Gene/Protein Disease Symptom Drug Enzyme Compound
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 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The most common ectopic production of a pituitary hormone is the one of ACTH leading to Cushing's syndrome. Ectopic ACTH-hypersecretion is the cause of Cushing's syndrome in 10-15% of all cases. The ACTH-secreting tumours are often oat-cell carcinomas of the lung, less frequently pancreatic cancers, hypernephromas, or C-cell carcinomas of the thyroid. Some of these tumours may be benign or semi-benign as the rare carcinoid tumours and cause great problems in the differential diagnosis of ACTH-dependent hypercortisolism. Out of 173 of our patients with Cushing's syndrome observed in the last 12 years 21 were caused by ectopic ACTH-production. Of these 21 patients 13 have a small cell carcinoma of the lung. The ectopic ACTH-syndrome often has typical clinical features caused by the levels of ACTH and cortisol leading to hypocalcemic alkalosis with muscle weakness and wasting, carbohydrate intolerance, and hypertension with oedema. The survival time in many of these patients is not long enough to allow them to develop typical signs of Cushing's syndrome though they are often highly pigmented. These patients are easily diagnosed. However, patients with small tumours which do not cause very elevated ACTH-levels and who have the more typical clinical signs of full-blown Cushing's syndrome are difficult to recognize. For the differential diagnosis of ACTH-dependent Cushing's syndrome the corticotropin-releasing hormone (CRH) stimulation test and dexamethasone suppression test with high doses are helpful. In special cases the venous sampling procedure for ACTH-measurements is necessary, also CT or NMR is helpful. Ectopic CRH-production is a rare cause of ACTH-dependent Cushing's syndrome. Patients with ectopic CRH-production and consecutive ACTH-hypersecretion from the pituitary have not been studied extensively. There are especially no well documented results of the use of the CRH-stimulation test in vivo in this group of patients with Cushing's syndrome. On the other hand, in the documented cases, not only CRH-, but also ACTH-production was found in the tumours. So far, this rare cause of ACTH-dependent Cushing's syndrome has to be excluded or confirmed by the measurement of endogenous CRH-levels. But until now we have not been able to detect one single case of ectopic CRH-production using a sensitive homologous CRH-radioimmunoassay over a period of more than 8 years in which we have seen nearly 120 newly diagnosed patients with ACTH-dependent Cushing's syndrome. Only in the plasma and tumour tissue of two patients of other groups have we found high CRH-levels.
J Steroid Biochem Mol Biol 1992 Oct
PMID:Ectopic production of ACTH and corticotropin-releasing hormone (CRH). 132 73

Recent advances concerning the genetic and biochemical basis of Duchenne and Becker muscular dystrophies have resulted in a good understanding of the etiology of these common dystrophies. An important secondary consequence of the genetic and biochemical research has been the generation of gene-based and protein-based diagnostic tools which enable a 'molecular diagnosis' for patients and their families. This review summarizes our current understanding of the genetics, biochemistry, and pathophysiology of Duchenne dystrophy, and gives an overview of the molecular diagnostic tools and their applications. Recent correlations of clinical, genetic and biochemical data have indicated that dystrophinopathies can present with a wide range of neuromuscular symptoms, and that neither male sex nor proximal weakness are diagnostic prerequisites for consideration of an underlying dystrophin abnormality.
Mol Aspects Med 1991
PMID:Dystrophin and disease. 177 Aug 36

Recent lattice polymer simulations by Chan & Dill suggest that compactness may be a significant driving force in the formation of secondary structure. We have addressed the robustness of this conclusion for non-lattice polymers using a rotational isomeric model of proteins. Boundary conditions are used to enforce compactness and excluded volume effects are explicitly incorporated. As in the cubic lattice studies, compactness is seen to influence secondary structure content. This effect is modest for densities comparable to native proteins but dramatic for chains that are approximately 30% more dense than native proteins. alpha-Helical structure is common but beta-sheet structure is rare. It appears that lattices impart to compact chains an organizational bias that favors beta-sheet structure. The strengths and weakness of various simplified representations of polypeptide chains are also discussed.
J Mol Biol 1991 May 05
PMID:Protein folding. Effect of packing density on chain conformation. 202 56

A 37-year-old man suffered from photosensitivity and urinary casts with serological findings of positive anti-DNA antibody, LE cells and false positive VD reaction in September of 1979. He developed general fatigue, dyspnea and diplopia with ptosis of bilateral eyelids in November of 1979, which were improved by the anti-cholinesterase drugs. In January of 1980, he had an attack of unconsciousness and his chest X-ray film showed several tumorous shadows in the anterior mediastinum and middle and lower lung fields. Treating him with chemotherapy of VEMP, the pulmonary shadows disappeared. However, he developed severe muscle weakness with an elevated CPK (430 mU/ml) and a myogenic EMG pattern along with an increased anti-acetylcholine receptor antibody (243 n Mol/l), dysphagia and eyelid-ptosis. He died in September of 1985 and his autopsy disclosed a malignant thymoma of mixed type in the anterior mediastinum and an atrophy and fibrosis with infiltration of inflammatory cells in the striated muscles.
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PMID:[An autopsy case of a patient with myasthenia gravis who showed various symptoms of collagen diseases and complicated with malignant thymoma]. 281 7

Daily administration of dithiobiuret (DTB, 1 mg/kg X 6 days, ip) produced delayed onset muscle weakness in rats as indicated by failure in a treadmill test. In nerve-muscle preparations from DTB-intoxicated rats neuromuscular toxicity was manifested as contractile fatigue during tetanic nerve stimulation. As muscle weakness developed, feed intake decreased and the animals lost body weight. Water intake was not altered during this time, but urine output was increased concomitant with the development of muscle weakness and resulted in a state of negative water balance. Daily administration of d-penicillamine (d-PEN) antagonized DTB-induced treadmill failure in a dose-dependent fashion. A daily dose of d-PEN (1 mMol/kg, ip) that completely antagonized treadmill failure also antagonized the contractile fatigue, reduced feed intake, weight loss and negative water balance caused by DTB administration. In rats already intoxicated with DTB, initiating daily d-PEN treatment or discontinuing further DTB administration, caused the animals to recover normal treadmill performance after a latent period of five days. A single dose of d-PEN (1 mMol/kg, iv) was not effective in reversing treadmill failure or contractile fatigue in rats already intoxicated with DTB. Thus, continuous daily administration of d-PEN was necessary for it to be effective. A single dose of d-PEN (1 m Mol/kg, ip) administered one hr after [14C]-DTB (1 mg/kg, ip) did not affect the plasma and tissue concentrations of DTB-derived radioactivity or their corresponding elimination kinetics. Cumulative urinary and fecal excretion of DTB-derived radioactivity were also unaffected by d-PEN administration as were the relative proportions of DTB and two of its metabolites, monothiobiuret and thiuret, in urine. Other agents that produced dose-dependent antagonism of DTB toxicity were diethyldithiocarbamate, disulfiram, cysteamine and 2,2'-dipyridyl. Considering the chemical and biological properties of DTB and its antagonists, a mechanism of antagonism involving an alteration of the thiol-disulfide and/or divalent metal cation status of motor axon terminals is postulated.
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PMID:Antagonism of dithiobiuret toxicity in rats. 301 25

To assess the distribution of insulin-like growth-factor-related proteins during autoimmune CNS demyelination and remyelination, experimental autoimmune encephalomyelitis was produced by injecting Lewis rats with an emulsion containing guinea pig spinal cord and complete Freund's adjuvant. Tail weakness appeared at 10-12 days and was followed by hind and forelimb weakness. Paraplegia and incontinence were observed in some animals. From 8-40 days postinoculation (dpi), spinal cord sections were used to correlate lesion location and severity with mRNA distributions of insulin-like growth factor I (IGF-I), IGF-binding protein 2 (IGFBP-2), IGF-I-receptor (IGFR-I), glial fibrillary acidic protein (GFAP), and myelin basic protein (MBP). These were determined semiquantitatively by in situ hybridization. Fourteen dpi, there were inflammatory infiltrates and demyelination in both white matter (WM) and grey matter (GM). IGF-I and GFAP mRNAs were increased in these lesions and transcripts encoding myelin basic protein (MBP) were greatly reduced. Large lesions with extensive demyelination were evident in both WM and GM when mRNA levels of GFAP and IGF-I peaked 26 dpi. MBP mRNA levels began increasing 21 dpi and peaked 26 dpi, when a few thin regenerating myelin sheaths were found morphologically. Astrocytes, identified by their morphology and GFAP immunoreactivity, expressed very low levels of IGFBP-2 mRNA and peptide in normal controls; their levels were significantly higher 14 dpi, peaked 26 dpi, and then gradually decreased. Some neurons, as well as oligodendroglia in areas undergoing remyelination, expressed IGFR-I. Although levels of IGF-I, IGFBP-2, and GFAP mRNAs were highest in lesion areas, levels were also elevated around lesions and in some normal-appearing areas of WM and GM 14-40 dpi. The gene expression of both IGF-I and IGFBP-2 by hypertrophic GFAP-positive astrocytes was demonstrated 14-40 dpi by combined in situ hybridization and immunocytochemistry as well as by double immunostaining. Coexpression of IGF-I and IGFBP-2 in the same astrocyte was a frequent finding. Relative increases in both IGF-I, GFAP, IGFBP-2, IGFR-I, and MBP mRNAs peaked at about the same time. This suggests that during lesion progression and recovery, astrocytic expression of IGF-I-related peptides may reduce immune-mediated myelin injury. We also suggest that astrocytic IGFBP-2 in lesions may help target IGF-I to IGFR-I-expressing oligodendrocytes and promote remyelination of demyelinated axons.
Mol Cell Neurosci 1994 Oct
PMID:Astrocytes express insulin-like growth factor-I (IGF-I) and its binding protein, IGFBP-2, during demyelination induced by experimental autoimmune encephalomyelitis. 752 31

The stability of phosphodiester bonds in tRNA(Trp) (E. coli, bovine) and tRNA(Phe) (yeast) synthesized in vitro was studied in the complexes with cognate aminoacyl-tRNA synthetases. In contrast to E. coli tRNA(Gln) where synthetase-induced cleavage has been reported, we have failed to observe this effect with tRNA(Trp) and tRNA(Phe). Consequently, the weakness of sugar-phosphate backbone of tRNA-transcripts in the complexes is not a common feature for all tRNA-synthetase pairs. The cleavage mechanism in the case of tRNA(Gln) remains obscure.
Mol Biol (Mosk)
PMID:[Stability of phosphodiester tRNA bonds lacking minor nucleosides, in aminoacyl tRNA-synthetase complexes]. 772 67

The purpose of this investigation was to analyze the CTG expansion in muscle as compared to lymphocytes DNA in a sample of selected myotonic dystrophy (DM) patients of different ages and degrees of clinical severity, ranging from severe congenital to minimally affected. Results from the present study showed that the size of the CTG repeat was markedly larger in skeletal muscle than in lymphocytes in all DM patients. In contrast to lymphocytes, no significant correlation was found between the size of the CTG expansion in muscle and age at onset. In addition, large expansions were observed in muscle from all adult symptomatic patients independently of the presence of muscle weakness, which raises the question of the value of analyzing CTG expansions in muscle for predicting the severity of the phenotype. Differences between the size of the CTG expansions in muscle as compared to lymphocytes were smaller in affected children suggesting an apparent tendency to increase with aging and reaching a plateau in adulthood.
Hum Mol Genet 1995 Mar
PMID:Analysis of the CTG repeat in skeletal muscle of young and adult myotonic dystrophy patients: when does the expansion occur? 779 94

Two brothers presented with a clinical picture characterized by sideroblastic anemia, mild pancreatic insufficiency and progressive muscle weakness. The presence of an associated permanent basal lactic acidemia raised the suspicion of a mitochondrial disease. A muscle biopsy performed in both siblings proved the presence of a significant number of ragged-red fibers, and respiratory chain enzymatic determinations demonstrated a reduced activity of complexes I, III and IV. Mitochondrial DNA studies disclosed the presence of multiple deletions both in skeletal muscle and, to a lesser extent, in leukocytes. Similar, but not identical deletions were also present in the leukocytes and muscle from their mother. Deletions were flanked by short direct repeats. We conclude that such patients suffer from a familial form of mitochondrial disease clinically resembling Pearson's syndrome, with a probably autosomal dominant inheritance.
Hum Mol Genet 1994 Nov
PMID:Multiple deletions of mtDNA in two brothers with sideroblastic anemia and mitochondrial myopathy and in their asymptomatic mother. 787 10

The only calcium channel mutation reported to date is a deletion in the gene for the DHP-receptor alpha 1-subunit resulting in neonatal death in muscular dysgenesis mice (1). In humans, this gene maps to chromosome 1q31-32. An autosomal dominant muscle disease, hypokalemic periodic paralysis (HypoPP), has been mapped to the same region (2). Sequencing of cDNA of two patients revealed a G-to-A base exchange of nucleotide 1583 predicting a substitution of histidine for arginine528. This affects the outermost positive charge in the transmembrane segment IIS4 that is considered to participate in voltage sensing. By restriction fragment analysis, the mutation was detected in the affected members of 9 out of 25 HypoPP families. The results indicate that the DHP-receptor alpha 1-subunit mutation causes HypoPP. An altered excitation-contraction coupling may explain the occurrence of muscle weakness.
Hum Mol Genet 1994 Aug
PMID:A calcium channel mutation causing hypokalemic periodic paralysis. 798 25


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