QM/MM study of l-lactate oxidation by flavocytochrome b2.

In this work, we have performed molecular dynamics simulations using a hybrid Quantum Mechanics/Molecular Mechanics (QM/MM) scheme to study the mechanism of l-lactate oxidation by flavocytochrome b2 (Fcb2). Our results obtained at the QM(AM1)/MM level have been improved by single-point corrections using density functional theory (DFT) methods. Free energy surfaces have been calculated in the framework of the hydride transfer hypothesis. This mechanism involves the transfer of the lactate hydroxyl proton to H373 while the substrate αH atom is transferred as a hydride to the flavin mononucleotide (FMN) prosthetic group anchored in the active site. Four different systems have been modeled: wild-type enzyme considering R289 in a distal or a proximal conformation observed in crystal structures and the D282N and Y254L variants (with R289 in a distal position). Simulation results highlight the influence of the environment on the catalytic mechanism by describing a step-wise process in the WT enzyme with R289 in a distal position and a concerted mechanism for the other systems. In the step-wise mechanism, the hydride transfer to flavin can occur only after a proton transfer from substrate to H373. Modifications of the electrostatic field around l-lactate or H373 disfavor the highly charged complex resulting from this proton transfer. Simulations of the Y254L variant also reveal some effect of steric changes.

[Cellular dynamics of pathogenesis induced by bovine leukemia virus]. / Dynamique cellulaire de la pathogenèse induite par le virus de la leucémie bovine.

Bovine leukemia virus (BLV) is the etiological agent of a lymphoproliferative disease in cattle. This retrovirus can also be experimentally transmitted to sheep, in which the pathology is more rapid and more frequent. This review summarizes the current knowledge on the BLV virus and more particularly on its role in lymphocyte homeostasis and induction of pathogenesis. This system has been informative for understanding pathogenesis induced by human T-lymphotropic virus type I (HTLV-1).

[Placental teratoma: differential diagnosis with fetal acardia]. / Tératome placentaire: diagnostic différentiel avec le foetus acardiaque.

The acardiac fetus is a rare congenital malformation observed only in monozygotic twin pregnancies (1/35.000 pregnancies). Placental teratoma is extremely rare (less than 20 cases have been reported in the literature since 1925). A case of placental teratoma, misdiagnosed as fetus acardius amorphus, is presented with ultra-sound follow-up, delivery and outcome of the normal fetus. Pathological findings, histogenesis, differential diagnosis with the acardiac fetus and finally review of the literature will be discussed.

Peritoneal endometriosis and "endometriotic" nodules of the rectovaginal septum are two different entities.

OBJECTIVE: To compare histologically and stereologically the endometriotic nodule of the rectovaginal septum to peritoneal endometriosis. DESIGN: Morphometric investigation, cytokeratin and vimentin content, and steroid receptor evaluation were performed on endometriotic tissue from the peritoneum (n = 52) and rectovaginal nodules (n = 68). SETTING: An academic teaching hospital. PATIENTS: Biopsies were taken from 120 patients undergoing a laparoscopy for infertility and/ or pelvic pain (52 from typical black peritoneal endometriotic implants and 68 from endometriotic nodule of the rectovaginal septum). None of the patients were treated. RESULTS: Mitotic activity was found to be significantly different in peritoneal and rectovaginal endometriosis. The evaluation suggested that the stroma is not mandatory for the invasion of glandular epithelium in the rectovaginal nodule, which is, like a adenomyoma, a circumscribed nodular aggregate of smooth muscle and glandular elements. Cytokeratin and vimentin content as well as the estrogen receptor (ER) and P receptor (PR) content were significantly lower in both types of lesion when compared with eutopic endometrium. But vimentin immunoreactivity in epithelium, as well as the ER and PR content, were significantly lower in nodules when compared with black peritoneal lesions. CONCLUSION: It is suggested that the rectovaginal endometriotic nodule is a different disease from peritoneal endometriosis and must be called rectovaginal adenomyosis or rectovaginal adenomyoma. Its histopathogenesis probably is not related to the implantation of regurgitated endometrial cells but to the metaplasia of Müllerian rests.

Large ovarian endometriomas.

The management of large endometriomas was described in a series of 814 patients. Combined therapy using gonadotrophin-releasing hormone agonist (GnRHa) and carbon dioxide laser laparoscopy was proposed. Drainage and GnRHa for 12 weeks provoked a reduction of the endometrioma size up to 50% of the initial value. After vaporization of the internal wall, a cumulative pregnancy of 51% after 1 year was achieved. A recurrence rate of 8% was observed for a follow-up of 2-11 years. Histological data demonstrated that the epithelium covering the ovary which is the mesothelium can invaginate in the ovarian cortex. Some of the invaginations were seen to be continuous with endometrial tissue, strongly suggesting the metaplasia theory in the pathogenesis of ovarian endometrioma.