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Biomedical subjects

Merav Leiba

Publications and source records attributed to Merav Leiba.

6 recordsLinked to original sources

Changes in gene expression pattern following granulocyte colony-stimulating factor administration to normal stem cell sibling donors.

UNLABELLED: Granulocyte colony-stimulating factor (G-CSF) is widely used for the mobilization of hematopoietic stem cells from normal donors. The mechanism of induced mobilization has recently been elucidated. Treatment with G-CSF is considered safe; however, long-term effects are largely unknown. The aim of this study was, therefore, to determine whether it leads to significant changes in gene expression modifications. Affymetrix Gene Chip array technology was used. Samples were collected before and at various time points (up to 9 months) after mobilization. The expression levels of 122 genes were transiently modified before and after mobilization (p < 0.05). Fifty-three genes belonging to cell growth, proliferation and communication gene ontology categories were upregulated, while 69 genes were downregulated. CONCLUSION: The administration of G-CSF is associated with transient DNA and gene expression modifications in the lymphocytes of normal mobilized donors. A long-term follow-up of stem cell donors is recommended.

Down-Regulation↗

Characterization of HPSE gene single nucleotide polymorphisms in Jewish populations of Israel.

Heparanase is a mammalian endoglucuronidase responsible for heparan sulfate (HS) degradation. HS is a major constituent of the extracellular matrix (ECM) and HS-degrading activity plays a decisive role in fundamental biological processes associated with remodeling of the ECM, such as cancer metastasis, angiogenesis and inflammation. There is great interest in the prospect of genome-wide association studies to identify genetic factors underlying complex diseases. It is important to establish a detailed description of the heparanase (HPSE) gene single nucleotide polymorphisms (SNPs). In this study, four Israeli Jewish populations (Ashkenazi, North African, Mediterranean and Near Eastern) were examined for 7 HPSE gene SNPs. Four out of 7 SNPs (rs4693608, db11099592, rs4364254, db6856901) were found to be polymorphic. Population comparisons revealed significant differences in SNPs allele frequency between Near Eastern and each of the other three populations. Genotype and allele frequencies in Jewish populations were different from non-Jewish populations, except for a certain similarity to Caucasians. Although the distance between SNPs is relatively small, the db11099592 SNP was in linkage disequilibrium (LD) only with the proximal SNP rs4693608. LD between distal SNPs rs4364254 and db6856901 was found only in Mediterraneans and North Africans. The current study provides a characterization of the normally occurring HPSE gene SNPs in different populations. This information is obligatory for further studies on the linkage between these SNPs and heparanase expression and function in various pathological processes, primarily cancer progression.

Africa, Northern↗

Behcet's Disease: Current Therapeutic Perspectives.

Behcet's disease is a chronic relapsing systemic vasculitis of small and large vessels, of unknown etiology, characterized by recurrent oral and genital ulcers, and ocular inflammation. Other involved organs may include the joints, skin, and gastrointestinal tract, as well as the pulmonary, renal, central nervous, and the cardiovascular systems. The treatment of Behcet's disease is basically empiric, geared to control the symptoms, suppress the inflammatory process, and prevent organ damage. Thus, various anti-inflammatory and immunosuppressive agents have been used as the main therapeutic modalities, although none of them has been effective in controlling the diverse symptoms. Earlier, these drugs included colchicine, azathioprine, systemic corticosteroids, dapsone, cyclosporine A, and tacrolimus. Recently emerging studies show the effectiveness of thalidomide, interferon alpha, interferon gamma, acyclovir, low-dose weekly methotrexate, cyclophosphamide pulse therapy, and anti-tumor necrosis factor (TNF) therapy. Anti-TNF agents, such as infliximab, are emerging as being effective in rapid control of sight-threatening panuveitis and cerebral vasculitis, as well as in orogenital ulcerations, gastrointestinal disease, and skin lesions of Behcet's disease. Limited anecdotal case reports have been published with the use of the fusion protein etanercept in Behcet's disease. Hopefully, prospective clinical trials, which are now ongoing, will provide more data as to the efficacy of the anti-TNF agents, compared with the conventional immunosuppressive therapy.

Journal Article↗

Philadelphia-chromosome-positive T-lymphoblastic leukemia: acute leukemia or chronic myelogenous leukemia blastic crisis.

The Ph1 chromosome has rarely been reported in T-lineage acute lymphoblastic leukemia (T-ALL), and the clinical relevance of this translocation in T-ALL is currently unknown. In chronic myelogenous leukemia (CML) some data indicate derivation of T-cells from the leukemic clone and only a few cases of T-derived blastic crisis have been reported and quite often disputed. Particularly in cases identified initially in blastic crisis it may be difficult to distinguish those from Ph1-positive T-ALL. We herein report 2 patients who presented with a clinical picture of Ph1-positive T-ALL and who raised a differential diagnosis from T-cell blastic crisis of CML. We review the literature and suggest clinical and laboratory features that can help in the diagnosis. According to our literature review, 23 cases of Ph1-positive T-ALL and 44 cases of T-cell blastic crisis of CML, including ours, were reported. Some major differences between the two entities could help in establishing a diagnosis of Ph1-positive T-cell blastic crisis of CML vs. Ph1-positive T-ALL: Male sex and younger age was more predominant in T-ALL. While in most cases of CML blastic crisis there was a history of CML there was no such history in the T-ALL cases. Medullary involvement with lymphoblastic leukemia was present in all cases of T-ALL but only in about half of the cases of CML blastic crisis. None of the CML-blastic crisis cases tested by RT-PCR showed the minor breakpoint transcript, while 2 cases with T-ALL had the minor breakpoint transcript and 1 had both transcripts. Combined morphologic and FISH analysis can help to distinguish between the two entities and was applied in one of our cases. Although both entities carry a severe prognosis, differentiating between them might have clinical relevance, especially in the imatinib era.

Blast Crisis↗

Acute respiratory failure in a patient with sarcoidosis and immunodeficiency--an unusual presentation and a complicated course.

Pulmonary sarcoidosis is usually a chronic, insidious disease resulting from granuloma formation in the lung parenchyma. The epithelioid non-caseating granulomata of sarcoidosis are the result of a T-helper1-mediated immune reaction to an unknown self or foreign antigen. We describe the case of a patient with sarcoidosis and a coexistent common variable immunodeficiency who presented with rapidly progressive respiratory failure. This unusual presentation was followed by a complicated course with recurrent pneumoccocal infections, which could be explained by the coexistence of common variable immunodeficiency. Physicians should be alert to the possibility of sarcoidosis even when the clinical presentation is of acute respiratory distress syndrome (ARDS) since early treatment with steroids can be lifesaving. The detection of accompanying hypogammaglobulinemia is also crucial, as treatment with intravenous immunoglobulins (IVIG) together with steroids can improve the patient's outcome.

Acute Disease↗