A case of multiple sclerosis with granulomatous uveitis in Japan--use of the antilipoarabinomannan (LAM)-B test in differential diagnosis.

PURPOSE: To report a patient with multiple sclerosis and associated with granulomatous uveitis, and how anti-lipoarabinomannan (LAM)-B antibody can play a key role in differential diagnosis. METHODS: Case report. RESULTS: A 35-year-old Japanese woman with multiple sclerosis, diagnosed 3 years ago, presented with blurred vision in her left eye. Ophthalmological examinations revealed granulomatous iridocyclitis in her left eye and retinal periphlebitis in both eyes. The diagnosis of tuberculosis was suspected because of a positive tuberculin skin test. However, a further examination by an anti-LAM-B antibody test excluded active tuberculosis. Her clinical findings were thought most likely to be caused by multiple sclerosis and treated with corticosteroids. CONCLUSION: We should consider the possibility of multiple sclerosis as the underlying origin in patients with granulomatous uveitis. A measurement of anti-LAM-B antibody titer may be useful in the differential diagnosis of granulomatous uveitis.

Two cases of frosted branch angiitis with central retinal vein occlusion.

BACKGROUND: Frosted branch angiitis usually occurs in children, and has a good prognosis. We report two cases of unilateral frosted branch angiitis in adults. Both had poor visual outcomes because of associated central retinal vein occlusion and neovascular glaucoma. CASES: Case 1 was a 36-year-old woman. Almost all retinal veins and some retinal arteries showed vasculitis in her right eye, and veins were slightly dilated and sheathed. Case 2 was a 23-year-old woman. Angle hypopyon was observed in her left eye. Retinal veins were dilated, meandering, and sheathed. Retinal hemorrhages were also observed. In both cases, after systemic steroid therapy the retinal vasculitis gradually decreased, but central retinal vein occlusions gradually developed. Despite systemic administration of urokinase and panretinal photocoagulation, neovascular glaucoma developed, and visual acuity diminished in both cases. CONCLUSIONS: Two cases of frosted branch angiitis complicated by retinal vein occlusion are reported. Careful observation of retinal blood flow is necessary in frosted branch angiitis in adults.

Human leukocyte antigens in forms of leprosy among Japanese patients.

Human leukocyte antigens (HLA) class II alleles were analyzed among Japanese leprosy patients to ascertain whether immunogenetic differences exist among the leprosy classification forms of Ridley and Jopling. Ninety-three unrelated Japanese leprosy patients (21 lepromatous, 24 borderline lepromatous, 17 mid-borderline, 26 borderline tuberculoid, 5 tuberculoid) and 114 healthy control subjects were investigated. The frequencies of HLA-DRB1*1501, -DRB5*0101, -DQA1*0102 and DQB1*0602 were significantly increased in all of the Japanese leprosy patients. The frequencies of HLA-DRB1*0405, -DQA1*03 and -DQB1*0401 were significantly decreased in the Japanese patients after correction of the p value. Conversely, there were no significantly different distributions of the HLA-DRB1, -DRB5, -DQA1, DQB1 alleles in the five subgroups of these patients. We conclude that HLA class II alleles were not associated with the form of leprosy. Other HLA, a non-HLA gene, and/or environmental factors may play a critical role in the different manifestations of leprosy.

Ciclosporin microemulsion preconcentrate treatment of patients with Behçet's disease.

PURPOSE: The new microemulsion preconcentrate (MEPC) formulation of ciclosporin has been developed to reduce problems in intestinal absorption and to stabilize fluctuations in blood levels. A multicenter, open-label clinical trial of MEPC was conducted to assess its efficacy and safety in Behçet's disease patients with ocular involvement. METHODS: The patient population comprised 17 de novo patients (patients not previously treated with ciclosporin in the currently available formulation) and 30 patients whose ciclosporin formulation was switched from the conventional formulation to MEPC. The patients were treated with the test formulation for 16 weeks in the former (de novo) group and for 12 weeks in the latter (switched) group. RESULTS: In the de novo group, ocular attacks decreased significantly as compared to the pretreatment incidence in 11 of the 14 patients (78.6%) evaluated after MEPC therapy. Ocular attacks also decreased significantly in the switched group. In the de novo group, visual acuity improved with MEPC therapy in 20 of the 28 eyes (71.4%) examined, and the overall efficacy evaluation was "improved" or "markedly improved" in 13 of the 16 patients evaluated (81.3%). The one case each of onset of neuro-Behçet's disease and intestinal Behçet's disease observed in the de novo group were regarded as adverse reactions. CONCLUSION: It was concluded that ciclosporin MEPC is useful for controlling the ocular symptoms of Behçet's disease, and that it can be used as effectively and safely as the conventional formulation.

[Two cases of frosted retinal angiitis with central retinal vein occlusion].

BACKGROUND: Frosted retinal angiitis usually occurs in children, and has a good prognosis. We report two cases of unilateral frosted retinal angiitis in adults. They resulted in visual degradation because of associated central retinal vein occlusion and neovascular glaucoma. CASES: Case 1 was a 36-year-old female. Almost all retinal veins and some retinal arteries had vasculitis in her right eye, and the veins were slightly dilated and sheathed. Case 2 was a 23-year-old female. Angle hypopyon was observed in her left eye. Retinal veins were dilated, meandered, and sheathed. Retinal hemorrhages were also observed. In both cases, systemic steroid therapy gradually improved the retinal vasculitis, but central retinal vein occlusions gradually developed, and in spite of systemic administration of urokinase and panretinal photocoagulation, neovascular glaucoma developed, and visual acuity became degraded in both cases. CONCLUSION: Two cases of frosted retinal angiitis complicated by retinal vein occlusion were reported. Careful observation of retinal blood flow is necessary in frosted retinal angiitis in adults.

Immunogenetics of uveitis in leprosy.

PURPOSE: To identify any possible determinants in the development of uveitis in leprosy patients. METHODS: Human leukocyte antigen (HLA) class I and II antigen, and HLA class II genotypings were analyzed among Japanese leprosy patients. Ninety-three unrelated Japanese leprosy patients (46 patients with a history of uveitis and 47 patients without uveitis) and 114 healthy control subjects were investigated. RESULTS: The occurrence of HLA-DR2 was significantly higher in patients with uveitis (78.3%) than in those without uveitis (57.4%; odds ratio = 2.7, P<.05) and in the controls (33.3%; odds ratio = 7.2, P<.0000005, Pc<.00005). The occurrence of HLA-DR4 was significantly lower in patients with uveitis (15.2%) than in those without it (38.3%; odds ratio = 0.29, P<.05) and in the controls (46.5%; odds ratio = 0.21, P<.0005, Pc<.05). Furthermore, the frequencies of DR2-positive and DR4-negative genotypes were significantly higher in patients with uveitis (69.6%) than in those without it (38.3%; odds ratio = 3.7, P<.005) and in the controls (21.9%; odds ratio = 8.1, P<.00000005). At the genomic level, the occurrence of HLA-DQB1*0302 was significantly lower in the patients with uveitis (8.7%) than in those without it (25.5%; odds ratio = 0.28, P<.05). The distribution of HLA-DRB1 and DQA1 alleles was not significantly different between the patients with and those without uveitis. However, the frequencies of DRB1*1501-positive, as well as DRB1*0405- and DQB1*0302-negative genotypes were significantly higher in the patients with uveitis (47.8%) than in those without it (25.5%; odds ratio = 2.7, P<.05) and in the controls (8.8%; odds ratio = 9.5, P<.00000005). CONCLUSIONS: Our results suggest that HLA Class II genes confer susceptibility to or protection from leprous uveitis.

Immunogenetics of episcleritis in leprosy.

Human leukocyte antigens (HLA) were analyzed among Japanese leprosy patients to identify any possible determinants in the development of episcleritis in leprosy patients. Seventy-nine Japanese leprosy patients (33 patients with history of episcleritis and 46 patients without episcleritis) and 114 healthy control subjects were investigated. Human leukocyte antigen-class I and class II specificities were determined serologically by the standard microcytotoxicity test. The HLA-DRB1, -DRB5, -DQA1, and -DQB1 genotypings were performed by using the polymerase chain reaction (PCR)-single strand conformation polymorphism and PCR-restriction fragment length polymorphism analyses. The frequency of HLA-Cw3 was significantly increased among the patients with episcleritis (66.7%) compared to patients without episcleritis (43.5%; odds ratio = 2.6, P < 0.05). The frequency of HLA-DR4 was significantly decreased among the patients with episcleritis (15.2%) compared to patients without episcleritis (39.1%; odds ratio = 0.28, P < 0.05) and the controls (46.5%; odds ratio = 0.21, P < 0.001). At the genomic level, frequencies of the HLA-DRB1*0405, -DQB1*0401, and -DQB1*0302 alleles were significantly decreased among the patients with episcleritis (0%, 0%, and 6.1%, respectively) compared to patients without episcleritis (15.2%, 13.0%, and 26.1%, respectively; odds ratio = 0.07, 0.09, and 0.18, P < 0.05). HLA-DRB1*0405 and -DQB1*0401 were also significantly decreased among the patients with episcleritis compared to the controls (29.8% and 29.8%; odds ratio = 0.04, P < 0.0001). Our results suggest that HLA-Cw3 antigen confers the susceptibility to the development of episcleritis among Japanese leprosy patients. Concurrently, the DRB1 (the -DBR1*0405), and/or DQB1 (the -DQB1*0401 and -DQB1*0302) alleles might provide protection against leprous episcleritis.

[Human leukocyte antigens and episcleritis in leprosy (Hansen's disease)].

Human leukocyte antigens (HLA) were analyzed in Japanese leprosy patients to ascertain whether immunogenetic differences exist between leprosy patients with episcleritis (ES) and those without it. The subjects were 79 Japanese leprosy patients, including 33 patients with a past history of ES, and 49 patients without ES. Controls were 114 healthy subjects. A standard microcytotoxicity test was used for typing HLA-A, -B, -C, -DR and -DQ antigens. HLA-DRB1 and DQB1 genotypings were performed by using the polymerase chain reaction (PCR)-single strand conformation polymorphism and PCR-restriction fragment length polymorphism methods. The occurrence of HLA-Cw3 was significantly greater in the patients with ES (66.7%) than in those without ES (43.5%; odds ratio = 2.6, p < 0.05). The occurrence of HLA-DR4 was significantly lesser in the patients with ES (15.2%) than in those without ES (39.1%; odds ratio = 0.28, p < 0.05) and the controls (46.5%; odds ratio = 0.21, p < 0.005). At the genomic level, the occurrence of HLA-DRB1*0405, DQB1*0401, and DQB1*0302 was significantly lesser in the patients with ES (0%, 0% and 6.1%, respectively) than in those without ES (15.2%, 13.0%, and 26.1%, respectively; odds ratio = 0.07, 0.09 and 0.18, p < 0.05). HLA-DRB1*0405 and DQB1*0401 were also significantly lesser in the patients with ES than in the controls (29.8% and 29.8%; odds ratio = 0.04, p < 0.0001). Our results suggest that HLA-Cw3 causes susceptibility to episcleritis in Japanese patients with leprosy, whereas DR4 (DRB1*0405), DQB1*0401, and DQB1*0302 provide some protection against leprous episcleritis.

[Phacoemulsification-aspiration technique with intraocular lens implantation in leprosy patients].

The author analyzed the results of cataract surgery performed in 25 eyes of 22 leprosy patients. All the eyes were treated by phacoemulsification-aspiration technique with intraocular lens implantation. The subjects consisted of 15 eyes of 14 leprosy patients with past history of uveitis and 10 eyes of 8 leprosy patients without uveitis. The mean follow-up time after surgery was 20 months and 23 months, respectively. In 93% of eyes with uveitis and 90% of eyes without uveitis, the postoperative vision improved by 2 lines or more. Postoperative complications were higher among patients with uveitis (93%) compared with patients without uveitis (40%). But no serious complications were encountered in patients with uveitis.

[HLA class II alleles and leprosy (Hansen's disease) classified by WHO-MDT criteria].

Human leukocyte antigens (HLA) class II alleles were analyzed in Japanese leprosy patients to ascertain whether immunogenetic differences exist among the forms of leprosy in classification of World Health Organization-recommended multidrug therapy (WHO-MDT). The subjects were 86 unrelated Japanese leprosy patients, including 62 multibacillary leprosy (MBL), 24 paucibacillary leprosy (PBL). Controls were 114 unrelated healthy subjects. Genotyping of HLA class II alleles was performed by using the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and PCR-restriction fragment length polymorphism (RFLP) methods. The frequencies of HLA-DRB1* 1501, * 1502 and DRB5* 0101,* 0102 and DQA1* 0102 and DQB1* 0602 were significantly increased in the whole patients (44.2%, 34.9%, 44.2%, 34.9%, 53.4% and 41.9%, respectively) as compared with the control subjects (14.0%, 21.1%, 14.0%, 21.1%, 27.2% and 13.2%, respectively). On the other hand, the frequencies of HLA-DRB1* 0405, * 0803, * 0901 and DQA1* 03 and DQB1* 0401 were significantly decreased in the whole patients (10.5%, 5.8%, 16.3%, 41.9% and 9.3%, respectively) as compared with the control subjects (29.8%, 17.5%, 30.7%, 78.1% and 29.8%, respectively). When MBL and PBL patients were compared, the frequencies of HLA-DRB1* 1501, DRB5* 0101 and DQB1* 0602 were significantly increased in the MBL patients (51.6%, 51.6% and 48.4%, respectively) as compared with the PBL patients (25.0%, respectively). Our results suggest that HLA-DRB1* 1501, DRB5* 0101 and DQB1* 0602 contribute to the susceptibility to the Japanese MBL.

[Uveitis in leprosy patients].

We examined 24 dermatologically cured leprosy patients with ongoing uveitis (UV+) and 22 age and type matched controls (UV-) to study the late phase leprous UV. All patients have been skin smear negative for more than 10 years. The history of chemotherapy, 5 years before and after a accomplishing bacterial negativity, was evaluated and represented by "SCORE". It was found that anti-PGL-I and anti-LAM-B antibodies were significantly higher in UV+ group compared to the controls. The mean SCORE of chemotherapy in UV+ group was significantly lower than in the controls. Iris pearls were seen in 10 cases or 42% out of 24 UV+ patients. No iris pearls were seen in control group. These results suggest that insufficient chemotherapy and consequent incomplete elimination of bacilli are the risk factors for leprous UV in the quiescent stage of the disease.

[HLA and uveitis in leprosy].

In order to investigate the role of immunogenetic factors in the pathogenesis of uveitis in leprosy, human leukocyte antigens (HLA) were analyzed among leprotics with and without uveitis. The subjects were 85 Japanese leprosy patients, 44 with uveitis and 41 without uveitis. Controls were 138 healthy subjects. A modified two-stage complement dependent microcytotoxicity test was used for typing HLA-A, -B, -C, -DR and -DQ antigens. The occurrence of HLA-DR2 antigen was significantly increased in patients as a whole (69.4%), and in the patients with uveitis (79.5%) as compared with the control subjects (35.5%). The association with DR2 was even stronger in the patients with uveitis (odds ratio = 7.1, Pc < 0.000005) than in the patients as a whole (odds ratio = 4.1, Pc < 0.0001). On the other hand, HLA-DR53 antigen was significantly decreased in the patients as a whole (43.5%) and in the patients with uveitis (36.4%) as compared with the control subjects (69.6%). No significant difference in the distribution of HLA antigens was observed in the patients without uveitis. Our results suggest that HLA-DR2 contributes to the susceptibility to uveitis in Japanese leprosy patients.

[HLA-DR2 alleles and uveitis in leprosy].

In order to investigate the role of immunogenetic factors in the pathogenesis of uveitis in leprosy, HLA antigens were analyzed between the leprotics with and without uveitis. Sixty-five Japanese leprosy patients comprised 32 with uveitis and 33 without uveitis. Controls consisted of 138 healthy subjects. A lymphocyte cytotoxicity test was used for typing HLA-A, -B, -C, -DR and -DQ antigens. HLA-DR2 genotyping was performed by the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and PCR-restriction fragment length polymorphism (RFLP) methods. The frequency of HLA-DR2 antigen was significantly increased in the patients with uveitis as compared with the control subjects (Pc < 0.0005), whereas HLA-DR53 antigen was significantly decreased (Pc < 0.05). At the genomic level the frequency of HLA-DRB1*1501 was significantly increased in the patients with uveitis and without uveitis as compared with that in the controls. The association with DRB1*1501 was even stronger in patients with uveitis (odds ratio = 7.1, Pc < 0.000005) than in the patients without uveitis (odds ratio = 4.1, Pc < 0.005). Our results suggest that HLA-DRB1*1501 contribute to the susceptibility to uveitis in the Japanese with leprosy.

[Image analysis of optic disk swelling in diabetic retinopathy].

Optic disc swelling was measured by computerized image analysis in diabetic patients. The subjects were divided into four groups. Group 1 contained 13 eyes without diabetic retinopathy, group 2, 14 eyes with a mild stage of simple diabetic retinopathy, group 3, 14 eyes with a severe stage of simple diabetic retinopathy and group 4, 14 eyes with preproliferative diabetic retinopathy. There were statistically significant differences in the optic disc swelling between group 1 and group 4, and between group 2 and group 4 (p < 0.05). The optic disc swelling increased as the stage of diabetic retinopathy progressed.

1H NMR study on amide proton exchange of calmodulin-mastoparan complex.

Amide proton exchange rates of Ca2(+)-saturated calmodulin and Ca2(+)-saturated calmodulin-mastoparan complex were studied by 1H NMR spectroscopy. Exchange rates of Gly25, Gly61, Gly98, Gly134, Ile27, Ile100, and Asn137 were determined for Ca2(+)-saturated calmodulin and for Ca2(+)-saturated calmodulin-mastoparan complex, and were found to be less than 10(-4)s-1. All these residues of which the amide proton resonances appear at lower fields were considered to form hydrogen bonds, based on the results of X-ray analysis. Exchange rates of Ile27 and Asn137 became an order of magnitude smaller when mastoparan bound to Ca2(+)-saturated calmodulin, while those of the four glycines and Ile100 did not change appreciably. The reduction in accessibility of Asn137 to water cased by mastoparan binding suggests that a part of the mastoparan binding site is probably located in or near the hydrophobic cluster of the C-terminal-half domain. The reduction in accessibility of Ile27 also suggests that another part of the mastoparan binding site is located in or near the hydrophobic cleft of the N-terminal-half domain.