Interaction of microbiology and pathology in women undergoing investigations for infertility.

BACKGROUND: Cases of endometriosis with no tubal damage are associated with infertility, suggesting an immunological rather than mechanical barrier to reproduction. Laparoscopy and falloposcopy results of clinically asymptomatic women undergoing investigation of infertility were correlated with the outcomes of microbiological screening for Chlamydia trachomatis, Mycoplasma pneumoniae, Mycoplasma hominis, ureaplasma species, Neisseria gonorrhoeae, Neisseria meningitidis and Chlamydia pneumoniae. METHODS: A total of 44 women presenting to a hospital IVF service for laparoscopic or laparoscopic/falloposcopic investigation of infertility provided endocervical swabs, fallopian tube washings, and peripheral whole blood for analysis. RESULTS: Of these 44 women, 15.9% (7) showed evidence of C. trachomatis infection as detected by either PCR or EIA serology. Of these 7 women, 5 (71%) had no or mild endometriosis and 2 (29%) had moderate or severe endometriosis. Of the remaining 37 women who showed no evidence of chlamydial infection, 15 (40.5%) had no or mild endometriosis. CONCLUSION: Women with infertility, but without severe endometriosis at laparoscopy, showed a trend towards tubal damage and a higher rate of previous C. trachomatis infection. Although not statistically significant, this trend would suggest that, where moderate to severe tubal damage is found to be the primary cause of infertility, C. trachomatis infection could be a likely cause for such tubal damage

The violent frontline: space, ethnicity and confronting the state in Edwardian Spitalfields and 1980s Brixton

This article discusses in comparative terms the relationship between space, ethnic identity, subaltern status and anti-state violence in twentieth century London. It does so by comparing two examples in which the control of the state, as represented by the Metropolitan Police, was challenged by minority groups through physical force. It will examine the Spitalfields riots of 1906, which began as strike action by predominantly Jewish bakers and escalated into a general confrontation between the local population and the police, and the Brixton riots of 1981, a response to endemic police harassment of mainly Caribbean youth and long-term economic discrimination in that area of South London. It will begin by dissecting the association of physical metropolitan space with the diasporic ‘other’ in the Edwardian East End and post-consensus South London, and how this ‘othering’ was influenced both by the state and the anti-migrant far right. It will then interrogate the difficult relationship between the Metropolitan Police and Jewish and Caribbean working class communities, and how this deteriorating relationship exploded into in extreme violence in 1906 and 1981. The article will conclude by assessing how the relationships between space, identity and violence influenced long-term national and communal narratives of Jewish and Caribbean interactions with the British state

Localization of the mosaic transmembrane serine protease corin to heart myocytes

Corin cDNA encodes an unusual mosaic type II transmembrane serine protease, which possesses, in addition to a trypsin-like serine protease domain, two frizzled domains, eight low-density lipoprotein (LDL) receptor domains, a scavenger receptor domain, as well as an intracellular cytoplasmic domain. In in vitro experiments, recombinant human corin has recently been shown to activate pro-atrial natriuretic peptide (ANP), a cardiac hormone essential for the regulation of blood pressure. Here we report the first characterization of corin protein expression in heart tissue. We generated antibodies to two different peptides derived from unique regions of the corin polypeptide, which detected immunoreactive corin protein of approximately 125±135 kDa in lysates from human heart tissues. Immunostaining of sections of human heart showed corin expression was specifically localized to the cross striations of cardiac myocytes, with a pattern of expression consistent with an integral membrane localization. Corin was not detected in sections of skeletal or smooth muscle. Corin has been suggested to be a candidate gene for the rare congenital heart disease, total anomalous pulmonary venous return (TAPVR) as the corin gene colocalizes to the TAPVR locus on human chromosome 4. However examination of corin protein expression in TAPVR heart tissue did not show evidence of abnormal corin expression. The demonstrated corin protein expression by heart myocytes supports its proposed role as the pro-ANP convertase, and thus a potentially critical mediator of major cardiovascular diseases including hypertension and congestive heart failure

The Glycosylphosphatidylinositol-Anchored Serine Protease PRSS21 (Testisin) Imparts Murine Epididymal Sperm Cell Maturation and Fertilizing Ability1

An estimated 25%–40% of infertile men have idiopathic infertility associated with deficient sperm numbers and quality. Here, we identify the membrane-anchored serine protease PRSS21, also known as testisin, to be a novel proteolytic factor that directs epididymal sperm cell maturation and sperm-fertilizing ability. PRSS21-deficient spermatozoa show decreased motility, angulated and curled tails, fragile necks, and dramatically increased susceptibility to decapitation. These defects reflect aberrant maturation during passage through the epididymis, because histological and electron microscopic structural analyses showed an increased tendency for curled and detached tails as spermatozoa transit from the corpus to the cauda epididymis. Cauda epididymal spermatozoa deficient in PRSS21 fail to mount a swelling response when exposed to hypotonic conditions, suggesting an impaired ability to respond to osmotic challenges facing maturing spermatozoa in the female reproductive tract. These data suggest that aberrant regulation of PRSS21 may underlie certain secondary male infertility syndromes, such as “easily decapitated” spermatozoa in humans

Testisin, a new human serine proteinase expressed by premeiotic testicular germ cells and lost in testicular germ cell tumors

We have cloned and characterized a cDNA encoding a new human serine proteinase, testisin, that is abundantly expressed only in the testis and is lost in testicular tumors. The testisin cDNA was identified by homology cloning using degenerate primers directed at conserved sequence motifs within the catalytic regions of serine proteinases. It is 1073 nucleotides long, including 942 nucleotides of open reading frame and a 113-nucleotide 3* untranslated sequence. Northern and dot blot analyses of RNA from a range of normal human tissues revealed a 1.4-kb mRNA species that was present only in testis, which was not detected in eight of eight testicular tumors. Testisin cDNA is predicted to encode a protein of 314 amino acids, which consists of a 19-amino acid (aa) signal peptide, a 22-aa proregion, and a 273-aa catalytic domain, including a unique 17-aa COOH-terminal hydrophobic extension that is predicted to function as a membrane anchor. The deduced amino acid sequence of testisin shows 44% identity to prostasin and contains features that are typical of serine proteinases with trypsin-like substrate specificity. Antipeptide antibodies directed against the testisin polypeptide detected an immunoreactive testisin protein of Mr 35,000–39,000 in cell lysates from COS-7 cells that were transiently transfected with testisin cDNA. Immunostaining of normal testicular tissue showed that testisin was expressed in the cytoplasm and on the plasma membrane of premeiotic germ cells. No staining was detected in eight of eight germ cell-derived testicular tumors. In addition, the testisin gene was localized by fluorescence in situ hybridization to the short arm of human chromosome 16 (16p13.3), a region that has been associated with allellic imbalance and loss of heterozygosity in sporadic testicular tumors. These findings demonstrate a new cell surface serine proteinase, loss of which may have a direct or indirect role in the progression of testicular tumors of germ cell origin