Follistatin and activin A production by the male reproductive tract

Follistatin is a binding protein for the activin and inhibin family of hormones, regulating their biological activity. In the male reproductive tract, the interaction of these factors is likely to be involved in the regulation of the proliferation of several cell types. We have investigated the presence of follistatin and activin A in seminal plasma using specific immunoassays and have localized follistatin and activin/inhibin subunits in the adult human testis, prostate and seminal vesicle to establish their likely sources. High concentrations of immunoreactive follistatin were present in seminal plasma in normal men (mean 97.9 ng/ml; 1.43 ng/ml in peripheral plasma) and were similar in men with oligo/azoospermia and following vasectomy. Follistatin immunoreactivity was localized to both Leydig and Sertoli cells of the testis, and to epithelial cells of the prostate gland and seminal vesicle, which are likely to be the predominant sources of the hormone in seminal plasma. Activin A was also present in seminal plasma in normal men but was undetectable following vasectomy, thus deriving from the testis. Consistent with this finding, the betaA-subunit was immunolocalized in Sertoli and Leydig cells but was not present in seminal vesicle or prostate gland. The functional significance of the high concentrations of follistatin secreted into seminal plasma by the prostate gland and/or seminal vesicle is uncertain, but they may regulate the biological activity of testis-derived activin A and inhibin B.      

Effect of resin hydrophilicity and water storage on resin strength

This study evaluated the change in the ultimate tensile strength (UTS) of five polymerised resin blends of increasing hydrophilicity, after ageing in distilled water or silicon oil. Resin blocks were prepared from each resin blend by dispensing the uncured resin into a flexible, embedding mould, containing multiple cavities. The resins were polymerised in the moulds under nitrogen at 551.6 kPa and light-activated at 125 degrees C for 10 min. After dry ageing for 24 h at 37 degrees C, the middle third of each resin specimen was trimmed into an 'I' shape. Fifteen control specimens were randomly selected from each resin blend for baseline UTS evaluation. The UTS of the experimental specimens were determined after 1, 3, 6 and 12 months of ageing in water or oil. The UTS of each group of resins at different storage periods in water or oil were analysed using the Friedman multiple ANOVA on ranks and Dunn's multiple comparison tests at 95% confidence level. Significant reduction (p < 0.01) in UTS was observed in Groups II-V resins after 12-month storage in water, while the most hydrophobic Group I resin showed no significant change (p > 0.05) in the same period. The percentage reduction in UTS increased with the hydrophilicity of the resin blends. Long-term water storage of hydrophilic resin blends such as those employed in dentine adhesives, resulted in a marked reduction in their mechanical strength that may compromise the durability of resin-dentine bonds.     

The CTLA-4 gene region of chromosome 2q33 is linked to, and associated with, type 1 diabetes. Belgian Diabetes Registry

Susceptibility to autoimmune insulin-dependent (type 1) diabetes mellitus is determined by a combination of environmental and genetic factors, which include variation in MHC genes on chromosome 6p21 (IDDM1) and the insulin gene on chromosome 11p15 (IDDM2). However, linkage to IDDM1 and IDDM2 cannot explain the clustering of type 1 diabetes in families, and a role for other genes is inferred. In the present report we describe linkage and association of type 1 diabetes to the CTLA-4 gene (cytotoxic T lymphocyte associated-4) on chromosome 2q33 (designated IDDM12). CTLA-4 is a strong candidate gene for T cell- mediated autoimmune disease because it encodes a T cell receptor that mediates T cell apoptosis and is a vital negative regulator of T cell activation. In addition, we provide supporting evidence that CTLA-4 is associated with susceptibility to Graves' disease, another organ- specific autoimmune disease.      

Immunotactoid glomerulopathy with fingerprint immune deposits

Summary Immunotactoid glomerulopathy is a distinct clinico-pathological entity which has recently been defined. The term immunotactoid refers to highly organized immune depositions appearing as rod-like microtubular structures in ultrastructural examination. We describe a patient with mixed connective tissue disease who demonstrates characteristic features of immunotactoid glomerulopathy. The diagnosis was made after excluding amyloidosis, cryoglobulinaemia and lupus nephritis. In addition to immunotactoid microtubules, ultrastructural examination also demonstrated presence of fingerprint depositions which were intimately mixed with immunotactoid structures. Fingerprint deposits have been described in lupus nephritis and cryoglobulin-related nephropathy, but rarely in other glomerulonephritis. These unique findings in our patient may suggest a previously unsuspected relationship between the syndrome of immunotactoid glomerulopathy and systemic lupus erythematosus.     

Y chromosome microdeletions, in azoospermic or near-azoospermic subjects, are located in the AZFc (DAZ) subregion

Submicroscopic deletions of the Y chromosome and polymorphisms of the androgen receptor (AR) gene in the X chromosome have been observed in men with defective spermatogenesis. To further define the subregions/genes in the Y chromosome causing male infertility and its relationship to polymorphisms of the AR polyglutamine tract, we screened the genomic DNA of 202 subfertile males and 101 healthy fertile controls of predominantly Chinese ethnic origin. Y microdeletions were examined with 16 sequence-tagged site (STS) probes, including the RBM and DAZ genes, spanning the AZFb and AZFc subregions of Yq11, and related to the size of trinucleotide repeat encoding the AR polyglutamine tract. Y microdeletions were detected and confirmed in three out of 44 (6.8%) of azoospermic and three out of 86 (3.5%) severely oligozoospermic patients. No deletions were detected in any of the patients with sperm counts of >0.5 x 10(6)/ml, nor in any of the 101 fertile controls. All six affected patients had almost contiguous Y microdeletions spanning the entire AZFc region including the DAZ gene. The AZFb region, containing the RBM1 gene, was intact in five of the six subjects. Y deletions were not found in those with long AR polyglutamine tracts. Our study, the first in a Chinese population, suggest a cause and effect relationship between Y microdeletions in the AZFc region (possibly DAZ), and azoospermia or near-azoospermia. Y microdeletions and long AR polyglutamine tracts appear to be independent contributors to male infertility.