Post-translational processing in the Golgi plays a critical role in the trafficking of the luteinizing hormone/human chorionic gonadotropin receptor to the cell surface

Point mutations in the luteinizing hormone/human chorionic gonadotropin (LH/hCG) receptor have been shown to cause constitutive activation which results in precocious puberty in affected males. We introduced one of these mutations, Asp-556 --> Gly, into the rat LH/hCG receptor and demonstrated that the mutant receptor constitutively activated adenylate cyclase in transfected 293 T cells. The cell surface expression of the mutant receptor was lower than that of the wild type receptor. Pulse-chase studies showed that the 73-kDa precursor of both the mutant and wild type receptors was synthesized at comparable efficiencies. However, post-translational processing of the mutant receptor to the mature 92-kDa form, which has N-linked complex type oligosaccharide chains, was impaired. Sensitivity of the mutant receptor to peptide-N-glycanase F and endoglycosidase H, and insensitivity to sialidase indicated that the 73-kDa species represents the high mannose form that has not yet been trafficked through the medial and trans Golgi. Additionally, although the wild type receptor was palmitoylated, the mutant receptor was not. Although the high mannose 73-kDa species is capable of binding LH/hCG, our results show that post-translational processing in the Golgi is required for the mature 92-kDa receptor to reach the cell surface.     

Outcome of tunneled hemodialysis catheters placed by radiologists

PURPOSE: To compare the outcomes of hemodialysis catheters placed by interventional radiologists with those placed by surgeons. MATERIALS AND METHODS: The outcomes were retrospectively analyzed of 237 hemodialysis catheters placed in 140 patients by a radiology service from January 1991 through December 1992. Follow-up data were available for 222 catheters (94%). Catheter secondary patency and freedom from infection were analyzed statistically and by means of life-table analysis. RESULTS: Pneumothorax occurred after the placement of six catheters (2.5%); in two patients, a chest tube was required for decompression. Other short-term complications included air embolism with no clinical sequelae (two procedures) and prolonged oozing from the tunnel (two procedures). Long-term complications included infection and catheter failure. Infection occurred in 26 patients (18%) with 32 catheters (14%) and resulted in removal of 25 catheters. Ninety-three catheters (42%) failed, and 63 catheters (28%) were removed because of failure. CONCLUSION: Hemodialysis catheters placed by radiologists do not have a higher rate of complications or failure than catheters placed by surgeons.     

Pediatric airway in health and disease

The most common cause of pediatric anesthetic morbidity is the failure to adequately oxygenate. Problems with pediatric airways are the major cause of this inability to provide adequate oxygenation. Problems with pediatric airways and the diseases that affect them require not only knowledge about their pathophysiology but also considerable hands-on experience and respect for the complications that subsequently occur. It is hoped that by sharing knowledge and experiences, pediatricians can improve the care all of us strive to give our young patients.     

计算DES监控中优于闭可识别语言的闭可观子语言

本文给出一种求闭能观子语言的算法，该算法经ｍ步（系统中离散事件个数）收敛；并且证明无论对系统中事件如何排序，由该算法求出的闭能观子语言总包含最大闭可识别子语言。     

Design automation to suppress cable discharge event (CDE) induced latchup in 90 nm CMOS ASICs

Design automation tools have been developed to suppress CDE-induced latchup in CMOS ASICs. The tools govern the placement of I/Os and cores subject to CDE and automate the insertion of well and substrate contacts with varying periodicities around CDE susceptible cells according to rules derived from an analytical latchup model.     

N-acetylcysteine depresses contractile function and inhibits fatigue of diaphragm in vitro

We have previously shown that antioxidant enzymes (superoxide dismutase and catalase) depress contractility of unfatigued diaphragm fiber bundles and inhibit development of acute fatigue. In the present study, we tested for similar effects of N-acetyl-cysteine (NAC), a nonspecific antioxidant approved for clinical use. Diaphragms were excised from deeply anesthetized rats. Fiber bundles were removed, mounted isometrically at 37 degrees C, and stimulated directly using supramaximal current intensity. Studies of unfatigued muscle showed that 10 mM NAC reduced peak twitch stress (P < 0.0001), shortened time to peak twitch stress (P < 0.002), and shifted the stress-frequency curve down and to the right (P < 0.05). Fiber bundles incubated in 0.1-10 mM NAC exhibited a dose-dependent decrease in relative stresses developed during 30-Hz contraction (P < 0.0001) with no change in maximal tetanic (200 Hz) stress. NAC (10 mM) also inhibited acute fatigue. Throughout 10 min of intermittent contraction at 30-40 Hz, treated bundles developed higher stresses than time-matched control bundles (P < 0.0001). NAC concentrations > or = 30 mM were toxic, causing a prompt irreversible decrease in maximal tetanic stress (P < 0.0001). Because NAC effects mimic the effects of other antioxidant agents with different mechanisms of action, we conclude that exogenous antioxidants exert stereotypical effects on contractile function that differ between unfatigued and fatiguing muscle. Unlike antioxidant enzymes, however, NAC has been approved for clinical use and may be used in future studies of human muscle fatigue.     

The paradoxical hedonic valence of acute ethanol withdrawal (hangover) states in rats: place and taste conditioning

We describe the synthesis and pharmacological properties of two series of analogues: one which consists of three peptides having L-1-naphthylalanine in position 3 and the second composed of analogues substituted in position 3 with L-2-naphthylalanine. All peptides were tested in bioassays for pressor and antidiuretic activities. We also checked the uterotonic activity in vitro. We observed that the activity of counterparts in both series is, in two cases, strikingly different. One of the new analogues, [(L-2-Nal)3,(D-Arg)8]VP is among the most potent antagonists of the vasopressor response to AVP. Moreover, it is the first potent V1 antagonist devoid of antiuterotonic activity. This analogue was designed without modification of position 1, which was previously thought to be essential for substantial pressor antagonism. Two other peptides, [Mpa1;(L-2-Nal)3;(D-Arg)8]VP and [Mpa1,(L-1-Nal)3,D-Arg)8]VP, are highly potent V2 agonists. The second analogue is highly selective. With the exception of [(L-2-Nal)3]AVP, which showed weak antioxytocic activity, (L-Nal)3 modification resulted in the almost complete removal of interaction of our analogues with oxytocic receptors in vitro. Our results suggest that position 3 in AVP and its analogues is important not only for binding and recognition as previously though, but also for pressor, antidiuretic and uterotonic activities. We also assume that the hindering effect caused by bulky naphthyl moiety has a significant impact on the bioactive conformations of molecules which contain Nal residue, and can thus influence their interaction with V1, V2 and oxytocic receptors.