Citations

Cysts of the vallecula are rare, accounting for 10.5% to 20.1% of all laryngeal cysts. Vallecular cysts may present with diverse symptoms affecting the voice, airway, and swallowing. We describe the evaluation and treatment of a 70-year-old woman who presented with dysphagia caused by large bilateral vallecular cysts.

We previously reported that small mesenteric arteries from hypertensive rats have increased NOS-derived H2O2 and reduced NO/cGMP signaling. We hypothesized that antihypertensive therapy lowers blood pressure through a tetrahydrobiopterin (BH4)-dependent mechanism restoring NO/cGMP signaling and endothelial NOS (NOS3; eNOS) phosphorylation in small arteries. To test this hypothesis, small mesenteric arteries from normotensive rats (NORM), angiotensin II-infused rats (ANG), ANG rats with triple therapy (reserperine, hydrochlorothiazide, and hydralazine), or ANG rats with oral BH4 therapy were studied. Both triple therapy and oral BH4 therapy attenuated the rise in systolic blood pressure in ANG rats and restored NO/cGMP signaling in small arteries similarly. Triple therapy significantly increased vascular BH4 levels and BH4-to-BH2 ratio similar to ANG rats with BH4 supplementation. Furthermore, triple therapy (but not oral BH4 therapy) significantly increased GTP cyclohydrolase I (GTPCH I) activity in small arteries without a change in expression. NOS3 phosphorylation at Ser1177 was reduced in small arteries from ANG compared with NORM, while NOS3 phosphorylation at Ser633 and Thr495 were similar in ANG and NORM. NOS3 phosphorylation at Ser1177 was restored with triple therapy or oral BH4 in ANG rats. In conclusion, antihypertensive therapy regulates NO/cGMP signaling in small arteries through increasing BH4 levels and NOS3 phosphorylation at Ser1177.

Substance P is a neuropeptide released by afferent neurons in the respiratory tract during inflammatory reactions. It produces effects on blood vessels, bronchial smooth muscle, nasal glands, and respiratory cilia. We studied the in vitro effect of substance P on the ciliary beat frequency of human adenoid explants and its mechanism of action. Substance P was added to cultured adenoid at concentrations of 10−10, 10−8, 10−6, and 10−4 mol/L. Ciliary beat frequency was determined with phase‐contrast microscopy and microphotometry. Substance P increased ciliary beat frequency a maximum of 11.9% ± 3.8% (p < 0.01). Diclofenac (10−6 mol/L) significantly blocked the ciliostimulatory effects of SP (p < 0.022), indicating that prostaglandin synthesis is an intermediate step in the action of substance P on ciliary beat frequency. The L‐arginine analogs, NG‐nitro‐L‐arginine methyl ester and NG‐monomethyl‐L‐arginine, inhibit nitric oxide synthesis from L‐arginine. L‐Arginine analogs (10−4 to 10−2 mol/L) inhibited the effect of substance P (p < 0.02 at the higher concentration). This inhibition was reversed by adding L‐arginine, demonstrating that nitric oxide production is a required step in substance P‐induced ciliostimulation. Substance P stimulates ciliary activity in human nasal mucosa as a result of secondary production and release of endogenous prostaglandins and nitric oxide. It is likely that inflammatory disease processes that stimulate release of substance P and subsequent prostaglandin and nitric oxide production modify mucociliary transport. Pharmacologic modification of substance P and its second messengers may eventually permit regulation of this important defense mechanism and control of neurogenic inflammation.

It has been suggested that leukotrienes C4 (LTC4) and D4 (LTD4) released from upper respiratory mucosa influence mucociliary transport during allergic reactions. We studied the in vitro effects of leukotrienes C4 and D4 on the ciliary beat frequency (CBF) of human adenoid explants over a 5‐hour period. Tissue explants were cultured at 35° C in Minimum Essential Medium Eagle (MEM). The CBF was measured using phase contrast microscopy and microphotometry. Measurements of CBF were recorded in medium alone and in medium containing LTC4 or LTD4 at concentrations of 10−8 and 10−6 M. LTC4 and LTD4 increased CBF at concentrations of 10−8 and 10−6 M with increases of 20.51% ± 2.69% and 29.84% ± 4.06%, respectively. To determine the specificity of the LTC4 and LTD4 effects, the ciliated epithelium was treated with the specific leukotriene receptor antagonist LY‐171,883 before administration of LTC4 and LTD4. LY‐171,883 (10−6 M) significantly inhibited the ciliostimulatory effects of both leukotrienes. Our findings indicate that LTC4 and LTD4 increase CBF in vitro by activation of the LTD4 receptor.

Abstract The Task Force on Nomenclature was commissioned in 2007 by the Association for Applied Psychophysiology and Biofeedback, the Biofeedback Certification Institute of America, and the International Society for Neurofeedback and Research to develop an updated official definition of biofeedback. The article describes the task force participants and the process and publishes the task force's definition of biofeedback, which was approved by the three participating professional organizations.

Abstract CXCR4, like other G protein-coupled receptors, signals via heterotrimeric guanine nucleotide-binding proteins (G proteins) to regulate gene transcription, migration, development, growth, and transformation. We describe a formerly uncharacterized function of a G protein: a role in receptor trafficking. We previously showed that CXCR4 and the TCR physically associate and form a heterodimer upon stromal cell-derived factor-1 or CXCL12 (SDF-1) stimulation in human T cells to prolong ERK activation and, thereby, lead to gene upregulation and cytokine secretion. The CXCR4–TCR heterodimers occur on the cell surface and in an intracellular compartment in response to SDF-1. Neither the intracellular compartment to which the CXCR4–TCR heterodimers localize nor the mechanism for localization has been elucidated. In this article, we characterize molecular mechanisms required for postendocytic trafficking of CXCR4. Upon SDF-1 stimulation, CXCR4 localizes to Rab11+ vesicles, a recycling compartment near the microtubule organizing center and Golgi apparatus. This trafficking requires the CXCR4 C-terminal tail domain but not the CXCR4 ubiquitination sites. The TCR also constitutively localizes to this Rab11+ compartment. Trafficking of CXCR4 into the Rab11+, TCR-containing endosomes requires actin polymerization. Furthermore, inhibiting Rho activation or depleting Gα13 prevented trafficking of CXCR4 into the Rab11+ endosomes without hindering the ability of CXCR4 to endocytose. These results indicated that, upon SDF-1 treatment, Gα13 and Rho mediate the actin polymerization necessary for trafficking CXCR4 into the Rab11+, recycling endosomal compartment, which also contains constitutively recycling TCR and, thus, CXCR4–TCR heterodimers. To our knowledge, this is the first report of Gα13 as a mediator of receptor trafficking.