Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0015674 (chronic fatigue syndrome)
 2,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Toxigenic mold activities produce metabolites that are either broad-spectrum antibiotics or mycotoxins that are cytotoxic. Indoor environmental exposure to these toxigenic molds leads to adverse health conditions with the main outcome measure of frequent neuroimmunologic and behavioral consequences. One of the immune system disorders found in patients presenting with toxigenic mold exposure is an abnormal natural killer cell activity. This paper presents an overview of the neurological significance of abnormal natural killer cell (NKC) activity in chronic toxigenic mold exposure. A comprehensive review of the literature was carried out to evaluate and assess the conditions under which the immune system could be dysfunctionally interfered with leading to abnormal NKC activity and the involvement of mycotoxins in these processes. The functions, mechanism, the factors that influence NKC activities, and the roles of mycotoxins in NKCs were cited wherever necessary. The major presentations are headache, general debilitating pains, nose bleeding, fevers with body temperatures up to 40 degrees C (104 degrees F), cough, memory loss, depression, mood swings, sleep disturbances, anxiety, chronic fatigue, vertigo/dizziness, and in some cases, seizures. Although sleep is commonly considered a restorative process that is important for the proper functioning of the immune system, it could be disturbed by mycotoxins. Most likely, mycotoxins exert some rigorous effects on the circadian rhythmic processes resulting in sleep deprivation to which an acute and transient increase in NKC activity is observed. Depression, psychological stress, tissue injuries, malignancies, carcinogenesis, chronic fatigue syndrome, and experimental allergic encephalomyelitis could be induced at very low physiological concentrations by mycotoxin-induced NKC activity. In the light of this review, it is concluded that chronic exposures to toxigenic mold could lead to abnormal NKC activity with a wide range of neurological consequences, some of which were headache, general debilitating pains, fever, cough, memory loss, depression, mood swings, sleep disturbances, anxiety, chronic fatigue, and seizures.
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PMID:The neurological significance of abnormal natural killer cell activity in chronic toxigenic mold exposures. 1462 99

Since 1996 in our clinic, the regular practice of megadose vitamin C infusion with dehydroepiandrosterone-cortisol annex and the continuous intake of erythromycin and chloramphenicol have been found useful for the clinical control of the autoimmune disease interstitial pneumonia, also known as chronic fatigue syndrome. The long-term use of these two systems for the treatment of the autoimmune disease has led to the emergence of four problems of theoretical or practical importance, as described below: i) Should maintenance of the above core treatments be continued for prophylactic purposes in the absence of acute signs of pneumonia? Evidence indicated that their use was essential to arrest the dynamic activity of an intrapulmonary bacterial colony in the immunodeficient host, and that the 5-year survival rate of interstitial pneumonia patients would have been worse without the prophylactic practice of the 2 treatments. ii) Evidence was presented to suggest that the activity of the intrapulmonary bacterial colony was becoming less responsive because of the emergence of a drug-resistent mutant bacterium. The introduction of new antibiotics (kanamycin) was found to improve the acute signs of pneumonia. iii) The bone marrow function of one male patient with interstitial pneumonia was found to decline during the observation period of 9 years. It was speculated that his bone marrow, like his lungs, was in the course of fibrosis. iv) One female patient was diagnosed with breast cancer in the course of interstitial pneumonia treatment--an example indicating that the persistence of an autoimmune disease in an elderly subject might be associated with the emergence of malignancy. Dehydroepiandrosterone was shown to promote the recovery of hepatic function in the course of cancer chemotherapy with cyclophosphamide. The beneficial effect of the adrenal androgen was dose-dependent. The significance of this finding is discussed in the light of the steroid carcinogenesis concept. The reasoning behind the view that interstitial pneumonia and chronic fatigue syndrome are one disease is also discussed.
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PMID:Four problems with the clinical control of interstitial pneumonia, or chronic fatigue syndrome, using the megadose vitamin C infusion system with dehydroepiandrosterone-cortisol annex. 1663 32

Xenotropic murine leukemia virus-related virus (XMRV) is an authentic, newly recognized human retrovirus first identified in prostate cancer tissues from men with a deficiency in the innate immunity gene RNASEL. At present, studies have detected XMRV at widely different rates in prostate cancer cases (0-27%) and in patients with chronic fatigue syndrome (CFS; 0-67%). Indirect or direct modes of carcinogenesis by XMRV have been suggested depending on whether the virus was found in stroma or malignant epithelium. Viral replication in the prostate might be affected by androgens, which stimulate XMRV through a transcriptional enhancer site in viral DNA. By contrast, host restriction factors, such as APOBEC3 and tetherin, inhibit virus replication. Immune dysfunction mediated by XMRV has been suggested as a possible factor in CFS. Recent studies show that some existing antiretroviral drugs suppress XMRV infections and diagnostic assays are under development. Although other retroviruses of the same genus as XMRV (gammaretroviruses) cause cancer and neurological disease in animals, whether XMRV is a cause of either prostate cancer or CFS remains unknown. Emerging science surrounding XMRV is contributing to our knowledge of retroviral infections while focusing intense interest on two major human diseases.
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PMID:The human retrovirus XMRV in prostate cancer and chronic fatigue syndrome. 2051 89

The recent discovery of xenotropic murine leukaemia virus-related virus (XMRV) in prostate cancer tissues and in the blood of individuals suffering from chronic fatigue syndrome has attracted considerable interest. However, the relevance and significance of XMRV to human disease remain unclear, since the association has not been confirmed in other studies. XMRV is the first gammaretrovirus to be found in humans. XMRV and murine leukaemia viruses share similar structures and genomic organisation. Human restriction factors such as APOBEC3 or tetherin inhibit XMRV replication. Although XMRV induces low rates of transformation in cell culture, it might be able to induce cancer by low-frequency insertional activation of oncogenes or through the generation of highly active transforming viruses. A preference for regulatory regions of transcriptional active genes has been observed after a genomic-wide analysis of XMRV integration sites. Genes related to carcinogenesis and androgen signalling have been identified in the vicinity of integration sites. The XMRV genome contains a glucocorticoid responsive element, and androgens could modulate viral replication in the prostate. Evidence supporting the involvement of XMRV in chronic fatigue syndrome is still very weak, and needs further confirmation and validation. Currently approved anti-retroviral drugs such as zidovudine, tenofovir and raltegravir are efficient inhibitors of XMRV replication in vitro. These drugs might be useful to treat XMRV infection in humans. The identification of XMRV has potentially serious health implications for the implementation of novel techniques including gene therapy or xenotransplantation, while raising concerns on the need for screening donated blood to prevent transmission through transfusion.
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PMID:Evidence and controversies on the role of XMRV in prostate cancer and chronic fatigue syndrome. 2129 12

Double strand break (DSB) repair mechanisms guard genome integrity and their deterioration causes genomic instability. Common and rare fragile sites (CFS and RFS, respectively) are particularly vulnerable to instability, and there is an inverse correlation between fragile site (FS) expression and DSB repair protein levels. Upon DSB repair dysfunction, genes residing at these sites are at greater risk of deregulation compared to genes located at non-FS. In this regard, it remains enigmatic why the incidence of miRNA genes at FS is higher compared to non-FS. Herein, using bioinformatics, we examined whether miRNA genes localized at FS inhibit components of DSB repair pathways and assessed their effects on cancer. We show that such miRNAs over-accumulate in RFS, and that FRAXA, which is expressed in Fragile X syndrome, is a conserved hotspot for miRNAs inhibiting DSB repair. Axes of FRAXA-residing miRNAs/DSB repair targets affect survival in a cancer type-specific manner. Moreover, copy number variations in the region encompassing these miRNA genes discriminate survival between male and female patients. Given that, thus far, only CFS have been considered relevant for carcinogenesis, our data are the first to associate RFS with cancer, through the impairment of DSB repair by the FRAXA-residing miRNAs.
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PMID:MiRNAs Targeting Double Strand DNA Repair Pathways Lurk in Genomically Unstable Rare Fragile Sites and Determine Cancer Outcomes. 3226 Mar 17