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)

The study was carried out in 89 men aged 21 to 57 years with a history of exposure to mercury vapour from 2 to 26 years during occupational work involving chlorine production by the method of mercury electrolysis. The workers were divided into three groups depending on the duration of occupational exposure: 1) 32 workers with a short history of exposure 2-10 years, 2) 37 workers with medium-long exposure - 11-20 years, and 3) 20 workers with a history of long exposure - 21-26 years. The urinary concentrations of mercury in these individuals was 73 +/- 60 microliters x 1(-1), and in blood this concentration was not exceeding 50 microliters x 1(-1). The control group comprised 40 men aged 17 to 52 years. They had not had any occupational exposure to chemicals, or harmful physical factors. On the basis of clinical, haematological and biochemical studies 89 workers with occupational exposure to mercury vapour were regarded as clinically healthy. None of them had any symptoms and signs of the complete neurasthenic syndrome or organic brain injury. Increased nervous excitability was the complaint of 24 workers, 9 had headaches, sleep disturbances were reported by 5, and a feeling of tiredness and apathy was mentioned by 5 men. EEG recording demonstrated 81 normal tracings, and moderately pathological records in 8 men. The parameters of immunity and proteins acute phase reaction were determined, measuring the concentration of immunoglobulins, lysozyme, C3c, C4, alpha 1-acid glycoprotein, haptoglobin and ceruloplasmin in serum. A lower level of IgA, IgG and lysozyme was only noted in individuals with occupational exposure exceeding 20 years.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Parameters of immunity acute phase reaction in men in relation to exposure duration to mercury vapours. 172 75

In a phase I trial 34 patients with pancreatic cancer were treated with the murine monoclonal antibody (MAb) BW 494 (BI 51.011) directed against a glycoprotein antigen. The patients received repeated doses of MAb over a time period from 5 to 14 days (highest single dose 100 mg, highest cumulative dose 490 mg). During this treatment serum levels of murine IgG increased to 43.4 micrograms/ml. The serum half life of murine IgG ranged from 2 to 3 days. Repeated injections of MAb BW 494 were normally well-tolerated when given within the first 15 days. Two patients presented with fatigue and a neuritis-like syndrome 2 weeks after the last IgG infusion which had resolved spontaneously by the next day. Severe allergic reactions were observed in 3 patients after repeated injections of the MAb. These 3 patients had high levels of human anti-murine antibodies (HAMA). Four weeks after the first application of MAb BW 494, 17/18 patients presented with HAMA (IgG). It could be demonstrated that the anti-murine response was in part anti-idiotypic. At the moment 16/34 patients are eligible for evaluation of tumor response. There was no complete or partial remission; however, 2 patients responded with minor tumor regression up to 32 weeks documented by reduction of liver metastases and primary tumor in CAT scan. Five additional patients presented with a long period of stable disease after immunotherapy (up to 40 weeks). Nine patients had progressive tumor disease in spite of MAb treatment.
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PMID:Immunotherapy of pancreatic cancer with monoclonal antibody BW 494. 316 51

High-dose chemotherapy is increasingly accepted as a treatment approach in a number of tumour types. However, there are controversies surrounding its efficacy and there is a need to consider its safety. In view of this, much effort has been directed towards the provision of adequate supportive care strategies to prevent toxicities and to ameliorate myelosuppression. Severe anaemia and its associated symptoms, for example, fatigue can have a debilitating effect on a patient's quality of life and often necessitates red blood cell transfusions. Erythropoietin, a glycoprotein hormone which stimulates red blood cell production, has been established for the treatment of anaemia in patients with chronic renal insufficiency. It is currently approved in most countries for treating anaemia associated with cancer, and its role is emerging especially in patients undergoing high-dose chemotherapy. This paper gives an overview of the studies conducted to date with epoetin alfa (recombinant human erythropoietin) in patients receiving allogeneic and autologous bone marrow transplants or peripheral blood stem cells in conjunction with high-dose chemotherapy. In addition, there are some novel clinical applications for epoetin alfa: for example, in delayed anaemia, as a supportive strategy prior to high-dose chemotherapy and as a synergistic enhancer of blood progenitor cell mobilisation in combination with granulocyte-colony-stimulating factor (G-CSF).
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PMID:Haematological toxicities associated with dose-intensive chemotherapy, the role for and use of recombinant growth factors. 934 59

A 47-year-old woman was admitted to our hospital for evaluation of general fatigue and dyspnea. She had been diagnosed with progressive systemic sclerosis (PSS) when she was 39 years of age, on the basis of Raynaud's phenomenon, proximal sclerosis, and pigmentation of the skin. On admission, her blood pressure was 206/128 mmHg. Funduscopy revealed grade III (Keith & Wagener) hypertensive retinopathy. Laboratory data showed positivity for anti-nuclear antibody and anticardiolipin beta 2 glycoprotein I antibody, and the plasma level of renin activity (PRA) was abnormally high. Chest X-ray and UCG revealed massive pericardial effusion. On the second hospital day, she was operated on for pericardiodiaphragmatic fenestration. The volume of pericardial effusion amounted to more than 2000 ml. Post operative malignant hypertension persisted. Laboratory data showed thrombocytopenia, hemolytic anemia, and acute renal failure. We diagnosed scleroderma renal crisis (SRC) associated with antiphospholipid syndrome. Following the initiation of angiotensin converting enzyme inhibitor (ACE-I) combined with calcium antagonist and alpha-one blocker, her blood pressure and PRA decreased. She also had been treated with aspirin 81 mg daily. These therapies were effective in recovering the platelet count and stopped the progression of anemia and renal failure. Although either the finding of large pericardial effusion or SRC is associated with poor prognosis in PSS, this case has had a good clinical course. In this case, the findings suggested that anti-phospholipid antibody may have contributed to the pericarditis and SRC.
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PMID:[A case of scleroderma renal crisis with massive pericardial effusion and positivity on antiphospholipid antibody test]. 965 14

Human herpesvirus 8 (HHV-8) is a recently discovered gammaherpesvirus that is the etiologic agent of Kaposi sarcoma (KS). The natural history of primary HHV-8 infection, including clinical outcome and host immune responses that may be important in preventing disease related to HHV-8, has not been elucidated. The present study characterized the clinical, immunologic, and virologic parameters of primary HHV-8 infection in 5 cases detected during a 15-year longitudinal study of 108 human immunodeficiency virus type 1 seronegative men in the Multicenter AIDS Cohort Study. Primary HHV-8 infection was associated with mild, nonspecific signs and symptoms of diarrhea, fatigue, localized rash, and lymphadenopathy. There were no alterations in numbers of CD4(+) or CD8(+) T cells or CD8(+) T-cell interferon gamma (IFN-gamma) production to mitogen or nominal antigen. CD8(+) cytotoxic T-lymphocyte precursor (CTLp) and IFN-gamma reactivity were detected during primary HHV-8 infection, with broad specificity to 5 lytic cycle proteins of HHV-8 encoded by open reading frame 8 (ORF 8; glycoprotein B homolog of Epstein-Barr virus), ORF 22 (gH homolog), ORF 25 (major capsid protein homolog), ORF 26 (a minor capsid protein homolog), or ORF 57 (an early protein homolog), in association with increases in serum antibody titers and appearance of HHV-8 DNA in blood mononuclear cells. CD8(+) T-cell responses to HHV-8 decreased by 2 to 3 years after primary infection. This antiviral T-cell response may control initial HHV-8 infection and prevent development of disease.
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PMID:Primary human herpesvirus 8 infection generates a broadly specific CD8(+) T-cell response to viral lytic cycle proteins. 1129 May 99

Corticosteroid-binding globulin is a 383-amino acid glycoprotein that serves a hormone transport role and may have functions related to the stress response and inflammation. We describe a 39-member Italian-Australian family with a novel complete loss of function (null) mutation of the corticosteroid-binding globulin gene. A second, previously described, mutation (Lyon) segregated independently in the same kindred. The novel exon 2 mutation led to a premature termination codon corresponding to residue -12 of the procorticosteroid-binding globulin molecule (c.121G-->A). Among 32 family members there were 3 null homozygotes, 19 null heterozygotes, 2 compound heterozygotes, 3 Lyon heterozygotes, and 5 individuals without corticosteroid-binding globulin mutations. Plasma immunoreactive corticosteroid-binding globulin was undetectable in null homozygotes, and mean corticosteroid-binding globulin levels were reduced by approximately 50% at 18.7 +/- 1.3 microg/ml (reference range, 30-52 microg/ml) in null heterozygotes. Morning total plasma cortisol levels were less than 1.8 microg/dl in homozygotes and were positively correlated to the plasma corticosteroid-binding globulin level in heterozygotes. Homozygotes and heterozygote null mutation subjects had a high prevalence of hypotension and fatigue. Among 19 adults with the null mutation, the systolic blood pressure z-score was 12.1 +/- 3.5; 11 of 19 subjects (54%) had a systolic blood pressure below the third percentile. The mean diastolic blood pressure z-score was 18.1 +/- 3.4; 8 of 19 subjects (42%) had a diastolic blood pressure z-score below 10. Idiopathic chronic fatigue was present in 12 of 14 adult null heterozygote subjects (86%) and in 2 of 3 null homozygotes. Five cases met the Centers for Disease Control criteria for chronic fatigue syndrome. Fatigue questionnaires revealed scores of 25.1 +/- 2.5 in 18 adults with the mutation vs. 4.2 +/- 1.5 in 23 healthy controls (P < 0.0001). Compound heterozygosity for both mutations resulted in plasma cortisol levels comparable to those in null homozygotes. Abnormal corticosteroid-binding globulin concentrations or binding affinity may lead to the misdiagnosis of isolated ACTH deficiency. The mechanism of the association between fatigue and relative hypotension is not established by these studies. As idiopathic fatigue disorders are associated with relatively low plasma cortisol, abnormalities of corticosteroid-binding globulin may be pathogenic.
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PMID:Familial corticosteroid-binding globulin deficiency due to a novel null mutation: association with fatigue and relative hypotension. 1150 97

Atypical depression, somatoform disorder, neurasthenia and fibromyalgia seem to form a spectrum of disorders, who share a common biological basis, i.e. a reduced activity of the hypothalamus-pituitary-adrenocortical (HPA)-system. This is similar to the situation in Cushing's disease, where the central part of the hypothalamus-pituitary-adrenocortical-system is decreased by an increased feedback via increased intracerebral cortisol concentration. Cushing's disease is accompanied by features of atypical depression and of somatisation. Treatment with hypericum seems to disinhibit the hypothalamus-pituitary-adrenocortical-system in healthy subjects and patients with a depression. Furthermore it decreases intracerebral corticosteroids, possibly by increasing the expression of p-glycoprotein at the blood brain barrier. Therefore hypericum might be especially effective in patients with a symptom cluster of atypical depressive features and somatisation. Clinical studies with patients with depression with atypical features like the seasonal affective disorder (SAD) and with patients with a depressive syndrome accompanied by somatic complaints or fatigue support this view.
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PMID:[Atypical depression and related illnesses--neurobiological principles for their treatment with Hypericum extract]. 1224 86

In renal failure, severe anemia and associated fatigue, cognitive and sexual dysfunction have a significant impact on the patient's quality of life. Anemia has also been identified as an important etiologic factor in the development of left ventricular hypertrophy. The major cause of anemia in presence of a reduction of glomerular filtration rate is an inadequate production of a glycoprotein hormone, the erythropoietin (EPO). EPO is the primary regulator of the growth and survival of erythroid progenitor. The introduction of recombinant human erythropoietin (rHuEPO) has revolutionized the treatment of anemia in chronic renal failure. The vast majority of patients respond very well to treatment, but 5-10% of patients show some resistance to EPO, the most common cause of which is iron deficiency. Several studies are recently commenced to investigate the effects of preventing renal anemia ever developing. The target of hemoglobin concentration in pre-dialysis and dialysis patients are object of continuous re-examinations.
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PMID:Anemia in renal insufficiency. 1273 11

Hashimoto's thyroiditis and membranous nephropathy are believed to be mediated by immune mechanisms. A 12 year-old patient is reported who presented with fatigue, dislike of cold, pallor and growth retardation. Initial laboratory assessment showed moderate proteinuria and impaired renal function (serum creatinine 2.3 mg/dl), and hypothyroidism due to autoimmune thyroiditis. Light, immunofluorescence and electron microscopy of the renal biopsy showed membranous nephropathy. The patient recovered from nephropathy after substitution of thyroid hormone and therapy with prednisone. Megalin can be envisaged as a potential pathogenetic link between the two disease entities. The glycoprotein megalin is expressed on thyroid cells in a TSH-dependent manner and may have a crucial role in the immunopathogenesis of glomerular injury in membranous nephropathy. For similar cases, we want to encourage colleagues to consider this hypothesis and to examine blood and renal biopsy specimens for the presence of megalin and antibodies against it.
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PMID:Autoimmune thyroiditis in association with membranous nephropathy. 1496 28

Ectopic production of biologically active glycoprotein hormones other than hCG has been reported in exceptional cases. A 61-yr-old man came to our Unit complaining of weakness, fatigue and reduced libido with erectile dysfunction. There was also a history of polycythemia, known for about 10 yr and never further investigated. The physical examination showed acne and redness of facial skin and upper chest; no other significant abnormalities were detected. Serum levels of LH were very high, whereas alpha-subunit and hCG were only slightly increased. Testosterone and 17beta-estradiol levels were increased too. Abdominal computed tomography (CT) scan revealed a large hypervascularized mass within the pancreatic tail, which was surgically removed by distal splenopancreatectomy. Diffuse immunoreactivity for LH was detected in more than 70% of the tumor cells. The alpha-subunit was also positive, while chorionic gonadotropin had only a focal reactivity. Reverse transcriptase-polymerase chain reaction (RT-PCR) and Southern Blot analysis confirmed the synthesis of LH by the tumor. Four weeks after surgery, serum levels of LH, alpha-subunit, testosterone, hCG and 17beta-estradiol were all undetectable. The redness of facial skin and upper chest had disappeared, but libido was still reduced. At a further control, 3 months after surgery, serum levels of LH, FSH, hCG, alpha-subunit and 17beta-estradiol were all within the normal range, as well as hemoglobin concentration and the red blood cells count. Testosterone was slightly below normal, but the patient reported an increase of libido. This is an unusual case of ectopic secretion of LH from an endocrine tumor of the pancreas.
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PMID:Ectopic secretion of LH by an endocrine pancreatic tumor. 1523 57


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