We found that MAGED2 mutations caused X-linked polyhydramnios with prematurity and a severe but transient form of antenatal Bartter's syndrome. MAGE-D2 is essential for fetal renal salt reabsorption, amniotic fluid homeostasis, and the maintenance of pregnancy. (Funded by the University of Groningen and others.).

The uterosacral ligaments are thought to contribute to pelvic support. The objective of this study was to compare the structural components of these ligaments in women with and without pelvic organ prolapse (POP). We characterized uterosacral ligaments of 25 postmenopausal women with POP and 16 controls histomorphologically and immunohistochemically by quantifying their content of collagen I, III, and smooth muscle using a computerized image analysis. In 84% the uterosacral ligaments were composed of more than 20% of smooth muscle cells. There was no difference in collagen I expression and smooth muscle cell amount between women with POP and those without. In contrast, the collagen III expression was significantly related to the presence of POP (p<0.001) rather than age or parity. Our findings suggest that the higher collagen III expression might be a typical characteristic of POP patients' connective tissue. The considerable amount of smooth muscle cells in uterosacral ligaments may provide pelvic support.

No abstract

Objective-To assess the possible role of proinflammatory CD28Ϫ T cells in abdominal aortic aneurysms (AAAs). Animal studies and human tissue studies suggest a role for interferon (IFN)-␥-producing T cells in the development and progression of AAAs. Methods and Results-Fluorescence-activated cells sorter analysis of peripheral blood samples and measurement of AAA size using sonography were performed in 101 AAA patients and 38 healthy controls. Key Words: aortic disease Ⅲ aneurysms Ⅲ leukocytes Ⅲ immune system Ⅲ human A bdominal aortic aneurysm (AAA) is a common disease with a prevalence of 3% of individuals aged 60 years and older and is a potentially lethal disorder causing Ϸ15 000 deaths annually in the United States. 1 Recent human tissue studies and animal models have led now to a paradigm shift in the pathogenetic concept of AAAs. Rather than a simple degenerative process, the majority of AAAs has proven to be a complex and dynamic remodeling process. In brief, studies of human AAA tissues have identified extensive inflammatory infiltrates in both the media and the adventitia, 2 leading to an increased expression of proinflammatory cytokines and C-reactive protein (CRP) in aneurysmal tissue. [3][4][5] The presence of vascular-associated lymphoid tissue (VALT) with lymphoid follicles and lymph node-like structures in the adventitia of AAAs suggests a role for immunocompetent and antigen presenting cells not only in atherosclerosis 6 but also in AAA disease. 2 The role for T cells has been further supported by immunogenetic findings with associations between AAA and human leukocyte antigen class II molecules. 7 Infiltration of the adventitia usually occurs together with medial thinning. This inflammatory process triggers the production of metalloproteinases and apoptosis of medial smooth muscle cells thus explaining the disruption of the orderly lamellar structure in aortic aneurysms.Recently, a subgroup of proinflammatory T cells has been identified in patients with immune-mediated disorders including rheumatoid arthritis, 8 -9 ankylosing spondylitis, 10 multiple sclerosis, 11 Wegener granulomatosis, 12 and unstable angina, 13 which lack the costimulatory molecule CD28 on their surface and are considered as markers for chronic inflammation and early aging. 14 Under these circumstances the CD28 Ϫ T cells are part of the CD4 ϩ as well as the CD8 ϩ T cell compartment, persist over years, and include most of the oligoclonally expanded T cells. Phenotypically, CD4 ϩ CD28 Ϫ T cells from rheumatoid arthritis and ankylosing spondylitis patients and CD8 ϩ CD28 Ϫ T cells from aged persons, rheumatoid arthritis, and melanoma patients share the expression of various natural killer (NK) cell receptors and lack the expression of the lymphocyte marker CD7. 9,15-16 Functionally these T cells are capable to release large amounts of interferon (IFN)-␥, perforin, and granzyme B, providing them with the possibility to lyse target cells. 17 In the pathogenesis of coronary arteriosclerosis, the critical role of IFN-␥ was alread...

Due to lack of familiarity with PH and its heterogeneous clinical expression, diagnosis is often delayed until advanced disease is present, a condition, requiring intensive hemodialysis and timely transplantation. Achieving the most beneficial outcome largely depends on the knowledge of the clinical spectrum, early diagnosis, and initiation of treatment before renal failure ensues. A number of preconditions required for substantial improvement in the care of orphan disease like PH have now been achieved or soon will come within reach, so new treatment options can be expected in the near future.