Biomedical subjects

R Takada

Publications and source records attributed to R Takada.

At least 19 recordsLinked to original sources

PubMed2006

Interferon-gamma is causatively involved in experimental inflammatory bowel disease in mice.

Cytokines may be crucially involved in the pathogenesis of inflammatory bowel diseases (IBD), but it remains controversial whether interferon (IFN)-gamma, a typical proinflammatory cytokine, is an essential mediator to cause the disorders. In the present study, IFN-gamma(-/-) and wild-type (WT) C57BL/6 mice were fed 2.5% dextran sodium sulphate (DSS) in drinking water for 7 days, in order to investigate DSS-induced intestinal inflammation. The DSS-treated WT mice exhibited a robust production of IFN-gamma in the gut, a remarkable loss of body weight, as well as high rate of mortality (60%). In striking contrast, IFN-gamma deficient mice did not develop DSS-induced colitis, as indicated by the maintenance of body weight and survival rate of 100%. Severe intestinal inflammation was demonstrated exclusively in WT animals in terms of the shortening of the bowel as well as the elevation of the disease activity index, myeloperoxidase (MPO) activity and serum haptoglobin level. Histological study of DSS-treated WT intestine revealed disruption of mucosal epithelium and massive infiltration of inflammatory cells, while the organ from IFN-gamma(-/-) mice remained virtually normal in appearance. Enzyme-linked immunosorbent assay (ELISA) analyses indicated abundant production of three chemokines, i.e. monokine induced by interferon-gamma (MIG), interferon-inducible protein 10 (IP-10) and monocyte chemoattractant protein-1 (MCP-1), in the DSS-irritated intestine of WT but not of IFN-gamma(-/-) mice. The present results demonstrate clearly that IFN-gamma plays indispensable roles in the initiation of DSS colitis, and some chemokines are produced in an IFN-gamma-dependent fashion.

Acute Disease↗

PubMed2002

Differential regulation of porcine hepatic IGF-I mRNA expression and plasma IGF-I concentration by a low lysine diet.

The influence of dietary lysine on hepatic insulin-like growth factor-I (IGF-I) gene expression and plasma IGF-I level was investigated. Two male 6-wk-old pigs from each of six litters were used. Each littermate was assigned to one of two diets, control or low lysine (LL), that were isoenergetic and similar in protein content and provided 14.3 MJ digestible energy/kg for both diets, 185 g protein/kg for the control diet and 180 g protein/kg for the LL diet. The control diet contained all essential amino acids in the recommended amounts, including 11.5 g lysine/kg. The LL diet was similar but contained only 7 g lysine/kg. Pigs were pair-fed these diets for 3 wk. Growth rates and feed efficiencies of pigs fed the LL diet were significantly lower than those of pigs fed the control diet (P < 0.01). Plasma IGF-I levels in pigs fed the LL diet were 52% lower than in those fed the control diet (P < 0.01), and the LL group also had lower plasma IGF-binding protein-3 (IGFBP3) levels (P < 0.05). Despite the strikingly lower plasma IGF-I in pigs fed the LL diet, hepatic IGF-I mRNA abundance did not differ between the two treatment groups. We conclude that the reduction in plasma IGF-I caused by reduced dietary lysine may have been due in part to suppression of post-transcriptional events in IGF-I expression. The lower plasma IGFBP3 in pigs fed the LL diet suggests that increased clearance rates of circulating IGF-I may have been involved in this response.

Animals↗

PubMed2001

p73beta, a variant of p73, enhances Wnt/beta-catenin signaling in Saos-2 cells.

The Wnt/beta-catenin pathway and p53 are very common targets for genetic alterations in colorectal cancer, and relationships between them have been reported. Here, we describe the relation between Wnt/beta-catenin signaling and the p53-related gene p73. p73, but not p53, activated a promoter containing the Tcf-binding sequence in Saos-2 cells, and the degree of activation was positively correlated with that on a p53-responsive promoter. Moreover, p73beta enhanced Wnt/beta-catenin signaling synergistically with Wnt-3a or exogenously expressed beta-catenin, unlike p53, and the enhancement was not caused by the accumulation of beta-catenin. These results show that the effects of p73 on Wnt/beta-catenin signaling differ from those of p53.

Base Sequence↗

PubMed2001

T-helper (Th)1/Th2 imbalance in patients with previously untreated B-cell diffuse large cell lymphoma.

T-helper (Th)1/Th2 imbalance has been observed in a variety of pathological conditions, including malignant diseases. We evaluated the Th1/Th2 balance in peripheral blood Th cells by means of intracellular cytokine analysis in 19 patients with previously untreated B-cell diffuse large cell lymphoma (DLCL) and in 18 patients with B-cell DLCL who had achieved complete remission (CR) after chemotherapy. The mean percentage of Th2 in CD4 cells in patients with DLCL (5.00 +/- 2.20) and that of Th1 in CD4+ cells in patients in CR (32.42 +/- 11.30) were significantly increased in comparison with those in healthy volunteers, respectively (Th1; 23.02 +/- 9.45, Th2; 3.25 +/- 0.90; P<0.01). The mean ratio of Th1/Th2 was significantly lower in patients with DLCL (4.74 +/- 0.52) than in patients in CR (9.31 +/- 1.06; P<0.01) and in healthy volunteers (7.25 +/- 0.65; P<0.01). We conclude that the Th1/Th2 balance was polarized to Th2 in untreated DLCL patients and to Th1 in patients in CR, which suggests that a Th1/Th2 imbalance could play a role in lymphomagenesis and durable remission.

Adult↗

PubMed2001

Inhibitory effect of a presenilin 1 mutation on the Wnt signalling pathway by enhancement of beta-catenin phosphorylation.

Mutations in the presenilin 1 (PS1) gene are the most common genetic factor underlying the development of early onset familial Alzheimer's disease (FAD). Accumulating evidence has shown that FAD-linked mutations of PS1 enhance the generation of amyloid-beta (1-42) protein. Recently, beta-catenin has been shown to interact with PS1. beta-catenin is essential for the Wnt signalling pathway. However, the biological significance of the interaction between beta-catenin and PS1 in this signalling pathway remains to be clarified. In this study, we investigated the effect of FAD-linked PS1 (M146L) mutation in the Wnt signalling pathway using the conditioned medium containing Wnt-3A. The expression of mutated PS1 inhibited the Wnt-3A-induced accumulation of beta-catenin. Chase analysis of beta-catenin in Wnt-3A-stimulated cells following cycloheximide treatment revealed that PS1 mutation enhanced the generation of the higher molecular mass form of beta-catenin, most likely, ubiquitinated beta-catenin. In addition, the expression of mutated PS1 elevated the level of phosphorylated beta-catenin, which is targeted to the ubiquitin/proteasome pathway. Thus, it appears that PS1 (M146L) mutation down-regulates the Wnt-3A-induced accumulation of beta-catenin due to an increase in the level of phosphorylated beta-catenin.

Acetylcysteine↗

PubMed2000

Quantitative Evaluation of Nystagmus by an Image-analysis System.

Purpose: We attempted to apply a newly developed image-analysis system for measurement and analysis of nystagmus.Method: Eye movements were recorded by digital video through a head-mounted charge coupled device (CCD) camera. The recorded movie was converted into black and white in order to detect the area of the pupil. Horizontal and vertical eye positions were determined by calculating the centroid of the pupil. Torsional angle was calculated using the iris striate pattern around the pupillary margin.Results: The parameters (amplitude, cycle, etc.) of nystagmus were calculated easily by the new image-analysis system from the recorded images. As examples, the foveation period was measured accurately in a case of jerky-type congenital nystagmus. Very regular cycles of intorsional attack period were revealed in a case of superior oblique myokymia. A case of cork-screw-like nystagmus showed a characteristic combination of large and small cycles unassociated with torsion.Conclusion: This image-analysis system was useful for quantitative analysis of nystagmus, and especially for measurement of torsion. Detailed waveforms and specific rhythms of nystagmus, which could not be recognized by observation, were demonstrated by this system.

Journal Article↗

PubMed2000

Multifocal Electroretinogram in Central Serous Chorioretinopathy.

Purpose: An assessment of retinal function topographically in the affected eyes with central serous chorioretinopathy (CSC).Participants and Method: We recorded multifocal electroretimogram (mERG) in 5 patients with unilateral CSC, and analyzed the topographical properties in the central visual field (rings #1 + 2).Results: mERG amplitudes in the CSC eyes were significantly reduced compared with the fellow eyes, for P 1-N 1 (58.5 +/- 23.5%, p < 0.05) and for P 1-N 2 (47.5 +/- 15.0%, p < 0.05). mERG latencies in the CSC eyes were significantly increased compared with those in the fellow eyes, for N 1 (by 9.0 +/- 8.1%, p < 0.05) and for P 1 (by 8.4 +/- 7.0%, p < 0.05). mERG in the CSC eyes gradually recovered in the follow-up period. However, the responses did not recover to normal value during follow-up, even when the subretinal fluid disappeared ophthalmoscopically.Conclusions: These results show that a topographical analysis of the mERG is useful for clinical observation of CSC.

Journal Article↗

PubMed2000

Induction of melanocyte-specific microphthalmia-associated transcription factor by Wnt-3a.

Microphthalmia-associated transcription factor (Mitf) plays a critical role in the development of neural crest-derived melanocytes. Here, we show that exogenously added Wnt-3a protein, an intercellular signaling molecule, up-regulates the expression of endogenous melanocyte-specific Mitf (Mitf-M) mRNA in cultured melanocytes. The melanocyte-specific promoter of the human MITF gene (MITF-M promoter) contains a functional LEF-1-binding site, which is bound in vitro by LEF-1 and confers the preferential expression on a reporter gene in melanocytes and melanoma cells, as judged by the transient transfection assays. Moreover, the LEF-1-binding site is required for the transactivation of a reporter gene by LEF-1, beta-catenin, or their combination. Exogenously added Wnt-3a protein also transactivates the MITF-M promoter via the LEF-1-binding site; this activation was abolished when a dominant-negative form of LEF-1 was coexpressed. These results suggest that Wnt-3a signaling recruits beta-catenin and LEF-1 to the LEF-1-binding site of the MITF-M promoter. Therefore, the present study identifies Mitf-M/MITF-M as a direct target of Wnt signaling.

Base Sequence↗

PubMed2000

Effects of localized lesions in the lateral suprasylvian cortex on convergence eye movement in cats.

We evaluated the effects of electrolytic lesions in the extrastriate cortical area on the amplitudes and velocities of vergence eye movements in six alert cats that were trained to track a target moving in depth. Bilateral or unilateral lesions in the lateral suprasylvian (LS) cortex reduced the amplitudes and velocities of vergence eye movements, but the positive correlation between them was maintained. Furthermore, unilateral lesions changed the symmetry of eye movements. Movements of the left eye were decreased by lesions in the right LS cortex, resulting in asymmetric vergence eye movement with right eye predominance, and vice versa. These results support the hypothesis that the LS cortex plays an essential role in controlling vergence eye movement.

Animals↗

PubMed2000

A case of superior oblique myokymia observed by an image-analysis system.

Superior oblique myokymia is a microtremor of the eye that causes monocular torsional oscillopsia. A modified Harada-Ito procedure was used to treat a case of the disease in a 20-year-old woman. The authors used video-image analysis pre- and postoperatively to evaluate the effect of the surgery on abnormal torsional eye movements. This analysis revealed that before surgery, the abnormal torsional movement had a very regular cycle (duration of attack, 8.0 +/- 0.5 s; time interval between attacks, 18.7 +/- 3.2 s; n = 9). After the surgery, amplitude of the abnormal torsional eye movement was reduced, and the oscillopsia had subjectively improved, although the movement cycle remained unchanged. The authors' video-image analysis, which used iris striation, proved to be a useful method for clinical measurement of torsional eye movements.

Adult↗

PubMed2000

Isolated cardiac metastasis from sacral chordoma.

A 64-year-old woman presented with right heart failure caused by a cardiac tumor centered in the free wall of the right ventricle, accompanied by pericardial effusion. A match between the biopsy specimen and tissue removed 4 years earlier resulted in the diagnosis of a cardiac metastasis from a chordoma. Immunohistochemical staining was also useful in establishing the diagnosis. To alleviate the right ventricular outflow obstruction, a palliative operation was planned, resecting the tumor and performing a right ventriculoplasty, which was cancelled due to the extent of infiltration of the tumor, and instead a right atrium to pulmonary artery shunt was attempted using a vascular prosthesis, only to fail due to an inability to maintain blood flow through the prosthesis. Presently there are no definitive treatment options available, and some palliative chemotherapy is being performed. Single cardiac metastases from a chordoma are extremely rare.

Antigens, Neoplasm↗

PubMed2000

[Multifocal electroretinogram in central serous chorioretinopathy].

PURPOSE: To assess retinal function topographically in the affected eyes with central serous chorioretinopathy (CSC). PARTICIPANTS AND METHOD: We recorded multifocal electroretimogram (mERG) in 5 patients with unilateral CSC, and analyzed the topographical properties in the central visual field (rings #1 + 2). RESULTS: mERG amplitudes in the CSC eyes were significantly reduced compared with the fellow eyes, for P 1-N 1 (58.5 +/- 23.5%, p < 0.05) and for P 1-N 2 (47.5 +/- 15.0%, p < 0.05). mERG latencies in the CSC eyes were significantly increased compared with those in the fellow eyes, for N 1 (by 9.0 +/- 8.1%, p < 0.05) and for P 1 (by 8.4 +/- 7.0%, p < 0.05). mERGs in the CSC eyes gradually recovered in the follow-up period. However, the responses did not recover to normal value during follow-up, even when the subretinal fluid disappeared ophthalmoscopically. CONCLUSIONS: These results show that a topographical analysis of the mERG is useful for clinical observation of CSC.

Adult↗

PubMed2000

Waveform changes of the first-order multifocal electroretinogram in patients with glaucoma.

PURPOSE: To investigate the relationship between the components of the first-order multifocal electroretinogram (M-ERG) and glaucomatous visual field loss. METHODS: Twenty-six eyes of 14 patients with primary open-angle glaucoma (POAG) were evaluated with the M-ERG techniques. Twenty-six eyes of 26 normal subjects also were tested as control subjects. To record the M-ERG, a stimulus matrix of 103 scaled hexagonal elements was displayed on a monitor driven at a 75-Hz frame rate according to a binary m-sequence. The M-ERG responses were averaged in each quadrant of the stimulus field and the peak-to-trough amplitudes and peak implicit times of the first trough (N1), the first peak (P1), and the second trough (N2) of the M-ERG were compared with the mean sensitivity values (dB) of the corresponding quadrant of the Humphrey static perimetric field. RESULTS: The changes in the peak latencies of P1 and N2 in the POAG group were small but significant compared with those in the normal group (P < 0.01). However, no significant differences in the amplitudes of (P1-N1) and (P1-N2) between the two groups were found. Significant negative correlations between the peak implicit times of N1, P1, and N2 and the mean sensitivity values (dB) of static perimetry were observed. The correlation coefficients were -0.20 (P < 0.05) for the N1, -0.41 (P < 0.001) for the P1, and -0.59 (P < 0.001) for the N2. No significant correlations were observed between the amplitudes (P1-N1 and P1-N2) and the mean sensitivity values. CONCLUSIONS: The present study findings suggest that the peak implicit times, but not the amplitudes, of the M-ERG increase as the glaucomatous visual field deteriorates. The amplitudes of the M-ERG did not decrease as the glaucomatous optic nerve dysfunction progressed.

Electroretinography↗

PubMed2000

[Quantitative evaluation of nystagmus by an image-analysis system].

PURPOSE: We attempted to apply a newly developed image-analysis system for measurement and analysis of nystagmus. METHOD: Eye movements were recorded by digital video through a head-mounted charge coupled device (CCD) camera. The recorded movie was converted into black and white in order to detect the area of the pupil. Horizontal and vertical eye positions were determined by calculating the centroid of the pupil. Torsional angle was calculated using the iris striate pattern around the pupillary margin. RESULTS: The parameters (amplitude, cycle, etc.) of nystagmus were calculated easily by the new image-analysis system from the recorded images. As examples, the foveation period was measured accurately in a case of jerky-type congenital nystagmus. Very regular cycles of intorsional attack period were revealed in a case of superior oblique myokymia. A case of cork-screw-like nystagmus showed a characteristic combination of large and small cycles unassociated with torsion. CONCLUSION: This image-analysis system was useful for quantitative analysis of nystagmus, and especially for measurement of torsion. Detailed waveforms and specific rhythms of nystagmus, which could not be recognized by observation, were demonstrated by this system.

Adult↗

PubMed1999

Axin prevents Wnt-3a-induced accumulation of beta-catenin.

When Axin, a negative regulator of the Wnt signaling pathway, was expressed in COS cells, it coeluted with glycogen synthase kinase-3beta (GSK-3beta), beta-catenin, and adenomatous polyposis coli protein (APC) in a high molecular weight fraction on gel filtration column chromatography. In this fraction, GSK-3beta, beta-catenin, and APC were co-precipitated with Axin. Although beta-catenin was detected in the high molecular weight fraction in L cells on gel filtration column chromatography, addition of conditioned medium expressing Wnt-3a to the cells increased beta-catenin in the low molecular weight fraction. However, Wnt-3a-dependent accumulation of beta-catenin was greatly inhibited in L cells stably expressing Axin. Axin also suppressed Wnt-3a-dependent activation of Tcf-4 which binds to beta-catenin and acts as a transcription factor. These results suggest that Axin forms a complex with GSK-3beta, beta-catenin, and APC, resulting in the stimulation of the degradation of beta-catenin and that Wnt-3a induces the dissociation of beta-catenin from the Axin complex and accumulates beta-catenin.

Adenomatous Polyposis Coli Protein↗

PubMed1999

Human cortical areas activated in relation to vergence eye movements-a PET study.

Human cortical areas activated in relation to vergence eye movements were determined using positron emission tomography. Binocular disparity-driven visual stimuli were presented using a head-mounted display. Eye movements were monitored continuously by an infrared limbus tracker. A combination of a bar and a cross was used as the target. In the vergence task, subjects were instructed to follow an approaching bar, while ignoring a stationary cross. Activation in relation to vergence eye movement was discriminated from activation in relation to motion vision by using the ignore-bar task as the control. In the ignore-bar task, subjects were instructed to fixate on a stationary cross, while ignoring an approaching bar. The fixation task was used as the basic control for both the vergence and the ignore-bar tasks. Areas of activation in relation to vergence eye movements were found in the bilateral temporooccipital junction, the left inferior parietal lobule, and the right fusiform gyrus by comparing regional cerebral flow between the vergence and ignore-bar tasks and by the conjunctive analyses of vergence-vs-ignore comparison with vergence-vs-fixation comparison.

Accommodation, Ocular↗

PubMed1999

[Multifocal electroretinograms in patients with branch retinal artery occlusion].

PURPOSE: We recorded multifocal electroretinograms (m-ERGs) in patients with branch retinal artery occlusion (BRAO) and compared the waveform in the area of retinal artery occlusion with that in the normal area, to evaluate the influence of the damage of the inner retina on the m-ERG. SUBJECTS AND METHODS: Three patients who had normal visual acuity and visual field loss of more than one quadrant due to BRAO were examined. The waveform of first-order and second-order kernel responses of m-ERG in the area of retinal artery occlusion were compared with those of the vertically symmetrical, normally perfused area of the same eye. RESULTS: Prolongation of latency and decrease of amplitude were noted for the first negative wave (N 1), the first positive wave (P1), and the second negative wave (N2) in the first-order kernel responses in the area of retinal artery occlusion in comparison with the normally perfused area. Second-order kernel responses were not detected in the area of retinal artery occlusion. CONCLUSIONS: The damage to the inner retina affected portions N1, P1, and N2 of the first-order kernel responses, and N2 was the most seriously affected. Second-order kernel responses appear to reflect more strongly the function of the inner retina.

Child↗

PubMed1998

Antibodies specific to outer membrane antigens of Moraxella catarrhalis in sera and middle ear effusions from children with otitis media with effusion.

OBJECTIVE: Recent studies have shown that bacterial DNA is present in a significant percentage of middle ear effusions, suggesting that persistent bacterial infection may be more important in pathogenesis and recurrence of otitis media with effusion (OME) than previously considered. Although Moraxella (M.) catarrhalis is one of the most common pathogens of otitis media, relatively little is known about immune response to the organism. The objective of the present study is to investigate how systemic and local immune activities against M. catarrhalis may be associated with severity of OME. METHODS: The antibody levels specific to outer membrane antigens of M. catarrhalis in sera and middle ear effusions (MEEs) from 59 children with OME were measured by enzyme-linked immunosorbent assay. Their ages ranged from 1 to 12 years with a median 5.0 years. The children were followed 1 year prospectively and classified into two groups with or without recurrent/persistent OME according to severity of OME during the follow-up 1 year. RESULTS: Serum IgG, IgM, and IgA antibodies specific to outer membrane antigens of M. catarrhalis were detected in all samples and the median levels were 35, 0.93, and 1.2 microg/ml respectively. The MEE IgG, IgM, IgA, and secretory IgA antibodies were detected in over 95% samples tested and the median levels were 371, 158, 20, and 50 ng/mg total protein respectively. A comparison between acute and subacute/chronic phases revealed that the median levels of MEE IgG and IgM antibodies were higher at the acute phase (692 vs. 340, P = 0.06; 35 vs. 10, P = 0.02, respectively); while the MEE secretory IgA antibody level was increased at the subacute/chronic phase (74 vs. 35, P = 0.02). Either serum or MEE IgG antibody level was significantly lower in recurrent/persistent OME group than that in nonrecurrent/non-persistent OME group (13 vs. 43 ,microg/ml, P = 0.009; 238 vs. 577 ng/mg protein, P = 0.006, respectively). CONCLUSIONS: These data provide additional information on the immunologic aspects of children with OME. Decreased serum and MEE IgG antibody levels specific to outer membrane antigens of M. catarrhalis may lead to failure to eliminate this organism, resulting in persistent and/or recurrent appearance of MEE.

Antibodies, Bacterial↗