Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002986 (Fabry)
 5,646 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A Japanese male patient with Fabry disease who had no activity of the lysosomal hydrolase alpha-galactosidase A (alpha-GalA) and female members of his family were analyzed. We cloned a cDNA encoded the mutant alpha-GalA, determined its nucleotide sequence, and found two nucleotide differences between the mutant and the wild-types cDNAs. The one difference, a C-to-T transition at nucleotide number 118, resulted in an amino acid substitution of Pro-40 by Ser. A transient expression assay demonstrated that this missense mutation was the cause of the deficiency of alpha-GalA activity in the patient. Gene analysis of the patient's family by PCR and subsequent sequencing demonstrated that all females were heterozygotes.
Nihon Rinsho 1993 Sep
PMID:[Molecular genetic analysis of a Japanese family with Fabry disease]. 841 4

There are no reports of anesthesia for a patient with Fabry's Disease in Japan. Fabry's Disease is a rare hereditary disease that is characterized by alpha-galactosidase deficiency caused by deposition of glycolipid in many organs. The disease may be complicated by cardiac ischemic disease, neurological disorder and renal failure. The patient is a 45-year-old female with cholelithiasis who underwent cholecystectomy. This patient had been hospitalized repeatedly for the past 15 years because of the chronic pyelits, and hyperglycemia, and nephrosis. She developed chronic renal failure, hemodialysis was started when diagnosis of Fabry's Disease was made at age of 41. Preoperative electrocardiogram revealed ischemic change on leads II, V5 and V6. Nifedipine was administered for hypertension. The anesthesia was induced with thiopental followed by vecuronium for endotracheal intubation, and maintained with nitrous oxide, oxygen and isoflurane. Accompanied by nicardipine for hypertension, and vecuronium for muscle relaxation using a neurotransmission monitor (Relaxograph), nitroglycerin was continuously infused. We avoided the effect of atropine for reversal of muscle relaxation because most of the patients were complicated with hypohidrosis. During administration of nitroglycerin and nicardipine, the neuromuscular blocking effects of vecuronium could be prolonged. The neuromuscular monitoring was useful in this case.
Masui 1995 Sep
PMID:[The anesthetic management of a patient with Fabry's disease]. 852 62

Four alpha-galactosidase gene mutations were identified in Japanese male patients with Fabry disease who had no detectable alpha-galactosidase activity. Two of them were novel mutations, an 11-bp deletion in exon 2 and a g-1 to t substitution at the 3' end of the splice acceptor site in intron 1. The former caused a frameshift and led to the creation of a new stop codon at codon 118. The latter was predicted to provoke aberrant mRNA splicing followed by accelerated degradation of the mRNA. A nonsense mutation, R301X, and a 2-bp deletion starting at nucleotide position 718, which were reported previously, were also identified in unrelated patients.
Jpn J Hum Genet 1996 Sep
PMID:Two novel mutations in the alpha-galactosidase gene in Japanese classical hemizygotes with Fabry disease. 899 67

There are several syndromes in which neurological and cutaneous alterations of vascular origin, among other symptoms, occur. The key point of this fact is that these cutaneous signs permit early diagnosis, thus helping in further recognition of more complex syndromes and preventing unnecessary, harmful and costly diagnostic procedures or having to wait until the appearance of neurological signs. Therefore, these diseases should be classified attending to the most notorious vascular lesions they show, though they may show other less frequent cutaneous vascular lesions. In this way, these syndromes can be classified as associated with nevus flammeus (Sturge-Weber, Shapiro-Shulman, Bonnet-Dechaume-Blanc, Cobb, Klippel-Trenaunay, Fegeler, Robert), cavernous hemangiomas (Maffucci, blue-rubber-bleb-nevus, Proteus, Bannayan-Zonana, Riley-Smith, familial cavernous angiomatosis, POEMS syndrome), capillary hemangiomas (Rubinstein-Tayabi, Coffin-Siris, PHACE syndrome), telangiectasia (congenital telangiectatic cutis marmorata, Rendu-Osler-Weber, ataxia telangiectasia, Cockayne, De Sanctis-Cacchione), livedo reticularis (Sneddon, Divry-van-Bogaert), angioqueratoma (Fabry disease, Fucosidosis) and hemangioblastoma (Von Hippel-Lindau). Though we have tried that these vascular lesions should be named as angiomas if they are malformations and hemangiomas if they are benign neoplasias, they are called following morphological aspects rather than other criteria, due to their unknown origin.
Rev Neurol 1997 Sep
PMID:[Neurocutaneous syndromes with vascular alterations]. 927 70

Human alpha-galactosidase A (EC 3.2.1.22; alpha-Gal A) is the lysosomal exoglycosidase responsible for the hydrolysis of terminal alpha-galactosyl residues from glycoconjugates and is the defective enzyme causing Fabry disease (McKusick 301500). An unusally elevated level of plasma alpha-Gal A activity (> 2.5 times the normal mean) was detected in two unrelated normal males and the elevated activities were inherited as X-linked traits in their families. Sequencing of the alpha-Gal A coding region, intron/exon boundaries and 5'-flanking region from the proband identified a single mutation, a G-->A transition 30 nt upstream from the initiation of translation codon in exon 1. The -30G-->A mutation occurred in a putative NF kappa B/Ets consensus binding site that was recently shown to inhibit protein binding to the 5'-untranslated region of the gene, providing a possible explanation for its high activity. To further characterize the mutation, the mRNA and protein expressed by this variant allele were studied. Purified plasma and lymphoblast alpha-Gal A activity from individuals with the -30G-->A mutation had normal physical and kinetic properties. In vitro translation of mRNAs from the cloned normal and high plasma activity alleles resulted in similar levels of alpha-Gal A protein, indicating that this mutation did not enhance translation. These findings suggest that the -30G-->A mutation in the 5'-untranslated region of the alpha-Gal A gene enhances transcription, presumably by interfering with the binding of negatively-acting transcription factors which normally decrease alpha-Gal A expression in various cells. Preliminary studies of the frequency of the -30G-->A mutation in 395 unrelated normal males of mixed ancestry revealed two additional unrelated individuals who had high plasma enzymatic activity and the mutation, confirming the effect of this mutation on enzyme expression and suggesting that about 0.5% of normal individuals have high plasma alpha-Gal A activity due to this variant allele.
J Inherit Metab Dis 1997 Sep
PMID:Human alpha-galactosidase A: high plasma activity expressed by the -30G-->A allele. 932 59

The rotational spectrum of (CH3OH)2 has been observed in the 8 to 24 GHz region with a pulsed-beam Fabry-Perot cavity Fourier-transform microwave spectrometer. Previously we demonstrated that each transition of the a-type R(J), Ka = 0 is split into 15 states of the 16 theoretically expected states by tunneling motions. Here we show that the K = 1 states are split into the 16 expected states through the assignment of the Ka = 1 a-type transitions and DeltaKa = 1 b-type transitions. The internal-rotation analysis of the two inequivalent methyl groups presented here was guided by the previous experimental observations and theory for multidimensional tunneling, which predicts 16 tunneling components for each R(J) transition from 25 distinct tunneling motions. The effective barrier to internal rotation for the donor methyl group of (CH3OH)2 is V3 = 183.0 cm-1, and is one-half of the value for the methanol monomer (370 cm-1), while the barrier to internal rotation of the acceptor methyl group is 120 cm-1, one-third of the methanol monomer. The structure of the methanol dimer complex is similar to that of water dimer with a hydrogen bond distance of 1.96(2) A and tilt of the acceptor methanol of 77(2)degrees from the O-H-O axis (one standard deviation uncertainty). This structure shows good agreement with the angular orientation of the methyl groups derived in the internal-rotation analysis. Copyright 1997 Academic Press. Copyright 1997Academic Press
J Mol Spectrosc 1997 Sep
PMID:The Microwave Spectrum of the Methanol Dimer for K = 0 and 1 States 934 99

An examination of the roots of Lycium chinense (Solanaceae) has resulted in the discovery of 14 calystegines, a cycloheptane bearing an amino group and three hydroxyl groups, and two polyhydroxylated piperidine alkaloids. Calystegines A7 and B5, in addition to the previously known calystegines A3, A5, A6, B1, B2, B3, B4, C1, C2 and N1, were isolated and determined as 1alpha,2beta,4alpha-trihydroxy-nortropane and 1alpha,2alpha,4alpha,7alpha-tetrahydroxy-nort ropane, respectively. L. chinense also had two polyhydroxytropanes bearing a methyl group on the nitrogen atom, unlike the previously reported nortropane alkaloids. They were established as N-methylcalystegines B2 and C1, and their N-methyl groups were found to be axially oriented from NOE experiments. 1Beta-amino-3beta,4beta,5alpha-trihydroxycyclohepta ne was also present in L. chinense and may be a biosynthetic precursor of the calystegines that occur in this plant. Two polyhydroxypiperidine alkaloids, fagomine and 6-deoxyfagomine, were isolated. Calystegine B2 is a potent competitive inhibitor of almond beta-glucosidase (Ki = 1.9 microM) and coffee bean alpha-galactosidase (Ki = 0.86 microM), while N-methylcalystegine B2 was a more potent competitive inhibitor of the latter enzyme (Ki = 0.47 microM) than the parent compound but showed a marked lack of inhibitory activities towards most other glycosidases. Since this compound is a very specific inhibitor of alpha-galactosidase and inhibits rat liver lysosomal alpha-galactosidase with a Ki of 1.8 microM, it may provide a useful experimental model for the lysosomal storage disorder, Fabry's disease. The addition of a hydroxyl group at C6exo, as in calystegines B1 and C1, enhances the inhibitory potential towards beta-glucosidase and beta-galactosidase but markedly lowers or abolishes inhibition towards alpha-galactosidase. Hence, the N-methylation of calystegine C1 did not enhance its inhibition of alpha-galactosidase. The chemical N-methylation of calystegines A3 and B4 markedly enhanced inhibition of coffee bean alpha-galactosidase, with Ki values of 5.2 microM and 36 microM, respectively, but almost eliminated their inhibitory potential towards beta-glucosidase and trehalase, respectively. Thus, methylation of the nitrogen atom significantly altered the specificity of the inhibitors.
Eur J Biochem 1997 Sep 01
PMID:Specific alpha-galactosidase inhibitors, N-methylcalystegines--structure/activity relationships of calystegines from Lycium chinense. 934 81

Inherited kidney diseases are frequently encountered in adults; the diagnosis is often made and they usually progress to renal failure at this age. Autosomal dominant polycystic kidney disease is the most prevalent. It is one of the most common inherited diseases, involving 1 in 400 to 1,000 individuals. Renal cysts growth is responsible for hypertension and renal failure; polycystic kidney disease represents 6 to 7% of the causes of end-stage renal failure in adults. The disease also encompasses extra-renal localisations, i.e. liver cysts and intra-cranial aneurysms. Multiple renal cysts may be found in other inherited disorders, such as tuberons sclerosis and von Hippel-Lindau disease. Alport syndrome is the second most prevalent inherited kidney disease, characterized by various abnormalities of type IV collagen molecules. Molecular diagnosis is possible in some families, which makes genetic counselling more reliable. Finally renal involvement is frequent in a great variety of inherited metabolic (Fabry's disease, glycogen storage disease type 1, hyperuricemic nephropathy) or non-metabolic (nail-patella or Bardet-Biedl syndrome) diseases.
Rev Prat 1997 Sep 15
PMID:[Hereditary kidney diseases in adults]. 936 16

The pathophysiology of gastrointestinal symptoms in patients with Fabry's disease is uncertain, despite the demonstration of histological and radiographic abnormalities of the gastrointestinal tract. The aims of this study were to determine if the gastrointestinal symptoms reported by patients with Fabry's disease are associated with abnormal gastric emptying and, if they are, whether prokinetic drug therapy would be beneficial. Ten patients with Fabry's disease had radionuclide gastric emptying studies performed to determine if gastrointestinal symptoms correlated with objective evidence of abnormal gastric emptying. A second study was performed in seven patients who received 5 days of therapy with oral metoclopramide. The mean percent solid gastric emptying for Fabry's patients was significantly less than that of a normal control group (40 vs 67%, P < 0.005). Five of seven patients with symptoms had abnormal gastric emptying. Six of seven symptomatic patients reported clinical improvement with metoclopramide. Of four symptomatic patients who had a repeat study after treatment, two showed improved emptying. In conclusion, our results suggest that gastrointestinal symptoms in Fabry's disease are frequently associated with delayed gastric emptying and that treatment with metoclopramide produces symptomatic and sometimes functional improvement.
Nucl Med Commun 1998 Sep
PMID:Gastrointestinal symptoms and delayed gastric emptying in Fabry's disease: response to metoclopramide. 1058 95

Using a laser that is frequency locked to a Fabry-Perot etalon of high finesse and stability, we probe the 5d(10)6s (2)S(1/2)(F = 0)<-->5d(9)6s(2) (2)D(5/2)(F = 2) Deltam(F) = 0 electric-quadrupole transition of a single laser-cooled 199Hg+ ion stored in a cryogenic radio-frequency ion trap. We observe Fourier-transform limited linewidths as narrow as 6.7 Hz at 282 nm ( 1.06x10(15) Hz), yielding a line Q approximately 1.6x10(14). We perform a preliminary measurement of the 5d(9)6s(2) (2)D(5/2) electric-quadrupole shift due to interaction with the static fields of the trap, and discuss the implications for future trapped-ion optical frequency standards.
Phys Rev Lett 2000 Sep 18
PMID:Sub-dekahertz ultraviolet spectroscopy of 199Hg+ 1097 82


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