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Biomedical subjects

M D Daniel

Publications and source records attributed to M D Daniel.

At least 73 records · Page 4Linked to original sources
PubMed1985

Serologic identification and characterization of a macaque T-lymphotropic retrovirus closely related to HTLV-III.

Human T-lymphotropic virus type III (HTLV-III) is thought to play an etiologic role in the development of the acquired immune deficiency syndrome (AIDS). In this study the serologic characterization of a new simian retrovirus that is related to HTLV-III is described. This new virus, here referred to as STLV-III, was isolated from sick macaques at the New England Regional Primate Research Center. Radioimmunoprecipitation analysis revealed STLV-III-specific proteins of 160, 120, 55, and 24 kilodaltons, all similar in size to the major gag and env proteins of HTLV-III. These antigens were recognized by representative macaque serum samples and human reference serum samples positive for HTLV-III antibodies. Monoclonal antibodies directed to p24, the major core protein of HTLV-III, also immunoprecipitated a 24-kilodalton species in lysates of cells infected with the macaque virus. This HTLV-III-related virus, which naturally infects a nonhuman primate species, may provide a useful model for the study of HTLV-III and the pathogenesis of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Retrovirus D/New England and its relation to Mason-Pfizer monkey virus.

Seventeen isolates of retrovirus D/New England have been obtained from three species of macaques at the New England Regional Primate Research Center. Seven of the isolates were obtained from macaques who subsequently died with the macaque immunodeficiency syndrome; other isolates were obtained from macaques with less severe or other forms of illness. Attempts to isolate type D retrovirus from peripheral lymphocytes of 97 apparently healthy macaques have not been successful. Cloned DNA was prepared from Hirt supernatants of cells infected with one of these isolates (D/New England 398). By restriction endonuclease analysis, cloned pD398 DNA represented full-length viral DNA with one long terminal repeat. A detailed restriction endonuclease map of pD398 was derived and compared with a map of the cloned Mason-Pfizer monkey virus genome. Forty-six percent (13 of 28) of restriction endonuclease sites were found to be conserved when these related viruses were compared. Five of the D/New England isolates, including those from three different macaque species, were examined for strain variability by restriction endonuclease typing. Comparison of over 30 restriction endonuclease sites has not distinguished any of these D/New England isolates. It thus appears that a single strain of type D retrovirus is infecting three different species of macaques in the New England colony. Markedly reduced cross-hybridization was observed between cloned pD398 and Mason-Pfizer monkey virus DNAs at high stringency; this reduced cross-hybridization was localized to the pol-env regions of the genome. Only very weak hybridization of D/New England DNA to cloned squirrel monkey type D retrovirus DNA could be detected even at low-stringency conditions. What role type D retrovirus plays in the immunodeficiency syndrome of macaques remains to be determined.

Animals↗
PubMed1984

Lymphoma in macaques: association with virus of human T lymphotrophic family.

Human T-cell leukemia virus has been linked with adult T-cell leukemia-lymphoma (ATLL), a tumor of mature T cells that occurs at elevated rates in southwestern Japan and in the Caribbean Basin. Human T-cell leukemia virus (HTLV) or a closely related virus, has also been found in varying proportions of healthy individuals of several species of Old World monkeys. In the present study, conducted with macaques from Taiwan and the New England Regional Primate Research Center, antibodies to membrane antigens of HTLV-infected cells (HTLV-MA) were found in 11 of 13 macaques with malignant lymphoma or lymphoproliferative disease but in only 7 of 95 of healthy macaques. This indicates that antibodies to HTLV are significantly associated with the development of naturally occurring lymphoid neoplasms in at least some species of nonhuman primates.

Animals↗
PubMed1984

A new type D retrovirus isolated from macaques with an immunodeficiency syndrome.

Macaque monkeys with the recently described acquired immunodeficiency syndrome show a marked defect in T-lymphocyte function and die with opportunistic infections and lymphoproliferative abnormalities. In the study described here a new type D retrovirus was isolated from two Macaca cyclopis with this syndrome. This virus is related to, but distinct from, Mason-Pfizer monkey virus, a type D retrovirus previously isolated from a mammary tumor of a rhesus monkey (Macaca mulatta).

Animals↗
PubMed1984

Increased cancericidal activity of PTT.119, a new synthetic bis-(2-chloroethyl)amino-L-phenylalanine derivative with carrier amino acids. I. In vitro cytotoxicity.

A new synthetic tripeptide (p-F-Phe-m-bis-(2-chloroethyl)amino-Phe-Met ethoxy HCl), PTT.119, was demonstrated to have significant cancericidal activity against seven in vitro tumor cell lines of different origins and etiologies and against primary human AMML, ALL, and hairy cell leukemias. Viabilities of each murine tumor and rabbit, marmoset, and human leukemia and lymphoma line were significantly reduced by treatment with 1-50 micrograms PTT.119 in media containing serum. Continuous 24-h exposure or pulse treatment as short as 15 and 30 min with the tripeptide resulted in irreversible damage to the tumor cells. Under identical treatment conditions, freshly isolated human leukemic cells, particularly ALL lymphoblasts, were even more susceptible to PTT.119 than any of the tested tumor cell models. Examination of the parameters of PTT.119 activity revealed that reductions of tumor cell survival were dependent on the concentration of the tripeptide. Prolongation of PTT.119 exposure from 15 min to 24 h increased the rates of tumor cell death but did not proportionally reduce the numbers of surviving cells. Assessment of tumor cell viabilities for 5 consecutive days following pulse exposure to PTT.119 demonstrated increasing reductions in tumor cell survival, which were greatest 5 days after treatment of PTT.119 was compared with its three parental components either as individual agents or as a mixture. Both the alkylator moiety, m-sarcolysin (m.L.SL) alone or together with p-fluoro-phenylalanine and L-methionine ethoxy HCl, and L-PAM (L-phenylalanine and L-methionine ethoxy HCl, and L-PAM (L-phenylalanine mustard), the p-isomer of m.L.SL, were 1,5- to 3-fold less cytotoxic to L1210 leukemia and MJY-alpha mammary tumor cells than PTT.119. Covalent linkage of the amino acid residues to m.L.SL yielded a molecule with greatly augmented cancericidal activity capable of acting against a broad spectrum of tumor cells.

Animals↗
PubMed1984

Experimental infection of rhesus monkeys with type D retrovirus.

The naturally occurring immunodeficiency syndrome of macaque monkeys is an important animal model for the acquired immunodeficiency syndrome in humans. A new type D retrovirus, distinct from Mason-Pfizer monkey virus, has been isolated from affected animals at the New England Regional Primate Research Center. We now report the results of experimental infection of macaques with retrovirus D/New England after 13 months of study. Inoculated macaques developed lymphadenopathy without follicular hyperplasia, profound neutropenia, and a transient decrease in peripheral blood lymphocyte blastogenic responsiveness. Despite our varying the strain of virus, the manner in which the virus was grown, the size of the inoculum, and the age of the inoculated animals, infected macaques have not developed opportunistic infections or profound, prolonged loss of T cell function, key features of the macaque immunodeficiency syndrome. Therefore, experimental infection of naive macaques with D/New England has not reproduced the naturally occurring macaque immunodeficiency syndrome.

Acquired Immunodeficiency Syndrome↗
PubMed1983

Experimental transmission of macaque AIDS by means of inoculation of macaque lymphoma tissue.

Acquired immuno-deficiency syndrome (AIDS) of macaques, an animal model for human AIDS, was transmitted to previously healthy macaque monkeys by means of inoculation of either tissue or a cell-free filtrate of a macaque lymphoma. The recipients showed evidence of profound lymphocyte dysfunction or died with infections from such opportunistic agents as Candida albicans, Cryptosporidium, and cytomegalovirus.

Acquired Immunodeficiency Syndrome↗
PubMed1980

Comparative studies of interferon and three antiviral agents on neurotropic and oncogenic herpesviruses.

The antiviral effects of four compounds, phosphonoacetate, phosphonoformate, acycloguanosine, and purified human lymphoblastic interferon, were tested against two neurotropic herpesviruses, herpesvirus platyrrhine and herpes simplex virus, and two oncogenic herpesviruses, herpesvirus saimiri and herpesvirus ateles. All four compounds induced different degrees of inhibition of these herpesviruses. Phosphonoacetate and phosphonoformate at concentrations of 50 micrograms/ml or greater showed powerful antiviral activities. Interferon was more effective against herpesvirus saimiri and herpesvirus ateles, the two oncogenic viruses. Herpes simplex virus and the oncogenic herpesviruses were effectively inhibited by acycloguanosine, whereas herpesvirus platyrrhine proved to be resistant. The simian herpesviruses required a higher concentration of phosphonoformate, phosphonoacetate, and acycloguanosine for antiviral action. The antiviral action of all four compounds was contingent on the continued presence of the compounds in the infected cell culture medium.

Antigens, Viral↗
PubMed1980

Immunological relationships of OMC-1, an endogenous virus of owl monkeys, with mammalian and avian type C viruses.

The relationships between OMC-1, an endogenous oncovirus of owl monkey, and representatives of the three oncoviral genera have been investigated by radioimmunological techniques. The major structural protein of OMC-1 was shown to share antigenic determinants with the corresponding proteins of certain type C viruses of rodent, feline, and cervine origin. It was not possible to demonstrate antigenic cross-reactivity between OMC-1 and endogenous type C viruses of baboons. These findings argue that OMC-1 and baboon endogenous viruses do not represent direct descendants of an ancestor virus that became integrated within primates prior to the divergence of New and Old World species. A close antigenic relationship was established between the major structural proteins of OMC-1, an endogenous virus of deer (deer kidney virus), and avian reticuloendotheliosis viruses. These findings establish OMC-1 and deer kidney virus in the evolutionary lineage that may have led to the generation of avian reticuloendotheliosis virus, a group of oncogenic viruses capable of crossing the interclass barrier between mammals and birds.

Animals↗
PubMed1979

Detection of a nuclear antigen in Herpesvirus ateles-carrying marmoset lines by the acid-fixed nuclear binding technique.

In vitro binding of a Herpesvirus ateles (HVA)-associated soluble antigen to amphibian erythrocyte nuclei was demonstrated by the acid-fixed nuclear binding technique in combination with anticomplement immunofluorescence. Incubation of concentrated salt-extracted soluble antigens derived from HVA-carrying marmoset lines with methanol/acetic acid-fixed erythrocytes of frogs and salamanders resulted in a brilliant nuclear fluorescence after exposure to a live virus-boostered, anti-HVS-positive squirrel monkey serum. Anti-HVS-negative sera did not stain. The activity of the positive serum could be abosrbed completely with extracts of HVA-carrying cells but not with Epstein-Barr virus-carrying or Herpesvirus papio-carrying cells. The HVA-associated antigen was also present in lytically HVA-infected marmoset kidney cells.

Animals↗
PubMed1978

Endogenous New World primate type C viruses isolated from owl monkey (Aotus trivirgatus) kidney cell line.

A type C virus (OMC-1) detected in a culture of owl monkey kidney cells resembled typical type C viruses morphologically, but was slightly larger than previously characterized mammalian type C viruses. OMC-1 can be transmitted to bat lung cells and cat embryo fibroblasts. The virions band at a density of 1.16 g/ml in isopycnic sucrose density gradients and contain reverse transcriptase and a 60-65S RNA genome composed of approximately 32S subunits. The reverse transcriptase is immunologically and biochemically distinct from the polymerases of othe retroviruses. Radioimmunoassays directed to the interspecies antigenic determinants of the major structure proteins of other type C viruses do not detect a related antigen in OMC-1. Nucleic acid hybridization experiments using labeled viral genomic RNA or proviral cDNA transcripts to normal cellular DNA of different species show that OMC-1 is an endogenous virus with multiple virogene copies (20-50 per haploid genome) present in normal owl monkey cells and is distinct from previously isolated type C and D viruses. Sequences related to the OMC-1 genome can be detected in other New World monkeys. Thus, similar to the Old World primates (e.g., baboons as a prototype), the New World monkeys contain endogenous type C viral genes that appear to have been transmitted in the primate germ line.

Animals↗
PubMed1978

Herpesvirus ateles DNA and its homology with Herpesvirus saimiri nucleic acid.

Analysis of the structural organization of Herpesvirus ateles DNA shows that two types of viral DNA molecules are encapsidated in virions: (i) M-genomes, which contain 74% light sequences (L-DNA, 38% guanine plus cytosine) and 26% highly repetitive heavy sequences (H-DNA, 75% guanine plus cytosine), and (ii) defective H-genomes, which consist exclusively of repetitive H-DNA. The structure of M-genomes from H. ateles consists of an L-DNA region of about 70 x 10(6) daltons inserted between H-DNA termini of variable length. M-genomes with a shorter H-DNA region at one end of the molecule have a long stretch of H-DNA at the other end, resulting in a total molecular weight of 89.8 +/- 8.5 x 10(6). Thus it resembles the structure of M-genomes of H. saimiri. H-DNA of the two independent H. ateles isolates, strains 810 and 73, reveals different patterns after cleavage with restriction endonuclease Sma I. H-DNA of H. ateles 810 appears to consist of identical tandem repeat units with a molecular weight of 1,035,000; the H-DNA repeat unit of strain 73 is shorter (930,000 molecular weight). Corresponding DNA sequences of the two H. ateles strains (810 and 73) are completely homologous in cross-hybridizations. However, a discrete nucleotide sequence divergence between these virus strains is detected by measuring melting temperatures (T(m)) of DNA hybrid molecules. Some homology exists between H. ateles and H. saimiri DNA. Hybridization of L-DNA from H. ateles with L-DNA from H. saimiri shows about a 35% homology between the respective L-DNA sequences; the resulting heteroduplex molecules show a decrease of T(m) by 13.5 degrees C, corresponding to about a 9% mismatching in cross-hybridizing parts of L-regions. Very little homology is found between H-DNA of H. ateles and H. saimiri.

Base Sequence↗
PubMed1977

Biologic and antigenic characteristics of Epstein-Barr virus-related Herpesviruses of chimpanzees and baboons.

Leukocyte-transforming agents were isolated in baboon leukocytes inoculated with oral excretions from immunosuppressed chimpanzees. The transformed lymphoblasts had B cell surface markers and harbored herpes-type virus particles; 5-10% of the cells contained cytoplasmic antigens reactive with Epstein-Barr virus (EBV)-antibody-positive chimpanzee, human and baboon sera. These sera also neutralized the transforming activity of the chimpanzee virus. Long-term lymphoid cell lines were established from circulating lymphocytes of normal baboons: two from Papio cynocephalus and three from P. hamadryas. The cells had B cell surface markers, contained herpes-type virus particles and produced virus with leukocyte-transforming activity. No virus-associated nuclear antigen was detectable with reference baboon and chimpanzee sera; however, the cells reacted with selected human sera containing antibodies to EBV nuclear antigen (EBNA). Absorption experiments confirmed the specificity of this reaction. Baboon lymphoblasts produced baboon virus-associated soluble complement-fixing (CF/S) antigen. Baboon sera had CF antibodies to viral (CF/V) antigen derived from EBV but failed to react with EBV-associated CF/S antigen. Chimpanzee and baboon herpesviruses had similar in vitro host cell ranges but were different from those of EBV. Inoculation of baboons, rhesus monkeys and cottontop marmosets failed to produce detectable illness or palpable tumors.

Animals↗