Detection of antibodies against Borrelia burgdorferi in patients with uveitis.

We determined the antibody response against Borrelia burgdorferi strains isolated from Japanese Ixodes ovatus and Ixodes persulcatus ticks by enzyme-linked immunosorbent assay and indirect immunofluorescence assay of serum specimens from 127 patients with uveitis. We examined samples of serum from Japanese patients with unclassified uveitis, iridocyclitis caused by herpes zoster virus, Behçet's disease, Vogt-Koyanagi-Harada syndrome, sarcoidosis, or other conditions (sympathetic ophthalmia, Posner-Schlossman syndrome and acute anterior uveitis with ankylosing spondylitis). Serum from healthy individuals and patients with Lyme disease served as negative and positive control samples, respectively. Significantly higher antibody titers were demonstrated in patients with uveitis than in control subjects. Of 29 patients with unclassified uveitis, nine (31) had significantly increased antibody titers against B. burgdorferi strain H014 by ELISA testing. Five patients also showed higher IgG and IgM responses than in three control subjects with Lyme disease. All positive controls showed joint problems characteristic of rheumatoid arthritis. One of three patients had uveitis. The patients were diagnosed as having Lyme disease on the basis of their history and serologic tests. A positive antibody response was recognized in several patients with Behçet's disease, Vogt-Koyanagi-Harada syndrome, sarcoidosis, and other conditions (acute anterior uveitis with ankylosing spondylitis), but not in control subjects.

Characterization of mutations in the two-component histidine kinase gene that confer fludioxonil resistance and osmotic sensitivity in the os-1 mutants of Neurospora crassa.

Osmotic-sensitive (os-1) mutant alleles in Neurospora crassa exhibit resistance to dicarboximides, aromatic hydrocarbons and phenylpyrroles. We have previously reported that the os-1 mutants can be classified into two groups based on their resistance to fungicides and osmotic stress: type I, which are highly resistant to iprodione and fludioxonil but moderately sensitive to osmotic stress, and type II, which are highly sensitive to osmotic stress but moderately resistant to fungicides. To explain the mechanism of resistance to these fungicides, we cloned and sequenced the mutant os-1 genes that encode putative osmo-sensing histidine kinase. Within the os-1 gene product (Os1p), the type I strains, NM233t and Y256M209, carried a stop codon at amino acid position 308 and a frameshift at amino acid position 294, respectively. These mutation sites were located on the upstream of histidine kinase and the response regulator domains of Os1p, strongly suggesting that type I strains are null mutants. The null mutants, NM233t and Y256M209, were highly resistant to iprodione and fludioxonil; thus Os1p is essential for these fungicides to express their antifungal activity. The amino acid changes in Os1p, 625Pro from Leu, 578Val from Ala, and 580Arg from Gly were found in the type II strains, M16, M155-1 and P5990, respectively. Os1p is novel in having six tandem repeats of 90 amino acids in the N terminal. Each amino acid change of the type II strains was located on the fifth unit of six tandem repeats. Type II strains with single amino acid changes were more sensitive to osmotic stress than the null mutants (type I), indicating that the amino acid repeats of Os1p were responsible for an important function in osmo-regulation.

Familial occurrence of Behçet's disease.

The familial occurrence of Behçet's disease in the 564 Behçet's patients treated in the Uveitis Survey Clinic of the Hokkaido University Hospital between 1967 and 1992 was investigated. Familial occurrence of Behçet's disease was found in 18 patients from 9 families. The male-to-female ratio was 3.5 in the familial cases, which was significantly higher than in the sporadic cases. Familial occurrence was most frequently seen among siblings. Most patients, including all female patients, had the complete type. They had typical ocular lesions, and exhibited bilateral uveoretinitis with poor visual prognosis, particularly the female patients. Frequency of HLA-B5 was 92% in the familial patients, which was much higher than in both the controls and the sporadic cases. It seems probable that patients with familial occurrence of this disease have a poorer prognosis with more susceptible immunogenetic backgrounds.

Posterior sub-Tenon injections of repository corticosteroids in uveitis patients with cystoid macular edema.

Repository corticosteroid was injected into the posterior sub-Tenon space in 29 cases (39 eyes) of cystoid macular edema (CME) secondary to uveitis. There were 12 cases of Behçet's disease, 7 cases of sarcoidosis, one case of tuberculous uveitis, and 9 cases of etiology unknown uveitis. In some of the patients injections were repeated 2 to 7 times at intervals of more than 2 weeks. Twenty-two of the 39 treated eyes (56.4%) showed visual improvement in at least two lines of visual acuity. Fifteen of the 22 eyes had maintained improved visual acuity over 6 months. Eleven eyes showed no improvement in vision. Most of them already had poor visual acuity (0.2 or less) before the injections. Complications of the treatment included cataract in 6 eyes, glaucoma in one, and blepharoptosis in one. Injection of repository corticosteroids into the posterior sub-Tenon space is of value in the treatment of CME secondary to uveitis. However, we have to beware of the complications of treatment.

[Familial occurrence of Behçet's disease].

Familial occurrence of Behçet's disease was studied in the Uveitis Survey Clinic of Hokkaido University Hospital. Eighteen patients in the nine families had familial occurrence of this disease. Male to female ratio was 0.28 in the familial cases, which was significantly higher than in the sporadic cases. Familial occurrence was most frequently seen among siblings. Most patients, including all of the females, belonged to the complete type. They had typical ocular lesions and exhibited bilateral uveoretinitis with poor visual prognosis, particularly in the females. The frequency of HLA-B5 was 92% in the familial patients, which was significantly higher than in the normal controls and the sporadic cases. It is probable that patients with familial occurrence of this disease have poorer prognosis with stronger immunogenetic backgrounds.

[Studies on HLA system of family members with Behçet's disease].

In order to investigate the immunogenetic mechanism of Behçet's disease, frequencies of HLA antigens were studied in family members of patients with this disease. The subjects consisted of 37 patients, 74 family members and 49 normal controls. It was shown that the frequencies of HLA-B51 were equally higher in the patients, fathers, mothers and siblings of the patients than in the normal controls. On the other contrary, the frequency of HLA-DQw1 was significantly decreased only in the patients with this disease. These results may suggest that family members of the patients have resistant genetic factors, unlike the patients.

[Posterior sub-Tenon's injections of repository corticosteroids in uveitis patients with cystoid macular edema].

Repository corticosteroid was injected into the posterior sub-Tenon's space in 29 cases (39 eyes) of cystoid macular edema (CME) secondary to uveitis. They included 12 cases of Behçet's disease, 7 cases of Sarcoidosis, one case of tuberculous uveitis and 9 cases of etiology unknown uveitis. In some of the patients injections were repeated twice to seven times at intervals of more than 2 weeks. Twenty two of the 39 treated eyes (56.4%) showed visual improvement in at least two lines of visual acuity. Eleven eyes showed no improvement in vision. Most of them had already had bad visual acuity (0.2 or less) before the injections. Complications of the treatment included cataract in 6 eyes, glaucoma in one, and blepharoptosis in one. Injection of repository corticosteroids into the posterior sub-Tenon's space was effective in the treatment of CME secondary to uveitis. However, we have to beware of the complications of this treatment.

[The diagnosis of sarcoidosis based on ocular manifestations].

A total of 131 patients with typical ocular manifestations of sarcoidosis were studied. From systemic examinations, 56 cases were confirmed histologically as sarcoidosis, 59 cases were clinically diagnosed as sarcoidosis and 16 cases were not diagnosed as sarcoidosis. There were no differences among the three groups in terms of laterality of eye involvement, sex distribution, ocular findings and prognosis. The only difference was that the age of patients not diagnosed as sarcoidosis was lower than the other two groups. In systemic examinations, patients diagnosed as sarcoidosis histologically or clinically had higher ratios of positive findings of bilateral hilar lymphadenopathy, 67Ga scanning, bronchoalveolar lavage fluid and serum angiotensin converting enzyme than patients who were not diagnosed as sarcoidosis. Some cases of the third group may be diagnosed as sarcoidosis in the future by repeated systemic examinations. The difficulty of diagnosis of sarcoidosis from ocular findings alone was discussed.

[Low dose cyclosporin treatment for ocular lesions of Behçet's disease].

Cyclosporin is an immunosuppressant that has recently been used for the treatment of Behçet's disease. We evaluated the clinical effect of low doses of cyclosporin (5 mg/kg/day) on 20 patients of Behçet's disease with refractory ocular involvement. The therapeutic effect of cyclosporin was judged by the frequency of ocular inflammatory attacks. It was effective in more than 70% of the patients. On the other hand, it had some adverse side effects such as renal dysfunction, indigestion, and neurological disorders. Most side effects were mild with low dose treatment, but neurological side effects were similar in frequency and severity to those seen with 10 mg/kg/day usage. These findings indicate that low dose cyclosporin (5 mg/kg/day) administration may be acceptable as a standard plan for treatment of Behçet's disease, but that we have to use cyclosporin with great attention to its side effects, especially neurological symptoms.

Hypotensive effect of carteolol on intraocular pressure elevation and secondary glaucoma associated with endogenous uveitis.

The therapeutic effects of carteolol hydrochloride were evaluated in the treatment of 44 uveitis patients (51 eyes) with intraocular pressure elevation or secondary glaucoma. Carteolol ophthalmic solutions, either 1% or 2%, were given twice day for more than 4 weeks in glaucomatocyclitic crisis and for more than 8 weeks in other forms of uveitis. Intraocular pressure significantly decreased from week 1 of treatment and persisted within normal limits until week 8 in glaucomatocyclitic crisis. Similarly, intraocular pressure decreased significantly from week 2 in other forms of uveitis. Intraocular pressure was well controlled in patients with open-angle glaucoma, but the control was insufficient in patients with angle-closure glaucoma. No adverse reactions such as systemic hemodynamic effects or exacerbations of intraocular inflammation were observed during this study. Carteolol therefore seems to be effective for the treatment of intraocular pressure elevation and secondary glaucoma associated with endogenous uveitis.

Cellulosome and noncellulosomal cellulases of Clostridium cellulovorans.

This paper reviews the properties of the cellulosome and noncellulosome cellulases produced by Clostridium cellulovorans, an anaerobic, mesophilic, spore-forming microorganism that produces copious amounts of cellulase. The three major subunits of the cellulosome, CbpA, exoglucanase S (ExgS), and P100, are described, as well as the properties of the functional domains of CbpA. The properties of two noncellulosomal endoglucanases, EngD and EngF, are compared. The functions of the cellulose-binding domain (CBD) of CbpA indicate its potential uses in biotechnology.