Immunoreactions for P53 isoforms are associated with ultrastructural proliferative profiles in benign thyroid nodules.

BACKGROUND: P53 isoforms originate from the alternative initiation of P53 gene translation through usage of an internal promoter located in intron 4. All P53 isoforms are spliced in intron 9 and may modulate cell proliferation and cell fate outcome in response to DNA damage. AIM: To examine immunoexpression of P53 isoforms in benign proliferative lesions occurring in multinodular thyroids and to assess the ultrastructural phenotype of P53 distribution in the thyrocytes of those lesions by electron microscopy. MATERIALS AND METHODS: By immunohistochemistry and transmission electron microscopy (TEM), we evaluated 38 multinodular thyroids containing a total of 102 benign lesions: 38 nodular goiters (NG; colloid=20, parenchymatous=18), 52 follicular adenomas (FA) and 12 Hashimoto's thyroditis (HT). FA were classified into 10 normo-follicular, 9 macro-follicular, 28 micro-follicular and 5 solid variants. RESULTS: Immunoreaction for P53 isoforms was observed in approximately 50% of all lesions, except macrofollicular variant FA (33%). At TEM analysis, immunoreactive NG, FA and TH lesions showed signs of proliferation by simultaneous appearance of dispersed chromatin, increased amounts of cytoplasmic organelles and dilation of the rough endoplasmic reticulum. TEM signs of apoptosis and proliferation were also detected in FA, but with different rates compared to NG. CONCLUSION: The immunohistochemical expression of P53 isoforms in NG, FA and HT suggests their role in the development of these lesions. Ultrastructural findings support the hypothesis that P53 immunoexpression correlates with reactive proliferative changes in thyrocytes.

Ultrastructural and quantitative study of clitoral cavernous tissue from living subjects.

INTRODUCTION: There has never been an investigation about the in vivo clitoral structure. AIM: To study the "in vivo" age-related structural changes of the clitoris in healthy women and in those affected by metabolic disorders. METHODS: Forty-three women subgrouping in (i) five teenagers, aged 14-18; (ii) eight young premenopausal women, aged 23-32; (iii) 10 premenopausal women, aged 38-47; (iv) nine diabetic premenopausal women, aged 27-43; and (v) 11 naturally postmenopausal women aged 51-55. Each woman underwent microbiopsy of the clitoral body by means of an 18G needle, length 100 mm, using a semiautomatic gun during total anesthesia for a benign gynecological pathology. The tissue removed was processed for electron microscopy. A morphometric procedure was used on electron micrographs. MAIN OUTCOME MEASURE: Micro ultrastructure observation of clitoral tissue. RESULTS: The cavernous tissue from the teenagers and young women showed large amounts of smooth muscle cells (SMCs). The intercellular connective tissue showed scanty, small isometric collagen fibers and amorphous extracellular matrix. In the premenopausal diabetic women, ultrastructural abnormalities of SMCs were observed, consisting of increase of glycogen deposits, infolding cell borders, and cytoplasmic vacuoles. Moreover, the intercellular connective tissue was increased by densely packed collagen fibers. Finally, in the healthy, natural postmenopausal women, the SMCs were moderately reduced in number. We observed age-related structural changes of the vascular spaces and of the vascular lacunae. The SMC mean thickness was reduced with age; vascular abnormalities appeared to be correlated with the presence of metabolic diseases, such as diabetes. CONCLUSION: Our "in vivo" study could help to understand some aspects of the physiology of the clitoris and its role in sexual response. Apart from data obtained by studying healthy women and women affected by diabetes, other investigations are needed to study subgroups of otherwise healthy sexually dysfunctional women.

Immunoprotective activities of a Streptococcus suis pilus subunit in murine models of infection.

Pili of gram-positive bacteria are key virulence factors and their subunits are considered excellent vaccine candidates. Streptococcus suis is an emerging zoonotic agent that can cause epidemics of life-threatening infections in humans, but the functional role or immunoprotective potential of its pilus components have not been studied yet. Using a selective proteomics approach, we have identified a surface protein of serotype 2 S. suis showing features of an ancillary pilus subunit, as evidenced by bioinformatics analysis, immunoblot and immunoelectron microscopy. Immunization with recombinant fragments of this protein, designated herein as PAPI-2b, markedly protected mice from systemic S. suis infection.