Japanese case of follicular lymphoma of ocular adnexa diagnosed by clinicopathologic, immunohistochemical, and molecular genetic techniques.

BACKGROUND: Follicular lymphomas of the ocular adnexa are very rare in Japan, with only two reported cases. CASE: A 44-year-old woman visited our clinic for treatment of ocular adnexal tumors in both eyes. FINDINGS: Histologic examination showed that the neoplastic lesions consisted of atypical lymphoid cells, and the tentative diagnosis was malignant lymphoma. Immunophenotypic analyses by flow cytometry and immunohistochemistry showed that the atypical lymphoid cells expressed CD45, bcl-2, CD10, CD19, CD20, IgM, and kappa light chains. The cells were negative for CD5 and other T, natural killer, or myelomonocyte antigens. Southern blot hybridization demonstrated gene rearrangement bands in the immunoglobulin JH region. Fluorescence in situ hybridization studies showed a translocation at t(14,18)(q32,q21). Systemic evaluations detected enlargements of both the inguinal lymph nodes and parabronchial lymph nodes. CONCLUSION: Our results show that flow cytometry, molecular genetic analyses, and chromosomal examination can be useful in differentiating follicular lymphoma from marginal zone B cell lymphoma of mucosa-associated lymphoid tissue and reactive lymphoid hyperplasia.

Presence of myocilin sequence variants in Japanese patients with open-angle glaucoma.

PURPOSE: To examine the myocilin (MYOC) gene for mutations in Japanese patients with primary open-angle glaucoma (POAG) and to determine the phenotypes of the patients with the mutations. METHODS: One-hundred thirty-eight unrelated Japanese patients with POAG were studied. Genomic DNA was extracted from leukocytes of peripheral blood, and the three coding exons including the intron-exon boundaries were amplified by polymerase chain reaction (PCR) and directly sequenced bi-directionally. RESULTS: Two sequence variants were identified, one novel non-synonymous amino acid change (p.Gln297His) and one reported synonymous amino acid change (p.Ala363Thr). These mutations were not detected in the 118 ethnically-matched controls. p.Gln297His was found in a 70-year-old man, who developed POAG at a late age, and his intraocular pressure was high. p.Ala363Thr was found in two cases, and both patients developed POAG at an early age and had high intraocular pressures that responded poorly to medical treatment. CONCLUSIONS: Two non-synonymous variants, p.Gln297His and p.Ala363Thr, indicate that they are involved in the pathogenesis of POAG. p.Ala363Thr has been found in another Japanese population and would be useful in genetic testing.

Association between primary open-angle glaucoma and WDR36 DNA sequence variants in Japanese.

PURPOSE: To determine whether mutations in the WD repeat domain 36 gene (WDR36) are associated with primary open-angle glaucoma (POAG) in Japanese. Subjects with high tension glaucoma (HTG) and normal tension glaucoma (NTG) were analyzed separately. METHODS: One hundred and thirty-six unrelated Japanese patients with HTG and 103 unrelated patients with NTG were studied. Genomic DNA was extracted from peripheral blood leukocytes, and all 23 exons were amplified by polymerase chain reaction (PCR) and directly sequenced bidirectionally. RESULTS: Twenty sequence alterations were identified: 10 have already been reported (p.I264V, c.1494+90C>T, c.1494+143A>G, c.1609+89G>A, c.1775+89C>A, c.1965-30A>G, p.V714V, c.2170+217C>T, p.V727V, and c.2518+60G>C) and 10 were novel (p.D179D, p.Q270Q, p.M283R, c.898+63C>G, c.1074+20C>T, p.G459G, c.1884+26C>G, p.S664L, p.S664S, and p.P744P). One nonsynonymous amino acid change in exon 17, p.S664L, was identified in a patient with HTG. The frequency of the p.I264V variant was significantly higher in the HTG group than in the control group (p=0.01), but the frequency in the NTG group was not significantly different from the control group (p=0.12). The frequency of the c.1965-30A>G variant was also significantly higher in the HTG group than in the control group (p=0.03), but the frequency in the NTG group was not significantly different from the control group (p=0.06). CONCLUSIONS: One nonsynonymous variant, p.S664L, and the association of the allelic variants (p.I264V and c.1965-30A>G) in WDR36 and their prevalence in unrelated Japanese patients with HTG suggest that they are probably involved in the pathogenesis of HTG.

Visual function with acupuncture tested by visual evoked potential.

Visual evoked potential (VEP) testing is used frequently and is an important ophthalmologic physiological test to examine visual functions objectively. The VEP is a complicated waveform consisting of negative waveform named N75 and N135, and positive waveform named P100. Delayed P100 latency and greatly attenuated amplitude on VEP are known characteristics for diagnosing optic nerve disease. Acupuncture has been used to treat wide clinical symptoms with minimal side effects. The confirmation of the efficacy of acupuncture generally relies on subjective symptoms. There is not much scientific evidence supporting the acupuncture treatments for eye diseases up to today. However, the VEP test can evaluate objectively and numerically the efficacy of the treatment by the acupuncture. We analyzed 19 healthy subjects (38 eyes). The P100 latencies in the group of less than 101.7 msec (total average) before acupuncture stimulations were not different than those after treatment (98.2 +/- 3.0 msec, 98.2 +/- 4.0 msec, respectively, p = 0.88, n = 17), but the latencies in those subjects with longer or equal to 101.7 msec were statistically different after acupuncture (104.6 +/- 2.8 msec, 101.9 +/- 3.7 msec, respectively, p = 0.006, n = 21). These results show that the acupuncture stimulation contributes to the P100 latencies of pattern reversal (PR)-VEP to some subjects who have delayed latencies, and this electrophysiological method is a valuable technique in monitoring the effectiveness of acupuncture therapy in the improvements of visual functions. The purpose of this study is to evaluate the physiological effects by acupuncture stimulations using PR-VEP in normal subjects.

Molecular genetic analysis of optineurin gene for primary open-angle and normal tension glaucoma in the Japanese population.

PURPOSE: To determine whether mutations in the optineurin (OPTN) gene are associated with the incidence of primary open-angle glaucoma (POAG) and normal tension glaucoma (NTG) in the Japanese. METHODS: Eighty-nine unrelated Japanese patients with POAG and 65 unrelated patients with NTG were studied. Genomic DNA was extracted from leukocytes of the peripheral blood, and thirteen exons of the OPTN gene were amplified by polymerase chain reaction (PCR) and directly sequenced. RESULTS: Sequence alterations in exons 4 (His26Asp), 5 (Met98Lys), and 16 (Arg545Gln) were found. The His26Asp and Arg545Gln mutations were not detected in 100 ethnically matched controls. The frequency of the missense Met98Lys variant was higher in the POAG and NTG groups than in the control group (16.9% versus 5%, 15.4% versus 5%; P = 0.009 and P = 0.029, and odds ratio 3.85 and 3.45, respectively, for the dominant effect of the OPTN A allele). Polymorphisms in exons 4 and 12, and in introns 6 and 7 were also detected. CONCLUSIONS: The association of the allelic variation (Met98Lys) in the OPTN gene and the prevalence of POAG and NTG in unrelated Japanese patients suggest that they are involved in the pathogenesis of POAG and NTG.