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61.
KL Nicholson M Munson RB Miller TJ Filip R Fairman FM Hughson 《Canadian Metallurgical Quarterly》1998,5(9):793-802
The fusion of intracellular transport vesicles with their target membranes requires the assembly of SNARE proteins anchored in the apposed membranes. Here we use recombinant cytoplasmic domains of the yeast SNAREs involved in Golgi to plasma membrane trafficking to examine this assembly process in vitro. Binary complexes form between the target membrane SNAREs Sso1p and Sec9p; these binary complexes can subsequently bind to the vesicle SNARE Snc2p to form ternary complexes. Binary and ternary complex assembly are accompanied by large increases in alpha-helical structure, indicating that folding and complex formation are linked. Surprisingly, we find that binary complex formation is extremely slow, with a second-order rate constant of approximately 3 M(-1) s(-1). An N-terminal regulatory domain of Sso1p accounts for slow assembly, since in its absence complexes assemble 2,000-fold more rapidly. Once binary complexes form, ternary complex formation is rapid and is not affected by the presence of the regulatory domain. Our results imply that proteins that accelerate SNARE assembly in vivo act by relieving inhibition by this regulatory domain. 相似文献
62.
G Shi V Faúndez J Roos EC Dell''Angelica RB Kelly 《Canadian Metallurgical Quarterly》1998,143(4):947-955
Hereditary nonpolyposis colorectal cancer (HNPCC) is a syndrome involving a predisposition to cancers of the colon, endometrium and several other extra-colonic sites, accounting for approximately 1-5% of all colorectal cancer cases. It is not easily recognized because of a lack of distinctive clinical markers, making diagnosis and management of this disease problematic. To provide a basis for uniformity in diagnosis of HNPCC, the Amsterdam criteria were proposed and are currently in use. More recently, the discovery of four human mismatch repair genes (hMSH2, hMLH1, hPMS1 and hPMS2) has provided novel insight into the genetic basis of this disease, and raised the possibility of genetic diagnosis for management of HNPCC patients and their family members. This report summarizes the clinicopathologic aspects of HNPCC, reviews the recent genetic findings and surveillance strategies, and suggests a novel designation of certain patients as suspected HNPCC. 相似文献
63.
AC Robinson J Burke S Robinson DG Johnston RS Elkeles 《Canadian Metallurgical Quarterly》1998,21(5):701-705
The edentulous ridge expansion has been introduced in recent years to reestablish an appropriate alveolar ridge width. This technique consists of the placement of implants in the space formed after the dislocation of the buccal plate in a labial direction. In guided bone regeneration, the quantity of bone regenerated under the membranes has been demonstrated to be directly related to the amount of the space under the membranes. This space can diminish as a result of membrane collapse. To avoid this problem, a new technique of edentulous ridge expansion, which involved the use of a titanium mesh barrier to protect the regenerating tissues and to achieve a rigid fixation of the bone segments, was used in association with autologous bone in 25 patients. At second-stage surgery in all patients, it was possible to see tissue, under the mesh, that had the macroscopic characteristics of mature bone and was superficially covered by a thin soft tissue layer. The microscopic examination showed that all autologous bone particles were embedded in newly formed bone. The use of a rigid mesh can assist bone regeneration in non-space-making defects, since it probably does not interfere with the blood flow to the underlying tissues because of the presence of microholes within the mesh. 相似文献
64.
JB Thomas MJ Fall JB Cooper RB Rothman SW Mascarella H Xu JS Partilla CM Dersch KB McCullough BE Cantrell DM Zimmerman FI Carroll 《Canadian Metallurgical Quarterly》1998,41(26):5188-5197
A three-component library of compounds was prepared in parallel using multiple simultaneous solution-phase synthetic methodology. The compounds were biased toward opioid receptor antagonist activity by incorporating (+)-(3R,4R)-dimethyl-4-(3-hydroxyphenyl)piperidine (a potent, nonselective opioid pure antagonist) as one of the monomers. The other two monomers, which included N-substituted or unsubstituted Boc-protected amino acids and a range of substituted aryl carboxylic acids, were selected to add chemical diversity. Screening of these compounds in competitive binding experiments with the kappa opioid receptor selective ligand [3H]U69,593 led to the discovery of a novel kappa opioid receptor selective ligand, N-?(2'S)-[3-(4-hydroxyphenyl)propanamido]-3'-methylbutyl?-(3R, 4R)-dimethyl-4-(3-hydroxyphenyl)piperidine (8, RTI-5989-29). Additional structure-activity relationship studies suggested that 8 possesses lipophilic and hydrogen-bonding sites that are important to its opioid receptor potency and selectivity. These sites appear to exist predominantly within the kappa receptor since the selectivity arises from a 530-fold loss of affinity of 8 for the mu receptor and an 18-fold increase in affinity for the kappa receptor relative to the mu-selective ligand, (+)-N-[trans-4-phenyl-2-butenyl]-(3R, 4R)-dimethyl-4-(3-hydroxyphenyl)piperidine (5a). The degree of selectivity observed in the radioligand binding experiments was not observed in the functional assay. According to its ability to inhibit agonist stimulated binding of [35S]GTPgammaS at all three opioid receptors, compound 8 behaves as a mu/kappa opioid receptor pure antagonist with negligible affinity for the delta receptor. 相似文献
65.
JJ Callaghan EE Forest JP Olejniczak DD Goetz RC Johnston 《Canadian Metallurgical Quarterly》1998,80(5):704-714
We evaluated the results twenty to twenty-five years after ninety-three consecutive, nonselected Charnley total hip arthroplasties performed with cement by the senior one of us in sixty-nine patients who were less than fifty years old at the time of the procedure. Seventy of the seventy-two hips in the living patients were followed radiographically for at least twenty years. Twenty-seven hips (29 per cent) had a revision or a resection of the prosthesis during the follow-up period. The revision or the resection was performed because of aseptic loosening in twenty-one hips (23 per cent), infection in four (4 per cent), dislocation in one (1 per cent), and fracture of the femur in one. Eighteen acetabular components (19 per cent) and five femoral components (5 per cent) were revised because of aseptic loosening, and an additional fourteen acetabular components (15 per cent) and seven femoral components (8 per cent) demonstrated definite or probable radiographic loosening. The present study demonstrates the long-term durability of total hip arthroplasty performed with cement in an active population of patients. The fixation of the femoral component was found to perform better than that of the acetabular component at twenty to twenty-five years after the procedure. 相似文献
66.
67.
CJ Frary RB Devereux R Kramer-Fox RB Roberts HS Ruchlin 《Canadian Metallurgical Quarterly》1994,73(4):263-267
In 1990-1991, a national survey was conducted to estimate the prevalence of Salmonella species among Canadian commercial turkey flocks. Two hundred and seventy flocks were randomly selected across Canada. The proportion sampled from each province was selected according to each province's share of the national turkey market. Samples, consisting of 12 pooled litter and four pooled dust samples, were used to determine the Salmonella status of the environment of each flock. Additionally, a one kilogram sample of feed was taken from each flock premise. Salmonella was recovered from environmental samples in 234/270 (86.7%) of flocks and from feed samples in 26/266 (9.8%) of flocks. Forty-eight different Salmonella serovars were isolated from flock environmental samples. The most prevalent serovars were S. anatum, S. hadar, S. agona, S. heidelberg and S. saintpaul which were isolated from 53/270 (19.6%), 49/270 (18.1%), 49/270 (18.1%), 42/270 (15.6%) and 34/270 (12.6%) flocks, respectively. 相似文献
68.
69.
The present study characterised seven species of the Chabertiidae (Nematoda: Strongyloidea) belonging to either the subfamily Oesophagostominae (Oesophagostomum radiatum, Oesophagostomum venulosum, Oesophagostomum dentatum, Oesophagostomum quadrispinulatum, Oesophagostomum columbianum, Oesophagostomum bifurcum) or to the subfamily Chabertiinae (Chabertia ovina) by their second internal transcribed spacer rDNA sequence, assessed the extent of intraspecific variation and interspecific differences in the sequence, and inferred the phylogenetic relationship of C. ovina with respect to members of the Oesophagostominae. In both the phenetic and cladistic analyses of the sequence data, Chabertia was nested within Oesophagostomum, suggesting either that the species examined represent members of the same genus, or alternatively, that Oesophagostomum may represent more than one genus. 相似文献
70.
The Drug Evaluation Classification Program: using ocular and other signs to detect drug intoxication
EM Kosnoski RL Yolton K Citek CE Hayes RB Evans 《Canadian Metallurgical Quarterly》1998,69(4):211-227
BACKGROUND: A systematic approach to determining drug intoxication has been developed for use by police officers. By considering specific physiological signs, trained officers can detect the effects of seven major drug types. METHODS: Officers follow a 12-step testing sequence and evaluate signs such as pupil sizes and responses, eye movements, heart rate, body temperature, mental timing, and balance. A matrix is then used to compare that subject's signs to those that would be produced by the seven types of drugs. If a pattern match is found, the officer concludes that the subject is under the influence of a drug and specifies the drug type. RESULTS: Several field and laboratory validation studies have been conducted using these procedures. In general, officers were 70% to 90% accurate in determining intoxication status and drug classification, but poly-drug use and drug rebound effects can sometimes cause problems in interpretation. CONCLUSION: Ocular and other physiological signs can be used to detect drug intoxication and classify the type of drug taken. Knowledge of the procedures used in the Drug Recognition Program can enable optometrists to serve as consultants to the police and as expert witnesses in cases involving the use of ocular signs that indicate illicit drug use. 相似文献