Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1762617 (weakness)
 37,932 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

2'-Chloro-2,4-dinitro-5',6-di(trifluoromethyl)diphenylamine (CDTD) is a potent uncoupler of oxidative phosphorylation in isolated rat liver or brain mitochondria. The concentration of CDTD causing 50% uncoupling in vitro is dependent on the mitochdonrial protein concentration and is 2 nM at 0.9 mg protein/ml for rat liver mitochondria. Oxidative phosphorylation can be restored to CDTD uncoupled liver mitochondria by the addition of a 10 000-fold molar excess of bovine serum albumin to DCTD. Rats given a lethal dose (7.0 mumol/kg) of CDTD intrapertioneally show signs of toxicity typical of uncoupling agents. Mitochondria isolated from the livers of these rats show almost complete inhibition of ATP synthesis and mitochondria obtained from the livers of rats at various times after a single oral dose show maximal inhibition of ATP synthesis 4 h after dosing with complete recovery by about 24 h. A single oral administration of 58 mumol/kg or above, but not intraperitoneal injection, of CDTD into rats produced an increase in the water content of the brain and spinal cord. The additional fluid has been shown to contain Na+ ions. The increase in cerebral fluid is dose related, no effect being seen at 23 mumol/kg. This extra fluid is thought to be responsible for the hind limb weakness observed in these rats. These observations suggest that there are two facets to CDTD toxicity: early deaths (within 2 h), which appear to be due to uncoupling of oxidative phosphorylation, and delayed deaths, 2--3 days after dosing which are probably related to an increase in fluid in the brain and spinal cord.
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PMID:Toxic action of 2'-chloro-2,4-dinitro-5',6-di(trifluoromethyl) diphenylamine in the rat. 49 64

Forty-three patients who had sepsis and multiple organ failure (critical illness) were studied prospectively to determine the incidence and severity of peripheral nerve function and to correlate such function with a number of variables. Electrophysiologic studies indicated a primary axonal degeneration of motor and sensory fibers in 30 (70 percent). Fifteen (30 percent) had the clinical signs of difficulty in weaning from assisted ventilation, weakness of limb muscles, and reduced or absent deep tendon reflexes. Full recovery from the polyneuropathy occurred among the 23 (53 percent) who survived, except three who had a very severe polyneuropathy. A peripheral nerve function index, computed from electrophysiologic measurements, showed statistically significant (p less than 0.01) negative correlations with the time in the critical care unit, and the serum glucose value; the serum albumin level showed a positive correlation. Multiple regression analyses indicated all three factors accounted for 47 percent (r2 = 0.4678) of all potential variables. In a separate analysis, the nerve function index correlated with the amplitude of the diaphragm compound muscle action potential (p less than 0.01). The results were consistent with the polyneuropathy being due to the same mechanisms that are currently postulated to cause dysfunction in this syndrome of other organ systems (including the neuromuscular respiratory system).
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PMID:Peripheral nerve function in sepsis and multiple organ failure. 184 61

CB6 (Balb/c x C57Bl/6 F1) and C57Bl/6 (B6) mice were hyperimmunized with Torpedo acetylcholine receptor (AChR) for 7 months. Control groups were hyperimmunized with bovine serum albumin. Antibody titers against Torpedo AChR rose quickly, reaching plateau levels by 3-4 months, while antibody to mouse AChR lagged by a few months, reaching plateau levels in 5 months. After the last immunization the mice maintained a state of stable autoimmunity for 9 months with high levels of antibodies against Torpedo and mouse AChR. Fatigability was measured on a programmable treadmill and remained present through the 9 months after the last immunization. CB6 mice had less weakness than the B6 mice, but the latter strain when immunized with BSA had more "false-positive" weakness. Titers of antibodies did not correlate with the degree of weakness measured on the treadmill. Despite the weakness and the high titers of anti-AChR antibodies, sera from myasthenic mice, in contrast to sera from myasthenic humans, were not able to block bungarotoxin binding to native AChR on the surface of BC3H1 cells.
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PMID:Chronic murine experimental myasthenia gravis: strength testing and serology. 202 92

Advanced emphysema with bronchitis is associated with significant weight loss and malnutrition, the true cause of which has not been clearly identified. The purpose of this exploratory study was to compare plasma amino acids and related compounds and catecholamines in a group of patients with advanced end-stage emphysema with a control group of similar age and sex in an effort to further understand this malnourished state. Fasting blood samples were obtained by venipuncture after a rest period. Plasma amino acid levels were determined by ion exchange high pressure liquid chromatography with fluorometric detection. Plasma catecholamines were determined by radioenzymatic analysis. Anthropometric measurements, the usually accepted biochemical markers of nutrition, dietary analysis, pulmonary function tests, and a historical analysis of the state of health including drug use and smoking history in each subject were analyzed. Ages and heights were comparable, whereas weights were significantly decreased in the patients with emphysema. Total serum protein and serum albumin values were significantly lower in the patient group. Significant respiratory muscle weakness was indicated by reduced negative inspiratory force in these end-stage patients, contrasting with well-preserved muscle strength usually found in obstructive lung disease. The dietary caloric intake of the patients was comparable to that of the control subjects. We conclude that the fine balance of the amino acid pool in patients with bronchitis and emphysema is well preserved, except for significant elevations of aspartic acid, glutamine, and cystine, and a decreased level of leucine. In addition, norepinephrine levels were significantly increased. Weight loss in patients with emphysema and bronchitis is likely due to increased energy demands related to hypermetabolism.
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PMID:The nutritional status in advanced emphysema associated with chronic bronchitis. A study of amino acid and catecholamine levels. 232 54

Region 65-102 of the myelin basic protein (MBP) houses a number of antigenic determinants known to induce delayed-type hypersensitivity, experimental allergic encephalomyelitis (EAE), suppressor cell function, and antibodies. In this report we describe the biological activity of synthetic peptides S53, S55, and S49 with sequence homology to region 69-84 of the rat, guinea pig, and bovine MBP. Peptide S53-A, defined by residues 75-84 of the guinea pig (SQRSQDEN) and of the rat (SQRTQDEN) MBP induced clinical signs of disease in Lewis rats. These included weight loss, flaccid tail, "muscle wasting," and hind-leg weakness. Histological examination of brain, spinal cord, and sciatic nerve sections of diseased rats revealed the complete absence of focal and perivascular lymphocytic infiltrates characteristics of demyelinating EAE lesions. Elongation of peptide S53 by three or six residues to residue sequences naturally found at its N-terminal end gave rise to peptides S55S (PQKSQRSQDEN) and S49S (GSLPQKSQRSDQDEN), respectively. Lewis rats challenged with either S55S or S49S developed classical clinical and histological signs of EAE. Severe hind-leg paralysis was accompanied by incontinence and sometimes death. Injected in the form of carrier-free peptide, S53 was a meager B cell immunogen. S53 conjugated with methylated-bovine serum albumin was also a potent immunogen and produced clinical signs of disease without CNS pathology. By comparison, carrier-free S55S and S49S were potent immunogens giving rise to antibodies that cross reacted completely and competitively with S55S but considerably less so with S53. The results show that the sequence of S53 defines an epitope responsible for the formation of anti-S53 antibodies. Elongation of the S53 sequence at its N-terminal end generated an additional epitope which induced cell-mediated immunity responsible for the concomitant development of pathological signs of EAE. It may be concluded that the induction of classical signs of EAE requires specific and defined sequences capable of expressing both B cell and T cell functions.
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PMID:Biological activity of region 65-102 of the myelin basic protein. 243 Jan 4

The antiarrhythmic agent amiodarone is associated with numerous adverse effects, but clinically significant liver disease is rare. A patient is described who presented with muscle weakness, hepatomegaly, and ascites following 28 months of amiodarone usage. His condition deteriorated despite discontinuation of amiodarone therapy. A postmortem liver biopsy demonstrated necrosis, fibrosis, hyalin, and phospholipid-laden lysosomal lamellar bodies. Resolution of hepatic dysfunction may not necessarily occur on withdrawal of amiodarone if irreversible damage is already established. We speculate as to the reasons for the reportedly low incidence of overt liver disease, and suggest that hepatic enzyme levels, as well as other indicators of hepatic function, such as the serum albumin concentration, be monitored indefinitely in all patients while taking amiodarone.
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PMID:Fatal amiodarone hepatoxicity. 334 40

Plasma exchange has been reported to be efficacious in chronic inflammatory demyelinating polyradiculoneuropathy. We performed a prospective double-blind trial in which patients with static or worsening disease were randomly assigned to plasma exchange (n = 15) or to sham exchange (n = 14) for three weeks. After three weeks, we observed statistically significant differences in combined measurements of nerve conduction (total, motor, proximal, velocity, and amplitude) favoring patients who had received plasma exchange. Improvement to a greater degree than for any patient receiving sham exchange was detected in the neurologic-disability score in five patients (P = 0.025) and in subset scores for weakness and reflex in four patients (P less than 0.057). We conclude that for some patients with chronic inflammatory demyelinating polyradiculoneuropathy, plasma exchange has an ameliorating effect on neurologic dysfunction and nerve conduction, but in others no improvement is observed. Because plasma was replaced with normal serum albumin, a humoral factor or factors may have a role in the neurologic deficit of this disorder.
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PMID:Plasma exchange in chronic inflammatory demyelinating polyradiculoneuropathy. 351 82

trans-3,3'-Bis[alpha-(trimethylammonio)methyl]azobenzene bromide (BisQ) is a potent agonist of the acetylcholine receptor (AcChoR) of Electrophorus electricus. BisQ is highly constrained, suggesting that its structure is complementary to the combining site of the AcChoR when the latter is in its activated state. Antibodies produced in rabbits to a conjugate of bovine serum albumin and a derivative of BisQ mimicked the binding characteristics of the AcChoR with respect to the order of binding of a variety of agonists and to the preferred recognition of decamethonium ion (an agonist) over hexamethonium ion (an antagonist). Immunization of three rabbits with purified anti-BisQ yielded antisera having binding characteristics of anti-AcChoR in that, by complement fixation and enzyme immunoassay, crossreactions with receptor preparations from rat, Torpedo, and eel could be demonstrated in sera of all three rabbits immunized. Two of the three rabbits showed signs of muscle weakness similar to that seen after immunization with the AcChoR. One of the rabbits was injected intramuscularly with neostigmine and showed temporary improvement. Another showed post-tetanic exhaustion of hind-limb muscles after stimulation of the sciatic nerve at 50 Hz. Antibodies reactive with the AcChoR, therefore, were elicited by immunization with an antibody to a potent ligand of the AcChoR without the necessity of isolating the receptor itself. A similar mechanism may play a part in the etiology of at least some autoimmune diseases in which antibodies to various other receptors are involved.
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PMID:Anti-idiotypic route to anti-acetylcholine receptor antibodies and experimental myasthenia gravis. 618 15

Plasma tryptophan (Trp) concentration in its total (TTrp) and non-protein-bound free form (FTrp) and its metabolite 5-hydroxyindole-3-acetic acid (5-HIAA) as well as muscle Trp contents (MTrp) were studied in 12 uraemic patients undergoing continuous ambulatory peritoneal dialysis (CAPD), 10 renal transplant patients, and 10 healthy control subjects. The CAPD patients exhibited signs of muscle weakness, as assessed by dynamometry, and signs of protein malnutrition with a decreased ratio of alkali-soluble protein relative to DNA in muscle as well as low serum albumin concentration. In the uraemic patients TTrp was markedly reduced, whereas in the transplant patients it did not differ from the controls. The FTrp, which was separated by the process of equilibrium dialysis, was less in the uraemic (P < 0.01) as well as transplant patients (P < 0.01) than in the controls. The plasma FTrp/TTrp ratio was increased in the uraemic patients (40 +/- 8%) but less in the transplant patients (16 +/- 4%), as compared to the controls (25 +/- 5%). The uraemic patients had increased plasma concentrations of 5-HIAA, whereas this metabolite could not be found in the plasma of renal transplant patients and healthy controls. MTrp was increased by an average of 33% in the uraemic patients whereas it did not differ between the transplant patients and the controls. The results indicate that the abnormal Trp metabolism in uraemic patients is to a large extent corrected by a successful renal transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tryptophan and its metabolites in patients on continuous ambulatory peritoneal dialysis and following renal transplantation. 752 76

Inspiratory muscle weakness has been demonstrated in ambulatory, stable chronic heart failure (CHF) and may contribute to dyspnea during daily living. However, the mechanisms underlying this weakness are unknown. Malnutrition and electrolyte depletion are recognized complications of CHF that may impair skeletal muscle function, and limb muscle weakness and myopathic changes have also been demonstrated in CHF. We examined whether nutrition and electrolyte status contribute to the reduced skeletal muscle strength and whether inspiratory muscle weakness in CHF is part of general skeletal muscle weakness. We measured maximum inspiratory and expiratory mouth pressures as indices of respiratory muscle strength, maximum hand-grip strength as an index of limb muscle strength, anthropometric indices, serum albumin, and total lymphocyte count as indices of nutritional status, and serum electrolytes in 15 stable patients with chronic cardiac pump failure who had no evidence of primary lung disease, and in 15 age-and-sex-matched healthy controls. As compared with the matched controls, the CHF patients had reduced inspiratory muscle strength (p < 0.0025), but their expiratory and limb muscle strength were not significantly reduced. CHF patients were not malnourished; they were heavier than matched controls because of increased body fat (p < 0.05). Serum sodium was significantly lower in the CHF patients than in the controls (p < 0.01), but was within the normal range in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inspiratory muscle weakness in chronic heart failure: role of nutrition and electrolyte status and systemic myopathy. 769 38


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