Congenital cataract-causing mutation ßB1-L116P is prone to amyloid fibrils aggregation and protease degradation with low structural stability.

Congenital cataract, a common disease with lens opacification, causes blindness in the newborn worldwide and is mainly caused by abnormal aggregation of crystallin. As the main structural protein in the mammalian lens, ßB1-crystallin has an important role in the maintenance of lens transparency. Recently, the L116P mutation in ßB1-CRY was found in a Chinese family with congenital nuclear cataracts, while its underlying pathogenic mechanism remains unclear. In the current study, the ßB1 wild-type protein was purified, and the mutated form, ßB1-L116P, was examined for examining the effect on structural stability and susceptibility against environmental stresses. Our results reveal low solubility and structural stability of ßB1-L116P at physiological temperature, which markedly impaired the protein structure and the oligomerization of ßB1-crystallin. Under guanidine hydrochloride-induced denaturing conditions, ßB1-L116P mutation perturbed the protein unfolding process, making it prone to amyloid fibrils aggregation. More importantly, the L116P mutation increased susceptibility of ßB1-crystallin against UV radiation. ßB1-L116P overexpression led to the formation of more serious intracellular aggresomes under UV radiation or oxidative stress. Furthermore, the ßB1-L116P mutation increased the sensitivity to the proteolysis process. These results indicate that the low structural stability, susceptibility to amyloid fibrils aggregation, and protease degradation of ßB1-L116P may contribute to cataract development and associated symptoms.

[Prevalence of benign prostatic hyperplasia in Pingliang, Gansu: investigation and clinical analysis].

OBJECTIVE: To investigate the prevalence of benign prostatic hyperplasia (BPH) in Pingliang City of Gansu Province. METHODS: We performed a cross-sectional randomized study of 836 men aged > or = 40 years from 26 communities of Pingliang, obtained their IPSS, measured the prostate volume by transabdominal ultrasonography, recorded the maximum flow (Qmax) by uroflowmetry, and processed the data by one-way analysis of variance. RESULTS: Totally 820 subjects meeting the study criteria were included in the investigation. The men ranged in age from 40 to 83 years, averaging 61.5 years. The mean IPSS, prostate volume and Qmax were 9.3 +/- 7.8, (29.2 +/- 18.6) ml and (15.3 +/- 7.2) ml/s, respectively, all correlated with age. The prevalence of moderate-severe lower urinary tract symptoms (LUTS) was 46.8% (384/820). The prostate volume was > 20 ml in 63.5% (521/820), and Qmax <15 ml/s in 48.5% (398/805) of the subjects. The incidence rate of BPH, defined as IPSS >7, Qmax <15 ml/s and prostate volume > 20 ml, was 23.5% (193/820). CONCLUSION: Among the men aged > or = 40 years in Pingliang, LUTS and prostate volume were correlated positively, while Qmax negatively with age, and the prevalence of BPH was 23.5%.