PubMed Health⌕ Search

Biomedical subjects

F Lejbkowicz

Publications and source records attributed to F Lejbkowicz.

17 recordsLinked to original sources
PubMed2004

Blastocystis hominis as a cause of hypoalbuminemia and anasarca.

The protozoan Blastocystis hominis has been considered nonpathogenic, but this classification has come under scrutiny in light of reports in the medical literature indicating it could be the cause of intestinal disorders and, in one case, hypoalbuminemia. Reported here is a severe case of infection with B. hominis that caused acute gastroenteritis with prolonged diarrhea, hypoalbuminemia and anasarca. The diagnosis was based on the parasitological finding, since no other pathological evidence was found. The patient responded favorably to treatment with metronidazole for 10 days. This case supports the idea that B. hominis should be considered as a cause of opportunistic infection in debilitated patients despite the controversy surrounding its pathogenicity.

Animals↗
PubMed2001

Leprosy in Israel: an imported disease--the support of histopathological examination for its detection.

Leprosy is rare and non-endemic in Israel. Cases of leprosy are invariably imported by immigrants or foreign workers arriving from endemic areas. In view of the relative rarity of the disease, clinicians and pathologists are not always alert to the possibility of the disease or recognize potential symptoms. A case history is presented of a 31-year-old immigrant presenting symptoms of skin lesions and nodules on the hands and facial region, especially the ear lobe. Confirmation of the infection was provided by histopathology of suspected lesions stained for acid-fast bacilli (modified Fite-Faraco staining).

Adult↗
PubMed2000

Nuclear eukaryotic initiation factor 4E (eIF4E) colocalizes with splicing factors in speckles.

The eukaryotic initiation factor 4E (eIF4E) plays a pivotal role in the control of protein synthesis. eIF4E binds to the mRNA 5' cap structure, m(7)GpppN (where N is any nucleotide) and promotes ribosome binding to the mRNA. It was previously shown that a fraction of eIF4E localizes to the nucleus (Lejbkowicz, F., C. Goyer, A. Darveau, S. Neron, R. Lemieux, and N. Sonenberg. 1992. Proc. Natl. Acad. Sci. USA. 89:9612-9616). Here, we show that the nuclear eIF4E is present throughout the nucleoplasm, but is concentrated in speckled regions. Double label immunofluorescence confocal microscopy shows that eIF4E colocalizes with Sm and U1snRNP. We also demonstrate that eIF4E is specifically released from the speckles by the cap analogue m(7)GpppG in a cell permeabilization assay. However, eIF4E is not released from the speckles by RNase A treatment, suggesting that retention of eIF4E in the speckles is not RNA-mediated. 5,6-dichloro-1-beta-d-ribofuranosylbenzimidazole (DRB) treatment of cells causes the condensation of eIF4E nuclear speckles. In addition, overexpression of the dual specificity kinase, Clk/Sty, but not of the catalytically inactive form, results in the dispersion of eIF4E nuclear speckles.

Autoantigens↗
PubMed2000

Laryngotracheobronchial involvement in a patient with nonendemic rhinoscleroma.

We report the first case of rhinoscleroma in an Israeli citizen, a former sailor with a transatlantic shipping company. Characteristic histologic changes from a tracheal biopsy and isolation of Klebsiella rhinoscleromatis from a blood culture after diagnostic bronchoscopy confirmed the diagnosis. Extreme delay in the diagnosis, a not uncommon feature in nonendemic areas, was associated with severe advanced laryngotracheobronchial disease. Treatment with quinolones was followed by significant improvement, but the patient died 1 month after presentation, apparently from upper airway obstruction.

Adult↗
PubMed1999

Incidence of bacteraemia following fibreoptic bronchoscopy.

Guidelines for antibiotic prophylaxis of infective endocarditis prior to fibreoptic bronchoscopy, are based on only five studies, which showed a bacteraemia rate of <1% among 291 patients studied. T his study was designed to expand the current data regarding the frequency of bacteraemia following fibreoptic bronchoscopy. Aerobic and anaerobic cultures of venous blood and of lavage fluid were drawn from 200 consecutive patients undergoing fibreoptic bronchoscopy without respiratory infection or antibiotic treatment prior to the procedure. The true bacteraemia rate was calculated after excluding probable "contaminated" blood cultures. A possible correlation between type of procedure performed during the bronchoscopy and occurrence of bacteraemia was investigated. Positive blood cultures were noted following 26 bronchoscopy examinations. Coagulase negative Staphylococcus was found in the cultures of 18 patients, coagulase positive Staphylococcus in 3 patients, nonhaemolytic streptococci and a Klebsiella species in 2 patients each, and beta haemolytic streptococcus in one patient. After exclusion of 13 "contaminated" specimens the bacteraemia rate was 6.5% (13/200 patients). This study showed a bacteraemia rate of 6.5%, significantly higher than previously recognized in a cohort of patients undergoing fibreoptic bronchoscopy without either pulmonary infection or an unusually high rate of invasive procedures. These findings should be taken into account in future evaluations of recommendations for antibiotic prophylaxis of endocarditis.

Adolescent↗
PubMed1997

Ectopic expression of 2-5A synthetase in myeloid cells induces growth arrest and facilitates the appearance of a myeloid differentiation marker.

Two variants of the human myeloid leukemia cell line HL-60 were used to study the possible involvement of the IFN-induced protein 2-5A synthetase in cell growth arrest and differentiation. The two variants, HL-205 and HL-525, are equally susceptible to differentiation to the granulocyte lineage by exposure to DMSO, but only HL-205 cells acquire the macrophage phenotype following exposure to phorbol esters. The kinetics of 2-5A synthetase activity was established in both variants exposed to either DMSO or phorbol 12-myristate 13-acetate. With DMSO treatment, 2-5A synthetase activity was markedly induced in both variants, although with slightly different kinetics. With phorbol 12-myristate 13-acetate treatment, 2-5A enzymatic activity increased only in HL-205; no activity was detected up to 96 h after treatment in HL-525. The induction of 2-5A synthetase activity is apparently alpha/beta-IFN dependent, because only antibodies directed against a mixture of alpha- and beta-IFN completely abolished the increase in activity detected during differentiation of HL-205 cells. To directly establish the role of 2-5A synthetase in differentiation, HL-205 cells were transfected with an expression vector harboring the cDNA for the 43-kDa isoform of murine 2-5A synthetase fused to the inducible metallothionein promoter. Two clones, clone 6, which yielded a low level of 2-5A synthetase activity in response to ZnCl2 (which activates the promoter), and clone 7, which was a high responder, were further analyzed and compared with the control clone, neo. Reductions in the rates of cell growth and thymidine incorporation were observed with both clone 6 and clone 7 cells exposed to ZnCl2; clone 7 was more responsive. In addition, the level of c-myc-specific RNA transcript was greatly reduced in ZnCl2 or beta-IFN-treated clone 7 cells, whereas the neo cells responded similarly only after beta-IFN treatment. Treatment of clone-neo cells with beta-IFN resulted in conversion of pRb protein from the phosphorylated to the underphosphorylated form within 24 h; ZnCl2 had no effect, even after 72 h. In contrast, the accumulation of the underphosphorylated form of pRb was observed in clone 7 cells treated either with beta-IFN or ZnCl2. Finally, a significant increase in nitro blue tetrazolium-positive cells, an indication of differentiation, was evident with ZnCl2-treated clone 6 and clone 7 cells; no such increase was observed with clone-neo cells under similar conditions. We conclude that ectopic expression of 2-5A synthetase in HL-205 cells results in cell growth arrest and facilitates the appearance of a myeloid differentiation marker.

2',5'-Oligoadenylate Synthetase↗
PubMed1997

Distinct sensitivity of normal and malignant cells to ultrasound in vitro.

The effect of ultrasonic irradiation on the viability of human normal (foreskin fibroblast and amniotic fluid epithelial) and tumor (breast carcinoma, melanoma, and lung carcinoma) cells lines was studied. Cells were subjected to ultrasonic irradiation with a frequency of 20 kHz and an intensity of 0.33 W/cm2 for variable periods of time. Several parameters were tested to determine the effects of ultrasonic irradiation on cell viability and cellular function. Normal cells were relatively resistant to ultrasonic irradiation, whereas malignant cells were much more sensitive. Maximum damage occurred 4 min after exposure of the malignant cells to irradiation. Cellular DNA and protein synthesis were significantly affected as a function of time of irradiation and cloning efficiency of malignant cells exposed to irradiation was greatly reduced. To generalize the consistency of the ultrasonic effect, studies on additional normal and malignant human cells of distinct origin are under way to test their sensitivity to ultrasonic irradiation. Thus, the applicability of ultrasonic irradiation as an antitumor agent may be important in the development of a new methodology in the treatment of cancer.

Breast Neoplasms↗
PubMed1995

Functional domain analysis of interferon consensus sequence binding protein (ICSBP) and its association with interferon regulatory factors.

Interferon consensus sequence binding protein (ICSBP) is a member of the interferon regulatory factor (IRF) family of proteins that include IRF-1, IRF-2, and ISGF3gamma which share sequence similarity at the putative DNA binding domain (DBD). ICSBP is expressed exclusively in cells of the immune system and acts as a repressor of interferon consensus sequence (ICS) containing promoters that can be alleviated by interferons. In this communication, we have searched for functional domains of ICSBP by dissecting the DBD from the repression activity. The putative DBD of ICSBP (amino acids 1-121) when fused in frame to the transcriptional activation domain of the herpes simplex VP16 (ICSBP-VP16) is a very strong activator of ICS-containing promoters. In addition, ICSBP-VP16 fusion construct transfected into adenovirus (Ad) 12 transformed cells enabled cell surface expression of major histocompatibility complex class I antigens as did treatment with interferon. On the other hand, the DBD of the yeast transcriptional activator GAL4 was fused in frame to a truncated ICSBP in which the DBD was impaired resulting in a chimeric construct GAL4-ICSBP. This construct is capable of repressing promoters containing GAL4 binding sites. Thus, ICSBP contains at least two independent domains: a DBD and a transcriptional repressor domain. Furthermore, we have tested possible interactions between ICSBP and IRFs. The chimeric construct GAL4-ICSBP inhibited the stimulated effect of IRF-1 on a reporter gene, implying for a possible interaction between IRF-1 and ICSBP. Electromobility shift assays, demonstrated that ICSBP can associate with IRF-2 or IRF-1 in vitro as well as in vivo. Thus, ICSBP contains a third functional domain that enables the association with IRFs. These associations are probably important for the fine balance between positive and negative regulators involved in the interferon-mediated signal transduction pathways in cells of the immune system.

Base Sequence↗
PubMed1994

Hemoglobin is a late event in the differentiation of Friend erythroleukemic cells in-vitro. I. The role of interferon-induced proteins.

Here we report that the interferon (IFN)-induced proteins, 2'-5'-oligoadenylate synthetase (OAS) and IFN-induced protein kinase (PKI), appearance and activity precede that of hemoglobin (Hb) in the differentiation process of Friend erythroleukemic cells (FLC). Since our results are correlative, we assume that OAS and PKI are activated, and act at an early stage in the differentiation process, enabling the late onset of Hb synthesis. It is, thus, suggested that red blood cells harboring specific differentiating genes may be used as more efficient carriers of oxygen-binding molecules.

2',5'-Oligoadenylate Synthetase↗
PubMed1993

The response of normal and malignant cells to ultrasound in vitro.

The effect of ultrasonic irradiation on the viability of normal and tumor cell cultures derived from human and mouse origins was investigated. The cells were irradiated with a frequency of 2 MHz and intensity of 0.33 W/cm2, up to 4 min and immediately tested for cell viability using four different parameters: vital staining for the determination of the rate of cell growth; [3H]-thymidine and [3H]-leucine incorporation as an indication of the rate of DNA and protein synthesis respectively; and cloning efficiency as a measurement of the cell ability to multiply. Two human normal cell lines used in our studies, FS11 foreskin fibroblasts and Wish cells, were relatively resistant to ultrasonic irradiation effect although the growth rate of the latter was somewhat affected, particularly after 2 or 4 min of irradiation. However, cells derived from either malignant melanoma or breast carcinoma were highly sensitive to irradiation as demonstrated by a reduction of 96% and 65%, respectively, in cloning efficiency even after irradiation for 1 min. A third tumor cell line derived from lung carcinoma was more resistant. Two normal clones derived from NIH/3T3 mouse fibroblasts were used. These clones revealed some degree of sensitivity, particularly after 4 min of irradiation. However, their murine-sarcoma-virus transformed counterparts were found to be even more sensitive at identical times of ultrasonic irradiation, although the differences are not as striking as demonstrated with cells from human origin.(ABSTRACT TRUNCATED AT 250 WORDS)

3T3 Cells↗
PubMed1993

La autoantigen enhances and corrects aberrant translation of poliovirus RNA in reticulocyte lysate.

Translation initiation on poliovirus RNA occurs by internal binding of ribosomes to a sequence within the 5' untranslated region. We have previously characterized a HeLa cell protein, p52, that binds to a fragment of the poliovirus 5' untranslated region (K. Meerovitch, J. Pelletier, and N. Sonenberg, Genes Dev. 3:1026-1034, 1989). Here we report the purification of the HeLa p52. Protein microsequencing identified p52 as La autoantigen. The La protein is a human antigen that is recognized by antibodies from patients with autoimmune disorders such as systemic lupus erythematosus and Sjögren's syndrome. We show that the La protein stimulates translation of poliovirus RNA, but not brome mosaic virus, tobacco mosaic virus, and alfalfa mosaic virus 4 RNA, translation in a reticulocyte lysate. In addition, La corrects aberrant translation of poliovirus RNA in a reticulocyte lysate. Subcellular immunolocalization showed that La protein is mainly nuclear, but after poliovirus infection, La is redistributed to the cytoplasm. Our results suggest that La protein is involved in poliovirus internal initiation of translation and might function through a similar mechanism in the translation of cellular mRNAs.

Amino Acid Sequence↗
PubMed1993

ferT encodes a meiosis-specific nuclear tyrosine kinase.

ferT is a mouse testis-specific mRNA, shown previously to potentially encode a 51 kilodalton tyrosine kinase termed p51ferT. The accumulation of ferT RNA is restricted to primary spermatocytes that are at the prophase stage of the first spermatogenic meiotic division. By using antibodies raised against a synthetic peptide which was designed according to a putative p51ferT unique amino acid sequence, we have shown that testicular cells indeed contain a 51 kilodalton protein that is recognized by the anti-p51ferT antibodies. The protein was not detected in six nontesticular mouse tissues, nor was it detected, like the ferT RNA, in the testes of 14-day-old mice. These findings strongly suggest that the 51 kilodalton protein is p51ferT. Immunohistochemical staining localized p51ferT to meiotically dividing spermatocytes. Transfection experiments in CHO cells confirmed the nuclear localization of p51ferT in eukaryotic cells. p51ferT seems thus to be the first meiosis-specific nuclear tyrosine kinase described to date.

Animals↗
PubMed1992

A fraction of the mRNA 5' cap-binding protein, eukaryotic initiation factor 4E, localizes to the nucleus.

The 5' cap structure m7GpppN (where N is any nucleotide) is a ubiquitous feature of cellular eukaryotic mRNAs. The cap is multifunctional as it is involved in translation, nucleocytoplasmic transport, splicing, and stabilization of mRNA against 5' exonucleolytic degradation. The cap binding protein, eukaryotic initiation factor 4E (eIF-4E), is a translation initiation factor that binds to the cap structure and is part of a complex (eIF-4F) that promotes mRNA binding to ribosomes. Overexpression of eIF-4E in fibroblasts results in cell transformation. To test the hypothesis that some of the biological effects of eIF-4E might be effected by a nuclear function, we determined the cellular distribution of eIF-4E. By means of indirect immunofluorescence experiments using polyclonal and monoclonal antibodies against eIF-4E as well as transfected epitope-tagged eIF-4E, we demonstrate that a fraction of eIF-4E localizes to the nucleus. These results suggest that eIF-4E is also involved in a nuclear function.

Amino Acid Sequence↗
PubMed1992

Biological effects of photoactivated-HPD and cholesteryl hemisuccinate on erythroid differentiation.

In order to establish the ability of porphyrins to distinguish between differentiated and undifferentiated cells of the erythropoietic pathway, the cytotoxic effects of hematoporphyrin derivative (HPD) on Friend erythroleukemic cells (FLC) were derivative (HPD) on Friend erythroleukemic cells (FLC) were studied. Since cholesterol affects the fluidity of cell membranes, the inhibitory effect of cholesteryl hemisuccinate (CHS) on HPD was similarly tested. FLC were induced with either dimethyl sulfoxide (DMSO), hemin, or both. The cells responded to DMSO-treatment by the synthesis of a large amount of hemoglobin and a decrease in both the cell volume and rate of cell-growth. Hemin, on the other hand, did not drive FLC to synthesize hemoglobin and reduced only moderately the growth rate compared to untreated cultures. The combined effect of DMSO and hemin led to a profound inhibition of the growth rate, but did not increase the synthesis of hemoglobin compared to the level observed in cells treated with DMSO only. The binding property of HPD to FLC was also determined. DMSO-treatment significantly reduced the amount of HPD-binding, and combined treatment with DMSO and hemin resulted in even a lower level of HPD-binding. On the other hand, induced as well as non-induced cells showed the same sensitivity to photoactivated HPD when both DNA and protein synthesis were examined. Pretreatment of both differentiated and undifferentiated cells with CHS reduced the cytotoxicity of photoactivated HPD to the same level. We conclude that the decreased binding of HPD to differentiated cells is a result of a reduction in their cell volume. Thus, the differentiation process per se does not protect cells against the photodynamic effect of HPD. Moreover, CHS may act as a scavenger or first acceptor of singlet oxygen blocking the photodynamic effect.

Animals↗
PubMed1988

Photosensitization of differentiating Friend erythroleukemic cells by hematoporphyrin derivative and the cholesterol effect.

The Friend erythroleukemia cell line was used to study the binding and biological properties of the photosensitizer hematoporphyrin derivative (HPD) on a differentiating system. In addition, the effect of cholesterol hemisuccinate (CHS) enrichment of cell membranes on HPD activity was tested on the same cell system. Differentiation of Friend erythroleukemia cells (FLC) was induced with dimethyl sulfoxide (DMSO) and resulted in a decreased cell volume and an increased rate of hemoglobin synthesis as a function of the duration of DMSO treatment. Differentiated cells seem to bind less porphyrin than their undifferentiated counterparts. Thus, cells treated for 6 days with DMSO bound 30-40% less dye than an identical number of untreated FLC. In contrast, a similar inhibition of both DNA and protein synthesis by photoactivated HPD was evident in either DMSO-treated or untreated FLC. Enrichment of cell membranes with CHS led to the same degree of protection from the damaging activity of the photoactivated dye in both differentiated and undifferentiated FLC. The decreased binding of HPD to DMSO-treated FLC is most likely a result of a reduction in cell volume of differentiated cells and is not related to an intrinsic property of the differentiation process.

Animals↗
PubMed1985

Protective effect of cholesterol on Friend leukemic cells against photosensitization by hematoporphyrin derivative.

The cytotoxic effects of hematoporphyrin derivative (HPD) on Friend erythroleukemic cells were studied. Upon binding of the porphyrin to the cells, the fluorescence spectra was shifted from 613 to 633 nm regarding the main band and from 676 to 667 nm concerning the secondary band. The kinetics of HPD binding was then determined. Maximum binding already occurred at 60 s after exposure of the cells to HPD. It could be demonstrated that the effect of the photoactivated HPD on cell viability was drug, dose, and light fluorescence dependent. Cellular protein synthesis and Friend virus complex release from the cells were equally inhibited by the photodynamic sensitization of the drug, indicating no specific effect on virus maturation. Since cholesterol affects the fluidity of cell membranes, it was important to study the effect of cholesterol enrichment on the photodynamic sensitization by HPD. It was found that, while a 50% reduction in protein synthesis was monitored following treatment with 20 micrograms of HPD per ml and illumination by a 6-milliwatt white light for 60 s, no inhibition was observed following preenrichment of the cells with 0.5, 1, or 2% of cholesterol hemisuccinate. The same trend of cholesterol protection was demonstrated with longer illumination periods up to 10 min. The protective effect of cholesterol hemisuccinate was also seen using scanning electron microscopy. It is thus concluded that the cholesterol hemisuccinate content of Friend erythroleukemic cell membranes is an important factor in regulating the cytotoxicity of photoactivated HPD.

Animals↗