Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0015674 (chronic fatigue syndrome)
2,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies have provided evidence supportive of the clinical importance of widespread pain in patients with chronic fatigue syndrome (CFS): pain severity may account for 26-34% of the variability in the CFS patient's activity limitations and participation restrictions. The etiology of widespread pain in CFS remains to be elucidated, but sensitisation of the central nervous system has been suggested to take part of CFS pathophysiology. It is hypothesised that a nitric oxide (NO)-dependent reduction in inhibitory activity of the central nervous system and consequent central sensitisation accounts for chronic widespread pain in CFS patients. In CFS patients, deregulation of the 2',5'-oligoadenylate synthetase/RNase L pathway is accompanied by activation of the protein kinase R enzyme. Activation of the protein kinase R and subsequent nuclear factor-kappaB activation might account for the increased production of NO, while infectious agents frequently associated with CFS (Coxsackie B virus, Epstein-Barr Virus, Mycoplasma) might initiate or accelerate this process. In addition, the evidence addressing behavioural changes in CFS patients fits the central sensitisation-hypothesis: catastrophizing, avoidance behaviour, and somatization may result in, or are initiated by sensitisation of the central nervous system.
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PMID:Pain in patients with chronic fatigue syndrome: does nitric oxide trigger central sensitisation? 1561 66

Hyperactivition of an unwanted cellular cascade by the immune-related protein RNase L has been linked to reduced exercise capacity in persons with chronic fatigue syndrome (CFS). This investigation compares exercise capacities of CFS patients with deregulation of the RNase L pathway and CFS patients with normal regulation, while controlling for potentially confounding gender effects. Thirty-five male and seventy-one female CFS patients performed graded exercise tests to voluntary exhaustion. Measures of peak VO2, peak heart rate, body mass index, perceived exertion, and respiratory quotient were entered into a two-way factorial analysis with gender and immune status as independent variables. A significant multivariate main effect was found for immune status (p < 0.01), with no gender effect or interaction. Follow-up analyses identified VO2(peak) as contributing most to the difference. These results implicate abnormal immune activity in the pathology of exercise intolerance in CFS and are consistent with a channelopathy involving oxidative stress and nitric oxide-related toxicity.
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PMID:Exercise capacity and immune function in male and female patients with chronic fatigue syndrome (CFS). 1579 2

A dysregulation in the 2',5'-oligoadenylate (2-5A)-dependent RNase L antiviral pathway has been detected in peripheral blood mononuclear cells (PBMC) of chronic fatigue syndrome (CFS) patients, which is characterized by upregulated 2-5A synthetase and RNase L activities, as well as by the presence of a low molecular weight (LMW) 2-5A-binding protein of 37-kDa related to RNase L. This truncated protein has been shown to originate from proteolytic cleavage of the native 83-kDa RNase L by m-calpain and human leukocyte elastase (HLE). We investigated the possible role of 2-5A oligomers in the proteolytic action toward the endonuclease and show that incubation of CFS PBMC extracts with 2-5A trimer and tetramer, but not with the dimer, results in a significant protection of the native 83-kDa RNase L against cleavage by endogenous and purified proteases. Similar results are obtained with a purified recombinant RNase L. An analysis of the size of 2-5A oligomers produced by the catalytic activity of the 2-5A synthetase present in PBMC extracts further shows that samples containing the 37-kDa RNase L preferentially produce 2-5A dimers instead of higher oligomers. Taken together, our results indicate that homodimerization of RNase L by 2-5A oligomers higher than the dimer prevents its cleavage by proteolytic enzymes. The presence of the truncated 37-kDa RNase L in PBMC extracts is therefore likely to result, not only from the abnormal activation of inflammatory proteases, but also from a dysregulation in 2-5A synthetase induction or activation towards the preferential production of 2-5A dimers.
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PMID:2',5'-Oligoadenylate size is critical to protect RNase L against proteolytic cleavage in chronic fatigue syndrome. 1592 78

This paper provides an overview of the evidence addressing the impairments of the 2'-5' oligoadenylate (2-5 A) synthetase/RNase L pathway in Chronic Fatigue Syndrome (CFS) patients. The 2-5A synthetase/RNase L pathway in CFS patients appears to be both up-regulated (i.e. increased levels of bioactive 2-5A synthetase and increased activity of the RNase L enzyme) and deregulated (elastase and calpain initiate 83 kDa RNase L proteolysis, generating two major fragments with molecular masses of 37 and 30 kDa, respectively). The deregulation of the 2-5A synthetase/RNase L pathway in CFS accompanies decreased NK-function and deregulation of apoptotic pathways. Since various components of the pathway appear to be related to performance during a graded exercise stress test, some evidence supportive of the clinical importance of the impaired pathway in CFS patients has been provided. Studies addressing the treatment of the deregulation of the 2-5A synthetase/RNase L pathway in CFS are warranted.
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PMID:Impairments of the 2-5A synthetase/RNase L pathway in chronic fatigue syndrome. 1627 15

This study examined possible interactions between immunological abnormalities and symptoms in CFS. Sixteen CFS patients filled in a battery of questionnaires, evaluating daily functioning, and underwent venous blood sampling, in order to analyse immunological abnormalities. Ribonuclease (RNase) L cleavage was associated with RNase L activity (rs=0.570; p=0.021), protein kinase R (PKR) (rs=0.716; p=0.002) and elastase activity (rs=0.500; p=0.049). RNase L activity was related to elastase (rs=0.547; p=0.028) and PKR activity (rs=0.625; p=0.010). RNase L activity (rs=0.535; p=0.033), elastase activity (rs=0.585; p=0.017) and RNase L cleavage (rs=0.521; p=0.038) correlated with daily functioning. This study suggests that in CFS patients an increase in elastase activity and subsequent RNase L cleavage is accompanied by increased activity of both the PKR and RNase L enzymes. RNase L and elastase activity are related to daily functioning, thus evidence supporting the clinical importance of these immune dysfunctions in CFS patients was provided.
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PMID:Unravelling intracellular immune dysfunctions in chronic fatigue syndrome: interactions between protein kinase R activity, RNase L cleavage and elastase activity, and their clinical relevance. 1839 93

Cancer and chronic fatigue syndrome (CFS) are both characterised by fatigue and severe disability. Besides fatigue, certain aspects of immune dysfunctions appear to be present in both illnesses. In this regard, a literature review of overlapping immune dysfunctions in CFS and cancer is provided. Special emphasis is given to the relationship between immune dysfunctions and fatigue. Abnormalities in ribonuclease (RNase) L and hyperactivation of nuclear factor kappa beta (NF-kappaB) are present in CFS and in prostate cancer. Malfunctioning of natural killer (NK) cells has long been recognised as an important factor in the development and reoccurrence of cancer, and has been documented repeatedly in CFS patients. The dysregulation of the RNase L pathway, hyperactive NF-kappaB leading to disturbed apoptotic mechanisms and oxidative stress or excessive nitric oxide, and low NK activity may play a role in the two diseases and in the physiopathology of the common symptom fatigue. However, in cancer the relation between the immune dysfunctions and fatigue has been poorly studied. Immunological abnormalities to such as a dysregulated RNase L pathway, hyperactive NF-kappaB, increased oxidative stress and reduced NK cytotoxicity, among others, are present in both diseases. These anomalies may be part of the physiopathology of some of the common complaints, such as fatigue. Further studies to confirm the hypotheses given here are warranted.
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PMID:Immunological similarities between cancer and chronic fatigue syndrome: the common link to fatigue? 2003 25

Xenotropic murine leukemia virus-related virus (XMRV) is a gamma retrovirus that has been associated with chronic fatigue syndrome (CFS) and prostate cancer. The search for viral causes of these syndromes was reignited by the finding that RNase L activity was low in hereditary prostate cancer and some CFS patients. The six strains of XMRV that have been sequenced have greater than 99% identity, indicating a new human infection rather than laboratory contamination. DNA, RNA, and proteins from XMRV have been detected in 50% to 67% of CFS patients and in about 3.7% of healthy controls. XMRV infections could be transmitted to permissive cell lines from CFS plasma, suggesting the potential for communicable and blood-borne spread of the virus and potentially CFS. This troubling concept is currently under intense evaluation. The most important steps now are to independently confirm the initial findings; develop reliable assays of biomarkers; and to move on to investigations of XMRV pathophysiology and treatment in CFS, prostate cancer, and potentially other virus-related syndromes, if they exist.
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PMID:Xenotropic murine leukemia virus-related virus in chronic fatigue syndrome and prostate cancer. 2042 7

There is a significant 'comorbidity' between depression and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Depressive symptoms frequently occur during the course of ME/CFS. Fatigue and somatic symptoms (F&S), like pain, muscle tension, and a flu-like malaise, are key components of depression. At the same time, depression and ME/CFS show major clinical differences, which allow to discriminate them with a 100% accuracy. This paper aims to review the shared pathways that underpin both disorders and the pathways that discriminate them. Numerous studies have shown that depression and ME/CFS are characterized by shared aberrations in inflammatory, oxidative and nitrosative (IO&NS) pathways, like systemic inflammation and its long-term sequels, including O&NS-induced damage to fatty acids, proteins and DNA; dysfunctional mitochondria; lowered antioxidant levels, like zinc and coenzyme Q10; autoimmune responses to neoepitopes formed by O&NS; lowered omega-3 polyunsaturated fatty acid levels; and increased translocation of gram-negative bacteria. Some IO&NS-related pathways, like the induction of indoleamine 2-3-dioxygenase, neurodegeneration and decreased neurogenesis, are more specific to depression, whereas other pathways, like the 2'-5' oligoadenylate synthetase/RNase L pathway, are specific to ME/CFS. Most current animal models of depression, e.g. those induced by cytokines, are not reminiscent of human depression but reflect a mixture of depressive and F&S symptoms. The latter symptoms, sometimes called sickness behavior, differ from depression and ME/CFS because the former is a (sub)acute response to infection-induced pro-inflammatory cytokines that aims to enhance recovery, whereas the latter are characterized by long-term sequels in multiple IO&NS pathways. Depression and ME/CFS are not 'comorbid' disorders, but should be regarded as 'co-associated disorders' that are clinical manifestations of shared pathways.
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PMID:An intriguing and hitherto unexplained co-occurrence: Depression and chronic fatigue syndrome are manifestations of shared inflammatory, oxidative and nitrosative (IO&NS) pathways. 2060 77

Xenotropic murine leukemia virus-related virus (XMRV) is a new human retrovirus originally identified in prostate cancer patients with a deficiency in the antiviral enzyme RNase L. XMRV has been detected with varying frequencies in cases of prostate cancer and chronic fatigue syndrome (CFS), as well as in a small proportion of healthy individuals. An etiologic link between XMRV infection and human disease, however, has yet to be established. Here, we summarize existing knowledge regarding the characteristics of XMRV replication, association of XMRV with prostate cancer and CFS, and potential mechanisms of XMRV pathophysiology. We also highlight several areas, such as the establishment of standardized assays and the development of animal models, as future directions to advance our current understanding of XMRV and its relevance to human disease.
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PMID:Biology and pathophysiology of the new human retrovirus XMRV and its association with human disease. 2071 43

Xenotropic murine leukemia virus-related virus (XMRV) was first reported in 2006 in a study of human prostate cancer patients with genetic variants of the antiviral enzyme, RNase L. Subsequent investigations in North America, Europe, Asia, and Africa have either observed or failed to detect XMRV in patients (prostate cancer, chronic fatigue syndrome-myalgic encephalomyelitis (CFS-ME), and immunosuppressed with respiratory tract infections) or normal, healthy, control individuals. The principal confounding factors are the near ubiquitous presence of mouse-derived reagents, antibodies and cells, and often XMRV itself, in laboratories. XMRV infects and replicates well in many human cell lines, but especially in certain prostate cancer cell lines. XMRV also traffics to prostate in a nonhuman primate model of infection. Here, we will review the discovery of XMRV and then focus on prostate cancer-related research involving this intriguing virus.
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PMID:XMRV Discovery and Prostate Cancer-Related Research. 2231 43


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