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91.
The m5 muscarinic acetylcholine receptor was constitutively activated by a wide range of amino acid substitutions at a residue (serine 465) that is positioned at the junction of the sixth transmembrane domain and the extracellular loop. Of 13 substitutions tested, 11 produced significant increases in constitutive activity. Replacement of serine 465 with large (phenylalanine and valine) or basic residues (arginine and lysine) increased the constitutive activity of the receptor to between 55 and 110% of the maximum response of the wild-type receptor to the agonist carbachol. Other substitutions (e.g., cysteine and leucine) increased the constitutive activity to an intermediate level (30%), while small and acidic residues (glycine, aspartate, and glutamate) caused small or insignificant increases. The increase in the constitutive activity of each mutant receptor correlated with an increase in the potency of carbachol in both binding and functional assays, with the most constitutively activated receptors showing a 40-fold decrease in the EC50 of carbachol. The negative antagonist atropine bound to and reversed the constitutive activity of all mutant receptors with equal potency. These data were fitted to a two-state model of receptor function. The data are consistent with the primary effect of substitutions to serine 465 being to selectively destabilize the inactive state of the receptor, thus favoring formation of the active state in the absence of agonists. Our data strongly support this two-state model of receptor function and identify a critical role of this domain in the activation of muscarinic receptors. 相似文献
92.
SM Lele ES Gloster ER Heilman PC Chen CK Chen AP Anzil JN Pozner MJ Reardon 《Canadian Metallurgical Quarterly》1997,24(3):193-196
In adult mammals fever is associated with the reduction of blood plasma iron level. Immature mammals, however, show either a decrease (precocial animals such as guinea pig neonates) or a lack of reduction (altricial animals such as human neonates) of plasma iron in response to endotoxin. In order to determine whether this difference is connected with maturity just after delivery, plasma iron concentration, hematocrit, body temperature and body mass were measured in rat pups injected with E. coli endotoxin in doses of 50 or 200 micrograms kg-1. Rat pups, like human neonates, are altricial animals. In 7-day-old rats injection of LPS led to a dose-dependent decrease in plasma iron level. The fall in plasma iron was accompanied by changes in body temperature and body mass. The results showed that plasma iron response to endotoxin in altricial rat neonates is similar to that observed in precocial guinea pig pups. 相似文献
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94.
ES Hansen 《Canadian Metallurgical Quarterly》1997,32(3):223-233
The present study aimed to demonstrate conditioned inhibition of Pavlovian conditioning of autonomic responses in humans. Subjects (N = 21) were presented initially with four geometric shapes (A, B, C and D). An electric shock served as the unconditioned stimulus (US) during acquisition. Conditional stimuli lasted for 8 s and US onset coincided with CS offset. Subjects were trained with A-US, C-US, and AC-US pairings and AB alone and B alone presentations. The subsequent summation test consisted of C-US pairings and CB alone and CD alone presentations. Conditioning was evident in self-reported US expectancy and first and second interval electrodermal responses. Evidence for conditioned inhibition during the summation test was found in US expectancy and second interval electrodermal responses. 相似文献
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We report a case of gastric outlet obstruction simulating gastric antral neoplasm resulting from a perforated Meckel's diverticulum. Presentation of this nature has not been previously reported. 相似文献
98.
SD Detera-Wadleigh JA Badner T Yoshikawa AR Sanders LR Goldin G Turner DY Rollins T Moses JJ Guroff D Kazuba ME Maxwell HJ Edenberg T Foroud D Lahiri JI Nurnberger OC Stine F McMahon DA Meyers D MacKinnon S Simpson M McInnis JR DePaulo J Rice A Goate ES Gershon 《Canadian Metallurgical Quarterly》1997,74(3):254-262
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100.
ES Wiener RJ Touloukian BM Rodgers JL Grosfeld EI Smith MM Ziegler AG Coran 《Canadian Metallurgical Quarterly》1996,31(8):1166-1169
The members of the Section on Surgery of the American Academy of Pediatrics were surveyed to determine the practice of North American pediatric surgeons in infants with inguinal hernia (IH). Case-scenario multiple-choice-design questionnaires regarding hernias and hydroceles were sent to all members of the Surgical Section, and responses were received from 292 (50%). In healthy full-term infant boys with asymptomatic reducible IH, 82% of responders perform repair electively, no matter what the age or weight. In full-term girls with a reducible ovary, 59% perform surgery at the next available time; if the ovary is nonreducible but asymptomatic, 44% operate emergently or urgently and 42% at the next elective slot. In former preemies, the pattern of repair is as follows. (1) For those recently discharged after 2 months in the neonatal intensive care unit (NICU) with reducible IH, 65% perform the repair when convenient. (2) A general anesthetic is used in 70%; 15% use spinal anesthesia, and 11% use caudal block with sedation. (3) If the repair is done in the hospital outpatient (same-day) unit, 36% wait until 50 weeks postconception (PC) and 33% wait until 60 weeks PC. (4) if the baby's weight is at least 1,000 g. 71% perform the repair before discharge. The pain control choice after childhood IH repair is Tylenol for 30%, local infiltration biquivacaine for 30%, caudal block for 22%, regional block for 11%, and Tylenol/codeine combined for 7%. In 6-week-old full-term infants with communicating hydroceles without definite "hernia," two thirds treat as an IH with elective repair as soon as possible. With respect to contralateral exploration in infants with unilateral IH, 65% perform it in males if they are < or = 2 years of age and 84% use it in females of up to 4 years of age. This approach is not influenced by presenting side, presence of hydrocele, or history of prematurity. Laparoscopic evaluation of the contralateral IH is performed by only 6% of responders, 40% of whom use the open ipsilateral sac for laparoscope introduction. 相似文献