[Ocular findings in 304 children with Down syndrome].

PURPOSE: To identify the characteristics and frequency of ocular findings in Japanese children with Down syndrome. METHODS: A total of 304 Japanese children with Down syndrome at an average age of 7 years and 4 months were examined for ocular findings from June 2009 to January 2011. RESULTS: Most had hyperopia (69.1%) and astigmatism (58.5%). Both normal and oblique astigmatism were common. Spectacles were necessary in 91.3%. The average visual acuity at 8 years was 0.305 logMAR. Under 6 years, stripe and picture visual acuity charts were useful. Strabismus (36.5%, esotorpia 23.3%), nystagmus (25.7%), stereopsis (46.0%), entropion of eyelids (18.8%), cataract (10.5%), and corneal disease (3 cases) were found. Medullated nerve fibers (3 cases), pseudo disc edema (2 cases), and other retinal changes including Leber congenital amaurosis like chorioretinal degeneration (3 cases) were also found. CONCLUSION: The high incidence of refractive errors and strabisums in Down syndrome were confirmed. These must be treated during the sensitive period of visual development. For other ocular findings intensive ophthalmic care is important for children with Down syndrome from the time of infancy.

Assessment of cardiovascular regulation during head-up tilt and suspension in swimmers.

PURPOSE: The purpose of the present study was to compare cardiovascular responses in competitive swimmers with those in track and field (T and F) athletes during head-up tilt with engagement of the antigravity muscles in the lower extremities and during passive head-up suspension without the engagement of the antigravity muscles. METHODS: Blood pressure and heart rate during head-up tilt were compared among T and F athletes (N = 11), competitive swimmers (N = 15), and untrained subjects (N = 11). Moreover, stroke volume, cardiac output, and total peripheral resistance during head-up tilt and head-up suspension were also measured in T and F athletes and competitive swimmers. RESULTS: The heart rate increased significantly in all subject groups during head-up tilt; however, the MBP decreased in untrained subjects but did not change significantly in T and F athletes or competitive swimmers. Moreover, the DBP did not change significantly in untrained subjects or T and F athletes but increased significantly in swimmers. As with the head-up tilt, during the head-up suspension, the SBP decreased significantly and the heart rate increased significantly in both types of athletes, though the MBP decreased significantly. The ratios of decrease in stroke volume and cardiac output were significantly larger in swimmers than in T and F athletes during head-up tilt, but no significant difference was noted during head-up suspension. In T and F athletes, the ratios of decrease in stroke volume and cardiac output were significantly larger during head-up suspension than during head-up tilt, but no significant difference was noted in swimmers. CONCLUSION: The action of the antigravity muscles on cardiovascular regulation during upright standing is smaller in competitive swimmers than in T and F athletes.

Z-100, an immunomodulatory arabinomannan extracted from Mycobacterium tuberculosis strain Aoyama B, augments anti-tumor activities of X-ray irradiation against B16 melanoma in association with the improvement of type 1T cell responses.

In this study, the effects of combination therapy consisting of X-ray irradiation and Z-100 on the survival time of C57BL/6 mice inoculated with B16F10 melanoma were investigated. Survival time was significantly prolonged in B16F10 melanoma-bearing mice treated with the X-ray irradiation (5 Gy) and Z-100 (10 mg/kg s.c.) combination therapy compared with mice irradiated with X-rays alone. The weight of primary tumors and number of metastatic colonies were also significantly suppressed by the combination therapy compared with that in the X-ray irradiation group. These results indicated that Z-100 could enhance the anti-tumor effects of radiotherapy against B16F10 melanoma. On the other hand, the survival time of CD4 knockout mice bearing the same tumors was not prolonged by the combination therapy compared with mice irradiated with X-rays alone, suggesting that CD4+ cells are partly involved in augmentation of the anti-tumor effect of radiotherapy by Z-100. In addition, type 1 cytokine (IL-2, IFN-gamma) production was significantly increased and type 2 cytokine (IL-4, IL-10) production was significantly suppressed in the tumor-bearing mice treated with the combination therapy compared with the X-ray irradiation group. Moreover, interleukin-12 production by CD11c+ cells was also significantly increased in mice treated with the combination therapy compared with the X-ray irradiation group. These results indicate that Z-100 augmented the anti-tumor effects of X-ray irradiation. Moreover, we demonstrated that the effects of Z-100 were expressed at least in part, by the improvement of the T cell responses from type 2-dominant to type 1-dominant via up-regulation of IL-12 production.

Antimetastatic effect of an immunomodulatory arabinomannan extracted from Mycobacterium tuberculosis strain Aoyama B, Z-100, through the production of interleukin-12.

In this study, the role of interleukin (IL)-12 on the antimetastatic effect of Z-100 was investigated using wild-type C57BL/6 mice or IL-12p40 knockout (IL-12p40 KO) mice inoculated with highly metastatic B16F10 melanoma. When C57BL/6 mice were inoculated with B16F10 melanoma (2x10(5) cells/mouse i.v.), Z-100 (10 mg/kg i.p.) significantly suppressed the pulmonary metastasis of B16F10 melanoma 14 d after tumor inoculation. On the other hand, the antimetastatic effect of Z-100 was not observed in IL-12p40 KO mice inoculated with B16F10 melanoma. These results indicate that IL-12 is essentially required for the appearance of the antimetastatic effect of Z-100. Since helper T (Th) 2 cell responses have been reported to have a role in tumor metastasis, the regulatory effect of Z-100 on the immune balance of Th1/Th2 cell responses was investigated. In both C57BL/6 mice and IL-12p40 KO mice bearing B16F10 melanoma, Th1 cytokine production (IL-2, interferon-gamma) was significantly suppressed as compared with those in normal mice. On the other hand, Th2 cytokine production (IL-4, IL-10) in these mice was increased. The administration of Z-100 (10 mg/kg i.p.) in C57BL/6 mice bearing B16F10 melanoma improved the balance of Th1/Th2 cell responses from the Th2-dominant state to the normal state. However, the improvement of Th1/Th2 cell responses by Z-100 was not observed in IL-12p40 KO mice bearing the same tumors. In addition, Z-100 significantly increased IL-12 production by macrophages in a concentration-dependent manner, while Z-100 significantly decreased IL-10 production by these cells in vitro. These results suggested that up-regulation of IL-12 production and down-regulation of IL-10 production by Z-100 are related to the improvement of Th1/Th2 cell responses from the Th2-dominant state to the normal state, which resulted in suppression of tumor metastasis.

Anti-tumor mechanism of Z-100, an immunomodulatory Arabinomannan extracted from Mycobacterium tuberculosis strain Aoyama B, on pulmonary metastases of B16F10 melanoma: restoration of helper T cell responses via suppression of glucocorticoid-genesis.

In the present study, the anti-tumor mechanism of Z-100 was investigated with the use of pulmonary metastasis of B16F10 melanoma. In B16F10 mice, Th1 cytokine production (IL-2, IFN-gamma) was suppressed in comparison with normal mice. On the other hand, Th2 cytokine production (IL-4, IL-10) was increased in the B16F10 mice. The administration of Z-100 to B16F10 mice restored the balance of Th1/Th2 cell responses from the Th2 dominant state to the normal state. Z-100 significantly suppressed the pulmonary metastasis of B16F10 melanoma in a dose-dependent manner. These results suggest that Z-100 restored the breakdown of Th1 cell responses, resulting in the suppression of pulmonary metastasis of B16F10 melanoma. Moreover, Z-100 decreased the corticosterone levels, which is known to suppress the Th1 cell responses, in both serum specimens and splenic tissue, and the steroidogenic CYP11A1 mRNA expression in CD4+ T cells. These results suggest that a suppression of pulmonary metastasis and restoration of Thl/Th2 cell responses by Z-100 may be due to the decrease in the corticosterone levels and the steroidogenic CYP11A1 mRNA expression of CD4+ T cells in B16F10 mice. Further, the role of Th1 cytokine, IFN-gamma, on these activities of Z-100 was examined. The suppressive effects of Z-100 on pulmonary metastasis and restoration of Th1/Th2 cell responses were eliminated by the administration of anti-IFN-gamma mAb. Moreover, the suppressive effects of Z-100 on glucocorticoid-genesis were eliminated by the administration of anti-IFN-gamma-mAb. These results suggest that Z-100 restores the balance of Th1/Th2 cell responses via the suppression of glucocorticoid-genesis by Z-100-induced IFN-gamma. IFN-gamma acts as a key cytokine in anti-tumor activities of Z-100.