蕪城 俊克

BACKGROUND: Chemokines are a family of chemoattractants of leukocytes that play a critical role for leukocyte recruitment in various inflammatory diseases. The purpose of this study is to investigate the involvement of chemokines, interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) in the peripheral blood, with a special reference to disease activities of the patients with Behçet's disease (BD). METHODS: The study population consisted of totally 55 patients with BD who had panuveitis (20 patients with active BD, 35 patients with inactive BD) as well as 19 healthy volunteers as control. Disease activity was defined according to the existence of ocular inflammation. IL-8 and MCP-1 concentration levels in the plasma and whole-blood samples were measured by enzyme-linked immunosorbent assay. Whole-blood samples were obtained by lysing cell membranes of peripheral blood cells. RESULTS: Most of the plasma IL-8 samples were below the detectable limit. Whole-blood IL-8 levels were readily measured. The levels in the patients with active BD were significantly higher than the other two groups. The patients with active and inactive BD showed higher plasma and whole-blood levels of MCP-1 than controls. The plasma and whole-blood MCP-1 levels of the samples collected at the same time showed a linear correlation. CONCLUSION: A close relationship was found to exist between the cell-associated IL-8 and the disease activity, while a persistent role of MCP-1 was observed in BD. Measuring the whole-blood levels of chemokines is useful for monitoring the disease activity.

AIMS: To investigate the genetic differences among the strains of adenovirus type 8 (Ad8) circulating in Hiroshima city, Japan, and to study their circulation pattern. METHODS: One hundred and twenty nine strains of adenovirus type 8 (Ad8) were isolated in Hiroshima City over a 15 year period (1983-97) from patients with keratoconjunctivitis, and analysed with six restriction enzymes-BamHI, HindIII, PstI, SacI, SalI, and SmaI-to investigate possible relations among the isolates and their genetic variability. Seven hypervariable regions of the hexon gene that carry the type specific epitope were also sequenced to investigate the variation among the genome types. RESULTS: Restriction endonuclease analyses yielded three known genome types (Ad8A, 13 samples; Ad8B, seven samples; and Ad8E, 35 samples) and a novel genome type (Ad8I, 74 samples). Ad8A, Ad8B, and Ad8E were closely related, with 96% homology, whereas Ad8I had only 71% homology. Ad8A, Ad8B, and Ad8E shared 91.8% and 96.4% homology with regard to their amino acid and nucleotide sequences, respectively, with the isolate 1127 (accession no X74663). However, when compared with Ad8A, Ad8B, Ad8E, and isolate 1127, Ad8I shared only 62.7% and 69.9% homology with regard to amino acid and nucleotide sequences, respectively. Ad8A, Ad8B, and Ad8E had a unique 31 amino acid deletion in the hypervariable region 1 of the hexon gene, whereas Ad8I had a 33 residue deletion. The Ad8E strain that circulated from 1984 to 1995 was stable among the study population. Ad8I was isolated from an outbreak of epidemic keratoconjunctivitis in 1995 and was also isolated from sporadic cases until 1997. CONCLUSIONS: These results confirmed that genetic variability occurs in Ad8 in the microenvironment and revealed the emergence of a new genome type (Ad8I).

We examined the effect of a monoclonal antibody (mAb) against interferon (IFN)-inducible protein 10 (IP-10)/CXCL10 on the development of experimental autoimmune encephalomyelitis (EAE) in rats induced by injecting xenogeneic brain homogenates into footpads. Treatment with neutralizing mAb against CXCL10 exacerbated EAE with increased infiltrating CD4+ cells in the central nervous system. Furthermore, the exacerbation by the mAb treatment was accompanied by less enlarged draining popliteal lymph nodes (LN) in parallel with cell number compared with those of EAE rats treated with control mAb, whereas other lymphoid organs such as the spleen and thymus were not significantly different between rats treated with anti-CXCL10 and the control mAb. Induction of gene expression of CXCL9/Mig and CXCL10 and their receptor CXCR3 was confirmed in the draining LN in EAE rats. Induction of the third CXCR3 ligand, CXCL11/I-TAC was not seen in the draining LN, whereas all three CXCR3 ligands and CXCR3 itself were markedly detected in the spinal cords following the development of EAE. These findings suggest that CXCL10 produced in the LN plays a specific inhibitory role in the development of Th1-mediated diseases such as EAE by holding sensitized and activated Th1s expressing CXCR3 in the draining LN.

PURPOSE: To develop a new detection and typing method of oculopathogenic strains of subgenus D adenoviruses directly from conjunctival scrapings by a combination of polymerase chain reaction (PCR) and restriction enzyme analysis (REA). METHODS: A new PCR method using primer pairs of AF2/AR2, which are specific for the fiber genes, were developed to amplify 1150-bp products from nine oculopathogenic prototypes of subgenus D adenoviruses. Amplicons were cleaved with three restriction enzymes: DdeI, HinfI, and RsaI. Clinical specimens of 102 conjunctival scrapings were also evaluated by this PCR method. Restriction patterns of prototypes were used for the typing of clinical samples. Detection limit was determined by the PCR amplification of a known amount of purified adenovirus serotype 8 DNA. RESULTS: A novel PCR method based on the fiber genes allowed the amplification of nine oculopathogenic serotypes of subgenus D (Ad8, Ad9, Ad15, Ad17, Ad19, Ad22, Ad28, Ad37, and Ad39). As little as 38.4 fg of adenovirus type 8 could be detected by this method. Positive results were obtained from 48 of 102 samples (47%) by both hexon- and fiber-based PCR, whereas only 29 of 102 (28.4%) yielded positive results by culture isolation/neutralization test (NT). All positive specimens (29 samples) of culture isolation and PCR-RFLP methods showed positive results by our new fiber-based PCR method, and no positive products were detected from other subgenus of adenovirus or nonadenoviral DNA. CONCLUSIONS: A newly developed fiber-based PCR-REA method for the detection and typing of adenoviruses is faster than any former PCR methods. This all-in-1-day detection and typing method will be quite useful to the rapid diagnosis of subgenus D adenovirus infection.

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.

Transforming growth factor beta (TGF-beta) transduces signals through mediation of type I and type II serine/threonine kinase receptors. The expression of TGF-beta type I (T beta R-I) and II (T beta R-II) receptors in rat eyes was investigated immunohistochemically. T beta R-I and T beta R-II immunoreactivity was detected in corneal and conjunctival epithelial cells, corneal endothelial cells, ciliary epithelial cells, lens epithelial cells, retinal pigment epithelial cells, and choroidal vessels. This co-expression of T beta R-I and T beta R-II indicates that the above cells respond to TGF-beta and, because TGF-beta is reported to be produced in ocular tissues, that it may have important autocrine and/or paracrine roles in the growth and metabolism of ocular tissues in situ.

We investigated the effects of long-term instillation of bunazosin hydrochloride--alpha 1 specific adrenergic antagonist--on the aqueous humor dynamics and blood-aqueous barrier in rabbit eyes. We examined intraocular pressure, aqueous flow rate, and blood-aqueous barrier permiability for albumin after four weeks application of 0.05% bunazosin. The effect of bunazosin on blood-aqueous barrier destruction by laser iridophotocoagulation was also examined. During four weeks, bunazosin reduced the intraocular pressure by 1.7 +/- 0.6 mmHg (mean +/- SEM). Continuous application of bunazosin had no significant influence on aqueous flow rate and fluorescein isothiocyanate-labeled rabbit albumin (FITC-Alb) concentration in the anterior chamber. Bunazosin had no effect on the rise of the FITC-Alb concentration after iris photocoagulation, but the intraocular pressure in bunazosin treated eyes was significantly lower than in control eyes one hour after photocoagulation.