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81.
Oral appliances for the treatment of obstructive sleep apnea (OSA) produce either mandibular or tongue protrusion, and are thought to enlarge the upper airway (UA). We used videoendoscopy to measure UA cross-sectional area (CSA) and shape in the hypopharynx, oropharynx, and velopharynx during various stages of active mandibular and tongue protrusion during wakefulness in 10 patients with OSA and nine control subjects. Measurements were made in the supine position at end-tidal expiration, and were normalized to the CSA in the normal bite position. Airway shape was expressed as the anteroposterior/lateral (AP/L) diameter ratio. There were no differences between OSA patients and controls in the effects of mandibular and tongue protrusion on UA caliber. Both mandibular and tongue protrusion increased CSA in the hypopharynx and oropharynx (p < 0.001), whereas only tongue protrusion increased CSA in the velopharynx (p < 0.001). Tongue protrusion caused a greater increase in oropharyngeal and velopharyngeal CSA than did mandibular protrusion (p < 0.05). Mandibular protrusion caused a greater increase in CSA in the hypopharynx than in the oropharynx or velopharynx (p < 0.05). Obese patients had a larger relative increase in oropharyngeal CSA with mandibular and tongue protrusion than did subjects of normal weight. Tongue protrusion increased the AP/L diameter ratio in the oropharynx and velopharynx (p < 0.001), and mandibular protrusion did so to a lesser extent in the oropharynx (p < 0.01), resulting in a more circular airway shape. We conclude that mandibular and tongue protrusion increase the CSA and alter the shape of the UA during wakefulness. 相似文献
82.
V O'Connor C Heuss WM De Bello T Dresbach MP Charlton JH Hunt LL Pellegrini A Hodel MM Burger H Betz GJ Augustine T Sch?fer 《Canadian Metallurgical Quarterly》1997,94(22):12186-12191
The membrane protein syntaxin participates in several protein-protein interactions that have been implicated in neurotransmitter release. To probe the physiological importance of these interactions, we microinjected into the squid giant presynaptic terminal botulinum toxin C1, which cleaves syntaxin, and the H3 domain of syntaxin, which mediates binding to other proteins. Both reagents inhibited synaptic transmission yet did not affect the number or distribution of synaptic vesicles at the presynaptic active zone. Recombinant H3 domain inhibited the interactions between syntaxin and SNAP-25 that underlie the formation of stable SNARE complexes in vitro. These data support the notion that syntaxin-mediated SNARE complexes are necessary for docked synaptic vesicles to fuse. 相似文献
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AR Jude DV Greathouse RE Koeppe LL Providence OS Andersen 《Canadian Metallurgical Quarterly》1999,38(3):1030-1039
In the linear gramicidins, the four aromatic residues at positions 9, 11, 13, and 15 are well-known to be important for the structure and function of membrane-spanning gramicidin channels. To investigate whether the "spacer" residues between the tryptophans in gramicidin A (gA) are important for channel structure and function, D-Leu-10, -12. and -14 of gA were replaced by Ala, Val, or Ile. (For practical reasons, the Ile substitutions were introduced into the enantiomeric gramicidin A-, gA-.) Circular dichroism spectra of [D-Ala10,12,14]gA, [D-Val10,12,14]gA, or [Ile10,12,14]gA- incorporated into sodium dodecyl sulfate micelles or 1, 2-dimyristoyl-sn-glycero-3-phosphocholine vesicles differ from the spectrum of the native [D-Leu10,12,14]gA. All the analogue spectra display reduced ellipticity at both 218 and 235 nm, indicating the presence of double-stranded conformers with the Ala analogue spectra showing the largest departure from the native gA spectra. Size-exclusion chromatograms of the Val and Ile analogues show both monomer and dimer peaks, accompanied by peak broadening; the chromatograms for the Ala analogue show broad, overlapping peaks and suggest the presence of higher oligomers and/or (rapidly) interconverting conformations. All three analogues form membrane-spanning channels, with the channel-forming potency of the Ala analogue being much less than that of gA or the other analogues. In 1.0 M CsCl, the conductance of each analogue channel is approximately 25% less than that of [D-Leu10,12,14]gA channels. The lifetimes of the analogue channels also are less than of [D-Leu10,12, 14]gA channels, with the largest (8-fold) reduction being for [D-Ala10,12,14]gA channels. Hybrid channel experiments show that the beta6.3-helical backbone folding pattern is retained in the channel-forming subunits and that the substitutions primarily influence ion entry. Both the bulk and the stereochemistry of the aliphatic residues between the tryptophans of gA are important for channel structure and function. 相似文献
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JT Queenan LL Veeck JP Toner S Oehninger SJ Muasher 《Canadian Metallurgical Quarterly》1997,12(7):1573-1576
In-vitro fertilization patients (n = 15) at risk of ovarian hyperstimulation syndrome (OHSS) (oestradiol > or =4500 pg/ml on the day of human chorionic gonadotrophin administration and 25 or more follicles of intermediate or large size) underwent aspiration of all follicles and cryopreservation of all fertilized oocytes at the pronuclear stage. Patients were monitored for up to 2 weeks post-retrieval. Subsequent transfer of cryopreserved-thawed embryos was performed in programmed cycles using exogenous oestrogen and progesterone for endometrial preparation. Two patients (13%) developed OHSS necessitating hospitalization and vaginal aspiration of ascitic fluid. Two other patients (13%) developed moderate OHSS requiring ascitic fluid vaginal aspiration in the office setting, with dramatic improvement of the condition. Subsequent transfer of cryopreserved-thawed embryos yielded a clinical pregnancy rate of 58% per transfer and ongoing or delivery rates of 42 and 67% per transfer and per patient respectively. By eliminating pregnancy potential with cryopreservation of all prezygotes and examining the pregnancy potential with subsequent cryopreserved-thawed transfers, it is concluded that OHSS is reduced, but not eliminated for patients at risk. Subsequent transfer of cryopreserved-thawed prezygotes in a programmed cycle with exogenous steroids yields an excellent pregnancy rate. 相似文献
88.
To address the hypothesis that tumor necrosis factor (TNF)-alpha has a role in obesity-associated insulin resistance or the regulation of in vivo lipid metabolism, mice with targeted disruption of the TNF-alpha gene were generated and studied. The absence of TNF-alpha protein in TNF-null (-/-) mice was confirmed. Lean or obese (gold-thioglucose [GTG]-injected) homozygous (-/-) mice were compared with lean or obese age- and sex-matched wild-type (+/+) mice derived from the same line at 13, 19, and 28 weeks of age. The following parameters were significantly affected in lean -/- versus +/+ mice: Body weight was not affected until week 28 (decreased by 14%); epididymal fat pad weight also decreased (25%) at this time, as did percentage body fat (16%), while percentage body protein was increased 13%. Fed plasma insulin levels decreased 47% (28 weeks), triglyceride levels decreased (all three ages; maximum 35% at 19 weeks), and fed plasma leptin decreased 33% (28 weeks). Fasting glucose was slightly (10%) reduced, but the glucose response to an oral glucose tolerance test (OGTT) was not affected. There was a trend (NS) toward increased total adipose tissue lipoprotein lipase in -/- versus +/+ mice. GTG-treatment resulted in obese -/- and +/+ mice with equal mean body weights (42 and 58% increased weight versus lean mice). The following parameters were significantly different in obese -/- mice: fasting plasma glucose decreased 13% (28 weeks), fed plasma insulin decreased 67% (28 weeks), and insulin response to OGTT was decreased by 50%. For both groups of obese mice, glucose levels during the OGTT were substantially increased compared with those in lean mice; however, mean stimulated glucose levels were 20% lower in obese -/- versus +/+ mice. We conclude 1) that TNF-alpha functions to regulate plasma triglycerides and body adiposity and 2) that although TNF-alpha contributes to reduced insulin sensitivity in older or obese mice, the absence of TNF-alpha is not sufficient to substantially protect against insulin resistance in the GTG hyperphagic model of rodent obesity. 相似文献
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P Malik TC Fisher LL Barsky L Zeng P Izadi AL Hiti KI Weinberg TD Coates HJ Meiselman DB Kohn 《Canadian Metallurgical Quarterly》1998,91(8):2664-2671
Hemoglobinopathies, such as beta-thalassemias and sickle cell anemia (SCA), are among the most common inherited gene defects. Novel models of human erythropoiesis that result in terminally differentiated red blood cells (RBCs) would be able to address the pathophysiological abnormalities in erythrocytes in congenital RBC disorders and to test the potential of reversing these problems by gene therapy. We have developed an in vitro model of production of human RBCs from normal CD34(+) hematopoietic progenitor cells, using recombinant growth factors to promote terminal RBC differentiation. Enucleated RBCs were then isolated to a pure population by flow cytometry in sufficient numbers for physiological studies. Morphologically, the RBCs derived in vitro ranged from early polylobulated forms, resembling normal reticulocytes to smooth biconcave discocytes. The hemoglobin pattern in the in vitro-derived RBCs mimicked the in vivo adult or postnatal pattern of beta-globin production, with negligible gamma-globin synthesis. To test the gene therapy potential using this model, CD34(+) cells were genetically marked with a retroviral vector carrying a cell-surface reporter. Gene transfer into CD34(+) cells followed by erythroid differentiation resulted in expression of the marker gene on the surface of the enucleated RBC progeny. This model of human erythropoiesis will allow studies on pathophysiology of congenital RBC disorders and test effective therapeutic strategies. 相似文献
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