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)

Inbred mice bearing certain alleles at the Mottled locus have defects in connective tissue which result in weakness of skin and of blood vessels. Previous studies have established that cross-links in collagen and elastin are decreased in these animals due to impaired formation of lysine-derived aldehydes. Lysyl oxidase activity in extracts of skin is markedly lower in those prepared from affected animals than control mice. An inhibitor of lysyl oxidase is present in equal amounts in affected and control skins and does not account for diminished activity found in affected animals.
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PMID:Decreased lysyl oxidase activity in the aneurysm-prone, mottled mouse. 1 40

A 42-year-old man and a 51-year-old woman with a positive history of weakness and gastrointestinal complaints were shown to have low basal plasma cortisol and ACTH levels, and low daily urinary excretion of free cortisol. An empty sella was found in patient no. 1, while patient no. 2 was hypothyroid. Both patients showed a normal plasma cortisol response to ACTH and an increment in plasma ACTH and lipotropin levels after ovine CRH (oCRH), lysine vasopressin (LVP) and oCRH-LVP stimulation tests. These studies clearly report an isolated idiopathic ACTH deficiency due to a deficit in CRH in two adult subjects.
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PMID:Isolated adrenocorticotropic hormone deficiency secondary to hypothalamic deficit of corticotropin releasing hormone. 131 44

Myoclonus epilepsy with ragged-red fibers (MERRF) has been shown to be associated with a specific point mutation at the nucleotide 8344 in the tRNA(Lys) gene of mitochondrial DNA (mtDNA). We screened 6 patients with clinically diagnosed MERRF and 1 patient with ocular myopathy for point mutations in the tRNA(Lys) gene, using single strand conformation polymorphism (SSCP) analysis, which can detect even a 1-basepair difference between 2 DNA sequences. Using SSCP and consequent DNA sequencing, we identified the known MERRF mutation in 4 out of 6 MERRF patients, as well as in 1 patient with a new clinical phenotype associated with this mutation: progressive external ophthalmoplegia, muscle weakness and a lipoma, but no myoclonus or epilepsy. Two of the patients with clinical MERRF had neither the MERRF-mutation nor any other mutations in the tRNA(Lys) gene. Using SSCP analysis, we also detected a new polymorphism in 1 patient. Thus, SSCP analysis can be applied to search effectively and rapidly for point mutations or polymorphisms in mitochondrial DNA.
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PMID:Use of single strand conformation polymorphism analysis to detect point mutations in human mitochondrial DNA. 143 90

A 21-year-old woman, who had no particular familial history, was admitted to our hospital because of hand tremor and gait disturbance. On neurological examination, she showed muscle weakness in the proximal extremities. There was an ataxia on heel-to-shin testing. Action and postural myoclonus involving the extremities were also noted. In addition, with dorsiflexion of the hands, asterixis-like movement was manifested. Pyruvate was 1.0 mg/dl and lactate was 24.1 mg/dl in cerebrospinal fluid. Brain CT scan revealed mild cerebellar atrophy. EEG showed synchronous diffuse slow wave. Median nerve SEPs showed a large N20-P25 component (20 microV). Median nerve C-reflex was not evoked. With dorsiflexion of the hands, the asterixis-like movement was induced with brief cessation of surface EMG activity in the forearm muscles, as shown by the accelerometer trace. Biopsy specimens of the biceps brachii muscle revealed numerous ragged-red fibers. By PCR-RFLP method with use of a mismatched primer, we analyzed mitochondrial DNA extracted from peripheral leukocytes. The A to G mutation at nucleotide position 8,344 in a tRNA(Lys) gene of a mitochondrial genome was detected. In this patient, clonazepam was effective on the asterixis-like movements. From existence of positive myoclonus, giant SEPs and efficacy of clonazepam, we considered this movement to be negative myoclonus. Our study indicated the possibility that such an involuntary movement could be induced by certain posture in patients with MERRF.
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PMID:[Myoclonus epilepsy associated with ragged-red fibers--report of a patient with negative myoclonus]. 149 Mar 14

A number of mitochondrial DNA (mtDNA) mutations have been identified which cause familial, late onset neuromuscular degenerative diseases. These include missense mutations in most of the mtDNA polypeptide genes as well as base substitutions in several tRNA genes. Missense mutations in the mitochondrial electron-transport genes cause Leber hereditary optic neuropathy. Ten mutations have been associated with this disease, but four at nps 11,178, 3460, 4160 and 15,257 appear sufficient in themselves to cause the disease. One missense mutation in the ATPase 6 gene at np 8993 causes a second phenotype, neurogenic muscle weakness, ataxia and retinitis pigmentosum. Transfer RNA mutations have been identified for myoclonic epilepsy and ragged-red fibre disease in the tRNA(Lys) gene at np 8344 and for the mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes syndrome and for maternal mitochondrial myopathy and cardiomyopathy syndrome in the tRNA(Leu)(UUR) gene at nps 3234 and 3260, respectively. Deficiencies in mitochondrial oxidative phosphorylation enzymes have been observed in several common neurodegenerative diseases such as Alzheimer and Parkinson diseases. Perhaps mtDNA mutations play a role in these as well.
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PMID:Diseases resulting from mitochondrial DNA point mutations. 152 7

Acute toxicity of N2-[(N-acetylmuramoyl)-L-alanyl-D-isoglutaminyl]-N6-stearoyl-L-lysine (MDP-Lys(L18), muroctasin), a synthetic muramyl dipeptide derivative, was studied in Std-ddy mice, Std-Wistar rats and beagle dogs by subcutaneous and intravenous administration. Subcutaneous LD50 values were 436 mg/kg for male, 625 mg/kg for female in mice, 761 mg/kg for male, 801 mg/kg for female in rats and more than 200 mg/kg for dogs. Toxic signs included screaming, decrease of locomotor activity, weakness, emaciation and loss of hair, crust formation, necrosis and ulceration around the injection site in all species. Death occurred within 7 days after treatment. Pathological examination revealed inflammation around the injection site. In dogs a subcutaneous cavity with puruloid fluid and enlargement of the axillary lymphnodes were seen in addition. No marked toxic signs and pathological findings were observed in mice and rats after intravenous administration of 90 mg/kg, a critical dose of treatment.
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PMID:Acute toxicity of muroctasin in mice, rats and dogs. 319 Jul 94

We have compared the mechanical and chemical properties of the skin and its collagen from 24-week-old obese-hyperglycaemic (ob/ob) and lean mice. The skin from obese mice was mechanically weaker and generated a lower hydrothermal isometric force. However, there were no significant differences from lean mice in the type of reducible cross-links in the collagen or in its solubility, although it contained more reducible cross-links and glycosylated lysine. The total amount of skin collagen was similar in obese and lean mice from 3 to 24 weeks of age but the skin surface area was 60% greater in 24-week-old obese mice. When corrected for collagen content the tensile strength of skin from obese mice was greater than that from lean mice and we suppose that the weakness of obese mouse skin is caused by a failure of collagen deposition to match the increase in skin surface area as the animals become obese.
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PMID:Mechanical and chemical properties of the skin and its collagen from lean and obese-hyperglycaemic (ob/ob) mice. 646 98

Lysinuric protein intolerance is an autosomal recessive disease, due to a defect in intestinal, renal and hepatic dibasic amino acid transport. Two new cases in the same family are reported. The disease appears progressively during the first months of life with failure to thrive, anorexia, vomiting, diarrhea, hepatosplenomegaly, muscular weakness, osteoporosis, anemia, leukothrombocytopenia, hyperammonemia and orotic aciduria after a high-protein intake. Hyperdibasicamino-aciduria was associated with subnormal plasma concentrations of the same aminoacids. Oral l-arginine, l-ornithine, l-lysine, and lysyl-glycine loads confirmed the diagnosis. The supplementation of the diet with l-citrulline resulted in normal levels of blood ammonia. However, hepatosplenomegaly, muscular weakness, osteoporosis remained unchanged and growth was not improved. These may be due to lysine deficiency.
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PMID:[Lysinuric protein intolerance: a severe hyperammonemia secondary to l-arginine deficiency (author's transl)]]. 680 Mar 34

We performed a 5-year clinical and electrophysiologic follow-up study on two sibling cases with myoclonus epilepsy with ragged-red fibers. Both had myoclonus, intention tremor, slight muscle weakness, slight mental disturbance, hearing impairment, and optic atrophy. Neither had epileptic attacks or truncal or gait ataxia. Biochemical activity of cytochrome c oxidase was at the lower limit of the normal range of values, and an adenine to guanine transition mutation at nucleotide 8344 in the transfer RNA specific for lysine of mitochondrial DNA was detected in both cases. The electroencephalograms showed slowing of basic patterns, diffuse spike-and-wave complexes, occipital dominant wave-and-spike phantoms, 6- and 14-Hz positive spikes, and photosensitivity. No definite deterioration of basic patterns was seen, and diffuse spike-and-wave complexes and photosensitivity gradually disappeared during the slowly progressive clinical course. P2 latencies of pattern-reversal visual evoked potentials throughout the clinical course and III through V interpeak latencies of auditory brainstem responses at follow-up were prolonged without giant sensory evoked potentials in both cases.
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PMID:Myoclonus epilepsy with ragged-red fibers: a clinical and electrophysiologic follow-up study on two sibling cases. 822 33

We report myoclonic epilepsy with ragged-red fibers (MERRF) syndrome in a Chinese family with confirmed mitochondrial DNA point mutation. Six members of the family including the grandmother, two siblings, and three grandchildren were affected. Among them, action myoclonus was seen in five; short stature, muscle weakness, and mental retardation in four; lactic acidosis, hearing impairment, and ataxia in two; and seizures in one. Muscle biopsy from two affected siblings revealed ragged-red fibers and abundant subsarcolemmal mitochondria with paracrystalline inclusions. Pedigree analysis suggests a maternal transmission. Analysis of mitochondrial DNA showed a point mutation from A to G at the 8344th nucleotide position located in the tRNA(Lys) gene. To our knowledge, this is the first report of MERRF syndrome with such genetic defect from a Chinese family. The present and previous reports support the notion that mitochondrial DNA point mutation at the 8344th nucleotide position is the most common cause of MERRF syndrome.
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PMID:Myoclonic epilepsy with ragged-red fibers (MERRF) syndrome: report of a Chinese family with mitochondrial DNA point mutation in tRNA(Lys) gene. 793 36


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