Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Deficiency of complex I (reduced nicotinamide adenine dinucleotide dehydrogenase-ubiquinone oxidoreductase) of the mitochondrial respiratory chain may be seen as a pure myopathy or as a neuromuscular disorder at presentation. Efficacy of long- term therapy for these disorders is yet to be established. We report the case of a female patient with complex I deficiency and skeletal myopathy, who has had a sustained clinical response to riboflavin during 3 years of therapy. Molecular studies found no mutations in the putative flavin mononucleotide binding site in the 51 kd subunit of complex I, but a T-to-C transition at nucleotide 3250 in the mitochondrial DNA tRNA(Leu(UUR)) gene was identified. This mutation has been reported in one other family in that five members had fatigue with or without muscle weakness. There were also five cases of unexplained infant deaths in that family and two cases in the family reported here. Riboflavin therapy should be attempted in all patients with complex I deficiency when the clinical presentation is one of isolated skeletal myopathy.
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PMID:Mitochondrial myopathy with tRNA(Leu(UUR)) mutation and complex I deficiency responsive to riboflavin. 900 64

DNA from Epstein-Barr virus (EBV) Types A, B and Herpesvirus-6 (HHV-6) Variants A and B was detected by the Polymerase chain reaction (PCR) in the saliva of 51 non-immunocompromised donor patients and in the blood of seventy non-immunocompromised donor patients with specific signs and symptoms. The minimum selection criteria for each patient included acute or recurrent upper respiratory infection, unilateral thoracolumbar muscle spasm and fatigue. PCR DNA detection in the saliva of selected donors revealed 80% of the donors had either Type A or B EBV (41 of 51), 34.1% Type B EBV only (14 of 41), 9% Type A only (4 of 41), and 56.1% Type A and B EBV (23 of 41). HHV-6 DNA was detected in 45.0% (23 of 51). PCR for EBV in blood of selected donors revealed 68.5% Type A or B EBV (48 of 70), 0% type B EBV alone, 64.8% Type A EBV only (31 of 48) and 35.4% both Type A and B EBV (17 of 48). HHV-6 was detected in 96.4% (64 of 70). The association of Type B EBV in the pathogenesis of these patients is explored based on the PCR quantitation of B type EBV DNA present in the samples.
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PMID:Epstein-Barr virus (herpesvirus 4) types A, B and herpesvirus-6 variants A and B in patients presenting with recurrent upper respiratory inflammation, persistent paravertebral thoraco-lumbar muscle spasm and fatigue by polymerase chain reaction (PCR). 906 69

Between 1971 and 1989 we have treated 19 patients with hepatitis-associated aplastic anemia by marrow transplantation from their HLA-identical siblings following conditioning with 200 mg/kg cyclophosphamide (Cy) administered over a period of 4 days. One patient failed to engraft by day 34 and was given a second transplantation. He died from infection 15 days after the second transplantation. Eighteen patients had sustained engraftment. Six patients developed acute graft-vs.-host disease (GVHD) and two of these patients died 2.8 and 3.3 months after transplantation. Fifteen patients are surviving 4 to 24 (median 13) years after transplantation, while one patient died in a car accident 17 years after successful transplantation. Six of the surviving patients developed chronic GVHD. Two of the patients with chronic GVHD had preceding acute GVHD and four did not. Five of the six patients with chronic GVHD received donor buffy coat cells in addition to the marrow inoculum to prevent graft rejection. Twelve of the 15 surviving patients have Karnofsky performance scores of 100%. One patient, living more than 4 years after transplantation, has a Karnofsky score of 40% because of persistent cognitive deficits following non-A, non-B hepatitis with hepatic coma. Two patients developed hepatitis C infection 12 and 18 years after transplantation, respectively. Except for mild fatigue and mildly elevated liver function tests, these patients are doing well with Karnofsky performance scores between 95 and 100%. One patient developed severe coronary artery disease 10 years after transplantation, decreasing his Karnofsky performance score to 80%. Serum samples before and after transplantation from 13 patients were tested for hepatitis B virus (HBV) DNA and hepatitis C virus (HCV) RNA by polymerase chain reaction (PCR). Only one patient tested positive for HCV RNA before transplantation. Seven of 15 sera were hepatitis C RNA-positive posttransplantation, but only one of these patients has developed active hepatitis C. All 13 patients were were negative for hepatitis B surface antigen and HBV DNA. Only one patient had IgM antibodies against hepatitis A virus (HAV) before transplantation, which suggested HAV infection. Hepatitis-associated aplastic anemia apparently was caused in most patients by a non-A, non-B, non-C agent. HLA-identical marrow transplantation for hepatitis-associated aplastic anemia with Cy as conditioning regimen is well-tolerated and has a long-term event-free survival in excess of 80%, not different from results of marrow transplantations for aplastic anemia of other etiologies.
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PMID:Marrow transplantation for hepatitis-associated aplastic anemia: a follow-up of long-term survivors. 911 4

In patients with Lyme neuroborreliosis, inflammation and symptoms of fatigue and malaise occur out of proportion to the relatively low number of spirochetes present. Previous studies have identified interleukin-6 (IL-6) as a candidate molecule for amplification of CNS inflammation in this disease. We pursued this possibility by measuring cytokine gene expression by reverse-transcriptase polymerase chain reaction (RT-PCR) in the brain of rhesus macaques actively infected with Borrelia burgdorferi. Samples of brain tissue were screened for IL-6 and interferon gamma using RT-PCR-ELISA, a technique that uses RT-PCR, subsequent hybridization of the PCR product with a biotinylated probe, and capture and ELISA readout of hybridization product. The number of copies in positive samples was then quantitated using qRT-PCR-ELISA, in which wild-type cytokine cDNA competes with recombinant competitor DNA in the PCR. Elevated levels of IL-6 cDNA and, to a lesser extent, interferon gamma were detected in three of three nonhuman primates with persistent infection with B burgdorferi, whereas the brains of three uninfected animals and undetectable levels of gene expression of these cytokines. These data support the hypothesis that cytokines such as IL-6 are important amplification molecules for CNS inflammation in Lyme neuroborreliosis.
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PMID:Interleukin-6 is expressed at high levels in the CNS in Lyme neuroborreliosis. 922 83

Although a number of reports have now described an association between polymorphism of the LMP2 gene and disease phenotype in HLA-B27 positive individuals with ankylosing spondylitis (AS), some describe associations with acute anterior uveitis, others with juvenile onset disease, and one report provides no association. A recent study describes yet a further association with disease severity in patients with juvenile rheumatoid arthritis. We therefore hypothesized that the discrepant findings in adult disease may be a reflection of an underlying association with disease severity. Our study population consisted of 100 HLA-B27 positive Caucasians with AS of ten or more years duration. Clinical assessment of disease severity was based on a metrology index scoring five measurements, the modified health assessment questionnaire for the spondyloarthropathies, and a disease activity index consisting of a visual analog scale to score the amount of pain, stiffness and fatigue. LMP2 genotypes were assigned following polymerase chain reaction amplification from genomic DNA and restriction enzyme digestion with CfoI. Despite confirmation of a significantly higher prevalence of the LMP2 BB genotype in AAU positive (66.0%) versus AAU negative (45.2%) patients (P < 0.05), we observed no association between LMP2 genotypes and any of the indices of disease severity. Furthermore, although a significant association was noted between the presence of peripheral synovitis and the functional index score (P < 0.05), a history of AAU was not associated with more severe disease. Our data is thus internally consistent in demonstrating no association between LMP2 genotypes and either disease severity or peripheral arthritis, and supports the notion that polymorphism of LMP2 primarily influences the development of AAU and not some other phenotype of AS.
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PMID:Polymorphism of the LMP2 gene and disease phenotype in ankylosing spondylitis: no association with disease severity. 934 40

Two mitochondrion-specific fluorochromes, 10-N-nonyl acridine orange (NAO) and rhodamine 123 (Rh123), were used to determine the mechanism responsible for alterations in energy metabolism of transformed rat embryo fibroblast cells isolated from different locations within multicellular spheroids. Accumulation of Rh123 depends on intact mitochondrial membrane potential, whereas NAO is taken up by mitochondria independently of their function and thus represents mitochondrial distribution only. A reproducible selective dissociation procedure was used to isolate cells from different locations within the spheroids. After isolation, cells were simultaneously stained with one mitochondrial stain and the DNA dye Hoechst 33342, and several parameters, including cell volume, were monitored via multilaser-multiparameter flow cytometry. Our data clearly show a decrease in the uptake of Rh123 in cells from the periphery to the inner regions of the tumor spheroids, reflecting a persistent alteration in mitochondrial function. However, NAO staining experiments showed no reduction in the total mitochondrial mass per unit cell volume. Because cells were exposed to stain under uniform conditions after isolation from the spheroid, these data indicate the downregulation of mitochondrial function is associated with cell quiescence rather than a transient effect of reduced nutrient availability. This result, which is in accordance with data from two other cell lines (EMT6 and 9L), might reflect a general phenomenon in multicellular spheroids, supporting the hypothesis that quiescent cells in the innermost viable spheroid layer stably reduce their mitochondrial function, presumably to compensate for lower nutrient supply and/or decreased energy demand.
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PMID:Mitochondrial function in oncogene-transfected rat fibroblasts isolated from multicellular spheroids. 937 33

A 79-year-old woman was admitted with general fatigue, jaundice and hepatosplenomegaly. Perpheral blood examination showed 8.0 g/dl Hb, 15 x 10(3)/microliter platelet and 10,490/microliter leukocytes with 86% abnormal lymphocytes. Immunophenotypic analysis of abnormal lymphocytes demonstrated CD2(+), CD3(+/-), CD4(-), and CD8(-). Serum antibody for HTLV-1 was positive. In addition, the monoclonal integration of HTLV-1 proviral DNA into the genome of leukemic cells was demonstrated on Southern blot hybridization. Bone marrow revealed ATL cell in vasion with myelofibrosis and hemophagocytic cell proliferation. Therefore, adult T-cell leukemia with hemophagocytic syndrome was diagnosed. She was treated with methyl prednisolone pulse therapy and gammaglobulin. But she died of hepatic failure 14 days after hospitalization. On autopsy, EB virus LMP-1 was detected in ATL cells in bone marrow. ATL with hemophagocytosis is relatively rare. The association of both pathological states was discussed.
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PMID:[Double negative adult T-cell leukemia with hemophagocytic syndrome]. 942 38

A benign, transient proliferation of atypical lymphocytes and a monoclonal rearrangement of the T-cell receptor beta (TRB) locus was found in a 60-year-old woman who presented with low-grade fever, anorexia and fatigue. A marked and transient atypical lymphocytosis (white blood cell count 90.5 x 10(9)/l) with CD8 surface antigen improved without specific treatment. Although tests for IgM antibodies to hepatitis A, varicella zoster, Epstein-Barr virus (EBV), and cytomegalovirus (CMV) were all negative, a monoclonal gene rearrangement of TRB locus was observed in the DNA of the proliferated atypical lymphocytes by Southern blotting. The clonal rearrangement and the atypical lymphocytes disappeared after 14 d, and the patient has remained well for 7 years. These results suggest that monoclonal proliferation of CD8 lymphocytes can occur based on a non-neoplastic aetiology.
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PMID:Transient appearance of CD3+CD8+ T lymphocytes with monoclonal gene rearrangement of T-cell receptor beta locus. 948 37

Reactive oxygen species, including free radicals, are produced through a number of biochemical reactions, often as a consequence of aerobic metabolism. A system of antioxidant enzymes and scavenger substrates provides protection of membrane lipids, proteins, and DNA. An imbalance between production of reactive oxygen species and antioxidant protection results in "oxidative stress." Oxidative stress is believed to contribute to numerous pathological conditions including atherosclerosis, obstructive lung disease, aging, and fatigue of skeletal muscles including the diaphragm. Strenuous exercise, inflammation, infection, obstructive lung diseases, etc. increase exposure of the diaphragm to reactive oxygen species. Emerging data indicate that reactive oxygen species alter diaphragm contractions primarily in response to low-frequency stimulation. The response of the diaphragm is profoundly influenced by the degree of oxidative stress, fatigue state, glutathione status, and age. Exercise training results in an upregulation of antioxidant enzyme activities in the diaphragm and thus could provide additional protection against oxidative stress.
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PMID:Oxidative stress, antioxidant status, and the contracting diaphragm. 949 38

T-tubules of skeletal muscle fibres easily transform into large vacuoles under the influence of various factors. These include osmotic shock produced by the efflux of small molecular weight molecules (e.g. glycerol), hypertonic shock, muscle fatigue and muscle damage. In most cases, vacuolation is reversible but the molecular mechanisms involved are not clear. Also, the functional role of reversible vacuolation has not been established. However, three possibilities may be considered. (1) Redistribution of ions and water between the cytoplasm and the extracellular space comprised by the T-system. Thus, the formation of large vacuoles may be a mechanisms for rapid osmoregulation that corresponds to regulated volume decrease in other types of cell. However, in our hands, inhibitors of various pathways that participate in volume regulation had no effect on reversible vacuolation. (2) Resealing of mechanical damage of the plasma membrane. This is usually accompanied by the development near the damaged membrane of numerous vacuoles which we have observed by confocal microscopy and use of a hydrophobic dye (RH414), to arise in part from T-tubules. (3) By confocal microscopy, it has also been shown that extracellular fluorescein dextran (Mr = 10,000), and both plasmid DNA (pUC18) and sonicated high molecular weight DNA stained with YOYO, enter vacuoles derived from T-tubules. This finding may indicate that reversible vacuolation, in the absence of membrane damage, could provide a pathway from the extracellular environment to the cytoplasm that is additional or complimentary to endocytosis; it may also be particularly relevant to the ability of muscle to be transfected by the direct injection of DNA. These several observations strongly indicate that the function of the T-system in skeletal muscle fibers is not restricted to excitation-contraction coupling.
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PMID:[Functional role of vacuolization of the T-system of skeletal muscle fibers]. 950 35


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