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PubMed1996

A critical role for the TAR element in promoting efficient human immunodeficiency virus type 1 reverse transcription.

The regulation of human immunodeficiency virus type 1 (HIV-1) gene expression is dependent on the transactivator protein Tat and an RNA element extending from the transcription initiation site to +57 known as TAR. TAR forms a stable RNA secondary structure which is critical for high levels of HIV-1 gene expression and efficient viral replication. Using a genetic approach, we isolated HIV-1 mutants in TAR that were competent for high levels of gene expression but yet were markedly defective for viral replication. Single-cycle infections with these viruses demonstrated that they were defective in the initiation of reverse transcription. Additional mutational analysis revealed a variety of other HIV-1 TAR mutants with the same defective phenotype. Thus, in addition to the well-characterized role of the primer binding site, other RNA elements within the HIV-1 genome are also critical in the regulation of reverse transcription. These studies demonstrate that HIV-1 TAR RNA is a key regulator of the reverse transcription and illustrate how a unique RNA structure can modulate diverse regulatory processes in the HIV-1 life cycle crucial for efficient viral replication.

Base Sequence↗
PubMed2000

Interactions between equine cyclin T1, Tat, and TAR are disrupted by a leucine-to-valine substitution found in human cyclin T1.

Transcriptional transactivators (Tat) from human immunodeficiency and equine infectious anemia viruses (HIV and EIAV) interact with their transactivation response elements (TAR) to increase the rates of viral transcription. Whereas the human cyclin T1 is required for the binding of Tat to TAR from HIV, it is unknown how Tat from EIAV interacts with its TAR. Furthermore, Tat from EIAV functions in equine and canine cells but not in human cells. In this study, we present sequences of cyclins T1 from horse and dog and demonstrate that their N-terminal 300 residues rescue the transactivation of Tat from EIAV in human cells. Although human and equine cyclins T1 bind to this Tat, only the equine cyclin T1 supports the binding of Tat to TAR from EIAV. Finally, a reciprocal exchange of the valine for the leucine at position 29 in human and equine cyclins T1, respectively, renders the human cyclin T1 active and the equine cyclin T1 inactive for Tat transactivation from EIAV. Thus, the collaboration between a specific cyclin T1 and Tat for their high-affinity interaction with TAR is a common theme of lentiviral transactivation.

Amino Acid Sequence↗
PubMed1993

Relatedness of an RNA-binding motif in human immunodeficiency virus type 1 TAR RNA-binding protein TRBP to human P1/dsI kinase and Drosophila staufen.

TRBP is a human cellular protein that binds the human immunodeficiency virus type 1 TAR RNA. Here, we show that the intact presence of amino acids 247 to 267 in TRBP correlates with its ability to bind RNA. This region contains a lysine- and arginine-rich motif, KKLAKRNAAAKMLLRVHTVPLDAR. A 24-amino-acid synthetic peptide (TR1) of this sequence bound TAR RNA with affinities similar to that of the entire TRBP, thus suggesting that this short motif contains a sufficient RNA-binding activity. Using RNA probe-shift analysis, we determined that TR1 does not bind all double-stranded RNAs but prefers TAR and other double-stranded RNAs with G+C-rich characteristics. Immunoprecipitation of TRBP from human immunodeficiency virus type 1-infected T lymphocytes recovered TAR RNA. This is consistent with a TRBP-TAR ribonucleoprotein during viral infection. Computer alignment revealed that TR1 is highly homologous to the RNA-binding domain of human P1/dsI protein kinase and two regions within Drosophila Staufen. We suggest that these proteins are related by virtue of sharing a common RNA-binding moiety.

Amino Acid Sequence↗
PubMed2004

Lead, arsenic, and polycyclic aromatic hydrocarbons in soil and house dust in the communities surrounding the Sydney, Nova Scotia, tar ponds.

This study evaluated lead, arsenic, and polycyclic aromatic hydrocarbon (PAH) contamination in the residential communities adjacent to the Sydney, Nova Scotia, tar ponds, the area considered Canada's worst contaminated site. The tar pond remediation policy has been limited to the site and some residential properties. We compared background concentrations in 91 soil samples taken 5-20 km from the coke oven site with those in soil samples from the three communities surrounding the tar ponds: Whitney Pier, Ashby, and North End. These surrounding communities were statistically different from background regarding arsenic, lead, and PAHs. Twenty percent of the background soil samples and 95% of the tar pond soil samples were above the Canadian health-risk-based soil guidelines for arsenic (12 ppm), and 5% of the background samples and 80% of the tar pond soil samples were above the Canadian guidelines for lead (140 ppm). Regarding dust lead and arsenic loading, the results provide no evidence that Whitney Pier is significantly different than Ashby and North End. Children in these communities are predicted to have a 1-15% chance of blood lead > 10 microg/dL. The results suggest that lead and arsenic found in the homes originate outside. The lead content of paint in the homes was not evaluated, but consideration of painted wood at the doorway did not confound the results of the study. The results indicate that the residential environment has been adversely affected by PAHs, lead, and arsenic and should be considered for remediation.

Air Pollution, Indoor↗
PubMed2003

HIV-1 TAR as anchoring site for optimized catalytic RNAs.

Ribozymes have a great potential for developing specific gene silencing molecules. One of the main limitations to ensure the efficient application of ribozymes is to achieve effective binding to the target. Stem-loop domains support efficient formation of the kissing complex between natural antisense molecules and their target sequence. We have characterized catalytic antisense RNA hybrid molecules composed of a hammerhead ribozyme and a stem-loop antisense domain. A series of artificial RNA substrates containing the TAR-RNA stem-loop and a target for the hammerhead ribozyme were constructed and challenged with a catalytic antisense RNA carrying the TAR complementary stem-loop. The catalytic antisense RNA cleaves each of these substrates significantly more efficiently than the parental hammerhead ribozyme. Deletion of the TAR domain in the substrate abolishes the positive effect. These results suggest that the enhancement is due to the interaction of both complementary stem-loop motifs. A similar improvement was corroborated when targeting the LTR region of HIV-1 with either hammerhead- and hairpin-based catalytic antisense RNAs. Our results indicate that the TAR domain can be used as an anchoring site to facilitate the access of ribozymes to their specific target sequences within TAR-containing RNAs. Finally, we propose the addition of stable stem-loop motifs to the ribozyme domain as a rational way for constructing catalytic antisense RNAs.

Base Sequence↗
PubMed2002

Driving in vitro selection of anti-HIV-1 TAR aptamers by magnesium concentration and temperature.

In vitro selection with either DNA or RNA libraries was performed against the TAR RNA element of HIV-1. The role of the selection conditions on the outcome of the selection was evaluated by varying the magnesium concentration and the temperature. The selection stringency was demonstrated to determine i) the affinity of the best identified aptamers for the TAR target, and ii) the type of interaction between the two partners. Selections performed with a DNA library under low (4 degrees C, 10 mM magnesium) and high stringency (23 degrees C, 3 mM magnesium) led to the emergence of "kissing aptamers"; but even if the motif interacting directly with the TAR loop were identical in the two kinds of aptamers, the consensus was extended from eight to thirteen nucleotides when the Mg(2+) concentration was decreased from 10 to 3 mM. Similar kissing aptamers were selected at 23 degrees C and 37 degrees C starting with two different RNA libraries under identical ionic conditions. In addition, selection performed at 37 degrees C yielded a significant proportion of antisense sequences. Only antisense RNAs complementary to the TAR loop competitively inhibited the association of a Tat peptide with TAR.

Base Sequence↗
PubMed1996

Toxicity of weathered coal tar for shortnose sturgeon (Acipenser brevirostrum) embryos and larvae.

Weathered coal tar collected from the Connecticut River near Holyoke, Massachusetts, was toxic to shortnose sturgeon embryos and larvae in whole sediment flow-through and elutriate static-renewal laboratory exposures. Sterile laboratory sand and clean Connecticut River sand, collected upstream from the coal tar deposits, produced no significant difference in toxicity to sturgeon embryos-larvae, while coal tar-contaminated sediment produced over 95% embryo-larval mortality. Hydrocarbon transfer and subsequent toxicity appeared to be via direct contact of the embryos with contaminated sediment, rather than via exposure to soluble hydrocarbons. This conclusion was supported by exposure of embryos and larvae to elutriates (e.g., water soluble extract) of coal-tar sediments, that resulted in embryo and larval mortality at low molecular weight PAH concentrations-0.47 mg/L, higher than would occur naturally. No decrease in petroleum hydrocarbon concentration was observed in sediments exposed to flowing water for 14 d, supporting the contention that soluble hydrocarbons were not responsible for the observed toxicity in whole sediment exposures under the conditions employed in this study.

Animals↗
PubMed1989

Long-term effects of switching to cigarettes with lower tar and nicotine yields.

On switching to cigarettes with lower tar and nicotine yields, most individuals smoke more intensively, but it is not clear if this effect persists over a long period. Smoking behaviour was monitored in 10 male and 18 female volunteers at five monthly visits, smoking commercially available cigarettes (tar yield greater than 10 mg), then for six more visits at 6-week intervals after switching (mean reduction of 5.9 mg tar and 0.45 mg nicotine). Puffing behaviour was monitored with a flow sensing holder, and measurements were made before and after smoking of plasma cotinine, carboxyhaemglobin and alveolar carbon monoxide. After switching, cotinine levels only fell 40% of that predicted from the fall in nicotine yields, and there were no systematic trends for the rest of the study. Puff volumes rose (reflecting perhaps the reduced draw resistance of the lower yield cigarettes), and remained higher thereafter. The number of puffs per cigarette appeared to rise on switching, but then decreased again. In conclusion, most effects of switching to lower yield cigarettes appeared to persist for at least 36 weeks, suggesting that the strategy of reducing exposure to cigarette smoke by lowering tar and nicotine yields may be of limited value.

Adolescent↗
PubMed1997

[Longitudinal study of the excretion of 1-hydroxypyrene in urine after external treatment with coal tar].

In order to study the dermal uptake, time course, and urinary excretion of polycyclic aromatic hydrocarbons, the concentration of 1-hydroxypyrene in urine was determined by means of high performance liquid chromatography with fluorescence detection before, during, and after the topical treatment with coal tar in 19 patients suffering from prurigo simplex subacuta, microbial eczema, atopic dermatitis, eczematization after scabies, exanthematous lichen ruber, pityriasis lichenoides and cutaneous sarcoidosis. Beginning with a value of 6.04 +/- 2.06 micrograms 1-hydroxypyrene/g creatinine before treatment, the urinary excretion significantly increased during the therapy with coal tar (p < 0.0001 at 3rd, 5th, and 6th day of therapy). A maximum was reached at day 8 of topical treatment with a value of 584.35 +/- 191.96 micrograms 1-hydroxypyrene/g creatinine (p < 0.002). Already during treatment at day 10 there was a beginning decrease of 1-hydroxypyrene to 361.63 +/- 170.13 micrograms/g creatinine. After the end of treatment, the excretion further decreased reaching a value of 5.31 +/- 2.85 micrograms 1-hydroxypyrene/g creatinine at the 10th day after therapy. Skin carcinomas due to therapeutical use of coal tar occur extremely rarely and only after vergoten, non-controlled use. We suggest that the duration of exposure is the most important factor for the carcinogenic effect of coal tar.

Administration, Cutaneous↗
PubMed1986

Estimates of maximum or average cigarette tar, nicotine, and carbon monoxide yields can be obtained from yields under standard conditions.

Average yields of tar, nicotine, and carbon monoxide per liter of smoke and per cigarette were determined for 10 brands of cigarettes smoked under 27 different conditions (one standard and 26 nonstandard). Per cigarette yields were highly variable across smoking conditions due to differences in the total volume of smoke taken for analysis. The results of a simple linear regression analysis indicated that up to 95% of the variation in tar yield per cigarette could be explained by variations in the total volume of smoke produced per cigarette. Per liter yields for tar, nicotine, and carbon monoxide were almost constant over the conditions investigated. Since most smokers inhale less than this amount, yields per liter provide a rough estimate of the maximum amount to which a smoker might be exposed. Yields per liter, taken over all 26 conditions, are highly correlated with per cigarette yields under standard conditions. Consequently, values on one scale can be converted to the other, at least for the 10 brands investigated. The average conversion factor for tar, nicotine, and carbon monoxide is 2.5 when proceeding from milligrams per king-size cigarette under standard conditions to milligrams per liter. This relationship is true for both vented and nonvented cigarettes when ventilation holes are not blocked.

Carbon Monoxide↗
PubMed1996

A study of the synergistic interaction of asbestos fibers with cigarette tar extracts for the generation of hydroxyl radicals in aqueous buffer solution.

Several models attempt to explain the synergistic increase in lung cancer among workers exposed to asbestos fibers, who were smokers at the same time. It is known that reactive oxygen species (ROS) are important mediators in asbestos-induced diseases, especially cancer. We studied quantitatively the formation of ROS (by spin trapping with DMPO) in aqueous buffer suspensions containing crocidolite (UICC), chrysotile (UICC and commercial, long fibers) alone, and in combination with aqueous cigarette tar extracts. It was observed that asbestos and cigarette tar act in a cooperative or synergistic way in the generation of hydroxyl radical spin adducts. Grinding of asbestos fibers and addition of EDTA (iron chelator) enhanced the intensity of the ESR signal. This enhancement progressed with time, probably due to the reaction of the extracted iron with the slow released hydrogen peroxide from tar extracts. It was observed a fivefold increase in the ESR signal (for crocidolite and aqueous tar extracts) in the formation of hydroxyl radicals via an iron-catalyzed Fenton reaction. These experimental results are suggest to be strong evidence to the fact that lung cancer has been found in asbestos workers exposed to high concentrations of fibers in the working environment who were smokers, and only rarely in nonsmokers.

Asbestos↗
PubMed2005

Polycyclic aromatic hydrocarbons, carbon monoxide, "tar", and nicotine in the mainstream smoke aerosol of the narghile water pipe.

A smoking machine protocol and yields for "tar", nicotine, PAH, and CO are presented for the standard 171-puff steady periodic smoking regimen proposed by Shihadeh et al. [Shihadeh, A., Azar, S., Antonios, C., Haddad, A., 2004b. Towards a topographical model of narghile water-pipe cafe smoking: A pilot study in a high socioeconomic status neighborhood of Beirut, Lebanon. Pharmacology Biochemistry and Behavior 79(1), 75]. Results show that smokers are likely exposed to more "tar" and nicotine than previously thought, and that pyronsynthesized PAH are present in the "tar" despite the low temperatures characteristic of the tobacco in narghile smoking. With a smoking regimen consisting of 171 puffs each of 0.53l volume and 2.6s duration with a 17 s interpuff interval, the following results were obtained for a single smoking session of 10 g of mo'assel tobacco paste with 1.5 quick-lighting charcoal disks applied to the narghile head: 2.94 mg nicotine, 802 mg "tar", 145 mg CO, and relative to the smoke of a single cigarette, greater quantities of chrysene, phenanthrene, and fluoranthene. Anthracene and pyrene were also identified but not quantified. The results indicate that narghile smoke likely contains an abundance of several of the chemicals thought to be causal factors in the elevated incidence of cancer, cardiovascular disease and addiction in cigarette smokers.

Aerosols↗
PubMed2002

Time scales of organic contaminant dissolution from complex source zones: coal tar pools vs. blobs.

Groundwater contamination due to complex organic mixtures such as coal tar, creosote and fuels is a widespread problem in industrialized regions. Although most compounds in these mixtures are biodegradable, the contaminant sources are very persistent for many decades after the contamination occurred (e.g., more than 100 years ago at gasworks sites). This limited bioavailability is due to slow dissolution processes. This study presents results from a large scale tank experiment (8 m long) on the long-term (354 days) dissolution kinetics of BTEX and PAHs from a 2.5 m long coal tar pool and 0.5 m long (smear) zone containing coal tar blobs distributed in a coarse sand. The results inidicate (1) that Raoult's law holds for estimation of the saturation aqueous concentrations of the coal tar constituents, (2) that for the dissolution of smear zones longer than approximately 0.1 m and with more than 3-5% residual saturation, the local equilibrium assumption is valid and (3) that although very small (< 0.1 mm), the transverse vertical dispersivity dominates the pool dissolution processes. Typical time scales for removal of the pollutants from the blob zone and the pool are in the order of a few weeks to more than 10,000 years, respectively.

Coal Tar↗
PubMed1987

Combined tar-anthralin versus anthralin treatment lowers irritancy with unchanged antipsoriatic efficacy. Modifications of short-contact therapy and Ingram therapy.

In 44 patients with chronic plaque psoriasis anthralin therapy was used as high-strength short-contact therapy in a bilateral comparison of anthralin versus 5% crude coal tar-anthralin combination. These two trials were undertaken with and without ultraviolet (UV) irradiation immediately after anthralin therapy. The combined tar-anthralin therapy was significantly less of an irritant during the first 3 weeks of treatment than anthralin alone, and it did not decrease the antipsoriatic efficacy. The use of UV irradiation, either with anthralin or tar-anthralin combination, did not produce an additional therapeutic effect. These findings lead us to prefer combined tar-anthralin therapy because of its lower irritancy in comparison with anthralin alone and they show the ineffectiveness of additional UV irradiation under the conditions of this study.

Administration, Topical↗
PubMed1997

Sunflower oil in the treatment of hot tar burns.

Hot tar burns compose a unique class of thermal injury, because removal of this highly sticky compound may be very difficult without inflicting additional tissue damage. Early removal of tar facilitates assessment of the burn and improves patient comfort. Although the use of many substances for the painless removal of tar has been described, we used sunflower oil effectively in the treatment of four tar burn patients. This first report describes the practical and successful use of sunflower oil which was easily obtained from the hospital kitchen.

Accidents, Occupational↗
PubMed1997

Coal tar therapy in palmoplantar psoriasis: old wine in an old bottle?

BACKGROUND: Palmoplantar psoriasis (PPP) is a disabling condition which is usually resistant to most of the available therapeutic modalities. Coal tar is an accepted therapy for psoriasis which has not been well studied for PPP. METHODS: Thirty patients with a plaque type of PPP were allocated into two groups: Group A (19 patients) were treated with 6% crude coal tar (CCT) ointment and Group B (11 patients) were treated with white petrolatum and salicylic acid. In both groups, ointment was applied and left on overnight. Wearing of gloves and socks during the night and application of emollients in the day was routinely advised. The lesions were assessed for erythema, scaling, and induration (ESI) every 2 weeks for a total of 8 weeks. Patients with greater than 50% improvement were considered to have good improvement. Side-effects, if any, were also monitored. RESULTS: In Group A, 76.5% of patients (13/17) showed good improvement, whereas only 45.5% of patients (5/11) in Group B showed the same magnitude of improvement (P < 0.05). No side-effects were reported by any patient in either of the groups. CONCLUSIONS: Crude coal tar is a safe, effective, and inexpensive modality for the treatment of PPP. We recommend coal tar under occlusion, along with the liberal use of emollients, as the first line of therapy for all cases of PPP.

Administration, Topical↗
PubMed1976

Particle size distribution and chemical composition of coal-tar fumes.

The study was intended to characterize the chemical and physical nature of coal-tar fumes emitted from spreading applications of coal tar. Two separate experiments were performed. The first resulted in the determination of a coal-tar fume particle size distribution. The second experiment resulted in the identification of the primary compounds found in collected tar fumes and a determination of their relative concentration.

Air Pollutants↗
PubMed1987

Microcomputer-aided measurement of puff parameters during smoking of low- and medium-tar cigarettes.

A portable microcomputer-assisted flow transducer was developed for analysing puff parameters during smoking of low- and medium-tar cigarettes. Smoke flow was determined by measuring pressure difference between two sites within an orifice flowmeter. According to the Bernoulli equation, the pressure difference is proportional to the square of flow. For calibration of the method, various sizes of air volumes were puffed through the flowmeter by a piston syringe. The calibration curve, which consisted of the flow as a function of the square root of pressure difference, was linear (r = 0.98). The automatic microcomputer analysis consists of the following variables: mean flow and mean volume of inhaled smoke gas, puff duration, time interval between two puffs, number of puffs and total volume inhaled. Eight volunteers smoked 10 low- and 10 medium-tar cigarettes during the cross-over experiments. The investigation indicated that the total inhalation volume of smokers in the case of low-tar cigarettes is twice as large as in the case of medium-tar cigarettes.

Humans↗