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Biomedical subjects

S K Arya

Publications and source records attributed to S K Arya.

79 records · Page 5Linked to original sources
PubMedDate not supplied

Relation of HTLV-4 to simian and human immunodeficiency-associated viruses.

Human immunodeficiency virus type 1 (HIV-1) is the aetiologic agent of AIDS (acquired immune deficiency syndrome) in most countries and probably originated in Central Africa like the AIDS epidemic itself. Evidence for a second major group of human immunodeficiency-associated retroviruses came from a report that West African human populations like wild-caught African green monkeys had serum antibodies that reacted more strongly with a simian immunodeficiency virus (STLV-3Mac) (ref.6) than with HIV-1. Novel T-lymphotropic retroviruses were reported to have been isolated from healthy Senegalese West Africans (HTLV-4) (ref. 4) and from African green monkeys (STLV-3AGM) (ref. 7), and a different retrovirus (HIV-2) was identified in other West African AIDS patients. Genomic analysis of HIV-2 clearly distinguished it from STLV-3 (ref. 9), but restriction enzyme site-mapping of three different HTLV-4 isolates and six different STLV-3AGM isolates showed them to be essentially indistinguishable. In this report we clone, restriction map, and partially sequence three isolates of HTLV-4 (PK82, PK289, PK190) (ref. 4). We find that these viruses differ in nucleotide sequence from each other and from three isolates of STLV-3AGM (K78, K6W, K1) (ref. 7) by 1% or less. We also report the isolation of a T-lymphotropic retrovirus from the peripheral blood of a healthy Senegalese woman which hybridizes preferentially to HIV-2 specific DNA probes. We conclude that HTLV-4 (ref. 4) and STLV-3AGM (ref. 7) are not independent virus isolates and that HIV-2 is present in Senegal as it is in other West African countries.

Base Sequence↗
PubMedDate not supplied

In vitro phenotype of SDF1 gene mutant that delays the onset of human immunodeficiency virus disease in vivo.

OBJECTIVE: Inheritance of a mutant allele of the SDF1 gene delays the onset of human immunodeficiency virus type 1 (HIV-1) disease. Because the mutation lies in the 3' untranslated region of the gene, it was suggested that this mutation may upregulate transcription of the gene, resulting in more abundant SDF1, which in turn inhibits T-tropic HIV-1 and delays disease onset. This implies that this segment of SDF1 gene contains a negative regulatory element. We directly tested this hypothesis in vitro. STUDY DESIGN/METHODS: We cloned the wild-type and the mutant SDF1 gene in an HIV-2 gene transfer vector as well as in a baculovirus expression vector. We expressed the cloned genes in human and insect cells in culture and analyzed the abundance of SDF1 RNA by hybridization and protein using antiviral assays. RESULTS: The abundance of SDF1 RNA synthesized by the mutant clone with the mutation in the 3' untranslated region was no different from that synthesized by the wild-type clone in cultured cells. This was the case for both the HIV-2 long terminal repeat (LTR)-directed expression in human cells and baculovirus promoter-directed expression in insect cells. Both clones apparently synthesized SDF1 with equivalent biologic activity. Similar results were obtained for a mutant with the deletion of a GC-rich segment in the 5' untranslated region. CONCLUSIONS: Mutation of the 3' untranslated exon did not affect SDF1 RNA synthesis in vitro. It also did not appear to affect translation of SDF1 RNA. A similar mutational analysis of the 5' noncoding exon suggested that this region also did not regulate SDF1 expression.

3' Untranslated Regions↗
PubMedDate not supplied

Antiviral chemokines: intracellular life of recombinant C-C chemokine RANTES.

OBJECTIVE: Select C-C and C-X-C chemokines can suppress HIV infection. This is because their receptors are the gateways for HIV-1 entry, determinants of viral tropism and sensitivity. C-C chemokines are most effective against macrophage-tropic viruses, and C-X-C chemokines are most effective against T-tropic viruses. The epitopes on the chemokine molecule responsible for virus inhibition and for chemokines' specificities are not known. The objective of this study was to map the functional domains of prototypic antiviral chemokine, namely, RANTES (regulated-on-activation normal T-expressed and secreted). STUDY DESIGN: Optimal folding of the chemokine molecule is thought to be important for its biologic activity. Anticipating that it will provide a native milieu for folding, we expressed recombinant RANTES molecules in an HIV-2-derived lentivirus mammalian expression system. We focused on the structural landmarks of RANTES to determine their role in its life and function. RESULTS: We found that the flexible amino-terminal region of RANTES was not important for its structural integrity or antiviral activity, either positively or negatively. It was also not important for binding to the CCR5 receptor. Modification of all other domains was detrimental, implying a functional role. However, a more careful analysis revealed that these domains were crucial for controlling stability, transport, and secretion of the molecule. Although all recombinant clones contained signal sequence and were transcriptionally active, they presented three different phenotypes: normal synthesis and secretion, normal synthesis but blocked secretion, and presumed normal synthesis but rapid degradation. Structural considerations and preliminary experiments showing a lack of effect of proteasome inhibitors suggested that the signal recognition particle pathway of translocation and proteasomal pathway of destruction may not be the major determinant of the life of the chemokine. CONCLUSIONS: The amino-terminal domain of RANTES was not essential for its antiviral activity or for its binding to the CCR5 receptor. Although the 1-domain of the core and carboxy-terminal domain may contribute to the antiviral activity of RANTES, they were more important for its intracellular life.

Amino Acid Sequence↗
PubMedDate not supplied

Cyclodialysis cleft diagnosed by conventional ultrasonography.

This case report describes the diagnosis and management of a traumatic cyclodialysis cleft, in the absence of newer investigating modalities like ultrasonic biomicroscopy (UBM). This entity is frequently difficult to recognize clinically owing to the extreme hypotony and media haze that these patients usually present with, which makes gonioscopy particularly taxing. Adding to the diagnostic dilemma is the difficulty in delineating the lesion ultrasonically due to the extreme anterior location of the cleft. In these situations, high frequency ultrasound has been found to be extremely helpful, but the availability of such sophistication is difficult. Presented here is demonstration of the cleft with a microconvex ultrasound probe of 9 MHz frequency. The patient was successfully managed conservatively. This modality could prove to be a valuable adjunct to the diagnosis of such cases even in the situations of nonavailability of high frequency ultrasonography.

Adult↗
PubMedDate not supplied

The search for "virogene" in human prostatic tissues: prostatic DNA polymerases.

The "virogene-oncogene" hypothesis of Huebner and Todaro and the "provirus" hypothesis of Temin implicate RNA tumor viruses in the neoplastic transformation of mammalian cells. These hypotheses have been substantiated in several animal systems including primates and, presumably, in man. Because the detection in a tissue of one or two activities allegedly related to RNA tumor virus may not be conclusive evidence for viral presence, we have developed a scheme of coordinated morphologic, biologic, and biochemical investigations of human prostatic tissues. We report here the more recent progress we have made in one of the segments of our scheme of investigations. Two, possibly three, DNA polymerase activities from human prostatic tissue have been isolated and partially purified by DEAE-cellulose and phosphocellulose chromatography. These activities have been partially characterized. Based on template preferences and non-inhibition by selective inhibitors of reverse transcriptase, neither of the major polymerase activities appears to be the reverse transcriptase-type activity.

Adenine↗
PubMedDate not supplied

RNA tumor virus-like activities in human prostate: possible novel pharmacologic approaches.

The cytoplasmic extracts of human prostatic tissues yield two classes of "particles" when centrifuged to equilibrium in a sucrose density gradient, one class banding at a density of 1.15-1.18 g/cm3 ("high density particles") and another at a density of 1.07-1.14 g/cm3 ("low density particles"). Both bands display endogenous DNA polymerase activity which is largely resistant to actinomycin D inhibition. The endogenous DNA products synthesized by high density particles give some indication of high molecular weight RNA:DNA complexes. The tissue extracts from normal, hyperplastic, and neoplastic prostate behave similarly in these assays. In addition, explant cultures of hyperplastic and neoplastic prostate either release, or can be induced to release, particles by treatment with bromodeoxyuridine. These particles band at a density of 1.15-1.18 g/cm3 in a sucrose density gradient and possess RNA and associated DNA polymerase activity which utilizes poly(A):oligo(dT). Our results suggest that human prostatic tissues may contain functions analogous in some ways to those of known RNA tumor viruses of other species.

Bromodeoxyuridine↗