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1.
Genet Med ; 21(1): 44-52, 2019 01.
Article in English | MEDLINE | ID: mdl-29543226

ABSTRACT

PURPOSE: Plasma globotriaosylsphingosine (lyso-Gb3) is a promising secondary screening biomarker for Fabry disease. Here, we examined its applicability as a primary screening biomarker for classic and late-onset Fabry disease in males and females. METHODS: Between 1 July 2014 and 31 December 2015, we screened 2,359 patients (1,324 males) referred from 168 Japanese specialty clinics (cardiology, nephrology, neurology, and pediatrics), based on clinical symptoms suggestive of Fabry disease. We used the plasma lyso-Gb3 concentration, α-galactosidase A (α-Gal A) activity, and analysis of the α-Gal A gene (GLA) for primary and secondary screens, respectively. RESULTS: Of 8 males with elevated lyso-Gb3 levels (≥2.0 ng ml-1) and low α-Gal A activity (≤4.0 nmol h-1 ml-1), 7 presented a GLA mutation (2 classic and 5 late-onset). Of 14 females with elevated lyso-Gb3, 7 displayed low α-Gal A activity (5 with GLA mutations; 4 classic and 1 late-onset) and 7 exhibited normal α-Gal A activity (1 with a classic GLA mutation and 3 with genetic variants of uncertain significance). CONCLUSION: Plasma lyso-Gb3 is a potential primary screening biomarker for classic and late-onset Fabry disease probands.


Subject(s)
Biomarkers/blood , Fabry Disease/blood , Genetic Testing , Glycolipids/blood , Sphingolipids/blood , Aged , Fabry Disease/genetics , Fabry Disease/pathology , Female , Galactosidases/blood , Galactosidases/genetics , Glycolipids/genetics , Humans , Male , Middle Aged , Mutation , Patient Selection , Risk Factors , Sphingolipids/genetics
2.
Rev Med Suisse Romande ; 122(9): 449-53, 2002 Sep.
Article in French | MEDLINE | ID: mdl-12422475

ABSTRACT

Fabry disease is a X-linked sphingolipid storage disorder resulting from the defective activity of the lysosomal enzyme, alpha-galactosidase A. Hemizygotes develop severe multisystemic disease, dominated by renal failure and progressive neurological and cardiac involvement, causing premature death. Thirty percent of heterozygotes have severe involvement of one or several organs. With developments in molecular biology, it is now possible to produce the human recombinant enzyme alpha-galactosidase A. More than 20 patients are now treated in Switzerland.


Subject(s)
Fabry Disease/diagnosis , Biopsy , Chromosomes, Human, X/genetics , Fabry Disease/drug therapy , Fabry Disease/genetics , Galactosidases/blood , Galactosidases/therapeutic use , Humans , Male , Middle Aged , Pedigree , alpha-Galactosidase/blood , alpha-Galactosidase/therapeutic use
3.
J Clin Lab Anal ; 5(3): 197-205, 1991.
Article in English | MEDLINE | ID: mdl-2061744

ABSTRACT

A novel enzyme immunoassay (immune complex transfer enzyme immunoassay) for anti-thyroglobulin IgG using beta-D-galactosidase from Escherichia coli as label was reported previously. This immunoassay was highly sensitive in demonstrating anti-thyroglobulin IgG not only in all patients with Graves' disease and chronic thyroiditis but also in a large proportion of healthy subjects. However, the detection of anti-thyroglobulin IgG at low levels in some serum samples was difficult, probably due to the presence of anti-beta-D-galactosidase antibodies. In the present study, the use of inactive beta-D-galactosidase was tested for elimination of interference by anti-beta-D-galactosidase antibodies. Preincubation of serum samples with excess of inactive beta-D-galactosidase resulted in sufficiently low backgrounds to detect low levels of anti-thyroglobulin IgG with little effect on the dose-response of anti-thyroglobulin IgG. As a result, it was revealed that anti-thyroglobulin IgG was present in almost all healthy subjects as well as all patients with Graves' disease and chronic thyroiditis.


Subject(s)
Autoantibodies/immunology , Galactosidases , Graves Disease/blood , Immunoglobulin G/analysis , Thyroiditis/blood , Adult , Aged , Aged, 80 and over , Antigen-Antibody Complex , Escherichia coli/enzymology , Female , Galactosidases/blood , Graves Disease/enzymology , Graves Disease/immunology , Humans , Immunoenzyme Techniques , Male , Middle Aged , Thyroiditis/enzymology , Thyroiditis/immunology
4.
J Biol Chem ; 265(26): 15889-93, 1990 Sep 15.
Article in English | MEDLINE | ID: mdl-2118533

ABSTRACT

The mechanism of decline in the catalytic activity of intestinal lactase during neonatal maturation has not been defined, but a shift in the lactase subunit synthesis from an active 130-kDa subunit to an inactive 100-kDa species has now been noted in the adult rat (Quan, R., Santiago, N. A., Tsuboi, K. K., and Gray, G. M. (1990) J. Biol. Chem. 265, 15882-15888). The subunit structure, synthesis, intracellular assembly, and subsequent degradation of lactase from the brush-border surface membrane was examined in 15-day-old pre-weaned and 30-day-old post-weaned intact rats. Lactase was labeled intraintestinally with [35S]methionine, isolated from Triton-solubilized membranes with monospecific polyclonal anti-lactase, and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. The protein-stained gel revealed subunits of 225 and 130 kDa, the latter species predominating in both the pre- and post-weaned state. The distinct adult-type 100-kDa moiety was present in post-weaned animals while only a trace of a slightly larger (approximately 110 kDa) species was observed in pre-weaned animals. Quantitation of radioactivity in newly synthesized lactase revealed an increasing prominence of the 100-kDa species in post-weaned rats (130/100 incorporation ratio: pre-weaned 6.2; post-weaned 3.3). Accumulation of newly labeled lactase in brush-border membranes after intraperitoneal [35S]methionine labeling was similar in both groups at 3 h. Despite these comparable rates of lactase synthesis, assembly and insertion in the pre- and post-weaned state, subsequent removal of the 130-kDa unit was more rapid in post-weaned animals (t1/2 = 11 h; pre-weaned t1/2 = 37 h). In intact rats, the neonatal maturational decline in lactase catalytic activities involves both a shift to production of the inactive 100-kDa subunit and increased membrane surface degradation of the active 130-kDa subunit.


Subject(s)
Galactosidases/blood , Intestine, Small/enzymology , Microvilli/enzymology , Protein Processing, Post-Translational , beta-Galactosidase/blood , Aging , Animals , Animals, Newborn , Intestine, Small/growth & development , Kinetics , Lactase , Macromolecular Substances , Methionine/metabolism , Molecular Weight , Muscle Development , Muscle, Smooth/enzymology , Muscle, Smooth/growth & development , Rats , Rats, Inbred Strains , beta-Galactosidase/genetics , beta-Galactosidase/metabolism
6.
Z Gesamte Hyg ; 36(1): 48-50, 1990 Jan.
Article in German | MEDLINE | ID: mdl-2156384

ABSTRACT

Progressive systemic sclerosis (PSS) is a rare disease belonging to the collagen diseases. PSS is frequently observed in workers with an intensive exposure to crystalline silica and with silicosis in the GDR. The recognition as an occupational disease is regulated by law. The elevated beta-galactosidase activity in the serum of patients with silicosis and beginning PSS can be used for detecting of early stages of PSS. References are given to medical care of patients with silicosis and exposure to quartz.


Subject(s)
Dust/adverse effects , Galactosidases/blood , Occupational Diseases/diagnosis , Quartz/adverse effects , Scleroderma, Systemic/diagnosis , Silicon Dioxide/adverse effects , Silicosis/complications , beta-Galactosidase/blood , Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Occupational Diseases/enzymology , Scleroderma, Systemic/enzymology
9.
Clin Chim Acta ; 176(1): 1-8, 1988 Aug 15.
Article in English | MEDLINE | ID: mdl-3139330

ABSTRACT

The circadian and circannual group rhythms in the plasma concentrations of the following lysosomal enzymes were studied in women and men: beta-D-N-acetylglucosaminidase, beta-D-glucuronidase, beta-D-glucosidase, beta-D-galactosidase, alpha-D-galactosidase, alpha-L-fucosidase and alpha-D-mannosidase. The circadian rhythm was detected in all the tested enzymes of women, and only in alpha-D-galactosidase, beta-D-glucosidase, alpha-D-mannosidase and beta-D-N-acetylglucosaminidase of men. A statistically significant difference between genders in the circadian rhythm was exhibited by beta-D-galactosidase, beta-D-glucosidase, beta-D-N-acetylglucosaminidase, beta-D-glucuronidase, alpha-D-galactosidase and alpha-L-fucosidase. A circannual rhythm was detected in all the tested enzymes, with the exception of beta-D-glucuronidase and beta-D-N-acetylglucosaminidase, without any statistically significant difference between genders. The group rhythms of some of the enzymes (alpha-D-galactosidase, beta-D-glucosidase, beta-D-galactosidase) showed similar values of both circadian and circannual acrophases, suggesting that they may be subjected as a group to the same chronobiological coordination. The chronobiological rhythms of lysosomal enzymes were different from those of lactate dehydrogenase and alpha 1-antitrypsin, indicating that these rhythms are not merely reflecting fluctuations of the water content of plasma. No in-phase relationship was observed between the circadian and circannual rhythms of plasma cortisol and those of the tested lysosomal enzymes, excluding a direct chronobiological relationship between this hormone and lysosomal enzymes.


Subject(s)
Circadian Rhythm , Lysosomes/enzymology , Acetylglucosaminidase/blood , Adolescent , Adult , Female , Galactosidases/blood , Glucuronidase/blood , Humans , Hydrocortisone/blood , Male , Mannosidases/blood , Periodicity , Reference Values , alpha 1-Antitrypsin/blood , alpha-Glucosidases/blood , alpha-L-Fucosidase/blood , alpha-Mannosidase , beta-Glucosidase/blood
10.
Vopr Med Khim ; 34(4): 129-31, 1988.
Article in Russian | MEDLINE | ID: mdl-3195126

ABSTRACT

A procedure was developed for estimation of galactocerebroside beta-D-galactosidase activity in leukocytes using a new fluorogenic compound 6-hexadecanoylamino-4-methylum-belliferyl-beta-D-galactop yra noside (HMGal) as a substrate. Some patterns of the fluorometric procedure were compared with corresponding parameters of the spectrophotometric method in which a chromogenic substrate HNGal was used. Sensitivity of the fluorometric procedure with HMGal as a substrate was increased 100-fold as compared with the spectrophotometric method. At the same time, the fluorometric procedure enabled to reduce considerably the incubation period and the cell protein content per an assay. High sensitivity and reproducibility of the procedure with HMGal as a substrate allowed to carry out biochemical diagnosis of Krabbe disease in leukocytes.


Subject(s)
Fluorometry , Galactosidases/blood , Galactosylceramidase/blood , Leukocytes/enzymology , Spectrometry, Fluorescence , Humans
12.
Hum Hered ; 38(2): 76-82, 1988.
Article in English | MEDLINE | ID: mdl-2837434

ABSTRACT

alpha-Galactosidase and beta-galactosidase activities have been determined in leukocyte preparations from 100 randomly selected Chinese adults. For alpha-galactosidase, two groups with low activities were identified: group I consisted of 3 females having activities below 40% of normal, and group II consisted of 5 males and 1 female with activities about 60% of normal. Family studies suggested that these low alpha-galactosidase activities are genetically determined. Only 1 individual was found to have about 50% of normal beta-galactosidase activity; presumably he is a carrier for beta-galactosidase deficiency (GM1 gangliosidosis).


Subject(s)
Fabry Disease/genetics , Galactosidases/blood , Gangliosidoses/genetics , Leukocytes/enzymology , Lysosomes/enzymology , alpha-Galactosidase/blood , beta-Galactosidase/blood , Adult , China/ethnology , Fabry Disease/enzymology , Female , G(M1) Ganglioside , Gangliosidoses/enzymology , Genetic Carrier Screening , Humans , Male , Pedigree , United States , beta-Galactosidase/deficiency
13.
Biochem Med Metab Biol ; 38(3): 331-7, 1987 Dec.
Article in English | MEDLINE | ID: mdl-3124873

ABSTRACT

Our results of the study of the human leukocyte and plasma beta-fuc show that it is possible to measure the enzyme, although enzyme activity is low and long incubation times are necessary for the plasma enzyme. We were interested to know if beta-gal and beta-fuc are enzyme activities of a single protein. For the leukocytes, our observations on enzyme inhibition by galactonic acid-y-lactone and derivatives of beta-D-galactose, together with an enzyme deficiency in GM1 gangliosidosis confirm the previous observation that beta-fuc and beta-gal are enzyme activities of a single protein (5). In plasma, the high correlation coefficient, similar thermoinactivation profiles of beta-gal and beta-fuc, the inactivation of the two enzymes by beta-D-galactopyranosylmethyl-p-nitrophenyltriazene, and inhibition of beta-fuc by galactonic acid-y-lactone and paranitrophenyl-beta-D-galactose strongly suggest that beta-gal and beta-fuc are enzyme activities of a common protein. Because of the very low specific activities, we do not recommend the determination of beta-fuc in leukocytes or plasma for the biochemical diagnosis of GM1 gangliosidosis.


Subject(s)
Galactosidases/blood , Leukocytes/enzymology , alpha-L-Fucosidase/blood , beta-Galactosidase/blood , Enzyme Stability , Humans , Hydrogen-Ion Concentration , In Vitro Techniques , Kinetics , Temperature
15.
Clin Orthop Relat Res ; (215): 248-53, 1987 Feb.
Article in English | MEDLINE | ID: mdl-3100122

ABSTRACT

Both osteoporosis and lactase deficiency are seen commonly in the United States. Since the latter may lead to avoidance of calcium sources and may exacerbate the bone disease in populations at risk, we studied lactose tolerance and histomorphometrically analyzed undecalcified transiliac bone biopsies in a consecutive group of postmenopausal women with the osteoporotic spinal compression fracture syndrome. Oral lactose tolerance tests prior to the biopsy clearly separated two groups. Sixty-five percent had abnormal test results. The bone biopsies in the lactase deficient group showed more osteoid volume and osteoid seam widths on examined trabecular bone. Analysis of tetracycline-labeled bone revealed significant increases in both single, double, combined single and double tetracycline labels, and the percent osteoid labeled with tetracycline. There was no difference in the calcification rates. These findings indicate different mineralization activity in lactase deficient patients, possibly reflecting their lower dietary calcium intake.


Subject(s)
Fractures, Spontaneous/diagnosis , Galactosidases/blood , Lactose Intolerance/diagnosis , Osteoporosis/diagnosis , Spinal Injuries/diagnosis , beta-Galactosidase/blood , Biopsy , Female , Fractures, Spontaneous/ethnology , Fractures, Spontaneous/pathology , Humans , Ilium/pathology , Lactose , Lactose Intolerance/ethnology , Lactose Intolerance/pathology , Menopause , Middle Aged , Osteoporosis/ethnology , Osteoporosis/pathology , Spinal Cord Compression/diagnosis , Spinal Cord Compression/ethnology , Spinal Cord Compression/pathology , Spinal Injuries/ethnology , Spinal Injuries/pathology
20.
Clin Chem ; 32(1 Pt 1): 16-21, 1986 Jan.
Article in English | MEDLINE | ID: mdl-3510090

ABSTRACT

In this clinically useful enzyme immunoassay of digoxin in serum, we mix sample, beta-galactosidase-labeled digoxin, and anti-digoxin Fab fragments for 30 min at room temperature, then use Sepharose-bound second antibody for phase separation, and measure the unbound enzyme activity directly in the supernate of the equilibrium reaction mixture. The immunoassay buffer--phosphate-buffered isotonic saline with added rabbit globulin (4 g/L), hydrolyzed gelatin (2 g/L), Brij 96 detergent (5 g/L), glycerol (0.25 mol/L), and N-acetyl-8-anilinonaphthalene-1-sulfonic acid (2 mmol/L)--minimizes serum matrix effects for convenient measuring of unbound enzyme--digoxin conjugate. The immunoassay developed with Fab fragments has better displacement characteristics than that with intact antibody. Performance of the assay compares favorably with that of other manual digoxin immunoassays; in comparison studies with EMIT involving 110 clinical specimens, the coefficient of correlation was 0.97.


Subject(s)
Digoxin/blood , Antibody Formation , Antibody Specificity , Buffers , Digoxin/immunology , Galactosidases/blood , Galactosidases/immunology , Humans , Immunoenzyme Techniques , Immunoglobulin Fab Fragments , Temperature
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