Indoleamine 2,3-dioxygenase is expressed in the endometrium of cycling mice throughout the oestrous cycle

Indoleamine 2,3-dioxygenase (IDO), an enzyme responsible for tryptophan catabolism, is thought to be required to prevent the rejection of the allogenic fetus by maternal T cells and to protect against intra- and extra-cellular pathogens. Consequently, we studied the expression of IDO in the endometrium of female Balb/c mice during the oestrous cycle. At each phase, the endometrium was peeled away and the relative expression of IDO mRNA was detected by semi-quantitative RT-PCR. The presence of IDO protein was confirmed in each phase by Western blotting and immunohistochemistry. Our results showed that IDO is expressed in the endometrium of cycling mice during all the phases of oestrous cycle. The expression of IDO was highest at the oestrus and lowest at the dioestrus. By means of Western blotting and immunohistochemistry, we obtained evidence that IDO protein is synthesised in the endometrium of cycling mice throughout the oestrous cycle. In accordance with RT-PCR results, IDO protein was predominant at the oestrus phase. IDO protein was mainly localised in the glandular and luminal epithelial cells. Our results support the concept of IDO providing a mechanism of innate immunity to protect from ascending infections of the female reproductive tract. In addition, considering the fact that mating only occurs during the oestrus phase, the high expression of IDO in this phase is likely to be a mechanism that induces immunological tolerance of the fetus.     

Clinical and histologic spectrum of nonalcoholic fatty liver disease associated with normal ALT values

A retrospective study was performed to (1) characterize the clinical and histologic features of those with nonalcoholic fatty liver disease (NAFLD) and normal alanine aminotransferase (ALT) values, (2) compare the spectrum of NAFLD associated with normal versus elevated ALT levels, and (3) determine whether there were differences in the clinical or histologic spectrum of NAFLD between those with a low normal versus high normal ALT value. A total of 51 subjects with NAFLD and normal ALT were identified and compared with 50 consecutive subjects with NAFLD and elevated ALT. The major indications for liver biopsy in those with normal ALT were unexplained hepatomegaly (n = 21) and evaluation as a potential donor for living donor liver transplantation (n = 16). The 2 groups were comparable with respect to age, gender distribution, and ethnicity. Approximately 80% of cases in both groups had at least 1 feature of the metabolic syndrome, the major risk factor for NAFLD. The 2 groups were also comparable with respect to the grade of the individual histologic parameters of NAFLD. A total of 12 subjects with normal ALT levels had bridging fibrosis, whereas 6 had cirrhosis. Diabetes was the only factor independently associated with an increased risk of advanced fibrosis (bridging fibrosis or cirrhosis) by multivariate analysis (relative risk: 2.3, P <.01). The mean steatosis (1.6 vs. 2.16, P <.04) and perisinusoidal fibrosis scores (0.35 vs. 0.9, P <.049) were lower in those with low normal (<30 IU/L) ALT versus high normal ALT. However, the prevalence of advanced fibrosis was similar (5 of 15 vs. 13 of 36, respectively). In conclusion, (1) the entire histologic spectrum of NAFLD can be seen in individuals with normal ALT values, (2) the histologic spectrum in these individuals is not significantly different from those with elevated ALT levels, and (3) a low normal ALT value does not guarantee freedom from underlying steatohepatitis with advanced fibrosis.     

The role of endoscopic endonasal surgery in the management of prolactinomas based on their invasiveness into the cavernous sinus

Pituitary - To review our institutional experience with the&nbsp;surgical management of prolactinomas through the endoscopic endonasal approach with specific focus on cavernous sinus invasion....     

Pituitary Society Delphi Survey: An international perspective on endocrine management of patients undergoing transsphenoidal surgery for pituitary adenomas

Pituitary - In adults and children, transsphenoidal surgery (TSS) represents the cornerstone of management for most large or functioning sellar lesions with the exception of prolactinomas....     

Evaluation of thyroglobulin expression in murine reproductive organs during pregnancy

Citation Moravej A, Jeddi‐Tehrani M, Salek‐Moghaddam AR, Dokouhaki P, Ghods R, Rabbani H, Kazemi‐Sefat GE, Shahbazi M, Zarnani AH. Evaluation of thyroglobulin expression in murine reproductive organs during pregnancy. Am J Reprod Immunol 2010; 64: 97–103 Problem In pregnant women with antithyroglobulin antibody, prevalence of abortion is 2–4 fold higher compared to normal controls. Direct effect of such harmful autoantibodies on female reproductive organs may serve a role in pregnancy loss. Method of study Expression of thyroglobulin in decidua, placenta, and ovary of pregnant Balb/c mice ((Balb/c×Balb/c and Balb/c×C57BL/6) during early, middle, and late stages of pregnancy was evaluated. Expression of thyroglobulin was investigated in these tissues by semi‐quantitative RT‐PCR. In addition, polyclonal antithyroglobulin antibody was produced, and expression of thyroglobulin protein in aforesaid tissues was evaluated by immunohistochemistry and dot‐blot analysis. Results The results showed that thyroglobulin message is not expressed in placenta, decidua, or ovary in any stages of pregnancy. The same results were obtained at the protein level. Conclusion It is likely that antithyroglobulin antibodies have no direct detrimental effect on such organs in patients with thyroid autoimmunity suffering from recurrent abortion.     

Tissue microarrays in the study of non-neoplastic disease of the nervous system

Tissue microarrays (TMAs), also known as "tissue chips," are a recently developed method that allows small cores or discs of tissue from dozens or hundreds of (usually paraffin-embedded) specimens to be re-embedded in a tissue block, which can then be further sectioned. The tissue cores can subsequently be studied using any combination of techniques, including immunohistochemistry, in situ hybridization (ISH). fluorescence ISH, and in situ polymerase chain reaction (PCR). To date, the technique has found greatest use in the analysis of neoplasms, including gliomas. We describe, and provide examples of, how TMAs might be utilized in investigation of autopsy (or biopsy) tissues from individuals with non-neoplastic disease, especially to address questions that require systematic review of multiple (nearly) identical brain regions across dozens or hundreds of cases. Specific questions related to patterns of protein expression (e.g. tau, Abeta, alpha-synuclein) in multiple regions of large numbers of brain specimens (from patients with neurodegenerative diseases) can be efficiently examined using TMA technology. One possible use of TMAs in the area of infectious disease might be to examine patterns of HIV-related brain injury or AIDS-related opportunistic CNS infections in the epochs before and after highly active antiretroviral therapy came into widespread use.     

Neurotrophins promote revascularization by local recruitment of TrkB+ endothelial cells and systemic mobilization of hematopoietic progenitors

The neurotrophin brain-derived neurotrophic factor (BDNF) is required for the maintenance of cardiac vessel wall stability during embryonic development through direct angiogenic actions on endothelial cells expressing the tropomysin receptor kinase B (TrkB). However, the role of BDNF and a related neurotrophin ligand, neurotrophin-4 (NT-4), in the regulation of revascularization of the adult tissues is unknown. To study the potential angiogenic capacity of BDNF in mediating the neovascularization of ischemic and non-ischemic adult mouse tissues, we utilized a hindlimb ischemia and a subcutaneous Matrigel model. Recruitment of endothelial cells and promotion of channel formation within the Matrigel plug by BDNF and NT-4 was comparable to that induced by VEGF-A. The introduction of BDNF into non-ischemic ears or ischemic limbs induced neoangiogenesis, with a 2-fold increase in the capillary density. Remarkably, treatment with BDNF progressively increased blood flow in the ischemic limb over 21 days, similar to treatment with VEGF-A. The mechanism by which BDNF enhances capillary formation is mediated in part through local activation of the TrkB receptor and also by recruitment of Sca-1+CD11b+ pro-angiogenic hematopoietic cells. BDNF induces a potent direct chemokinetic action on subsets of marrow-derived Sca-1+ hematopoietic cells co-expressing TrkB. These studies suggest that local regional delivery of BDNF may provide a novel mechanism for inducing neoangiogenesis through both direct actions on local TrkB-expressing endothelial cells in skeletal muscle and recruitment of specific subsets of TrkB+ bone marrow-derived hematopoietic cells to provide peri-endothelial support for the newly formed vessels.     

Human Vδ1-T cells regulate immune responses by targeting autologous immature dendritic cells

Recent studies suggest that tissue resident Vδ1-T cells may downregulate immune responses in human beings. However, the function of peripheral blood Vδ1-T cells and their mechanisms of action remain largely unknown because of their limited numbers and the difficulties encountered in expanding these cells. In this study, we provide direct evidence demonstrating that peripheral human Vδ1-T cells can abrogate adaptive immune responses by direct killing of autologous dendritic cells through a perforin-mediated pathway. These findings advance our basic understanding of this unique T-cell subset.     

Brain-derived neurotrophic factor: a newly described mediator of angiogenesis

Recent studies indicate that, in addition to its neuropoietic actions, brain derived neurotrophic factor (BDNF) promotes endothelial cell survival and induces neoangiogenesis in ischemic tissues. Unlike many vascular growth factors that act on many vascular beds, BDNF activity is relatively restricted to central arteries, vessels of cardiac and skeletal muscle, and skin. Studies of newly described biologic mediators that act on large-vessel and microvascular beds in these organs will help us to better understand organ-specific vascular development, as well as to develop novel therapeutic strategies to improve the condition of patients with cardiac and peripheral vascular disease. In this review, we summarize dual proangiogenic actions of BDNF, which, through local activation of TrkB receptor, expressed on a subpopulation of endothelial cells and, in addition, by recruitment of bone marrow-derived cells, contribute to neoangiogenesis.     

Marrow fat and preadipocyte factor-1 levels decrease with recovery in women with anorexia nervosa

Women with anorexia nervosa (AN) have elevated marrow fat mass despite low visceral and subcutaneous fat depots, which is inversely associated with bone mineral density (BMD). Whether marrow fat mass remains persistently elevated or decreases with recovery from AN is currently unknown. In this study, we investigated changes in marrow fat in women who have recovered from AN (AN-R). We also studied the relationship between preadipocyte factor (Pref)-1—a member of the EGF-like family of proteins and regulator of adipocyte and osteoblast differentiation—and fat depots and BMD in AN-R compared with women with AN and healthy controls (HC). We studied 29 women: 14 with active or recovered AN (30.7 + 2.2 years [mean ± SEM]) and 15 normal-weight controls (27.8 ± 1.2 years). We measured marrow adipose tissue (MAT) of the L4 vertebra and femur by ¹H-magnetic resonance spectroscopy; BMD of the spine, hip, and total body by DXA; and serum Pref-1 and leptin levels. We found that MAT of the L4 vertebra was significantly lower in AN-R compared with AN (p = 0.03) and was comparable to levels in HC. Pref-1 levels were also significantly lower in AN-R compared with AN (p = 0.02) and comparable to levels in healthy controls. Although Pref-1 was positively associated with MAT of the L4 vertebra in AN (R = 0.94; p = 0.002), we found that it was inversely associated with MAT of the L4 vertebra in HC (R = −0.71; p = 0.004). Therefore, we have shown that MAT and Pref-1 levels decrease with recovery from AN. Our data suggest that Pref-1 may have differential effects in states of nutritional deprivation compared with nutritional sufficiency. © 2012 American Society for Bone and Mineral Research.