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Many chronic human diseases may have an underlying autoimmune mechanism. In this review, the author presents a case of autoimmune CIU (chronic idiopathic urticaria) in stable remission after therapy with a retroviral integrase inhibitor, raltegravir (Isentress). Previous reports located using the search terms "autoimmunity" and "anti-viral" and related topics in the pubmed data-base are reviewed suggesting that novel anti-viral agents such as retroviral integrase inhibitors, gene silencing therapies and eventually vaccines may provide new options for anti-viral therapy of autoimmune diseases. Cited epidemiologic and experimental evidence suggests that increased replication of epigenomic viral pathogens such as Epstein-Barr Virus (EBV) in chronic human autoimmune diseases such as rheumatoid arthritis (RA), systemic lupus Erythematosus (SLE), and multiple sclerosis (MS) may activate endogenous human retroviruses (HERV) as a pathologic mechanism. Memory B cells are the reservoir of infection of EBV and also express endogenous retroviruses, thus depletion of memory b-lymphocytes by monoclonal antibodies (Rituximab) may have therapeutic anti-viral effects in addition to effects on B-lymphocyte presentation of both EBV and HERV superantigens. Other novel anti-viral therapies of chronic autoimmune diseases, such as retroviral integrase inhibitors, could be effective, although not without risk.  相似文献   

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Crohn's disease (CD) is a multifactorial disease with genetic heterogeneity. TNF-alpha plays a key role in the development of the mucosal lesions. The aim of our work was to study a single base pair polymorphism located in the promoter region of TNF gene, in a large population of CD patients with well defined phenotypes. One hundred and ninety-three patients with CD and 98 ethnically matched controls were studied. The -308 single base pair polymorphism of TNF gene was studied using an allele-specific polymerase chain reaction. Genotype and allelic frequencies were compared between patients and controls and between subgroups of patients defined by sex, age at diagnosis, familial history, location of disease, type of disease, extra-intestinal manifestations, and response to steroid treatment. In 29 patients a measure of TNF-alpha production by colonic biopsies was performed. The frequency of the allele TNF2 as well as the proportion of carriers of the allele TNF2 were slightly but not significantly lower in CD than in controls (11.9% versus 14.8% and 21.5% versus 27.6%, respectively). A more prominent difference in frequencies of allele TNF2 and in proportions of TNF2 carriers was found when comparing subgroups of patients. The frequency of allele TNF2 was significantly higher in steroid-dependent than in non-steroid-dependent disease (28.1% versus 10.3%; Delta = 17.8%, 95% confidence interval (CI) = 6.3-29.5%, P = 0.0027) and tended to be higher in colonic than in small bowel disease and in fistulizing than in stricturing disease. Furthermore, TNF2 carriers tended to be more frequent in patients with steroid-dependent than non-steroid-dependent disease (43.8% versus 19.3%; Delta = 24.5%, 95% CI = 3.6-45.4%, P = 0.022), in patients with fistulizing than stricturing disease (26.5% versus 9.6%; Delta = 16.9%, 95% CI = 1. 1-32.6%, P = 0.036), and in patients with colonic than small bowel disease (26.5% versus 11.1%; Delta = 15.4%, 95% CI = -0.8-31.6%, P = 0.063). Finally, patients carrying at least one copy of allele 2 were found to produce slightly more TNF-alpha at the colonic level. The -308 TNF gene polymorphism may have a slight influence on the behaviour of CD. The carriage of allele 2 may favour steroid-dependent disease and to a lesser extent fistulizing and colonic disease, possibly secondary to a more intense TNF-alpha-driven inflammatory reaction at the mucosal level.  相似文献   

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Melanoma metastasis is almost uniformly fatal. The identification of signal transduction as crucial effectors for tumorigenesis suggests modalities of gene therapy as well as design of specific drugs. the possible use of nPKCdelta as a therapeutic target is reviewed and discussed. Motivated by recent results, we propose a model in which nPKCdelta modulates melanin synthesis as well as metastasis.  相似文献   

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Thyroid disease is common, and the prevalence is rising. Traditional diagnosis and monitoring relies on thyroid stimulating hormone (TSH) levels. This does not always result in symptomatic improvement in hypothyroid symptoms, to the disappointment of both patients and physicians. A non-traditional therapeutic approach would include evaluation of GI function as well as a dietary history and micronutrient evaluation. This approach also includes assessment of thyroid peroxidase (TPO) antibodies, T3, T4, and reverse T3 levels, and in some cases may require specific T3 supplementation in addition to standard T4 therapy. Both high and low TSH levels on treatment are associated with particular medical risks. In the case of high TSH this is primarily cardiac, whereas for low TSH it is predominantly bone health. This article discusses these important clinical issues in more detail, with some practical tips especially for an approach to the “non-responders” to the current traditional therapeutic approach.  相似文献   

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Reactive oxygen species play an important role in a variety of (patho)physiological vascular processes. Recent publications have produced evidence of a role for putative non-phagocyte NADP oxidase(s) in the vascular production of reactive oxygen species. In the present review, we discuss the detection of the different components of NADP oxidase(s) in the vascular system, together with the putative role of reactive oxygen species produced by vascular NADPH oxidase(s), in both in vitro and in vivo studies.  相似文献   

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As we have become more familiar with the pathogenesis of atheroma, it has become recognized atherogenesis is mainly an inflammatory disease. Therefore, it is not surprising that a body of evidence demonstrates that endothelium injury is associated with the progression and severity of HIV infection. Another important question is: do antiretroviral drugs increase or reduce endothelial injury? Various studies support the hypothesis that HAART does induce activation of endothelial function. Thus, HIV virus as well as immune reconstitution and HAART itself promote premature endothelial activation. Such a prominent role played by inflammatory events could affect the structure of the arterial lesions in HIV patients that could present different characteristics with respect to the classical atheroma. In fact, in two HIV patients with severe stenosis of the carotid, histology revealed extensive inflammatory infiltration of the vascular wall. The characteristics of these lesions were similar to those of arteritis. Another study evidenced that the ultrasonographic structure of the lesions in HIV patients substantially differ from those found in atherosclerosis, sharing similar characteristics with arteritis. We hypothesize that the atherosclerotic lesions in HIV patients develop in two distinct phases: the first one characterized by an inflammation of the vascular wall, and subsequently, the lesions could evolve towards the classic feature of the atheroma. The lesions in the first phase are probably determined by immunodeficiency, immune reconstitution, and the same effect of HAART. In the second phase they could be maintained by the classic risk factors.  相似文献   

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BACKGROUND: For diagnosis and follow-up of celiac disease, pediatric societies advise that intestinal mucosal specimens should be obtained using suction capsule from the jejunum. This procedure is strenuous for patients, time-consuming, expensive and requires radiographic guidance. Mucosal biopsies from the distal duodenum can be obtained more easily under endoscopic vision using forceps. The aim of the present study was to compare biopsies taken from the duodenal mucosa by forceps and from the jejunal mucosa using suction capsule with respect to histological outcome. METHODS: For this study, 171 paired biopsies were taken from 109 patients (1-75 years) from the distal duodenal mucosa using jumbo forceps and from the jejunal mucosa using Crosby suction capsule. Histological interpretation was performed according to a modified Marsh classification, including partial-, subtotal and total villous atrophy as Marsh IIIA, B, and C. RESULTS: Fourteen suction capsule biopsies were of insufficient quality to be interpreted (8%). All duodenal forceps biopsies produced adequate material for histological scoring. No differences in histological scoring were seen in 145 of 157 compared biopsies (92%). Of 12 biopsies in which a discrepancy was present, 4 showed more severe lesions in the duodenum and 8 more severe lesions in the jejunum. The differences were of clinical significance, i.e., including the presence and absence of villous atrophy in 9 of 157 paired biopsies (6%). CONCLUSION: In the present study, we demonstrated that mucosal specimens taken from the distal duodenal and jejunal mucosa are strongly correlated. Clinically significant discrepancies were present in only 6% of paired biopsies. Therefore we suggest that, in diagnosis and follow-up of celiac disease, mucosal specimens may be taken from the duodenum using forceps to obtain adequate material for histological interpretation.  相似文献   

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BACKGROUND: The LC Polscope facilitates visualization of the meiotic spindle in human oocyte. This study aimed to investigate meiotic spindle assembly in correlation to time elapsed after HCG administration, and to determine whether spindle imaging may serve to indicate the likelihood of fertilization and embryo cleavage. METHODS: Metaphase II (MII) oocytes from 103 couples who were being treated for male infertility were imaged with the Polscope prior to sperm injection. Spindle imaging was correlated to time elapsed from HCG administration, fertilization rate and embryo cleavage. The main outcome measures were spindle visualization, fertilization and embryo cleavage on day 3. RESULTS: A total of 770 MII oocytes were imaged. A spindle was imaged in a significantly higher number of oocytes from >or=38 h after HCG administration compared with those in the <38 h group (78.1-81.5% versus 61.6%; P < 0.001). The fertilization rate in oocytes with a visible spindle was statistically higher compared with oocytes in which spindle could not be detected (70.4% versus 62.2%; P = 0.035). We found no relationship between spindle imaging and embryo cleavage on day 3. CONCLUSIONS: Spindle imaging, in addition to first polar body appearance, is an accurate indicator for oocyte maturity. We suggest that spindle imaging be performed prior to sperm injection.  相似文献   

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Allergic diseases are common and specific immunotherapy provides a therapeutic approach. Specific immunotherapy has its limits, as whole allergen extracts are used. These may contain proteins that patients might not be sensitized to. A required long-term treatment (3–5 years) might activate a potential risk of IgE-mediated severe allergic reactions. A new promising therapeutic approach is to apply short synthetic T-cell peptides. Such synthetic peptides consist of immunoregulatory epitopes (SPIREs) that are 13–17 amino acids in length. Recent clinical data, derived from chamber studies, suggest a clinical efficacy with a good tolerability of SPIREs.  相似文献   

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A new era for radiolabeled antibodies in cancer?   总被引:4,自引:0,他引:4  
Radioimmunotherapy (RIT), a therapy targeted to tumor cells, is a modality that can currently deliver radiation to tumor cells at levels 3-50-times higher than to the normal tissue with the next highest dose. RIT appears promising for future cancer therapy. Clinical responses in patients with advanced cancer have frequently been achieved with RIT as a single agent. Extended complete remissions and even increased survival have been achieved in lymphoma. Similar results in other cancers seem likely with RIT in combination therapy.  相似文献   

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Isolation of fetal cells from maternal blood is under active investigation as a noninvasive method of prenatal diagnosis. In the context of studying cell surface antigens expressed on fetal cells we discovered that fetal cells from a prior pregnancy also could be detected. This led to the appreciation of the persistence of fetal cells in maternal blood for as long as 27 years postpartum, and the realization that following pregnancy, a woman becomes a chimera. Quantitative polymerase chain reaction analyses have shown that a term pregnancy is not required for the subsequent development of fetal cell microchimerism. As many as 500,000 fetal nucleated cells are transfused following an elective first trimester termination of pregnancy. The relationship between fetal cell microchimerism and maternal disease is currently being explored. During pregnancy, fetal cells in the maternal skin are related to polymorphic eruptions of pregnancy and increased fetomaternal trafficking is detectable in cases of preeclampsia. After delivery, more male DNA of presumed fetal origin is present in the blood and skin of women with scleroderma as compared with healthy controls. Scleroderma is of particular interest because it shows a strong female predilection and it is an autoimmune disease with clinical similarities to graft‐versus‐host disease. Fetomaternal cell trafficking provides a potential explanation for the increased prevalence of autoimmune disorders in adult women following their childbearing years. Am. J. Med. Genet. 91:22–28, 2000. © 2000 Wiley‐Liss, Inc.  相似文献   

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We describe two sibs with geroderma osteodysplasticum (GO) who, in addition to the known clinical and radiologic manifestations of the disorder, presented a metaphyseal peg indenting the epiphysis of the long bones, particularly at the knees. The peg was visible only at the age of 4 to 5 years but was invisible in infancy and following physeal closure. This may explain why this anomaly was not described in previous reports of 23 patients in 11 families with GO. The metaphyseal peg is an abnormality of bone development so far unknown to us. We speculate that it represents a primary, age-dependent alteration of bone shape and hence a new genetic bone marker apparently specific to GO. © 1996 Wiley-Liss, Inc.  相似文献   

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Patients with Crohn's disease are at increased risk of developing intestinal adenocarcinoma. Dysplasia is both a marker and a precursor of adenocarcinoma in this setting. In a review of our cases of Crohn's-related adenocarcinoma, we noted a peculiar hyperplastic-like mucosal change (HPC) in mucosa both adjacent to and distant from the adenocarcinoma in some cases. However, the significance of this change is unknown. We evaluated 30 cases of Crohn's-related adenocarcinoma and 30 age- and site-matched resection specimens with Crohn's disease without adenocarcinoma to determine the prevalence of this mucosal alteration in these groups. HPC was recognized by a diffuse expanse of flat mucosa with an architecture resembling that seen in colorectal hyperplastic polyps and composed of cells with cytologically bland basal nuclei and apical cytoplasmic mucin distention. The relationship of the HPC to the adenocarcinoma was noted in the Crohn's-related adenocarcinoma cases. An immunohistochemical stain for p53 (antibody DO7) was performed on all cases with HPC in both groups. HPC was identified in 10 of 30 (33%) cases of Crohn's-related adenocarcinoma compared with 3 of 30 (10%) cases in the control group (P = .03). In the 10 cases of Crohn's-related adenocarcinoma with HPC, this alteration was found adjacent to the adenocarcinoma in 3 cases, distant to the adenocarcinoma in 5 cases, and both adjacent to and distal from the adenocarcinoma in 2 cases. In two specimens, HPC was seen immediately adjacent to adenocarcinoma in the absence of adjacent dysplasia. p53 immunoreactivity was noted in HPC in 5 of 10 (50%) Crohn's-related adenocarcinomas. In contrast, p53 immunoreactivity was not seen in HPC in the three control cases with this mucosal alteration. In conclusion, HPC is found significantly more commonly in mucosa both adjacent to and distant from Crohn's-related adenocarcinoma when compared with age- and site-matched controls. In addition, p53 immunoreactivity is more commonly seen in HPC in cases of Crohn's-related adenocarcinoma compared with controls. These data suggest that this mucosal alteration may, in some cases, represent an unusual form of dysplasia in this setting.  相似文献   

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Smoking is a very common addiction and is associated with several kinds of diseases including different forms of cancer. Nicotine is the only substance present in cigarettes that can cause dependence. There are pharmacological treatments available to smoking cessation, but all of them are associated with side effects and low efficacy. Therefore, the development of new strategies and treatments is necessary. A possibility is the supplementation with polyunsaturated fatty acids (PUFAs) of the omega 3 series. It is known that low concentration of omega 3 can affect the dopaminergic neurotransmission, resulting in hypofunctioning of the mesocortical system. This system controls the mesolimbic system, associated in rewarding and dependence mechanisms. New perspectives of treatment focus on the reestablishment of the omega 3 levels, having as a result the normalization of the dopaminergic system and the reduction of the negative symptoms of withdrawal.  相似文献   

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《Medical hypotheses》2013,80(6):867-868
Smoking is a very common addiction and is associated with several kinds of diseases including different forms of cancer. Nicotine is the only substance present in cigarettes that can cause dependence. There are pharmacological treatments available to smoking cessation, but all of them are associated with side effects and low efficacy. Therefore, the development of new strategies and treatments is necessary. A possibility is the supplementation with polyunsaturated fatty acids (PUFAs) of the omega 3 series. It is known that low concentration of omega 3 can affect the dopaminergic neurotransmission, resulting in hypofunctioning of the mesocortical system. This system controls the mesolimbic system, associated in rewarding and dependence mechanisms. New perspectives of treatment focus on the reestablishment of the omega 3 levels, having as a result the normalization of the dopaminergic system and the reduction of the negative symptoms of withdrawal.  相似文献   

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