DNA methylation studies on imprinted loci in a male monozygotic twin pair discordant for Beckwith–Wiedemann syndrome

Tierling S, Souren NY, Reither S, Zang KD, Meng‐Hentschel J, Leitner D, Oehl‐Jaschkowitz B, Walter J. DNA methylation studies on imprinted loci in a male monozygotic twin pair discordant for Beckwith–Wiedemann syndrome. Beckwith–Wiedemann syndrome (BWS) is one of the most prevalent congenital disorders predominantly caused by epigenetic alterations. Here we present an extensive case study of a monozygotic monochorionic male twin pair discordant for BWS. Our analysis allows to correlate BWS symptoms, like a protruding tongue, indented ears and transient neonatal hypoglycaemia, to an abnormal methylation at the KvDMR1. DNAs extracted from peripheral blood, skin fibroblasts, saliva and buccal swab of both twins, their sister and parents were analysed at 11 differentially methylated regions (DMRs) including all four relevant DMRs of the BWS region. The KvDMR1 was exclusively found to be hypomethylated in all cell types of the affected BWS twin, while the unaffected twin and the relatives showed normal methylation in fibroblasts, buccal swab and saliva DNA. Interestingly, the twins share a common blood‐specific hypomethylation phenotype most probably caused by a feto‐fetal transfusion between both twins. Because microsatellite analysis furthermore revealed a normal biparental karyotype for chromosome 11, our results point to an exclusive correlation of the observed BWS symptoms to locally restricted epimutations at the KvDMR1 of the maternal chromosome.     

1141154113Expression of natural cytotoxicity receptors in peripheral blood NK cell subsets of women with recurrent spontaneous abortions (RSA) or implantation failures

Aim:  To determine if IgA is required for protection against Chlamydia infection in the male reproductive tract (MRT).
Materials and Methods:  Male polyimmunoglobulin receptor knockout mice (PIgR^-/-) and wild-type C57BL/6 (WT) mice were immunised intranasally with chlamydial major outer membrane protein (MOMP) and cholera toxin (CT). MOMP-specific IgG and IgA in serum and prostatic fluids were measured by ELISA. Serum and PF were also assayed for inhibition of in vitro chlamydial infection. Immunized WT and PIgR^-/- mice were challenged by direct inoculation of C. muridarum into the meatus urethra. Four weeks post challenge Chlamydia levels in the penile urethra, epididymis and testis were determined by PCR.
Results:  Equivalent levels of IgG were found in the serum of both WT and PIgR^-/- mice however IgA in serum of PIgR^-/- mice was 19- to 20-fold higher than in WT animals consistent with the lack of the PIgR IgA transport molecule. IgA levels were significantly lower in PIgR^-/- PF compared to WT PF after both immunization and infection. Only PF from WT but not PIgR^-/- animals was able to inhibit in vitro chlamydial infection. Following challenge significantly higher levels of Chlamydia were recovered from the MRT of PIgR^-/- mice compared to WT animals.
Conclusions:  Male mice lacking a functional PIgR were unable to clear a genital tract Chlamydia infection despite high levels of serum IgA. These data show that mucosal IgA plays a major role in preventing chlamydial infection of the male genital tract and suggest that immunization strategies to protect males should target a strong mucosal IgA response.     

In silico genomic analysis of the human and murine guanylate-binding protein (GBP) gene clusters.

The guanylate-binding proteins (GBPs) were among the first interferon (IFN)-stimulated genes (ISGs) discovered, but until recently, little was known about their functions and even less about the composition of the gene family. Analysis of the promoter of human GBP-1 contributed significantly toward the understanding of Jak-Stat signaling and the delineation of the IFN-gamma activation site (GAS) and IFN-stimulated response element (ISRE) promoter elements. In this study, we have examined the genomic arrangement and composition of the GBPs in both mouse and humans. There are seven GBP paralogs in humans and at least one pseudogene, all of which are located in a cluster of genes on chromosome 1. Five of the six MuGBPs and a GBP pseudogene are clustered in a syntenic region on chromosome 3. The sixth MuGBP, MuGBP-4, and three GBP pseudogenes are located on chromosome 5. As might be expected, the GBPs share similar genomic organizations of introns and exons. Five of the MuGBPs had previously been shown to be coordinately induced by IFNs, and as expected, all of the MuGBPs have GAS and ISRE elements in their promoters. Interestingly, not all of the HuGBPs have GAS and ISRE elements, suggesting that not all GBPs are IFN responsive in humans.     

Critical review of the efficacy and safety of cryotherapy of the prostate

Modern cryoablation of the prostate is a procedure that has evolved since the early 1990s into a safer and more successful treatment of adenocarcinoma of the prostate. The improvement of this technique has taken place secondary to advancement in engineering, procedure refinement, temperature monitoring, and a better understanding of physiologic events during the freezing process. Long-term results are available that demonstrate durable efficacy equivalent to other therapies in low-risk groups. In moderate to high risk groups, results point toward equal to superior results than other standard therapies. New ideas on potency preservation using vacuum erection devices have improved men’s return to function over the course of the postoperative year. Early morbidity issues, such as fistula formation and incontinence, have become much less problematic, with results between 0% and 1% in some series. Cryoablation of the prostate now offers significantly improved outcomes with a parallel decrease in morbidity.     

OUTLOOKS ON THE FUTURE OF NURSE-MIDWIFERY*

It is essential that people and organizations stop to think about their personal and professional expectations of the future. Inherent in this is the need to explore societal as well as professional trends before adopting a plan for professional growth. This scenario was developed to be a futuristic look at nurse-midwifery from the year 1980 to the year 2005. The 25 years that will follow the 25th Anniversary Convention will be important for nurse-midwives, and this article explores some of the societal, women's, and health care issues that may impact the profession of nurse-midwifery.