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)

Gulf War Syndrome (GWS) is a multisystemic illness afflicting many Gulf War-era veterans. The molecular pathological basis for GWS has not been established. We sought to determine whether the presence of antibodies to squalene correlates with the presence of signs and symptoms of GWS. Participants in this blinded cohort study were individuals immunized for service in Desert Shield/Desert Storm during 1990-1991. They included 144 Gulf War-era veterans or military employees (58 in the blinded study), 48 blood donors, 40 systemic lupus erythematosus patients, 34 silicone breast implant recipients, and 30 chronic fatigue syndrome patients. Serum antibodies to squalene were measured. In our small cohort, the substantial majority (95%) of overtly ill deployed GWS patients had antibodies to squalene. All (100%) GWS patients immunized for service in Desert Shield/Desert Storm who did not deploy, but had the same signs and symptoms as those who did deploy, had antibodies to squalene. In contrast, none (0%) of the deployed Persian Gulf veterans not showing signs and symptoms of GWS have antibodies to squalene. Neither patients with idiopathic autoimmune disease nor healthy controls had detectable serum antibodies to squalene. The majority of symptomatic GWS patients had serum antibodies to squalene.
Exp Mol Pathol 2000 Feb
PMID:Antibodies to squalene in Gulf War syndrome. 1064 Apr 54

The disturbance of the central nervous system and immunological abnormalities have been suggested in patients with chronic fatigue syndrome (CFS). We focused on immunological abnormalities against neurotransmitter receptors in CFS. Using a sensitive radioligand assay, we examined serum autoantibodies to recombinant human muscarinic cholinergic receptor 1 (CHRM1), mu-opioid receptor (OPRM1), 5-hydroxytryptamine receptor 1A (HTR1A), and dopamine receptor D2 (DRD2) in patients with CFS (n=60) and results were compared with those in patients with autoimmune disease (n=33) and in healthy controls (n=30). The mean anti-CHRM1 antibody index was significantly higher in patients with CFS (p<0.0001) and autoimmune disease (p<0.05) than that in healthy controls, and positive reaction was found in 53.3% of patients with CFS. Anti-OPRM1 antibodies, anti-HTR1A antibodies, and anti-DRD2 antibodies were found in 15.2, 1.7, and 5.0% of patients with CFS, respectively. Anti-nuclear antibodies were found in 56.7% (34/60) of patients with CFS, but anti-nuclear antibody titers did not correlate with the activities of the above four autoantibodies. The patients with positive autoantibodies to CHRM1 had a significantly higher mean score (1.81) of 'feeling of muscle weakness' than negative patients (1.18) among CFS patients (p<0.01). Higher scores on 'painful node', 'forgetfulness', and 'difficulty thinking' were also found in CFS patients with anti-CHRM1 antibodies but did not reach statistical significance. In conclusion, autoantibodies to CHRM1 were detected in a large number of CFS patients and were related to CFS symptoms. Our findings suggested that subgroups of CFS are associated with autoimmune abnormalities of CHRM1.
Int J Mol Med 2003 Aug
PMID:Autoantibodies against muscarinic cholinergic receptor in chronic fatigue syndrome. 1285 22

Protein carbonyl levels, a measure of protein oxidation, were found to be significantly elevated (p < 0.0005) in the sera of chronic fatigue syndrome (CFS) patients vs. controls. In contrast, the total protein levels in sera CFS patients were unchanged from those of controls. The elevated protein carbonyl levels confirm earlier reports suggesting that oxidative stress is associated with chronic fatigue syndrome and are consistent with a prediction of the elevated nitric oxide/peroxynitrite theory of chronic fatigue syndrome and related conditions.
Mol Cell Biochem 2003 Jun
PMID:Elevated levels of protein carbonyls in sera of chronic fatigue syndrome patients. 1287 Jun 59

We used differential-display PCR of peripheral blood mononuclear cells (PBMCs) to search for candidate biomarkers for chronic fatigue syndrome (CFS). PBMCs were collected from a subject with CFS and an age- and sex-matched control before and 24 h after exercise. RNA expression profiles were generated using 46 primer combinations, and the similarity between the individuals was striking. Differentially expressed bands were excised, reamplified, and sequenced, yielding 95 nonredundant sequences, of which 50 matched to known gene transcripts, 38 matched to genes with unknown functions, and 7 had no similarity to any database entry. Most (86%) of the differences between the two subjects were present at baseline. Differential expression of ten genes was verified by real-time reverse-transcription PCR: five (cystatin F, MHC class II, platelet factor 4, fetal brain expressed sequence tag, and perforin) were downregulated, and the remaining five genes (cathepsin B, DNA polymerase epsilon4, novel EST PBMC191MSt, heparanase precursor, and ORF2/L1 element) were upregulated in the subject with CFS. Many of these genes have known functions in defense and immunity, thus supporting prior suggestions of immune dysregulation in the pathogenesis of CFS. Differential-display PCR is a powerful tool for identification of candidate biomarkers. Investigation of these markers in samples from well-designed epidemiological studies of CFS will be required to determine the validity of these candidate biomarkers. The real-time reverse-transcription PCR assays that we developed for assay of these biomarkers will facilitate high-throughput testing of these additional samples.
J Mol Med (Berl) 2004 Nov
PMID:Differential-display PCR of peripheral blood for biomarker discovery in chronic fatigue syndrome. 1549 94

The year 1995 marked the onset of interstitial pneumonia spread in Nagoya, Japan. For the last 9 years, we have been accumulating clinical experience with the disease control using the combination of prophylactic use of anti-biotics and regular practice of megadose vitamin C infusion with either dehydroepiandrosterone-annex or dehydroepiandrosterone-cortisol annex. The purpose of this study is to assess the usefulness of our new treatment system for the control of interstitial pneumonia alias chronic fatigue syndrome. The results obtained are given as follows: i) The long-term maintenance of the above treatment system was effective not only for decreasing the risk for recurrence of active form pneumonia, but also for prevention of malignancy emergence in aged patients with interstitial pneumonia. ii) Evidence is presented to indicate that interstitial pneumonia was associated with increased risk for depression of which the emergence is a candidate subject causally related to the long-term use of glucocorticoid. iii) A patient with both interstitial pneumonia and depression was found to be less responsive to our treatment system. It is suggested that the use of more dehydroepiandrosterone at the sacrifice of cortisol in the infusion annex may be a choice for the control of both interstitial pneumonia and depression. iv) The description of chronic fatigue syndrome as regards the endocrinological, epidemiological and psychiatric characteristics are in good agreement with our experience on patients having interstitial pneumonia, evidence in support of our proposal that there is no convincing reasoning to separate chronic fatigue syndrome from interstitial pneumonia. v) The long-term practice of our treatment system for the control of interstitial pneumonia (an autoimmune disease) was found to suppress the inflammatory process but not the fibrotic process in the long run. vi) A few innovations were made in our treatment system to reduce the risk of bleeding or thrombosis--vascular complications of pneumonia. vii) The merit of our treatment system is to create a new hormonal environment to improve the state of immunodeficiency by use of a non-steroid substance--vitamin C which encounters little resistance from the feedback mechanism of steroid metabolism in the in vivo system.
Int J Mol Med 2005 Jan
PMID:The clinical course of interstitial pneumonia alias chronic fatigue syndrome under the control of megadose vitamin C infusion system with dehydroepiandrosterone-cortisol annex. 1558 36

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.
Exp Mol Pathol 2005 Jun
PMID:2',5'-Oligoadenylate size is critical to protect RNase L against proteolytic cleavage in chronic fatigue syndrome. 1592 78

Since the first mitochondrial dysfunction was described in the 1960s, the medicine has advanced in its understanding the role mitochondria play in health, disease, and aging. A wide range of seemingly unrelated disorders, such as schizophrenia, bipolar disease, dementia, Alzheimer's disease, epilepsy, migraine headaches, strokes, neuropathic pain, Parkinson's disease, ataxia, transient ischemic attack, cardiomyopathy, coronary artery disease, chronic fatigue syndrome, fibromyalgia, retinitis pigmentosa, diabetes, hepatitis C, and primary biliary cirrhosis, have underlying pathophysiological mechanisms in common, namely reactive oxygen species (ROS) production, the accumulation of mitochondrial DNA (mtDNA) damage, resulting in mitochondrial dysfunction. Antioxidant therapies hold promise for improving mitochondrial performance. Physicians seeking systematic treatments for their patients might consider testing urinary organic acids to determine how best to treat them. If in the next 50 years advances in mitochondrial treatments match the immense increase in knowledge about mitochondrial function that has occurred in the last 50 years, mitochondrial diseases and dysfunction will largely be a medical triumph.
Exp Mol Pathol 2007 Aug
PMID:Mitochondrial dysfunction and molecular pathways of disease. 1723 70

Chronic fatigue syndrome (CFS) is a clinically defined condition characterized by long-lasting disabling fatigue. Because of the unknown mechanism underlying this syndrome, there still is no specific biomarker for objective assessment of the pathological fatigue. We have compared gene expression profiles in peripheral blood between 11 drug-free patients with CFS and age- and sex-matched healthy subjects using a custom microarray carrying complementary DNA probes for 1,467 stress-responsive genes. We identified 12 genes whose mRNA levels were changed significantly in CFS patients. Of these 12 genes, quantitative real-time PCR validated the changes in 9 genes encoding granzyme in activated T or natural killer cells (GZMA), energy regulators (ATP5J2, COX5B, and DBI), proteasome subunits (PSMA3 and PSMA4), putative protein kinase c inhibitor (HINT ), GTPase (ARHC), and signal transducers and activators of transcription 5A (STAT5A). Next, we performed the same microarray analysis on 3 additional CFS patients and 20 other patients with the chief complaint of long-lasting fatigue related to other disorders (non-CFS patients) and found that the relative mRNA expression of 9 genes classified 79% (11/14) of CFS and 85% (17/20) of the non-CFS patients. Finally, real-time PCR measurements of the levels of the 9 involved mRNAs were done in another group of 18 CFS and 12 non-CFS patients. The expression pattern correctly classified 94% (17/18) of CFS and 92% (11/12) of non-CFS patients. Our results suggest that the defined gene cluster (9 genes) may be useful for detecting pathological responses in CFS patients and for differential diagnosis of this syndrome.
Mol Med
PMID:Identification of marker genes for differential diagnosis of chronic fatigue syndrome. 1859 70

Since the first mitochondrial dysfunction was described in the 1960s, the medicine has advanced in its understanding the role mitochondria play in health and disease. Damage to mitochondria is now understood to play a role in the pathogenesis of a wide range of seemingly unrelated disorders such as schizophrenia, bipolar disease, dementia, Alzheimer's disease, epilepsy, migraine headaches, strokes, neuropathic pain, Parkinson's disease, ataxia, transient ischemic attack, cardiomyopathy, coronary artery disease, chronic fatigue syndrome, fibromyalgia, retinitis pigmentosa, diabetes, hepatitis C, and primary biliary cirrhosis. Medications have now emerged as a major cause of mitochondrial damage, which may explain many adverse effects. All classes of psychotropic drugs have been documented to damage mitochondria, as have stain medications, analgesics such as acetaminophen, and many others. While targeted nutrient therapies using antioxidants or their precursors (e. g., N-acetylcysteine) hold promise for improving mitochondrial function, there are large gaps in our knowledge. The most rational approach is to understand the mechanisms underlying mitochondrial damage for specific medications and attempt to counteract their deleterious effects with nutritional therapies. This article reviews our basic understanding of how mitochondria function and how medications damage mitochondria to create their occasionally fatal adverse effects.
Mol Nutr Food Res 2008 Jul
PMID:Medication-induced mitochondrial damage and disease. 1862 87

Complement activation resulting in significant increases of C4a split product may be a marker of postexertional malaise in individuals with chronic fatigue syndrome (CFS). This study focused on identification of the transcriptional control that may contribute to the increased C4a in CFS subjects after exercise. We used quantitative reverse-transcription polymerase chain reaction to evaluate differential expression of genes in the classical and lectin pathways in peripheral blood mononuclear cells (PBMCs). Calibrated expression values were normalized to the internal reference gene peptidylpropyl isomerase B (PPIB), the external reference gene ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit (rbcL), or the geometric mean (GM) of the genes ribosomal protein, large, P0 (RPLP0) and phosphoglycerate kinase 1 (PGK1). All nine genes tested, except mannose-binding lectin 2 (MBL2), were expressed in PBMCs. At 1 hour postexercise, C4, mannan-binding lectin serine protease 2 (MASP2) and ficolin 1 (FCN1) transcripts were detected at higher levels (> or = 2-fold) in at least 50% (4 of 8) of CFS subjects and were detected in 88% (7 of 8) CFS subjects when subjects with overexpression of either C4 or MASP2 were combined. Only an increase in the MASP2 transcript was statistically significant (PPIB, P = 0.001; GM, P = 0.047; rbcL, P = 0.045). This result may be due to the significant but transient downregulation of MASP2 in control subjects (PPIB, P = 0.023; rbcL, P = 0.027). By 6 hours postexercise, MASP2 expression was similar in both groups. In conclusion, lectin pathway responded to exercise differentially in CFS than in control subjects. MASP2 down-regulation may act as an antiinflammatory acute-phase response in healthy subjects, whereas its elevated level may account for increased C4a and inflammation-mediated postexertional malaise in CFS subjects.
Mol Med
PMID:Transcriptional control of complement activation in an exercise model of chronic fatigue syndrome. 1901 37


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