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N Horton

Publications and source records attributed to N Horton.

6 recordsLinked to original sources
PubMed1997

The use of hibernation induction triggers for cardiac transplant preservation.

Cardiac transplant is hindered by donor shortage and preservation time. Extended extracorporeal preservation could increase the number and distribution of hearts for transplantation. Interestingly, mammalian hibernation biology closely parallels the altered cardiac cellular physiology noted with hypothermic organ storage. The present study undertook to test whether treatment with hibernation induction triggers could improve myocardial functional recovery following prolonged ischemic storage in a nonhibernating mammalian model. To study this hypothesis, isolated rabbit hearts had baseline functional and metabolic parameters recorded and then received either hypothermic storage only or standard cardioplegia, or cardioplegia containing 1 mg/kg D-Ala2-Leu5-enkaphalin (DADLE), which mimics natural hibernation, or preperfusion with DADLE, administered for 15 min at 2 mmol, 25 min prior to cardioplegic ischemia. Hearts were then subjected to 18 hr of global ischemic storage at 4 degrees C. Isovolumic developed pressure, coronary flows, and myocardial oxygen consumption were significantly improved with DADLE pretreatment vs. all groups after storage and reflow. Furthermore, DADLE hearts demonstrated better histological ultrastructure preservation following prolonged storage ischemia. This study demonstrates that hibernation protection with DADLE is beneficial for prolonged cardiac storage. The use of hibernation induction triggers is promising for organ preservation and deserve further mechanistic study.

Analysis of Variance↗
PubMed1997

Escherichia coli lac repressor-lac operator interaction and the influence of allosteric effectors.

The wild type E. coli lac operator is embedded in a 35 base-pair DNA sequence containing extensive 2-fold symmetry, suggesting a symmetric repressor operator complex. However, deviations from strict 2-fold symmetry occur at the central base-pair and at three additional base-pairs. Using an operator fragment binding analysis we have determined: (a) a relative contribution each pair provides to the lac repressor-lac operator DNA complex, (b) the operator DNA length necessary for maximum binding to lac repressor; and (c) the contribution of the several non-symmetric base in the wild-type operator to the binding affinity. Since lac repressor-lac operator DNA interaction is reduced upon binding of the gratuitous inducer, isopropyl-beta-D-galactoside (IPTG), the same DNA fragment binding analysis was performed with the low affinity form of lac repressor. In the presence of inducer, the affinity for the left half site of the wild-type lac operator is reduced without significant reduction on the right half of the operator. Conversely, the anti-inducer orthonitrophenylfucoside (ONPF) which stabilizes the lac repressor-lac operator complex increases the binding affinity, particularly to the right half of the operator.

Allosteric Regulation↗
PubMed1992

Calculation of the free energy of association for protein complexes.

We have developed a method for calculating the association energy of quaternary complexes starting from their atomic coordinates. The association energy is described as the sum of two solvation terms and an energy term to account for the loss of translational and rotational entropy. The calculated solvation energy, using atomic solvation parameters and the solvent accessible surface areas, has a correlation of 96% with experimentally determined values. We have applied this methodology to examine intermediates in viral assembly and to assess the contribution isomerization makes to the association energy of molecular complexes. In addition, we have shown that the calculated association can be used as a predictive tool for analyzing modeled molecular complexes.

Capsid↗
PubMed1990

Androsterone glucuronide is a marker of adrenal hyperandrogenism in hirsute women.

Androsterone glucuronide (Andros-G), a dihydrotestosterone metabolite, is present in serum at concentrations at least tenfold greater than those of androstanediol glucuronide. To investigate the significance of serum androsterone glucuronide, we developed a direct radioimmunoassay for this compound and measured its levels in normal women, women with mild or severe idiopathic hirsutism (IH), hirsute women with polycystic ovarian syndrome (PCO), and non-hirsute obese women. To determine the source of Andros-G precursors, serum levels were measured before and after selective ovarian suppression with leuprolide, combined ovarian and adrenal suppression with leuprolide and dexamethasone, and adrenal stimulation with ACTH. Androsterone glucuronide levels (nmol/l; mean +/- SD) were significantly higher (P less than 0.025) in women with mild idiopathic hirsutism (IH) (185 +/- 91), severe IH (173 +/- 97), and hirsute women with polycystic ovarian syndrome (PCO) (178 +/- 102) than in normal women (110 +/- 26). Levels in non-hirsute obese women (64 +/- 19) were lower than in normal women (P less than 0.01). Baseline levels (mean +/- SEM) in hirsute women given 20 micrograms/kg/day leuprolide for 5-9 months (171 +/- 15) were not significantly changed after leuprolide alone (153 +/- 18), and were decreased after adding dexamethasone (19 +/- 6; P less than 0.001). Andros-G levels did not increase significantly in normal women 60 min after i.v. ACTH (112 +/- 14 to 126 +/- 19), but rose in IH (170 +/- 24 to 216 +/- 26; P less than 0.001) and in PCO (179 +/- 26 to 238 +/- 31; P = 0.002). We conclude that Andros-G in women arises primarily from adrenal gland precursors and is elevated in hirsute women as a group. Its levels do not correlate with the severity of hirsutism, or the presence or absence of PCO, but reflect an increased production of adrenal androgens in both IH and PCO.

Adrenal Glands↗
PubMedDate not supplied

Syntaxin 1A up-regulates GABA transporter expression by subcellular redistribution.

Neurotransmitter transporters are regulated through a variety of signal transduction mechanisms which appear to operate in order to maintain appropriate levels of transmitter in the synaptic cleft. One such mechanism is the trafficking of the transporter in association with synaptic vesicle release machinery. This report examines the specifics of trafficking regulation of the rat brain GABA transporter GAT1 by syntaxin 1A, a plasma membrane component of the SNARE complex which is involved in vesicle membrane fusion. In hippocampal neurons, botulinum neurotoxin 1C, which specifically cleaves syntaxin 1A, down-regulates plasma membrane GAT1 levels as assessed by surface biotinylation, suggesting that syntaxin 1A is a positive regulator of GAT1 surface expression. The up-regulation correlates with a decrease in intracellular GAT1 levels and is complete within several minutes. These data suggest that syntaxin 1A mediates the redistribution of GAT1 on a time scale important for the rapid regulation of extracellular GABA levels. Expression of different syntaxin 1A constructs in Xenopus oocytes suggests that several portions of the syntaxin 1A molecule are required for the trafficking of GAT1. These data suggest that the trafficking of GAT1 will be subject to regulatory control by the many molecules known to interact with various domains of syntaxin 1A.

Animals↗