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A Zimran

Publications and source records attributed to A Zimran.

At least 109 records · Page 6Linked to original sources
PubMed1990

Detection of the 1226 (Jewish) mutation for Gaucher's disease by color PCR. A means for studying the gene frequency of the disorder.

The authors applied the polymerase chain reaction- (PCR) based color complementation assay for rapid detection of the 1226 ("Jewish") mutation of the glucocerebrosidase gene. Fifty-seven unrelated patients with Gaucher's disease and 50 unrelated normal Ashkenazi Jewish volunteers were studied. This mutation was identified in more than 75% of the Jewish Gaucher's disease alleles and in 4 (8%) of the 50 normal Jewish volunteers. The reliability of the technique was verified both by DNA sequencing and by leukocyte beta-glucosidase assay. This method is suggested as the simplest and most suitable one for a large-scale screening for the 1226 mutation for Gaucher's disease.

Adolescent↗
PubMed1990

A glucocerebrosidase fusion gene in Gaucher disease. Implications for the molecular anatomy, pathogenesis, and diagnosis of this disorder.

The molecular diagnosis of Gaucher disease has been difficult due to the existence of several different point mutations in the glucocerebrosidase gene and due to the presence of a tightly linked, highly homologous pseudogene. We now report the occurrence of a "Lepore-like" glucocerebrosidase fusion gene in which the 5' end is the functional gene and the 3' end is the pseudogene. This further complicates the molecular diagnosis of Gaucher disease but sheds light on the molecular anatomy of the glucocerebrosidase gene complex and on the pathogenesis of this important storage disease.

Adult↗
PubMed1990

Identification of the heterozygotes for deficiency of the beta-subunit of the eighth component of complement by reduced levels of C8 beta and increased amounts of free C8 alpha-gamma.

Sera from obligate heterozygotes for deficiency of the C8 beta subunit of the eighth component of human complement (C8) were analyzed for the molecular composition of C8. The C8 alpha-gamma and C8 beta subunits were separated by SDS-PAGE, visualized by immunoblotting, and the resulting bands were quantitated by laser densitometry. The laser densitometric absorption data were set to 100 arbitrary units (AU) for both subunits of pooled normal human sera. The AU values of individual normal sera ranged from 45 to 150 AU for C8 alpha-gamma (median 99 AU) and from 45 to 140 AU for C8 beta (median 101), whereas the C8 alpha-gamma/C8 beta-ratio varied from 0.7 to 1.4. Sera from C8 beta-deficient heterozygotes differed, as expected, from the normal sera for the markedly reduced levels of C8 beta (20 to 90 AU, median 55 AU) and for the higher C8 alpha-gamma/C8 beta-ratio (1.3 to 3.5). High voltage agarose gel electrophoresis was used to separate free and C8 beta-bound C8 alpha-gamma. The migration of free and C8 beta-bound C8 alpha-gamma subunit was checked by hemolytic overlay gels and by second dimension SDS-PAGE and immunoblotting. Immunochemical evaluation of C8 alpha-gamma using this system revealed about 5-14% free C8 alpha-gamma in sera with normal C8 and higher levels, from 33-71%, in the C8 beta D heterozygous sera. Functional analysis confirmed the substantial increase of free C8 alpha-gamma in the heterozygous group. We conclude that the C8 in C8 beta D heterozygous sera is characterized by increased amounts of free C8 alpha-gamma due to reduced concentrations of the C8 beta subunit. This finding may help to identify individuals heterozygous for C8 beta deficiency.

Complement C8↗
PubMed1990

Linkage of the PvuII polymorphism with the common Jewish mutation for Gaucher disease.

We have localized the PvuII polymorphism of the glucocerebrosidase gene complex to intron 6 of the active gene. Using the polymerase chain reaction (PCR) to amplify intron 6 of DNA samples from Pv1.1-/Pv1.1+ individuals, we defined the mutation causing this polymorphism as a G----A single-base substitution at position 3931 of the active gene. By analyzing 54 unrelated Gaucher patients we show strong linkage disequilibrium between the Pv1.1- genotype and the common Jewish mutation 1226 causing the adult type of this disease. Gaucher disease patients heterozygous for the 1226 allele and one unidentified allele (1226/?), particularly those of Jewish ancestry, were predominantly of the Pv1.1-/PV1.1+ genotype. This suggests that one of the unknown alleles may be relatively common and linked to the Pv1.1+ genotype.

Cell Line↗
PubMed1989

Prediction of severity of Gaucher's disease by identification of mutations at DNA level.

The polymerase chain reaction was used to detect four mutations in the DNA of 47 unrelated patients with type I Gaucher's disease (94 Gaucher's disease alleles). Two of the mutations, 1226 and 1448, and a new mutation (XOVR) representing cross-over between the glucocerebrosidase gene and its closely linked pseudogene, were found. There were five genotypes--namely, 1226/1226, 1226/1448, 1226/XOVR, 1226/?, and ?/? (where "?" indicates that none of the four known mutations was present). Severity of the disease was assessed with a scoring index according to age at diagnosis and extent of organ involvement. Mutation 1226 was associated with a mild clinical phenotype, and mutation 1448 with a more severe phenotype. Mutation 1226 is the most common cause of Gaucher's disease in Jewish patients.

Adolescent↗
PubMed1989

Quality of life and survival following intensive medical care.

The relation between quality of life before admission and the outcome of admissions to the intensive care unit (ICU) was studied prospectively among 126 patients in a community hospital with a predominantly geriatric patient population. Fifty-four per cent of our patients were older than 65 years and 66 per cent suffered from chronic ill health. Their mean APACHE score was 18 +/- 8 (mean +/- SD). Quality of life was assessed by the Karnofsky index of physical performance; the linear analogue self assessment (LASA) score; sleep index; level of employment; sexual activity; housing status. Thirty-seven per cent of the patients died in ICU and another 10 per cent in hospital. The one year survival of the entire group was 37 per cent. Survival rates were significantly higher in patients with a Karnofsky index of 6 or more, LASA score of 55 or more, in employment, and with sleep index of 2 or more (p less than 0.05). The 12-month survival among patients with four favourable indicators was 59 per cent, with two or three favourable indicators 36 per cent (p less than 0.05), and in patients with no favourable indicators of quality of life or only one 17 per cent (p less than 0.001). Quality of life in patients who survived longer than six months after ICU care was high (Karnofsky index 7.9 +/- 2.0; LASA score 71 +/- 20 (mean +/- SD) and unimpaired when compared with their ratings before admission to the unit. These findings indicate that quality of life before admission is an important predictor of survival and that a high proportion of critically-ill subjects whose quality of life was relatively good before the episode requiring admission will be long-term survivors whose quality of life is comparable to that preceding critical care.

Activities of Daily Living↗
PubMed1988

The in vivo ageing of red cell enzymes: direct evidence of biphasic decay from polycythaemic rabbits with reticulocytosis.

The rate at which the activities of red cell enzymes decay during maturation of the reticulocyte and ageing of the erythrocyte is poorly understood. It has recently been suggested that loss of enzyme activity may be rapid during reticulocyte maturation and occur slowly thereafter. We have now devised a rabbit model in which reticulocytosis is combined with transfusional polycythaemia. This makes it possible to follow the enzymatic activity of a cohort of reticulocytes without the interfering effect of newly formed cells. In this model the reticulocyte count of the experimental animals falls from about 60% to subnormal levels within 4 d. Red cell hexokinase activity declined rapidly with more than half of the activity being lost within 7 d, little change occurring thereafter. Glucose-6-phosphate dehydrogenase activity declined more gradually, but also followed a biphasic course. The fall of pyrimidine 5' nucleotidase activity was the slowest of the three age-dependent enzymes studied. This is consistent with our observations in children with transient erythroblastopenia of childhood, in which this enzyme, alone of the age-dependent enzymes, was found to be decreased in a senescent red cell population. In contrast to the three age-dependent enzymes studied, the activity of lactate dehydrogenase remained unchanged during the course of the experiment. These studies provide direct verification of the suggestion that the decline of red cell enzyme activities may be biphasic. They show, moreover, that enzyme decay is not only rapid in reticulocytes, but also in young erythrocytes.

5'-Nucleotidase↗
PubMed1988

Reduced incidence of hyperkalemia and azotemia in patients receiving sulindac compared with indomethacin.

The incidence and severity of hyperkalemia and azotemia was investigated in a prospective randomized study involving 74 patients receiving either sulindac 200 mg p.o. b.i.d. or indomethacin 25 mg p.o. t.i.d. and 100 mg p.r. The mean +/- SE posttreatment increment in serum potassium was 0.8 +/- 0.1 mmol/l in patients treated by indomethacin compared to 0.5 +/- 0.1 in those receiving sulindac (p less than 0.025). The mean +/- SE posttreatment increment in blood urea nitrogen (BUN) was 3.1 +/- 0.4 mmol/l in patients on indomethacin compared to only 0.9 +/- 0.3 in patients on sulindac (p less than 0.001). In 5 patients who developed hyperkalemia while on indomethacin, changing to sulindac resulted in a sharp reduction of serum potassium in 3, and normalization of BUN in all patients. These data support the claim of a reduced risk of impaired renal function associated with the use of sulindac.

Aged↗
PubMed1987

Hereditary complement deficiency in survivors of meningococcal disease: high prevalence of C7/C8 deficiency in Sephardic (Moroccan) Jews.

The prevalence of complement deficiency was studied among 111 survivors of sporadic meningococcal disease located through the medical records of 10 Israeli hospitals. There were 11 patients with CH50 = 0: one with systemic lupus erythematosus and 10 with hereditary terminal complement deficiency (four with homozygous C7 and six with C8 deficiency). There was no hereditary complement deficiency among 39 Ashkenazi subjects as against 18 per cent among 38 Sephardi subjects and 40 per cent among 15 of Moroccan ancestry (p less than 0.05). The age at first presentation of meningococcal disease in complement deficient patients was 14.7 +/- 7.6, years compared with 8.1 +/- 10.9 in the non-deficient patients (p less than 0.025). None of the complement deficient patients had meningitis below the age of 5 years vs. 49 per cent of non-deficient subjects. Recurrent meningitis was observed in 40 vs. 4 per cent (p less than 0.01) and meningitis in siblings in 40 vs. 2 per cent respectively (p less than 0.001). In addition to the 10 propositi, 11 non-propositus siblings were identified with severe complement deficiency (six with homozygous C7 and five with C8 deficiency). Seven of the non-propositi had no history at all of meningitis or any other serious systemic disease, underlining the relatively favourable prognosis of terminal complement deficiency. With increasing familiarity with the clinical features of this hereditary disease, it is possible now to identify on clinical grounds patients with meningococcal disease with a high likelihood of terminal complement deficiency.

Adolescent↗
PubMed1986

Hyperkalemia associated with sulindac therapy.

Hyperkalemia has recently been recognized as a complication of nonsteroidal antiinflammatory agents (NSAID) such as indomethacin. Several recent studies have stressed the renal sparing features of sulindac, owing to its lack of interference with renal prostacyclin synthesis. We describe 4 patients in whom hyperkalemia ranging from 6.1 to 6.9 mEq/l developed within 3 to 8 days of sulindac administration. In all of them normal serum potassium levels reached within 2 to 4 days of stopping sulindac. As no other medications known to effect serum potassium had been given concomitantly, this course of events is suggestive of a cause-and-effect relationship between sulindac and hyperkalemia. These observations indicate that initial hopes that sulindac may not be associated with the adverse renal effects of other NSAID are probably not justified.

Adult↗
PubMed1986

Histomorphometric evaluation of reversible heparin-induced osteoporosis in pregnancy.

Transilial bone biopsy confirmed heparin-induced osteopenia in a 23-year-old postpartum patient. Histomorphometric measurements during the reversible stage of bone disease that followed discontinuation of the heparin sodium therapy revealed signs of recovery; these were superimposed on a loose trabecular structure typical of osteoporosis. The histomorphometric evidence of recovery correlated well with signs of clinical improvement. In the majority of patients, heparin therapy during pregnancy is innocuous; however, discontinuation of treatment is recommended at the earliest signs of osteoporosis.

Adult↗