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E Sidransky

Publications and source records attributed to E Sidransky.

At least 73 records · Page 4Linked to original sources
PubMed1992

Animal model of Gaucher's disease from targeted disruption of the mouse glucocerebrosidase gene.

Gaucher's disease is the most prevalent lysosomal storage disorder in humans and results from an autosomally inherited deficiency of the enzyme glucocerebrosidase (beta-D-glucosyl-N-acylsphingosine glucohydrolase), which is responsible for degrading the sphingolipid glucocerebroside. An animal model for Gaucher's disease would be important for investigating its phenotypic diversity and pathogenesis and for evaluating therapeutic approaches. A naturally occurring canine model has been reported but not propagated. Attempts to mimic the disease in animals by inhibiting glucocerebrosidase have been inadequate. Here we generate an animal model for Gaucher's disease by creating a null allele in embryonic stem cells through gene targeting and using these genetically modified cells to establish a mouse strain carrying the mutation. Mice homozygous for this mutation have less than 4% of normal glucocerebrosidase activity, die within twenty-four hours of birth and store glucocerebroside in lysosomes of cells of the reticuloendothelial system.

Animals↗
PubMed1992

DNA mutation analysis of Gaucher patients.

We evaluated 62 Gaucher patients to determine whether patients with similar phenotypes had the same DNA point mutations. Genomic DNA from these Gaucher patients was screened for the 3 most frequent single-point mutations, occurring in 69% of the 124 patient alleles, and resulting in changes in amino acids 370, 444, and 463. Many different genotypes were observed, at least one of which is present in all 3 types of Gaucher disease. No specific symptom complex could be correlated with a unique genotype. Even the more clinically homogeneous subgroups of Gaucher patients contained several genotypes. This study further emphasizes the need for caution in making clinical predictions on the basis of current genotype analysis, especially since one might not discern a fetus affected with type 2 disease by current DNA studies. The severity of involvement in type 1 disease could also not be predicted. Thus, even limiting our focus to 3 isolated common point mutations, a given genotype cannot be uniquely correlated with a specific prognosis.

Adolescent↗
PubMed1992

Gaucher patients with oculomotor abnormalities do not have a unique genotype.

Sixteen non-Ashkenazic American children with Gaucher disease who demonstrate slowing of the horizontal saccades are described. Attempts to correlate this specific clinical phenotype with a unique genotype were unsuccessful. Focusing on the three most common mutations, at least five different genotypes were present in these patients. Children with this isolated oculomotor abnormality generally had a diffusely slowed background on EEG, but an otherwise normal neurologic examination, and exhibited earlier and more severe systemic manifestations and mortality. This study emphasizes the need for careful sequential neuro-ophthalmologic examinations in Gaucher patients and the need for caution in attempting to make clinical predictions regarding the course of Gaucher disease on the basis of current DNA mutational analysis.

Adolescent↗
PubMed1992

Gaucher disease in the neonate: a distinct Gaucher phenotype is analogous to a mouse model created by targeted disruption of the glucocerebrosidase gene.

A group of neonates with Gaucher disease with a particularly devastating clinical course is described. The phenotype of these infants is analogous to that of a Gaucher mouse, which was created by targeted disruption of the mouse glucocerebroside gene. Similar to the homozygous mutant mice with glucocerebrosidase deficiency, these infants present at or shortly after birth, have rapidly progressing fulminant disease, and many have associated ichthyotic skin and/or hydrops fetalis. This transgenetic mouse model of Gaucher disease has helped us to appreciate a distinct Gaucher phenotype. Potentially, as this technology is applied to create other animal models of metabolic diseases, it may enable the recognition of other, as yet unappreciated presentations of inherited disorders.

Animals↗
PubMed1990

Transvaginal chorionic villus sampling.

Chorionic villus sampling (CVS) with either transcervical catheters or transabdominal needles is a widely-accepted method for prenatal diagnosis. However, there exists a small subset of patients in whom sampling is difficult or impossible with either route because of individual anatomic variations. A new method of chorionic villus biopsy has been developed to circumvent these problems, utilizing transvaginal chorionic needle aspiration guided by an intravaginal ultrasound probe. This technique was performed successfully in 15 patients in whom villi could not be obtained by either of the conventional methods. This method now makes CVS possible in essentially all women regardless of their uterine anatomy or placental placement; it may also prove useful for very early chorionic sampling.

Adult↗
PubMed1990

Childhood mortality from accidents in Israel, 1980-84.

There were on average 1.5 million children aged 0-17 in Israel during the period 1980-84, with an average accidental mortality rate of 10.9/100,000. Although 77% of the children were Jewish and 23% non-Jewish, 45% of the accidental deaths occurred in the non-Jewish population. The accidental mortality rate among non-Jewish children was 20.9/100,000, which was 2.6-fold greater than that among Jewish children (7.9/100,000). Among both population groups, the male death rates were considerably higher than the female rates (10.5 vs. 5.1 among Jewish males and females, respectively, and 25.1 vs. 16.5 among non-Jewish children). The non-Jewish death rates were highest among infants less than 1 year of age, with females outnumbering males. Inspection of the male to female rate ratios showed a greater disparity between the sexes in both population groups as age increased. The proportion of motor vehicle accident (MVA) deaths was 52.7% among Jews and 40.4% among non-Jews. Drowning was the second ranking cause of accidental death (approximately 15%) in Israeli children, followed by falls (approximately 8%). The age distribution of MVA mortality was strikingly different in the two Israeli population groups. Among the Jews the rates peaked in the 15-17 age group in both sexes; however, among the non-Jews the rates peaked in the 1-4 age-group, with most of these deaths probably representing pedestrian deaths. On the average, the MVA serious injury rates were about ten times greater than the MVA mortality rates. Variations of mortality from accidents in different age, sex and population groups clearly indicate that preventive intervention programs must be targeted specifically to each age-sex-population group.

Accidental Falls↗
PubMed1987

Ichthyosis-cheek-eyebrow (ICE) syndrome: a new autosomal dominant disorder.

A family presenting with ichthyosis vulgaris, prominent full cheeks, sparse lateral eyebrows and other craniofacial and musculoskeletal defects is described in detail. This constellation of physical findings represents a new syndrome, transmitted in an autosomal dominant fashion. For reasons of simplicity it has been termed the I (ichthyosis), C (cheek), E (eyebrow) syndrome.

Abnormalities, Multiple↗
PubMed1985

Hypernatremic dehydration in children with severe psychomotor retardation.

Three cases of hypernatremic dehydration in children with severe psychomotor retardation are described. All the children were receiving processed foods that contained extremely high amounts of sodium and were unintentionally deprived of free water. Salt and water intake must be monitored closely in children who can neither communicate thirst nor regulate their diet.

Child, Preschool↗
PubMed1978

Studies on the differential inhibition by azide on the nitrite/nitrous oxide level of denitrification.

A gas chromatographic method was used to demonstrate that nitrite can counteract the inhibition by azide of nitrous oxide reductase activity in denitrifiers. This effect explains why azide (and cyanide) can inhibit nitrogen production from nitrous oxide in these organisms but have little effect on nitrogen production from nitrite. Although the physiological basis by which nitrite opposes the action of azide remains unknown, extensive destruction of azide by nitrite can be ruled out as an explanation.

Azides↗