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

Sixteen patients with advanced cancer were treated with recombinant-DNA-produced pure leukocyte A interferon (IFLrA) intramuscularly in doses ranging from 3 to 198 X 10(6) units. with interval periods of 72 to 96 hours between doses. At the two lowest doses of 3 and 9 million units, there was a cross-over evaluation between IFLrA and partially pure leukocyte interferon (IFN-C) produced from human cells. THe maximum observed serum concentration of IFLrA measured by enzyme immunoassay and bioassay increased with increasing doses. The mean serum concentrations of IFLrA and IFN-C were similar. Clinical effects produced by IFLrA and IFN-C were similar, including fever, chills, myalgias, headache fatigue, and reversible leukopenia and granulocytopenia. Eight patients had transient and mild numbness of the hands or feet, or both. Three patients developed low titers of antibody to IFLrA, Seven of 16 patients showed objective evidence of tumor regression during the study.
 ...
PMID:Recombinant leukocyte A interferon: pharmacokinetics, single-dose tolerance, and biologic effects in cancer patients. 617 59

Interferons have now been used in both prophylaxis and treatment of a number of human viral infections. The major action has been as a prophylactic for sites within the body that are not yet involved by disease. Such a prophylactic effect can be obtained early in the treatment of acute viral infection or even during chronic viral disease. Both local and systemic prophylaxis have been achieved with regard to both respiratory and herpesviral illness. In addition, Dane particle suppression can be achieved consistently with dosages of 10(6) units or greater daily to patients with chronic hepatitis B virus infection. In certain cases with prolonged therapy there can be permanent eradication. With leucocyte-derived material of approximately 10(6) or 10(7) units per milligram protein, the major side effects have been an initial febrile response, fatigue, malaise, marrow suppression, and inhibition of hair growth. So far, side effects have been rapidly reversible on lowering of dosage. Present studies with the use of lymphoblastoid interferon and bacterial-derived interferon employ materials of significantly greater specific activity. Such experience suggests that the same general side effects that were limiting with leucocyte interferon are present with interferon produced from recombinant DNA by bacterial as well as with lymphoblastoid interferon.
 ...
PMID:Interferons as antivirals in man. 618 84

Guaran, tragacanth, gum arabic, carrageenan, gum karaya, and methylcellulose were used in a long-term feeding study to evaluate their effects upon adaptive responses of nutritionally controlled parameters in rats by feeding a fiber-free diet containing increasing additions of polysaccharides. In general, supplements reduced weight increases due to lower energy intakes. Only in the case of microbiologically inert polysaccharides the dilution of the the energy density was partially compensated by an increased food intake. Neither of the polysaccharides fed, however, decreased energy utilization. All polysaccharides similarily increased small intestinal length up to about 30% without grossly altering mucosal protein and DNA per unit of length. Concerning their effects on the colon and the cecum, polysaccharides behaved differentially according to their accessibility to microbiological degradation. Inert polysaccharides exerted a more pronounced effect on the colon whereas the others mainly increased cecum weight. Degree and locus of the observed changes are determined mainly by the dietary concentration of the polysaccharides and their accessibility to bacterial degradation within the intestinal tract.
 ...
PMID:Long-term feeding of unavailable carbohydrate gelling agents. Influence of dietary concentration and microbiological degradation on adaptive responses in the rat. 626 17

Nineteen patients with advanced refractory metastatic breast cancer no longer responsive to chemotherapy were treated in the first phase II efficacy trial of recombinant leukocyte A interferon (IFL-rA), a highly purified single molecular species of alpha interferon prepared by recombinant DNA methods. Patients received a previously determined maximum tolerated dose for this agent (50 X 10(6) U/m2 body surface area) by intramuscular injection three times weekly for up to 3 months. The symptoms of toxicity observed in this trial resemble those previously reported for alpha interferons and include fever, chills, fatigue, anorexia, and leukopenia. All patients required dose reductions, most often for reasons of severe fatigue. Of the 17 patients evaluable for tumor response, one patient had stable disease and 16 had evidence of tumor progression. We conclude that IFL-rA is not an active agent in the treatment of advanced, refractory breast cancer when used at a maximum tolerated dose on this treatment schedule.
 ...
PMID:Recombinant leukocyte A interferon in advanced breast cancer. Results of a phase II efficacy trial. 634 90

PH is an uncommon manifestation of SLE. The symptoms of PH develop within a few years after the onset of the multisystem disease. The most common presenting complaints of SLE patients with PH are dyspnea on exertion, chest pain, nonproductive cough, edema, and fatigue or weakness. The important physical findings are a loud second pulmonic heart sound and a right ventricular lift. The chest roentgenogram shows a cardiomegaly, a prominent pulmonary segment, and usually clear lung fields. Pulmonary function tests may show evidence of restrictive lung disease; however, the physiologic abnormalities are mild and out of proportion to the severity of the PH. The diagnosis of PH is established by cardiac catheterization showing elevated pulmonary artery pressure, normal capillary wedge pressure, and no evidence of intracardiac or extracardiac shunts. Pathologic examination of the lung demonstrates angiomatoid lesions involving muscular pulmonary arteries. There is a thickening of the media and subintima of the arterioles. Immunoglobulin and complement deposits are found in the walls of pulmonary arteries. Immunoglobulin eluted from the lung contains rheumatoid factor and antinuclear antibody including antibody to DNA activity. DNA antigen is also present in walls of blood vessels. These results suggest an immune complex deposition process as a mechanism in the pathogenesis of PH in SLE. The clinical course of PH in SLE is variable. Symptoms may be mild and the disease follows a stable and protracted course for several years. It can, however, develop a progressive course ending in death in a few years. The clinical response of SLE patients with PH to treatment with high doses of systemic corticosteroids is not consistent or predictable.
 ...
PMID:Immunopathologic and clinical studies in pulmonary hypertension associated with systemic lupus erythematosus. 637

Mitochondrial myopathies are a clinical condition characterized by muscle weakness and fatigue in which the primary defect is localized at the level of the mitochondria. Microscopic examination shows accumulations of mitochondria at the fibre periphery (ragged red fibres) and in some cases mitochondrial paracrystalline inclusions. The spectrum of different mitochondrial defects so far described is reviewed and data from cases investigated in this laboratory are described. The first case was a 17-year-old boy with a multisystem disorder whose muscle mitochondria showed low respiratory activity with all substrates, which doubled in the presence of uncoupler. Further investigation showed that the mitochondrial ATPase activity was only 6% of normal. The next cases were a mother and daughter who showed a typical lipid storage myopathy. The latter was treated successfully with oral carnitine but the myopathy persisted. Mitochondrial investigations indicated a low respiratory activity with NAD-linked substrates but normal activity with succinate and ascorbate + TMPD. A defect in the NADH-CoQ reductase section of the respiratory chain was pinpointed possibly at an iron-sulphur centre. The fourth and fifth cases were two sisters who exhibited no lipid storage myopathy but whose mitochondrial activity was low with NAD-linked substrates but normal with succinate. Again a defect in the NADH-CoQ reductase (complex I) of the respiratory chain was determined. They were also investigated using 31P-NMR. It was found after exercise that their muscle creatine phosphate levels took seven times longer to return to pre-exercise concentrations than control subjects. These results are discussed with respect to the synthesis of mitochondrial proteins and the influence that both the mitochondrial and nuclear DNA have on this process.
 ...
PMID:Mitochondrial myopathies: disorders of the respiratory chain and oxidative phosphorylation. 643 47

Fifty-two patients with advanced cancer received sequentially escalating doses of 3 to 50 million units of recombinant DNA-produced alpha interferon by daily intramuscular injection. There were 23 patients with metastatic breast cancer, 17 patients with nodular poorly differentiated lymphocytic lymphoma, and 12 patients with multiple myeloma. Complete and partial remissions were obtained in 35 percent of patients with nodular poorly differentiated lymphoma, whereas rare activity was found in breast cancer and multiple myeloma. Dose-limiting toxicity occurred in patients receiving 36 million units or more and consisted of fatigue/asthenia, weight loss, and elevation of transaminase levels, requiring frequent interruption, reduction in dose, or cessation of treatment. Hematologic toxicity was rarely a limiting factor, but myelosuppression was severe in some patients with multiple myeloma. All toxicities were reversible on discontinuation of treatment. Antibodies to recombinant leukocyte A interferon were seen infrequently but may adversely affect therapy.
 ...
PMID:Collaborative phase I-II study of recombinant DNA-produced leukocyte interferon (clone A) in metastatic breast cancer, malignant lymphoma, and multiple myeloma. 654 79

Golden hamsters fed a high-fat diet do not overeat, but they become obese because of decreases in energy expenditure. This decrease in actual energy expenditure is accompanied by increases in thermogenic capacity and brown adipose tissue mass, protein content, and DNA content. Three experiments examined this phenomenon in more detail. Experiment 1 demonstrated that this form of dietary obesity is largely reversible simply by returning the animals to a high-carbohydrate chow diet. However, the obesity which develops solely because of decreased energy expenditure is reversed primarily by decreased energy intake. In this respect fat-fed hamsters resemble tube-fed rats. Experiment 2 revealed that the effects of high-fat diet are at least as robust in female hamsters as in males. Experiment 3 examined the interactions between diet and photoperiod. Short days (10 hr light per 24 hr) had almost no effect on male hamsters fed Purina chow. However, nearly all of the effects of the high-fat diet (i.e., increases in body weight gain, feed efficiency, carcass energy content, percent ingested energy stored in the carcass, carcass lipid content, brown adipose tissue protein, and brown adipose tissue DNA) were exaggerated in hamsters housed in short days. High-fat-diet-induced increases in metabolic efficiency and thermogenic capacity may be of value in readying hamsters for winter. Furthermore, as winter approaches, decreasing day length might synergize with changes in diet quality to promote these beneficial changes in energy metabolism. Finally, fat-fed hamsters could be a useful animal model of some kinds of human obesity.
 ...
PMID:Dietary obesity in golden hamsters: reversibility and effects of sex and photoperiod. 683 36

Ellipticine and some derivatives are highly cytotoxic substances which kill L1210 cells at concentrations ranging form 10(-8) to 10(-6)M. Some compounds in this series bind with high affinity to DNA (affinity constant between 10(7) M-1 and 10(5) M-1) by intercalation between base pairs. The antitumoral properties of these derivatives are thought to be related to their DNA-binding ability. Both 9-hydroxylation of ellipticine and quaternarization of 2-pyridinic nitrogen tend to increase DNA binding and antitumor activity. 2-Methyl-9-hydroxyellipticine (NSC 264-137) was selected for a phase I and later for a phase II trial in human cancer. This drug does not affect blood cell counts in animals or in man. It is not mutagenic in the Ames' test nor teratogenic in mice, but is endowed with anti-inflammatory properties and induces a marked decrease of motoricity in mice. Transient bradycardia and decrease of blood pressure are the most noticeable cardiovascular effects in dogs. This compound administered at 80-100 mg/m2/week in 1-h intravenous (IV) infusion induces objective remissions in about 25% of patients suffering from advanced breast cancer refractory to all other treatment. These remissions, which occurred after 3-4 weeks, lasted for 1-18 months. This drug seems particularly to improve the condition of patients suffering from oesteolytic breast cancer metastasis. Activity against anaplastic thyroid carcinoma and ovarian carcinoma has also been observed in some cases. Toxic side effects are nausea and vomiting (one-third of the patients), hypertension (less than 10% of the patients), muscular cramp (one-third of the patients), fatigue which can be very pronounced (in most patients after 3 months of treatment), mouth dryness, and mycosis of the tongue and esophagus (less than 20% of the patients).
 ...
PMID:Antitumor activity, pharmacology, and toxicity of ellipticines, ellipticinium, and 9-hydroxy derivatives: preliminary clinical trials of 2-methyl-9-hydroxy ellipticinium (NSC 264-137). 700 58

Chronic toxicity studies of fenofibrate were carried out in rats (3 months), dogs (7 et 24 months) and Rhesus monkeys (12 months). The results in the last named species (78 animals) were of particular interest, since the treated monkeys had normal size liver without histological abnormalities. Electron microscopy showed no increase in the number of hepatic peroxisomes. Long-term toxicity studies in rats failed to show any increase in the incidence of altered hepatocytes or of neoplastic tumours in treated animals. However, a few peroxisomes were found in animals receiving the highest doses of fenofibrate. In reproduction studies there was no evidence of teratogenic effects in rats with doses 45 times higher than the human dose, nor in rabbits with doses of 300 mg/kg/day. In mutagenicity studies fenofibrate proved unable to bind with DNA and could not, therefore, have any effect on genes. The side-effects encountered in clinical practice (e.g. digestive disorders, sexual fatigue, myalgia, alopecia) were rare and obliged to discontinue treatment in very few cases. Long-term clinical trials failed to demonstrate any fenofibrate-induced pathology, such as malignant or benign tumours, or biliary or urinary lithiasis. Serum transaminases were increased in 10 to 20% of the patients, but the rise was transient and never reached pathological levels. Electron microscope study of liver biopsies from patients treated with fenofibrate showed no proliferation of peroxisomes.
 ...
PMID:[Fenofibrate: animal toxicology in relation to side-effects in man (author's transl)]. 720 40


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>