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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report 2 cases of surgically resected vulval masses in women aged 27 and 40 years. One patient was wheelchair bound and the other was obese, both presented with bilateral vulvar swelling. One specimen measured 45 cm in maximum dimension and the other 5 cm and were described as grossly edematous or gelatinous. Histologically, in both cases, there was edema of the skin overlying the lesion. The lesion itself consisted of markedly edematous connective tissue with widely separated bland spindle-shaped cells and numerous dilated vascular channels, sometimes surrounded by cuffs of lymphocytes and plasma cells. In the larger of the 2 specimens, underlying edematous adipose tissue was present. To some extent, the appearances, especially the morphological features, mimicked aggressive angiomyxoma because of the presence of a mass, the lack of circumscription, the hypocellular, edematous appearance, and the presence of numerous vascular channels. However, a combination of clinical and pathological features, including bilateralism, lack of a true myxoid stroma, the presence of perivascular cuffs of lymphoid cells, and lack of staining with estrogen receptor, is against aggressive angiomyxoma. The appearances were interpreted as those of massive edema. In one case, there was recurrence of the mass after surgery. There has been a single previous report of a similar vulvar case in a quadriplegic female patient and of similar cases involving the upper and lower extremities of obese patients. Clinicians and pathologists should be aware of the existence of this lesion, which is likely due to lymphatic obstruction and lymphedema secondary to immobilization and obesity.
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PMID:Massive vulval edema secondary to obesity and immobilization: a potential mimic of aggressive angiomyxoma. 1858 Mar 26

The prevalence of overweight (body mass index, BMI, between 25 and 30 kg/m2) and obesity (BMI of 30 kg/m2 or higher) is increasing rapidly worldwide, especially in developing countries and countries undergoing economic transition to a market economy. One consequence of obesity is an increased risk of developing type II diabetes. Overall, there is considerable evidence that overweight and obesity are associated with risk for some of the most common cancers. There is convincing evidence of a positive association between overweight/obesity and risk for adenocarcinoma of the oesophagus and the gastric cardia, colorectal cancer, postmenopausal breast cancer, endometrial cancer and kidney cancer (renal-cell). Premenopausal breast cancer seems to be inversely related to obesity. For all other cancer sites the evidence of an association between overweight/obesity and cancer is inadequate, although there are studies suggesting an increased risk of cancers of the liver, gallbladder, pancreas, thyroid gland and in lymphoid and haematopoietic tissue. Far less is known about the association between diabetes mellitus type I (also called insulin dependent diabetes mellitus or juvenile diabetes), type II diabetes (called non-insulin dependent diabetes mellitus or adult onset diabetes mellitus) and cancer risk. The most common type of diabetes mellitus, type II, seems to be associated with liver and pancreas cancer and probably with colorectal cancer. Some studies suggest an association with endometrial and postmenopausal breast cancer. Studies reporting on the association between type I diabetes mellitus, which is relatively rare in most populations and cancer risk are scanty, but suggest a possible association with endometrial cancer. Overweight and obesity, as well as type II diabetes mellitus are largely preventable through changes in lifestyle. The fundamental causes of the obesity epidemic-and consequently the diabetes type II epidemic-are societal, resulting from an environment that promotes sedentary lifestyles and over-consumption of energy. The health consequences and economic costs of the overweight, obesity and type II diabetes epidemics are enormous. Avoiding overweight and obesity, as well as preventing type II diabetes mellitus, is an important purpose to prevent cancer and other diseases. Prevention of obesity and type II diabetes should begin early in life and be based on the life-long health eating and physical activity patterns. Substantial public investments in preventing overweight, obesity and type II diabetes mellitus are both appropriate and necessary in order to have a major impact on their adverse health effects including cancer.
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PMID:Obesity and diabetes epidemics: cancer repercussions. 1863 86

Milk is a complex physiological liquid that simultaneously provides nutrients and bioactive components that facilitate the successful postnatal adaptation of the newborn infant by stimulating cellular growth and digestive maturation, the establishment of symbiotic microflora, and the development of gut-associated lymphoid tissues. The number, the potency, and the importance of bioactive compounds in milk and especially in fermented milk products are probably greater than previously thought. They include certain vitamins, specific proteins, bioactive peptides, oligosaccharides, organic (including fatty) acids. Some of them are normal milk components, others emerge during digestive or fermentation processes. Fermented dairy products and probiotic bacteria decrease the absorption of cholesterol. Whey proteins, medium-chain fatty acids and in particular calcium and other minerals may contribute to the beneficial effect of dairy food on body fat and body mass. There has been growing evidence of the role that dairy proteins play in the regulation of satiety, food intake and obesity-related metabolic disorders. Milk proteins, peptides, probiotic lactic acid bacteria, calcium and other minerals can significantly reduce blood pressure. Milk fat contains a number of components having functional properties. Sphingolipids and their active metabolites may exert antimicrobial effects either directly or upon digestion.
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PMID:Beneficial health effects of milk and fermented dairy products--review. 1908 72

With the emerging obesity pandemic, identifying those who appear to be protected from adverse consequences such as type 2 diabetes and certain malignancies will become important. We propose that the circulating immune system plays a role in the development of these comorbidities. Clinical data and blood samples were collected from 52 patients with severe obesity attending a hospital weight-management clinic and 11 lean healthy controls. Patients were classified into metabolically "healthy obese" (n = 26; mean age 42.6 years, mean BMI 46.8 kg/m(2)) or "unhealthy obese" (n = 26; mean age 45 years, mean BMI 47.5 kg/m(2)) groups, based upon standard cutoff points for blood pressure, lipid profile, and fasting glucose. Circulating lymphoid populations and phenotypes were assessed by flow cytometry. Obese patients had significantly less circulating natural killer (NK) and cytotoxic T lymphocytes (CTL) compared to lean controls. There were significantly higher levels of NK cells and CTLs in the healthy obese group compared to the unhealthy obese group (NK: 11.7% vs. 6.5%, P < 0.0001, CD8 13.4% vs. 9.3%, P = 0.04), independent of age and BMI and these NK cells were also less activated in the healthy compared to the unhealthy group (CD69, 4.1% vs. 11.8%, P = 0.03). This is the first time that quantitative differences in the circulating immune system of obese patients with similar BMI but different metabolic profiles have been described. The significantly higher levels of CTLs and NK cells, which express fewer inhibitory molecules, could protect against malignancy, infection, and metabolic disease seen in obesity.
Obesity (Silver Spring) 2009 Mar
PMID:Are natural killer cells protecting the metabolically healthy obese patient? 1923 45

The last few years have witnessed a rapid increase in our knowledge of the retinoid-related orphan receptors RORalpha, -beta, and -gamma (NR1F1-3), their mechanism of action, physiological functions, and their potential role in several pathologies. The characterization of ROR-deficient mice and gene expression profiling in particular have provided great insights into the critical functions of RORs in the regulation of a variety of physiological processes. These studies revealed that RORalpha plays a critical role in the development of the cerebellum, that both RORalpha and RORbeta are required for the maturation of photoreceptors in the retina, and that RORgamma is essential for the development of several secondary lymphoid tissues, including lymph nodes. RORs have been further implicated in the regulation of various metabolic pathways, energy homeostasis, and thymopoiesis. Recent studies identified a critical role for RORgamma in lineage specification of uncommitted CD4+ T helper cells into Th17 cells. In addition, RORs regulate the expression of several components of the circadian clock and may play a role in integrating the circadian clock and the rhythmic pattern of expression of downstream (metabolic) genes. Study of ROR target genes has provided insights into the mechanisms by which RORs control these processes. Moreover, several reports have presented evidence for a potential role of RORs in several pathologies, including osteoporosis, several autoimmune diseases, asthma, cancer, and obesity, and raised the possibility that RORs may serve as potential targets for chemotherapeutic intervention. This prospect was strengthened by recent evidence showing that RORs can function as ligand-dependent transcription factors.
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PMID:Retinoid-related orphan receptors (RORs): critical roles in development, immunity, circadian rhythm, and cellular metabolism. 1938 6

Invariant NKT (iNKT) cells recognize lipid antigens presented by CD1d and respond rapidly by killing tumor cells and release cytokines that activate and regulate adaptive immune responses. They are essential for tumor rejection in various mouse models, but clinical trials in humans involving iNKT cells have been less successful, partly due to their rarity in humans compared with mice. Here we describe an accumulation of functional iNKT cells in human omentum, a migratory organ with healing properties. Analysis of 39 omental samples revealed that T cells are the predominant lymphoid cell type and of these, 10% expressed the invariant Valpha24Jalpha18 TCR chain, found on iNKT cells, higher than in any other human organ tested to date. About 15% of omental hematopoietic cells expressed CD1d, compared with 1% in blood (p<0.001). Enriched omental iNKT cells killed CD1d(+) targets and released IFN-gamma and IL-4 upon activation. Omental iNKT-cell frequencies were lower in patients with severe obesity (p=0.005), and with colorectal carcinoma (p=0.004) compared with lean healthy subjects. These data suggest a novel role for the omentum in immune regulation and tumor immunity and identify it as a potential source of iNKT cells for therapeutic use.
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PMID:Invariant NKT cells and CD1d(+) cells amass in human omentum and are depleted in patients with cancer and obesity. 1958 13

Since having been cloned in 1984, IL-1beta has been the subject of over 22,000 citations in Pubmed, among them over 800 reviews. This is because of its numerous effects. IL-1beta is a regulator of the body's inflammatory response and is produced after infection, injury, and antigenic challenge. It plays a role in various diseases, including autoimmune diseases such as rheumatoid arthritis, inflammatory bowel diseases and type 1 diabetes, as well as in diseases associated with metabolic syndrome such as atherosclerosis, chronic heart failure and type 2 diabetes. Macrophage are the primary source of IL-1, but epidermal, epithelial, lymphoid and vascular tissues also synthesize IL-1. IL-1beta production and secretion have also been reported from pancreatic islets. Insulin-producing beta-cells within pancreatic islets are specifically prone to IL-beta-induced destruction and loss of function. Macrophage-derived IL-1beta production in insulin-sensitive organs, leads to progression of inflammation and induction of insulin resistance in obesity. We summarize the mechanisms involved in inflammation and specifically the IL-1beta signals that lead to the progression of insulin resistance and diabetes. We highlight recent clinical studies and experiments in animals and isolated islets using IL-1beta as a potential target for the therapy of type 2 diabetes.
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PMID:Interleukin-1 beta targeted therapy for type 2 diabetes. 1960 25

As the expanding obese population grows older, their successful immunologic aging will be critical to enhancing the health span. Obesity increases risk of infections and cancer, suggesting adverse effects on immune surveillance. Here, we report that obesity compromises the mechanisms regulating T-cell generation by inducing premature thymic involution. Diet-induced obesity reduced thymocyte counts and significantly increased apoptosis of developing T-cell populations. Obesity accelerated the age-related reduction of T-cell receptor (TCR) excision circle bearing peripheral lymphocytes, an index of recently generated T cells from thymus. Consistent with reduced thymopoiesis, dietary obesity led to reduction in peripheral naive T cells with increased frequency of effector-memory cells. Defects in thymopoiesis in obese mice were related with decrease in the lymphoid-primed multipotent progenitor (Lin-Sca1+Kit+ Flt3+) as well as common lymphoid progenitor (Lin-Sca1+CD117(lo)CD127+) pools. The TCR spectratyping analysis showed that obesity compromised V-beta TCR repertoire diversity. Furthermore, the obesity induced by melanocortin 4 receptor deficiency also constricted the T-cell repertoire diversity, recapitulating the thymic defects observed with diet-induced obesity. In middle-aged humans, progressive adiposity with or without type 2 diabetes also compromised thymic output. Collectively, these findings establish that obesity constricts T-cell diversity by accelerating age-related thymic involution.
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PMID:Obesity accelerates thymic aging. 1972 Oct 9

Multiple sclerosis (MS) is a neurological disorder that affects more than a million people world-wide. The aetiology of MS is not known and there is no medical treatment available that can cure MS. Experimental autoimmune encephalomyelitis (EAE) is a T-cell-mediated autoimmune disease model of MS. The pathogenesis of EAE/MS is a complex process involving activation of immune cells, secretion of inflammatory cytokines and destruction of myelin sheath in the central nervous system (CNS). Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptor transcription factors that regulate cell growth, differentiation and homeostasis. PPAR agonists have been used in the treatment of obesity, diabetes, cancer and inflammation. We and others have shown that PPARgamma, alpha and delta agonists inhibit CNS inflammation and demyelination in the EAE model of MS. In this study we show that the PPARdelta agonists GW501516 and L165041 ameliorate MOGp35-55-induced EAE in C57BL/6 mice by blocking interferon (IFN)-gamma and interleukin (IL)-17 production by T helper type 1 (Th1) and Th17 cells. The inhibition of EAE by PPARdelta agonists was also associated with a decrease in IL-12 and IL-23 and an increase in IL-4 and IL-10 expression in the CNS and lymphoid organs. These findings indicate that PPARdelta agonists modulate Th1 and Th17 responses in EAE and suggest their use in the treatment of MS and other autoimmune diseases.
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PMID:Peroxisome proliferator-activated receptor delta agonists inhibit T helper type 1 (Th1) and Th17 responses in experimental allergic encephalomyelitis. 2040 5

Murine norovirus (MNV) is prevalent in SPF mouse facilities in the United States, and we currently lack sufficient data to determine whether it should be eliminated. It is generally accepted that the virus does not cause clinical symptoms in immuno-competent mice. However, we previously reported that MNV infection alters the phenotype of a mouse model of bacteria-induced inflammatory bowel disease in part through its effects on dendritic cells. The tropism of MNV toward macrophages and dendritic cells makes MNV a potential intercurrent variable in murine models of macrophage-driven inflammatory diseases, such as obesity, insulin resistance, and atherosclerosis. Therefore, we determined whether MNV infection altered obesity and insulin resistance phenotypes in C57BL/6 mice, a widely used model of diet-induced obesity. We found that MNV did not alter weight gain, food intake, and glucose metabolism in this model, but it did induce subtle changes in lymphoid tissue. Further studies using other models of metabolic diseases are needed to provide additional information on the potential role this 'subclinical' virus might have on disease progression in mouse models of inflammatory diseases.
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PMID:Effects of murine norovirus infection on a mouse model of diet-induced obesity and insulin resistance. 2057 33


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