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Makoto Nakamura

Publications and source records attributed to Makoto Nakamura.

At least 19 recordsLinked to original sources
PubMed2006

cAMP-responsive element binding protein mediates a cGMP/protein kinase G-dependent anti-apoptotic signal induced by nitric oxide in retinal neuro-glial progenitor cells.

Nitric oxide (NO) is cytoprotective to certain types of neuronal cells. The neuroprotective ability of NO in the retina was reportedly mediated by the cyclic GMP (cGMP) to protein kinase G (PKG) pathway. Cyclic AMP-responsive element binding protein (CREB) plays an essential role in the NO/cGMP/PKG-mediated survival of rat cerebellar granule cells. We tested whether CREB transduces the NO/cGMP/PKG anti-apoptotic cascade in R28 neuro-glial progenitor cells. Apoptosis was induced in R28 cells by serum deprivation for 24 h. Varying concentrations of two NO donors, sodium nitroprusside (SNP) and nipradilol, were added to medium with or without an NO scavenger, a soluble guanylyl cyclase inhibitor, or a PKG inhibitor. The cells were immunostained against activated caspase-3 and counterstained with Hoechst 33258. Apoptosis was quantified by counting activated caspase-3 positive or pyknotic cells. SNP and nipradilol rescued R28 cells from apoptosis in a dose-dependent manner, at an optimal concentration of 1.0 microM and 10 microM, respectively. Higher concentrations were cytotoxic. The NO scavenger and the inhibitors decreased the anti-apoptotic effect of the NO donors. Intracellular cGMP levels were increased after exposure to SNP and nipradilol. Western blotting showed that both NO donors increased CREB phosphorylation, which was blocked when pre-exposed to the inhibitors. Transfection with a dominant negative CREB construct defective of phosphorylation at Ser-133 interfered with the anti-apoptotic activity of SNP. These results indicate that CREB at least in part mediates the cGMP/PKG-dependent anti-apoptotic signal induced by NO in R28 cells.

Animals↗
PubMed2006

Quantification of retinal nerve fiber layer thickness reduction associated with a relative afferent pupillary defect in asymmetric glaucoma.

AIM: The relative afferent pupillary defect (RAPD) is an important clinical sign of asymmetrical retinal ganglion cell and axonal damage. Although glaucoma essentially affects bilateral eyes, a subset of patients manifests asymmetrical glaucomatous optic neuropathy (GON), which exhibits an RPAD in the more advanced eyes. However, the degree to which axonal loss occurs before an RAPD is clinically detectable has not been substantiated. The purpose of this study is to assess the relationship between the depth of a clinically detectable RAPD and the reduction ratio of retinal nerve fiber layer (RNFL) thickness in the more advanced eyes relative to that in the contralateral less advanced eyes of patients with asymmetrical GON. METHODS: Enrolled were 29 consecutive glaucoma patients with the clinically detectable RAPD. An RAPD was quantified by placing log-scaled neutral density filters over the less advanced eyes while performing the swinging flashlight test. Average RNFL thickness was determined using the Fast RNFL thickness programme of optical coherence tomography 3000. Correlation coefficient and Linear regression analyses were used in assessing the relationship between the RAPD and the ratio of RNFL thickness in the more advanced eyes relative to that in the less advanced. RESULTS: RAPD ranged from 0.6 to 2.4 log units. The log-scaled RAPD had a statistically significantly inversed correlation with the average RNFL thickness ratio (r(s) = -0.729, p<0.0001). Linear regression analysis found an equation that the average RNFL thickness ratio in the more affected eyes relative to that in the less advanced (%) = (0.827-0.169xRAPD (log units))x100 (R(2) = 0.557, p<0.0001). CONCLUSIONS: When an RAPD is clinically detected, the RNFL thickness in the more advanced eyes was in average reduced to about 73% of that in the less advanced.

Adolescent↗
PubMed2006

Latanoprost rescues retinal neuro-glial cells from apoptosis by inhibiting caspase-3, which is mediated by p44/p42 mitogen-activated protein kinase.

The purpose of this study was to investigate whether latanoprost, a prostaglandin F2alpha analogue, has a direct anti-apoptotic effect both in retinal neuro-glial cells in culture and in diabetic retina. R28 cells, immortalized retinal neuroglial progenitor cells, were induced apoptosis by 24h serum deprivation. Serum withdrawal made up to 15% of R28 cells pyknotic and activated caspase-3 immunoreactive, and latanoprost acid suppressed apoptosis with dose dependency at an optimum concentration of 1.0 microM (P<0.001). UO126, a mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase kinase (MEK) 1 and 2 inhibitor reversed this effect. Streptozotocin induced one- or three-month diabetic rats received balanced-salt-solution (BSS) in the left eye and latanoprost eye drops in the right for 5 days. Retinal wholemount was subjected to terminal dUTP nick end labeling (TUNEL) staining, whereas eyeballs were enucleated for cleaved caspase-3 immunofluorescence. Retinal homogenates were probed for phospho- or total p44/p42 MAPK and Akt. One- and three-month diabetic retina had 30.2+/-15.3 and 23.6+/-9.0 TUNEL positive cells per 0.5 cm(2), respectively, whereas control retina had few TUNEL positive cells. Latanoprost instillation significantly reduced these cells (10.0+/-3.1 and 11.3+/-3.1 cells per 0.5 cm(2) for 1M and 3M, respectively, P<0.01), whereas BSS did not. Latanoprost also significantly reduced cleaved caspase-3 immunoreactive cells in ganglion cell and inner nuclear layers (P<0.05). Latanoprost increased phosphorylated to total protein ratio of p44/p42 MAPK (P<0.05), but not of Akt. Taken together, the present findings suggest that latanoprost rescues retinal neurons and/or glial cells from apoptosis, which is probably mediated by p44/p42 MAPK through caspase-3 inhibition.

Animals↗
PubMed2006

A Japanese case of familial Mediterranean fever with onset in the fifties.

The patient was a 63-year-old woman with attacks of fever and abdominal pain, starting from the age of 53 years and recurring every month. Despite various examinations at another hospital, the etiology remained unclear. She was under symptomatic treatment, and was referred to our department for further evaluation. Although she had onset in middle age, the clinical symptoms and examination findings suggested familial Mediterranean fever, and administration of colchitine inhibited the attacks completely. Therefore, the patient was diagnosed as having the disease. We were not able to analyze the entire MEFV gene, but detected only a heterozygous M694I mutation. Amyloidosis did not develop as a complication. The disease is rare in Japan, and its onset in the fifties is extremely rare in the world.

Abdominal Pain↗
PubMed2006

Quantification of retinal nerve fiber layer thickness reduction associated with a relative afferent pupillary defect.

BACKGROUND: A relative afferent pupillary defect (RAPD) is known to develop only when more than 25% of retinal ganglion cells are ablated in monkeys' eyes. However, there was no prior study to estimate biometrically the degree of retinal nerve fiber layer (RNFL) thickness reduction leading to the development of RAPD in live human eyes. The purpose of this study was to examine the correlation between the amount of RNFL thickness reduction and the depth of a clinically detectable RAPD in patients with unilateral optic atrophy. METHODS: Enrolled were 20 patients with optic atrophy of various etiologies. We quantified RAPD by performing the swinging flashlight test with log-scaled neutral density filters placed over the unaffected eye. Average RNFL thickness was measured by OCT3000 with the average RNFL thickness program. Linear regression analysis was used in assessing the relationship between RAPD and the ratio of affected to unaffected average RNFL thickness. RESULTS: The mean of average RNFL thickness was 95.6+/-17.3 microm in the unaffected eyes and 50.7+/-19.3 microm in the affected eyes (P<0.001). Regression analysis between RAPD and the ratio of affected to unaffected average RNFL thickness revealed a correlation coefficient R2=0.48 (P=0.0007). The regression line intersected the y-axis at 0.77. CONCLUSIONS: RAPD was not clinically detected until at least approximately 25% of the retinal nerve fibers were lost when compared with the unaffected eyes. Substantial retinal ganglion cell damage is required for the development of RAPD.

Adolescent↗
PubMed2006

Case of chromosome 6p25 terminal deletion associated with Axenfeld-Rieger syndrome and persistent hyperplastic primary vitreous.

Axenfeld-Rieger syndrome is inherited in an autosomal dominant pattern and is characterized by anomalies of the anterior segment of the eye and systemic signs including craniofacial dysmorphic features and cardiac defects. The disorder is genetically heterogeneous and one causative gene, FOXC1, is located on chromosome 6p25. Persistent hyperplastic primary vitreous (PHPV) is a congenital ocular disorder in which there is a failure of the normal regression of the primary vitreous and a proliferation of fibrous tissue from the remnants of the primary vitreous. Deletions of chromosome 6p25 have been reported in a small number of patients with Axenfeld-Rieger syndrome; however, no case of chromosome 6p25 deletion has been reported with PHPV. We report a newborn girl who had both Axenfeld-Rieger syndrome and the combined type of PHPV, in whom the G-banding and spectral karyotyping revealed a 6p monosomy of terminal deletion with a breakpoint at chromosome 6p25.1. The karyotype was 46,XX,del(6)(p25.1). We conclude that PHPV in the context of Axenfeld-Rieger syndrome can be caused by 6p25 terminal deletion.

Abnormalities, Multiple↗
PubMed2006

Agreement of rebound tonometer in measuring intraocular pressure with three types of applanation tonometers.

PURPOSE: To evaluate the agreement of iCare rebound tonometer in measuring intraocular pressure (IOP) with Goldmann applanation tonometer (GAT), Tonopen XL, and noncontact tonometer, and the influence of the central corneal thickness (CCT) on IOP measurements made with these four tonometers in 45 (12 control and 33 glaucomatous or ocular hypertensive) eyes. DESIGN: Clinically relevant experimental study. METHODS: Tonometer intermethod agreement was assessed by the Bland-Altman method. The relations of CCT with absolute IOP values and intertonometer differences were analyzed by linear regression. RESULTS: The mean differences (95% limits of agreement) in IOP readings between iCare and GAT, Tonopen XL, and noncontact tonometer were 1.40 +/- 4.29, 0.00 +/- 4.78, and 2.22 +/- 4.19 mm Hg, respectively. All tonometries had a marked association with CCT. As the CCT got thicker, iCare considerably overestimated GAT and Tonopen XL. CONCLUSIONS: Although influenced by CCT, iCare agrees well with applanation tonometers.

Adult↗
PubMed2006

Novel mutations in the OPA1 gene and associated clinical features in Japanese patients with optic atrophy.

PURPOSE: Autosomal dominant optic atrophy (ADOA) is characterized by symmetrical bilateral optic atrophy associated with reduced corrected visual acuity (VA), central or centrocecal scotoma, and color vision disturbances. The disease is genetically heterogeneous, and the OPA1 gene has been identified as the only causative gene. The aims of this study were to identify and report mutations in the OPA1 gene in Japanese patients with ADOA and to describe the clinical features associated with the mutations. DESIGN: Molecular genetic study and observational case reports. PARTICIPANTS: Nine unrelated Japanese families with optic atrophy and 8 isolated cases of optic atrophy. METHODS: Genomic DNA was extracted from peripheral leukocytes, and all exons containing the open reading frame of the OPA1 gene and the flanking intron splice sites were sequenced directly. Complete ophthalmologic examinations were performed. MAIN OUTCOME MEASURES: Direct sequencing of the OPA1 gene and clinical evaluations including VA, visual field, color vision, and disc appearance. RESULTS: Ten different heterozygous mutations, including 6 novel mutations, were detected in the OPA1 gene. The identified mutations included 5 deletions/insertions (c.2061delA, c.2098_2103delCTTAAA, c.2538insT, c.2591insC, and c.2708_2711delTTAG), 4 nonsense mutations (c.112C>T [p.R38X], c.181C>T [p.Q61X], c.946A>T [p.R316X], and c.2713C>T [p.R905X]), and 1 missense mutation (c.1635C>A [p.S545R]). The most common mutation in Caucasians (c.2708_2711delTTAG) was found in 3 unrelated families, suggesting that it is a mutational hot spot. We detected an OPA1 mutation in 8 of 9 familial cases of optic atrophy and in 4 of 8 cases that were initially considered to be sporadic from the patients' family histories. Examinations of family members of 2 sporadic probands revealed the existence of other family members with the OPA1 mutations whose phenotype was very mild or within normal limits. This indicates that patients with ADOA sometimes seem to be sporadic because of the extensive variation in the phenotype or, alternatively, a low penetrance of ADOA. CONCLUSIONS: OPA1 gene mutations are causative in most familial cases of ADOA in Japanese. Sporadic cases of optic atrophy frequently may be caused by OPA1 mutations in the Japanese population. Molecular genetic examinations are useful in determining the hereditary patterns in some cases of optic atrophy.

Adult↗
PubMed2006

Medial sphenoid wing meningiomas: clinical outcome and recurrence rate.

OBJECTIVE: To provide clinical data concerning the visual outcome and recurrence rate of medial sphenoid wing meningiomas in consideration of two different subgroups of this tumor entity. METHODS: Among 256 sphenoid wing meningiomas, there were 108 medial sphenoid wing meningiomas of globoid shape. They were classified into Group 1 (without cavernous sinus involvement) and Group 2 (with cavernous sinus involvement). En plaque meningiomas were excluded from the analysis. The charts of the patients including surgical records, discharge letters, follow-up records, and imaging studies were analyzed retrospectively. RESULTS: There were 39 Group 1 tumors and 69 Group 2 tumors. For microsurgical tumor removal, the frontolateral (15.7%) or the pterional approach (84.3%) was performed. Total resection was achieved in 92.3% of patients with Group 1 tumors and 14.5% of those with Group 2 tumors. Radiological recurrence was observed in 7.7% (Group 1 tumors) and 27.5% (Group 2 tumors). The mean follow-up time was 79.04 months (6.59 yr). Improvement of visual function (or stable visual function) was observed in 56% (44%) of patients with Group 1 tumors, in 30% (60%) with newly diagnosed Group 2 tumors, and 10% (70%) undergoing recurrent surgery for Group 2 tumors. CONCLUSION: Group 1 meningiomas present a more favorable subgroup with fortunate visual outcome. In Group 2 tumors, visual improvement was less favorable and radical removal is limited because of cavernous sinus infiltration, with consequential higher recurrence rates. Patients harboring recurrent Group 2 tumors with deteriorating visual function profit from microsurgery because vision can be preserved on the same preoperative level in the majority.

Adult↗
PubMed2006

Tuberculum sellae meningiomas: clinical outcome considering different surgical approaches.

OBJECTIVE: Tuberculum sellae meningiomas present a special challenge because of their proximity to arteries of the anterior circulation, anterior visual pathways, and the hypothalamus. The authors report on the clinical outcome after surgical treatment of tuberculum sellae meningiomas in our neurosurgical department. METHODS: A retrospective study was conducted analyzing the charts of the patients, including surgical records, discharge letters, histological records, follow-up records, and imaging studies. Patients with associated neurofibromatosis Type 2 were excluded from the study. RESULTS: One thousand eight hundred meningiomas were operated on between 1978 and 2002. Seventy-two of these patients had tuberculum sellae meningiomas; four had undergone previous surgical procedures in outside hospitals. Fifty-five patients were women; 17 were men. Their mean age was 54.3 years (range, 30-86 yr). All patients had visual disturbances at presentation. Tumors were operated through the bifrontal approach (n = 21, from 1978 through 1995), the pterional/frontotemporal approach (n = 21, from 1982 through 2002), and the frontolateral approach (n = 30, from 1984 through 2002). Total tumor removal was achieved in most patients (Simpson 1 + 2, 91.7%). The perioperative mortality rate was 2.8% (two out of 72 patients). Immediate postoperative improvement of visual disturbance was observed in 65% of patients. Visual improvement was dependent on the duration of preoperative visual symptoms, but not on preoperative visual acuity or tumor size. The visual improvement rate was significantly better in patients who underwent frontolateral tumor resection (77.8%) compared with those who underwent bifrontal craniotomy (46.2%). The overall recurrence rate was 2.8% (two out of 72 patients). The mean follow-up time for all patients was 4 to 238 months (mean, 45.3 mo [3.8 yr]). CONCLUSION: From 1978 through 2002, tuberculum sellae meningiomas were removed microsurgically using three different surgical approaches. Considering the operative morbidity and mortality, the frontolateral and pterional approach provided remarkable improvement compared with the bifrontal approach. These approaches allowed quick access to the tumor and were minimally invasive with less brain exposure, but still engendered high rates of total tumor removal. By comparison, the frontolateral approach provided the best results concerning visual outcome while representing the least invasive surgical approach.

Adult↗
PubMed2006

Diabetes reduces basal retinal insulin receptor signaling: reversal with systemic and local insulin.

Diabetic retinopathy is characterized by early onset of neuronal cell death. We previously showed that insulin mediates a prosurvival pathway in retinal neurons and that normal retina expresses a highly active basal insulin receptor/Akt signaling pathway that is stable throughout feeding and fasting. Using the streptozotocin-induced diabetic rat model, we tested the hypothesis that diabetes diminishes basal retinal insulin receptor signaling concomitantly with increased diabetes-induced retinal apoptosis. The expression, phosphorylation status, and/or kinase activity of the insulin receptor and downstream signaling proteins were investigated in retinas of age-matched control, diabetic, and insulin-treated diabetic rats. Four weeks of diabetes reduced basal insulin receptor kinase, insulin receptor substrate (IRS)-1/2-associated phosphatidylinositol 3-kinase, and Akt kinase activity without altering insulin receptor or IRS-1/2 expression or tyrosine phosphorylation. After 12 weeks of diabetes, constitutive insulin receptor autophosphorylation and IRS-2 expression were reduced, without changes in p42/p44 mitogen-activated protein kinase or IRS-1. Sustained systemic insulin treatment of diabetic rats prevented loss of insulin receptor and Akt kinase activity, and acute intravitreal insulin administration restored insulin receptor kinase activity. Insulin treatment restored insulin receptor-beta autophosphorylation in rat retinas maintained ex vivo, demonstrating functional receptors and suggesting loss of ligand as a cause for reduced retinal insulin receptor/Akt pathway activity. These results demonstrate that diabetes progressively impairs the constitutive retinal insulin receptor signaling pathway through Akt and suggests that loss of this survival pathway may contribute to the initial stages of diabetic retinopathy.

Animals↗
PubMed2006

Cavernous angiomas within the internal auditory canal.

OBJECT: The aim of this study was to describe the symptomatology, radiological features, and surgical treatment of patients with cavernous angiomas within the internal auditory canal (IAC). METHODS: The authors reviewed the cases of seven patients with cavernous angiomas in the IAC that had been surgically treated in the 22-year period between 1983 and 2005. All the patients had presented with sensorineural hearing loss, and four suffered from tinnitus. Four patients also reported facial symptoms such as hemispasm or progressive palsy; one of these patients had presented with sudden facial paresis due to intrameatal tumor hemorrhage. According to computed tomography (CT) results, the lesions caused enlargement of the IAC. Interestingly, these same angiomas showed variable features on magnetic resonance (MR) imaging, making their differentiation from intrameatal vestibular schwannomas (VSs) sometimes impossible. In all patients the lesions were totally removed via the suboccipital retrosigmoid approach. They could be dissected away from the facial nerve in five cases, whereas in two cases, because of the location of the lesion, the seventh cranial nerve had to be sectioned and repaired with a sural nerve graft. Transient worsening of seventh cranial nerve symptoms occurred in two patients, with postoperative improvement in each of them. The cochlear nerve could not be functionally preserved because of its extreme adherence to the tumor, although its continuity was preserved in four patients. Complete deafness was the only postoperative complication. CONCLUSIONS: Cavernous angiomas of the IAC are very uncommon lesions that can imitate the symptoms of VSs. Although it is the most sensitive study available, MR imaging does not show sufficiently specific findings to differentiate the two lesion types. Thus, the preoperative diagnosis must be based on patient symptoms plus the CT and MR imaging features.

Adult↗
PubMed2006

[A case of multiple recurrence of Clostridium difficile-associated diarrhea--analysis of isolates from the patient using PCR ribotyping].

Recurrence of Clostridium difficile-associated diarrhea (CDAD) is a serious and still unsolved problem. Little is known about the precise mechanism of the recurrence with CDAD. To elucidate the issue, we analyzed C. difficile strains obtained from the patient with multiple recurrence of CDAD. A 72-year-old female received rectoidectomy was developed CDAD after administration of cefmetazole sodium for 5 days. She was recovered from illness by the administration 2g of vancomycin hydrochloride for 2 weeks. However she was recurred CDAD twice within 2 months thereafter. Six C. difficile isolates recovered from the stool specimens obtained during each episode were typed by polymerase chain reaction amplifying of rRNA intergenic spacer regions 8 PCR ribotyping was carried out. The PCR ribotype of the first episode was identical (ribotype smz) to that of the second episode, and the PCR ribotype of the third were distinct (ribotype hr) from those on previous two episodes. These findings indicate that the second episode was caused by the reactivation of continuously infected C. difficile strain (relapse) and the third episode was by reinfection of the new

Aged↗
PubMed2006

[Correlations among GDx-variable corneal compension, optical coherence tomography, and Heidelberg retina tomograph and relationships between these structural parameters and visual field indices].

PURPOSE: In glaucoma patients, to compare the correlations among parameters measured by Heidelberg Retina Tomography(HRT) and retinal nerve fiber layer thickness (RNFLT) measured by GDx-variable corneal compensation (GDx-VCC) and optical coherence tomography (OCT), and to assess the relationship among these structural parameters, and visual field damage. METHODS: A unilateral eye of 110 patients with open-angle glaucoma were included in this study. Each individual was analyzed by HRT (version 3.04), GDx-VCC (version 5.3.2), and OCT-1 (version A6 X1). The correlations among these parameters regarding global area, superior sector, and inferior sector were obtained from the 3 instruments and compared. The correlations among the mean deviation (MD) in the Humphrey field analysis and the parameters in global area from the 3 instruments were calculated. RESULTS: The MD showed quadratic regressions to each global parameter (GDx-VCC; 0.625 (nerve fiber indicator): OCT 0.616 (average RNFLT); HRT, 0.501 (rim area)). Most parameters in OCT and GDx-VCC had highly significant correlations. The rim area showed the highest correlation in each sector to RNFLT with GDx-VCC or OCT among HRT parameters. CONCLUSIONS: These structural parameters derived from GDx-VCC, OCT and HRT analyses had bilinear correlation to the MD. Retinal nerve fiber loss detected on GDx-VCC and OCT correlated linearly with the neuroretinal rim area measured by HRT. These instruments may be useful in monitoring structural changes in glaucoma.

Adult↗
PubMed2006

[A case of extrahepatic portal vein aneurysm with the remarkably bent bile duct by its displacement].

A 50-year-old man with type B liver cirrohosis was admitted with jaundice and ascites. He had undergone an operation for esophageal variceal rupture at another hospital. Abdominal CT scan and ultrasonography showed cystic dilatation of the extrahepatic portal vein, and Doppler ultrasonography showed it to be a portal vein aneurysm. After admission, jaundice progressed, and not only liver failure but also biliary tract obstruction was suspected as its etiology. Therefore, endoscopic retrograde cholangiography was performed, and it showed a remarkably bent extrahepatic bile duct thought to be caused by extrinsic compression. By combining the finding of endoscopic ultrasonography, we considered that the portal vein aneurysm had displaced the bile duct. We suspected that it also caused cholestasis and cholangitis.

Aneurysm↗
PubMed2005

The role of surgery in meningiomas involving the optic nerve sheath.

OBJECTIVE: Clinical presentation, radiological appearance and treatment options of patients with optic nerve sheath meningiomas (ONSM) vary. To provide a baseline for treatment of this tumour entity a series of 24 patients with ONSM is presented. METHOD: Clinical charts of the patients including surgical and histological records, imaging studies as well as meticulously focusing questionnaires of clinical outcome were reviewed. RESULTS: Twenty four patients with ONSM were treated at the Neurosurgical Department from 1981 to 2002. Mean age at diagnosis was 44 years (14-69) with a female:male ratio of 7:1. The preoperative duration of symptoms was negatively correlated with the preoperative visual acuity. The microsurgical approach consisted of pterional craniotomy, intra-/extradural subtotal excision of the meningioma and bony decompression of the optic canal. Surgical results showed low surgical morbidity and preserved or even improved vision in 8/16 patients (50%) all of whom had rapid visual decline preoperatively. In the long-term, visual loss occur again occurred due to recurrence in about 20% of cases. CONCLUSION: Microneurosurgery for treatment of ONSMs is still reserved for cases with intracranial extension, disfiguring proptosis and patients with rapid visual deterioration. Radiotherapy should be considered as treatment option in all other cases as it prolongs the time for functional vision in the affected eye with low morbidity.

Adolescent↗