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Biomedical subjects

Makoto Inoue

Publications and source records attributed to Makoto Inoue.

At least 91 records · Page 5Linked to original sources
PubMed2004

SOCS1 [corrected] inhibits HPV-E7-mediated transformation by inducing degradation of E7 protein.

Human papilloma viruses (HPVs) are small double-stranded DNA viruses that infect mucosal and cutaneous epithelium and induce cervical cancer. It has been shown that interferon (IFN)gamma suppresses proliferation of HPV-infected cells by suppressing expression of HPV E7. Here, we found that IFNgamma induces not only suppression of E7 transcription but also proteasome-dependent degradation. Suppressor of cytokine signaling-1 (SOCS1)/JAB, a suppressor of cytokine signaling, is known to be induced by IFNgamma, and functions as an antioncogene against various hematopoietic oncogenic proteins. SOCS1 contains the SOCS-box, which is shown to recruit ubiquitin transferase to the molecules that interact with SOCS1. We found that SOCS1 interacted with HPV E7 protein and induced ubiquitination and degradation of E7 in a SOCS-box-dependent manner. SOCS1 overexpression also increased Rb protein levels and suppressed proliferation of cervical cancer cell lines infected with HPV. Moreover, E7 protein levels were higher and Rb protein levels were lower in SOCS1-deficient fibroblasts infected with retrovirus vector carrying E7 gene than in wild-type fibroblasts. E7 induced anchorage-independent growth in SOCS1-deficient fibroblasts, but not in wild-type cells. These data suggested that SOCS1 plays an important role in regulating the levels of E7 protein and their transforming potential, and could be a new therapeutic tool for HPV-mediated tumors.

Animals↗
PubMed2004

A clinicopathologic case report on macular hole associated with von Hippel-Lindau disease: a novel ultrastructural finding of wormlike, wavy tangles of filaments.

BACKGROUND: We describe a novel ultrastructural finding observed in an epiretinal membrane excised from a patient with von Hippel-Lindau disease. METHODS: This interventional case report presents a 45-year-old woman who noted decreased vision in her right eye and was referred for treatment of a macular hole secondary to von Hippel-Lindau disease. Blindness had occurred previously in the left eye because of exudative retinal detachment. Funduscopic examination revealed a macular hole associated with a delicate epiretinal membrane, multiple retinal angiomas, and multiple old laser scars. Vitrectomy was performed in her right eye. The epiretinal membrane was peeled off and processed for light and electron microscopy. RESULTS: Postoperatively the macular hole was successfully closed, and vision recovered to 20/20 from 20/40. In the excised epiretinal membrane, flattened glial cells and extracellular matrix containing fibrous elements formed a multilayered pattern. Ultrastructurally, the fibrous elements appeared as wormlike, wavy tangles of filaments (WWTF) with an orientation parallel to the surface of the epiretinal membrane. Just above the WWTF, flattened glial cells frequently extended thin cytoplasmic processes with pinocytotic vesicles. CONCLUSION: The ultrastructure suggested that retinal glial cells had induced a remodeling of the collagenous stroma in the posterior vitreous cortex, resulting in tangential macular traction.

Basement Membrane↗
PubMed2004

Activity of peri-oral facial muscles and its coordination with jaw muscles during ingestive behavior in awake rabbits.

To study peri-oral facial muscle activity patterns and coordination with jaw muscles during ingestive behavior, electromyographic (EMG) activities in the peri-oral facial (buccinator: BUC, orbicularis oris: ORB) and jaw (masseter, digastric) muscles along with jaw movement trajectories were recorded in awake rabbits. A standardized amount of apple in a cylindrical shape was used as the test food. The period from food intake to just before swallowing (the masticatory sequence) was divided into three masticatory periods (preparatory period, rhythmic chewing period and preswallow period) based on the activity pattern of jaw muscles and jaw movement trajectories, and jaw movements and EMG activities in both the jaw and facial muscles during each masticatory period were assessed. Both the jaw and facial muscles were active throughout the masticatory sequence, and the activity patterns of facial muscles and the pattern of coordination between the facial and jaw muscles varied for each masticatory period. No consistent pattern was noted for the BUC activity during the preparatory period, whereas the ORB showed tonic activity throughout this period. During the rhythmic chewing and preswallow periods, both the ORB and BUC showed jaw-movement-related rhythmic bursts. However, significant differences were noted in the burst properties in both facial muscles and their temporal correlations with the jaw muscle activities between these two periods. Results suggest that the neural mechanisms regulating facial muscle activities may differ between the masticatory periods, and such mechanisms may contribute to the well-coordinated orofacial movements required for smooth masticatory sequence.

Analysis of Variance↗
PubMed2004

A novel zinc-binding motif revealed by solution structures of DNA-binding domains of Arabidopsis SBP-family transcription factors.

SQUAMOSA promoter binding proteins (SBPs) form a major family of plant-specific transcription factors related to flower development. Although SBPs are heterogeneous in primary structure, they share a highly conserved DNA-binding domain (DBD) that has been suggested to be zinc binding. Here we report the NMR solution structures of DBDs of two SBPs of Arabidopsis thaliana, SPL4 and SPL7. The two share essentially the same structural features. Each structure contains two zinc-binding sites consisting of eight Cys or His residues in a Cys3HisCys2HisCys or Cys6HisCys sequence motif in which the first four residues coordinate to one zinc and the last four coordinate to the other. These structures are dissimilar to other known zinc-binding structures, and thus represent a novel type of zinc-binding motif. The electrostatic profile on the surface suggested that a continuous region, including all the conserved basic residues, is involved in the DNA binding, the mode of which is likely to be novel as well.

Amino Acid Sequence↗
PubMed2004

Novel 473-bp deletion in XLRS1 gene in a Japanese family with X-linked juvenile retinoschisis.

PURPOSE: To present the clinical features of two brothers with molecularly confirmed X-linked juvenile retinoschisis (xlRS) but with non-characteristic electrophysiological findings. METHODS: Comprehensive ophthalmological examinations were performed. The electroretinograms (ERGs) were recorded under ISCEV standards, and ERGs elicited by long-duration stimuli were also evaluated. Standard genetic analysis of peripheral blood leukocytes was performed. RESULTS: Molecular testing revealed a novel 473-bp deletion including exon 4 in the XLRS1 gene in both siblings. This resulted in a frameshift mutation and a premature termination at codon 78. The scotopic and photopic ERGs were reduced, but the "negative-type" ERG, characteristic of xlRS, was not observed. Flicker ERGs were also highly reduced. Long-duration stimuli elicited ERGs with a complete loss of the b-wave and a preservation of the off-response, i.e., negative-type ERG. The phenotype/genotype relationship was not determined. CONCLUSION: The consistency of the ERGs elicited by long-duration stimuli in xlRS patients suggests that this type of stimuli provides responses that are a better indicator for the progression or stage of the disease.

Adult↗
PubMed2004

Solution structure of the SEA domain from the murine homologue of ovarian cancer antigen CA125 (MUC16).

Human CA125, encoded by the MUC16 gene, is an ovarian cancer antigen widely used for a serum assay. Its extracellular region consists of tandem repeats of SEA domains. In this study we determined the three-dimensional structure of the SEA domain from the murine MUC16 homologue using multidimensional NMR spectroscopy. The domain forms a unique alpha/beta sandwich fold composed of two alpha helices and four antiparallel beta strands and has a characteristic turn named the TY-turn between alpha1 and alpha2. The internal mobility of the main chain is low throughout the domain. The residues that form the hydrophobic core and the TY-turn are fully conserved in all SEA domain sequences, indicating that the fold is common in the family. Interestingly, no other residues are conserved throughout the family. Thus, the sequence alignment of the SEA domain family was refined on the basis of the three-dimensional structure, which allowed us to classify the SEA domains into several subfamilies. The residues on the surface differ between these subfamilies, suggesting that each subfamily has a different function. In the MUC16 SEA domains, the conserved surface residues, Asn-10, Thr-12, Arg-63, Asp-75, Asp-112, Ser-115, and Phe-117, are clustered on the beta sheet surface, which may be functionally important. The putative epitope (residues 58-77) for anti-MUC16 antibodies is located around the beta2 and beta3 strands. On the other hand the tissue tumor marker MUC1 has a SEA domain belonging to another subfamily, and its GSVVV motif for proteolytic cleavage is located in the short loop connecting beta2 and beta3.

Amino Acid Sequence↗
PubMed2004

Loss of peripheral morphine analgesia contributes to the reduced effectiveness of systemic morphine in neuropathic pain.

It is well known that the analgesic potency of morphine is reduced in neuropathic pain. In this study, we demonstrate that the decreased effectiveness of systemic morphine in neuropathic pain might be caused by the loss of morphine analgesia at the periphery. When given s.c. or i.t., the dose-response curves for morphine analgesia in Hargreaves thermal test were shifted rightward in partial sciatic nerve-injured mice compared with control sham-operated mice. The dose-response curves for i.c.v. morphine analgesia, however, were unchanged in nerve-injured mice, indicating no decrease in morphine potency at the supraspinal level. On the other hand, the dose-dependent analgesia produced by intraplantar (i.pl.) morphine in sham-operated mice almost completely disappeared in nerve-injured mice. With the more sensitive algogenic-induced nociceptive flexion test, significant reduction in the analgesic potency of systemic morphine was observed for bradykinin (BK) nociception in nerve-injured mice, and the analgesic effect of i.pl. morphine against BK nociception in sham-operated mice disappeared in nerve-injured mice. In immunohistochemical experiments, we found that, under normal state, mu-opioid receptors (MOPs) were mainly expressed in small-diameter unmyelinated dorsal root ganglion (DRG) neurons and colocalized with bradykinin B2 receptors. When we examined MOP expression in the DRG of nerve-injured mice, we observed a drastic decrease in MOP expression. Altogether, these data suggest that the lower potency of systemic morphine in neuropathic pain could be at least partly caused by the decreased MOP expression in DRG and subsequent loss of peripheral morphine analgesia in such a condition.

Analgesia↗
PubMed2004

Solution structure of a BolA-like protein from Mus musculus.

The BolA-like proteins are widely conserved from prokaryotes to eukaryotes. The BolA-like proteins seem to be involved in cell proliferation or cell-cycle regulation, but the molecular function is still unknown. Here we determined the structure of a mouse BolA-like protein. The overall topology is alphabetabetaalphaalphabetaalpha, in which beta(1) and beta(2) are antiparallel, and beta(3) is parallel to beta(2). This fold is similar to the class II KH fold, except for the absence of the GXXG loop, which is well conserved in the KH fold. The conserved residues in the BolA-like proteins are assembled on the one side of the protein.

Amino Acid Sequence↗
PubMed2004

Recombinant Sendai virus vectors deleted in both the matrix and the fusion genes: efficient gene transfer with preferable properties.

BACKGROUND: Sendai virus (SeV) is a new type of cytoplasmic RNA vector, which infects and replicates in most mammalian cells, directs high-level expression of the genes on its genome and is free from genotoxicity. In order to improve this vector, both the matrix (M) and fusion (F) genes were deleted from its genome. METHODS: For the recovery of the M and F genes-deleted SeV (SeV/DeltaMDeltaF), the packaging cell line was established by using a Cre/loxP induction system. SeV/DeltaMDeltaF was characterized and compared with wild-type and F or M gene-deleted SeV vectors in terms of transduction ability, particle formation, transmissible property and cytotoxicity. RESULTS: SeV/DeltaMDeltaF was propagated in high titers from the packaging cell line. When this vector was administered into the lateral ventricle and the respiratory tissue, many of the ependymal and epithelial cells were transduced, respectively, as in the case of wild-type SeV. F gene-deletion made the SeV vector non-transmissible, and M gene-deletion worked well to inhibit formation of the particles from infected cells. Simultaneous deletions of these two genes in the same genome resulted in combining both advantages. That is, both virus maturation into particles and transmissible property were almost completely abolished in cells infected with SeV/DeltaMDeltaF. Further, the cytopathic effect of SeV/DeltaMDeltaF was significantly attenuated rather than that of wild type in vitro and in vivo. CONCLUSIONS: SeV/DeltaMDeltaF is an advanced type of cytoplasmic RNA vector, which retains efficient gene transfer, gains non-transmissible properties and loses particle formation with less cytopathic effect.

Animals↗
PubMed2004

Regulation of NaPi-IIa mRNA and transporter protein in chronic renal failure: role of parathyroid hormone (PTH) and dietary phosphate (Pi).

Chronic renal failure (CRF) is associated with a high fractional phosphate excretion (FEPi), secondary hyperparathyroidism, and resistance to parathyroid hormone (PTH). This study was undertaken to characterize the role of PTH and dietary Pi in the regulation of PTH/PTH-related peptide receptor (PTHrP-R) mRNA and NaPi-IIa mRNA and protein in CRF. The following groups of rats were studied: (1) sham-operated (control); (2) CRF: 6 weeks after 5/6 nephrectomy (NPX); (3) NPX and parathyroidectomy (NPX + PTX); (4) NPX rats fed a low-Pi diet (NPX + LP); (5) sham-operated rats fed a low-Pi diet (control + LP); (6) sham-operated after PTX (control + PTX). Expression of NaPi-IIa mRNA and PTH/PTHrP-R mRNA was determined in the renal cortex by Northern hybridization. NaPi-IIa protein abundance was determined in cortical brush border membranes by immunoblotting. In NPX rats creatinine clearance decreased to 40 +/- 4%, PTH/PTHrP-R mRNA to 52.1 +/- 2% and NaPi-IIa mRNA to 41.2 +/- 5.5% of control. The PTH/PTHrP-R and NaPi-IIa mRNA in the NPX + PTX and NPX + LP group was similar to that in NPX. NaPi-IIa protein abundance was reduced in NPX compared with control, but was increased dramatically in NPX + PTX and NPX + LP compared to NPX, paralleled by a decrease in FEPi. These findings suggest that the elevated FEPi in CRF is maintained by decreased NaPi-IIa mRNA and NaPi-IIa protein abundance. In contrast, the observed decrease in FEPi with PTX or LP diet in CRF is mediated, at least partly, by increased NaPi-IIa protein abundance with no change in NaPi-IIa mRNA, suggesting post-transcriptional regulation of the NaPi-IIa transporter.

Administration, Oral↗
PubMed2004

Successful treatment of subfoveal choroidal neovascularization associated with combined hamartoma of the retina and retinal pigment epithelium.

PURPOSE: To describe a patient with subfoveal choroidal neovascularization (CNV) associated with combined hamartoma of the retina and retinal pigment epithelium (CHRRPE), treated successfully by submacular surgery. DESIGN: Interventional case report. METHODS: A 12-year-old girl was referred to our clinic for evaluation. Visual acuity was 20/30 in the affected left eye. Ophthalmoscopy disclosed juxtapapillary CHRRPE and subfoveal pigmented CNV. Vitreous surgery was carried out because of visual deterioration to 20/60. RESULTS: The posterior vitreous was strongly attached to glial tissue at the superior margin of the optic disk in the CHRRPE region. The CNV, which was not connected with the CHRRPE, was carefully removed, resulting in visual improvement to 20/20 5 months after surgery. Histologically, the excised membrane showed fibroblast-rich cellular component and a type 2 configuration. CONCLUSION: Submacular surgery can be effective for the treatment of secondary CNV associated with CHRRPE.

Child↗
PubMed2004

Vitreous concentrations of triamcinolone acetonide in human eyes after intravitreal or subtenon injection.

PURPOSE: To compare vitreous concentrations of triamcinolone acetonide (TA) achieved by prior therapeutic intravitreal and subtenon injections. DESIGN: Interventional case series. METHODS: Vitreous samples were collected from patients who required vitreous surgery, six having received a subtenon injection of TA and another six, an intravitreal injection. Vitreous concentrations of TA were measured by high-performance liquid chromatography. RESULTS: Vitreous concentrations of TA after intravitreal injection were 1.22 +/- 0.24 mug/ml, significantly higher than those after subtenon injection (<0.001 mug/ml, P = .003). Vitreous concentrations of TA after subtenon injection and TA-assisted vitrectomy performed in a few patients to visualize the transparent vitreous gel were 0.20 +/- 0.11 mug/ml, an intermediate amount between these two groups. CONCLUSION: Much higher vitreous concentrations of TA after intravitreal injection than subtenon injection may accelerate therapeutic effect when intravitreal injections are given to reduce macular edema. Subtenon injections of TA may act via the sclera as opposed to the vitreous.

Aged↗
PubMed2004

Intraoperative breakage of a 25-gauge vitreous cutter.

PURPOSE: To report breakage of a 25-gauge vitreous cutter during vitreous surgery. DESIGN: Interventional case report. METHODS: A 60-year-old woman was referred for management of an epiretinal membrane at the macula. Visual acuity was 20/100 in the affected left eye. Vitreous surgery using a 25-gauge vitrectomy system was carried out with a combination of conventional cataract surgery. RESULTS: The vitreous cutter was lodged within the sclerotomy cannula after peripheral vitrectomy and was pulled together with the cannula. The cannula was reinserted by trocar, but as the floating peeled epiretinal membrane was dissected with the vitreous cutter, the tip of the cutter was broken and was aspirated with the membrane. Stereoscopic microscopy and scanning electron microscopy demonstrated that the edge that had broken at the cutter port was smooth. CONCLUSION: Although 25-gauge instruments remain useful, care should be taken against rare surgical complications related to their fragility.

Catheterization↗
PubMed2004

Evaluation of calcification of a hydrogel intraocular lens by optical coherence tomography.

We describe 2 cases of calcification of hydrogel intraocular lenses (IOLs) evaluated by optical coherence tomography. Dense or slight surface opacities of hydrogel IOLs were detected initially by slitlamp biomicroscopy in a 55-year-old woman and a 77-year-old woman. The opacities resulted in complaints of hazy vision after uneventful phacoemulsification and IOL implantation. Optical coherence tomography was used to further assess the opacities and showed calcification by high reflectivity on the anterior and posterior IOL surfaces in the first patient and on the anterior surface in the second patient. No abnormal reflectivity was seen on the surface of a hydrophobic acrylic IOL in the second patient's fellow eye. Optical coherence tomography may be useful to detect calcification of a hydrogel IOL.

Aged↗
PubMed2004

The CAP-Gly domain of CYLD associates with the proline-rich sequence in NEMO/IKKgamma.

CYLD was originally identified as the human familial cylindromatosis tumor suppressor. Recently, it was reported that CYLD directly interacts with NEMO/IKKgamma and TRAF2 in the NF-kappaB signaling pathway. The two proteins bind to a region of CYLD that contains a Cys-box motif and the third cytoskeleton-associated protein-glycine conserved (CAP-Gly) domain. Here we report that the third CAP-Gly domain of CYLD specifically interacts with one of the two proline-rich sequences of NEMO/IKKgamma. The tertiary structure of the CAP-Gly domain shares the five-stranded beta sheet topology with the SH3 domain, which is well known as a proline-rich sequence-recognition domain. However, chemical shift mapping revealed that the peptide binding site of the CAP-Gly domain is formed without the long peptide binding loop characteristic of the SH3 domain. Therefore, CAP-Gly is likely to be a novel proline-rich sequence binding domain with a mechanism different from that of the SH3 domain.

Amino Acid Sequence↗
PubMed2004

Estimation of the time-course of dopamine D2 receptor occupancy in living human brain from plasma pharmacokinetics of antipsychotics.

Although the kinetic profile of antipsychotics at dopamine D2 receptor sites has been suggested to be important for antipsychotic action and dosing schedule, the kinetic profiles of the respective antipsychotic drugs in the brain have not yet been clearly defined. We aimed to estimate the time-course of dopamine D2 receptor occupancy from plasma pharmacokinetics and the apparent in-vivo affinity parameter (ED50; concentration required to induce 50% occupancy). Dopamine D2 receptor occupancies and plasma concentrations of risperidone were measured in five patients with schizophrenia using positron emission tomography with [11C]FLB 457. Measured dopamine D2 occupancies were compared with those estimated from plasma kinetics and in-vivo ED50. The time-course of dopamine D2 receptor occupancy was simulated with altered plasma kinetics or apparent in-vivo affinity parameters of the drug. Mean half-life of dopamine D2 receptor occupancy of risperidone was 80.2 h while that of the plasma concentration was 17.8 h. Dopamine D2 receptor occupancy estimated from plasma pharmacokinetics and in-vivo ED50 was within 1 S.D. of the mean measured occupancy. When the ED50 value was changed to one-tenth and 10-fold, the simulated half-life of receptor occupancy changed to 117.6 h and 27.3 h respectively. Using plasma pharmacokinetics and in-vivo ED50, the time-course of receptor occupancy could be calculated. Simulation of drug kinetics at receptors would provide useful information for the evaluation of antipsychotics.

Adult↗