Extended family studies for the identification of allogeneic stem cell transplant donors in Jewish and Arabic patients in Israel.

HLA-identified donors are the best source of allogeneic hematopoietic stem cell transplants, and are available in approximately 40% of cases. If no HLA-identical core family member is found, an extended family search may be performed. The aim of the study was to summarize the 10-year (1990-1999) experience of our tertiary care center with extended family donor search.

Allelic distribution of HLA-B*5 in HLA-B5-positive Israeli patients with Behçet's disease.

In order to investigate the sub-typing of the B5 antigen in Israeli (Jewish and Arabic) patients with Behçet's disease (BD) allele-specific genotyping of B51 and B52 alleles was performed in Israeli BD patients and healthy controls. Among the HLA-B51-positive BD patients, B*5101 was found to be the predominant allele, identified in 62% of all BD patients and 78% of Jewish BD patients. HLA-B*5101 was also the predominant allele in HLA-B51-positive healthy controls.

Lower frequency of Gaucher disease carriers among Tay-Sachs disease carriers.

The heterozygote frequency of Gaucher disease (GD) and Tay-Sachs disease (TSD) is distinctly high among Ashkenazi Jews (1:29 for TSD and 1:16 for GD). Two main theories have been suggested to explain this high occurrence: a founder effect with subsequent genetic drift, and a selective advantage of heterozygotes. We compared the frequency of the GD most common mutation (1226A-->G) among carriers of the common TSD mutation (+1277 TATC) with the frequency of this mutation in the general Ashkenazi population.

Linkage disequilibrium of common Gaucher disease mutations with a polymorphic site in the pyruvate kinase (PKLR) gene.

Gaucher disease (GD), caused by a deficiency of the lysosomal enzyme glucocerebrosidase (GBA), is the most common human glycolipid storage disease. The incidence of the disease is particularly high in the Ashkenazi Jewish population, with a carrier frequency of 0.068.

Type I Gaucher disease due to homozygosity for the 259T mutation in a Bedouin patient.

A 26-year-old Bedouin with moderate thrombocytopenia and enlarged spleen and liver was diagnosed as having type I Gaucher disease based on the presence of Gaucher cells in the bone marrow biopsy and enzymatic determination of glucocerebrosidase activity. Molecular analysis excluded 10 common mutations in the glucocerebrosidase gene. Homozygosity for the C --> T mutation in nucleotide 259 of the cDNA (1763 genomic) was detected by digestion with restriction enzyme StyI after an amplification of a portion of exon 3 by mismatched primers.

The outcome of patients with acute myocardial infarction ineligible for thrombolytic therapy. Israeli Thrombolytic Survey Group.

Purpose: The aim of this study was to determine the proportion of patients with acute myocardial infarction (AMI) excluded from thrombolytic therapy on a national basis and to evaluate the prognosis of these patients by reasons of ineligibility and according to the alternative therapies that they received during hospitalization.

Patients And Methods: During a national survey, 1,014 consecutive patients with AMI were hospitalized in all the 25 coronary care units operating in Israel.

Results: Three hundred and eighty-three patients (38%) were treated with a thrombolytic agent and included in the GUSTO study.

On-site catheterization laboratory and prognosis after acute myocardial infarction. Israeli Thrombolytic Survey Group.

Background: Since the introduction of thrombolytic therapy for patients with acute myocardial infarction, the use of coronary angiography has substantially increased. We sought to determine whether the presence of on-site coronary angiographic facilities influenced the utilization of coronary procedures in patients with acute myocardial infarction hospitalized in Israel's coronary care units.

Methods: A prospective survey was conducted in January and February 1992 in the 25 coronary care units operating in Israel, 15 of which had on-site catheterization facilities.

[Do on-site coronary angiographic facilities influence management and prognosis of acute myocardial infarction?].

Whether the presence of on-site coronary angiographic facilities (CAF) influences the use of invasive coronary procedures and the outcome of acute myocardial infarction in coronary care units was studied. A prospective survey was conducted early in 1992 when 1014 consecutive patients with acute infarction were admitted. Of them 707 (70%) were admitted to coronary care units of hospitals with, and 307 (30%) without CAF.

Influence of gender in the therapeutic management of patients with acute myocardial infarction in Israel. The Israeli Thrombolytic Survey Group.

A national study was performed in early 1992 in the 25 operating coronary care units in Israel, which enabled the assessment of whether the therapeutic management of patients with acute myocardial infarction was affected by patient gender. During a 2-month period, 1,014 consecutive patients with acute myocardial infarction were hospitalized. Thrombolytic therapy was given to 47% of men (362 of 769), and 43% of women (106 of 245) (p = NS).

Serum intracellular adhesion molecule-1 (sicam-1) and soluble hla class-1 antigens in breast-cancer patients in relation to tumor burden.

sICAM-1 and beta-2 microglobulin (beta-2M) serum levels were measured in 143 breast cancer patients and 43 controls. The patients were divided into three groups. A: new patients; B: patients on long term follow-up and C: metastatic patients.

The autosomal dominant polycystic kidney disease gene in a Jewish family from Uzbekistan is PKD1.

A large Jewish family from Tashkent (Uzbekistan) was studied for linkage of autosomal dominant polycystic kidney disease (ADPKD) to molecular markers on the short arm of chromosome 16. A restriction fragment length polymorphism (RFLP) analysis was performed on 28 family members, including 9 ADPKD diagnosed patients in 3 consecutive generations. A specific haplotype was found to segregate with the disease in eight of the nine affected individuals.

Responsiveness to 1,25-dihydroxyvitamin D3 is reduced in lymphocytes from osteoporotic women.

The purpose of this work was to test the hypothesis that reduced responsiveness of target organs to 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] is associated with osteoporosis. Peripheral blood mononuclear (PBM) cells have been previously shown to be a valid model for the action of 1,25(OH)2D3 on its classic target organs in various pathologic and physiologic situations. The responsiveness of lymphocytes to the hormone can be assessed by the extent of inhibition it exerts on the proliferative response to mitogenic lectins.

1,25-dihydroxyvitamin D3 and agents that increase intracellular adenosine 3',5'-monophosphate synergistically inhibit the mitogenic stimulation of human lymphocytes.

1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3], like the immune response modulators prostaglandin E2 (PGE2) and histamine, inhibits mitogen-induced proliferation of human peripheral blood mononuclear cells. 1,25-(OH)2D3 acts synergistically with PGE2 and histamine to inhibit lymphocyte mitogenesis. This is apparent at a wide concentration range of 1,25-(OH)2D3 (3 X 10(-11)-10(-8) mol/L).

Cystine accumulation and clearance in normal and cystinotic fibroblasts exposed to cystine dimethyl ester.

Exposure of cultured skin fibroblasts of normals and cystinotic patients to 0.5 mmol/l[35S]cystine dimethyl ester for 30 min resulted in an accumulation of cystine in excess to that naturally occurring in cystinotic skin fibroblasts. These equal levels of cystine accumulation achieved in both cystinotic and normal cells, permitted comparative experiments to look for differences in cystine disposal between normal and cystinotic cells.

Comparative study of cystine clearance in cystinotic and I-cell fibroblasts upon exposure to cystine dimethyl ester.

I-cell fibroblasts can accumulate cystine at levels comparable to those seen in homozygous cystinotic fibroblasts. Cystine accumulation in cystinosis is accounted for cystine clearance defect in situ. To unravel the question whether the same clearance defect or two different mechanisms cause cystine accumulation in I-cell disease, we used the cystine loading technique upon exposure of skin fibroblasts to radioactive cystine dimethyl ester.