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Biomedical subjects

Y Becker

Publications and source records attributed to Y Becker.

At least 109 records · Page 6Linked to original sources
PubMed1988

HSV-1 DNA sequence determining intraperitoneal pathogenicity in mice is required for transcription of viral immediate-early genes in macrophages.

The relationship between intraperitoneal (ip) pathogenicity in vivo of herpes simplex virus type 1 (HSV-1) and infection of macrophages (m phi) in vitro was studied. The apathogenic HSV-1 strain HFEM disappeared from the peritoneum of infected mice following ip inoculation, while the pathogenic F strain persisted in the peritoneum and penetrated the mouse nervous system, and eventually the mice died, showing severe neurological signs. When peritoneal m phi were infected in vitro, a direct correlation with pathogenicity in vivo was found with several HSV-1 strains and recombinants. HSV-1 strains (F, KOS, R-M1C1) which were pathogenic for mice by the ip route, induced cytopathic effect (CPE) in m phi in vitro. Strain F transcribed viral immediate-early genes and synthesized viral DNA in m phi that were treated with L-cell conditioned medium (as a source of colony-stimulating factor) prior to infection. Apathogenic HSV-1 strains (HFEM, R-15, R-19) did not cause CPE in m phi. The HFEM strain was already blocked in the transcription of viral alpha genes in the infected m phi, but replicated well in control BSC-1 cells. An intratypic recombinant (R-M1C1), produced by cotransfection of HFEM DNA with a cloned Mlul-Mlul DNA fragment (coordinates 0.7615-0.796) from HSV-1 strain F, that was shown [Becker et al. (1986). Virology 149, 255-259] to have regained partial ip virulence for mice, now transcribed alpha genes, synthesized viral DNA, and induced CPE in m phi. It appears that the viral DNA fragment responsible for ip virulence is involved in tissue-specific recognition of virus by infected m phi, a function necessary for transcription of viral alpha genes.

Animals↗
PubMed1988

Comparative analysis of the transcripts mapped in the BamHI DNA fragment B of avirulent HSV-1 HFEM, virulent HSV-1 F, and their intratypic recombinant viruses.

HSV-1 HFEM, whose genome harbors a deletion of 4.1 kbp (0.762 to 0.789 map units (mu] is avirulent for mice and tree shrews by the intraperitoneal (i.p.) application route. Insertion of the BamHI DNA fragment B (0.738 to 0.809 mu) and/or the MluI DNA fragment (0.7615 to 0.796 mu) molecularly cloned from virulent HSV-1 F, restored the i.p. pathogenicity to strain HFEM and led to the isolation of virulent intratypic recombinants. In order to determine the RNA transcripts mapped in the BamHI DNA fragment B of the HSV-1 HFEM, HSV-1 F, and their intratypic recombinants R15, R19, R26, and R-Ml-C1, a comparative analysis was performed using Northern blot hybridizations. Two novel RNA transcripts of 3.5 and 1.5 kb were detected which hybridize to the left terminus (0.738 to 0.746 mu) of the BamHI DNA fragment B. The 1.5 kb RNA transcript was missing in the avirulent HSV-1 HFEM. Hybridization with the BssHII DNA fragment F (0.760 to 0.762 mu) led to detection of a 3.5 kb RNA transcript by HSV-1 HFEM which was missing in all other viruses tested. In contrast a 1.5 kb RNA transcript was detectable in all other virus strains with the exception of HSV-1 HFEM. The 3.5 kb transcript hybridized to the right-hand flank of the deleted region in the genome of HSV-1 HFEM (Asp718/SalI DNA fragment; 0.786 to 0.79 mu). The detection of the novel 1.5 kb RNA, which is missing in HSV-1 HFEM, and the appearance of the newly transcribed 3.5 kb RNA in HSV-1 HFEM only, indicates a new open reading frame in this particular region as a consequence of the fusion of the DNA sequences at both ends of the deletion in the genome of HSV-1 HFEM.

Chromosome Deletion↗
PubMed1988

Multiple sclerosis autoantibodies and antibodies in AIDS may deplete a brain peptide hormone.

Computerized Chou-Fasman analysis of the secondary structure of human T-cell leukemia viruses (HTLV-I, HTLV-II) and human immunodeficiency virus (HIV) envelope proteins revealed that only one antigenic epitope (amino acids EAL) is shared by the three viruses. A similar antigenic epitope is also found in human and rat brain hormone vasopressin-neurophysin. If autoantibodies in multiple sclerosis (MS) are made to the epitope EAL, they may cross-react with the envelope proteins of HTVL. It is speculated that in AIDS patients, antibodies to the antigenic epitope EAL of HIV may cross-react with brain vasopressin-neurophysin, leading to a decline in this brain peptide hormone. Thus it is hypothesized that treatment of both MS and AIDS patients with a synthetic polymer containing the amino acids EAL might eliminate the antibodies to vasopressin-neurophysin and thus alleviate some of the clinical symptoms.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Differential expression of Epstein-Barr virus (EBV) genes BBRF3, BILF1, and BMRF2 in EBV-transformed lymphoblastoid lines from ataxia-telangiectasia patients.

The expression of three EBV open reading frames (ORF's), BBRF3, BILF1 and BMRF2 in Epstein-Barr virus (EBV)-transformed B lymphocytes from ataxia-telangiectasia (A-T) homozygotes, was studied. A-T is a human recessive genetic disorder which predisposes homozygotes and heterozygotes to cancer. Computer analysis (Robson-Garnier) was used to study the secondary structure of EBV ORF's. Three ORF's (BBRF3, BILF1 and BMRF2) found by the Kyte and Doolittle computer method to have multiple hydrophobic domains in the putative polypeptides were selected, and the polypeptides were selected, and the respective cloned EBV DNA fragments were used as probes to detect mRNA in the normal and L-6 A-T lines that was not present in the L-15 A-T line. The probe for BILF1 detected two mRNA species (3.7 and 2.0 kb) in the normal lymphoblastoid and A-T L-6 lines, while only the 3.7 kb mRNA was expressed in the A-T L-15 lymphoblasts. The probe for BMRF2 detected two mRNA species (3.7 and 2.1 kb) in the EBV-transformed normal lymphoblasts and in one A-T line (L6). The BMRF2 mRNAs were not detected in the other A-T line (L-15). This study indicated that regulation of the three EBV genes in two EBV-transformed A-T lymphoblastoid lines, differs from that in the EBV-transformed normal lymphoblastoid line. In the A-T line L-6, the three EBV genes were expressed as in EBV-transformed lymphoblastoid cells originating from a normal donor (L-21) and in the P3HR1 Burkitt's lymphoma cell line. The A-T line L-15 differed from L-6 and the other cell lines in that it expressed only one (3.7 kb) RNA species from BILF1 ORF, while ORFs BBRF3 and BMRF2 were not expressed. Since A-T L-15 line contains EBV DNA genomes, and EBV VCA is not present in these cells prior to or after TPA treatment, it is suggested that EBV gene expression is regulated by these A-T lymphoblastoid cells in a manner different from that which operates in other EBV transformed cell lines.

Antigens, Viral↗
PubMed1987

Polymorphs of tamoxifen citrate: detailed structural characterization of the stable form.

The structure of the stable polymorph of tamoxifen citrate (form B) has been analyzed by single crystal X-ray diffraction [monoclinic, a = 15.998 (4), b = 21.964 (3), c = 8.624 (5) A, beta = 96.28 (3) degrees, space group P2(1)/c]. The results include conformational details of the molecular structure as well as a description of the observed packing arrangement in the solid which is dominated by hydrogen-bonding interactions between the ionic entities. The proton transfer to the nitrogen atom of tamoxifen is from the central carboxyl group of the citric acid. There is a satisfactory correlation between the solid infrared spectrum of the carboxylic functions and the asymmetric environment observed around them in the crystal lattice. Additional results obtained from thermal and spectral analyses suggest that the second polymorph of tamoxifen citrate (form A) represents a metastable form of this compound. The two polymorphs are characterized by their powder diffraction spectra.

Chemical Phenomena↗
PubMed1987

HSV-1 virulence for mice by the intracerebral route is encoded by the BamHI-L DNA fragment containing the cell fusion gene.

The phenotype of pathogenicity by direct intracerebral inoculation of herpes simplex virus type 1 (HSV-1) was mapped in the viral genome. This phenotype could be rescued by cotransfection of unit length HSV-1 DNA of an avirulent strain with the BamHI fragment L (0.70-0.738 map units) cloned from a virulent strain. The virulence function was localized in the 2.0 Kb NruI-BamHI fragment in the right-hand side of BamHI-L, the same region that encodes a virus cell-fusion gene (3). Transduction of virulence was linked with the phenotype of a larger plaque size. It is concluded that a neurovirulence function resides in the BamHI-L fragment of the HSV-1 genome, closely linked to the viral gene for cell fusion.

Animals↗
PubMed1987

Determination of the nucleotide sequence flanking the deletion (0.762 to 0.789 map units) in the genome of an intraperitoneally avirulent HSV-1 strain HFEM.

Herpes simplex virus type 1 (HSV-1) strain HFEM which harbours a deletion of 4.1 kbp in its genome (0.762 to 0.789 map units, HpaI DNA fragment P of HSV-1), is apathogenic for mice and tree shrews by the intraperitoneal application route. The exact position of this deletion was determined by DNA sequence analysis. This analysis was performed using the recombinant plasmid pU18HSHF-XmI-B which harbours the flanking genome regions (0.752 to 0.762 and 0.789 to 0.7895 map units) of the deletion in the genome of HSV-1 HFEM, and the recombinant plasmids pU18HSF-XmI-B, pU18HSF-AS, and pHSF-BB-BsH-D, harbouring particular regions of the genome of the virulent HSV-1 strain F at the coordinates 0.752 to 0.761, 0.786 to 0.790, and 0.762 to 0.771, respectively. The comparison of the DNA sequence of this region with the DNA sequences of the corresponding genome regions of the pathogenic HSV-1 strain F and HSV-1 strain 17 showed that the 5' end of the deletion in the genome of HSV-1 HFEM starts at the nucleotide position 3774 of the BamHI DNA fragment B from HSV-1/17. This position is 71 bp upstream of the UL/RL junction of the HSV-1 genome. The 3' terminus of the deletion ends at the nucleotide position 7226 of the BamHI DNA fragment B from HSV-1/17. The position is within the incomplete ninth repetitive box (ACTCC-CACGCACCCCC) and is located 36 bp upstream of the 3' end of the IE 110 mRNA.

Animals↗
PubMed1987

Herpes simplex virus type 1 pathogenicity in footpad and ear skin of mice depends on Langerhans cell density, mouse genetics, and virus strain.

Skin Langerhans cells have been shown to be very efficient in presenting antigens to T-helper cells and stimulating the immune response. The present study demonstrates their essential role in the control of primary herpetic infections in the skin. Two unrelated stimuli (abrasion and steroids) were shown to cause depletion of the Langerhans cells in the murine epidermis, and both caused enhancement of the virulence of herpes simplex type 1 (HSV-1) in the skin. The Langerhans cell density was found to be lower in the skin of the ear than in the footpad. HSV-1 was consistently more virulent when injected into the ear epidermis than in the footpad. Thus, HSV-1 pathogenicity in mouse skin depends on the mouse age and strain, the virus strain, and the state of the epidermal Langerhans cells. These findings are discussed in relation to the antigen-presenting cell function of the Langerhans cells.

Age Factors↗
PubMed1987

Does radiation-induced abrogation of skin Langerhans cell functions lead to enhanced incidence of skin tumors in patients with genetic disorders of DNA repair?

A hypothesis is presented which states that persons with the genetic disorders xeroderma pigmentosum and ataxia-telangiectasia, manifested by a deficiency of DNA repair, develop cutaneous tumors due to the elimination of reticuloendothelial system cells (Langerhans cells) in the skin, and the subsequent loss of control of epidermal cellular elements.

Ataxia Telangiectasia↗
PubMed1986

Skin Langerhans cells play an essential role in the defense against HSV-1 infection.

The role of the Langerhans cells (LC) during HSV-1 infection in murine skin was examined. LC function as very potent antigen-presenting cells and represent the most peripheral immune cellular elements in the body. The footpad route was used to study the response of LC to infection with a pathogenic and non-pathogenic strain of HSV-1. Following infection with a pathogenic HSV-1 strain, there was an increase in the number of LC in the footpad skin. Depletion of LC from the skin by treatment with 10 per cent aqueous saline and abrasion led to the enhancement of HSV-1 virulence and the nonpathogenic virus became highly pathogenic. Progressive recovery of LC in the skin during the healing process was accompanied by a gradual increase in resistance to HSV-1 infection.

Animals↗
PubMed1986

A sequence in HpaI-P fragment of herpes simplex virus-1 DNA determines intraperitoneal virulence in mice.

The virulence of herpes simplex virus-1 (HSV-1) strains by the intraperitoneal (ip) route of injection in mice depends on the presence of an intact sequence in the HpaI DNA fragment P within coordinates 0.762 to 0.787. Deletion of the HpaI-P region (e.g., strain HFEM) abrogates the ability of the virus to infect mice by the ip route without affecting pathogenicity by the intracerebral (ic) route. A recombinant virus (M1C1) derived from DNA of the HSV-1 HFEM strain and the MLUIDNA fragment (coordinates 0.761 to 0.796) spanning the HpaI-P sequence of the pathogenic strain F regained pathogenicity for mice by the ip route.

Animals↗
PubMed1986

Detection of Marek's disease virus antigens and DNA in feathers from infected chickens.

Two novel tests, enzyme-linked immunosorbent assay (ELISA) and dot-blot hybridization, were developed to detect and quantify the antigens and DNA of Marek's disease virus (MDV) in feather tips from infected chickens. In both methods, buffered extracts of the feathers served as the same test material. The ELISA technique was compared to the conventional agar-gel precipitation (AGP) test, using the same convalescent serum from a MDV-infected bird. Of 86 feather samples tested, 34 were negative by both methods, while 6 out of 52 were ELISA positive but AGP negative. Viral antigen detection by the AGP and ELISA methods was compared with the detection of MDV DNA by the dot-blot DNA hybridization technique. At an ELISA reading (OD 405) of 0.3 and above, only 5 out of 48 DNA extracts failed to hybridize with the MDV-DNA probe. The use of the radioactively labelled MDV-DNA probe for hybridization with DNA extracts from feather tips of MDV-infected chickens was both sensitive and specific, and there was good correlation among the different tests.

Agar↗
PubMed1986

An improved ELISA method, using a streptavidin-biotin complex, for detecting Marek's disease virus antigens in feather-tips of infected chickens.

To improve sensitivity in the detection of Marek's disease virus (MDV) antigens in extracts of feather tips from infected chickens, we added a preformed streptavidin-biotin complex to the standard enzyme-linked immunosorbent assay (ELISA). Rabbit anti-chicken IgG-alkaline phosphatase that is used in the standard ELISA as the conjugate was replaced by a biotinylated rabbit anti-chicken IgG plus the streptavidin-biotin peroxidase complex (ABC) system. The ABC-ELISA system was correlated to the standard ELISA. There was increased sensitivity in the detection of MDV antigens present at low concentrations, while at the higher concentrations detection was similar to that in the standard ELISA. Both ELISA systems had the same increased sensitivity when compared with that of the agar gel precipitation (AGP) test.

Animals↗
PubMed1986

Use of lectins to detect and differentiate subtypes of Marek's disease virus and turkey herpesvirus glycoproteins in tissue culture.

Biotinylated lectins in conjunction with an avidin-biotin-peroxidase complex were used for the first time to reveal glycoproteins in chicken and duck embryo fibroblasts infected with three prototype members of the avian herpesvirus group, Marek's disease virus serotypes 1 and 2 and turkey herpesvirus. By using a panel of 10 lectins, a pattern of reactivity emerged which was both group- and type-specific. Morphological details of the lectin-stained cells include cytoplasmic granulation, capping and bleb-like protrusions of the cell membrane. Although no antibody is necessary for the reaction, this novel approach allows specific detection of the glycan moieties of viral glycoproteins as they are synthesized during infection.

Animals↗
PubMed1986

Replacement of the deletion in the genome (0.762-0.789 mu) of avirulent HSV-1 HFEM using cloned MluI DNA fragment (0.7615-0.796 mu) of virulent HSV-1 F leads to generation of virulent intratypic recombinant.

The HFEM strain of HSV-1 is apathogenic for the tree shrew by the intraperitoneal (i.p.) route because of a deletion in the genome coordinates 0.762-0.789. Insertion of the MluI DNA fragment (coordinates 0.7615-0.789) cloned from HSV-1 strain F, which is pathogenic for the tree shrew, restored the i.p. pathogenicity to strain HFEM. The recombinant designated R-M1-C1 was highly pathogenic for the tree shrew, but slightly virulent for inbred mouse strain A. It thus appears that the viral DNA sequence involved in the i.p. pathogenicity of HSV-1 is located within the genome coordinates 0.761-0.796. This sequence is recognized differently by the cellular elements involved in HSV-1 infection in the tree shrew and the mouse.

Animals↗
PubMed1986

Studies on a pancreatic cardiodepressant factor.

Myocardial depressant factor (MDF) was isolated from dog pancreas after incubation at 37 degrees C for 2 hr. A highly purified preparation of MDF was obtained by paper chromatography and high voltage electrophoresis. After paper chromatography of crude homogenates of the pancreatic tissue, cardiodepressant activity was found in spot F. High voltage electrophoresis of spot F produced five separate fractions. Bioassay using isolated perfused hearts and cultures of myocytic tissue showed that only one of these spots was associated with MDF activity. This spot contained a peptide with a molecular weight of 1000-2500 consisting of nine amino acids.

Amino Acids↗
PubMed1985

Cells from patients with ataxia telangiectasia are abnormally sensitive to the cytotoxic effect of a tumor promoter, phorbol-12-myristate-13-acetate.

Fibroblast strains from 6 patients with ataxia telangiectasia (A-T) were found to be markedly hypersensitive to the cytotoxic action of the tumor promoter phorbol-12-myristate-13-acetate (PMA), their D37 values being 5 times lower than those of two normal controls. Two A-T heterozygous strains were slightly hypersensitive to PMA, while a third one showed normal sensitivity. It is concluded that the DNA lesion which is critical in A-T cells is an important component of the damage caused by PMA-induced free radicals and may play a role both in the tumor-promoting activity of PMA and the cancer proneness of A-T patients.

Ataxia Telangiectasia↗