Sphingosine-1-phosphate receptor-2 (S1P2)-deficient mice develop diffuse large B cell lymphoma. However, the role of S1P2 in normal germinal center (GC) physiology is unknown. Here we show that S1P2-deficient GC B cells outgrow their wild-type counterparts in chronically-established GCs. We find that S1P2-, G12–G13- and p115RhoGEF-mediated antagonism of Akt regulates cell viability and is required for growth control in chronically proliferating GCs. We also find that S1P2 inhibits GC B cell responses to follicular chemoattractants and helps confine cells to the GC. Moreover, S1P2 overexpression promotes centering of activated B cells within the follicle. We suggest that by inhibiting Akt activation and migration, S1P2 helps restrict GC B cell survival and localization to an S1P-low niche at the follicle center.

Laidlaw et al. show that Ephrin-B1 is a specific marker of mature germinal center (GC) B cells. Use of Ephrin-B1 allows for the identification of phenotypically distinct GC B cell subsets, including a population that may represent memory precursor B cells.

Chemokine receptor CXCR4 promotes B cell localization to CXCL12+ perilymphatic zones and egress from Peyer’s patches.

Small modifications in hospital routines, especially in the timing of vital signs and routine medication administration, can significantly reduce sedative use in unselected hospital patients.

IMPORTANCE Understanding of the associations among cutaneous findings, systemic abnormalities, and fulfillment of the diagnostic criteria in women suspected of having polycystic ovary syndrome (PCOS) is incomplete. OBJECTIVE To identify cutaneous and systemic features of PCOS that help distinguish women who do and do not meet the diagnostic criteria. DESIGN, SETTING, AND PARTICIPANTS Retrospective cross-sectional study of a racially diverse referred sample of women seen at the University of California, San Francisco, Polycystic Ovary Syndrome Multidisciplinary Clinic over a 6-year period between May 18, 2006, and October 25, 2012. Participants were 401 women referred for suspected PCOS. In total, 68.8% (276 of 401) met the Rotterdam PCOS diagnostic criteria, while 12.0% (48 of 401) did not. Overall, 11.5% (46 of 401) had insufficient data to render a diagnosis, 1.7% (7 of 401) were excluded from the study, and 6.0% (24 of 401) refused to participate in the study. EXPOSURE Comprehensive skin examination and transvaginal ultrasonography. All patients were tested for levels of total testosterone, free testosterone, dehydroepiandrosterone (DHEAS), androstenedione, luteinizing hormone, and follicle-stimulating hormone. Levels of serum cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides were obtained, in addition to 0-hour and 2-hour oral glucose tolerance test (OGTT) results, with measurement of glucose and insulin levels.MAIN OUTCOMES AND MEASURES Findings from comprehensive skin examination, laboratory testing, and transvaginal ultrasonography. RESULTSIn total, 401 women with suspected PCOS were included in the study. The median patient age was 28 years. Compared with women who did not meet the diagnostic criteria for PCOS, women who met the criteria had higher rates of hirsutism (53.3% [144 of 270] vs 31.2% [15 of 48], P = .005) (with higher mean modified Ferriman-Gallwey scores of 8.6 vs 5.6, P = .001), acne (61.2% [164 of 268] vs 40.4% [19 of 47], P = .004), and acanthosis nigricans (AN) (36.9% [89 of 241] vs 20.0% [9 of 45], P = .03). Cutaneous distributions also varied. Women who met the PCOS criteria demonstrated more severe truncal hirsutism and higher rates of axillary AN. Women who met the PCOS criteria had elevated total testosterone levels (40.7% [105 of 258] vs 4.3% [2 of 47], P < .001). Among women with PCOS, the presence of hirsutism (43.9% [54 of 123] vs 30.9% [34 of 110], P = .04) or AN (53.3% [40 of 75] vs 27.0% [40 of 148], P < .001) was associated with higher rates of elevated free testosterone levels as well as several metabolic abnormalities, including insulin resistance, dyslipidemia, and increased body mass index. Although the prevalence of acne was increased among women with PCOS, there were minimal differences in acne types and distribution between the women meeting vs not meeting the PCOS criteria.CONCLUSIONS AND RELEVANCE Hirsutism and AN are the most reliable cutaneous markers of PCOS and require a comprehensive skin e...

No abstract

Polycystic ovary syndrome (PCOS) is an endocrine syndrome with variable phenotypic expression and important systemic associations and sequelae, including obesity, insulin resistance, infertility, risk of endometrial cancer, and possible risk of cardiovascular events. PCOS is recognized as a condition influenced by genetic and environmental factors and distinct manifestations in all stages of life, including the prenatal period, childhood, adolescence, and adulthood. Identification of this disorder in childhood and adolescence has received growing attention, in part because of emerging evidence of the benefit of early intervention, but the diagnosis and management of PCOS in children and adolescents can be challenging. Diagnostic and therapeutic considerations of PCOS in children are reviewed to enhance identification and evaluation of patients suspected of having this disorder. When a diagnosis of PCOS is suspected in a child but cannot be confirmed, a provisional diagnosis is strongly recommended so as to prompt ongoing monitoring with an emphasis on important early interventions such as obesity reduction.

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