Immune cells in colorectal cancer.
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CD4-Positive T-Lymphocytes↗
Biomedical subjects
Anna Maria Wolf
Publications and source records attributed to Anna Maria Wolf.
Prevalence of mental disorders in normal-weight and obese individuals with and without weight loss treatment in a German urban population.
OBJECTIVE: The aim of the study was to evaluate the prevalence rates of mental disorders in normal-weight individuals and obese individuals with and without weight loss treatment. METHODS: A sample of 251 participants in a conventional weight loss treatment, 153 pre-bariatric surgery patients, 174 normal-weight control participants, and 128 obese control participants not actively losing weight at the time of the investigation were examined. RESULTS: Lifetime prevalence rates of mental disorders in obese women ranged from 46.7% to 60.1% compared with 41.7% in normal-weight women and from 48.0% to 54.4% in obese men compared with 29.8% in normal-weight men. Prevalence rates of mental disorders did not differ significantly between normal-weight and obese women not currently in weight loss treatment; however, the rates were significantly lower compared with both obese treatment groups. Compared with normal-weight men, obese men not currently in weight loss treatment and obese men participating in conventional weight loss treatment showed significantly higher prevalence rates of mental disorders. CONCLUSION: Unlike obese male individuals, obese female participants not currently in weight loss treatment did not differ from normal-weight participants with regard to comorbidity of mental disorders. However, obese female participants who were engaged in weight loss treatment exhibited significantly higher prevalence rates than normal-weight participants.
Adult↗
The effect of zoledronic acid on the function and differentiation of myeloid cells.
BACKGROUND AND OBJECTIVES: Bisphosphonates are widely used for treatment of osteoporosis and metastases of the skeletal system. Recent data suggest that bisphosphonates may not only reduce bone loss but also exert direct anti-tumor, anti-angiogenic and E inverted exclamation markE not T-cell activating effects, properties which depend at least partially on their affinity to phagocytosing and antigen-presenting cells (i.e. osteoclasts and monocytes). The latter represent the major source of dendritic cells (DC). Thus, we determined the immunomodulatory properties of zoledronic acid (ZA), a member of the latest generation of bisphosphonates. DESIGN AND METHODS: Primary human monocytes, macrophages, immature and mature dendritic cells were incubated with increasing doses of ZA for subsequent analysis of cell surface marker expression and cytokine production. In addition, phagocytic and allo-stimulatory properties, differentiation capacity, and NF-kB activation were determined. RESULTS: Therapeutic doses of ZA inhibited the in vitro generation of DC from monocytes, as shown by an impaired up-regulation of maturation markers. In parallel, ZA also impaired lipopolysaccharide-induced activation of NF-kB, which represents a critical factor for DC differentiation. Accordingly, the activation of allogeneic T cells by ZA-treated DC in a mixed-lymphocyte reaction was significantly reduced. Finally, ZA inhibited the production of tumor necrosis factor-a in monocyte-derived cells and impaired the phagocytic capacity of macrophages and immature DC. INTERPRETATION AND CONCLUSIONS: Therapeutic doses of ZA modulate monocyte, macrophage and DC function and might thereby modulate immune function.
Antigens, CD↗
Up-regulation of the anti-inflammatory adipokine adiponectin in acute liver failure in mice.
BACKGROUND/AIMS: Recent reports suggest that the adipose tissue and adipokines are potent modulators of inflammation. However, there is only scarce knowledge on the functional role and regulation of endogenous adiponectin in non-fat tissues such as the liver under conditions of acute inflammation. METHODS: In the present study, we investigated adiponectin expression in healthy murine liver tissue and under inflammatory conditions in vivo. RESULTS: Adiponectin mRNA was readily detectable in healthy liver tissue and further increased in ConA-mediated acute liver failure. Adiponectin protein expression was mainly found in hepatic endothelial cells. In vitro adiponectin mRNA expression was detectable in several cell types, including primary hepatic sinusoidal endothelial cells, stellate cells, and macrophages. Mice pretreated with adiponectin before ConA administration developed reduced hepatic injury as shown by decreased release of transaminases and reduced hepatocellular apoptotis. Of note, TNF-alpha levels were not affected by adiponectin, whereas IL-10 production was increased. Neutralisation of IL-10 diminished the protective effect of adiponectin. CONCLUSIONS: Adiponectin expression is up-regulated in ConA-mediated acute liver failure. Therefore, adiponectin might play a role in the control and limitation of inflammation in the liver. Moreover, our data suggest a role for IL-10 in adiponectin-mediated hepatoprotection.
Adiponectin↗
The kinase inhibitor imatinib mesylate inhibits TNF-{alpha} production in vitro and prevents TNF-dependent acute hepatic inflammation.
Imatinib exerts potent antileukemic effects in vitro and in vivo. Despite its well known antitumor activity, the potential of imatinib for the treatment of inflammatory diseases remains elusive so far. Our current report provides strong evidence that imatinib has potent antiinflammatory effects. It potently inhibits LPS- and Con A-induced TNF-alpha production by human myeloid cells in vitro (peripheral blood mononuclear cells, CD14-selected monocytes, and monocyte-derived macrophages). Of note, the production of the antiinflammatory cytokine IL-10 was not significantly regulated by imatinib. In line with this observation, phosphorylation of IkappaB and subsequent DNA binding of NF-kappaB, which is critically involved in TNF-alpha, but not IL-10 expression, was reduced by imatinib. Using several murine models of acute hepatitis, we could corroborate our in vitro findings, as imatinib prevented macrophage- and TNF-alpha-dependent inflammatory damage of the liver induced by injection of either Con A or d-galactosamine/LPS by inhibition of hepatic TNF-alpha production. Of note, d-galactosamine/TNF-induced hepatitis was not affected, showing that imatinib does not directly inhibit TNF-alpha-induced hepatocellular cell death. These findings suggest a potent antiinflammatory role of imatinib by modulation of TNF-alpha production in monocytes/macrophages. This observation might be of therapeutic value for the treatment of TNF-mediated diseases.
Animals↗
Age-related loss of naïve T cells and dysregulation of T-cell/B-cell interactions in human lymph nodes.
In this study we analysed the effects of age on T and B lymphocytes in human lymph nodes by comparing lymphocyte subsets in paraffin sections from lymph node tissue taken from healthy young and elderly people. We demonstrate that the relative number of CD8(+) T cells decreases with age but that the relative number of CD4(+) T cells does not. There is also a very pronounced age-dependent loss of CD45RA(+) naive T cells. The number and size of follicles and the relative number of CD20(+) B cells are similar in young and elderly donors. For polymerase chain reaction analysis of the T-cell receptor (TCR) repertoire the TCR-gamma gene rearrangements were used as a marker of clonality. This is a reliable tool to detect not only clonal TCR-gammadelta populations but also TCR-alphabeta populations. Young donors with clonal T-cell expansions in their lymph node tissue do, however, have a higher number of CD20(+) B cells, a higher relative size of germinal centres compared to the follicle mantles and a higher number of immunoglobulin M-expressing cells than young donors without evidence of clonal T-cell expansions. Corresponding changes are not observed in elderly donors with clonal T-cell expansions in their lymph node tissue. In summary our findings demonstrate characteristic effects of aging on human lymph node tissue, the most striking feature being the depletion of naive T cells and the apparent dysregulation of T-cell/B-cell interactions in old age.
Adolescent↗
Histological changes in the liver of morbidly obese patients: correlation with metabolic parameters.
BACKGROUND: Obesity is a major risk factor for fatty liver disease. The purpose of this study was: 1) to determine the degree of steatosis, inflammation and fibrosis in liver biopsies of morbidly obese patients in relation to their body fat distribution and metabolic status, and 2) to examine the course of liver enzyme changes with surgically-induced weight loss. METHODS: The study population included 179 morbidly obese bariatric surgical patients (82% female, 18% male, mean age 39+/-0.7 (SEM) years, BMI 52+/-0.6 kg/m2, excess body weight 80+/-1.8 kg). All patients tested negative for hepatitis and HIV. Liver biopsies were taken intra-operatively. Hepatic enzyme activities were measured along with lipid parameters, fasting glucose, insulin and leptin. RESULTS: Liver biopsies showed that 47% of morbidly obese females and 85% of males had >30% of hepatocytes filled with fat droplets. Clinically significant hepatic steatosis was associated (P<0.01) with: a) metabolic aberrations, i.e.hyperlipidemia, hyperglycemia, b) male gender, c) abdominal adiposity, and d) elevated hepatic aminotransferase activities. Hepatic inflammation was found in 47% of females and 55% of males, and 'moderate' fibrosis occurred in 12% of males and 6% of females. Postoperatively, the activity of hepatic aminotransferases declined after an initial increase in response to weight loss, with normalization of values occurring at an excess weight loss of 50% (P<0.0001). CONCLUSION: The majority of morbidly obese patients have >30% steatosis of the liver. The incidence of steatosis is higher for males than females, possibly due to their visceral obesity and associated metabolic aberrations.
Adult↗
The influence of eating behavior and eating pathology on weight loss after gastric restriction operations.
BACKGROUND: Eating behavior before surgery is considered to have great predictive value for the course of weight after surgery. The present study investigates the predictive value of three dimensions of eating behavior and disturbed eating on weight loss after gastric restriction surgery. METHODS: 149 patients consisting of 47 males (32%), 102 females (68%), with mean age 38.8+10.3 years, were investigated by means of a structured interview and the Three Factor Eating Questionnaire (TFEQ) before (T1) and at least 12 months after (T2) (14.0+1.5 months) gastric restriction surgery. RESULTS: Mean BMI before surgery was 50.9+/-8.1 kg/m2; postoperatively, the BMI decreased on average by 12.8 kg/m2 to 38.6+/-6.8 kg/m2 (t=22.7, P=0.000) at T2. Point-prevalence of Binge Eating Disorder (BED) according to DSM-IV was 2.0%, and lifetime-prevalence 7.4%, respectively. Of our sample, 20.1% reported current binge episodes without fulfilling all criteria for BED. An eating pathology consisting of continual eating ("grazing") was reported in 19.5% of the patients. At T2, patients with a weight loss of at least 25% of their pre-surgery weight indicated significantly less hunger and disinhibition compared with patients with less weight loss. Patients with a distinct craving for sweets after surgery lost significantly less weight. Patients with binge episodes or "grazing" before surgery did not differ in average weight loss from patients without binge episodes or "grazing". CONCLUSION: Postoperative but not preoperative eating behavior is of predictive value for the extent of weight loss after gastric restriction surgery.
Adult↗
Adiponectin: a key fat-derived molecule regulating inflammation.
Adiponectin is the abundant adipocyte-derived protein with well-established anti-atherogenic and insulin-sensitising properties. Besides these well characterised biological functions, recent evidence supports a strong anti-inflammatory function. Whereas initial studies demonstrated that adiponectin suppresses the production of the potent pro-inflammatory cytokine TNF-alpha, current studies showed that this adipokine also induces various anti-inflammatory cytokines, such as IL-10 or -1 receptor antagonists. These effects are paralleled by various other immune-regulatory properties, such as specific effects on endothelial cell functions. These in vitro effects are directly translated into various animal models of inflammation, demonstrating a potent anti-inflammatory effect for adiponectin. Thiazolidinediones selectively upregulate peroxisome-proliferator-activated receptor-gamma, leading to increased tissue and serum concentrations of adiponectin. Adiponectin has emerged as a key mediator regulating and affecting the balance between fat and inflammation. Therefore, either adiponectin itself or its inducing agents, such as thiazolidinediones, might be of key therapeutic interest in the near future far beyond diseases being associated with insulin resistance.
Adipocytes↗
Overexpression of indoleamine 2,3-dioxygenase in human inflammatory bowel disease.
T-cells are causally involved in the pathogenesis of inflammatory bowel disease (IBD). The tryptophan-metabolizing enzyme indoleamine 2,3-dioxygenase (IDO) regulates T-cell proliferation and survival. We show in this report that IDO mRNA is markedly induced in lesional colonic biopsies of IBD patients. IDO is primarily expressed in CD123(+) mononuclear cells infiltrating the submucosal areas of the inflamed lesions. In Crohn's disease (CD), IDO is also strongly expressed in perifollicular regions of lymphoid follicles. Upregulation of IDO is of functional significance, as we detected an increase of kynurenine and of the kynurenine/tryptophan ratio in supernatants from colonic explant cultures (CECs) of CD patients. Immunohistochemistry of colonic biopsies taken from CD patients prior and after treatment with the TNF-blocking antibody Infliximab revealed reduced IDO expression in patients with good clinical response to Infliximab. In summary, high local expression of IDO may represent an anti-inflammatory mechanism tempting to counterbalance the tissue-damaging effects of activated T-cells infiltrating the colonic mucosa in IBD.
Adult↗
IL-4-producing CD8+ T cells with a CD62L++(bright) phenotype accumulate in a subgroup of older adults and are associated with the maintenance of intact humoral immunity in old age.
An increased production of proinflammatory cytokines occurs in a high percentage of elderly persons and is associated with an impaired humoral immune response. However, high IL-4 production has also been observed in old age. We now demonstrate an IL-4-producing subpopulation of CD8+ T cells in a subgroup of healthy older adults. This T cell subset is substantial in size and has a characteristic phenotype expressing CD45RO, CD28, CD62L, and CD25. IL-4-producing CD8+ T cells produce large amounts of IL-2 but not IFN-gamma or perforin, and these cells do not have a regulatory suppressive effect on other T cells. In vivo IL-4-producing CD8+ T cells can be stably detected over a year. When put into culture they also have a stable cytokine production pattern but fail to produce perforin even in the presence of IL-12. This special T cell type does not occur in persons under the age of 40, but is present in 36% of the persons >60 years of age. In this age group, IL-4-producing CD8+ T cells are more frequent in persons who are still capable of raising a humoral immune response following immunization than in others who fail to produce protective Abs after vaccination. Our results suggest that CD8+ T cells with a CD62L++(bright) phenotype accumulate in a subgroup of older adults. Due to their phenotype that enables them to migrate into lymphoid tissues and to their capacity to produce IL-4, these cells may counterbalance the overproduction of proinflammatory cytokines in old age.
Adult↗
[Mesenteric ischemia. Surgical epidemiology--when to take it into consideration?].
Diagnostic and therapeutic treatment modalities have developed over the last few years. However, the mortality rate of mesenteric ischemia is still high. The incidence amounts to 2-4 patients in 100,000 inhabitants. This is due to the fact that disturbances in the blood circulation of the intestine are not recognized early enough. While clinical symptoms are different during the acute and chronic course of mesenteric ischemia, the diagnostic and therapeutic consequences are similar. In order to decrease the mortality rate, it is important to keep mesenteric ischemia in mind when confronted with abdominal pain in elderly patients. This is particularly important as life expectancy in the western population is increasing.
Cross-Sectional Studies↗
Increase of regulatory T cells in the peripheral blood of cancer patients.
PURPOSE: T cells constitutively expressing both CD4 and CD25are essential for maintenance of self-tolerance and therefore have been referred to as regulatory T cells (Treg). Experimental tumor models in mice revealed that Tregs are potent inhibitors of an antitumor immune response. The current study was designed to determine whether cancer patients exhibit an expanded Treg pool. EXPERIMENTAL DESIGN: The frequency of Tregs in the peripheral blood of 42 patients suffering from epithelial malignancies and from 34 healthy controls was determined by flow cytometry. The immunoregulatory properties of CD4(+)CD25(+) and CD4(+)CD25(-) T cells were characterized by proliferation and suppression assays. Cocultures with natural killer (NK) cells were performed to determine the impact of Tregs on NK-mediated cytotoxicity. RESULTS: Patients with epithelial malignancies show an increase of CD4(+)CD25(+) T cells in the peripheral blood with characteristics of Tregs, i.e., they are CD45RA(-), CTLA-4(+), and transforming growth factor beta(+). Notably, CD4(+) T cells from cancer patients are characterized by an impaired proliferative capacity, which is restored to the extend of CD25-depleted CD4(+) T cells from control persons by prior removal of CD25(+) T cells. In contrast to CD4(+)CD25(-) T cells, isolated CD4(+)CD25(+) T cells from cancer patients were anergic towards T cell receptor stimulation. In addition, CD4(+)CD25(+) T cells suppressed the proliferation of CD4(+)CD25(-) T cells. When cultured together with CD56(+) NK-cells, CD4(+)CD25(+) T cells from cancer patients effectively inhibited NK-cell-mediated cytotoxicity. CONCLUSIONS: Thus, we provide evidence of an increased pool of CD4(+)CD25(+) regulatory T cells in the peripheral blood of cancer patients with potent immunosuppressive features. These findings should be considered for the design of immunomodulatory therapies such as dendritic cell vaccination.
Antigens, CD↗