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Biomedical subjects

Shigeo Mori

Publications and source records attributed to Shigeo Mori.

54 records · Page 3Linked to original sources
PubMed2003

Two types of response property in otolith-optokinetic interaction.

Otolithic influence on optokinetic eye-movements (visual-vestibular interaction) was investigated using oscillation of a lateral linear acceleration-step combined with optokinetic stimulation. According to our preliminary study using a 40-deg/s optokinetic stimulus speed at 0.3 and 0.5 G acceleration-steps, the interaction was characterized by a linear addition during the agonistic stimulus condition, but by suppression of the otolith-ocular reflex during the antagonistic stimulus condition. In the present study, we further examined the interaction using 3 different optokinetic speeds at an acceleration step of 0.3 G. It was revealed an additional type of response property that was characterized by marked elevation in the eye velocity with increase in the optokinetic stimulus speed, probably due to the gain increase in the optokinetic response velocity. In either type of the response property, however, the interaction seemed to be nonlinear in the otolith system, being in contrast to linear interaction postulated for the semicircular canal system.

Acceleration↗
PubMed2003

Function of otolith organ in goldfish revealed from analysis of eye movement induced by acceleration.

An otolith organ on ground behave as a detector of both gravity and linear acceleration, and play an important role in controlling posture and eye movement for tilt of the head or translational motion. On the other hand, a gravitational acceleration ingredient to an otolith organ disappears in microgravity environment. However, linear acceleration can be received by otolith organ and produce a sensation that is different from that on Earth. It is suggested that in microgravity signal from the otolith organ may cause abnormality of posture control and eye movement. Therefore, the central nervous system may re-interprets all output from the otolith organ to indicate linear motion. A study of eye movement has been done a lot as one of a reflection related to an otolith organ system. In this study, we examined function of otolith organ in goldfish revealed from analysis of eye movement induced by linear acceleration or the tilt of body. We analyzed both torsional and vertical eye movements from video images frame by frame. For tilting stimulation, torsional eye movements induced by head down was larger than that induced by head up for larger tilt angle than 30 degrees. In the case of linear acceleration below 0.4 G, however, no clear differences were observed in both torsional and vertical eye movement. These results suggest that body tilt and linear acceleration may not be with equivalent stimulation to cause eye movement on the ground.

Acceleration↗
PubMed2002

Methionine aminopeptidase 2 is a new target for the metastasis-associated protein, S100A4.

S100A4 is an EF-hand type calcium-binding protein that regulates tumor metastasis and a variety of cellular processes via interaction with different target proteins. Here we report that S100A4 physically interacts with methionine aminopeptidase 2 (MetAP2), the primary target for potent angiogenesis inhibitors, fumagillin and ovalicin. Using a yeast two-hybrid screen, S100A4 was found to interact with the N-terminal half of MetAP2. In vitro pull-down assays showed that S100A4 associates with MetAP2 in a calcium-dependent manner. In addition, the binding site of S100A4 was found located within the region between amino acid residues 170 and 229 of MetAP2. In vivo interaction of S100A4 with MetAP2 was verified by co-immunoprecipitation analysis. Immunofluorescent staining revealed that S100A4 and MetAP2 were co-localized in both quiescent and basic fibroblast growth factor-treated murine endothelial MSS31 cells, in the latter of which a significant change of intracellular distribution of both proteins was observed. Although the binding of S100A4 did not affect the in vitro methionine aminopeptidase activity of MetAP2, the cytochemical observation suggests a possible involvement of S100A4 in the regulation of MetAP2 activity through changing its localization, thereby modulating the N-terminal methionine processing of nascent substrates. These results may offer an essential clue for understanding the functional role of S100A4 in regulating endothelial cell growth and tumor metastasis.

Amino Acid Sequence↗
PubMed2002

Ligand-independent signaling by overexpressed CD30 drives NF-kappaB activation in Hodgkin-Reed-Sternberg cells.

Overexpression of CD30 and constitutive NF-kappaB activation characterizes tumor cells of Hodgkin's disease (HD), Hodgkin and Reed-Sternberg (H-RS) cells. We report that in H-RS cells overexpression of CD30 leads to self-aggregation, recruitment of TRAF2 and TRAF5, and NF-kappaB activation, independent of CD30 ligand. CD30 and TRAF proteins co-localized in H-RS cell lines and in lymph nodes of HD. An adenovirus-vector carrying a decoy CD30 lacking the cytoplasmic region or a dominant negative IkappaBalpha mutant blocks NF-kappaB activation, down regulates IL-13 expression and induces apoptosis. Thus, in H-RS cells, ligand-independent activation of CD30 signaling drives NF-kappaB activation and this leads to constitutive cytokine expression, which provides a molecular basis for HD. Inhibition of NF-kappaB activation by adenovirus vector-mediated gene transfer may provide a novel strategy of cell- and target molecule-specific therapy for patients with HD.

Adenoviridae↗
PubMed2002

Enhanced chemosensitivity after intermittent hypoxic exposure does not affect exercise ventilation at sea level.

The purpose of the present study was to test the hypothesis that the ventilatory response to exercise at sea level may increase after intermittent hypoxic exposure for 1 week, accompanied by an increase in hypoxic or hypercapnic ventilatory chemosensitivity. One group of eight subjects (hypoxic group) were decompressed in a chamber to 432 torr (where 1 torr=1.0 mmHg, simulating an altitude of 4,500 m) over a period of 30 min and maintained at that pressure for 1 h daily for 7 days. Oxygen uptake and pulmonary ventilation (V(E)) were determined at 40%, 70%, and 100% of maximal oxygen uptake at sea level before (Pre) and after (Post) 1 week of daily exposures to hypoxia. The hypoxic ventilatory response (HVR) was determined using the isocapnic progressive hypoxic method as an index of ventilatory chemosensitivity to hypoxia, and the hypercapnic ventilatory response (HCVRSB) was measured by means of the single-breath carbon dioxide method as an index of peripheral ventilatory chemosensitivity to hypercapnia. The same parameters were measured in another group of six subjects (control group). In the hypoxic group, resting HVR increased significantly ( P<0.05) after intermittent hypoxia and HCVRSB increased at Post, but the change was not statistically significant ( P=0.07). In contrast, no changes in HVR and HCVRSB were found in the control group. There were no changes in either V(E) or the ventilatory equivalent for oxygen during maximal and submaximal exercise at sea level throughout the experimental period in either group. These results suggest that the changes in resting hypoxic and peripheral hypercapnic chemosensitivities following short-term intermittent hypoxia have little effect on exercise ventilation at sea level.

Adaptation, Physiological↗
PubMed2002

CD30 and the NPM-ALK fusion protein (p80) are differentially expressed between peripheral blood and bone marrow in primary small cell variant of anaplastic large cell lymphoma.

The t(2;5)(p23;q35) translocation results in the formation of a unique chimeric NPM-ALK protein (p80). Expression of this protein is considered to be one of the clinical features of anaplastic large cell lymphoma (ALCL). Recently recognized as one clinical subtype of ALCL, the small cell variant is prone to have a leukemic presentation. Although the small cell variant has been recognized as a subtype of ALCL, the clinical properties of this subtype, especially the immunophenotype of lymphoma cells in peripheral blood, have not yet been fully described. This report shows that neither CD30 nor p80 is detected by immunostaining in the predominant small cell malignant clone and also in large lymphoma cells in peripheral blood, while large cells and occasionally observed small cells in bone marrow were found to be positive for CD30 and p80. Our findings suggest that differential expression of CD30 and p80 between peripheral blood and bone marrow lymphoma cells is a property of the small cell variant of ALCL.

Blood Cells↗
PubMed2002

Secretion of interleukin-6 and vascular endothelial growth factor by spindle cell sarcoma complicating Castleman's disease (so-called 'vascular neoplasia').

So-called 'vascular neoplasia' (VN) is a rare tumour of unknown origin that complicates hyaline vascular type Castleman's disease (CD). This paper reports a case of VN complicating CD of hyaline vascular type, in which neoplastic cells were shown to secrete interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF). In this case, VN first occurred in the retroperitoneum of a 60-year-old male. The lesion showed typical morphology, with three distinct areas: (1) a lymph node-like area with regressively transformed lymph follicles showing hyaline vascular changes and with a hypervascular interfollicular region filled with slit-like vascular channels; (2) an area composed of spindle cell sarcoma; and (3) an area showing angiolipomatous hamartoma. A proportion of the cells in the spindle cell area showed severe pleomorphism. Subcutaneous recurrence after 8 months was composed purely of pleomorphic spindle cells. A karyotypic analysis of the recurrent tumour showed 47, XXY with some instability. Supernatant from primary culture contained high levels of IL-6 and VEGF, suggesting high secretion of these cytokines from neoplastic cells. Immunohistochemically, p53 overexpression was identified only in the pleomorphic spindle cells of the primary lesion and metastatic tumour. No features suggestive of vascular origin were shown on immunohistochemical or electron microscopic analysis of the neoplastic cells. Human herpesvirus type 8 was not detected by immunohistochemistry or PCR analysis. High levels of IL-6 and/or VEGF have been reported to play a role in CD. This is the first case report that clarifies the site of such cytokine production, showing the possibility of CD as a paraneoplastic phenomenon.

Castleman Disease↗
PubMed2002

Carp, a cardiac ankyrin-repeated protein, and its new homologue, Arpp, are differentially expressed in heart, skeletal muscle, and rhabdomyosarcomas.

Arpp, a protein containing an ankyrin repeat domain, PEST sequence, and proline-rich region, is a novel ankyrin-repeated protein highly homologous to Carp, which is proposed to be the putative genetic marker for cardiac hypertrophy. In this study, we comparatively analyzed expression of Arpp and Carp protein in skeletal and cardiac muscles and rhabdomyosarcomas (RMSs). In adult skeletal muscle, Arpp was preferentially expressed in the nucleus and cytoplasm of type I fibers, whereas Carp was barely detectable in skeletal muscle. On the other hand, in adult cardiac muscle, interestingly, Arpp was expressed in ventricles mostly, whereas Carp was expressed throughout the atrium and ventricle. Furthermore, although Carp was identified in fetal heart at 11 developmental weeks, Arpp was very low or undetectable in these fetal hearts. These results suggest that Arpp and Carp are differentially expressed and function in both skeletal and cardiac muscle of fetus and adult. We found that Arpp expression was induced during the differentiation of C2C12 cells in vitro, suggesting that Arpp-expression may be associated with the differentiation stage during myogenesis. Both Arpp and Carp were found to be expressed in all of the RMS cases studied. Because the expression patterns of Arpp in RMS were different from those of muscle actin or desmin, Arpp may be detectable in RMS cases that do not express other existing RMS markers.

Actins↗
PubMed2002

Vertical eye-movement oscillation with a frequency double that of lateral linear acceleration in patients with long-standing unilateral vestibular loss.

OBJECTIVE: To examine our hypothesis that an unusual floating or tilting sensation claimed by patients with long-standing unilateral vestibular loss might be attributed to incomplete central compensation in the otolith system. METHODS: Seven patients who were with or without symptoms for 6-101 months after intratympanic gentamicin therapy for unilateral endolymphatic hydrops were sinusoidally exposed to lateral linear acceleration, and their compensatory eye movements were compared with those of 18 normal controls, using electro-oculography (EOG). The subjects, secured firmly in the chair of a linear accelerator (sled), were oscillated at three different G-loadings of 0.1 (0.11 Hz), 0.2 (0.16 Hz) and 0.3 G (0.19 Hz), respectively. During displacement, they gazed at a real (visible) or imaginary target which was located on the wall (earth-fixed), or moved on the wall in sync with the sled (body-fixed). RESULTS: Vertical EOG (V-EOG) with a frequency two-fold that of the stimulus frequency was characteristically evoked in all patients, but in none of the normal controls. One of the doubled V-EOG was larger in amplitude than the other, when the stimulus acceleration was directed from the affected ear to the intact ear in those patients whose symptoms still remained. Such a directional difference tended to be greater with the imaginary target than with the visible target. In the horizontal EOG, there was no marked difference between the patients and normal controls. Nobody reported tilt perception but only horizontal translation during the sled displacement, except one patient who was examined twice; a roll tilt was perceived in the first examination when she still had symptoms, but no tilt sensation in the second one when she no longer had symptoms. CONCLUSION: It was suggested that incomplete compensation in the otolith system could cause unusual sensations even after long-standing unilateral vestibular loss, and that V-EOG induced by a sled might be helpful in evaluating functional recovery.

Adult↗
PubMed2002

Arpp, a new homolog of carp, is preferentially expressed in type 1 skeletal muscle fibers and is markedly induced by denervation.

In this study, we isolated and characterized a murine counterpart of the human Arpp (hArpp) gene. Sequence analysis revealed that the murine Arpp (mArpp) gene is almost identical to the Ankrd2 gene, which has recently been isolated as a mouse gene induced in stretched skeletal muscle. The mArpp gene encodes a protein of 332 amino acids that contains four well-conserved ankyrin-repeat domains in the central portion of the protein. The amino acid sequence of mArpp protein (mArpp) is highly homologous to that of mouse cardiac-restricted ankyrin-repeat protein (Carp), which is proposed to be a putative genetic marker for cardiac hypertrophy. Immunohistochemical analysis revealed that mArpp is preferentially expressed in type 1 skeletal muscle fibers, and that mArpp is localized in both the nucleus and the sarcomeric I-band of muscle fibers, suggesting that Arpp may function as a nuclear and sarcomeric protein. Furthermore, mArpp was also expressed in neurons of the cerebellum and cerebrum, the islets of Langerhans in the pancreas, and the esophageal epithelium, suggesting that mArpp may play a functional physiologic role in brain, pancreas, and esophagus as well as in type 1 muscle fibers. Interestingly, although mArpp was localized in both nucleus and cytoplasm in neurons, its localization was restricted to nucleus in pancreas and esophagus, suggesting that intracellular localization of mArpp is regulated in a tissue-specific manner. Furthermore, we found that mArpp- and Carp-expression in skeletal muscle were markedly up-regulated after denervation. Although the elevated expression level of Carp was kept only for two weeks after denervation, that of Arpp was kept at least for 4 weeks, suggesting that mArpp and Carp may play distinct functional roles in denervated skeletal muscle.

Animals↗
PubMed2002

Observation of magnetic domain structure in phase-separated manganites by lorentz electron microscopy.

Magnetic domain structure in manganites was investigated by Lorentz electron microscopy, in order to understand some unusual physical properties, such as a colossal magnetoresistance (CMR) effect and a metal-to-insulator (MI) transition. In particular, we examined the spatial distribution of the charge/orbital ordered (CO/OO) insulator state and the ferromagnetic (FM) metallic state in phase-separated manganites, (La5/8-xPrx)Ca3/8MnO3 for x = 0.375, by obtaining both the dark-field and Lorentz images. We found an unusual coexistence of the CO/OO and FM metallic states with micrometer size below a MI transition temperature of 60 K. Our experimental findings provide direct evidence of the phase separation found in CMR manganites.

Journal Article↗
PubMed2002

High expression of methionine aminopeptidase type 2 in germinal center B cells and their neoplastic counterparts.

Methionine aminopeptidase type 2 (MetAP2) is a bifunctional protein that plays critical roles in the regulation of protein synthesis and post-translational processing by (a) protecting the alpha subunit of eukaryotic initiation factor 2 from inhibitory phosphorylation by eukaryotic initiation factor 2 kinases and (b) removing the amino-terminal methionine residue from nascent protein. MetAP2 is also known as the molecular target of the angiogenesis inhibitor TNP-470. In addition, it has been recently suggested that MetAP2 has an antiapoptotic function in mesothelioma. To know the pattern of expression of MetAP2 in normal and neoplastic tissues, we raised two specific rabbit polyclonal Abs and examined the pattern of MetAP2 expression in various normal and pathologic specimens. Unexpectedly, we found a very high and selective expression of MetAP2 in germinal center B cells. In the germinal center, dark zone B cells tended to express more MetAP2 than light zone B cells. When 200 malignant lymphomas of various subtypes were studied, a high level of MetAP2 expression, equivalent to that observed in germinal center B cells, was noted exclusively on B-cell lymphoma subtypes that are currently regarded as the neoplastic counterparts of germinal center B cells. The expression of MetAP2 in diffuse large B-cell lymphomas correlated well with that of BCL6 (p < 0.05) but not with that of either CD10 or BCL2. These data suggest that MetAP2 has specific function(s) in germinal center B cells and that the function is shared by neoplastic counterparts of germinal center B cells.

Aminopeptidases↗
PubMed2002

Maintenance and characterization of an Epstein Barr virus-infected CD56-negative T cell lymphoma.

T cell lymphoma carrying Epstein Barr virus (EBV(+) TL) is very rare among Western countries while it is much more common among Japanese. Here we report an EBV(+) TL which has been maintained for years by the use of mice with severe combined immune deficiency (SCID) mice. Lymphoma was obtained from a 55-year-old male suffering from oculomotor nerve palsy and lymphadenopathy. A small piece of biopsied tumor was transplanted into SCID mice and the lymphoma has been maintained for over 3 years with passages every 2 - 3 weeks. The maintained lymphoma, termed as TMS24, and the original lymphoma cells showed identical phenotype and genotype, including diffuse medium-sized cell morphology lacking granules, suppressor / cytotoxic immunophenotype and identical T cell receptor beta-chain gene rearrangement mode. Further, both were shown to carry an identical EBV clone in terms of the number of terminal repeats and the latency II-type restricted gene expression profile. Cytogenetically, TMS24 retained two characteristic chromosomal translocations of t(1;18)(q32;q21) and t(6;12)(p21;q24). Since only one cell line with such characters has been reported previously, TMS24 should be useful for detailed analysis of EBV(+) TL.

Animals↗
PubMed1999

Localization of a novel GAP family protein SPAL in the rat esophagus and heart.

Spa-1-like protein (SPAL) is a novel GTPase-activating protein (GAP) family protein. We generated anti-SPAL antibody, and examined localization of SPAL in the rat esophagus and heart by immunofluorescence microscopy. In the esophagus, SPAL was highly expressed in the spinous and granular layers and localized at the cell-cell border of the epithelial cells. SPAL in the spinous layer was almost colocalized with beta-catenin, an intracellular anchor protein of E-cadherin, while colocalization of SPAL with the tight junction protein ZO-1 was shown in the granular layer. In the heart, SPAL was localized at the intercalated disks, and there colocalized with both beta-catenin and ZO-1. In addition, much punctate localization of SPAL was seen along lateral borders of the cardiomyocytes, where beta-catenin and ZO-1 were absent. From these results, it is suggested that SPAL may regulate cell-cell adhesion in the rat esophagus and heart.

Journal Article↗
PubMedDate not supplied

Altered expression of cardiac ankyrin repeat protein and its homologue, ankyrin repeat protein with PEST and proline-rich region, in atrophic muscles in amyotrophic lateral sclerosis.

OBJECTIVES: Cardiac ankyrin repeat protein, CARP, is a protein that is restrictedly expressed in the heart but barely expressed in skeletal muscles. Since CARP is induced by pressure overload to the heart, it is proposed to be a genetic marker for cardiac hypertrophy. We recently identified a novel protein, ankyrin repeat protein with PEST and proline-rich region (ARPP), which is homologous to CARP and is preferentially expressed in type 1 skeletal muscle fibers (cf. slow fibers). We also found that both ARPP and CARP expression is induced in experimentally denervated skeletal muscles in mice. Based on these findings, we hypothesized that their expression may be induced in skeletal muscles in neurodegenerating disease. This work aimed to determine the expression pattern of ARPP and CARP in amyotrophic lateral sclerosis (ALS). METHODS: In this study, we immunohistochemically analyzed the expression of ARPP and CARP in skeletal muscles of 9 ALS cases. RESULTS: We found that CARP was aberrantly expressed in atrophic skeletal muscle fibers in ALS. Although ARPP-positive fibers were randomly scattered in a checkerboard-like pattern in normal skeletal muscle, this pattern was absent in ALS muscles. Furthermore, we also found that ARPP was expressed in fast myosin heavy chain-positive fibers (cf. type 2 fiber). CONCLUSION: These findings suggest that type-specific expression patterns of ARPP and CARP are altered in skeletal muscles of ALS.

Aged↗