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Biomedical subjects

P Tran

Publications and source records attributed to P Tran.

46 records · Page 3Linked to original sources

Heterodimeric receptor complexes determine 3,5,3'-triiodothyronine and retinoid signaling specificities.

Thyroid hormone receptors (TRs) and retinoic acid receptors (RARs) have been shown to interact with nuclear auxiliary proteins resulting in heteromeric complexes that bind strongly to their responsive elements. Recently the retinoid X receptors (RXRs) have been identified as one class of these nuclear proteins. RXRs strongly increase binding of TRs and RARs to a synthetic thyroid hormone (and retinoic acid) responsive element. Here results show that the binding of the heteromeric complexes to various natural response elements is highly specific and dictated by the partner of RXR in the complex. TR alpha and TR beta formed complexes with RXR alpha that strongly and selectively bound to natural thyroid hormone responsive elements, i.e. those from the rat alpha-myosin heavy chain gene and the rat malic enzyme gene. RXR alpha complexes with RAR alpha, RAR beta, and RAR gamma bound selectively to retinoic acid responsive elements from the human RAR beta 2 gene (hRAR beta 2), the gene of the rat cellular retinol binding protein I and the human apolipoprotein A1 gene. Under the conditions used here RXR alpha by itself did not bind to any of the responsive elements tested. Although TRs and RARs formed heterodimers with RXR in solution, these complexes were strongly stabilized by specific, high affinity response elements, but not by low affinity response elements. Transfection analyses showed strong synergism between receptors that formed effective heterodimers in transcriptional activation on several but not all response elements. Overall, these data demonstrate that RARs and TRs are unlikely to function as monomers or homodimers on the response elements investigated here and require RXRs or comparable proteins for effective response element activation.

Animals↗

Hypersensitivity pneumonitis associated with a portable home humidifier.

Hypersensitivity pneumonitis (HP) is an immunologically mediated inflammatory disorder of the pulmonary parenchyma which has been traditionally associated with the inhalation of organic dusts (farmer's lung, pigeon breeder's disease) and a variety of simple chemical compounds. More recently, the disease has been reported in association with the inhalation of aerosolized droplets in home and office settings. In Connecticut, the home and office, rather than the farm or factory, are the most common, although frequently unrecognized, environmental settings in which HP develops. We report here a case of a young, healthy woman who developed severe HP associated with the use of a portable home ultrasonic humidifier. This clinical entity should be suspected in the patient with a "recurrent viral illness" or "recurrent pneumonia." A review of the clinical and laboratory findings of humidifier-induced HP are discussed in relation to its pathogenesis, diagnosis, and treatment.

Adult↗

How electrolyte shielding influences the electrical potential in transmembrane ion channels.

The electrical potential due to fixed charge distributions is strongly altered in the vicinity of a membrane and notably dependent on aqueous electrolyte concentration. We present an efficient way to solve the nonlinear Poisson-Boltzmann equation applicable to general cylindrically symmetric dielectric geometries. It generalizes Gouy-Chapman theory to systems containing transmembrane channels. The method is applied to three channel systems: gramicidin, gap junction, and porin. We find that for a long, narrow channel such as gramicidin concentration variation has little influence on the electrical image barrier to ion permeation. However, electrolyte shielding reduces the image induced contribution to the energy required for multiple occupancy. In addition, the presence of electrolyte significantly affects the voltage profile due to an applied potential, substantially compressing the electric field to the immediate vicinity of the pore itself. In the large diameter channels, where bulk electrolyte may be assumed to enter the pore, the electrolyte greatly reduces the image barrier to ion permeation. At physiological ionic strengths this barrier is negligible and the channel may be readily multiply occupied. At all ionic strengths considered (l greater than 0.005 M) the image barrier saturates rapidly and is essentially constant more than one channel radius from the entrance to the pore. At lower ionic strengths (l less than 0.016 M) there are noticeable (greater than 20 mV) energy penalties associated with multiple occupancy.

Electrolytes↗