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Biomedical subjects

J D Jordan

Publications and source records attributed to J D Jordan.

At least 19 recordsLinked to original sources
PubMed2000

Tyrosine-kinase-dependent recruitment of RGS12 to the N-type calcium channel.

Gamma-aminobutyric acid (GABA)B receptors couple to Go to inhibit N-type calcium channels in embryonic chick dorsal root ganglion neurons. The voltage-independent inhibition, mediated by means of a tyrosine-kinase pathway, is transient and lasts up to 100 seconds. Inhibition of endogenous RGS12, a member of the family of regulators of G-protein signalling, selectively alters the time course of voltage-independent inhibition. The RGS12 protein, in addition to the RGS domain, contains PDZ and PTB domains. Fusion proteins containing the PTB domain of RGS12 alter the rate of termination of the GABA(B) signal, whereas the PDZ or RGS domains of RGS 12 have no observable effects. Using primary dorsal root ganglion neurons in culture, here we show an endogenous agonist-induced tyrosine-kinase-dependent complex of RGS12 and the calcium channel. These results indicate that RGS12 is a multifunctional protein capable of direct interactions through its PTB domain with the tyrosine-phosphorylated calcium channel. Recruitment of RGS proteins to G-protein effectors may represent an additional mechanism for signal termination in G-protein-coupled pathways.

Animals↗
PubMed2000

Persistent postoperative pain after the Chrisman-Snook ankle reconstruction.

One complication of the Chrisman-Snook ankle reconstruction is persistent postoperative pain. The incidence of this complication ranges from 7% to 60%. We report 10 cases of surgical exploration for persistent pain after Chrisman-Snook reconstructions. In 6 of the 10 cases a surgically correctable cause was found for the pain. The identified pathologic lesions in these 6 patients could have been prevented by careful attention to detail in the index operation. Surgical exploration should be considered for any of the following findings: persistent point tenderness (especially at the graft tunnel sites), localized swelling, a painful mass, recurrent instability/laxity, a symptomatic neuroma, or painful inversion and dorsiflexion. To prevent the complication of persistent postoperative pain after the Chrisman-Snook ankle reconstruction, we recommend the following: 1) avoid forced eversion when tensioning the graft, excessive posterior placement of the calcaneal tunnel, casting in eversion, and the use of nonabsorbable suture; 2) resect the distal muscle belly of the peroneus brevis muscle distal to the superior peroneal retinaculum; 3) check for tears in the peroneus brevis; 4) respect the sural nerve; and 5) obtain a watertight closure of the joint capsule. Although the Chrisman-Snook ankle reconstruction is an excellent technique, numerous pitfalls in surgical technique must be avoided.

Adolescent↗
PubMed1999

Modulation of rap activity by direct interaction of Galpha(o) with Rap1 GTPase-activating protein.

We used the yeast two-hybrid system to identify proteins that interact directly with Galpha(o). Mutant-activated Galpha(o) was used as the bait to screen a cDNA library from chick dorsal root ganglion neurons. We found that Galpha(o) interacted with several proteins including Gz-GTPase-activating protein (Gz-GAP), a new RGS protein (RGS-17), a novel protein of unknown function (IP6), and Rap1GAP. This study focuses on Rap1GAP, which selectively interacts with Galpha(o) and Galpha(i) but not with Galpha(s) or Galpha(q). Rap1GAP interacts more avidly with the unactivated Galpha(o) as compared with the mutant (Q205L)-activated Galpha(o). When expressed in HEK-293 cells, unactivated Galpha(o) co-immunoprecipitates with the Rap1GAP. Expression of chick Rap1GAP in PC-12 cells inhibited activation of Rap1 by forskolin. When unactivated Galpha(o) was expressed, the amount of activated Rap1 was greatly increased. This effect was not observed with the Q205L-Galpha(o). Expression of unactivated Galpha(o) stimulated MAP-kinase (MAPK1/2) activity in a Rap1GAP-dependent manner. These results identify a novel function of Galpha(o), which in its resting state can sequester Rap1GAP thereby regulating Rap1 activity and consequently gating signal flow from Rap1 to MAPK1/2. Thus, activation of G(o) could modulate the Rap1 effects on a variety of cellular functions.

Amino Acid Substitution↗
PubMed1999

Regulators of G protein signaling proteins as determinants of the rate of desensitization of presynaptic calcium channels.

Norepinephrine inhibits omega-conotoxin GVIA-sensitive presynaptic Ca2+ channels in chick dorsal root ganglion neurons through two pathways, one mediated by Go and the other by Gi. These pathways desensitize at different rates. We have found that recombinant Galpha interacting protein (GAIP) and regulators of G protein signaling (RGS)4 selectively accelerate the rate of desensitization of Go- and Gi-mediated pathways, respectively. Blockade of endogenous RGS proteins using antibodies raised against Galpha interacting protein and RGS4 slows the rate of desensitization of these pathways in a selective manner. These results demonstrate that different RGS proteins may interact with Gi and Go selectively, giving rise to distinct time courses of transmitter-mediated effects.

Amino Acid Sequence↗
PubMed1998

Modes of interactions between signaling pathways.

The study of signaling pathways has begun to uncover the mechanism by which cells respond and adapt to extracellular stimuli. It has become increasingly clear that the signaling pathways interact with one another to form a complex network through which regulation occurs. Here, we focus on three mechanisms by which signaling pathways interact and the physiological consequences of these interactions. Coincident signaling in long-term depression of synaptic responses in the cerebellum, protein kinase A gating of Ras to mitogen-activated protein kinase signal flow in proliferative responses, and a modified gating mechanism by phosducin resulting in feedback regulation of signal flow from rhodopsin to the cGMP phosphodiesterase in retinal light adaptation are analyzed as examples of different types of interactions between signaling pathways. These interactions allow the cell to spatially and temporally integrate complex information and respond in an appropriate and defined manner.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1996

Accessibility of the fluorescent reporter group in native, silica-adsorbed, and covalently attached acrylodan-labeled serum albumins.

Fluorescence quenching techniques are used to investigate the accessibility of a model biorecognition element-reporter group system when in buffer, surface-adsorbed, and covalently attached to a silica surface. The site-selective fluorescent reporter group, 6-acryloyl(dimethylamino)naphthalene (acrylodan, Ac), is attached covalently (at cysteine-34) to bovine and human serum albumin (BSA and HSA, respectively) and serves as a surrogate recognition element-reporter group system. Molecular oxygen is used to quench the Ac fluorescence and the accessibility, in the form of bimolecular rate constants (kq), in each model system is quantified. Although one might expect these systems to exhibit similar behavior, differences in quenching characteristics are observed, such as wavelength dependency of the Stern-Volmer quenching constant (KSV) for the native proteins in buffer. BSA-Ac exhibits wavelength dependent KSV values as well as a blue-shifted emission spectrum on O2 addition. Physisorption of BSA-Ac onto a fused-silica optical fiber lowers the accessibility of Ac to O2, whereas covalent attachment of BSA-Ac to APTES/glutaraldehyde-modified silica enhances the accessibility of the Ac reporter group to O2.

2-Naphthylamine↗
PubMed1995

Dynamics of acrylodan-labeled bovine and human serum albumin entrapped in a sol-gel-derived biogel.

We investigate acrylodan-labeled bovine and human serum albumin (BSA-Ac and HSA-Ac) entrapped within a tetramethylorthosilane-derived biogel composite. The effects of biogel aging and drying were studied by following the acrylodan steady-state and time-resolved emission, the decay of anisotropy, and the dipolar relaxation kinetics as a function of ambient storage time. The results indicate that there is a substantial amount of nanosecond and subnanosecond dipolar relaxation within the local environment surrounding cysteine-34 in both proteins, even when they are fully encapsulated in a dry biogel. Time-resolved anisotropy experiments show that the acrylodan residue and the protein are able to undergo nanosecond motion within the biogel. The semiangle through which the acrylodan can process is the same for a freshly formed biogel and the native protein in buffer. However, once the biogel begins to dry, the semiangle increases (approximately 20 degrees and 10 degrees for BSA-Ac and HSA-Ac, respectively). This suggests that the "pocket" hosting the acrylodan reporter group opens as the biogel dries.

2-Naphthylamine↗
PubMed1988

Subaortic stenosis and sudden death.

An obese white boy, 16 years old, collapsed and suddenly died while walking with friends. Since early childhood he had been known to have mild subaortic stenosis. At age 6 he exhibited first-degree heart block during an electrocardiographic exercise test. Neither then nor thereafter was he known to have any unusual symptoms until his death. Postmortem examination revealed marked cardiac enlargement without asymmetry or much dilatation. There was mild subaortic stenosis, but the heart was otherwise grossly normal. Special studies of his cardiac conduction system demonstrated fibrotic obliteration of the His bundle and proximal portions of both bundle branches. The same region had a much thickened central fibrous body from which the subaortic stenosis ridge protruded. Small arteries in the vicinity of the atrioventricular node were markedly narrowed. Because those vessels provide some of the blood supply to the His bundle region, their narrowing may have contributed to the fibrotic abnormalities observed. The extent of destruction of the His bundle makes a lethal failure of atrioventricular conduction the most likely terminal event.

Adolescent↗
PubMed1975

The retrotracheal triangle in pediatric patients.

The retrotracheal triangle is the posterior superior mediastinum and usually is well outlined on the routine lateral chest roentgenogram. It has characteristic features, and careful evaluation of this area on routine roentgenogram will be of assistance in identifying abnormalities producing respiratory or feeding difficulties in infants and children. Anomalies occurring in this area include vascular structures, esophageal lesions, tumor masses, and inflammatory lesions.

Aortic Arch Syndromes↗