 8 (7.4). RLS was detected in 32 of 184 (18%) patients. Malignancy was present in 11 (5%) patients. RLS was more frequent in patients with malignancy than in patients without malignancy (55% v 15%, respectively; p = 0.001). All six patients with RLS and malignancy displayed DVT or pulmonary embolism with severe disability (modified Rankin Scale 4-5) before stroke onset. CONCLUSION: Paradoxical brain embolism should be considered to be an important mechanism in patients with stroke and malignancy.

Aged↗

Alterations in D-amino acid levels in the brains of mice and rats after the administration of D-amino acids.

To mutant ddY/DAO(-) mice lacking D-amino-acid oxidase activity and normal ddY/DAO(+) mice, five D-amino acids (D-Asp, D-Ser, D-Ala, D-Leu and D-Pro) were orally administered for two weeks, and the D-amino acid levels were examined in seven brain regions. The levels of D-Asp markedly increased in the pituitary and pineal glands in both strains. In the ddY/DAO(+) mice, the levels of the other D-amino acids did not significantly change in most of the brain regions. While in the ddY/DAO(-) mice the levels of D-Ser significantly increased in most of the brain regions except for the cerebrum and hippocampus. The levels of D-Ala and D-Leu increased in all regions but the levels of D-Pro did not significantly change. The same five D-amino acids were intravenously injected into Wistar rats and the D-amino acid levels in their brains were examined for 60 min after the administration. The levels of D-Asp markedly increased in the pineal gland 3 min after the administration, while the levels of D-Ser, D-Ala, and D-Pro increased both in the pineal and pituitary glands, the levels of D-Leu increased in all brain regions. These results are useful for the elucidation of the origins and regulation of D-amino acids in the mammalian body.

Amino Acids↗

The monitoring of insects to maintain biodiversity in Ogawa Fores Reserve.

The results of a biodiversity monitoring program conducted in the Ogawa Forest Reserve and its vicinity, situated in a cool temperate region of Japan, identified three different patterns for species richness. Forests of the region are characterized by a mosaic of secondary deciduous stands of various ages scattered among plantations of conifers. The three different types of change in species richness observed in response to the stand age are as follows: Type I (butterflies, tube-renting bees and wasps, hoverflies, fruit flies, and longicorn beetles), the species diversity was highest in open areas, just after clear-cutting, decreasing with the stand age; Type II (mushrooms and mites associated with them), older stands showed greater diversity than younger stands; and, Type III (moths, oribatid mites, collembolas, carabid beetles, and ants), the number of species did not change greatly with the stand age, though ordination analysis revealed that there was variation in species compositions. These results indicate that combinations of stands of different ages, or heterogeneously arranged stands, can contribute to the maintenance of insect biodiversity at the landscape level.

Animals↗

Effect of prophylactic bronchodilator treatment with i.v. carperitide on airway resistance and lung compliance after tracheal intubation.

BACKGROUND: Lung resistance increases after induction of anaesthesia. We hypothesized that prophylactic bronchodilation with i.v. carperitide before tracheal intubation would decrease airway resistance and increase lung compliance after placement of the tracheal tube in both smokers and nonsmokers. METHODS: Ninety-seven adults aged between 24 and 59 yr were randomized to receive i.v. normal saline (0.9% saline) (control) or carperitide, 0.2 microg kg(-1) min(-1) throughout the study. The 97 patients included smokers and nonsmokers. Thus the patients were allocated to one of the four groups: smokers who received normal saline (n=21), nonsmokers who received normal saline (n=27), smokers who received carperitide (n=19) or nonsmokers who received carperitide (n=30). Thirty minutes after starting normal saline or carperitide infusion, we administered thiamylal 5 mg kg(-1) and fentanyl 5 microg kg(-1) to induce general anaesthesia and vecuronium 0.3 mg kg(-1) for muscle relaxation. Continuous infusion of thiamylal 15 mg kg(-1) h(-1) followed anaesthetic induction. Mean airway resistance (R(awm)), expiratory airway resistance (R(awe)) and dynamic lung compliance (C(dyn)) were determined 4, 8, 12 and 16 min after tracheal intubation and compared between the four groups. RESULTS: At 4 min after intubation, R(awm) and R(awe) were higher and C(dyn) lower in smokers than in nonsmokers in the control group. R(awm) and R(awe) were lower and C(dyn) higher in smokers in the carperitide group than in smokers in the control group. R(awm) and R(awe) were lower in nonsmokers in the carperitide group than in nonsmokers in the control group. CONCLUSIONS: Marked bronchoconstriction occurred in the control groups (smokers and nonsmokers) 4 min after tracheal intubation. Prophylactic treatment with carperitide before induction of anaesthesia and tracheal intubation was advantageous, particularly in smokers.

Adult↗

Citrullinated fibrinogen detected as a soluble citrullinated autoantigen in rheumatoid arthritis synovial fluids.

BACKGROUND: Anti-citrullinated protein antibodies (ACPA) are specifically and frequently detected in sera of patients with rheumatoid arthritis (RA). Citrullinated fibrin or fibrinogen is a candidate autoantigen of such antibodies. OBJECTIVE: To investigate the presence of citrullinated fibrinogen (cFBG) in the plasma or synovial fluid of patients with RA and control patients, and to determine cFBG levels and their relationship with serum markers for RA if it is present. METHODS: A sandwich enzyme linked immunosorbent assay (ELISA) to measure cFBG was established using monoclonal antibodies cF16.1 and cF252.1, generated by immunising mice with R16Cit and R252Cit, the fibrinogen Aalpha chain derived sequences with citrulline at position 16 and 252, respectively, and the presence of cFBG was further investigated with immunoprecipitation-western blotting. RESULTS: Positive signals were detected in 11/15 RA synovial fluids (RASFs), but not in osteoarthritis synovial fluids or RA plasma with sandwich ELISA for cFBG using cF16.1 and an anti-modified citrulline (AMC) antibody. The presence of cFBG in RASFs was confirmed by immunoprecipitation-western blotting. Furthermore, most RA sera strongly reacted against R16Cit. No relationship was seen between RASF cFBG levels and C reactive protein or anti-cyclic citrullinated peptide antibody levels of the paired sera. CONCLUSION: cFBG is detected as a soluble citrullinated autoantigen in RASFs and may therefore be a genuine candidate antigen for ACPA in patients with RA.

Animals↗

Basic and clinical research on photodynamic therapy at Tokyo Medical University Hospital.

BACKGROUND AND OBJECTIVES: We have been engaged in basic and clinical research on photodynamic therapy (PDT) and photodynamic diagnosis (PDD) for more than 25 years. STUDY DESIGN/MATERIALS AND METHODS: PDT for 264 centrally located early-stage lung cancer lesions yielded an initial complete response (CR) rate of 84.8%. PDT is now becoming a standard option for centrally located stage 0 (TisN0M0) and stage I (T1N0M0) lung cancer. It is an attractive option for elderly patients in poor physical condition. RESULTS: Recent results of interstitial PDT for peripheral-type lung cancers suggest that it may be a promising local curative treatment modality for lesions less than 1.0 cm in diameter. CONCLUSIONS: In this article, we introduce our recent clinical trials of PDT for lung cancers (both central and peripheral), and new techniques of PDD in sentinel node navigation biopsy for breast cancers. Moreover, we introduce basic research on cancers and infectious diseases in order to expand the clinical applications of PDT.

Adult↗

Biphasic clinical course and early white matter abnormalities may be indicators of neurological sequelae after status epilepticus in children.

Clinical course and serial neuroimaging findings are not fully described in children who have had neurological sequelae following status epilepticus. We found four patients who had neurological sequelae out of 42 children with status epilepticus in 2004. MRI studies were reviewed with specific attention to diffusion-weighted images (DWI) and the apparent diffusion coefficient (ADC). Proinflammatory cytokines, including tumor necrosis factor-alpha and interleukin-6, were measured in the cerebrospinal fluid (CSF) (3 patients). The clinical course showed biphasic; initial status epilepticus and neurological exacerbation along with seizure recurrence four to five days after onset. Within three days after initial status epilepticus, CT (all patients) and MRI (2 patients) did not show any abnormalities. From four to ten days after onset, MRI demonstrated diffuse hyperintensity in the cerebral white matter on DWI and hypointensity on ADC maps in all patients. Diffuse brain atrophy progressed thereafter. Tumor necrosis factor-alpha or interleukin-6 was elevated in all patients. A biphasic clinical course may be a specific feature for neurological sequelae. The preferential white matter involvement on MRI and elevated CSF cytokines indicate that glial dysfunction may play an important role in the pathophysiology of status epilepticus-associated cerebral damage.

Brain Mapping↗

Changes in the number of Merkel cells with the hair cycle in hair discs on rat back skin.

BACKGROUND: Hair discs are known to contain a large number of Merkel cells and are ideal for investigating Merkel cell biology. Hair follicles, which are important elements of hair discs, undergo unique cyclical morphological and biological changes. OBJECTIVES: To define the relationships between the number and the morphology of Merkel cells within the hair disc in association with the hair cycle on rat back skin. METHODS: Merkel cells in hair discs were observed three-dimensionally using immunohistochemistry. Epidermal sheets were incubated with monoclonal murine antibody to CK20. As a result, Merkel cells in hair discs were clearly demonstrated as whole shapes and were counted under a light microscope. RESULTS: Merkel cells in hair discs increased during the early to middle phase of anagen and decreased during the middle phase of anagen to catagen and telogen in perinatal and postnatal rat back skin. We observed the morphological variation of Merkel cells in hair discs of rat back skin, and consequently divided them into two subtypes at the light microscopic level: the oval type and the dendritic type. The number of oval-type Merkel cells was not markedly affected by the hair cycle. In contrast, the number of dendritic-type Merkel cells markedly changed with the hair cycle. CONCLUSIONS: This difference of the hair cycle dependency between oval and dendritic-type Merkel cells suggests some functional differences, such as a secretory function, related to the hair cycle.

Aging↗

Mast cells in diffuse large B-cell lymphoma; their role in fibrosis.

AIMS: Mast cells (MCs) are associated with fibrosis in various diseases. MCs comprise two phenotypes: the MC(TC) phenotype contains tryptase and chymase, whereas the MC(T) phenotype contains tryptase. Interleukin (IL)-4 promotes the development of MC(TC) from the MC(T) phenotype. The aim of this study was to determine the relationship between MC phenotypes and fibrosis in diffuse large B-cell lymphoma (DLBCL). METHODS AND RESULTS: We examined the distribution and density of MCs in 50 DLBCL and 20 reactive lymph nodes, and evaluated MC phenotypes and IL-4-expressing cells. To detect MCs, immunohistochemistry for tryptase and chymase was performed. The 50 DLBCLs were histologically divided into three groups: no fibrosis (32 cases), reticular type (eight cases) showing reticular fibrosis, and bundle type (10 cases) showing collagenous bundles. The density of tryptase-positive MCs was higher than that of chymase-positive MCs. The densities of tryptase-positive and chymase-positive MCs in fibrotic areas were significantly higher than those in the cellular areas in the reticular and bundle groups. Double immunostaining revealed that MCs in DLBCL comprised MC(T) and MC(TC) phenotypes. Chymase-positive MCs and T lymphocytes expressed IL-4. Although there were few chymase-positive MCs in reactive lymph nodes, the density of tryptase-positive MCs was not different from that in the 'no fibrosis' group. CONCLUSIONS: Tryptase-positive and chymase-positive MCs are associated with fibrosis in DLBCL.

Adult↗

Intracolony variation of bacterial gut microbiota among castes and ages in the fungus-growing termite Macrotermes gilvus.

The fungus-growing termites Macrotermes cultivate the obligate ectosymbiontic fungi, Termitomyces. While their relationship has been extesively studied, little is known about the gut bacterial symbionts, which also presumably play a crucial role for the nutrition of the termite host. In this study, we investigated the bacterial gut microbiota in two colonies of Macrotermes gilvus, and compared the diversity and community structure of bacteria among nine termite morphotypes, differing in caste and/or age, using terminal restriction fragment length polymorphism (T-RFLP) and clonal analysis of 16S rRNA. The obtained molecular community profiles clustered by termite morphotype rather than by colony, and the clustering pattern was clearly more related to a difference in age than to caste. Thus, we suggest that the bacterial gut microbiota change in relation to the food of the termite, which comprises fallen leaves and the fungus nodules of Termitomyces in young workers, and leaves degraded by the fungi, in old workers. Despite these intracolony variations in bacterial gut microbiota, their T-RFLP profiles formed a distinct cluster against those of the fungus garden, adjacent soil and guts of sympatric wood-feeding termites, implying a consistency and uniqueness of gut microbiota in M. gilvus. Since many bacterial phylotypes from M. gilvus formed monophyletic clusters with those from distantly related termite species, we suggest that gut bacteria have co-evolved with the termite host and form a microbiota specific to a termite taxonomic and/or feeding group, and furthermore, to caste and age within a termite species.

Age Factors↗

Morphology of Malassez's epithelial rest-like cells in the cementum: transmission electron microscopy, immunohistochemical, and TdT-mediated dUTP-biotin nick end labeling studies.

BACKGROUND AND OBJECTIVE: It is known that epithelial islands are embedded in the cementum during tooth root formation, but details of this process remain unknown. The purpose of this study was to investigate the dynamic characteristics of Malassez's epithelial rest cells in the cementum during tooth root formation in pigs in vivo. MATERIAL AND METHODS: The first molars of 6-mo-old pigs were used in this study. Specimens were decalcified before being embedded in paraffin. Paraffin sections were investigated using TdT-mediated dUTP-biotin nick end labeling (TUNEL), immunohistochemical, and ultrastructural techniques. RESULTS: Malassez's epithelial rest cells were located close to the root surface at the apical one-third of the periodontal ligament, and epithelial clusters surrounded by distinct lamina cementia were sometimes observed in the cementum. TUNEL-positive cells were detected only in the cementum. Malassez's epithelial rest cells in the periodontal ligament were completely surrounded by basement membranes, but epithelial clusters in the cementum were only intermittently surrounded by such membranes. Cytokeratin-positive cells in the superstratum of the cementum were directly connected by cementocytes and by desmosome-like structures. However, organelles were scarce in the cytokeratin-positive cells in the substratum of the cementum, and the matrix of the cementum was deposited in the cells. CONCLUSION: These results suggest that the majority of the fragmented Hertwig's root sheath remains in the periodontal ligament and that some cells, which are connected to cementoblasts, are embedded in the cementum and progress to apoptosis.

Animals↗