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Biomedical subjects

R Sharon

Publications and source records attributed to R Sharon.

107 records · Page 6Linked to original sources
PubMed1975

DNP-Lys-ficoll: a T-independent antigen which elicits both IgM and IgG anti-DNP antibody-secreting cells.

The 2,4-dinitrophenyl-lysyl derivative of Ficoll (DNP-Lys-Ficoll) was prepared and examined for immunogenicity. This antigen elicited large numbers of DNP-specific plaque-forming cells (PFC) of the IgM and IgG2 class in the spleens of C57BL/6 mice. Similar responses were observed in congenitally athymic (nu/nu) mice and in their littermates indicating that DNP-Lys-Ficoll is a T-independent antigen. The responses of nu/nu mice included a large number of IgG2 DNP-specific PFC, indicating that IgG responses can be initiated in the absence of mature thymus-dependent (T) lymphocytes. Cell transfer studies confirmed the T independence of the response and indicated that priming with DNP-Lys-Ficoll induces only a very meager degree of memory. Because they can be obtained in large quantities and in relatively pure form, DNP-Lys-Ficoll and other hapten conjugates of Ficoll should prove most valuable in the delineation of the mode of activation of precursors of antibody-secreting cells by T-independent antigens.

Animals↗
PubMed1974

Role of ATP in excision repair of ultraviolet radiation damage in Escherichia coli.

The effect of ATP on the first step of excision repair of ultraviolet damage in DNA has been studied using toluene-treated E. coli. During postirradiation incubation, five to six times more single-strand breaks are formed in DNA in the presence of exogenous ATP than in its absence. The ATP-dependent as well as the ATP-independent endonucleolytic activities appear to be catalyzed by the same enzyme since both activities are almost completely absent in uvrA and uvrB mutants. An ATP-dependent endonucleolytic activity has been detected in nonirradiated toluene-treated E. coli. It is concluded that ATP is required in vivo for either the incision step of repair or an enzymatic reaction preceding it.

Adenosine Triphosphate↗
PubMedDate not supplied

The interplay between X-ray crystallography, neutron diffraction, image reconstruction, organo-metallic chemistry and biochemistry in structural studies of ribosomes.

Crystals of ribosomes, their complexes with components of protein biosynthesis, their natural, mutated and modified subunits, have been subjected to X-ray and neutron crystallographic analyses. Electron microscopy and 3-dimensional image reconstruction, supported by biochemistry, genetic, functional and organo-metallic studies were employed for facilitating phasing of the crystallographic data. For example, a monofunctional multi heavy-atom cluster (undecagold) was designed for covalent and quantitative binding to ribosomes. The modified particles were crystallized isomorphously with the native ones. Their difference-Patterson maps contain indications for the usefulness of these derivatives for subsequent phasing. Models of the ribosome and its large subunit were reconstructed from tilt series of 2-dimensional sheets. The comparison of the various reconstructed images enabled an initial assessment of the reliability of these models and led to tentative assignments of several functional features. These include the presumed sites for binding mRNA and for codon-anticodon interactions, the path taken by the nascent protein chain and the mode for tRNA binding to ribosomes. These assignments assisted in the design of biologically meaningful crystal systems. The reconstructed models are being used to identify structural features in initial density maps derived from X-ray and neutron diffraction data.

Crystallography↗
PubMedDate not supplied

Formaldehyde-related antibodies in hemodialysis patients.

In a study of anti-N-like antibodies, we tested sera from 93 hemodialysis patients for hemagglutination reactions with untreated and formaldehyde-treated reagent red blood cells. Six of 22 sera from patients who had been dialyzed with formaldehyde-sterilized membranes had anti-N-like activity and 20 (91%) specifically agglutinated formaldehyde-treated red blood cells. Sera from 71 patients dialyzed with disposable membranes neither had anti-N-like activity nor agglutinated formaldehyde-treated red blood cells. The agglutination of formaldehyde-treated red blood cells by sera from hemodialysis patients was unrelated to MNU phenotypes and, therefore, identified a second serologic specificity, provisionally termed "anti-formaldehyde." "Anti-formaldehyde" was absorbed by and eluted from NN red blood cells as well as from formaldehyde-treated red blood cells regardless of MNU phenotype. All eluates and sera containing anti-N-like activity also agglutinated formaldehyde-treated red blood cells, typically after the addition of anti-human serum. These findings are consistent with the hypothesis that anti-N-like reactions of hemodialysis patients' sera represent cross reactions of formaldehyde related antibodies with N antigens of normal red blood cells.

Absorption↗
PubMedDate not supplied

Reduced antibody response in patients with chronic renal failure undergoing hemodialysis with formaldehyde sterilized units.

In an attempt to explain the relatively low incidence of antibody production seen in patients undergoing regular hemodialysis, sera from 200 patients were exposed to formaldehyde under conditions similar to those during dialysis. It was found that this procedure substantially reduced antibody titers, except when the initial titer was very high. The danger of missing low antibody titers after dialysis is pointed out.

ABO Blood-Group System↗
PubMedDate not supplied

Regulatory elements controlling the basal and drug-inducible expression of glutathione S-transferase Ya subunit gene.

The synthesis of the glutathione S-transferase Ya subunit is induced in the mammalian liver by chemicals such as phenobarbital and 3-methylcholanthrene. To study the mechanism of this induction, the 5'-flanking region of a mouse glutathione S-transferase Ya subunit gene was fused to the structural gene for chloramphenicol acetyltransferase. The fusion gene was introduced into hepatoma cells for the assay of the expressed acetyltransferase activity. At least two cis-regulatory elements were identified in the 5'-flanking region of the Ya gene: one, responsible for the basal level of expression, is present in the sequence up to -0.2 kb; another, responsible for the inducible expression by aromatic compounds such as beta-naphthoflavone and 3-methylcholanthrene, is located in the sequence from -0.2 kb to -1.6 kb. The inducible element was functional only in cells with normal aromatic compound receptors, and it retained responsiveness to beta-naphthoflavone when transfected into homologous (mouse) or heterologous (rat, human) hepatoma cells. A 150-bp region upstream from the transcription initiation site of the mouse Ya gene was investigated for cis-acting transcriptional elements that are recognized by specific DNA-binding proteins. We show by DNase I foot-printing assays using extracts from liver nuclei that the Ya gene promoter contains, in addition to the TATA and CCAAT boxes, a more distal element that binds a protein which is probably related to the family of nuclear factor 1 (NF1).

Animals↗
PubMedDate not supplied

Fever and neutropenia in children with malignant disease.

Treatment of episodes of fever and neutropenia in pediatric hematology-oncology patients includes hospitalization and administration of intravenous antibiotics until the patient is afebrile and no longer neutropenic. The present analysis characterizes retrospectively febrile episodes in neutropenic pediatric hematology-oncology patients with regard to frequency of documented infections, organisms associated with these infections, efficacy of a standardized antibiotic regimen, and safety of early antibiotic discontinuation under defined conditions. A total of 149 pediatric febrile neutropenic episodes were identified during a 4-year period between 1990 and 1994. These occurred in 47 male and 19 female patients, of a mean age of 7.6 years (range 0.5-15). The most frequent diagnoses were leukemia (41% of patients), lymphoma (21%), rhabdomyosarcoma (7%), soft tissue sarcoma (5%), Ewing's sarcoma (5%), and osteosarcoma (4%). Infection was certain in 36% of febrile episodes, probable in 14%, and not determined in 50%. Patients with severe neutropenia (absolute neutrophil count < 100) had a slightly, although not significantly higher incidence of documented and probable infection (57%). Patients with solid tumor had documented infection in 40% of their febrile episodes, and the detection rate in the children with leukemia was 31% (P < .20) Blood cultures were positive in 21 (14%) of 149 episodes. Staphylococci (both coagulase-negative and coagulase-positive strains) and Pseudomonas were the organisms most frequently isolated (six episodes each). Mouth and throat (11), lungs (10), and skin (10) were the next most frequent sites of localized infection. Initial treatment consisted of piperacillin and amikacin or of vancomycin and amikacin when the source of fever was thought to be an infected central line catheter, with addition of amphotericin B by the seventh day of treatment when fever with neutropenia persisted or upon clinical suspicion of underlying fungal infection. There was a single fatality, of a patient with Burkitt's lymphoma. Antibiotics were discontinued when initial blood cultures had no growth after at least 48 hours and no source of infection was found, the blood count was improving, and if the patient became afebrile and clinically well. No patient needed readmission during the fortnight that followed discontinuation of antimicrobial therapy. Patients with negative blood cultures under defined conditions, as described above, could safely be discharged early, thus shortening the duration of intravenous antibiotic therapy and hospital stay.

Adolescent↗