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)

Because of inadequate response to or intolerable side effects of oral medication, nine patients with segmental, generalized, and focal myoclonus were treated with intramuscular botulinum toxin type A. All patients were evaluated with neuroimaging, routine and limb-monitored electroencephalography, electromyography, evoked potentials and appropriate biochemical studies. Patients were aged 2 to 22 years, with duration of myoclonus from 1 month to 10 years. Multiple medication trials included antiepileptic drugs, benzodiazepines, tryptophan, L-dopa/carbidopa, baclofen, and dantrolene. Patients were injected with botulinum toxin in their affected area with electromyographic guidance to affected muscles with different doses (8 to 20 units/kg), except two patients who were injected with 32 and 45 units/kg, respectively, at 4- to 8-month intervals. One patient did not complete botulinum toxin treatment because of subjective weakness, although there were virtually no side effects reported in patients completing therapy. Patients reported a dramatic reduction in painful myoclonus. In addition, patients exhibited improved functional skills, as demonstrated by markedly improved use of affected extremities and improvements in ambulation. One patient, who was nonambulatory prior to treatment, was able to walk afterward. Long-term benefits could be related to higher dosage used or negative feedback effect.
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PMID:Treatment of childhood myoclonus with botulinum toxin type A. 1061 64

Ataxia is defined as a disturbance which, quite independent of any motor weakness, alters direction and extent of voluntary movement and impairs the sustained voluntary of reflex muscle contraction necessary for maintaining postiue and equilibrium [1]. Since pathophysiological basis of cerebeller ataxia is still not completely clear, the current therapeutic attempts are mainly symptom-oriented [3]. One possible approach could be a modification of potentially involved neurotransmitter systems of the cerebellum, where particularly interesting is the serotonergic system. However, attempts with levorotatory form of tryptophan (5-HT precursors) proved to be ineffective [4, 5]. Since receptors in the cerebellum are mainly of 5-HTIA subtype, the use of specific agonists might be a more reasonable therapy [6]. The study initially involved 11 patients, but only 9 completed the protocol due to unfavorable side effects. Our open label prospective study lasted for 15 weeks. The patients were tested before the beginning of the treatment (initial visit), at 7th (first visit) and 11th week (second visit) of continuous therapy, and eventually at 15th week (final visit). The daily dose was 40 mg at the first and 60 mg at the second visit. We used the evaluation scale gurposed for cerebellar functions testing (speech, gait, coordination and ocular movements). Significant improvement of cerebellar ataxia in patients under buspiron therapy has been noted. We analyzed the results obtained from our 9 patients (4 females and 5 males), of which 6 patients suffered from cerebellar degeneration, one from multiple sclerosis, one from Ramsey-Hunt syndrome, and one from pontine myelinolysis. At the initial visit the patient score was 18.9 (SD = 7.3), subsequently, at the iirst visit the score was 15.4 (SD = 8), while the second visit yielded the score of 12.9 (SD = 8.2), and finally, after a two-weeks lasting wash-out period, it was 17.7 (SD = 7.1) (Table 1). It was found that patients exhibiting mild ataxia showed a better improvement in comparison to the patients who had marked cerebellar symptoms at the beginning of the treatment (Table 2). In conclusion, our prospective study shows that buspiron treatment improves cerebellar symptoms.
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PMID:[Buspirone in the treatment of cerebellar ataxia]. 1064

Apolipophorin III (apoLp-III) is an exchangeable apolipoprotein whose structure is represented as a bundle of five amphipathic alpha-helices. In order to study the properties of the helical domains of apolipophorin III, we designed and obtained five single-tryptophan mutants of Locusta migratoria apoLp-III. The proteins were studied by UV absorption spectroscopy, time-resolved and steady-state fluorescence spectroscopy, and circular dichroism. Fluorescence anisotropy, near-UV CD and solute fluorescence quenching studies indicate that the Trp residues in helices 1 (N-terminal) and 5 (C-terminal) have the highest conformational flexibility. These two residues also showed the highest degree of hydration. Trp residues in helices 3 and 4 display the lowest mobility, as assessed by fluorescence anisotropy and near UV CD. The Trp residue in helix 2 is protected from the solvent but shows high mobility. As inferred from the properties of the Trp residues, helices 1 and 5 appear to have the highest conformational flexibility. Helix 2 has an intermediate mobility, whereas helices 3 and 4 appear to constitute a highly ordered domain. From the configuration of the helices in the tertiary structure of the protein, we estimated the relative strength of the five interhelical interactions of apoLp-III. These interactions can be ordered according to their apparent stabilizing strengths as: helix 3-helix 4 > helix 2-helix 3 > helix 4-helix 1 approximately helix 2-helix 5 > helix 1-helix 5. A new model for the conformational change that is expected to occur upon binding of the apolipoprotein to lipid is proposed. This model is significantly different from the currently accepted model (Breiter, D. R., Kanost, M. R., Benning, M. M., Wesemberg, G., Law, J. H., Wells, M. A., Rayment, I., and Holden, M. (1991) Biochemistry 30, 603-608). The model presented here predicts that the relaxation of the tertiary structure and the concomitant exposure of the hydrophobic core take place through the disruption of the weak interhelical contacts between helices 1 and 5. To some extent, the weakness of the helix 1-helix 5 interaction would be due to the parallel arrangement of these helices.
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PMID:Dynamics and hydration of the alpha-helices of apolipophorin III. 1074 49

Botulism is a paralytic disease caused by a toxin produced by the bacterium Clostridium botulinum. Outbreaks of the illness take place with a mortality rate of 10%, and the potential terrorist use of the toxin has become a serious concern. The current treatment includes administration of antitoxin, which can cause serious allergic reactions. Recently, we have successfully treated a 64 year old woman with the illness with IMMUSORBA TR350 (Asahi Medical, Tokyo, Japan), an extracorporeal adsorptive column containing polyvinylalcohol-tryptophan as an adsorptive agent, which has been widely used in Japan to treat myasthenia gravis and Guillain-Barre syndrome. Initially, the patient developed ocular muscle weakness and a variant of the Guillain-Barre syndrome was suspected. After extracorporeal treatment, her neurologic symptoms remarkably improved. After a series of treatments, botulinum toxin type B was isolated in the food she had eaten, establishing the diagnosis. An in vitro study revealed that the adsorptive column removed botulinum toxin to a significant extent. Our recent findings suggest that treatment with the adsorptive column TR350 can be a feasible option for botulism, which is a rare but potentially lethal disease.
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PMID:Extracorporeal adsorption as a new approach to treatment of botulism. 1111 Feb 82

A 49-year-old woman with seronegative myasthenia gravis (SNMG) was admitted to our hospital with severe respiratory failure, proximal muscle weakness and bulbar palsy. Permanent tracheostomy and continuous mechanical ventilation were performed. At a previous hospital, she was diagnosed as SNMG on the basis of the positive waning during 3 Hz repetitive stimulation of the ulnar nerve, although no acetylcholine receptor antibodies (Ab) were detected by serological examination. Before admission to our hospital, she was treated with corticosteroids, intravenous immunoglobulin and tryptophan column immuno-adsorption therapy without clinical improvement. At our hospital, serological examination detected muscle-specific receptor tyrosine kinase (MuSK) Ab and plasma exchange was performed as treatment. Plasma exchange and subsequent immunomodulating therapy with corticosteroids and tacrolimus showed a dramatic clinical improvement with a marked decline of MuSK Ab level in the serum. These results suggested that plasma exchange should be considered as first choice to treat patients with refractory MuSK Ab-positive MG.
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PMID:[A case of myasthenia gravis with anti-MuSK antibodies showing a dramatic improvement with plasma exchange]. 1611 34

Emery-Dreifuss muscular dystrophy (EDMD) is characterized by early-onset contractures, slowly progressive weakness, and muscle wasting in humeroperoneal muscles, and adult-onset cardiomyopathy with conduction block. We analyzed blood samples from an EDMD family, including a mother and two daughters, and found a novel mutation in codon 520 in exon 9 of the lamin A/C (LMNA) gene, resulting in a substitution of tryptophan (W) by glycine (G) in all three patients. The mother died after a stroke-like episode at the age of 43. The elder sister received pacemaker implantation, which improved symptoms of exercise intolerance and dizziness. These cases illustrate the necessity of correct diagnosis, evaluation, and follow-up of cardiac problems due to the wide clinical spectrum and high prevalence of cardiac conduction block in patients with autosomal dominant EDMD.
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PMID:Novel LMNA mutation in a Taiwanese family with autosomal dominant Emery-Dreifuss muscular dystrophy. 1749 93

We report a case of an immunocompetent Peruvian patient from the Andes with a one-month history of meningoencephalitis. Cryptococcus gattii was identified from a cerebrospinal fluid culture through assimilation of D-proline and D-tryptophan as the single nitrogen source. Initially, the patient received intravenous antifungal therapy with amphotericin B. The patient was discharged 29 days after hospitalization and continued with oral fluconazole treatment for ten weeks. During this period, the patient showed clinical improvement with slight right-side residual weakness. Through this case report, we confirm the existence of this microorganism as an infectious agent in Peru.
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PMID:Cryptococcus gattii meningoencephalitis in an HIV-negative patient from the Peruvian Andes. 2080 55

The chlamydiae are obligate intracellular parasites that have evolved specific interactions with their various hosts and host cell types to ensure their successful survival and consequential pathogenesis. The species Chlamydia pneumoniae is ubiquitous, with serological studies showing that most humans are infected at some stage in their lifetime. While most human infections are asymptomatic, C. pneumoniae can cause more-severe respiratory disease and pneumonia and has been linked to chronic diseases such as asthma, atherosclerosis, and even Alzheimer's disease. The widely dispersed animal-adapted C. pneumoniae strains cause an equally wide range of diseases in their hosts. It is emerging that the ability of C. pneumoniae to survive inside its target cells, including evasion of the host's immune attack mechanisms, is linked to the acquisition of key metabolites. Tryptophan and arginine are key checkpoint compounds in this host-parasite battle. Interestingly, the animal strains of C. pneumoniae have a slightly larger genome, enabling them to cope better with metabolite restrictions. It therefore appears that as the evolutionarily more ancient animal strains have evolved to infect humans, they have selectively become more "susceptible" to the levels of key metabolites, such as tryptophan. While this might initially appear to be a weakness, it allows these human C. pneumoniae strains to exquisitely sense host immune attack and respond by rapidly reverting to a persistent phase. During persistence, they reduce their metabolic levels, halting progression of their developmental cycle, waiting until the hostile external conditions have passed before they reemerge.
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PMID:Evolution to a chronic disease niche correlates with increased sensitivity to tryptophan availability for the obligate intracellular bacterium Chlamydia pneumoniae. 2468 24

The clinical data of 2 infants with infantile glycogen storage disease type II (GSD II) from one pedigree were collected. The method of dried blood spots (DBS) was applied to collect peripheral blood samples, and the activity of acid alpha-D-glucosidase (GAA) in leukocytes was measured. The coding region of GAA gene in this pedigree was amplified by polymerase chain reaction and then direct sequencing was used to analyze mutations in GAA gene. The two infants were twins, who were admitted to the hospital due to feeding difficulties, generalized muscle weakness and hypotonia, cardiomegaly, and cardiac insufficiency when they were 10 months old. The GAA activity in leukocytes in the two infants was significantly lower than in normal controls. Gene sequencing revealed 2 compound heterozygous mutations in the two infants, i.e., G1942A and G2214A, respectively. G1942A had been proved pathogenic, and the latter one, G2214A, was a nonsense mutation, resulting in the change of tryptophan, the 738th amino acid of GAA, into a stop codon. The two infants were diagnosed with GSD II by gene detection and no enzyme replacement therapy could be provided to them. Follow-up visits showed that the two infants died at home at the age of 15 months and 17 months, respectively. GSD II is caused by deficiency of GAA activity resulting from mutation of GAA gene. The detection of GAA activity in peripheral blood by DBS and GAA gene detection are effective and feasible methods for diagnosis of GSD II.
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PMID:[Clinical characteristics and gene mutation analysis of one pedigree with infantile glycogen storage disease type II]. 2657 83

Muscle atrophy is an unfortunate effect of aging and many diseases and can compromise physical function and impair vital metabolic processes. Low levels of muscular fitness together with insufficient dietary intake are major risk factors for illness and mortality from all causes. Ultimately, muscle wasting contributes significantly to weakness, disability, increased hospitalization, immobility, and loss of independence. However, the extent of muscle wasting differs greatly between individuals due to differences in the aging process per se as well as physical activity levels. Interventions for sarcopenia include exercise and nutrition because both have a positive impact on protein anabolism but also enhance other aspects that contribute to well-being in sarcopenic older adults, such as physical function, quality of life, and anti-inflammatory state. The process of aging is accompanied by chronic immune activation, and sarcopenia may represent a consequence of a counter-regulatory strategy of the immune system. Thereby, the kynurenine pathway is induced, and elevation in the ratio of kynurenine to tryptophan concentrations, which estimates the tryptophan breakdown rate, is often linked with inflammatory conditions and neuropsychiatric symptoms. A combined exercise program consisting of both resistance-type and endurance-type exercise may best help to ameliorate the loss of skeletal muscle mass and function, to prevent muscle aging comorbidities, and to improve physical performance and quality of life. In addition, the use of dietary protein supplementation can further augment protein anabolism but can also contribute to a more active lifestyle, thereby supporting well-being and active aging in the older population.
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PMID:Role of Dietary Protein and Muscular Fitness on Longevity and Aging. 2939 87


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