Biomedical subjects

Manabu Mochizuki

Publications and source records attributed to Manabu Mochizuki.

At least 19 recordsLinked to original sources

PubMed2006

Choroidal vein and artery occlusion following photodynamic therapy in eyes with pathologic myopia.

PURPOSE: To describe highly myopic patients in which either the large choroidal veins or arteries were occluded following PDT treatment. METHODS: Demographic features of two highly myopic patients in which large choroidal vessels were occluded at 1 week following PDT, among a total of 23 patients who received PDT due to choroidal neovascularization (CNV) caused by high myopia, were demonstrated. RESULTS: In case 1, ICG angiography demonstrated the complete occlusion of several large choroidal veins within the laser-applied area at 1 week after PDT. In case 2, ICG angiography demonstrated an occlusion of choroidal artery emanating from beneath the CNV. One month after PDT, re-perfusion of the occluded choroidal vessels was noted in both patients. CONCLUSION: Occlusion of choroidal veins has never been reported in eyes with CNV treated by verteporfin therapy. Although further studies are necessary, occlusion of large choroidal vessels might happen in highly myopic eyes more commonly than expected. ICG angiography at 1 week after PDT was useful to evaluate the impact of PDT on large choroidal vessels.

Aged↗

PubMed2006

SUV39H1 interacts with HTLV-1 Tax and abrogates Tax transactivation of HTLV-1 LTR.

BACKGROUND: Tax is the oncoprotein of HTLV-1 which deregulates signal transduction pathways, transcription of genes and cell cycle regulation of host cells. Transacting function of Tax is mainly mediated by its protein-protein interactions with host cellular factors. As to Tax-mediated regulation of gene expression of HTLV-1 and cellular genes, Tax was shown to regulate histone acetylation through its physical interaction with histone acetylases and deacetylases. However, functional interaction of Tax with histone methyltransferases (HMTase) has not been studied. Here we examined the ability of Tax to interact with a histone methyltransferase SUV39H1 that methylates histone H3 lysine 9 (H3K9) and represses transcription of genes, and studied the functional effects of the interaction on HTLV-1 gene expression. RESULTS: Tax was shown to interact with SUV39H1 in vitro, and the interaction is largely dependent on the C-terminal half of SUV39H1 containing the SET domain. Tax does not affect the methyltransferase activity of SUV39H1 but tethers SUV39H1 to a Tax containing complex in the nuclei. In reporter gene assays, co-expression of SUV39H1 represses Tax transactivation of HTLV-1 LTR promoter activity, which was dependent on the methyltransferase activity of SUV39H1. Furthermore, SUV39H1 expression is induced along with Tax in JPX9 cells. Chromatin immunoprecipitation (ChIP) analysis shows localization of SUV39H1 on the LTR after Tax induction, but not in the absence of Tax induction, in JPX9 transformants retaining HTLV-1-Luc plasmid. Immunoblotting shows higher levels of SUV39H1 expression in HTLV-1 transformed and latently infected cell lines. CONCLUSION: Our study revealed for the first time the interaction between Tax and SUV39H1 and apparent tethering of SUV39H1 by Tax to the HTLV-1 LTR. It is speculated that Tax-mediated tethering of SUV39H1 to the LTR and induction of the repressive histone modification on the chromatin through H3 K9 methylation may be the basis for the dose-dependent repression of Tax transactivation of LTR by SUV39H1. Tax-induced SUV39H1 expression, Tax-SUV39H1 interaction and tethering to the LTR may provide a support for an idea that the above sequence of events may form a negative feedback loop that self-limits HTLV-1 viral gene expression in infected cells.

Base Sequence↗

PubMed2006

Characteristics of peripapillary detachment in pathologic myopia.

OBJECTIVE: To evaluate the prevalence and clinical features of a newly recognized peripapillary lesion specific to high myopia, peripapillary detachment in pathologic myopia (PDPM), in a large series of patients with high myopia. METHODS: Three hundred twenty-four patients (632 eyes) with high myopia were enrolled in this study. We examined the prevalence, range, fluorescein and indocyanine green angiographic findings, and optical coherence tomography findings of PDPM for these patients. Visual field testing (Goldmann kinetic perimetry and the Humphrey 30-2 program) was also performed in the patients with PDPM. RESULTS: Peripapillary detachment in pathologic myopia was identified in 31 of 632 highly myopic eyes (4.9%). The optical coherence tomographic scan across the PDPM lesion revealed a localized detachment of retinal pigment epithelium adjacent to the optic nerve. Although PDPM was always situated adjacent to the inferior edge of the optic disc, in some patients it surrounded almost the entire optic disc. There was a steep excavation of the inferior myopic conus adjacent to the PDPM, and the inferotemporal retinal vein was markedly bent at the transition from the PDPM to the excavated myopic conus. Glaucomatous visual field defects were frequently detected in eyes with PDPM (71.0%). CONCLUSIONS: The findings of this study indicate that PDPM is not uncommon among highly myopic eyes. Although its pathogenesis and pathologic significance require further classification, PDPM might be another indicator of visual field defects in high myopia.

Adolescent↗

PubMed2006

Pattern-reversal visual evoked potentials in patients with human T-lymphotropic virus type 1 uveitis.

PURPOSE: The purpose of this study was to evaluate the possible injury in the optic pathway by measuring P100 peak latency of pattern-reversal visual evoked potentials (PVEPs) in patients with human T-lymphotropic virus type 1 uveitis (HU). METHODS: The P100 peak latency of PVEP was measured during the period without macular abnormalities observed by fluorescein angiography in 23 patients (46 eyes) with HU and 24 patients (48 eyes) with Vogt-Koyanagi-Harada disease (VKH) with a corrected visual acuity of 20/25 or more. To determine the normal upper limit of P100 peak latency, PVEPs were measured in 31 normal subjects (31 eyes). In addition, in the HU patients, the serum anti-HTLV-1 antibody titer was measured by particle agglutination assay within 3 months of PVEP recording, and the period of HU was retrospectively surveyed. RESULTS: Delayed latency was observed in 4 (7 eyes) of the 23 patients (46 eyes) with HU but none of the 24 patients (48 eyes) with VKH. All four patients with delayed latency showed a serum anti-HTLV-1 antibody titer of more than x4000. The HU period in the HU patients was 0.2-14.0 years, and the HU periods in the four patients with delayed latency were 0.8, 2.7, 4.2, and 14.0 years, respectively. CONCLUSIONS: We measured pattern-reversal visual evoked potentials and observed delayed P100 peak latency in 7 of the 46 eyes in 4 (17.4%) of the 23 HU patients. This suggests injury in the optic pathway including the optic nerve by HTLV-1 in some patients with HU. In the future, consideration should also be given to the possible development of optic neuropathy due to HTLV-1.

Adolescent↗

PubMed2006

Cytokine profile in aqueous humor and sera of patients with infectious or noninfectious uveitis.

PURPOSE: To determine the cytokine expression profile at the protein level in aqueous humor (AqH) and sera of patients with uveitis. METHODS: Patients with various clinical entities of strictly diagnosed infectious or noninfectious uveitis were tested. AqH and sera were collected from patients with uveitis. AqH was also collected during surgery from patients with cataract, as control specimens. Interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-2, -4, -5, and -10 were measured from nondiluted samples simultaneously, with microparticle-based flow cytometric analysis. RESULTS: In AqH IFN-gamma was the most abundant cytokine in both infectious (mean, 3240.5 pg/mL) and noninfectious (mean, 115.6 pg/mL) uveitis, and IL-10 was the second (mean, 402.1 pg/mL, infectious uveitis; 7.5 pg/mL, noninfectious uveitis). The expression level of other cytokines in AqH was generally higher in infectious uveitis than in noninfectious uveitis, but the levels were lower than that of IL-10. There was no remarkable difference, however, in the cytokine expression pattern in AqH of the different clinical entities of uveitis. Sera from patients with noninfectious uveitis contained IFN-gamma (mean, 45.0 pg/mL), but the other serum cytokines in both types of uveitis were low or under the detectable level. CONCLUSIONS: IFN-gamma is the most abundant cytokine in infectious and noninfectious uveitis, with a remarkable difference between the two groups. The data suggest that cytokines in AqH of infectious uveitis are locally produced, whereas in noninfectious uveitis, IFN-gamma is produced both in the eye and the peripheral blood.

Adult↗

PubMed2006

[Disc neovascularization in a patient with Vogt-Koyanagi-Harada disease and efficacy of steroid pulse therapy].

PURPOSE: To report a patient with Vogt-Koyanagi-Harada disease who developed neovascularization at the optic disc. CASE: A 19-year-old woman visited our hospital two months after becoming aware of fever, headache, tinnitus, hearing disturbance, and floaters in the right eye. Ophthalmic examination disclosed granulomatous inflammation in the anterior segment, sunset glow fundus and neovascularization at the optic disc. Vogt-Koyanagi-Harada disease was diagnosed and treated with corticosteroid pulse therapy, followed by oral corticosteroids. Three months after the systemic corticosteroid therapy, the neovascularization disappeared. CONCLUSIONS: Sufficient treatment with systemic corticosteroids is effective for the intraocular neovascularization associated with consecutive inflammation.

Adult↗

PubMed2005

Prognostic value of magnetic resonance imaging in dogs with paraplegia caused by thoracolumbar intervertebral disk extrusion: 77 cases (2000-2003).

OBJECTIVE: To determine whether magnetic resonance imaging findings in dogs with paraplegia caused by thoracolumbar intervertebral disk extrusion were predictive of clinical outcome. DESIGN: Retrospective case series. ANIMALS: 77 dogs. PROCEDURE: Medical records and magnetic resonance images were reviewed; clinical outcome was classified as successful (regained ability to walk with no more than mild neurologic deficits) or unsuccessful (severe neurologic deficits persisted). The prognostic value of magnetic resonance imaging was compared with prognostic value of deep pain perception, duration of clinical signs, and rate of onset of clinical signs. RESULT: 33 (43%) dogs had areas of hyperintensity of the spinal cord greater than or equal to the length of the L2 vertebral body on T2-weighted magnetic resonance images. All 44 dogs without areas of hyperintensity on T2-weighted images had a successful outcome, but only 18 of the 33 (55%) dogs with an area of hyperintensity did. Only 5 of 16 dogs with an area of hyperintensity that had also lost deep pain perception had a successful outcome. The odds ratio for an unsuccessful outcome for a dog with an area of hyperintensity (29.87) was higher than the odds ratio for a dog that had lost deep pain perception (5.24). Duration and rate of onset of clinical signs were not associated with clinical outcome. CONCLUSIONS AND CLINICAL RELEVANCE: Findings suggest that results of magnetic resonance imaging can be used to predict clinical outcome in dogs with paraplegia caused by intervertebral disk extrusion.

Animals↗

PubMed2005

Detection of paravascular retinal cysts before using OCT in a highly myopic patient.

PURPOSE: We describe a case of high myopia who developed paravascular retinal rarefaction generated by vitreoretinal adhesion on retinal vessels detected using optical coherence tomography (OCT). METHODS: A 31-year-old man received a regular ophthalmologic examination for high myopia including detailed fundus examination and OCT. RESULTS: Detailed fundus examination revealed retinal rarefaction and fissure-like findings alongside the superior temporal retinal artery and vein in the right eye. OCT images revealed vitreoretinal adhesions on the retinal artery and a paravascular cystoid space in the inner retina. There was no retinal detachment. The axial length had increased by 1.50 mm over 15 years. CONCLUSION: Paravascular retinal rarefaction as well as pseudohole formation caused by vitreoretinal adhesion on retinal vessels was detected in this patient using OCT. OCT might be useful to detect early-stage retinal pathologies caused by paravascular vitreoretinal traction in highly myopic patients.

Adult↗

PubMed2005

The potential role of amyloid beta in the pathogenesis of age-related macular degeneration.

Drusen are extracellular deposits that lie beneath the retinal pigment epithelium (RPE) and are the earliest signs of age-related macular degeneration (AMD). Recent proteome analysis demonstrated that amyloid beta (Abeta) deposition was specific to drusen from eyes with AMD. To work toward a molecular understanding of the development of AMD from drusen, we investigated the effect of Abeta on cultured human RPE cells as well as ocular findings in neprilysin gene-disrupted mice, which leads to an increased deposition Abeta. The results showed that Abeta treatment induced a marked increase in VEGF as well as a marked decrease in pigment epithelium-derived factor (PEDF). Conditioned media from Abeta-exposed RPE cells caused a dramatic increase in tubular formation by human umbilical vein endothelial cells. Light microscopy of senescent neprilysin gene-disrupted mice showed an increased number of degenerated RPE cells with vacuoles. Electron microscopy revealed basal laminar and linear deposits beneath the RPE layer, but we did not observe choroidal neovascularization (CNV). The present study demonstrates that Abeta accumulation affects the balance between VEGF and PEDF in the RPE, and an accumulation of Abeta reproduces features characteristic of human AMD, such as RPE atrophy and basal deposit formation. Some other factors, such as breakdown of integrity of Bruch membrane, might be necessary to induce CNV of AMD.

Amyloid beta-Peptides↗

PubMed2005

Differential activation of cerebral blood flow by stimulating amblyopic and fellow eye.

PURPOSE: Positron emission tomography (PET), the blood flow response in the primary visual cortex (V1) to two visual stimuli, low temporal frequency (6 Hz) to activate the parvocellular system, and high temporal frequency (25 Hz) to activate the magnocellular system were used to investigate pathophysiologic mechanism of amblyopia. METHODS: Five women and one man who were aged between 26 and 60 years, who were ophthalmologically normal except for amblyopia, and who had corrected visual acuity in the amblyopic eye of 0.6 or worse were examined. An intravenous injection of the H(2)(15)O was given, and the regional cerebral blood flow was measured by PET during full-field stimulation with either 6 Hz or 25 Hz flicker to the amblyopic or the sound eye. RESULT: The activation of blood flow in the contra-lateral area V1 by the 6-Hz stimulation of the sound eye was greater than that during the stimulation of the amblyopic eye (P<0.05, small volume correction, n=6). With 25-Hz stimulation of the sound and amblyopic eyes, the blood flow in the contra-lateral and ipsi-lateral areas V1 was not significantly different. CONCLUSION: The decreased activation of blood flow in the contra-lateral V1 by low temporal frequency stimuli supports the hypothesis that the parvocellular pathway in amblyopic eyes is depressed.

Adult↗

PubMed2005

The effects of amniotic membrane on retinal pigment epithelial cell differentiation.

PURPOSE: To examine the characteristics of retinal pigment epithelial (RPE) cells cultured on amniotic membrane (AM). The present study examined how AM modulates RPE cell differentiation. METHODS: Human RPE cells were cultured on the basement membrane side of dispase treated AM. After one week of cellular confluence, cultures were terminated, conditioned medium was collected, and total RNA was extracted. The expression pattern of several genes considered to participate in the function of differentiated RPE was evaluated. Ultrastructural changes were evaluated by transmission electron microscopy. RESULTS: Morphologically, RPE cells cultured on AM exhibited ultrastructural epithelial features such as microvilli of the apical membrane and intercellular junctions. Gene expression of RPE65, CRALBP, bestrophin, and tyrosinase related protein (TRP)-2 was upregulated in RPE cells cultured on AM compared to cells cultured on plastic. In addition, protein production of vascular endothelial growth factor, thrombospondin-1, and pigment epithelium derived factor was markedly increased in cells cultivated on AM. Gene expression of cathepsin D, brain derived neurotrophic factor, and basic fibroblast growth factor, however, did not differ between RPE cells cultured on plastic or AM. CONCLUSIONS: RPE cells cultured on AM demonstrated an epithelial phenotype morphologically and several growth factors important for maintaining retinal homeostasis were upregulated. AM might be a useful matrix substrate to retain the differentiated and epithelial phenotype of RPE for subretinal transplantation.

Actins↗

PubMed2005

Identification and characterization of a canine highly similar to retinoic acid receptor alpha.

A canine highly similar to retinoic acid receptor alpha (canine HS-RARa) cDNA was isolated from the spleen tissue. A database search and the alignment revealed that the canine cDNA was most similar to highly similar type of human RARa and was named canine HS-RARa. The expression of the genes encoding RARa in the dog was the highest in the testis and moderate in the blood, lymph node, mammary gland, pancreas, salivary gland, spleen, thyroid gland, tonsil and uterus. The nucleotide sequence encoded the 462-amino acid containing the conserved sequence motif of RARa. Though the amino acid sequences were well-conserved among species, some unique arrangements were observed within each class. In the phylogenetic analysis, each species separated according to their class. In the branch of mammals, the dog is in the cluster of humans, mice and western wild mice. However, hamsters and rats formed another branch.

Amino Acid Sequence↗

PubMed2005

Establishment and characterization of eight feline mammary adenocarcinoma cell lines.

Eight new feline mammary adenocarcinoma cell lines derived from either primary or metastatic lesions were established. The morphology of all the cell lines was epithelioid and round to spindle in shape, with cell growth occurring in a monolayer fashion. On immunohistochemistry, these cells reacted with anti-keratin and anti-vimentin antisera. The doubling time of these cells was between 19 and 54 hr. Tumor masses were developed in nude mice by subcutaneous inoculation of the cells that were histologically identical to their original mammary tumor lesions. Telomerase activities measured using the telomeric repeat amplification protocol assay revealed high telemetric activity in all of the cells.

Adenocarcinoma↗

PubMed2005

Magnetic resonance imaging of a canine eye with melanoma.

An 8-year-old Beagle dog had exophthalmos of the left eye for the last two past months. On ophthalmoscopy, the intraocular lesion could not be evaluated due to the opacity of the cornea. Ultrasonography revealed that the eyeball was distorted in shape and shifted in position, however, the precise lesion could not be identified. On magnetic resonance (MR) imaging, the lesion was observed as hyperintense on T1-weighted and hypointense on T2-weighted images, similar to those reported in human melanoma. The lesion was histologically diagnosed to be malignant intraocular melanoma. Though this is only a case report, canine ocular melanoma may show the similar characteristic MR images as in human uveal malignant melanoma.

Animals↗

PubMed2004

Characteristics of patients with a favorable natural course of myopic choroidal neovascularization.

OBJECTIVE: To identify the characteristics of patients with myopic choroidal neovascularization (CNV) who had a favorable visual prognosis without treatment. METHODS: We reviewed the medical records of 52 consecutive patients (57 eyes) with myopic CNV who were followed for at least 5 years after the onset of CNV. Clinical characteristics (patient age, CNV size and location, visual acuity at onset, chorioretinal atrophy development around CNV, and degree of myopia) were compared between patients whose visual acuity 5 years after CNV onset was better than 20/40 and those whose visual acuity was worse than 20/200. RESULTS: Among 57 eyes, eight eyes (14.0%; 8 patients) had a final visual acuity better than 20/40. On the other hand, 37 eyes (64.9%; 33 patients) had a final visual acuity worse than 20/200. Statistical analysis revealed that the patients with a good prognosis (final visual acuity better than 20/40) were significantly younger, had significantly smaller CNV, and significantly better initial visual acuity (Mann-Whitney U-test, p<0.05). Juxtafoveal CNV was more frequently observed in patients with a good prognosis than in those with a poor prognosis (Fisher's exact probability test, p<0.05). Only one patient (12.5%) in the good prognosis group developed a very limited area of chorioretinal atrophy around the regressed CNV, while 91.9% of the patients in the poor prognosis group developed chorioretinal atrophy. Refractive status and the axial length measurements did not differ between the two groups. CONCLUSIONS: Some young patients with myopic CNV retain favorable vision over the long term without active treatment. These information might be useful to predict the visual outcome of patients with myopic CNV.

Adult↗

PubMed2004

Tomographic image and visual recovery of acute macula-off rhegmatogenous retinal detachment.

PURPOSE: To observe the macula of acute rhegmatogenous retinal detachment involving the macula with optical coherence tomography (OCT) after scleral buckling and to study the relation between pre- and postoperative visual acuity and the OCT image. METHODS: Prospective study of 15 eyes of 15 patients with macula-off rhegmatogenous retinal detachment. We selected cases with preoperative visual acuity worse than 0.5 to analyze the improvement in postoperative visual acuity. The time period between macula-off retinal detachment and surgery was less than 1 week. RESULTS: Indirect ophthalmoscopy indicated that all retinal detachments were reattached at 2 weeks postoperatively. Accumulation of subretinal fluid at the fovea was observed in nine (60%) cases with OCT. In four of these nine eyes, the accumulation of subretinal fluid persisted up to 6 months after the operation. The presence of residual subretinal fluid did not influence visual recovery during the 6 months' postsurgical follow-up. CONCLUSIONS: OCT revealed postoperative residual subretinal fluid at the macula in some acute macula-off retinal detachment cases. Residual subretinal fluid did not influence the recovery of visual acuity for at least 6 months after surgery.

Acute Disease↗

PubMed2004

Reduction of retinal blood flow in high myopia.

PURPOSE: To investigate changes in retinal vessel diameter and blood velocity in high myopia using laser Doppler velocimetry. METHODS: Thirty-nine subjects (39 eyes) were enrolled in the study. The subjects were divided into three groups according to their refractive status; 15 eyes (15 patients) with emmetropia (within +/-3.0 diopters), 14 eyes (14 patients) with mild myopia (between -3.0 and -8.0 diopters), and 10 eyes (10 patients) with high myopia (>-8.0 diopters). Patient age was matched between groups. Blood velocity and vessel diameter of the upper or lower temporal retinal artery were measured using laser Doppler velocimetry with an eye-tracking system, and measurements were compared between groups. RESULTS: The average retinal blood flow and vessel diameter in highly myopic eyes were significantly decreased compared with emmetropic eyes or mild myopic eyes (Mann-Whitney U test, p<0.05). Also, there was significant difference regarding retinal blood flow and vessel diameter between eyes with mild myopia and the other groups. In addition, there was no significant difference in blood velocity between the three groups. CONCLUSIONS: Retinal blood flow was decreased in high myopia, mainly due to the narrowing of the retinal vessel diameter. Impaired retinal blood flow might have a role in the development of chorioretinal atrophy in high myopia.

Adult↗

PubMed2004

Long-term stability of bone tissues induced by an osteoinductive biomaterial, recombinant human bone morphogenetic protein-2 and a biodegradable carrier.

The long-term stability of bone tissues induced by recombinant human bone morphogenetic protein-2 (rhBMP-2) and poly[L-lactide-co-glycolide] copolymer-coated gelatin sponge (PGS) was examined. In 16 dogs, 2.5 cm unilateral bone defects were created in the left tibial diaphyses. Tibia was fixed with metal plate, and PGS impregnated with (0.4 mg/cm(3)) or without rhBMP-2 was implanted into 15 or one defects, respectively. The metal plates of rhBMP-2-treated limbs were removed 16 weeks after the implantation. The bilateral tibiae of five animals each of the rhBMP-2-treated group were harvested at 32, 52 or 104 weeks, and served for biomechanical testing and histology. Although the defect that received PGS alone resulted in nonunion at 16 weeks, all defects treated with rhBMP-2 achieved radiographic bony union by 8 weeks. Biomechanical properties of the regenerated bones restored to the levels of intact tibiae at 32 weeks, but torsional stiffness was significantly higher. No statistical significances were detected in all parameters between regenerated and intact tibiae at 104 weeks. No radiographic and histological findings suggesting enhanced resorption to the regenerated bones were observed. These results suggest the long-term stability of the bone tissues induced by rhBMP-2, and the usefulness of rhBMP-2-impregnated PGS as a biomaterial for long bone defect filling.

Animals↗