Publications by authors named "Miyuki Arai"

27 Publications

  • Page 1 of 1

Comparisons of One to Three Monthly Injections of Aflibercept for Diabetic Macular Edema by Practical Protocol.

J Diabetes Res 2021 12;2021:1374891. Epub 2021 Feb 12.

Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Chiba, Japan.

The purpose of this study was to compare the efficacies of one initial intravitreal injection of aflibercept followed by a (PRN; 1+PRN) regimen to those of three consecutive monthly injections followed by the PRN (3+PRN) regimen for diabetic macular edema (DME) with practical protocols. The medical records of 95 eyes of 71 cases that were diagnosed with DME and had received intravitreal aflibercept (IVA) injections were reviewed. Fifty-seven eyes had received IVA with the 1+PRN regimen, and 38 eyes had received IVA with the 3+PRN regimen. The best-corrected visual acuity (BCVA) and the central macular thickness (CMT) were measured at the baseline and at 1, 3, 6, and 12 months after the IVA. The mean number of injections of the 1+PRN group was 2.9 ± 1.7, which was significantly fewer than that of the 3+PRN group at 4.6 ± 1.4 ( < 0.001). The change of the mean BCVA before and after the IVA at 12 months of the 3+PRN group was -0.14 ± 0.17 logMAR units which was significantly better than that of the 1+PRN group of -0.045 ± 0.25 logMAR units ( = 0.02). The change of the CMT before and after the IVA at 6 months of the 3+PRN group was -141.3 ± 152.4 m which was significantly more than that of the 1+PRN group at -86.1 ± 117.8 m ( = 0.013). Although the mean number of injections was more than that in the 1+PRN regimen, the 3+PRN regimen had better visual outcomes at 12 months. In a practical protocol, we recommend the 3+PRN regimen for patients with DME (IRB#3541).
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http://dx.doi.org/10.1155/2021/1374891DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896872PMC
February 2021

Safety and Efficacy of Ranibizumab and Luseogliflozin Combination Therapy in Patients with Diabetic Macular Edema: Protocol for a Multicenter, Open-Label Randomized Controlled Trial.

Diabetes Ther 2020 Aug 15;11(8):1891-1905. Epub 2020 Jun 15.

Department of Endocrinology, Hematology and Gerontology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba, Chiba, 260-8677, Japan.

Introduction: Diabetic macular edema (DME) threatens daily life activities such as reading and driving and reduces the patients' quality-of-life. Recently, anti-vascular endothelial growth factor (VEGF) agents have become a first-line therapy in DME. However, therapy with anti-VEGF agents has several problems: repeated invasive injections are required; medical costs are high; and a certain proportion of patients with DME are resistant to treatment with anti-VEGF agents. While sodium-glucose co-transporter 2 (SGLT2) inhibitors have been widely used for the treatment of type 2 diabetes mellitus (T2DM), the effects of a combination therapy with anti-VEGF agent and SGLT2 inhibitor on DME are not yet known.

Methods: This study enrolls subjects with T2DM and DME, randomizes them into either a study agent treatment group (treated with ranibizumab as anti-VEGF agent and luseogliflozin as SGLT2 inhibitor) or a control group (treated with ranibizumab and glimepiride), and observes the subjects for 52 weeks after initiation of treatment. Planned outcomes: The primary endpoint is intergroup difference in the number of intravitreal anti-VEGF injections to the study eye from baseline to week 48. Secondary and exploratory endpoints include safety and ophthalmologic and internal medical clinical parameters.

Registration: This study is registered at the University Hospital Medical Information Network Clinical Trial Registry (UMIN000033961) and Japan Registry of Clinical Trials (jRCTs031180210).
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http://dx.doi.org/10.1007/s13300-020-00854-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7376811PMC
August 2020

Comparison of the Efficacy of Sub-Tenon versus Intravitreal Triamcinolone Acetonide Injection during Cataract Surgery for Diabetic Macular Edema.

Ophthalmologica 2019 24;241(1):17-23. Epub 2018 Jul 24.

Purpose: We compared the efficacy of sub-Tenon triamcinolone acetonide (STTA) to intravitreal triamcinolone aceto-nide (IVTA) injections during cataract surgery (CS) for patients with diabetic macular edema (DME).

Methods: The medical records of 33 eyes (26 patients) with DME which had undergone CS with STTA were compared to those of 34 eyes (27 patients) with DME which had undergone CS with IVTA. Central foveal thickness and best-corrected visual acuity (BCVA) were measured at the baseline and 1, 3, and 6 months after the surgery.

Results: The BCVAs after STTA and IVTA were significantly improved at 3 and 6 months. Thirteen eyes in the IVTA group and 21 eyes in the STTA group required other therapies (p < 0.05). One case developed intraocular pressure elevation after IVTA and underwent selective la ser trabeculoplasty.

Conclusions: Ophthalmologists should consider the merits and demerits of IVTA and STTA for DME treatment after CS.
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http://dx.doi.org/10.1159/000489716DOI Listing
February 2019

Efficacy of One-Year Treatment with Aflibercept for Diabetic Macular Edema with Practical Protocol.

Biomed Res Int 2017 4;2017:7879691. Epub 2017 Dec 4.

Department of Ophthalmology and Visual Science, Chiba University, Graduate School of Medicine, Chiba, Japan.

The purpose of this study was to determine the efficacy of one-year treatment of diabetic macular edema (DME) with intravitreal aflibercept (IVA) injections on a practical protocol. The medical records of 51 eyes of 43 patients who were diagnosed with DME and had received IVA treatments were reviewed. The best-corrected visual acuity (BCVA) and the central macular thickness (CMT) were measured at the baseline and at 1, 3, 6, and 12 months after the IVA. The mean number of IVA injections was 3.8 ± 2.4. The mean BCVA was significantly better and the CMT was thinner after the IVA at all follow-up times ( < 0.05). The BCVA was better in eyes with a serous retinal detachment (SRD) than without a SRD ( < 0.01). There was a significant correlation between the photoreceptor outer segment (PROS) length and BCVA at the baseline and at 12 months after the IVA ( < 0.05). A fewer number of IVA injections significantly improved the BCVA and the CMT in eyes with DME after one-year treatment. IVA was more effective in the SRD+ group than in the SRD- group. The PROS length may be a predictive marker for visual outcomes after one-year treatment with IVA for DME (IRB#2272).
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http://dx.doi.org/10.1155/2017/7879691DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5733831PMC
August 2018

Comparisons of Efficacy of Intravitreal Aflibercept and Ranibizumab in Eyes with Diabetic Macular Edema.

Biomed Res Int 2017 3;2017:1747108. Epub 2017 Jul 3.

Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Chiba, Japan.

We compared the efficacy of intravitreal aflibercept (IVA) to intravitreal ranibizumab (IVR) injections in eyes with diabetic macular edema (DME). The medical records of 49 eyes of 36 patients who were diagnosed with DME and had received IVR and 46 eyes of 40 patients who had received IVA treatment were reviewed. The central macular thickness (CMT) and best-corrected visual acuity (BCVA) were measured at the baseline and at 1, 3, and 6 months after the IVR or IVA. The mean number of injections of IVR was 2.6 ± 1.1 and of IVA was 2.7 ± 1.4. At 6 months, the CMT was significantly thinner than the baseline after IVR and after IVA. The mean BCVA was significantly better than the baseline after IVR only at 1 and 3 months and after IVA at 1 and 6 months. The BCVA of eyes with serous retinal detachment (SRD) was significantly better at 1 month after the IVR and at 1 month and 6 months after the IVA. The BCVAs improved more significantly in the SRD+ group than in the SRD- group. The effects of IVA persist longer than that of IVR. The effectiveness of both IVR and IVA was not dependent on the presence of SRD (IRB#2107).
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http://dx.doi.org/10.1155/2017/1747108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5512051PMC
April 2018

Neuregulin-1 type III knockout mice exhibit delayed migration of Schwann cell precursors.

Biochem Biophys Res Commun 2017 04 18;486(2):506-513. Epub 2017 Mar 18.

Laboratory of Molecular Neuroscience and Neurology, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan; Department of Pharmacology, National Research Institute for Child Health and Development, Setagaya, Tokyo 157-8535, Japan. Electronic address:

In an embryonic developmental stage of the peripheral nervous system (PNS), Schwann cell precursors migrate along neuronal axons to their final destinations. After birth, they eventually wrap around individual axons to form myelin sheaths, which insulate axons to increase the nerve conduction velocity. Some growth factors and adhesion molecules are known to control these developmental stages from in the fish to in the mammal. Neuregulin-1 (NRG1), which is composed of many alternative splicing variants, is such a growth factor. Among these variants, the type III isoform of NRG1, interacting with ErbB2 and ErbB3 receptors on Schwann cells, plays an essential role in myelination in the fish and the mammal. NRG1 type III is also known to promote migration of fish Schwann cell precursors; however, it still remains to be clarified whether mammalian type III isoform does it. We have therefore generated type III isoform-specific knockout mice in inbred strain. The mice result in delayed migration of the precursors from the dorsal to ventral root via a peripheral ganglion, comparing littermate controls. Similar results are observed in an in vitro migration assay using reaggregated Schwann cell precursors. Furthermore, the knockout mice exhibit reduced myelin thickness, consistent with the established role of NRG1 type III in myelination. These results indicate that in mice, NRG1 type III plays a key role not only in myelination but also in migration.
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http://dx.doi.org/10.1016/j.bbrc.2017.03.074DOI Listing
April 2017

Prasugrel for Japanese patients with acute coronary syndrome in short-term clinical practice (PRASFIT-Practice I): a postmarketing observational study.

Cardiovasc Interv Ther 2018 Apr 17;33(2):135-145. Epub 2017 Feb 17.

Pharmacovigilance Department, Daiichi Sankyo Co., Ltd., Tokyo, Japan.

Data on prasugrel use in Japanese patients are limited to phase II/III clinical trials. This early postmarketing observational study evaluated the safety and efficacy of short-term prasugrel use in patients with acute coronary syndrome (ACS) in real-world clinical settings in Japan. From May 2014 to January 2015, we enrolled consecutive patients with ACS requiring percutaneous coronary intervention in each institution. Each patient started prasugrel treatment ≥1 month before the end of the study period. Safety outcomes included incidence rates of adverse drug reactions (ADRs) and bleeding adverse events (AEs). Efficacy outcomes were incidence rates of cardiovascular events (including major adverse cardiovascular events [MACE]). Case report forms were collected from 749 patients, 732 of whom were eligible for the safety and efficacy analysis sets. Approximately 95% of patients had a prasugrel loading/maintenance dose of 20 mg/3.75 mg/day. The incidences of ADRs and bleeding AEs were 8.6 and 6.4%, respectively. Twelve patients experienced major bleeding AEs; approximately 60% (seven patients) of which were gastrointestinal disorders. The incidence of bleeding AEs was significantly higher primarily in patients of female sex, aged ≥75 years, with low body weight (≤50 kg), severe cardiovascular disease, or severe renal impairment. The incidence of MACE was 1.9% during prasugrel treatment, and 3.1% at the end of the study period. This short-term study indicated that prasugrel treatment at loading/maintenance doses of 20 mg/3.75 mg/day was safe and effective in Japanese ACS patients in an acute setting.

Clinical Trial Registration: This study is registered at http://www.umin.ac.jp/ctr/ under the identifier UMIN000014699.
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http://dx.doi.org/10.1007/s12928-017-0459-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5880844PMC
April 2018

Variation among individual bulls in the distribution of acrosomal tyrosine-phosphorylated proteins in epididymal and ejaculated spermatozoa.

Reprod Fertil Dev 2017 Jul;29(7):1297-1305

Northern Center of Agricultural Technology, General Technological Center of Hyogo Prefecture for Agriculture, Forest and Fishery, 123 Yasui, Wadayama, Asago, Hyogo, 669-5254, Japan.

In Japanese black cattle, AI severely subfertile males have occasionally been found. In order to solve this problem, we previously asserted the need for exact examinations of acrosomal tyrosine-phosphorylated proteins and acrosome morphology in cryopreserved spermatozoa. In the present study, we further investigated acrosomal tyrosine-phosphorylated proteins in spermatozoa before cryopreservation and examined possible relationships between these phosphoproteins and acrosome stability. Ejaculated, epididymal and cryopreserved spermatozoa were subjected to examinations of general characteristics (motility, shape and acrosome morphology) and indirect immunofluorescence of acrosomal phosphoproteins. Unlike all general characteristic parameters, the distribution of acrosomal tyrosine-phosphorylated proteins in ejaculated and cauda epididymal spermatozoa varied considerably among bulls and was linked to the maintenance of morphologically normal acrosomes in cryopreserved spermatozoa or ejaculated spermatozoa after 270min incubation. Moreover, the distribution of these phosphoproteins was arranged in the spermatozoa of the proximal epididymides. These findings indicate that acrosomal tyrosine-phosphorylated proteins are distributionally arranged during early process of sperm maturation, that their distribution of cauda epididymal and ejaculated spermatozoa are largely different among bulls, and that varied states of acrosomal phosphoproteins may result in individual differences in acrosome stability among bulls.
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http://dx.doi.org/10.1071/RD15483DOI Listing
July 2017

Effects of sub-Tenon's capsule triamcinolone acetonide injection combined with microaneurysm photocoagulation on diabetic macular edema.

Int Med Case Rep J 2015 7;8:321-6. Epub 2015 Dec 7.

Department of Ophthalmology and Visual Science, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan.

Purpose: To compare the effects of sub-Tenon's capsule triamcinolone acetonide (STTA) injection to that of STTA injection combined with microaneurysm photocoagulation (MAPC; STTA + MAPC) on eyes with diabetic macular edema (DME).

Patients And Methods: The medical records of 138 eyes of 138 patients with DME treated by either STTA or STTA + MAPC were reviewed. The degree of DME was determined by the optical coherence tomographic features: patients with serous retinal detachment (SRD+; 38 eyes) and patients without SRD (non-SRD; 100 eyes). The central macular thickness (CMT) and the best-corrected visual acuity (BCVA) were measured periodically for 6 months after the treatments.

Results: The BCVA was significantly improved in the non-SRD group after STTA + MAPC. The CMT was significantly improved in all groups and improved considerably more in the non-SRD group than in the SRD+ group after STTA + MAPC.

Conclusion: Our findings indicate that MAPC has an additive effect in the non-SRD type.
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http://dx.doi.org/10.2147/IMCRJ.S89970DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4676612PMC
December 2015

Conditional deletion of CD98hc inhibits osteoclast development.

Biochem Biophys Rep 2016 Mar 2;5:203-210. Epub 2015 Dec 2.

Department of Microbiology, College of Life and Health Science, Chubu University, 1200 Matumoto-Chou, Kasugai-City, Aichi-Prefecture 487-8501, Japan.

The CD98 heavy chain (CD98hc) regulates virus-induced cell fusion and monocyte fusion, and is involved in amino acid transportation. Here, we examined the role that CD98hc plays in the formation of osteoclasts using CD98hcLysM-cre peritoneal macrophages (CD98hc-defect macrophages). Peritoneal macrophages were stimulated with co-cultured with osteoblasts in the presence of 1,25(OH) vitamin D, and thereafter stained with tartrate-resistant acid phosphatase staining solution. The multinucleated osteoclast formation was severely impaired in the peritoneal macrophages isolated from the CD98hcdefect mice compared with those from wild-type mice. CD98hc mediates integrin signaling and amino acid transport through the CD98 light chain (CD98lc). In integrin signaling, suppression of the M-CSF-RANKL-induced phosphorylation of ERK, Akt, JNK and p130Cas were observed at the triggering phase in the CD98h-defect peritoneal macrophages. Moreover, we showed that the general control non-derepressible (GCN) pathway, which was activated by amino acid starvation, was induced by the CD98hc-defect peritoneal macrophages stimulated with RANKL. These results indicate that CD98 plays two important roles in osteoclast formation through integrin signaling and amino acid transport.
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http://dx.doi.org/10.1016/j.bbrep.2015.11.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5600448PMC
March 2016

Risk Factors for Refractory Diabetic Macular Oedema after Sub-Tenon's Capsule Triamcinolone Acetonide Injection.

J Ophthalmol 2015 20;2015:195737. Epub 2015 Sep 20.

Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Inohana 1-8-1, Chuo-ku, Chiba Prefecture, Chiba 260-8670, Japan.

The purpose of this study is to identify the risk factors for a recurrence or persistence of diabetic macular oedema (DME) after a sub-Tenon's capsule triamcinolone acetonide (STTA) injection. The medical records of 124 patients (124 eyes) treated by STTA were reviewed. The age, sex, HbA1c level, best-corrected visual acuity, central macular thickness, insulin use, pioglitazone use, systemic hypertension, serous retinal detachment, proteinuria, panretinal photocoagulation, microaneurysm photocoagulation (MAPC), subthreshold micropulse diode laser photocoagulation (SMDLP), cataract surgery, and history of vitrectomy were examined by logistic regression analysis. Procedures of MAPC and SMDLP were significantly associated with DME treated with STTA (P = 0.0315, P = 0.04, resp.). However, a history of vitrectomy was found to have significantly fewer recurrences or persistent DME after STTA (P = 0.0464). In conclusion, patients who required combined MAPC or SMDLP with a STTA injection had significantly higher refractoriness to STTA, but postvitrectomy may prevent the recurrence or persistence of DME after STTA injection.
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http://dx.doi.org/10.1155/2015/195737DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4592730PMC
October 2015

Effects of acrosomal conditions of frozen-thawed spermatozoa on the results of artificial insemination in Japanese Black cattle.

J Reprod Dev 2015 21;61(6):519-24. Epub 2015 Aug 21.

Division of Animal Science, Department of Bioresource Science, Graduate School of Agricultural Science, Kobe University, Kobe 657-8501, Japan.

The purposes of this study were to examine the relationship between male artificial insemination (AI) fertility and sperm acrosomal conditions assessed by new and conventional staining techniques and to identify possible reproductive dysfunctions causing low conception rates in AI using frozen-thawed spermatozoa with poor acrosomal conditions in Japanese Black bulls. We investigated individual differences among bulls in the results concerning (1) acrosomal conditions of frozen-thawed spermatozoa as assessed by not merely peanut agglutinin-lectin staining (a conventional staining technique) but also immunostaining of acrosomal tyrosine-phosphorylated proteins (a new staining technique), (2) routine AI using frozen-thawed spermatozoa as assessed by pregnancy diagnosis, (3) in vivo fertilization of frozen-thawed spermatozoa and early development of fertilized eggs as assessed by superovulation/AI-embryo collection tests and (4) in vitro fertilization of frozen-thawed spermatozoa with oocytes. The percentages of frozen-thawed spermatozoa with normal acrosomal conditions assessed by the abovementioned staining techniques were significantly correlated with the conception rates of routine AI, rates of transferable embryos in superovulation/AI-embryo collection tests and in vitro fertilization rates. These results are consistent with new suggestions that the distribution of acrosomal tyrosine-phosphorylated proteins as well as the acrosomal morphology of frozen-thawed spermatozoa are AI fertility-associated markers that are valid for the prediction of AI results and that low conception rates in AI using frozen-thawed spermatozoa with poor acrosomal conditions result from reproductive dysfunctions in the processes between sperm insemination into females and early embryo development, probably failed fertilization of frozen-thawed spermatozoa with oocytes.
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http://dx.doi.org/10.1262/jrd.2015-073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4685217PMC
October 2016

Distinct segment-specific functions of calyculin A-sensitive protein phosphatases in the regulation of cAMP-triggered events in ejaculated bull spermatozoa.

Mol Reprod Dev 2015 Mar 3;82(3):232-50. Epub 2015 Mar 3.

Laboratory of Reproductive Biology, Division of Animal Science, Department of Bioresource Science, Graduate School of Agricultural Science, Kobe University, Kobe, 657-8501, Japan.

Livestock spermatozoa possess more tenacious suppressors of cAMP-triggered events-including capacitation-associated changes-than laboratory animal spermatozoa, leading to flagellar hyperactivation. In order to identify the suppressors, we examined effects of an inhibitor of serine/threonine protein phosphatases (calyculin A) on cAMP-triggered changes in the protein phosphorylation state, and subsequent occurrence of hyperactivation and acrosome reaction in ejaculated bull spermatozoa. Ejaculated spermatozoa were incubated in cAMP-supplemented medium, then assessed for motility, acrosome morphology, and phosphorylated protein localization. The addition of calyculin A greatly enhanced cAMP-triggered protein phosphorylation at serine/threonine and tyrosine residues in the connecting piece and induction of flagellar hyperactivation. Most hyperactivated spermatozoa exhibited extremely asymmetrical bends at the middle piece, which produced intensive twisting or figure-eight movements. In the sperm head, however, cAMP-triggered dephosphorylation of serine/threonine-phosphorylated proteins and subsequent acrosome reaction were abolished by the addition of calyculin A. Based on these results, we suggest that calyculin A-sensitive protein phosphatases in the connecting piece are suppressors of cAMP-triggered events leading to hyperactivation. By contrast, similar protein phosphatases in the sperm head accelerate cAMP-triggered events leading to the acrosome reaction. These findings are consistent with the indication that calyculin A-sensitive protein phosphatases have distinct functions in the regulation of cAMP-triggered events in different regions of ejaculated bull spermatozoa.
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http://dx.doi.org/10.1002/mrd.22465DOI Listing
March 2015

In vivo knockdown of ErbB3 in mice inhibits Schwann cell precursor migration.

Biochem Biophys Res Commun 2014 Sep 6;452(3):782-8. Epub 2014 Sep 6.

Department of Pharmacology, National Research Institute for Child Health and Development, Setagaya, Tokyo 157-8535, Japan; Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo, Tokyo 113-8510, Japan. Electronic address:

The myelin sheath insulates neuronal axons and markedly increases the nerve conduction velocity. In the peripheral nervous system (PNS), Schwann cell precursors migrate along embryonic neuronal axons to their final destinations, where they eventually wrap around individual axons to form the myelin sheath after birth. ErbB2 and ErbB3 tyrosine kinase receptors form a heterodimer and are extensively expressed in Schwann lineage cells. ErbB2/3 is thought to be one of the primary regulators controlling the entire Schwann cell development. ErbB3 is the bona fide Schwann cell receptor for the neuronal ligand neuregulin-1. Although ErbB2/3 is well known to regulate both Schwann cell precursor migration and myelination by Schwann cells in fishes, it still remains unclear whether in mammals, ErbB2/3 actually regulates Schwann cell precursor migration. Here, we show that knockdown of ErbB3 using a Schwann cell-specific promoter in mice causes delayed migration of Schwann cell precursors. In contrast, littermate control mice display normal migration. Similar results are seen in an in vitro migration assay using reaggregated Schwann cell precursors. Also, ErbB3 knockdown in mice reduces myelin thickness in sciatic nerves, consistent with the established role of ErbB3 in myelination. Thus, ErbB3 plays a key role in migration, as well as in myelination, in mouse Schwann lineage cells, presenting a genetically conservative role of ErbB3 in Schwann cell precursor migration.
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http://dx.doi.org/10.1016/j.bbrc.2014.08.156DOI Listing
September 2014

The effect of posterior sub-Tenon's capsule triamcinolone acetonide injection to that of pars plana vitrectomy for diabetic macular edema.

Clin Ophthalmol 2014 30;8:825-30. Epub 2014 Apr 30.

Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Chiba, Japan.

Purpose: To compare the effect of posterior sub-Tenon's capsule triamcinolone acetonide (STTA) injection to that of pars plana vitrectomy (PPV) for diabetic macular edema (DME).

Patients And Methods: The medical records of 50 patients (52 eyes) with DME were reviewed. Twenty-six eyes underwent STTA (20 mg) and the other 26 eyes underwent vitrectomy combined with cataract surgery. The central macular thickness (CMT), measured by optical coherence tomography, and best-corrected visual acuity (BCVA) were determined before and 1, 3, and 6 months after treatment.

Results: The differences in the BCVA and the CMT between the STTA group and the PPV group were not significant before or at any time after the treatment. In both the STTA and PPV groups, there were significant differences between the pre-treatment CMT and BCVA at any time after treatment.

Conclusion: We recommend STTA injection for the treatment of DME.
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http://dx.doi.org/10.2147/OPTH.S59849DOI Listing
May 2014

[Comparison of visual acuity and central macular thickness after vitrectomy for diffuse diabetic macular edema with or without preoperative treatments].

Nippon Ganka Gakkai Zasshi 2013 Oct;117(10):785-92

Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine.

Purpose: To compare the surgical outcomes during pars plana vitrectomy (PPV) for diffuse diabetic macular edema (DME) with pretreatment to those without pretreatment.

Methods: The medical charts of 43 eyes of 46 patients who underwent PPV for DME were reviewed. The previously treated (Prev. Tx) group included 19 eyes of 20 patients who were pretreated with intravitreal bevacizumab, sub-Tenon injection of triamcinolone acetonide, and/or subthreshold micropulse diode laser photocoagulation before the PPV. The treatment naïve (Tx.Naïve) group included 24 eyes of 26 patients who underwent PPV alone. The central macular thickness (CMT) and best-corrected visual acuity (BCVA) were measured before treatment and 1, 3, and 6 months after.

Results: In both groups, BCVA at 3 and 6 months and CMT at 1 month or later were significantly better than preoperative visual acuity. CMT at 1 month or later significantly decreased from the preoperative value (p<0.05). The differences in the BCVA and CMT between the Prev. Tx and Tx.Naïve group were not significant.

Conclusions: PPV either with or without preoperative treatments can significantly improve the BCVA and reduce the CMT in patients with diffuse DME.
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October 2013

Comparison of vitrectomy with brilliant blue G or indocyanine green on retinal microstructure and function of eyes with macular hole.

Ophthalmology 2012 Dec 24;119(12):2609-15. Epub 2012 Aug 24.

Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Chiba, Japan.

Purpose: To evaluate the microstructure of the inner and outer retina and the visual function after macular hole (MH) surgery using brilliant blue G (BBG) or indocyanine green (ICG) to make the internal limiting membrane (ILM) more visible.

Design: Comparative, retrospective, interventional case series.

Participants: Sixty-three eyes of 63 consecutive cases with MH were studied. Thirty-five eyes of 35 cases were treated with BBG between January and August 2011. Twenty-eight eyes of 28 MH cases were treated with ICG from April 2009 through April 2010.

Methods: Vitrectomy was performed with a 23-gauge system and 0.25 mg/ml BBG or with 0.125% ICG.

Main Outcome Measures: The best-corrected visual acuity (BCVA) and the microperimetry-determined retinal sensitivity were measured at baseline and at 3 and 6 months after surgery. The length of the defect of the photoreceptor inner segment/outer segment (IS/OS) junction and external limiting membrane (ELM), the central foveal thickness (CFT), and the thickness of the ganglion cell complex (GCC) were measured in the spectral-domain optical coherence tomographic images.

Results: The average BCVA was significantly better in the BBG group than in the ICG group at 3 months (P = 0.021) and 6 months (P = 0.045) after surgery. The mean retinal sensitivity in the BBG group was improved significantly in the central 2° at 3 and 6 months (P = 0.001 and P = 0.030, respectively), but was not significantly improved in the adjacent 10°. The length of IS/OS junction defect was significantly shorter in the BBG group at 3 months (P = 0.048), but was not significantly different at 6 months (P = 0.135). The length of ELM defect and the GCC thickness were not significantly different between the 2 groups at 3 and 6 months. The CFT was significantly thinner in the ICG group than in the BBG group at 3 and 6 months (P = 0.013 and P = 0.001, respectively).

Conclusions: The postoperative BCVA and retinal sensitivity in the central 2° were better in eyes after BBG-assisted vitrectomy. The restoration of IS/OS junction was faster in the BBG group, and the CFT was significantly thinner in eyes after ICG. Brilliant blue G may be a better agent than ICG to make the ILM more visible.

Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
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http://dx.doi.org/10.1016/j.ophtha.2012.06.048DOI Listing
December 2012

[Macular ischemia following intravitreal bevacizumab therapy for diabetic macular edema].

Nippon Ganka Gakkai Zasshi 2012 Feb;116(2):108-13

Department of Ophthalmology, Hospital, National Center for Global Health and Medicine, Japan.

Purpose: To examine the effects of macular ischemia after intravitreal bevacizumab (IVB) in patients with diabetic macular edema(DME).

Methods: Thirty-three eyes of 33 patients with DME were treated with IVB. Fluorescein angiography (FA) was conducted before and 3 months after IVB, the pretreatment sizes of the foveal avascular zone (FAZ) calculated by FA were compared to the values at 3 months after IVB. This study was approved by the Chiba University Hospital Clinical Research Ethics Committee.

Results: After IVB, the size of the FAZ enlarged significantly (p = 0.03). Among the 33 patients treated with IVB, 2 patients (6%) had advanced macular ischemia with an FAZ enlarged by 50% or more. In both patients, the visual acuity did not worsen and the foveal thickness decreased.

Conclusions: It is possible that IVB led to macular ischemia.
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February 2012

Long-term therapeutic efficacy of the subthreshold micropulse diode laser photocoagulation for diabetic macular edema.

Jpn J Ophthalmol 2011 Jul 7;55(4):365-369. Epub 2011 Jun 7.

Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.

Purpose: To investigate the long-term efficacy of subthreshold micropulse diode laser photocoagulation (SMDLP) on diabetic macular edema (DME).

Methods: The effects of SMDLP (810 nm) were studied on 56 eyes of 44 patients with DME. Optical coherence tomography-determined foveal thickness and best-corrected visual acuity (BCVA) were evaluated at 1, 3, 6, and 12 months after the SMDLP.

Results: The mean foveal thickness was 504 μm before the SMDLP, and it was significantly reduced to 439 μm at 1 month (P = 0.001), 409 μm at 3 months (P < 0.0001), 358 μm at 6 months (P < 0.0001), and 320 μm at 12 months (P < 0.0001). The mean BCVA at baseline was 0.47 logarithm of the minimal angle of resolution (logMAR) units, and it was not changed significantly at all of the postoperative examinations. Among the 56 eyes, 10 (17.8%) had an improvement of BCVA of >0.2 logMAR units, 36 (64.2%) remained the same, and 10 eyes (17.8%) had a reduction of >0.2 logMAR units at 12 months postoperatively.

Conclusion: Our results indicate that SMDLP has a beneficial effect on DME. However, prospective studies are needed to evaluate this technique in more detail.
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http://dx.doi.org/10.1007/s10384-011-0033-3DOI Listing
July 2011

Successful salvage treatment of blastic natural killer cell lymphoma with methotrexate.

Int J Hematol 2010 Nov 9;92(4):634-7. Epub 2010 Oct 9.

Department of Hematology, Seirei Yokohama Hospital, 215 Iwai-cho Hodogaya-ku, Yokohama 240-8521, Japan.

A 69-year-old man with blastic natural killer cell lymphoma (BNKL) was treated mainly with methotrexate (MTX). He presented with skin and bone marrow involvement at onset. Neoplastic cells were blastic in appearance with CD3-, CD4-, CD8-, CD7-, CD16-, CD56+ and HLA-DR+ phenotype. Molecular studies showed germline configuration of both immunoglobulin H and T cell receptor genes, and negative results for Epstein-Barr virus-encoded small RNA (EBER). He was treated with standard acute lymphoblastic leukemia (ALL) induction therapy, followed by 1 cycle of high-dose MTX (HD-MTX) as consolidation therapy. However, BNKL relapsed during standard ALL maintenance therapy. Three cycles of HD-MTX were effective in achieving a second complete remission and then he received low dose MTX as maintenance therapy. BNKL remained well controlled for 4 years. Chemotherapeutic toxicity was mild and manageable. Since BNKL reportedly has a poor prognosis, this encouraging result warrants further investigation of MTX as either a single agent or in a combination regimen as a first-line treatment for patients with BNKL.
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http://dx.doi.org/10.1007/s12185-010-0660-3DOI Listing
November 2010

[Subthreshold micropulse diode laser photocoagulation for diabetic macular edema with hard exudates].

Nippon Ganka Gakkai Zasshi 2009 Aug;113(8):787-91

Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Japan.

Purpose: To examine the efficacy of subthreshold micropulse diode laser photocoagulation (SMDLP) in eyes with diabetic macular edema (DME) with hard exudates.

Methods: Ten eyes of 10 patients with diffuse DME were treated with SMDLP (810 nm). Hard exudates had accumulated within the foveal avascular zone (FAZ) in all patients. The mean retinal sensitivity within the central 10 degrees was measured with a fundus-related microperimeter (MP 1); the best corrected visual acuity (BCVA) in logMAR units and optical coherence tomography (OCT)-determined foveal thickness (FT) were recorded before and at 3 months after SMDLP.

Results: The FT did not decrease significantly after SMDLP, but the BCVA improved significantly from 0.51 +/- 0.25 to 0.40 +/- 0.31 logMAR units (p= 0.02). There was no significant change in the mean retinal sensitivity within the central 10 degrees after SMDLP.

Conclusions: SMDLP can improve the visual acuity even in eyes with DME and hard exudates. However, the therapeutic efficacy of SMDLP in these cases may be limited, because no significant improvement in either the foveal thickness or retinal sensitivity could be seen.
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August 2009

Efficacy of vitrectomy and internal limiting membrane removal for macular edema associated with branch retinal vein occlusion.

Ophthalmologica 2009 28;223(3):172-6. Epub 2009 Jan 28.

Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Chiba, Japan.

Aim: To compare the results of vitrectomy with internal limiting membrane (ILM) peeling to that without ILM peeling for macular edema associated with branch retinal vein occlusion (BRVO).

Methods: The medical records of 47 eyes of 47 patients with BRVO-associated macular edema were examined. To treat the macular edema, a posterior vitreous detachment (PVD) was created, and the ILM was removed in 13 eyes (ILM-removed group), whereas a PVD was created and the ILM was not removed in 34 eyes (ILM-preserved group). The best-corrected visual acuity (BCVA) and the optical-coherence-tomography-determined foveal thickness were obtained preoperatively and at 6 months postoperatively.

Results: The mean postoperative BCVA was significantly better than the preoperative BCVA in both the ILM-removed and in the ILM-preserved groups (p = 0.0017 and p = 0.0002, respectively). The fovea was significantly thinner at 1 month after surgery in both groups (p = 0.0007 and p < 0.0001, respectively). The postoperative improvement of the mean BCVA and the foveal thickness were not significantly different for the two groups at any postoperative period.

Conclusions: Because there was no significant difference in the improvement of BCVA between the two groups at 6 months postoperatively, there may be no additional benefit in removing the ILM for BRVO-associated macular edema.
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http://dx.doi.org/10.1159/000197113DOI Listing
August 2009

Correlation of visual recovery and presence of photoreceptor inner/outer segment junction in optical coherence images after successful macular hole repair.

Retina 2008 Mar;28(3):453-8

Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Chiba, Japan.

Purpose: To determine the relationship between the postoperative visual acuity (VA) and the presence of a photoreceptor inner segment (IS) and outer segment (OS) junction (IS/OS) in optical coherence tomographic (OCT) images after macular hole (MH) surgery.

Methods: Twenty-three eyes of 23 cases of idiopathic MH treated by vitrectomy were studied. The postoperative VA and OCT3 images of the fovea at 1, 3, and 6 months were examined. The relationship between the presence of the IS/OS junction and the visual acuity was studied.

Results: All MHs were successfully closed. The IS/OS junction appeared as a distinct, highly reflective line just vitread to the retinal pigment epithelial layer in the postoperative OCT3 images. A normal IS/OS junction was detected postoperatively in one eye at 1 month, three eyes at 3 months, and seven eyes at 6 months. The VA was significantly better in eyes in which a normal IS/OS junction was detected than in those not detected at 3 and 6 months postoperatively (P = 0.046 and P = 0.040, respectively).

Conclusion: The normal IS/OS junction observed in OCT3 images is associated with good visual recovery after MH closure. The presence of normal IS/OS junction may be important for visual recovery after MH repair.
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http://dx.doi.org/10.1097/IAE.0b013e3181571398DOI Listing
March 2008

[Community acquired pneumonia. Test kit for the detection of urinary antigen using immunochromatographic assay].

Rinsho Byori 2007 Jan;Suppl 138:173-8

Biochemical Research Laboratory, Eiken Chemical Co., Ltd.

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January 2007

Early postoperative macular morphology and functional outcomes after successful macular hole surgery.

Retina 2007 Feb;27(2):165-8

Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Chiba, Japan.

Purpose: To investigate the relationship between early postoperative macular morphology and postoperative visual acuity in eyes that had undergone successful macular hole (MH) surgery.

Methods: Pars plana vitrectomy and internal limiting membrane peeling were performed during surgery for idiopathic MHs on 25 eyes. The macular configuration was determined by optical coherence tomography, and best-corrected VA (BCVA) was measured postoperatively.

Results: Eleven eyes had nearly normal foveal morphology (normal group) and 14 eyes had subretinal fluid or intraretinal cysts (abnormal group) at 1 month. Among the 14 eyes in the abnormal morphology group, normal foveal morphology was confirmed in 9 eyes 3 months and in the remaining 5 eyes 6 months after surgery. Mean BCVA improved significantly from the preoperative values in both groups 6 months after surgery.

Conclusions: The morphology of the macular area was abnormal in more than one half of eyes that had successful MH surgery 1 month after surgery. However, by 6 months, all eyes had normal macular configuration, and BCVA was not significantly different in the two groups. We conclude that an abnormal morphologic appearance of the macular area in the early postoperative period does not predict the final visual outcome.
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http://dx.doi.org/10.1097/01.iae.0000224941.26720.55DOI Listing
February 2007

[Evaluation of Dipstick 'Eiken' Legionella for detection of Legionella pneumophila serogroup 1 urinary antigen using the immunochromatographical method].

Rinsho Biseibutshu Jinsoku Shindan Kenkyukai Shi 2005 ;16(1):29-35

Research and Development Headquarters, Eiken Chemical Co., Ltd., 5-26-20 Oji, Kita-ku, Tokyo 114-0002, Japan.

Dipstick 'Eiken' Legionella is a reagent for detection of Legionella pneumophila serogroup 1 antigen in urine using the immunochromatographical method. The reagent was evaluated using the reference and clinical isolated strains and clinical specimens. BinaxNOW Legionella and Legionella antigen [Mitsubishi] were evaluated simultaneously. Using four of L. pneumophila serogroup 1 strains, the minimal detectable concentration of Dipstick 'Eiken' Legionella was 5.0 x 10(4) to 2.0 x 10(5) colony forming unit/ml, it was approximate four times high in comparison with other two kits. And no positive reaction was obtained from 45 of non-L. pneumophila serogroup 1 strains. When Dipstick 'Eiken' Legionella was compared with BinaxNOW Legionella among 50 urine samples obtained from patients with pneumonia and 50 urine from healthy adults, the sensitivity was 94.7%, the specificity was 100.0% and the agreement was 99.0%. Dipstick 'Eiken' Legionella is found to be useful diagnostic reagent for Legionella infection in clinical laboratories.
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December 2005

[Evaluation of the diagnostic reagents which detect group A Streptococcus with the immunochromatographical method].

Rinsho Biseibutshu Jinsoku Shindan Kenkyukai Shi 2002 ;12(2):91-5

Department of Research and Development, Eiken Chemical Co., Ltd., 1-33-8 Hongo, Bunkyo-ku, Tokyo 113-8408, Japan.

Dipstick 'Eiken' Strep A was evaluated for this sensitivity and specificity. Dipstick 'Eiken' Strep A had a capacity to detect Group A Streptococcus in 1.5x10(5) cfu/swab. The sensitivity of Dipstick 'Eiken' Strep A was 4 times higher than the sensitivity of the latex agglutination test (Serodirect 'Eiken' Strep A) and was almost the same as the immunochromatography test (TESTPACK Plus STREP A, CLEARVIEW STREP A and ImmunoCard STAT! STREP A TEST). No cross reaction was observed among 27 strains of 25 species microorganisms with Dipstick 'Eiken' Strep A. Dipstick 'Eiken' Strep A was compared with TESTPACK Plus STREP A among throat swabs from 50 patients with pharyngitis. Dipstick 'Eiken' Strep A had a sensitivity of 92.9%, a specificity of 90.5% and an agreement of 91.8%. Dipstick 'Eiken' Strep A is found to be useful diagnostic assay in the clinical laboratories.
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June 2002
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