Citations

Nicotinic acetylcholine receptors (AChRs) mediate rapid excitatory synaptic transmission throughout the peripheral and central nervous systems. They transduce binding of nerve-released ACh into opening of an intrinsic channel, yet the structural basis underlying transduction is not fully understood. Previous studies revealed a principal transduction pathway in which αArg 209 of the pre-M1 domain and αGlu 45 of the β1–β2 loop functionally link the two regions, positioning αVal 46 of the β1–β2 loop in a cavity formed by αPro 272 through αSer 269 of the M2–M3 loop. Here we investigate contributions of residues within and proximal to this pathway using single-channel kinetic analysis, site-directed mutagenesis, and thermodynamic mutant cycle analysis. We find that in contributing to channel gating, αVal 46 and αVal 132 of the signature Cys loop couple energetically to αPro 272. Furthermore, these residues are optimized in both their size and hydrophobicity to mediate rapid and efficient channel gating, suggesting naturally occurring substitutions at these positions enable a diverse range of gating rate constants among the Cys-loop receptor superfamily. The overall results indicate that αPro 272 functionally couples to flanking Val residues extending from the β1–β2 and Cys loops within the ACh binding to channel opening transduction pathway.

Studies within the last 20 years have shown that the incidence of asthma is increased in children who have been hospitalized with bronchiolitis due to respiratory syncytial virus. To evaluate such respiratory consequences in an ambulatory population, a follow-up study was done of 37 children who had respiratory syncytial virus infection documented at a community pediatric clinic in 1968 when they were younger than 4 years. This study, done ten years later by chart review and parental interview, showed that asthma had sub sequently been diagnosed in three (8%). Thus, an increased risk for the development of asthma after respiratory syncytial virus infection was not found. Comparison of these data with those from previous reviews questions a causative role for respiratory syncytial virus in childhood asthma.

Carotid endarterectomy can lead to alterations in baroreceptor sensitivity. Impairment of this sensitivity can in turn lead to volatility of blood pressure (baroreflex failure syndrome—BFS). Rapid elevations in blood pressure can cause hypertensive encephalopathy in a patient with BFS. A patient is presented with hypertensive intra cerebral hemorrhage associated with BFS.

Recurrent dissections involving carotid, vertebral, or renal arteries have been described in patients with spontaneous cervical artery dissections, with a maximal interval between dissections of fourteen years. The authors describe 2 patients in whom aortic dissections developed twenty-five and forty years, respectively, following carotid artery dissections. These 2 patients constituted 8% of the total number of patients from Rochester, Minnesota, who were diagnosed with aortic dissection between 1987 and 1992. The first patient, a forty-five-year-old woman, presented in 1948 with right neck pain and headache, associated with several episodes of transient numbness of the right face and numbness and clumsiness of the left upper and lower extremities. Examination showed right miosis. Angiography showed a stenosis of the extracranial right internal carotid artery beginning several centimeters from the bifurcation. She died at age eighty- five from an aortic dissection. The second patient, a thirty-eight-year-old man, noted left orbital and frontotemporal headaches and drooping of the left eyelid in 1962. Examination showed left oculosympathetic palsy. Angiography showed stenosis and an aneurysm in the midportion of the extracranial left internal carotid artery. He died at age sixty-three from an aortic dissection. These cases suggest that following a carotid artery dissection the risk of a recurrent arterial dissection may remain elevated for a prolonged period of time and the recurrent dissection may involve the aorta.

There is interest in the role of growth factors in the genesis of arterial remodeling. We studied local administration of basic fibroblast growth factor (bFGF) to coronary lesions to determine whether there is a difference in remodeling and whether neovascularization could be induced in such stenoses and distal myocardium. Pigs were randomized to balloon infusion of either saline or bFGF at each thermally injured arterial site. After the animals were killed, their internal elastic lamina, neointima, and lumen areas were measured. Capillaries were counted in the arteries and myocardium. There was a greater loss of lumen and internal elastic lamina in the bFGF group. The neointima, media, and myocardium in the bFGF treated arteries had statistically more capillaries. This study showed that local intracoronary bFGF, at a dose that results in arterial luminal revascu larization in injured segments, adversely affects arterial remodeling. Thus, the angio genic response to exogenous bFGF may be offset by concomitant shrinkage of injured arterial segments.