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Biomedical subjects

H Shibuya

Publications and source records attributed to H Shibuya.

At least 55 records · Page 3Linked to original sources
PubMed2001

BIP, a BRAM-interacting protein involved in TGF-beta signalling, regulates body length in Caenorhabditis elegans.

BACKGROUND: The TGF-beta superfamily has diverse biological activities and is involved in the early development of animals. We previously identified a novel family member, BMP receptor associated molecule (BRAM), which binds to the intracellular domain of BMP type IA receptor and is involved in the BMP signalling pathway. RESULTS: To identify novel molecules involved in TGF-beta signalling pathways, we performed yeast two-hybrid screening using BRAM as bait. From a Xenopus cDNA library, we cloned a cDNA encoding 693 amino acids and containing the motif for an oxysterol binding protein (OSBP), which we designated BRAM interacting protein (BIP). We then isolated a BIP homologue from the Caenorhabditis elegans that encodes 733 amino acids and also contains the OSBP-like motif. Immunoprecipitation and Western blotting studies revealed that C. elegans BIP could interact with the C. elegans BRAM homologues BRA-1 and BRA-2. C. elegans BIP was expressed in pharyngeal muscle, hypodermis and several neuronal cells, an expression pattern overlaps with those of BRA-1 and BRA-2. Finally, we found that inhibition of BIP expression in C. elegans by double stranded RNA interference produces a Sma phenotype. CONCLUSIONS: BIP was isolated using the yeast two-hybrid systems. BIP may function in the TGF-beta pathway and regulate body length in C. elegans.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Regulation of the activity of the transcription factor Runx2 by two homeobox proteins, Msx2 and Dlx5.

BACKGROUND: Runx2, formerly called PEBP2alphaA or Cbfa1, is a transcription factor whose deletion causes a complete lack of ossification. It directly regulates the expression of osteoblast-specific genes through the osteoblast-specific cis-acting element found in the promoter region of these genes. RESULTS: In this study, we have found conditions in which induction of the expression of Runx2 is not accompanied by expression of an osteoblast-specific gene, osteocalcin in C2C12 cells. This finding suggests the existence of a repressor of the activity of Runx2. We have then found that the homeobox protein Msx2 is able to repress the transcription activity of Runx2 by interacting with it. Furthermore, our results have shown that the other homeobox protein Dlx5 has an activity which interferes with both abilities of Msx2 to interact with Runx2 and repress its transcription activity. It has previously been shown that a missense mutation of Msx2 (P148H) causes Boston-type craniosynostosis in humans. Interestingly, while this mutant form of Msx2 was able to bind to Runx2 and repress its activity, these abilities of Msx2 (P148H) were not subject to regulation by Dlx5. CONCLUSION: These results suggest that regulation of the activity of Runx2 by Msx2 and Dlx5 plays an important role in the mammalian skull development.

Animals↗
PubMed2001

Inhibition of BMP2-induced, TAK1 kinase-mediated neurite outgrowth by Smad6 and Smad7.

BACKGROUND: BMP2 is known to play a wide variety of roles, including some in the development of the nervous system. This cytokine has been reported to induce neurite outgrowth in rat pheochromocytoma PC12 cells via the activation of a p38 MAP kinase, although its regulatory mechanism remains largely to be elucidated. RESULTS: BMP2-induced neurite outgrowth in PC12 cells was inhibited by the introduction of a kinase-negative form of a MAP kinase kinase kinase, TAK1, an upstream regulatory kinase for p38 kinase. Following BMP2 stimulation, the expression of Smad6 and Smad7, inhibitory Smad species that are known to inhibit the BMP2-restricted Smad species, Smad1, Smad5 and Smad8, was up-regulated. Unexpectedly, over-expression of either Smad6 or Smad7 in PC12 cells repressed the BMP2-induced neurite outgrowth and severely impeded the p38 kinase pathway. Both of these inhibitory Smads were found to interact physically with TAK1-binding protein, a molecule required for TAK1 activation. CONCLUSIONS: This study demonstrates that BMP2-induced neurite outgrowth in PC12 cells involves activation of the TAK1-p38 kinase pathway which is inhibited by Smad6 and Smad7.

Animals↗
PubMed2001

Precursor effects of martensitic transformations in Ti-based alloys studied by electron microscopy with energy filtering.

Precursor effects of martensitic transformations in two well-known shape memory alloys, Ti50Ni48Fe2 and Ti50Pd34Fe16, were studied extensively by energy-filtered electron microscopy, including in-situ observations, and high-resolution electron microscopy. Energy-filtered dark-field images, where weak diffuse scattering was utilized, clearly showed the microstructure in the premartensitic state of Ti50Ni48Fe2. Tiny domains observable in this state were close to spherical rather than thin and slender, and the temperature dependence of the domain-like structure was clarified by the in-situ observations. It was found that Ti50Pd34Fe16 exhibited a domain-like structure similar to that of Ti50Ni48Fe2, which was attributed to a transverse lattice displacement. High-resolution images of Ti50Pd34Fe16 showed that a domain was coupled with other ones with different orientations of distortion, so as to reduce the total strain due to their formations. Furthermore, effects of including a fundamental reflection, in addition to the diffuse scattering, on dark-field images were discussed based on the observations and the image processing.

Journal Article↗
PubMed2001

Toxic shock-like syndrome with flu-like prodrome: a possible role of 'enhancing tissue focus' for streptococcal toxic shock.

We describe three patients with invasive group A streptococcal infection, admitted during the 3 months between November 1996 and February 1997. All patients were previously healthy Japanese women who developed a profound shock, with a rapidly fatal outcome, after experiencing flu-like symptoms. All cases conformed to the case definition of toxic shock-like syndrome (TSLS).Currently, the pathogenic mechanism of TSLS remains unclear. Known microbial virulence factors can not sufficiently explain the occurrence of TSLS, and it has been generally considered that host factors may be contributory. On pathological examination, each patient had one organ or tissue that was most severely involved: Case 1 a non-penetrating trauma; Case 2 a pregnant uterus; and Case 3 a pulmonary lesion reminiscent of lymphocytic interstitial pneumonia. On the basis of clinicopathological features of these cases, we propose that the coexistence of 'enhancing tissue focus' may be one of host factors for the progression of TSLS in patients infected with non-invasive GAS.

Adult↗
PubMed2001

Tc-99m DTPA renography in patients with collagen disease.

PURPOSE: This study evaluated the use of Tc-99m DTPA renography in patients with collagen disease. MATERIALS AND METHODS: Tc-99m DTPA renal scintigraphy was performed in 28 patients with clinically diagnosed collagen disease. Twenty-two other patients who underwent renal scintigraphy and were subsequently shown to have no kidney abnormalities served as the control group. RESULTS: One quarter of the patients with collagen disease had abnormal findings of renography, despite the absence of abnormal laboratory data. Renograms were 100% sensitive for the detection of renal disease in patients with collagen disease, and their specificity was 53% when serum blood urea nitrogen, serum creatinine concentration, and proteinuria were the only measures of renal impairment considered. The glomerular filtration rate was not significantly different between the groups, but the bilateral time to peak was significantly greater in the patients with collagen disease. Hydronephrosis was present in 7% of patients with collagen disease. CONCLUSION: Renography is useful for detecting early changes of renal involvement when the clinical state of collagen disease is evaluated.

Adult↗
PubMed2001

Differentiating between progressive supranuclear palsy and corticobasal degeneration by brain perfusion SPET.

The purpose of this study was to evaluate the usefulness of brain perfusion single photon emission computed tomography (SPET) to differentiate between progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Twelve patients with PSP and 12 with CBD were examined by brain perfusion SPET using 99Tc(m)-ethyl cysteinate dimer (99Tc(m)-ECD). The regions of interest (ROIs) were five cortical regions, the basal ganglia, the thalamus, the cerebellar cortex and the brain stem. The mean regional cerebral blood flow (CBF) and the mean right/left asymmetry index in each ROI were calculated. The asymmetry index of the regional CBF was significantly higher in CBD patients compared with PSP patients in all of the cortical regions and in the basal ganglia. The greatest differences in asymmetry were in the parietal cortex (P<0.001), high frontal cortex (P<0.001), frontal cortex (P<0.005), temporal cortex (P<0.01) and basal ganglia (P<0.01). Significant asymmetry was also detected in the occipital cortex (P < 0.05). No significant difference in asymmetry was found in the thalamus or the cerebellum. There were no significant differences between the two groups in any of the regional CBF values. In conclusion, brain perfusion SPET with 99Tc(m)-ECD is useful in detecting the significantly higher perfusion asymmetry in CBD patients compared with PSP patients in all cortical regions and in the basal ganglia. SPET may be a useful tool for differentiating between PSP and CBD.

Aged↗
PubMed2001

Early gastric carcinoma: evaluation with high-spatial-resolution MR imaging in vitro.

PURPOSE: To determine signal intensity characteristics of the gastric wall layers and to assess the accuracy of the evaluation of early gastric carcinomas in vitro by using resected specimens studied with high-spatial-resolution magnetic resonance (MR) imaging. MATERIALS AND METHODS: Fifteen gastric specimens obtained from patients suspected of having early gastric carcinoma were studied with a 1.5-T MR system with a 4-cm-diameter loop coil. High-spatial-resolution spin-echo MR images were obtained with a field of view of 50 mm, a matrix of 256 x 256, and a section thickness of 2 mm, resulting in a voxel size of 0.08 mm(3). Findings from MR images were compared with histopathologic findings. RESULTS: T1- and T2-weighted MR images clearly depicted the normal gastric wall as consisting of four and six layers, respectively, which corresponded well to the histologic layers. In 14 (93%) of 15 gastric carcinomas, the depth of mural invasion visualized with MR imaging correlated well with the histopathologic stage. The stage determined with MR imaging, however, was lower in one instance (7%) than the histopathologic stage. MR imaging also depicted the gross features of the tumor, presence of ulceration, and adjacent lymph node swelling. CONCLUSION: High-spatial-resolution MR imaging has a high diagnostic accuracy in the evaluation of the mural invasion of early gastric carcinoma in vitro and thus potentially enables preoperative histopathologic staging.

Adenocarcinoma↗
PubMed2001

Ionic mechanisms underlying burst firing of layer III sensorimotor cortical neurons of the cat: an in vitro slice study.

We examined the ionic mechanisms underlying burst firing in layer III neurons from cat sensorimotor cortex by intracellular recording in a brain slice. Regular spiking was observed in 77.4% of 137 neurons in response to constant intracellular current pulses of 0.5- to 1-s duration. The rest of the neurons showed burst firing. An initial burst followed by regular-spike firing was seen in 71.0% of 31 bursting neurons. The rest of the bursting neurons (n = 9) exhibited repetitive bursting. In the bursting neurons, spikes comprising the burst were triggered from the afterdepolarization (ADP) of the first spike of the burst. We examined the ionic mechanisms underlying the ADP by applying channel-blocking agents. The ADP was enhanced (rather than blocked) by Ca2+ channel blockade. This enhancement of the ADP by Ca2+ channel blockade was apparent even after blockade of the afterhyperpolarization by apamin or intracellular Ca2+ chelation by EGTA. The firing rate of the regular-spiking cells was increased by apamin, intracellular EGTA or Ca2+ channel blockers. In 17.9% of the neurons examined (n = 56), these agents switched the regular-spiking pattern into a bursting one. Burst firing could not be changed to regular spiking by these agents. Four neurons that responded with a single initial burst in control solution responded with repetitive bursting after application of these agents. We conclude that the main function of Ca2+ influx in layer III neurons is to activate Ca2+-dependent K+ conductance, which prevents or limits burst firing. At a time when spike amplitude was unchanged, the ADP was blocked and the burst firing changed to regular spiking by extracellularly applied tetrodotoxin (TTX) or intracellularly applied N-(2,6-dimethylphenylcarbamoylmethyl) triethyl ammonium bromide (QX314). We concluded that a TTX- and QX314-sensitive Na+ current underlies the ADP and therefore contributes to the burst firing of layer III neurons from the cat cortex.

Action Potentials↗
PubMed2001

High-resolution turbo magnetic resonance angiography for diagnosis of Moyamoya disease.

BACKGROUND AND PURPOSE: High-resolution turbo MR angiography with zero-filling interpolation (ZFI) technique is a new vascular imaging method with reduced scan time. The purpose of the present study was to evaluate high-resolution turbo MR angiography for the diagnosis and assessment of moyamoya disease. METHODS: Forty-six patients suspected of having moyamoya disease were examined with high-resolution turbo MR angiography with the ZFI technique, MRI, and conventional angiography. Moyamoya disease was diagnosed in 42 of these patients. Blind, separate interpretation of the images was performed. RESULTS: High-resolution turbo MR angiography and MRI accurately evaluated 349 (95%) and 325 (88%) of 368 arteries, respectively, but the degree of stenosis was overestimated in the other arteries. MR angiography and MRI depicted basal cerebral moyamoya vessels in 82 (98%) and 82 (98%) of 84 hemispheres, respectively. MR angiography also depicted leptomeningeal and transdural collateral vessels in 51 (100%) of 51 hemispheres and in 38 (88%) of 43 hemispheres, respectively. The sensitivity and specificity of high-resolution turbo MR angiography for the diagnosis of moyamoya disease were 98% and 100%, respectively. CONCLUSIONS: High-resolution turbo MR angiography in reduced scan time is highly accurate in the assessment of both steno-occlusive lesions and collateral vessels in moyamoya disease, thus providing a highly accurate (98%) diagnosis and assessment of moyamoya disease.

Adolescent↗
PubMed2001

Cloning and characterization of a rat ortholog of MMP-23 (matrix metalloproteinase-23), a unique type of membrane-anchored matrix metalloproteinase and conditioned switching of its expression during the ovarian follicular development.

In our attempt to study the role of matrix metalloproteinases (MMPs) in the process of mammalian ovulation, we isolated a rat ortholog of the recently reported human MMP-23 from gonadotropin-primed immature rat ovaries. Transient expression of epitope-tagged rat and human MMP-23 in COS-1 cells revealed that they were synthesized as a membrane-anchored glycoprotein with type II topology. Indirect immunofluorescent analysis showed that subcellular localization of MMP-23 was predominantly in the perinuclear regions. The transfected human MMP-23 protein was processed endogenously to the soluble form in COS-1 cells. However, cotransfection of MMP-23 with the mouse furin cDNA did not enhance this processing, indicating that furin may not be involved in this event. Notably, in situ hybridization analysis revealed a dramatic switching of MMP-23 mRNA localization from granulosa cells to theca-externa/fibroblasts and ovarian surface epithelium during the follicular development. In serum-free primary culture of rat granulosa cells, a drastic diminution of MMP-23 mRNA expression was observed in response to FSH action between 24 h and 48 h of culture. The observed effect of FSH on MMP-23 expression was mimicked by treatment of granulosa cells with forskolin or 8-bromo (Br)-cAMP. In contrast, MMP-23 mRNA levels increased in theca-interstitial cells regardless of the presence of LH in the culture. However, treatment of theca-interstitial cells with forskolin or 8-Br-cAMP markedly reduced the expression of MMP-23 with a concomitant increase in progesterone production. These results indicate that the MMP-23 gene is spatially and temporally regulated in a cell type-specific manner in ovary via the cAMP signaling pathway.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2001

Decreased longevity in Japanese men, associated with low-molecular-weight apolipoprotein(a) phenotypes.

Lipoprotein(a) [Lp(a)] is an established risk factor for atherosclerosis. High plasma Lp(a) concentrations are associated with low-molecular-weight (LMW) apolipoprotein(a) (apo a) phenotypes, which raises the question of whether LMW apo a phenotypes occur less frequently in the elderly. To assess this possibility, we studied apo A phenotype and allele frequencies in Japanese subjects > or = 80 years old (men:women = 40:34) in comparison with those <80 years old (men:women = 221:296). Significantly fewer LMW phenotypes and LMW alleles were observed in > or = 80 year old men compared with those < 80 years old: 2.5% versus 16.1% for the LMW phenotype frequency and 1.3% versus 9.7% for the LMW allele frequency (P<0.05, Fisher's exact probability test). Similar differences were not found in the women. Consistent with this, plasma Lp(a) concentrations were significantly lower in the men > or = 80 years old than in the younger group. These results indicate that LMW apo a phenotypes are associated with a shorter lifespan in men but not in women, possibly reflecting the higher susceptibility of men to atherosclerosis.

Adult↗
PubMed2001

Apocrine adenocarcinoma in a golden hamster.

An apocrine adenocarcinoma was observed in the subcutis of the abdomen of golden hamster. Histologically, the tumor cells irregularly formed multiple layers of cysts and some detached cells were presented in the cystic space. PAS stain with alpha-amylase digestion revealed PAS-positive alpha-amylase-resistant granules in the cytoplasm. Immunohistochemically, cytokeratin was demonstrated in the tumor cells. By electron microscopy, the tumor cells had an oval nucleus with invagination, abundant cytoplasmic organelles and microvilli protruding into the intercellular spaces.

Adenocarcinoma↗
PubMed2001

Study of quantitative oral radioactivity in salivary gland scintigraphy and determination of the clinical stage of Sjögren's syndrome.

UNLABELLED: In this study, the oral radioactivity seen in salivary gland scintigraphy, which was established entirely on the basis of radioactive saliva secreted by the parotid and submandibular glands, was evaluated quantitatively in healthy volunteers and in patients with Sjögren's syndrome. METHODS: Salivary gland scintigraphy and labial biopsy were performed on 70 patients with Sjögren's syndrome. After intravenous administration of 99mTc-sodium pertechnetate, dynamic scintigraphy was performed and time-activity curves for the oral cavity and four major salivary glands were generated. Lemon juice stimulation was delivered at 40 min. The prestimulatory oral activity index, poststimulatory oral activity index, and time interval between the vascular perfusion peak and the prestimulated maximum oral activity point were calculated to quantify the oral activity. Other glandular functional parameters-namely, maximum accumulation (MA), maximum secretion, secretion velocity, time at maximum count, time interval from stimulation to minimum count, and uptake ratio (UR) of the parotid and submandibular glands-were also calculated. Salivary gland scintigraphy was also performed on 21 healthy subjects with no evidence of salivary gland malfunction. RESULTS: Histopathologic grade 1 or 2 was found in 29 patients and grade 3 or 4 was found in 41 patients, and they were regarded as being in the early and advanced stages of Sjögren's syndrome, respectively. After overall analysis, all of the oral activity indices and the MA and UR of the submandibular gland clearly decreased as clinical severity progressed, and statistically significant differences were observed. CONCLUSION: New oral activity indices correlated with the stage of Sjögren's syndrome, and these quantitative oral indices together with certain glandular parameters (mainly MA and UR of the submandibular gland) were found to be sensitive enough to distinguish the disease severity of Sjögren's syndrome.

Biopsy↗
PubMed2001

[Preoperative PDT for early stage lung cancer accompanied with infiltration to the central airway].

For the treatment of central type lung cancers, it is often necessary to perform bronchoplasty or bi-lobectomy even in early stage cases in which tumor invasion is found at the bronchial bifurcation. To solve this contradictory situation, we applied PDT for central type early stage lung cancer to reduce the extent of superficial infiltration, enabling a simple surgical technique or decreasing the amount of resected lung parenchyma. Among 7 patients, the simplification of surgical technique and reduction of the range of resection were possible in 2 cases each respectively. However, these objectives were not satisfied in the remaining 3 cases and the operations performed were those that had been originally scheduled before PDT. The current problems are the establishment of appropriate laser irradiation technique and accurate assessment for extension of invasion.

Adult↗
PubMed2001

Antiapoptotic activity is dispensable for insulin-like growth factor I receptor-mediated clonogenic radioresistance after gamma-irradiation.

PURPOSE: The purpose of this study was to evaluate the relationship between apoptotic activity and clonogenic radiosensitivity in vitro using an insulin-like growth factor I receptor (IGF-IR) signaling model, which is known to exert tumorigenic and antiapoptotic effects. EXPERIMENTAL DESIGN: We used mouse embryo fibroblast cell lines expressing either human IGF-IR [R+(Wt) and R+] or the marker gene alone [R-(puro)]; these cell lines were derived from R- cells, which are deficient in IGF-IR. After gamma-irradiation, apoptotic activity was determined by the presence of DNA fragmentation and caspase-3-, -8-, and -9-like activities. Clonogenic radiosensitivity was determined by a colony-forming assay. RESULTS: R+(Wt) and R+ cells expressed similar levels of IGF-IR, transducing phosphorylation signals to major downstream substrates on insulin-like growth factor I stimulation. R+ cells were resistant to the induction of apoptosis after gamma-irradiation; however, both R+(Wt) and R-(puro) cells demonstrated significant DNA fragmentation and increase in caspase-3-, -8-, and -9-like activities. Both R+(Wt) and R+ cells were radioresistant (to a similar extent) compared with R-(puro) cells as measured by a colony-forming assay. Clonogenic radioresistance was not influenced by the inhibition of Akt/protein kinase B through treatment with wortmannin at low concentrations specifically inhibiting phosphatidylinositol 3'-kinase. CONCLUSIONS: Our findings indicate that apoptotic activity does not necessarily predict clonogenic survival after exposure to ionizing radiation. This study provides clinical implications in the evaluation of apoptotic activities observed during the course of radiotherapy to predict accurate tumor response or local control.

Androstadienes↗
PubMed2001

[An autopsied case of pachymeningitis associated with a ruptured, cerebral aneurysm due to Aspergillus infection].

We reported a 64-years-old woman with pachymeningitis associated with a ruptured mycotic cerebral aneurysm due to Aspergillus infection. She had suffered from diabetes mellitus and been treated since she was 49 years old. She complained of headache at the age of 62 and loss of her left visual acuity three months later. She was treated by the pulse therapy of methylprednisolone as neuritis retrobulbaris and her visual acuity recovered. But her headache continued. Three months later, her right visual acuity was lost, and the pulse therapy was not effective this time. Six months later, she died of subarachnoid hemorrhage following acute meningitis. The autopsy was granted, but limited to the cranial cavity. Macroscopically, it disclosed brownish thickened dura around sella turucica involving trigeminal ganglion and optic nerve, and fresh subarachnoid hemorrhage in the basal cisterns and a ruptured aneurysm (3 mm in diameter) between internal carotid and posterior cerebral artery on the left side. Histologically, the brownish thickened dura was infiltrated by lymphocytes, plasma cells, and multinucleated giant cells. The wall around the aneurysm was infiltrated by lymphocytes and plasma cells as well as many fungi. Immunohistochemistry demonstrated the presence of Aspergillus in the thickened dura and the arterial wall around the aneurysm. There were lymphocytes and plasma cell infiltration in the basal subarachnoid space and scattered microabcesses in the brain. Although the first entry of Aspergillus to the dura was unclear, we assume that the final intravascular dissemination of Aspergillus from the dura caused meningitis and mycotic aneurysm.

Aneurysm, Infected↗