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G Bach

Publications and source records attributed to G Bach.

At least 73 records · Page 4Linked to original sources
PubMed1988

Selection in favor of lysosomal storage disorders?

Four examples of Israeli communities or large families in which high consanguinity is common are presented, with two different lysosomal storage disorders within each community. In each of the four cases the stored substances share common chemical structure, despite the different lysosomal hydrolases involved in each disease. A similar phenomenon is known among the Ashkenazi Jews, in whom four of the most frequent hereditary disorders are lysosomal storage disorders, which are characterized by storage of sphingolipid derivatives. Similar findings are reported in the literature in other communities. We suggest that this phenomenon indicates a selection in favor of lysosomal storage disorders of similar nature in certain populations. The selection forces leading to this phenomenon have not been identified yet, and it has not yet been determined whether these forces are the same in the different communities presented here.

Consanguinity↗
PubMed1987

Aryl sulfatase A deficiency in psychiatric and neurologic patients.

Two hundred ninety-five psychiatric and neurologic patients were randomly screened for aryl sulfatase A (ASA) activity in lymphocyte extracts. Two of these patients showed very low ASA activity, in the range of metachromatic leukodystrophy (MLD)-affected patients. The residual activity in these low ASA patients showed normal enzyme behavior with regard to ASA kinetic features and the ability to catabolize 14C labeled sulfatide by intact fibroblasts. Taking into account that approximately 3% of the general population are homozygous for the pseudo-aryl sulfatase A gene and are clinically unaffected, the data obtained here indicate that the patients studied in this work, as well as most psychiatric patients reported in the literature with low ASA activity, represent the normal ASA polymorphism. Thus, the very low ASA activity patients are in fact homozygous for the pseudo-deficient allele, which does not result in clinical abnormalities. The clinical symptoms in these psychiatric patients and probably other "variant" MLD patients are therefore not related to low ASA activity.

Bipolar Disorder↗
PubMed1987

Diagnosis of arylsulfatase A deficiency in intact cultured cells using a fluorescent derivative of cerebroside sulfate.

A fluorescent derivative of cerebroside sulfate (12-(1-pyrene)dodecanoyl-sphingosylgalactosyl-0-3-sulfate (P12-sulfatide) has been synthesized as a potential substrate for the determination of cerebroside sulfatidase (or arylsulfatase A) activity. It was administered into cultured human skin fibroblasts and thereby utilized for the diagnosis of arylsulfatase A deficiency. Cultured skin fibroblasts from normal individuals and healthy persons suffering from a pseudoarylsulfatase A deficiency (PD) degraded the P12-sulfatide, while in cells derived from a metachromatic leukodystrophy (MLD) patient it remained essentially intact. This contrasts with in vitro determinations of enzymatic activity, where the MLD or PD-derived arylsulfatase A exhibit similar deficiency, in spite of a profoundly different clinical course. Administration of the fluorescent sulfatide into the intact cells permitted a sensitive and rapid diagnosis of MLD and its distinction from the PD-phenomenon. This might be of particular importance for cases in which a rapid diagnosis is required and for prenatal diagnosis of fetuses from families afflicted with both MLD and pseudo-deficiency mutant genes.

Cell Line↗
PubMed1987

Mucolipidosis type IV: clinical spectrum and natural history.

The clinical spectrum and developmental features of mucolipidosis type IV, a recessive lysosomal storage disorder, are presented. The evaluation was based on information from the clinical charts and information obtained from the families of 20 patients between the ages of 2 to 17 years. The clinical manifestations of the disease, profound psychomotor retardation and visual impairment, appear during the first year of life. Definitive diagnosis is made by electron microscopy which reveals storage organelles typical of the mucolipidoses. This study details, for the first time, the heterogeneity of the ophthalmologic features, specifically as pertains to the age of onset, degree and clinical course of the corneal opacities, and the retinal involvement. Although the top developmental level was found to be 12 to 15 months in language and motor function, the course of the disease is protracted for some children, who show only a slight improvement, and others, little if any deterioration despite the early infantile onset of the disease. This presentation provides guidelines for the clinical diagnosis of mucolipidosis type IV.

Adolescent↗
PubMed1986

[Panmyelopathy and myeloproliferative syndrome].

From the viewpoint of a territorial haematological centre with a certainly preselected number of patients the initial symptom of bi- or pancytopenia in 3/4 of the cases proves as first reference to a myeloproliferative or myelodysplastic syndrome. Of these cases 62.5% transferred into a crisis of blasts; that is, they must be regarded as real preleukemia. The morphology of the bone marrow as well as the stem cell cultures obtained from this give important references to the diagnostic classification of the early changes as well as to their prognosis.

Biopsy, Needle↗
PubMed1986

Internalization of exogenous gangliosides in cultured skin fibroblasts for the diagnosis of mucolipidosis IV.

The internalization of exogenous mixed brain gangliosides in ML IV cultured skin fibroblasts indicated an impairment of ganglioside catabolism in these cells. Incubation of ML IV, normal and various other lysosomal storage disorders cell lines for five days with exogenous tritium labelled GM3, GD1a or GT1 gangliosides allowed accurate quantitation of the retained gangliosides. This in vitro approach provides a reliable method for the diagnosis of ML IV.

Cells, Cultured↗
PubMed1986

Genetic heterogeneity in Gaucher disease.

Considerable clinical variability occurs in adult Gaucher disease type I and three main subtypes may be delineated: a very mild form, a severe form, and a moderate form which itself presents various clinical manifestations. A study based on 25 families from our clinic and a review of published reports showed that when both parents were heterozygous and more than one child was affected with Gaucher disease type I, there was always intrafamilial similarity concerning the three subtypes. In families where one parent and at least one child were affected, variability in the clinical subtype of Gaucher disease type I might occur among the affected members of the family. We propose that the three different clinical subtypes of this disease reflect the genetic heterogeneity of two alleles, G1a and G1b and the three corresponding genotypes represent the three different subtypes of the disease.

Gaucher Disease↗
PubMed1986

Hunter syndrome: prenatal diagnosis in maternal serum.

Iduronate sulfate sulfatase (ISS), the deficient hydrolase in Hunter syndrome, consistently increases in the serum of pregnant women, reaching a three- to fourfold increase from pre-pregnancy levels toward the end of pregnancy. In Hunter carriers, a correlation occurs between the status of the fetus with regard to Hunter syndrome and the ISS increase in maternal serum. Thus, in pregnancies with Hunter-affected fetuses, enzyme levels did not change in the serum of heterozygous mothers until abortion was performed, while in nonaffected fetuses, ISS increased usually very early in pregnancy--as early as the 6th-12th week. In heterozygote female fetuses, this increase might be delayed. These data imply that a prenatal diagnosis of Hunter syndrome might be accomplished in maternal serum at early conventional procedures for the prenatal diagnosis of Hunter syndrome.

Chromatography, DEAE-Cellulose↗
PubMed1985

Krabbe disease: increased incidence in a highly inbred community.

Krabbe disease (globoid cell leukodystrophy) was found with very high incidence (6/1,000 live births) in a large Druze kindred in Israel. The clinical data on 12 of the affected children demonstrated clinical variability even though these children are homozygous for the same mutation by descent from a common ancestor.

Age Factors↗
PubMed1985

Hunter syndrome among Ashkenazi Jews in Israel; evidence for prenatal selection favoring the Hunter allele.

Analysis of Ashkenazi families with Hunter patients in Israel demonstrated the complete absence of new mutations among the probands' mothers. Furthermore, in these families a significant deviation of the segregation ratio between the Hunter gene and the normal allele was demonstrated among offspring of heterozygous mothers or siblings of affected children. This may be due to pre- or postzygotic prenatal selection, favoring the X chromosome carrying the Hunter gene among Ashkenazi Jews.

Alleles↗
PubMed1985

Ganglioside sialidase distribution in mucolipidosis type IV cultured fibroblasts.

The subcellular distribution of ganglioside sialidase in Mucolipidosis IV (ML IV) cells was characterized by a series of Percoll gradients. Similar to normal cells, the enzyme cosedimented with plasma membrane markers, although this activity was reduced and exhibited decreased solubility in ML IV cells. Only trace amounts of ganglioside sialidase (less than 5%) was found in the lysosomes of normal cells. This activity was apparently reduced in ML IV cells but its minute activity in controls excluded further characterization of these differences. Plasma membranes on 6.7 and 5.6% Percoll gradients were biomodally distributed. Ganglioside sialidase in normal cells was found to be in both the heavier and the lighter membrane fractions, whereas the enzyme in ML IV cells was associated mainly with the denser membrane fraction. These data indicate that the enzyme in ML IV cells is characteristically different from normal in that it exhibits reduced activity and solubility and a different plasma membrane distribution.

Cell Membrane↗
PubMed1984

Prenatal diagnosis of Krabbe disease using a fluorescent derivative of galactosylceramide.

A fluorescent substrate 12-(N-methyl-N(7-nitro-2-oxa-1,3-diazol-4-yl) aminododecanoyl sphingosyl beta-D-galactoside ('NBD galactocerebroside') was synthesized and used for the detection of galactocerebrosidase activity. The enzyme determinations using this substrate were found to be extremely sensitive yielding unambiguous results. This substrate was used for the prenatal diagnosis of a fetus affected with Krabbe disease; the diagnosis was later confirmed in the aborted fetus.

Cells, Cultured↗
PubMed1984

Heterozygote detection in Hunter syndrome.

Iduronate sulfate sulfatase activity was determined in 36 women, relatives of Hunter syndrome patients. The use of serum and lymphocyte extracts for the determination of enzyme levels enabled the detection of 13 out of 15 (86%) obligate heterozygotes and identification of 10 of 21 other relatives as carriers. These methods are relatively simple and can easily be applied for routine examinations of all women at risk of being a Hunter heterozygote. These results permit for the first time meaningful genetic counseling for the families of Hunter patients.

Adult↗
PubMed1984

Arylsulfatase A in pseudodeficiency.

Arylsulfatase A (ASA) is found to be deficient in healthy individuals (pseudo arylsulfatase A deficiency) who usually show in vitro ASA levels in the range of metachromatic leukodystrophy patients. The in vitro properties of ASA in pseudodeficiency were studied in cultured fibroblasts. The residual ASA activity showed apparent Km with the synthetic substrate (2.6 mM), pH optimum of activity (pH 5.0), and sensitivity to heat denaturation at 65 degrees C (T1/2, 10 min) similar to those found in controls. To test whether the low in vitro activity is a result of extreme sensitivity to the homogenization procedure, cells were disrupted by five different techniques, including rapid freezing and thawing, hand homogenization, ultrasonication, mild osmotic shock, and nitrogen cavitation; all yielded similar ASA ratio of the pseudodeficient to control. The use of antiproteases phenylmethylsulfonyl fluoride and leupeptin did not affect the residual ASA activity in the pseudodeficient line. These results imply that the ASA that is formed in this condition has properties similar to those of the normal hydrolase, so that even if it is synthesized in lower amounts, it is still sufficient to promote normal catabolism of sulfatide. Screening for ASA activity in lymphocyte extracts of a random sample of 250 individuals revealed 7 individuals with enzyme level in the MLD heterozygote range or lower. These individuals apparently represent homozygosity for pseudodeficiency (pd/pd). This implies that the frequency of the pseudodeficient allele is about 15% in the general population, leading to polymorphism of the ASA.

Adult↗
PubMed1983

Synthesis and maturation of cross-reactive glycoprotein in fibroblasts deficient in arylsulfatase A activity.

The biosynthesis of arylsulfatase A was studied in cultured fibroblasts by pulse-chase labeling with [2-3H]mannose; the enzyme was isolated by immunoprecipitation and denaturing polyacrylamide gel electrophoresis. In normal fibroblasts, and in fibroblasts from a patient with multiple sulfatase deficiency, the enzyme was synthesized as a glycoprotein of apparent molecular weight of 59,000; half of it was processed over a period of 4 days to Mr = 57,000. The precursor chain of Mr = 59,000 was secreted in the presence of 10 mM NH4Cl. An immunoprecipitable glycoprotein of normal size was synthesized by fibroblasts from two unrelated patients with metachromatic leukodystrophy, but this material disappeared within twenty hours. In fibroblasts from an individual with pseudo-deficiency of arylsulfatase A, the immunoprecipitable precursor glycoprotein was smaller (Mr = 56,000). The synthesis of cross-reactive proteins with altered properties supports the concept of allelic mutations as the genetic basis of metachromatic leukodystrophy and of arylsulfatase A pseudo-deficiency.

Alleles↗