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)

Experiments were performed to determine how glycerol affects macromolecular syntheses and nucleoside triphosphate levels in a strain of Escherichia coli that lacks a functional sn-glycerol-3-phosphate dehydrogenase. The addition of glycerol to cultures of this strain, Lin 8, growing on a gluconeogenic carbon source causes immediate growth stasis (N. R. Cozzarelli, J. P. Koch, S. Hayashi, and E. C. C. Lin, J. Bacteriol. 90:1325-1329, 1965). Immediately after the addition of glycerol to cultures of Lin 8, the syntheses of DNA, RNA, and protein are completely inhibited. Phospholipid synthesis is not inhibited as severely by glycerol. The addition of glycerol to strain Lin 8 also results in a rapid decrease in its nucleoside triphosphate levels. The total intracellular concentration of ATP in strain Lin 8 was reduced by 85% within 30 s after the addition of glycerol. These results suggest that the glycerol-induced inhibition of growth and macromolecular syntheses may be a secondary consequence of the decreased energy supply in this strain. In addition, studies also suggest that phospholipid synthesis can continue (albeit at a reduced rate) under conditions of severe energy limitation.
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PMID:Changes in macromolecular synthesis and nucleoside triphosphate levels during glycerol-induced growth stasis of Escherichia coli. 36 98

Ten patients with chronic type B hepatitis were treated for four weeks with a rapidly tapered dose of oral prednisone (initial dose, 40 mg/d) followed by two weeks of no therapy followed by four weeks of oral acyclovir (600 mg/d). Liver biochemistry, HBsAg, HBeAg, DNA-polymerase and HBV-DNA levels in serum were determined prior to, during and for six months following therapy. The mean age +/- SD of the study population was 33 +/- 15 years (range 18-58). Nine of the patients were male. Four patients were Caucasian and six of Southeast Asian origin. Three patients were homosexual, all HIV antibody negative. The mean ALT level prior to treatment was 89 +/- 62 IU/L (range: 30-214). During the six month post-treatment follow-up period, 5/8 (63%) patients became DNA-P negative and 6/10 (60%) HBV-DNA negative. One responder reverted to DNA-P positive (final response, 50%) and another to HBV-DNA positive (final response, 50%) prior to completion of the study. Patients were more likely to become DNA-P or HBV-DNA negative if they had elevated pre-treatment ALT values and low levels of DNA-P and HBV-DNA. HBeAg became undetectable in 3/10 (30%) individuals, one of whom reverted to positive at the end of the follow-up period (final response, 20%). All patients remained HBsAg positive. Mild fatigue, which occurred in four individuals, was the most common side effect. The results of this study suggest that a controlled clinical trial of oral prednisone/acyclovir is warranted in the treatment of adults with chronic type B hepatitis.
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PMID:A pilot study of steroid withdrawal followed by oral acyclovir in the treatment of chronic type B hepatitis. 128 32

The application of recombinant DNA technology to the production of tumor necrosis factor has resulted in the availability of large quantities of a highly purified protein product. This product has been evaluated extensively in preclinical studies, which have documented a direct cytostatic and cytotoxic effect on human tumor cells, as well as a variety of immunomodulatory effects on various immune effector cells, including neutrophils, macrophages, and T cells. In addition, a number of anti-infective and metabolic effects have been documented. In addition to its in vitro effects, rTNF has been shown to have antitumor activity in vivo in preclinical studies involving both transplantable murine tumors and human tumor xenografts. Such observations have led to the evaluation of rTNF as a potential antineoplastic agent in humans. Both single- and multiple-dose phase I studies have confirmed that rTNF can be safely administered to patients with advanced malignancies in a dose range associated with anticancer effect without concomitant serious toxicities such as shock and cachexia. The most commonly observed clinical toxicities include constitutional symptoms, such as fever, chills, headache, and fatigue, and toxicities, which can be at least partially controlled with concomitant administration of nonsteroidal anti-inflammatory drugs, such as acetaminophen and meperidine. Hypotension, which occurs at high doses administered by short intravenous infusion, can usually be prevented by prehydration with intravenous fluids or otherwise controlled by the administration. An intense local inflammatory reaction at the injection site as well as thrombocytopenia appear to be the dose-limiting toxicities after subcutaneous and intramuscular administration. Neurologic toxicity is infrequent, except following continuous intravenous infusion, where it may manifest as transient focal neurologic deficits or seizure. Prolonged administration of rTNF at higher doses may be associated with transient, subclinical decreases in diffusing capacity. Patients with underlying cardiopulmonary disease should be excluded from rTNF therapy in future clinical studies until the end-organ toxicities of this agent are better defined. For at least one preparation of rTNF there appears to be no evidence for the formation of antibodies to rTNF in patients who receive multiple administrations of the agent. Pharmacokinetic studies have shown a relatively rapid clearance following intravenous infusion with a half-life of 15 to 30 min and dose-dependent pharmacokinetics. rTNF can be detected in the serum following intramuscular or subcutaneous injection at only relatively high doses, suggesting a decreased bioavailability with the routes of administration. Early phase I studies defined tolerable dose ranges for each route of administration and began to explore immunomodulatory and metabolic effects of rTNF.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Recombinant human TNF-alpha: preclinical studies and results from early clinical trials. 155 Aug 75

Human herpesvirus-6 (HHV-6) was first isolated in 1986 from peripheral blood leukocytes of patients with lymphoproliferative disorders. Although HHV-6 is distinct from the other human herpes viruses, DNA studies have revealed some genomic similarities with cytomegalovirus. It has recently become evident that up to 95% of older children and adults are HHV-6 seropositive. Infection is believed to occur early in life, after maternal antibody has waned. Up to 92% of healthy adults shed HHV-6 in saliva, and evidence indicates that this secretion is important in spread of the virus. In situ hybridization and immunochemical studies suggest that the salivary glands themselves may be the site of replication and persistence of HHV-6. There is good evidence that HHV-6 is causally linked to exanthema subitum, a common febrile disease of infants. Associations of HHV-6 with postviral fatigue syndrome, lymphoproliferative disorders and progression of AIDS have all been examined, but the evidence in these cases remains conflicting.
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PMID:Human herpesvirus-6: the latest human herpes virus. 166 30

Lean body mass, muscle biochemistry, enzymehistochemistry and muscle strength were analyzed before and after 10% and 18% body weight loss following gastroplasty in 16 obese patients. Subjective fatigue was also determined, using an arbitrary scale, before and after the operation. Lean body mass and alkali-soluble proteins (non-collagenic proteins) per DNA decreased significantly in the postoperative period. The proportions of type I and type II muscle fibers remained normal postoperatively. The muscle fiber area decreased significantly at 10% body weight loss, with a tendency towards restoration at 18% weight loss, despite continuing loss of lean body mass. Preoperatively the muscle strength, determined as maximum voluntary concentric and eccentric action of the knee extensor and flexor muscles, was not significantly different from that in sedentary, age-matched subjects, but was less than expected from the lean body mass, content of alkali-soluble proteins and muscle fiber size. Muscle strength was not significantly changed postoperatively. According to the fatigue scale, the patients' wellbeing was improved at 18% body weight loss compared with the preoperative status.
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PMID:The effect of excessive weight loss on skeletal muscle in man. A study of obese patients following gastroplasty. 167 49

The interferons (IFN) act too slowly to arrest acute viral infections, but interferon-alpha (IFN alpha) preparations have proved useful in some chronic infections and will clearly be used increasingly in these in the future. In the preparations derived from human leucocytes or cultured B lymphoblastoid cells, which are in routine clinical use, mixtures of a number of distinct subtypes of human IFN alpha have been identified. There are also 3 slightly different versions of the same single subtype, IFN alpha-2, made by recombinant DNA procedures in bacteria. IFN alpha preparations are injected intramuscularly or subcutaneously. Dose-related side effects are common but usually tolerable, but prolonged treatment may cause increasing fatigue and depression. Some patients form neutralising antibodies which block the effects of the IFN; these appear to be relatively more common after recombinant IFN alpha-2 than after IFN derived from human cells. Given intranasally, IFN alpha can prevent a subsequent experimental rhinovirus infection, or the spread of natural colds within a family. Repeated administration progressively damages the nasal mucosa, so that long term prophylaxis is not possible. IFN alpha has proved useful in patients with papillomavirus warts of the larynx, ano-genital region (condyloma acuminata) and skin (common warts). Treatment regimens remain to be optimised and are likely to include surgery or other treatments. IFN alpha and zidovudine (azidothymidine) synergistically inhibit the growth of HIV in vitro, and combination are on trial in patients with early AIDS. Very large doses of IFN alpha are effective against Kaposi's sarcoma in some AIDS patients. In chronic hepatitis B, continuing virus replication may lead to cirrhosis or primary liver cancer. Earlier clinical trials with IFN alpha gave inconclusive results, but recent large studies have confirmed that 25 to 40% of patients obtain benefit; this probably results from both the antiviral and the immunomodulatory effects of IFN alpha. In patients with chronic hepatitis C, the biochemical markers usually improve rapidly during IFN alpha administration, but relapse if treatment is stopped after only a few months; to increase the chances of sustained cure, the treatment period is now being prolonged.
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PMID:The use of interferon-alpha in virus infections. 172 72

A 49-year-old male with an 8 year history of lowered Hb level, granulocytopenia and fatigue presented in 1986 with progressive fatigue, a dramatically reduced Hb level (45 g/l) and an increased lymphocyte count (6.6 x 10(9)/l). Clinical picture and laboratory studies led to the diagnosis of chronic T lymphocytosis with expansion of CD8+ T cells expressing CD16 IgG Fc receptors (Fc gamma RIII). DNA analyzed with T-cell receptor (TcR) gamma and beta probes revealed extra rearranged bands representing a clonal expansion of T lymphocytes. These T lymphocytes expressed T-cell receptor alpha beta as evaluated by staining with monoclonal antibodies. Because of the severe progressive anemia the patient was transfused with packed red cells. He was then treated with cyclophosphamide. After one month of treatment the transfusions could be discontinued and two months later cyclophosphamide treatment was stopped because of normalized Hb level and lymphocyte counts. The patient remained in a hematologically stable condition, though a minor T-cell population representing the clonal expansion, an inverted CD4/CD8 ratio and low immunoglobulin levels persisted. This is the first report of regression of proven monoclonal CD8+ T gamma-cell expansion and the associated anemia following cyclophosphamide therapy. These observations implicate the expanded monoclonal CD8+ lymphocytes in the pathogenesis of the anemia and granulocytopenia.
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PMID:Remission of monoclonal chronic T-cell expansion associated with severe anemia. 176 65

Epstein-Barr viral infection, specifically infectious mononucleosis, typically has a more protracted course than other acute viral illnesses. Some recent observers have additionally suggested the possibility that Epstein-Barr virus (EBV) is the etiologic infectious agent in chronic fatigue syndrome, based on the finding of higher proportions of elevated antibodies to the EBV early antigen in some patients complaining of chronic fatigue. Straus et al reported on 23 patients with chronic fatigue, 83% of whom exhibited persistently elevated antibodies in modest titer to the early antigen. Ten of these patients had never fully recovered from an episode of acute infectious mononucleosis. Other studies had noted similar associations between persistently elevated antibodies to EBV-specific antigens and chronic symptoms in patients who presented with chronic symptoms after mononucleosis. Three important antigen complexes, demonstrable by immunofluorescence procedures, are expressed in EBV-infected cells. The early antigen is thought to function perhaps in early replication of viral DNA. A late antigenic complex, the viral capsid antigen, may represent, in addition to structural capsid proteins, components of the viral enzymatic machinery for late phases of replication or transformation. The Epstein-Barr nuclear antigen is felt to function in viral transformation of host cells.
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PMID:Infectious mononucleosis, Epstein-Barr virus, and chronic fatigue syndrome: a prospective case series. 202 31

Three siblings of a family affected with Leber's hereditary optic neuropathy (LHON) showed a mitochondrial DNA mutation at position 11778. The lactate response to a standardized effort was increased in only one case. Muscle biopsies and biochemistry of muscle and platelet mitochondrial enzymes were normal. All patients showed an altered energy metabolism during exercise and during recovery after exercise on phosphorus 31-magnetic resonance spectroscopy (31P-MRS) of muscle. Brain 31P-MRS showed a decreased energy reserve (decreased PCr/Pi ratio) in all patients. 31P-MRS noninvasively demonstrated an altered mitochondrial energy metabolism in muscle and, for the first time, in the brains of LHON patients.
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PMID:Leber's hereditary optic neuropathy: genetic, biochemical, and phosphorus magnetic resonance spectroscopy study in an Italian family. 186 7

Lymph nodes were examined from four patients with incipient adult T-cell leukemia-lymphoma (ATLL) who had mild lymphadenopathy, fatigue, no or a few atypical lymphocytes in their peripheral blood, and integrated proviral human T-cell lymphotrophic virus type I (HTLV-I) DNA in the nodes. The HTLV-I DNA was detected by southern blot analysis and/or polymerase chain reaction in the lymph nodes of all cases. The nodal architecture was preserved. Some scattered or aggregated highly lobular, cerebriform, or Reed-Sternberg-like giant cells were observed, with occasional mitoses and diffuse infiltration of small to medium-sized lymphocytes, with no or minimal nuclear abnormalities in the enlarged paracortex. The giant cells were usually positive for Ki-1 and also for UCHL-1 and other T-cell markers but negative for Ber-H2. Rearrangement and/or deletion of T-cell receptors were found in three of four patients. All patients died within 2 years, with transformation to overt leukemia-lymphoma occurring in three patients, and pulmonary carcinoma in one. The incipient or prelymphomatous phase of ATLL should be differentiated from Hodgkin's disease because of the distinctly different prognoses of these two diseases.
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PMID:Lymph nodes in incipient adult T-cell leukemia-lymphoma with Hodgkin's disease-like histologic features. 200 51


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