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Biomedical subjects

R Sharon

Publications and source records attributed to R Sharon.

At least 19 recordsLinked to original sources
PubMed2003

Diagram X-ray emission spectra of a hollow atom: the Kh alpha1,2 and Kh beta1,3 hypersatellites of Fe.

High-resolution Fe K(h) beta(1,3) and K(h) alpha(1,2) hypersatellite spectra were measured, using monochromatized synchrotron radiation photoexcitation. The lines' energies, splitting, excitation thresholds, and the K(h) alpha(1)/K(h) alpha(2) intensity ratio were derived with high accuracy. Having both spectra, not hitherto available for any atom with high resolution, allows separating out the energy shifts of the outer levels caused by a K shell spectator vacancy. Comparison with ab initio relativistic multiconfigurational Dirac-Fock calculations reveals that while the influence of relativity and QED effects is mostly accounted for, discrepancies remain in the lines' intensity ratio, which sensitively measures the intermediacy of the coupling. Similar discrepancies, of unknown origin, are found in the energy shifts of the outer levels due to the final-state K shell spectator vacancy.

Journal Article↗
PubMed2001

alpha-Synuclein occurs in lipid-rich high molecular weight complexes, binds fatty acids, and shows homology to the fatty acid-binding proteins.

alpha-Synuclein (alphaS) is a 140-residue neuronal protein that forms insoluble cytoplasmic aggregates in Parkinson's disease (PD) and several other neurodegenerative disorders. Two missense mutations (A53T and A30P) are linked to rare forms of familial PD. The normal function of alphaS is unknown, and cultured cell systems that model its modification from soluble monomers to aggregated forms have not been reported. Through a systematic centrifugal fractionation of mesencephalic neuronal cell lines and transgenic mouse brains expressing wild-type or A53T human alphaS, we observed unusual, previously unrecognized species of alphaS that migrate well above the 17-kDa monomeric form in denaturing gels. Incubation at 65 degrees C of high-speed cytosols from cells or brains revealed a modified alphaS species migrating at approximately 36 kDa and an extensive higher molecular mass alphaS-reactive smear. Extraction of the cytosols with chloroform/methanol or with a resin (Lipidex 1000) that binds fatty acids resulted in a similar pattern of higher molecular mass alphaS forms. On the basis of this effect of delipidation, we reexamined the primary structure of alphaS and detected a motif at the N and C termini that is homologous to a fatty acid-binding protein signature. In accord, we found that purified human alphaS binds oleic acid, with an apparent K(d) of 12.5 microM. We also observed an enhanced association of A53T alphaS with microsomal membranes in both mesencephalic cells and transgenic mouse brains. We conclude that alphaS has biochemical properties and a structural motif that suggest it is a novel member of the fatty acid-binding protein family and may thus transport fatty acids between the aqueous and membrane phospholipid compartments of the neuronal cytoplasm.

Amino Acid Sequence↗
PubMed2001

Plasminogen activator inhibitor-1 in cardiovascular cells: rapid induction after injecting mice with kainate or adrenergic agents.

OBJECTIVES: Plasminogen activator inhibitor-1 (PAI-1) is a major anti-fibrinolytic glycoprotein thought to promote vascular diseases. Recently we have shown that systemically injecting mice with kainate, an analog of the principal brain excitatory neurotransmitter glutamate, immediately induced PAI-1 mRNA in brain vascular cells which are not known to contain glutamate receptors. Here we further investigated whether: (a) kainate also increases PAI-1 gene expression in the cardiac vascular bed; (b) subunits of kainate/AMPA receptors could be expressed in cardiac and brain vascular cells; and (c) PAI-1 mRNA could be similarly induced by agonists of adrenergic receptors that are candidates to act downstream in kainate-activated pathways. METHODS: We analyzed cardiac and brain cryosections for PAI-1 mRNA, as well as mRNAs encoding three receptor subunits, by in situ hybridization using 35S-labeled specific riboprobes. PAI-1 activity was tested in cardiac homogenates using one-phase reverse zymography. RESULTS: Prominent PAI-1 mRNA hybridization signals were induced in the vascular cells of the heart, and unexpectedly, also in cardiocytes, within 1-2 h after injection of kainate (i.p., 11-25 mg/kg body weight); the signals persisted for at least 8 h and disappeared after 24 h. In addition, PAI-1 activity increased ( approximately 5 fold) 2-10 h after the treatment. In contrast, mRNAs encoding the kainate/AMPA receptor subunits could not be detected. The adrenergic agents adrenaline (3.5 mg/kg) and isoproterenol (200 mg/kg) exerted kainate-like effects in cardiovascular cells. CONCLUSIONS: These results revealed, for the first time, that PAI-1 gene expression can be enhanced locally in the cardiovascular system by a fast-acting neurological mechanism triggered by glutamate receptors, whose pathway and relation to catecholamines, which exerted similar effects, have yet to be resolved. These findings raised the possibility that excessive glutamate, or stress-related catecholamines, may increase the risk of stroke and myocardial infarction.

Adrenergic Agonists↗
PubMed2001

Plasminogen.

Plasminogen activator inhibitor-2 (PAI-2) specifically inhibits plasminogen activators, extracellular fibrinolytic serine proteases that are also implicated in brain plasticity and toxicity. Primarily localized intracellularly, PAI-2 is thought to also counteract apoptosis mediated by a currently undefined intracellular protease. Here we localized PAI-2 mRNA through in situ hybridization in brain cryosections derived from normal adult mice or after kainate excitation. We found that in the normal brain PAI-2 mRNA was confined to an area within the accumbens nucleus shell. After kainate was injected (i.p.), PAI-2 mRNA was substantially and rapidly (within 2 h) induced in neuron-like cells primarily in layers II-III of the neocortex; the cingulate, piriform, entorhinal and perirhinal cortices; the olfactory bulb, nucleus and tubercle; in the accumbens nucleus, shell and core; throughout the caudate putamen and the amygdaloid complex; in the CA1 and CA3 areas of the hippocampus, and in the parasubiculum. These findings suggest that PAI-2 could play a role in the accumbens nucleus as well as in activity-related events associated with olfactory, striatal, and limbic structures.

Journal Article↗
PubMed2001

Prophylactic therapy with enoxaparin during L-asparaginase treatment in children with acute lymphoblastic leukemia.

Forty-one consecutive children with acute lymphoblastic leukemia (ALL) received prophylaxis therapy with the low molecular weight heparin (LMWH) enoxaparin during L-asparaginase treatment. Enoxaparin was given every 24 h subcutaneously at a median dose of 0.84 mg/kg per day (range, 0.45-1.33 mg/kg per day) starting at the first dose of L-asparaginase until 1 week after the last dose. Molecular analysis for thrombophilic polymorphisms documented prothrombin G20210A mutation in 3/27 (11%), homozygosity for MTHFR C677T mutation in 5/27 (18.5%, and heterozygosity for factor V Leiden mutation in 5/27 (18.5%) children. There were no thrombotic events during 76 courses of L-asparaginase in 41 patients who had received enoxaparin. One patient suffered brain infarct 7 days after enoxaparin was stopped. There were no bleeding episodes. In a historical control group of 50 ALL children who had not received prophylactic enoxaparin during L-asparaginase treatment, two had thromboembolisms (one deep vein thrombosis and one pulmonary embolism). Enoxaparin is safe and seems to be effective in prevention of thromboembolism in ALL patients during L-asparaginase therapy. This study provides pilot data for a future randomized trial of the use of LMWH during ALL therapy for the prevention of asparaginase-associated thrombotic events.

Adolescent↗
PubMed2001

The polymorphonuclear leukocyte--a new target for erythropoietin.

A previous study from our laboratory has shown that erythropoietin (EPO), beside its traditional role in erythropoiesis, acts as an alleviator of oxidative stress and inflammation in chronic hemodialysis (HD) patients, conferred in part by activated polymorphonuclear leukocytes (PMNLs). To substantiate this phenomenon, the existence of EPO receptors (EPO-Rs) on PMNL membrane was examined at the transcriptional and translational levels. mRNA for EPO-R was detected in PMNLs using specific primers directed towards the extracellular region of human EPO-R cDNA. The predicted 300-bp fragment was amplified by reverse transcriptase-polymerase chain reaction. Subcloning and sequence analysis revealed 100% homology of this fragment with human EPO-R. The receptor protein was detected on the surface of intact PMNLs using (125)I-EPO. The protein was further demonstrated by flow cytometric analysis using a fluorescent monoclonal anti-EPO-R. The percentage of PMNLs expressing EPO-R showed a strong correlation with the level of EPO in the serum, suggesting an upregulation of the receptor by the hormone. Taken together with our recent findings that EPO attenuates the oxidative stress and inflammation contributed by PMNLs in HD patients, the detection of functional EPO-R expression in PMNLs places these cells among the nonerythroid, EPO-responsive target populations.

Adult↗
PubMed2000

Effective preventive central nervous system therapy with extended triple intrathecal therapy and the modified ALL-BFM 86 chemotherapy program in an enlarged non-high risk group of children and adolescents with non-B-cell acute lymphoblastic leukemia: the Israel National Study report.

BACKGROUND: Preventive cranial radiotherapy (CRT) in childhood acute lymphoblastic leukemia (ALL), although effective, may be associated with neurologic sequelae and second malignancies. Attempts to replace CRT with intensified intrathecal therapy (IT) have shown promise in lower risk subgroups. In the Israel National Study (INS) 89 trial, the efficacy of extended triple IT (TIT) alone for cranial prophylaxis in an enlarged non-high risk group (Non-HRG) was assessed in the context of a modified ALL-Berlin-Frankfurt-Munster (BFM) systemic chemotherapy program. METHODS: Non-HRG patients included the standard-risk group (SRG) and the risk group (RG), as defined in ALL-BFM 86. In the INS 89 protocol, all Non-HRG patients were treated with extended TIT x 18 times and systemic therapy based on the BFM 86 protocol, with the addition of etoposide x 4 times. The HRG patients, classified according to BFM 86 criteria, were treated with the BFM 90 HRG protocol including CRT. RESULTS: A total of 250 patients were enrolled. At a median follow-up of 58 months (range, 2-8.5 years), the overall 5-year event free survival (EFS) was 73.5% +/- 3% (standard error ¿SE), and the cumulative central nervous system (CNS) recurrence rate was 4.3% +/- 1.4% (SE) (isolated, 2.3%; combined, 2%). Of the 220 eligible children, 189 (86%) were in the Non-HRG group, and their 5-year EFS was 77.8% +/- 3% (SE). The cumulative CNS recurrence rate for patients without CNS disease at presentation was 3.1% +/- 1% (SE) (isolated, 1.7%; combined, 1.4%). Within the risk subsets defined by the BFM 86 of the Non-HRG, the 5-year EFS rates of the RG (148 patients) and the SRG (41 patients) were 74.8% +/- 4% (SE) and 89.5% +/- 5% (SE), respectively, and the rates of CNS recurrence (isolated and combined) were 4% and 0%, respectively. For the HRG (31 patients), the 5-year EFS and CNS recurrence rates were 47.9% +/- 9% (SE) and 8. 5% +/- 6% (SE), respectively. CONCLUSIONS: Early extended TIT therapy in the context of modified BFM 86 systemic chemotherapy was found to provide adequate CNS protection and systemic leukemia control in patients with non-high risk ALL. However, no benefit for etoposide could be proven in this study.

Antimetabolites, Antineoplastic↗
PubMed2000

Paroxysmal nocturnal hemoglobinuria associated with in vitro inhibition of erythropoiesis by bone marrow T lymphocytes.

BACKGROUND: The etiology of bone marrow failure, a prominent feature of paroxysmal nocturnal hemoglobulinuria, is presently unknown. OBJECTIVES: To evaluate the possible influence of cellular immune mechanisms in the bone marrow failure of PNH. METHODS: We studied marrow erythroid colony formation in a patient with paroxysmal nocturnal hemoglobinuria without hypoplastic/aplastic marrow complications. RESULTS: In vitro assays revealed a pronounced inhibition of primitive erythroid (BFU-E) progenitor cell growth by marrow T lymphocytes. Removal of T cells prior to culture resulted in a 4.5-fold enhancement of BFU-E numbers. Reevaluation of in vitro erythropoiesis during steroid administration indicated a persistent, albeit less prominent, T cell inhibitory effect. CONCLUSION: Our findings provide the first direct evidence for a cellular immune inhibitory phenomenon accompanying PNH.

Adult↗
PubMed1997

[Angioedema caused by splenectomy with malignant lymphoma followed by multiple myeloma 7 years later].

Acquired C1-inhibitor (C1-INH) deficiency has been reported in patients with immunoglobulin abnormalities and lymphoproliferative disorders, and angioedema has appeared simultaneously with the lymphoproliferative disease. We present a 50-year-old woman with acquired C1-INH deficiency and angioedema which preceded by 7 years the diagnosis of malignant mantle cell lymphoma. During the interval she was treated with Danazole and there were no attacks of angioedema. When routine follow-up bone marrow aspiration revealed infiltration of nonspecified lymphoma cells, exploratory laparotomy and splenectomy were performed. A month later Danazol was stopped, C1-INH levels returned to normal and there were no attacks of angioedema. Mantle cell lymphoma consisting of lymphocytes with cytoplasmic IgM-lambda was diagnosed in the excised spleen but chemotherapy was not initiated. 6 months later, a second lymphoproliferative disorder, multiple myeloma IgA kappa, was diagnosed.

Angioedema↗
PubMed1997

Reasons for student attrition on nursing courses: a study.

Student attrition (dropping out) wastes time and resources which schools of nursing can ill afford. This study from Israel sets out to identify the reasons for student attrition and finds that academic failure is only one factor. The authors suggest some ways in which high risk students can be identified and helped.

Education, Nursing, Baccalaureate↗
PubMed1997

Ovarian steroid levels in Salamandra salamandra infraimmaculata during the reproductive cycle.

Gonadal steroid levels were determined in the ovary of Salamandra salamandra infraimmaculata during the reproductive cycle in populations from a xeric region in northern Israel. Varying proportions of previtellogenic and vitellogenic oocytes were present throughout the year, and mature oocytes were present in winter and spring. The numbers of mature oocytes were greater between December and April, after parturition. The levels of 17 beta-estradiol and testosterone rose during oocyte vitellogenesis and maturation. Levels of progesterone and 17 alpha-hydroxy progesterone appeared to be related to the level of vitellogenesis. Gravid females contained greater quantities of all four steroids than did nongravid females.

17-alpha-Hydroxyprogesterone↗
PubMed1997

Young people considering nursing as a career: starters vs. non-starters.

This study focused on applicants who were accepted to a nursing education program but did not begin their studies, thus wasting time, effort and money. Of 953 accepted applicants, 27% did not enter the program. Significant variables differentiating starters from non-starters were higher psychometric score, higher paternal education, lower priority for nursing studies, older age, non-Israeli country of birth and not completed army service. The study relating to starters vs. non-starters is one aspect of a large study (Ehrenfeld, Rotenberg, Sharon, & Bergman, 1995). In most nursing education programs the number of applicants exceed the faculty's capacity, and suitable candidates must be rejected. It is therefore both wasteful and disappointing when accepted applicants change their mind and do not actually begin in the program. In light of the costs and complexities involved in the student screening process and the continuous efforts extended today all over the world to raise the standards of nursing education and care, the factors differentiating starters from non-starters may have important implications. The aim of the present study was to evaluate the screening process at the Tel Aviv University baccalaureate nursing program and determine which variables were predictive of starters and non-starters among accepted applicants.

Discriminant Analysis↗
PubMed1995

VEGF121, a vascular endothelial growth factor (VEGF) isoform lacking heparin binding ability, requires cell-surface heparan sulfates for efficient binding to the VEGF receptors of human melanoma cells.

Four vascular endothelial growth factor (VEGF) splice variants containing 121, 165, 189, and 206 amino acids are produced from a single human gene as a result of alternative splicing. VEGF121 is not a heparin-binding protein, while the other VEGF species possess heparin binding ability. YU-ZAZ6 human melanoma cells expressed the mRNA encoding the VEGF receptor flt-1, but not the mRNA encoding the VEGF receptor KDR/flk-1. Both VEGF121 and VEGF165 bound to the VEGF receptors of these cells. Unexpectedly, heparin inhibited the binding of VEGF121 as well as the binding of VEGF165 to the VEGF receptors of the melanoma cells. Digestion of the cells with heparinase also inhibited the binding of both VEGF variants. The VEGF165 binding ability of heparinase-digested cells could be partially restored by the addition of exogenous heparin to the binding reaction. In contrast, the addition of heparin to heparinase-digested cells did not restore VEGF121 binding. These results suggest that cell-surface heparan sulfates may regulate the binding ability of the VEGF receptors of the melanoma cells. They also indicate that heparin is not able to fully substitute for cell surface-associated heparan sulfates since VEGF121 binding to the VEGF receptors of heparinase-treated cells is not restored by heparin. These data suggest that changes in the composition of cell-surface heparin-like molecules may differentially affect the interaction of various VEGF isoforms with VEGF receptors.

Alternative Splicing↗
PubMed1995

A correlation between the expression of the bcr-abl chimeric gene and severity of the clinical state of CML patients with time.

Using the reverse polymerase chain reaction, four Ph' positive CML patients were followed for 2 years; a correlation between the severity of the clinical state and the b3a2 expression was noted with time. Additionally, amplification of the c-myc proto-oncogene was observed, using Southern blot analysis, in one patient prior to his entry to the blast phase. No reorganization of the bcr-abl rearrangement site was found in the latter patient. The data suggest that a routine follow-up of CML patients using the Southern blot analysis and the reverse transcription-polymerase chain reaction might be of importance in evaluating the progression of the disease.

Adult↗
PubMed1994

[Neonatal alloimmune thrombocytopenia].

Neonatal alloimmune thrombocytopenia (NAIT) was first described in the 1950s. The disease results from maternal antiplatelet antibodies against surface antigens on fetal platelets due to feto-maternal platelet incompatibility. Although NAIT is transient, during its active phase thrombocytopenia can cause intracranial hemorrhage with grave neurological sequelae or death. We characterized the alloimmune antibodies in 29 mothers and found anti-HPA-1a (in 11 cases), anti-HPA1b (1), anti-HPA-5a (1) and anti-HPA-5b (5). In 11 women no specific antibodies were identified despite characteristic disease in the newborns. 3 neonates in the anti-HPA-1a, and 1 in the anti-HPA-1b groups were born with intracranial hemorrhage and are severely disabled. We described a case of successful prenatal treatment by a combination of steroids, high-dose immunoglobulins and intraumbilical platelet transfusion in a mother known to have anti-HPA-1, whose previous child was severely affected. It is important to examine antibodies in any woman whose neonate has thrombocytopenia of unknown etiology.

Antigens, Human Platelet↗
PubMed1994

Low fetal morbidity in pregnancy associated with acute and chronic idiopathic thrombocytopenic purpura.

Forty-six mothers with immune thrombocytopenic purpura (ITP) gave birth to 72 babies. Sixty-two babies were delivered vaginally and 10 babies by cesarean section. There was no mortality among mothers or babies. Eighteen infants were born thrombocytopenic (PLT < 100 x 10(9)/l). Eleven infants had a platelet count of less than 50 x 10(9)/l. All the severely thrombocytopenic babies (except 1) were born to post splenectomy thrombocytopenic mothers, regardless of steroid treatment during pregnancy. Five babies had clinical manifestations of bleeding; 3 had mild purpura, 1 severe gastrointestinal bleeding, and 1 intracranial bleeding. The latter 2 babies were born prematurely to the same mother who was severely thrombocytopenic despite splenectomy in childhood. In view of very low morbidity in babies of ITP mothers, we suggest that they be delivered vaginally. Cesarean delivery should be performed in selected cases where the mother is severely thrombocytopenic despite splenectomy or where prematurity or obstetrical complications are encountered.

Acute Disease↗