Summary
Surfactant protein A (SP‐A), first identified as a component of the lung surfactant system, is now recognized to be an important contributor to host defence mechanisms. SP‐A can facilitate phagocytosis by opsonizing bacteria, fungi and viruses, stimulate the oxidative burst by phagocytes and modulate pro‐inflammatory cytokine production by phagocytic cells. SP‐A can also provide a link between innate and adaptive immune responses by promoting differentiation and chemotaxis of dendritic cells. Because of the obvious relevance of these mechanisms to the host defence and ‘gate keeping’ functions of the lower genital tract, we examined human vaginal mucosa for SP‐A protein and transcripts and analysed vaginal lavage fluid for SP‐A. By immunocytochemistry, SP‐A was identified in two layers of the vaginal epithelium: the deep intermediate layer (the site of newly differentiated epithelial cells); and the superficial layer (comprising dead epithelial cells), where SP‐A is probably extracellular and associated with a glycocalyx. Transcripts of SP‐A were identified by Northern blot analysis in RNA isolated from vaginal wall and shown, by sequencing of reverse transcription–polymerase chain reaction products, to be derived from each of the two closely related SP‐A genes, SP‐A1 and SP‐A2. SP‐A was identified in vaginal lavage fluid by two‐dimensional gel electrophoresis, and confirmed by mass spectrometry. This study provides evidence, for the first time, that SP‐A is produced in a squamous epithelium, namely the vaginal mucosa, and has a localization that would allow it to contribute to both the innate and adaptive immune response. The findings support the hypothesis that in the vagina, as in lung, SP‐A is an essential component of the host‐defence system. A corollary hypothesis is that qualitative and quantitative alterations of normal SP‐A may play a role in the pathogenesis of lower genital tract inflammatory conditions.
Our analysis of cDNA and genomic clones unexpectedly revealed that the chicken gata-5 gene is differentially expressed from alternative first exons. Moreover, we show that the respective transcripts are differentially processed to yield mRNAs for two distinct isoforms of GATA-5. The major isoform, which we described previously, has two CXNCX 17 CNXC zinc fingers typical of a vertebrate GATA factor. The minor isoform, on the other hand, has only one such zinc finger. We show that this novel isoform localizes within the nuclei of transfected cells and can bind to a consensus GATA site. This truncated isoform of GATA-5 is compromised in its ability to transactivate a simple target gene, however, and thus is functionally distinct from the major isoform of GATA-5.
PROBLEM
Our knowledge of the innate host-defenses in the vagina, a site where these defenses are essential to protecting the host upper reproductive tract from invasion by pathogens, is as yet rudimentary. Specifically, little is known about the pattern-recognition component of vaginal innate immunity, the relationship of pattern-recognition molecules to known cytokine levels, and the role of gonadal hormones in their regulation.
METHOD OF STUDY
We measured levels of Surfactant Protein-A (SP-A), a prototypic innate pattern-recognition protein, in vaginal fluid (VF) and correlated them with levels of IL-1β and IL-8, two cytokines known to be present in VF. Assays were carried out on VF collected over three consecutive cycles from ten healthy naturally cycling women who were sampled at three specific time points in the menstrual cycle. The three time points were chosen to enable correlation with distinct hormonal states.
RESULTS
Both SP-A and cytokines levels were highest 5–6 days after menses (p < 0.05) and were significantly lower at ovulation and mid-luteal phase.
CONCLUSION
SP-A, like other host-defense molecules in the reproductive tract, appears to be regulated by gonadal hormones.
Abstract. Background:The association of DLG5 R30Q with IBD has been replicated in several populations, but is not statistically significant in others. We studied the incidence of DLG5 alleles in a population of IBD patients from Pennsylvania. Methods: DLG5 R30Q (rs1248696) and G1066G (rs1248634) were analyzed with PCR-based RFLP methods in a total of 521 subjects, that included 105 individuals with IBD and 139 without IBD from a familial IBD registry, 107 with sporadic IBD, and 170 unrelated healthy controls. R30Q was further analyzed with SNPlex TM Genotyping System in 473 samples. Results: RFLP genotyping data showed that, DLG5 R30Q was significantly associated with IBD overall (p = 0.006), and separately with CD (p = 0.009) and UC (p = 0.024). The association of R30Q with IBD was entirely due to a male-associated effect (male vs female p = 0.015 vs 0.241 (IBD), p = 0.024 vs 0.190 (CD), and p = 0.019 vs 0.575 (UC)). The frequency of the A allele carriage was elevated in both affected and unaffected members in the familial IBD cohort compared to healthy controls (p = 0.037). In the family pedigrees, we observed differences in the expression of IBD in individuals carrying the A allele between families. Conclusions: In the studied population, DLG5 R30Q was associated with all forms of IBD. An elevated presence of the R30Q variant was observed in all members of a familial IBD registry. This association of the R30Q variant with IBD was male-specific.
Dyspareunia, better termed women's sexual pain, is a poorly understood disorder once believed to be purely psychologic. Thanks to cooperative research efforts from several specialties toward defining subsets of the disorder, understanding the etiology of subsets and their comorbidities and new concepts for diagnosis and management are being validated or are being put into practice. This review describes the surprising prevalence of sexual pain, outlines new definitions for subtypes of sexual pain and diagnostic criteria for them, and applies these diagnoses to the task of selecting treatment options.
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