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S K Arya

Publications and source records attributed to S K Arya.

At least 73 records · Page 4Linked to original sources
PubMed1980

Search for retrovirus-like particles in human breast cancer cells in culture.

We have recently established four new human breast cancer cell lines that were characterized as being of human mammary origin. We examined these cell lines for particles morphologically resembling retroviruses by electron microscopy, for extracellular and intracellular particles containing high-molecular-weight RNA and RNA-directed DNA polymerase by biochemical assays, and for mouse mammary tumor virus (MMTV)-related sequences in the cell genomes by molecular hybridization. An extensive search for budding particles by thin-section electron microscopy of cells did not provide evidence for retrovirus-like particles. Similarly, 1000- to 2000-fold concentrated samples of medium harvested from 10(8) cells did not contain particles of a density of 1.14 to 1.16 g/ml containing RNA-directed DNA polymerase. Compared with DNA polymerase activity of MMTV, and taking into account the particle weight and protein content of retroviruses, we estimate that, if these cells produce retrovirus-like particles, this production would be less than 1.6 particles/cell every 24 to 72 hr. The hybridization of cell DNA with MMTV complementary DNA also did not show detectable amounts of virus-related sequences in the cell genome. Analysis of the hybridization results suggested that, if the human breast cells contained MMTV-related sequences, they must be present in less than one copy per 100 cells. Thus, we have obtained no convincing evidence for the presence of retrovirus-like particles or subviral components in these cells. It is of course possible that these cells contain virus information but at levels below the sensitivity of our assay procedures.

Breast Neoplasms↗
PubMed1979

Effect of bromodeoxyuridine and interferon on cellular and viral functions in human prostatic cells.

Some of the human prostatic cells in culture apparently produce oncornavirus-like particles. Bromodeoxyuridine does not enhance the production of these particles. On the contrary, this drug depresses such production. This depression is likely to be due to the cytotoxic effects of bromodeoxyuridine for these cells. These results can be interpreted to suggest that the human prostatic cells used in this study do not contain endogenous oncornavirus genetic information that is inducible. Purified human interferon inhibits the production of oncornavirus-like particles by these prostatic cells. It is also inhibits the rate of cellular DNA synthesis in these cells. These results are consistent with the notion that the inhibitory effects of interferon are mediated through its effect on cellular biosynthetic machinery.

Adenocarcinoma↗
PubMed1979

Oncornavirus-like particles released by human prostatic explant cultures.

Explant cultures from several human prostatic tissues have been examined for oncornavirus production. Some of these explants, epithelial in morphology, appear to release oncornavirus-like particles. The extracellular particulate material, obtained from the culture medium of these explants display the following characteristics: (1) It contains particles that band at a density of 1.1-1.2 g/cm3 in a sucrose density gradient. (2) The particles contain RNA-directed DNA polymerase. This polymerase utilizes poly(Cm) as a template and shows preference for poly(A) over poly(dA) and manganese over magnesium. (3) Apparently, the particles also contain RNA that directs the synthesis of DNA in vitro. The DNA thus synthesized is associated with RNA, some of it with high molecular weight RNA. Such particles are not observed in the culture medium from monolayers of monkey kidney CV-1 cells. We have found that explant cultures from 5 out of 15 tissue specimens with prostatic hyperplasia and 3 out of 4 with prostatic adenocarcinoma release particles that band at a density of 1.1-1.2 g/cm3 and contain RNA-directed DNA polymerase. Explant cultures of two normal prostates examined did not release such particles.

Adenocarcinoma↗
PubMed1978

Reverse transcriptase activity in extracts of human prostatic tissues.

The extracts of human prostatic tissue specimens contain oncornavirus-like reverse transcriptase activity. This activity was isolated by banding the tissue extract in an equilibrium sucrose density gradient followed by phosphocellulose chromatography of the lysate of the material banding at a density of 1.14--1.20 g/cc. It was characterised by its utilisation of poly (Cm) as a template and its inhibition by selective inhibitors of viral reverse transcriptase. Human prostatic tissues of three histo-pathologic types--normal, hyperplastic and adenocarcinoma--were examined. One out of four normal, five out of six hyperplastic, and two out of two adenocarcinoma specimens displayed virus-like reverse transcriptase activity.

Adenocarcinoma↗
PubMed1977

A status report: human prostatic carcinoma, with emphasis on potential for viral etiology.

Several parameters of the biology of cancer of the prostate have been reviewed with a continuing assessment of the possible etiologic role of virus. These aspects include epidemiology, clinical studies, morphology, pathology, enzymology, immunology, endocrinology, model animal studies, in vitro systems, and viral investigations. From available literature it is concluded that, to date, the association with several urogenital tissues of herpes-type viruses has been best documented. It is suggested that a fundamental barrier to more sophisticated virologic and biologic studies is the lack of long term cell cultures of normal and pathologic prostate epithelium from males of all ages.

Acid Phosphatase↗
PubMed1976

RNA tumor virus-like activities in human solid tissues: endogenous RNA:DNA polymerase activities in the prostate.

Several human prostatic tissues have been examined for possible particles and associated DNA polymerizing activity generally associated with the C-type RNA tumor virus family. Partially purified tissue extracts, when centrifuged to equilibrium in sucrose gradients, yield fractions which contain actinomycin D resistant, endogenous DNA polymerase activity; this activity bands at a density of 1.15-1.18 gm/cm3. Further analysis of the endogenous products by sucrose gradient sedimentation suggested the presence of high molecular weight RNA:DNA hybrids generally felt to be indicative of a faithful copy of a lengthy stretch of viral specific RNA. However, most of the DNA products synthesized in these endogenous reactions sedimented in much lower molecular weight regions of these sucrose gradients. Clearly, the relative distributions of "high" and "low" molecular weight products could critically depend on the nuclease content of the subcellular fraction under study, and the prostate may be relatively enriched in nucleases. Further, oligo (dT) stimulated the endogenous DNA polymerase activity contained in these extracts, and omission of one of the DNA precursor nucleotides depressed it. Thus, it seems unlikely that terminal transferase activity, rather than genuine DNA polymerization, was being measured primarily. Because of the spectrum of molecular weight classes formed by these DNA:RNA hybrids, as well as their apparent presence in normal prostatic tissue, we find it difficult to ascribe their presence with certainty either to the presence of typical C-type RNA viruses or to the exclusive behavior of the neoplastic prostatic tissue. Thus, our studies lend support to the growing evidence for functions similar to those of C-type RNA viruses being relatively widespread in human tissues without the apparent necessity for a possible etiologic role in neoplastic production (Strand and August, 1974; Sherr et al., 1974). At the same time, our current studies emphasize the need for caution in drawing conclusions from results utilizing probes generally felt quite useful in scoring for presence of virus in lower animals at least in the human prostate.

Centrifugation, Density Gradient↗
PubMed1975

Interaction of steroids with nucleic acids.

17beta-Estradiol and testosterone bind to both native and denatured DNA, and to RNA and poly(A)-poly(U). Binding affinity depends on the conformation of nucleic acid. Lowering the electrolyte concentration and raising the temperature increase the binding of 17beta-estradiol to native DNA and decrease that to denatured DNA. In 0.01 M NaCl and at 37 degrees, more 17beta-estradiol is bound to native DNA than to denatured DNA. Higher binding of steroid to denatured DNA relative to native DNA at low temperature and high ionic strength is related to larger fraction of binding sites per unit nucleotide in denatured DNA. In addition to 17beta-estradiol and testosterone, 17alpha-estradiol, 17beta-estradiol-3-methyl ether and 19-nortestosterone also stabilize the structure of nucleic acids and poly(A)-poly(U) against thermal denaturation. The 17beta-estradiol induced elevation of the T-m of DNA is diminished by methanol or high NaCl concentration. These results indicate the involvement of hydrogen bonding and hydrophobic interactions between steroids and nucleic acids. The results of binding isotherms and optical studies suggest a conformational dependence of the binding of steroids to nucleic acids.

Animals↗
PubMedDate not supplied

Molecular cloning and characterization of the HTLV-III virus associated with AIDS.

We recently reported the isolation and characterization of a novel human T-lymphotropic retrovirus, HTLV-III, in patients with acquired immune deficiency syndrome (AIDS) and in those at risk for the disease. After extensive sero-epidemiological studies, together with numerous virus isolations from these patients, we concluded that HTLV-III is the causative agent of AIDS. Here we report the molecular cloning and characterization of two highly related but distinct forms of the HTLV-III genome. The viral genome is approximately 10 kilobases long and is detected in HTLV-III-infected cells but not in uninfected cells, including normal human tissue, indicating that this virus is exogenous to man. We also demonstrate distant nucleic acid sequence homology between the cloned genome of HTLV-III and those of HTLV-I and HTLV-II. The availability of the cloned HTLV-III genome will now allow an unambiguous comparison of this virus with other retroviruses that also have been associated with the pathogenesis of AIDS, and moreover, with facilitate the development of diagnostic and therapeutic measures in the treatment of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

New human and simian HIV-related retroviruses possess functional transactivator (tat) gene.

New human retroviruses antigenically related to HIV and even more closely to STLV-III have been recently isolated from individuals from some West African countries. One of these viruses, HTLV-IVP, was reportedly isolated from lymphocytes of a healthy female prostitute. Another isolate, LAV-2FG, was obtained from an AIDS patient and third, SBL-6669, from an individual with lymphadenopathy. Current epidemiological studies indicate that some of these virus isolates cause immune deficiency whereas others may not or may be less efficient at inducing immune deficiency. Similarly, STLV-III apparently does not cause immune deficiency in its natural host, African green monkey. A novel feature of HIV is the possession of a gene termed tat, which is implicated in its pathobiology. We report here that, like HIV, HTLV-IVP, LAV-2FG (HIV-2) and SBL-6669, as well as STLV-IIIAGM possess the putative tat gene, irrespective of their pathogenic potential in vivo. Interestingly, HTLV-IVP/LAV-2FG long terminal repeat (LTR) is equally well transactivated by the HTLV-IVP/LAV-2FG and HTLV-IIIB tat function, HTLV-IIIB LTR responds better to its own tat function.

Acquired Immunodeficiency Syndrome↗