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Biomedical subjects

Manabu Mochizuki

Publications and source records attributed to Manabu Mochizuki.

At least 37 records · Page 2Linked to original sources

[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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

PRBS-determined temporal frequency characteristics of VEP in glaucoma.

The purpose of this study was to determine whether the PRBS-VEP-determined temporal frequency characteristics (TFCs) of the visual pathways are useful for evaluating the properties of the visual system of glaucomatous patients. The VEPs elicited by pseudorandom stimulation (PRBS) with red LEDs were recorded from 26 eyes with primary open angle glaucoma and 11 age-matched normal eyes. The glaucomatous patients were divided into 3 groups according to the size and shape of their visual field defect; early (9), moderate (9), and severe (8). The cross-spectrum between the PRBS and PRBS-VEPs was used as the TFCs. The TFC of each glaucomatous group were compared to those of the normal controls. A depression of the TFC was found for the middle and high frequencies (18-28 Hz) in the moderate group, and the depression spread to lower frequencies (4-16 Hz) in the severe groups. The TFC values at 14-20 Hz were depressed in the moderate group and most frequencies were depressed significantly with the progression of glaucoma (p < 0.05). The sensitivity of the TFC at 18-20 Hz was 56%, 89% and 100% in the early, moderate and severe glaucoma groups, respectively, and the specificity was 82%. We conclude that the PRBS-determined TFC is altered in glaucomatous eyes, and the frequencies depressed were related to the degree of glaucoma. These findings indicate that the PRBS-determined TFC can be useful for evaluating visual function of glaucomatous eyes.

Aged↗

Characteristics of first and second order kernels of visually evoked potentials elicited by pseudorandom stimulation.

The characteristics of the first and the second order kernels of the visually evoked potentials (VEPs) elicited by pseudorandom binary sequence (PRBS) stimuli were investigated. VEPs were recorded from six eyes of four normal volunteers. The effects of stimulus luminance on the latency and amplitude of the first and the second order kernels were determined. The temporal interactions of transient VEPs elicited by single and double pulse stimuli were compared with the first and the second order kernels of the PRBS-VEPs. The correlation coefficient between the logarithm of the stimuli luminance (log I) and VEP amplitude of the first order kernels was 0.45 (p < 0.05), and that between log I and P1 latency was -0.62 (p < 0.005). The second order kernels were not equal to the temporal interactions of the responses. However, the latency of the negative peak of the fourth slice was similar to the temporal interaction to double pulse stimulation with an inter-stimulus interval of 40 ms. An inhibitory component at 40 ms following the first stimulus was detected in the analysis of both PRBS-VEPs second order kernel and transient VEPs. This function may help to increase the frequency of critical flicker fusion in normal subjects.

Adult↗

Effects of dopamine, dobutamine, amrinone and milrinone on regional blood flow in isoflurane anesthetized dogs.

The effects of cyclic AMP increasing cardiotonics (dopamine, dobutamine, amrinone and milrinone) on the blood flow in most organs were compared using colored microsphere technique in isoflurane-anesthetized dogs. Dopamine increased blood flow in ventricular myocardium. Furthermore dopamine induced the increase in blood flow in intestine and kidney at low to middle dose, but not at high dose. Dobutamine induced the highest increase in blood flow in ventricular myocardium and skeletal muscle among the drugs evaluated at middle and high doses. Amrinone and milrinone increased blood flow in ventricular myocardium almost same with catecholamines, and milrinone decreased vascular resistance moderately in most other organs. Milrinone might be more useful than catecholamines for improvement of congestive heart failure or peripheral circulatory failure accompanied with exceeded vasoconstriction.

Amrinone↗

Establishment and characterization of four canine melanoma cell lines.

Four canine melanoma cell lines were established from the subcutaneous, oral gingival and mucosal melanoma tissues at the primary and metastatic sites. These cell lines were designated as CMeC-1, CMeC-2, KMeC and LMeC. The cells were spindles in shape, similar to that of primary tumor cells. The doubling times of these cells ranged from 34.1 +/- 5.61 to 57.9 +/- 3.28 hr and their chromosome number ranged from 46 to 80. When transplanted into nude mice, CMeC-1 and LMeC produced tumors, whereas CMeC-2 and KMeC did not. The morphology of the tissue formed by xenotransplantation of these cells was similar to their primary tumors.

Animals↗

Secondary erythrocytosis associated with schwannoma in a dog.

An 11-year-old, spayed female mixed-breed dog showed clinical signs of right forelimb lameness and pain by palpation around the neck. Radiography and computed tomography (CT) revealed an extradural mass at the 6th and 7th cervical vertebrae, which compressed the spinal cord. The mass was surgically removed and histopathologically diagnosed as schwannoma. The dog recovered her normal gait after hemilaminectomy and removal of the mass. Ten months after the surgery, the tumor recurred with absolute erythrocytosis and was surgically removed again. This removal temporarily resolved the erythrocytosis with a decrease in plasma erythropoietin (EPO) concentration. EPO protein was detected immunohistochemically in the tumor cells. Erythrocytosis in this dog may be caused by ectopic EPO produced in the schwannoma tissues.

Animals↗