Mouse model for endometriosis is characterized by proliferation and inflammation but not epithelial-to-mesenchymal transition and fibrosis

Endometriosis is a common disorder of unknown etiology, and non-surgical therapies are still a challenge. Tounderstand the pathogenesis and preclinical testing of drugs for endometriosis, animal models are highlydesirous. Herein, we carried out longitudinal characterization of a mouse model for endometriosis whereuterine tissue was transplanted onto the intestinal mesentery. During the course of lesion development from day15 to 60 post-induction, the ectopic endometrium became pale, fluid-filled and the animals developed peritoneal adhesions. Most lesions resembled a well-differentiated type of endometriosis and * 13% of animalshad mixed type of lesions. There was extensive stromal compaction in the ectopic tissue. During the progression of endometriosis, there was increased proliferation of epithelial and stromal cells as evident by PCNAstaining. Cyp19a1 (aromatase) mRNA was detected in the ectopic lesions on day 15 and 30 post-induction ofendometriosis, by day 60 the expression was reduced. As compared to the control endometrium, the mRNAlevels of Esr1 progressively reduced while the levels of inflammation associated genes (Esr2, Ifng, Tnf andIl1b) increased in the ectopic lesions. Infiltration of macrophages and polymorphonuclear leucocytes was alsoobserved in the ectopic lesions indicative of inflammation. As compared to control, there was no change inlevels of Cytokeratin and E-cadherin in the epithelial cells of ectopic endometrium. We did not observeexcessive collagen deposition or a-SMA positive myofibroblasts in the stroma of the ectopic endometrium.Thus, epithelial-to-mesenchymal transition and fibrosis are not detected in the mouse model of endometriosis.Our results show that the mouse model of endometriosis mimics some but not all the features of humanendometriosis.

de novo Histoid leprosy: an expatriate case recently diagnosed in Johannesburg

Abstract: Histoid leprosy (HL) is a rare variant of lepromatous leprosy with unique clinical, histopathological, and microbiological features. A 32-year-old man from Malawi who immigrated to Johannesburg 1-year-ago, presented with a 4-month history of flesh-colored nodules on the face and trunk and hyperpigmented plaques on the chest and limbs. Skin slit smears confirmed multibacillary leprosy, and skin punch biopsies showed proliferation of spindled cells containing a large number of acid-fast bacilli. The prevalence of de novo HL is increasing in the era of leprosy elimination. HL cases may act as reservoirs and negatively affect the global control of leprosy.

Subcutaneous nodules of cysticercosis as a sign of asymptomatic neurocysticercosis in an HIV positive patient

Abstract Cysticercosis is caused by the hematogenous dissemination of the larval form (cysticercus) of Taenia solium. It can affect any organ or tissue in the body but commonly affects the subcutaneous tissue, central nervous system, eyes, and skeletal muscle. Skin lesions can assist as a marker in the diagnosis of asymptomatic neurocysticercosis in endemic areas. A 49-year-old HIV positive man presented with multiple cutaneous nodules confirmed as cysticercomas which led to the diagnosis of asymptomatic neurocysticercosis. He was successfully treated with albendazole and steroids at recommended doses with no adverse effects.

Cellular ontogeny of RBMY during human spermatogenesis and its role in sperm motility.

The Y-chromosome-encoded gene RBMY (RNA-binding motif on Y) is a male germline RNA-binding protein and is postulated to be a RNA-splicing regulator. In order to understand the roles of RBMY in different stages of male gamete maturation, the present study aimed at determining its cellular expression during spermatogenesis, spermeogenesis and in mature spermatozoa. In the spermatogonia (cKIT-positive cells), RBMY immunolocalized as two distinct foci, one in the nucleolus and the other in the subnuclear region; in the spermatocytes (cKIT-negative cells), the nucleus had punctuate staining with a subnuclear foci; in the pachytene cells, the protein was localized as a punctuate pattern in the nucleus spread along the elongating chromosomes. In the round and the elongating spermatids, the protein expression was polarized and restricted to the cytoplasm and in the developing mid-piece. In testicular and ejaculated sperm, RBMY was localized to the mid-piece region and weakly in the tail. Incubation of spermatozoa with the RBMY antibody reduced its motility. The spatial differences in expression of RBMY in the germ cells and the presences of this protein in post-meiotic cells and in transcriptionally inert spermatozoa suggest its involvement in multiple functions beyond RNA splicing. One such possible function of RBMY could be its involvement in sperm motility.

Progesterone receptors on human spermatozoa.

Progesterone, primarily recognized as a female steroid hormone, is reported to affect several sperm functions especially capacitation, motility and acrosome reaction. These effects of progesterone on the spermatozoa are mediated via the progesterone binding sites/progesterone receptor (PR) on the acrosomal membrane. These receptors in response to progesterone increase the intercellular Ca2+ levels and stimulate Ca2+ influx in the mature human spermatozoa via non-genomic mode of actions. Characterization of this receptor reveals that the sperm PR is masked protein and is exposed to the surface by some non-ionic detergents. Localized on to the acrosome region of the spermatozoa, these receptors are recognized by most antibodies directed towards the C-terminal region of the conventional PR. The estimated molecular weight of PR on spermatozoa varies from 27 kDa to 85 kDa. At the molecular level, sequences encoding for the entire DNA and hormone binding domains of the conventional PR are detected in the mRNA derived from spermatozoa. No insertions, deletions or mutations are detected in this region. These results are suggestive of the fact that at least the C terminal region of the conventional PR is conserved in the sperm. It is hypothesized that post-translational modifications or peptide splicing of the conventional PR in spermatozoa may possibly lead to the variant of the steroid hormone receptor. Detailed characterization of the sperm PR will be important in understanding the alternate non-genomic mode of action of steroid hormone receptors.

Clinical experience with the use of Fluorescence in Situ Hybridization on uncultured cells for prenatal diagnosis.

The aim of the study was to prospectively evaluate the usefulness and limitations of Fluorescence In Situ Hybridization (FISH) on uncultured cells for prenatal diagnosis of numeric aneuploidies of chromosomes 13, 18, 21, X and Y. Hundred prospectively selected pregnant women that were at high risk of giving birth to an abnormal child were offered prenatal diagnosis by FISH after appropriate counseling. Fetal tissue was obtained by chorionic villus sampling (n=26), amniocentesis (n=62) and or fetal blood sampling (n=12) and processed for FISH using commercial probes. Six cases were excluded initially owing to maternal blood contamination or inadequate sample. FISH results were available in 98% of cases, in 2% of cases there was FISH failure. Of the remaining 92 cases, chromosome aneuploidy was detected in eleven cases. FISH was found extremely valuable in cases presenting with fetal abnormalities detected on ultrasonography and also for rapid screening of aneuploidies in cases of abnormal triple marker test. But as the diagnosis is limited to only a small number of chromosomes, appropriate evaluation of the cases with counseling regarding the limitations of FISH is mandatory before offering this test for prenatal diagnosis.