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)

In a retrospective study of 632 patients with pituitary disease we diagnosed pituitary insufficiency without hypersecretion of any pituitary hormone in 122 patients. Patients were substituted with sex hormones (76%), hydrocortisone (74%) and/or L-thyroxine (77%). 76% had additional growth hormone deficiency, as shown by an increase of growth hormone of less than 5 ng/ml after i.v. administration of L-arginine. In 17% of all patients the diagnosis of osteoporosis was proven or suspected radiologically. 57% had low bone mass of lumbar spine (dualphotonabsorptiometry) and 73% had low bone mass of the proximal forearm (singlephotonabsorptiometry). BMD values of pituitary insufficient patients were in the same range as those of patients with established osteoporosis. More than half of all patients (53%) complained of tiredness, exhaustion and muscle weakness. 40% suffered from adipositas. 77% had hyperlipidemia (68% hypertriglyceridemia and 42% hypercholesterinemia), 18% had hypertension. 14% of the patients had arteriosclerotic events in their history (myocardial infarction or stroke). These figures are higher than incidences shown in the German PROCAM-study. These data show an increased prevalence of osteoporosis and vascular diseases. This is in contrast to the general opinion, that patients with pituitary insufficiency are adequately treated by substitution with adrenal, thyroid and sex hormones. Whether other factors such as the additional growth hormone deficiency are responsible for these diseases has to be examined in prospective studies.
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PMID:[Increased prevalence of osteoporosis and arteriosclerosis in conventionally substituted anterior pituitary insufficiency: need for additional growth hormone substitution?]. 176 81

Duchenne and Becker muscular dystrophy (DMD and BMD) genes are located in Xp21 on the short arm of the X chromosome. DMD patients display a much more severe clinical course than BMD patients, and yet about 10% of cases of each have been reported to have deletions for parts of the gene. Using a complementary DNA subclone of the DMD gene we have screened 66 DMD and BMD patients who had not previously shown deletions with the probes then available. Fifteen patients have a deletion of this part of the gene, indicating a higher deletion frequency in this region (22%). Exons were deleted in five severely affected DMD patients and in ten BMD patients. Significantly, most of these deletions begin in the same region of the cDNA, which implies that there is a common mechanism for the generation of many of these mutations. An apparently identical deletion in one family gave classical BMD in two brothers (presenting in their teens) and only very mild muscle weakness in their 86-year-old great-great-uncle. Taking these data together with data using the probes previously published, we are able to detect deletions directly in 40% of our families requiring antenatal diagnosis or carrier detection.
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PMID:Preferential deletion of exons in Duchenne and Becker muscular dystrophies. 282 6

GH is a potent anabolic hormone for bone and calcium metabolism, not only via direct effects but also mediated through other systems. The individual effects on bone metabolism are summarized in Table 1. Some of the signs (low BMD and low serum osteocalcin) and symptoms (increased prevalence of vertebral fractures) seen in patients with GHD may be due to the lack of GH itself, others may be due to secondary hormone deficiencies or changes in body composition induced by GHD. GH treatment can reverse changes of calcium metabolism. Whether it is able to increase bone mass still needs to be determined in larger and longer studies. Some patients with established osteoporosis and vertebral fractures seem to suffer from GHD. Treatment of osteoporosis with GH has not previously been successful, but studies with more patients over several years to investigate the effects of GH treatment on vertebral fracture rates are lacking. As GH seems to reverse some signs of old age, such as muscle weakness and reduced exercise capacity, it is possible to speculate that GH could prevent the occurrence of hip fractures in elderly people.
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PMID:Growth hormone and bone metabolism. 834 85

Duchenne and Becker muscular dystrophy (DMD and BMD) are X-linked recessive diseases caused by defective expression of dystrophin. The mdx mouse, an animal model for DMD, has a mutation that eliminates expression of the 427K muscle and brain isoforms of dystrophin. Although these animals do not display overt muscle weakness or impaired movement, the diaphragm muscle of the mdx mouse is severely affected and shows progressive myofibre degeneration and fibrosis which closely resembles the human disease. Here we explore the feasibility of gene therapy for DMD by examining the potential of a full-length dystrophin transgene to correct dystrophic symptoms in mdx mice. We find that expression of dystrophin in muscles of transgenic mdx mice eliminates the morphological and immunohistological symptoms of muscular dystrophy. In addition, overexpression of dystrophin prevents the development of the abnormal mechanical properties associated with dystrophic muscle without causing deleterious side effects. Our results provide functional evidence for the feasibility of gene therapy for DMD.
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PMID:Overexpression of dystrophin in transgenic mdx mice eliminates dystrophic symptoms without toxicity. 835 80

Duchenne and Becker muscular dystrophy (DMD and BMD) are progressive disorders, which almost exclusively affect males. DMD is the more severe type with an onset at 2-3 years of age. Patients become wheelchair-bound before the age of 13 and often die due to cardiac arrest or respiratory insufficiency. BMD, a more varying phenotype which may overlap with limb girdle muscular dystrophy (LGMD), has a less severe muscle weakness which starts later than in DMD patients. DMD carriers may show some muscle weakness. The dystrophin gene (2.4 Mb), known to be involved in DMD/BMD, codes for a 427 kilodalton muscle-specific protein named dystrophin as well as several tissue-specific isoforms. Dystrophin, as part of a membrane-bound complex of proteins, connects the cytoskeleton of the muscle cell to the extracellular matrix. Since 1985, when highly reliable carrier detection and prenatal diagnosis at the DNA level became possible, over 250 prenatal tests have been performed. Molecular genetic analysis, highlighted a phenomenon called germinal mosaicism, which explains the recurrence of de novo mutations and led to the discovery of the so-called reading-frame rule, which helps to discriminate between DMD and BMD. Fifteen years after the discovery of the dystrophin gene, mutations can be detected in 95% of the patients, while the remaining 5% are still hiding within this very large gene.
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PMID:[From gene to disease; the dystrophin gene involved in Duchenne and Becker muscular dystrophy]. 1188 23

The effects of chronic exposure to cadmium (Cd) on the mineral status, mechanical properties and incidence of deformities and fractures of the lumbar spine (L1-L5) were studied in a rat model of human exposure. Young female Wistar rats were exposed to 1, 5, 50 or 100 mg Cd/l for 12 months. Cd, dose and time dependently, disturbed the mineral status of the lumbar vertebrae as reflected in decreased bone mineral content (BMC) and density (BMD) at the L1-L5 (DEXA technique) and ash weight (AW) of the fourth lumbar vertebral body (L4). However, the changes were too small to be evident radiographically. Cd had no effect on the ratio of nonorganic to organic component content, except for its decrease at the 100 mg Cd/l. Weakness in the mechanical properties (compression test; Instron machine) of the L4 was noted. At the 1 mg Cd/l, a decrease was observed in the deformation at the yield point, with a simultaneous increase in the L4 stiffness, but not in strength (defined by load at yield or ultimate load). In the 5 mg Cd/l group, similar changes took place and a decrease in the ultimate load was evident as well. At the 50 and 100 mg Cd/l, Cd more seriously affected the L4 mechanical properties. At all levels of Cd exposure, the L4 deformities and/or fractures took place. Intact L4 was noted only in the 1 and 5 mg Cd/l groups. The study clearly revealed that chronic exposure to Cd disturbs the L1-L5 mineral status resulting in weakness in its mechanical properties and in turn in vertebral body (cancellous bone) deformities and fractures. The results allow us to conclude that the critical Cd concentration for these effects is very low [about 0.06-0.09 microg/g dry defatted weight (DW)] and seem to indicate an osteoporotic character of changes. A very important finding of the study is that Cd affects cancellous bone even at low-level intoxication corresponding to the general population exposure. Thus, we hypothesize that environmental exposure to Cd may be a risk factor for the lumbar spine demineralization and increased incidence of vertebral deformities and fractures.
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PMID:Mineral status and mechanical properties of lumbar spine of female rats chronically exposed to various levels of cadmium. 1500 99

In this study, based on a rat model of human environmental exposure to cadmium (Cd), it has been examined whether low-level lifetime Cd exposure increases the risk of vertebral osteoporosis and vertebrae fractures in the elderly. For this purpose, the lumbar vertebral bodies (L4 or L3) of control and Cd-exposed (1 mg Cd/l in drinking water for 24 months) female Wistar rats were assigned to densitometric, radiographic, biomechanical (compression test), and biochemical studies, as well as to assess their dimensions and chemical composition. The exposure to Cd affected the mineral status of the L4. The decreased mineral content, density (BMD) and bone mineral area of the vertebral body together with the unchanged ratio of non-organic and organic components indicate osteoporotic nature of the Cd-induced changes. The activity of alkaline phosphatase in the L3 decreased. Cd also influenced the mechanical properties of the L4. The yield load and ultimate load decreased indicating a weakness in the vertebral body compression strength. Stiffness of the L4 decreased and the displacement at ultimate increased suggesting its enhanced susceptibility to deformities. Indeed, in the Cd group vertebral deformities (in 30% of females) or even fractures (in 40% of females), including those with disruption of bone continuity were evident. Z-score values for the L4 BMD revealed vertebral osteopenia in 30% and osteoporosis in 70% of the Cd-exposed females. The results allow for the conclusion that low lifetime exposure to Cd may become an important factor increasing the risk of lumbar spine osteoporosis with vertebral deformities and fractures in the elderly.
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PMID:Low-level exposure to cadmium during the lifetime increases the risk of osteoporosis and fractures of the lumbar spine in the elderly: studies on a rat model of human environmental exposure. 1537 91

Immunohistochemistry using antibodies to dystrophin is the pathological basis for the diagnosis of Duchenne and Becker muscular dystrophy (DMD and BMD). While the sarcolemma of DMD muscle is negative, BMD muscle generally shows variable labelling because of the translation of a partially functional dystrophin that is localized to the sarcolemma. In rare cases, however, this labelling is equivocal and similar to that observed in controls making diagnosis difficult. We report here that in such instances immunolabelling with antibodies to the neuronal form of nitric oxide synthase (nNOS) can be useful in suspecting a dystrophinopathy with a mutation in the 'hot-spot' rod domain and help to direct molecular analysis. nNOS localizes to the sarcolemma of mature muscle fibres via several components of the dystrophin-associated protein complex (DAPC) including dystrophin but sarcolemmal nNOS is lost when dystrophin levels are very low or absent because of deletions in critical regions of the rod domain. We report three cases who presented with only mild or no muscle weakness but had elevated serum creatine kinase activity and dystrophin immunolabelling indistinguishable from normal, making a pathological diagnosis difficult. All three cases had a complete absence of sarcolemmal nNOS and were subsequently found to have an in-frame deletion in the common rod domain exons (in these cases 48, 45-51, 47-53) compatible with a BMD. In addition, we observed that nNOS appears to be developmentally regulated with the antibody used and was often absent from the sarcolemma of immature fibres. These findings demonstrate the value of including antibodies to nNOS in routine immunohistochemical studies and that absence of nNOS can be a more sensitive marker than up-regulation of utrophin for diagnosis of BMD. Immaturity of fibres, however, needs to be taken into account, especially in neonates.
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PMID:Absence of neuronal nitric oxide synthase (nNOS) as a pathological marker for the diagnosis of Becker muscular dystrophy with rod domain deletions. 1548 30

A 33-year-old man with BMD manifesting severe mental retardation is reported. This patient has mild pseudohypertrophy in his calf muscles and showed an elevation of creatine kinase (CK) level in the serum (2215 IU/L). He was diagnosed as autistic at the age of three. His intellectual level was estimated to be two years old in social intelligence and four months old in speech ability at the age of 33. However his muscle strength remains within the normal range. All of his three siblings have similar symptoms, such as severe mental retardation and elevated CK level in the serum (1735-3641 IU/L) and lack apparent muscular weakness. Gene analyses by multiplex PCR and Southern blotting showed all of the siblings had the deletion of exon 4 in the dystrophin gene. Pathological findings of a muscle biopsy specimen showed a mild irregular dystrophin stain of the muscle surface membrane. This is a rare familial case of Becker muscular dystrophy manifesting severe mental retardation with scarce muscular weakness.
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PMID:[Four siblings with becker muscular dystrophy (BMD) manifesting severe mental retardation]. 1654 98

Mutations in the dystrophin gene give rise to Duchenne and Becker muscular dystrophies (DMD and BMD), in which both skeletal and cardiac muscles are affected, but also to X-linked dilated cardiomyopathy (XLDC), a condition characterised by exclusive cardiac involvement. XLDC patients with mutations at the 5' end of the gene typically have a cardiac specific severe transcriptional pathology, with absent dystrophin in the heart, while reduced levels of virtually normal dystrophin transcript and protein are present in the skeletal muscle. We now report the identification of a new XLDC family and the detailed characterisation of the levels of dystrophin protein present in skeletal muscle of this family, and of three previously studied XLDC families. We found that dystrophin levels comprised between 29% and 57% were sufficient to avoid muscle weakness in these XLDC families. This information will be of help for the development of therapeutic approaches aimed at restoring dystrophin levels sufficient to prevent the muscle pathology in DMD.
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PMID:Dystrophin levels as low as 30% are sufficient to avoid muscular dystrophy in the human. 1782 93


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