Post-translationally modified human lens crystallin fragments show aggregation in vitro.

BACKGROUND: Crystallin fragments are known to aggregate and cross-link that lead to cataract development. This study has been focused on determination of post-translational modifications (PTMs) of human lens crystallin fragments, and their aggregation properties. METHODS: Four crystallin fragments-containing fractions (Fraction I [∼3.5 kDa species], Fraction II [∼3.5-7 kDa species], Fraction III [∼7-10 kDa species] and Fraction IV [>10-18 kDa species]), and water soluble high molecular weight (WS-HMW) protein fraction were isolated from water soluble (WS) protein fraction of human lenses of 50-70 year old-donors. The crystallin fragments of the Fractions I-IV were separated by two-dimensional (2D)-gel electrophoresis followed by analysis of their gel-spots by mass spectrometry. The Fractions I-IV were examined for their molecular mass, particle-diameters, amyloid fibril formation, and for their aggregation by themselves and with WS-HMW proteins. RESULTS: Crystallin fragments in Fractions I-IV were derived from α-, ß- and γ-crystallins, and their 2D-gel separated spots contained multiple crystallins with PTMs such as oxidation, deamidation, methylation and acetylation. Crystallin fragments from all the four fractions exhibited self-aggregated complexes ranging in Mr from 5.5×105 to 1.0×108 Da, with diameters of 10-28 nm, and amyloid fibril-like formation, and aggregation with WS-HMW proteins. CONCLUSION: The crystallin fragments exhibited several PTMs, and were capable of forming aggregated species by themselves and with WS-HMW proteins, suggesting their potential role in aggregation process during cataract development. GENERAL SIGNIFICANCE: Crystallin fragments play a major role in human cataract development.

Hormone receptor status of breast cancer in India: a study of 798 tumours.

The objectives of this study were to document the oestrogen and progesterone receptor (ER & PR) status of breast cancer in the Indian population (as done by immunohistochemistry on paraffin blocks), and correlate the steroid receptor status of breast cancer with all relevant patient and tumour characteristics. Our current data have been compared with previously published data from other centres. In contrast to the higher rates reported in the Western literature, only 32.6% of our tumours were ER positive and 46.1% were PR positive. Tumours were separated into four categories: ER+PR+ (25%), ER+PR- (7.4%), ER-PR+ (21.1%) and ER-PR- (46.5%). ER and PR immunoreactivity increased with advancing age, and correlated with the presence of elastosis. Infiltrating lobular carcinoma, mucinous carcinoma, and mixed tumours were more frequently ER & PR positive. High-grade infiltrating duct carcinomas, pure comedo ductal carcinoma in situ, and medullary carcinoma were predominantly ER & PR negative. The presence of necrosis and lymphovascular invasion showed an inverse relationship with ER and PR reactivity.

Social aspects of leprosy in Malaysia.

This paper attempts to explain both the persistence of traditional misconceptions about leprosy as well as the relative ineffectiveness of the Leprosy Control Programme. It has been pointed out that leprosy is a disease with tremendous social significance. To improve the Programme therefore, the human element which is of paramount importance must be identified and rectified. It is felt however, that we the providers should set our own house in order first. We need to find out the knowledge, attitudes and practices of the medical personnel and auxiliaries relating to leprosy, and identify the factors that contribute to their lack of motivation and undesirable attitudes which in turn deter patients from seeking and continuing treatment. Interventions based on the findings of such studies will contribute considerably towards the successful implementation of the Programme.