Breton F. Barrier

Human decidual stromal cells suppress cytokine secretion by allogenic CD4+ T cells via PD-1 ligand interactions

BACKGROUND Although previous reports suggest an antigen-presenting function for decidual stromal cells (DSCs), the relevance of cell-to-cell communication between DSCs and T cells at the human feto-maternal interface has not been fully elucidated. Therefore, we investigated the presence and function of human DSC-expressed B7-H1 and B7-DC co-stimulatory ligands. B7-H1 and B7-DC on peripheral antigen-presenting cells (APC) typically inhibit T cell activation after binding to their corresponding receptor, programmed death-1 (PD-1). METHODS DSCs were isolated from human term decidua. The expression of B7-H1/B7-DC and HLA-DR and their alteration following IFN-gamma and/or TNF-alpha stimulation were assessed. DSCs with or without IFN-gamma pretreatment were co-cultured with allogenic CD4(+) T cells. The effect of PD-1:B7-H1/B7-DC and T cell receptor (TCR):HLA-DR interactions on T cell cytokine production was evaluated by adding blocking antibodies. RESULTS DSCs constitutively expressed B7-H1 and B7-DC, as well as small amounts of HLA-DR. Exogenous IFN-gamma and TNF-alpha up-regulated the B7-H1/-DC expression on DSCs, whereas HLA-DR expression was increased only by IFN-gamma. IFN-gamma pretreatment of DSCs stimulated T cell cytokine production through HLA-DR up-regulation. B7-H1 blockade on DSCs strongly enhanced T cell cytokine production (IFN-gamma, TNF-alpha and IL-2), whereas B7-DC blockade had similar but more modest effects. Blockade of both B7-H1 and B7-DC resulted in additive effects. CONCLUSIONS Our findings support the categorization of human DSCs as non-professional APCs and suggest that PD-1 ligands on DSCs, together with major histocompatibility complex class II, may play a crucial role in the regulation of decidual CD4(+) T cell cytokine production. This helps to maintain a balanced cytokine milieu at the feto-maternal interface.

Culdoscopy: A Foundation for Natural Orifice Surgery—Past, Present, and Future

C I w v p w a c c w or more than 100 years, transvaginal endoscopy, later nown as culdoscopy, has been performed to visualize the bdominal and pelvic cavity. At one time, culdoscopy lourished as both a diagnostic and therapeutic procedure. he technique came under criticism for its restricted visulization and limited operative capabilities balanced against are but concerning complications. With rising advances in igid endoscopic technology, laparoscopy rapidly replaced uldoscopy, pushing it to the edge of obscurity for decades. ow recent interest in natural orifice transluminal endocopic surgery has resulted in a reconsideration of culdosopy as a means of facilitating this promising surgical pproach.

Expression of soluble adhesion molecules in sera of women with stage III and IV endometriosis.

Objective: To determine the effect os stage III and IV endometriosis on serum concentration of soluble intracellular adhesion molecule-1 (ICAM-1), vascular cellular adhesion molecule-1 (VCAM-1), and E-selectin. Methods: Sera from women with laparoscopically proven stage III and IV endometriosis were analyzed for the presence of soluble ICAM-1, VCAM-1, and E-selectin using enzyne-linked immunosorbent assays. Concentrations of these molecules were compared with those of laparoscopically proven disease-free controls. Results: When compared with controls, women with stage III and IV endometriosis had higher serum concentration of soluble E-selectin. Conclusion: Significant aberrations in levels of circulating adhesion molecules were found in women with stage III and IV endometriosis. These findings might shed light on the pathogenesis of endometriosis and be useful in the development of biochemical markers for disease stage.

The regulation of T-cell cytokine production by ICOS–B7H2 interactions at the human fetomaternal interface

Although T cells are the most common decidual lymphocyte subset in late pregnancy, little is known about the mechanisms controlling their function. Costimulatory signaling, mediated by inducible costimulator (ICOS)–B7H2 interactions, is a known potent regulator of T‐cell activation. We aimed to determine its role in fetomaternal immunity. T cells from matched peripheral blood and term decidua were assessed for ICOS, CD4/CD8, CD45RA/CD45RO and Foxp3 expression and for alterations in cytokine production upon ICOS–B7H2 ligation. We also assessed ICOS–B7H2 communication between T cells and a trophoblast cell line (JEG3). Strong ICOS expression was observed on CD4 and CD8 decidual (d)T cells, but not peripheral (p)T cells. Among dT cells, ICOS expression was higher on the predominant CD45RO+ cell population compared with CD45RA+ cells. Strong ICOS expression was also seen on CD4+Foxp3+ regulatory T cells in the decidua. ICOS ligation enhanced T‐cell secretion of interferon‐gamma (IFN‐γ) and interleukin‐10 (IL‐10), but not IL‐2. The impact of ICOS stimulation was more remarkable in dT cells when compared with pT cells. T cells co‐cultured with JEG3 cells promoted T‐cell production of IFN‐γ and IL‐10, an effect blocked by antibody‐specific masking of major histocompatibility class I or B7H2. These findings suggest that T‐cell cytokine modulation by ICOS–B7H2 interactions is important in the delicate immune balance at the fetomaternal interface.

Outcomes of a comprehensive nonsurgical approach to pelvic floor rehabilitation for urinary symptoms, defecatory dysfunction, and pelvic pain.

Objective The authors’ intent was to determine the clinical efficacy of comprehensive pelvic floor rehabilitation among women with symptoms of pelvic floor dysfunction (PFD). Methods We performed a retrospective analysis of women referred to an academic female pelvic medicine and reconstructive surgery practice for PFD. Data were gathered from the records of 778 women referred for pelvic floor therapy for urinary, bowel, pelvic pain, and sexual symptoms over the course of 4 years. Results Patients who completed at least 5 therapy sessions reported a mean symptom improvement of 80% in each of the 3 main categories analyzed, namely, urinary incontinence, defecatory dysfunction, and pelvic pain. Conclusions Comprehensive, nonoperative management of PFD including pelvic floor muscle training, biofeedback, electrogalvanic stimulation, constipation management, behavioral modification, incontinence devices, and pharmacotherapy including vaginal estrogen is effective in the treatment of women with PFD.

The Fetal Allograft Revisited: Does the Study of an Ancient Invertebrate Species Shed Light on the Role of Natural Killer Cells at the Maternal-Fetal Interface?

Human pregnancy poses a fundamental immunological problem because the placenta and fetus are genetically different from the host mother. Classical transplantation theory has not provided a plausible solution to this problem. Study of naturally occurring allogeneic chimeras in the colonial marine invertebrate, Botryllus schlosseri, has yielded fresh insight into the primitive development of allorecognition, especially regarding the role of natural killer (NK) cells. Uterine NK cells have a unique phenotype that appears to parallel aspects of the NK-like cells in the allorecognition system of B. schlosseri. Most notably, both cell types recognize and reject “missing self” and both are involved in the generation of a common vascular system between two individuals. Chimeric combination in B. schlosseri results in vascular fusion between two individual colonies; uterine NK cells appear essential to the establishment of adequate maternal-fetal circulation. Since human uterine NK cells appear to de-emphasize primary immunological function, it is proposed that they may share the same evolutionary roots as the B. schlosseri allorecognition system rather than a primary origin in immunity.

Characterization of spontaneous mammary gland carcinomas in female baboons

Spontaneous mammary gland carcinomas occurred in five baboons during a 13‐year period at Southwest Foundation for Biomedical Research. The affected baboons ranged in age from 21 to 33 years. Menopause in the baboon occurs at approximately 26 years of age. All five animals had typical invasive ductal carcinoma. Morphologically, the tumors were characterized by neoplastic cells arranged from pseudopapillary and cribiform to more poorly differentiated solid cellular growth patterns. Additional features included lack of tubule formation (4/5), marked nuclear pleomorphism (5/5), a high mitotic rate (4/5) and tumor necrosis (4/5). Applying a grading system used for breast cancer in women, four tumors were graded as poorly differentiated carcinomas and one was graded as moderately differentiated. Co‐existant ductal carcinoma in situ (DCIS) was observed in three of the mammary tumors. Metastases to the regional lymph nodes were confirmed in two animals, both with histological evidence of lymphovascular invasion in the primary tumor. Distant metastases were observed in only one animal. Immunohistochemical staining for human therapeutic markers revealed 2/5 tumors strongly positive for estrogen receptor, 1/5 strongly positive for progesterone receptor and 4/4 negative for HER2 expression. Although the incidence appears to be low, these five cases of mammary carcinoma in female baboons suggest that when present baboon mammary carcinoma is usually of ductal origin and behaves similar to a human breast carcinoma.

A Simple Device Prevents Hysterotomy Extensions during Cesarean Delivery for Failed Second Stage of Labor

Background/ Aims: During arrest of descent, maternal tissues conform to the fetal head, resulting in a suction-cup like effect during cesarean delivery. We hypothesize that breaking this suction might ease delivery. A novel device was designed for this purpose and tested in this series of 23 patients. Methods: University-based retrospective cohort feasibility study. Term pregnant women with second-stage labor arrest (n = 23) provided written consent for use of the experimental device, inserted vaginally prior to cesarean delivery. Delivering obstetricians rated device effectiveness. Following case collection, the presence of hysterotomy extensions in study patients was retrospectively compared with controls (n = 49) from the same study period. Results: On a 7-point Likert scale, consultant obstetricians rated overall device effectiveness as 6.0, and resident obstetricians rated it 6.3, consistent with a moderate improvement in ease of delivery. The device performed optimally at mid-pelvic stations (0 to +1), with no hysterotomy extensions (n = 0/17), which was significantly better than controls (n = 14/41, 34%, p < 0.01). Conclusion: A simple device prevented hysterotomy extension during second-stage cesarean delivery at 0 and +1 station. Obstetricians perceived that the device afforded a moderate improvement in delivery compared with previous deliveries in which the device was not used.

External cephalic version of the term breech baboon (Papio sp.) fetus

Background  Breech presentation in baboons may be associated with head entrapment and stillbirth during vaginal delivery. For this reason, pregnant dams at our institution typically undergo cesarean delivery for known breech presentation, leading to problems with maternal–infant bonding and increased nursery utilization.

Recumbent thunderclap headache in the postpartum period.

BACKGROUND: Reversible cerebral vasoconstriction syndrome is characterized by thunderclap headache and reversible cerebral vasoconstriction, with or without other neurologic signs and symptoms. CASE: A 33-year-old woman presented 13 days postpartum with a 4-day history of multiple thunderclap headaches while in the recumbent position, prompting her to attempt to sleep while standing or sitting. Cerebral angiogram demonstrated segmental cerebral artery vasoconstriction. Spinal fluid sampling excluded vasculitis, thereby confirming the diagnosis of reversible cerebral vasoconstriction syndrome. Treatment with a calcium channel antagonist rapidly attenuated her symptoms, and cerebral angiogram was normal at 3 months. CONCLUSION: Thunderclap headache during the postpartum period precipitated by valsalva or recumbent positioning may indicate reversible cerebral vasoconstriction syndrome, which, if untreated, places a patient at risk for serious neurologic injury.