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)

Chronic fatigue syndrome (CFS) is characterized by idiopathic fatigue of greater than 6 months' duration with postexertional exacerbation and many other symptoms. A trend toward relative hypocortisolism is described in CFS. Twin and family studies indicate a substantial genetic etiologic component to CFS. Recently, severe corticosteroid-binding globulin (CBG) gene mutations have been associated with CFS in isolated kindreds. Human leukocyte elastase, an enzyme important in CBG catabolism at inflammatory sites, is reported to be elevated in CFS. We hypothesized that CBG gene polymorphisms may act as a genetic risk factor for CFS. A total of 248 patients with CFS defined by Centers for Disease Control criteria, and 248 controls were recruited. Sequencing and restriction enzyme testing of the CBG gene coding region allowed detection of severe CBG gene mutations and a common exon 3 polymorphism (c.825G-->T, Ala-Ser224). Plasma CBG levels were measured in 125 CFS patients and 198 controls by radioimmunoassay. Total and free (calculated and measured) cortisol levels were ascertained in single samples between 8-10 a.m. The age of onset (mid 30s) and gender ratio (2.2:1, female:male) of the patients were similar to those reported in U.S. epidemiologic studies. A trend toward a preponderance of serine224 homozygosity among the CFS patients was noted, compared with controls (chi2 = 5.31, P = 0.07). Immunoreactive-CBG (IR-CBG) levels were higher in Serine/Alanine (Ser/Ala) than Ala/Ala subjects and higher again in Ser/Ser subjects, this effect was strongest in controls; Ser/Ser: 46.1+/-1.8 (n = 31, P = 0.03) vs. Ser/Ala: 42.4+/-1.0 (n = 56, P = 0.05) vs. Ala/Ala: 40.8+/-1.7 microg/mL (n = 21). Despite higher CBG levels, there was a nonsignificant trend toward lower total and free plasma cortisol in serine allele positive patients, total cortisol: Ser/Ser: 13.3+/-1.4 (n = 34) vs. Ser/Ala: 14.0+/-0.7 (n = 66) vs. Ala/Ala: 15.4+/-1.0 (n = 23). Homozygosity for the serine allele of the CBG gene may predispose to CFS, perhaps due to an effect on hypothalamic-pituitary-adrenal axis function related to altered CBG-cortisol transport function or immune-cortisol interactions.
...
PMID:Association between chronic fatigue syndrome and the corticosteroid-binding globulin gene ALA SER224 polymorphism. 1555 58

Previous work by others have suggested the occurrence of one or more chemical or metabolic 'markers' for ME/CFS including specific amino acids and organic acids and a number of unidentified compounds (CFSUM1, CFSUM2). We have shown elsewhere that CFSUM1 is partially derivatised pyroglutamic acid and CFSUM2 partially derivatised serine and have suggested and demonstrated that the analytical methods used were unsuitable to identify or to accurately quantify urinary metabolites. We have now made a detailed analysis of plasma and urinary amino acids and of urinary organic acids from patients with ME/CFS and from three control groups. Fasting blood plasma and timed urine samples were obtained from 31 patients with CFS, 31 age and sex-matched healthy controls, 15 patients with depression and 22 patients with rheumatoid arthritis. Plasma and urinary amino acids and urinary organic acids were determined using established and validated methods and data compared by statistical analysis. None of the previously reported abnormalities in urinary amino acids or of organic acids could be confirmed. Results however provide some evidence in patients with ME/CFS for underlying inflammatory disease and for reduced intramuscular collagen with a lowered threshold for muscle micro-injury. These factors in combination may provide a basis for the fatigue and muscle pain that are the major symptoms in these patients.
...
PMID:Urinary and plasma organic acids and amino acids in chronic fatigue syndrome. 1599 88

McGregor et al. reported increased levels of an unidentified urinary compound (CFSUM1) in patients with chronic fatigue syndrome (CFS), with reduced excretion of another unidentified compound (CFSUM2), and suggested the possibility of chemical or metabolic 'markers' for CFS. The identity of CFSUM1 as reported was erroneous and the identities of these compounds have remained unknown until now. Urine samples were obtained from 30 patients with ME/CFS, 30 age- and sex-matched healthy controls, 20 control patients with depression and 22 control patients with rheumatoid arthritis. Samples were prepared using the published methods of McGregor et al. to produce heptafluorobutyryl-isobutyl derivatives of urinary metabolites. Alternative preparations utilised isopropyl, n-butyl and trifluoroacetyl derivatives. These were separated and identified using gas chromatography-mass spectrometry. CFSUM2 was identified as being partially derivatised [isobutyl ester-mono-heptafluorobutyryl (HFB)] serine. CFSUM1 was identified as partially derivatised pyroglutamic acid, being the isobutyl ester without formation of a HFB derivative. Both CFSUM1 and CFSUM2 are artefacts of the sample preparation procedure and previously reported quantitative abnormalities of CFSUM1 and CFSUM2 in urine from patients with ME/CFS are also artefactual. Pyroglutamic acid may be of primarily dietary origin. The methods used cannot provide reliable qualitative or quantitative data on urinary metabolites. No clinical or biochemical significance can be drawn between these compounds in ME/CFS or any other clinical conditions.
...
PMID:CFSUM1 and CFSUM2 in urine from patients with chronic fatigue syndrome are methodological artefacts. 1609 85

This study examined 328 CFS sera in a study with 17 CCFP, 8 Gulf War Veterans (GWV), 24 Prostate Cancer (PC), and 52 normal sera in the modified Membrane Immunobead Assay (MIA) procedure for CTX. Three hundred and twenty-eight CFS patients' sera were examined by the modified MIA with purified MAb-CTX and 91.2% gave a titre > or =1:40. 76% of the 17 CCFP sera samples and 100% of the 8 GWV sera samples also had a titre > or =1:40. 92.3% of 52 normal sera showed titres of 1:20 or less, while 4 gave titres of > or =1:40. In addition, 41 sera were examined for Anti-Cardiolipin (aCL) by a commercial ELISA procedure with 87.8% demonstrating IgM, IgM+IgA, or IgM+IgG aCL antibodies. These results showed mostly the IgM aCL antibody alone in the sera samples. In addition, 41 serum samples were examined for aCL, with 37 showing positive for aCL, representing 90.2% positive for the three disease categories examined: CFS, CCFP and GWV. Examination for antiMitochondrial-M2 autoantibody (aM-M2) in 28 patients (CFS (18), CCFP (5), and GWV (5)) was negative for aM-M2. Inhibition analysis with antigens, CTX, CFS "Acute Phase Lipids", commercial Cardiolipin (CL) and 1,2-Dipalmitoyl-sn-Glycero-3-[Phospho-L-Serine] (PS) and antibodies, MAb-CTX and aCL from patients' serum show that the phospholipids in CL and CTX are antigenically indistinguishable with antibodies MAb-CTX and CFS-aCL. Preliminary chemical analyses have shown the lipids to be phospholipids associated with CL of the mitochondria. We designate this "Acute Phase Lipid" comparable to "Acute Phase Proteins" (C-reactive protein (CRP) and Serum Amyloid A (SAA)) in inflammatory conditions.
...
PMID:Acute phase phospholipids related to the cardiolipin of mitochondria in the sera of patients with chronic fatigue syndrome (CFS), chronic Ciguatera fish poisoning (CCFP), and other diseases attributed to chemicals, Gulf War, and marine toxins. 1834 9

Streptomyces exfoliatus CFS 1068, an isolate of cultivated field soil, produced maximum collagenase activity (58.19 +/- 0.83 U ml-1 min-1) in 5 days when soybean meal and starch were used as nitrogen and carbon sources, respectively at pH 7 and 30 degrees C in shake cultures (150 rpm). Production of collagenase was higher (40.43 +/- 0.63 U ml(-1) min(-1)) when poultry feathers were used as nitrogen source. Thus, the strain was found to be of biotechnological importance. The purified enzyme showed 30.34 fold increase in collagenase activity and was stable at 70 degrees C for 1h. The enzyme was found to be of serine type.
...
PMID:Production and partial characterization of collagenase of Streptomyces exfoliatus CFS 1068 using poultry feather. 2045 27

A metabolomics approach was used to explore the effects of Panax quinquefolius (PQ) and Acorus gramineus (AG) on learning and memory in rats with diabetic-induced cognitive impairment. Thirty Wistar rats were divided into three groups, namely the normal-group, model-group, and Panax quinquefolius-Acorus gramineus-group (PQ-AG-group, 1.80g/kg/d). Diabetes was induced by intraperitoneal injection of streptozotocin (STZ, 65mg/kg). Cerebrospinal fluid (CSF) was collected via cisterna magna puncture, and the Morris water maze method was used to evaluate learning and memory in rats after 11 weeks of PQ-AG treatment. Metabolic profiling of CFS samples wasperformed by using UPLC-Q-TOF-MS. Compared to the normal-group, the escape latency of the Morris water mazewas significantly prolonged in model-group rats after 12 weeks (p<0.01). Compared with the model-group, however, the escape latency was significantly shortened in PQ-AG-group rats (p<0.05). In multivariate statistical analysis, we identified 33 potential biomarkers, and six biomarkers were alteredby PQ-AG. These biomarkers were involved in the metabolism of pyrimidine; nicotinate and nicotinamide; glycine, serine, and threonine; and ascorbate and aldarate. Taken collectively, our results indicate that PQ-AG can attenuate diabetic-induced cognitive impairment by affecting a variety of metabolic pathways. Our results provide an experimental basis for studying the mechanism of action of PQ-AG.
...
PMID:Metabolomics study of cerebrospinal fluid from diabetic rats with cognitive impairment simultaneously treated with Panax quinquefolius and Acorus gramineus. 3327 56