Opsonic function and concentration of human serum ficolin/P35.

Collectins, C-type (Ca2+-dependent) animal lectins with both collagenous and carbohydrate recognition domains, function as opsonins against pathogens. We previously described an N-acetylglucosamine (GlcNAc)-binding lectin (ficolin/P35) with a collagen- and a fibrinogen-like sequence present in human serum. In this report we show that ficolin/P35 can serve as an opsonin and enhance the clearance of pathogens having surface GlcNAc. Ficolin/P35 bound to an Ra chemotype strain of Salmonella typhimurium (TV119) which has an exposed GlcNAc at the non-reducing termini of the polysaccharide. On the other hand, ficolin/P35 did not bind to LT2, a smooth type strain of S. typhimurium with additional O-polysaccharides covering GlcNAc. Ficolin/P35 enhanced the uptake of TV119 by monocytes or polymorphonuclear leukocytes but had no opsonic activity towards LT2. These results suggest that, like collectins, ficolin/P35 is a collagenous lectin which has a role in innate immunity against certain pathogenic organisms by acting as an opsonin. We prepared monoclonal antibodies against ficolin/P35 and developed an enzyme-linked immunosorbent assay (ELISA) for measuring ficolin/P35 concentrations in humans. The mean serum concentration of ficolin/P35 from 130 normal individuals was estimated to be 13.7 microg/ml.     

Tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) stimulate osteoclastic bone resorption

As both tissue inhibitor of metalloproteinases-1 (TIMP-1) and TIMP-2 have been reported to inhibit bone resorption, we examined whether TIMP-1 or TIMP-2 in fetal calf serum (FCS), with which culture media were supplemented, affected osteoclastic bone resorption in vitro. Contrary to our expectation, almost complete suppression of osteoclastic bone resorption was observed when both TIMP-1 and TIMP-2 were removed from the FCS. Bone resorption was, however, almost fully restored by the addition of recombinant TIMPs. TIMPs stimulate bone resorption at significantly lower concentrations (∼ng/ml) than those (∼μg/ml) required to inhibit bone resorption. To understand the mechanism of TIMP-dependent bone resorption, we counted and compared the number of tartrate-resistant acid phosphatase-(TRAP-) positive and multinuclear cells in cultures containing either 10% FCS or TIMP-1-free and/or TIMP-2-free FCS. There was essentially no difference in number among these, suggesting that the TIMP role seems to be related to the functional expression of osteoclasts. Metallo-proteinase inhibitors, either BE16627B[l-N-(N-hydroxy-2-isobutylsuccinynamoyl)-seryl-l-valine] or R94138 {N-methyl-(3S)-2-[(2R)-2-hydroxycarbamoylmethylundecanoyl] hexahydropyridazine-3-carboxamide}, could not replace TIMPs, suggesting that the osteoclast-stimulating activity of TIMPs cannot be ascribed to merely their inhibitory effect on matrix metalloproteinases. Received: Oct. 15, 1998 / Accepted: April 5, 1999     

Prevalence of nocturia among Japanese adults

The prevalence of nocturia among Japanese community-dwelling adults was associated with insomnia, taking into account other correlates of insomnia.     

Radiation tolerance of the cochlear nerve at the γ-knife in rabbits

Since the first treatment of acoustic neurinoma using the γ-knife by Leksell, a series of cases have been reported with good control rates. However, the most frequent complication is delayed hearing loss which occurs in more than 50% of patients. The purpose of this study was to define a safe dose by analyzing the radiosurgical dose-response relationship and histological effects on the normal cochlear nerve in rabbit. The rabbits had computed tomography (CT)-guided stereotactic radiosurgery on their cochlear nerves in the internal auditory canal with a 4 mm collimator focusing of a γ-unit. Maximum doses of 10, 20, 30, 40, 60, 80, 100, 200 and 500 Gy were administered. After the radiosurgery, auditory brain stem responses (ABR) and the behavior of the rabbits were evaluated periodically. At the conclusion, histological investigations were performed. No physiological or histological findings were observed from doses of 30 Gy or below during the 12 month period after the radiosurgery. A dose of 100 Gy caused a severe ABR threshold elevation, vestibular dysfunction and facial palsy. Necrosis and demyelination of nerves were observed pathologically. In this study, we determined that the safe dose to the normal cochlear nerve during radiosurgery was under 40 Gy in rabbits, and complications seemed to vary due to individual differences in radiation tolerance.     

The influence of human T lymphotropic virus type I infection on the outcome of cardiovascular surgery

OBJECTIVE: Human T lymphotropic virus type I infects CD4(+) T cells and affects cell-mediated immunity. Cardiopulmonary bypass transiently alters lymphocyte subsets, resulting in a reduction in CD4(+) T cells and an increase in CD8(+) T cells. We proposed that cardiovascular operations and human T lymphotropic virus type I infection may act synergistically, resulting in serious damage to cell-mediated immunity. METHODS: A total of 517 consecutive patients who were preoperatively screened for anti-human T lymphotropic virus type I antibody and underwent cardiovascular operations with cardiopulmonary bypass were enrolled in this study. Of the 517 patients, 82 (16%) had positive test results for anti-human T lymphotropic virus type I antibody. The surgical outcome of patients with positive and negative results for anti-human T lymphotropic virus type I antibody was analyzed retrospectively. RESULTS: There was no difference between the 2 groups with respect to early mortality. Distribution of survival curve was also not significantly different (P =.5; mean follow-up duration, 2.4 +/- 1.8 years [range, 0-9.4 years] and 3.2 +/- 2.8 years [range, 0-9.8 years]) in the groups with positive and negative antibody results, respectively). In particular, long-term follow-up did not reveal adult T-cell leukemia or human T lymphotropic virus type I-associated myelopathy, and occurrence of neoplasm did not differ between groups. Early infectious complication was, however, significantly higher in the group with positive antibody results than in the group with negative results (P =.02). Logistic regression analysis revealed human T lymphotropic virus type I infection as a significant risk for this complication (P =.04; odds ratio, 2.5; 95% confidence interval, 1. 0-5.8). CONCLUSION: A combination of human T lymphotropic virus type I infection and cardiovascular operation is believed to increase the potential risk of infectious complications shortly after the operation. However, this synergistic effect seems to be transient and has little influence on long-term prognosis.