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71.
NM Goudgaon FN Naguib MH el Kouni RF Schinazi 《Canadian Metallurgical Quarterly》1993,36(26):4250-4254
Lithiation of 5-bromo-2,4-bis(benzyloxy)pyrimidine (3) with n-BuLi at -80 degrees C followed by the addition of diphenyl diselenide or diphenyl disulfide as an electrophile furnished the corresponding 5-(phenylhetera)-2,4-bis(benzyloxy)pyrimidine, which on exposure to trimethylsilyl iodide in CH2-Cl2 at room temperature yielded the 5-(phenylhetera)uracils in 70-75% yield. Similarly, the 6-(phenylhetera)uracils were prepared from 6-bromo-2,4-bis(benzyloxy)pyrimidine (10). 1-[(2-Hydroxyethoxy)methyl]-5-(phenylselenenyl)uracil (PSAU, 18) and 1-(ethoxymethyl)-5-(phenylselenenyl)uracil (17) were synthesized by the electrophilic addition of benzeneselenenyl chloride to the acyclic uracils under basic conditions. These compounds were evaluated for their ability to inhibit dihydrouracil dehydrogenase (DHUDase, E.C. 1.3.1.2), orotate phosphoribosyltransferase (OPRTase, E.C. 2.4.2.10), uridine phosphorylase (UrdPase, E.C. 2.4.2.3), and thymidine phosphorylase (dThdPase, E.C. 2.4.2.4). 5-(Phenylselenenyl)uracil (PSU, 6) and 5-(phenylthio)uracil (PTU, 7) inhibited DHUDase with apparent K(i) values of 4.8 and 5.4 microM, respectively. The corresponding 6-analogues, compounds 13 and 14, demonstrated inhibitory activity against OPRTase. PTU as well as PSU and its riboside, 2'-deoxyriboside, and acyclonucleosides were inhibitors of UrdPase, with PSAU (18) being the most potent with an apparent K(i) value of 3.8 microM. None of the compounds evaluated had any effect on dThdPase. Interestingly, most of the compounds showed modest selective anti-human-immunodeficiency-virus activity in acutely infected primary human lymphocytes. 相似文献
72.
HD Tazelaar FN Nilsson M Rinaldi P Murtaugh JC McDougall CG McGregor 《Canadian Metallurgical Quarterly》1993,105(4):674-678
Transbronchial biopsy has become the procedure of choice for the diagnosis of acute lung rejection after transplantation, but the sensitivity of the technique in this setting remains unknown. In this study, 14 mongrel dogs underwent left lung transplantation, after which triple-drug immunosuppression was given for 5 days and then all immunosuppression was stopped. All animals had clear chest radiographs at this time. Transbronchial biopsy was performed in nine lung regions (two to six pieces of lung tissue were obtained per region, with a mean of 4.3 pieces per region) before the animals were killed 2 to 4 days later, at which time varying degrees of rejection had occurred. Rejection was graded histologically on a scale of 0 to 3 (0 = no rejection, 1 = mild rejection, 2 = moderate rejection, 3 = severe rejection) in each piece of lung tissue obtained at transbronchial biopsy. After the dogs were put to death, the true state of lung rejection was determined by histologic examination of the entire lung. We calculated the sensitivity of transbronchial biopsy with 95% confidence intervals. Five pieces of lung tissue were needed to yield a sensitivity of 92% (82%, 100%) to identify mild rejection in the entire lung with transbronchial biopsy. Three pieces of lung tissue were needed to yield a sensitivity of 92% (84%, 100%) to identify the presence of moderate to severe rejection in the entire lung (that is, rejection that requires pulse therapy) on transbronchial biopsy. These results indicate that three to five pieces of lung tissue that are suitable for diagnostic purposes obtained at transbronchial biopsy are adequate for the diagnosis of acute pulmonary rejection after lung transplantation. 相似文献
73.
The present study investigated the effects of the cannabinoid receptor agonist CP 55,940 (1-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl) phenyl]-trans-4-(3-hydroxypropyl)cyclohexanol) and the cannabinoid receptor antagonist SR 141716A (N-(piperidin-l-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-me thyl-1 H-pyrazole-3-carboxamide hydrochloride) on ultrasonic vocalizations, body temperature and activity in 11-13-day-old rat pups. Testing occurred in a 5-min session 30 min following drug administration. CP 55,940 produced a dose-dependent decrease in ultrasonic vocalizations, with a 1000-micrograms/kg dose causing an almost complete inhibition of calls. Doses of 100 and 1000 micrograms/kg of CP 55,940, but not 10 micrograms/kg, caused significant hypothermia in the pups and the 1000 micrograms/kg dose also inhibited activity. The cannabinoid receptor antagonist SR 141716A (20 mg/kg) reversed the effects of 1000 micrograms/kg CP 55,940 on ultrasonic vocalizations and body temperature, but the benzodiazepine receptor antagonist flumazenil (20 mg/kg), the dopamine D1 receptor antagonist SCH 23390 (0.5 mg/kg) and the opioid receptor antagonist naloxone (1 mg/kg) did not. When administered alone, SR 141716A (20 mg/kg) increased pup ultrasonic vocalizations without affecting body temperature or activity. These results indicate that cannabinoids modulate ultrasonic vocalization production in rat pups in a manner that is independent of hypothermia. The increase in ultrasonic vocalizations produced by SR 141716A is one of the first reported behavioural effects of this drug and suggests that the endogenous cannabinoid ligand anandamide may be involved in the regulation of ultrasonic vocalizations. 相似文献
74.
JR Buck JJ Fath SK Chung VJ Sorensen HM Horst FN Obeid 《Canadian Metallurgical Quarterly》1995,61(8):655-7; discussion 657-8
A surgeon has many options available to aid in the closure of abdominal wall defects in the elective setting. In the emergent setting, active infection or contamination increases the likelihood of infection of permanent prosthetic material and limits the surgical options. In such settings, we have used absorbable mesh (Dexon) as an adjunct to fascial closure until the acute complications resolve. To evaluate the effectiveness of this technique, we reviewed the outcome of such closures in 26 critically ill patients. Between July 1987 and June 1993, 26 patients were identified who had placement of absorbable mesh as part of an emergent laparotomy at a major urban trauma center. Through a retrospective chart review, the incidence of complications and outcome of the closure were tabulated. Seven patients were initially operated on for trauma. Two of the patients had mesh placement at their initial procedure secondary to fascial loss from trauma. The remainder of the patients hd mesh placement during a subsequent laparotomy for complications related to their initial procedure. Indications for these laparotomies included combinations of wound dehiscence, intra-abdominal abscess, anastomotic disruption, and perforation. Mesh placement in patients with intra-abdominal infection created effectively open abdominal wounds that allowed continued abdominal drainage, but required extensive wound care. Despite the absorbable nature of the mesh and often prolonged hospital stay in these ill patients, none of them required reoperation for dehiscence, recurrence of intra-abdominal abscess, or infection of the mesh.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
75.
FN Ko 《Canadian Metallurgical Quarterly》1997,17(7):1274-1282
We examined the binding properties and mitogenic effects of U46619, using cultured vascular smooth muscle cells (VSMCs), by ligand-binding assay, measuring [3H]thymidine and [3H]leucine incorporation, checking with flow cytometry, and counting the cell number. The U46619-activated mitogenic signal-transduction pathway was assessed by measuring formation of inositol monophosphate (IP); [Ca2+]i; mitogen-activated protein kinase (MAPK), MAPK kinase (MAPKK), and p74raf-1 activities; and GTP-bound Ras. [3H]U46619 bound to cultured VSMCs from Wistar-Kyoto (WKY) rats at a single class of site (Kd: 15.5 +/- 2.6 nmol/L). However, it bound to VSMCs from spontaneously hypertensive rats (SHRs) at two classes of sites (Kd: 2.3 +/- 0.6 nmol/L and 1.4 +/- 0.5 mumol/L). U46619 increased DNA and protein synthesis, cell number, IP formation, [Ca2+]i, and MAPK and MAPKK activities, with EC50 values close to its Kd value for the low-affinity binding site in VSMCs from SHR. Prostaglandin (PG) E2 and PGF2 alpha showed little of such mitogenic effects. All these effects of U46619 were inhibited by SQ29548, staurosporine, or pretreatment of VSMCs with phorbol 12-myristate 13-acetate for 24 hours. However, U46619 stimulation did not lead to a significant increase in the Ras-GTP complex or p74raf-1 activity. In conclusion, the mitogenic effect of U46619 appears to be mediated via the activation of low-affinity thromboxane binding sites that trigger phosphoinositide hydrolysis and activate the MAPK pathway, leading to DNA synthesis and cell proliferation. 相似文献
76.
77.
78.
Kürkcü M Benlidayi ME Ozsoy S Ozyeğin LS Oktar FN Kurtoğlu C 《Journal of materials science. Materials in medicine》2008,19(1):59-65
Objectives The aim of this study was to compare osseous healing characteristics of titanium implants coated with enamel-derived fluoride-substituted
apatite (EFSA) or dentin-derived fluoride-substituted apatite (DFSA).
Methods Fluoride-substituted apatite was derived from extracted human teeth with calcination method at 850 °C. DFSA and EFSA were
separated and carefully ground with a blade grinder. Twenty-four titanium implants were prepared from a 99.99% pure titanium
bar. EFSA and DFSA powders were sprayed separately on implants. As control group, unsprayed and sandblasted pure titanium
implants were used. Eight adult rams were used in the study. One EFSA coated, 1 DFSA coated and 1 control implants were placed
into right tibia of each rams. The rams were sacrificed after 6 months of healing. Undecalcified sections were prepared according
to Donath’s method and histomorphometric evaluation of implants was made.
Results The mean bone contact percentage of DFSA-coated, EFSA-coated and control implants was 89.88% ± 2.34, 70.19% ± 13.11 and 53.12% ± 5.76
respectively. This study suggests that DFSA-coated implants achieved better bone contact than EFSA-coated implants (P < 0.05). Also study groups presented better bone contact than control group (P < 0.05).
Conclusions The results of this study show that although DFSA-coated implants achieved better bone contact, both DFSA and EFSA can be
considered as appropriate coating materials. 相似文献
79.
After the "silent" perforative duodenal ulcer closure the gap till the complications would occur, which need reoperation, by two times more than such period of time in patients with typical ulcer anamnesis, preceding the perforation. The reoperation causes are the recurrence (in 50.6% of observations), newly occurred ulcer (in 26.9%) or nonhealing of already existing (in 22.5%) duodenal ulcer. The reoperation method of choice is gastric resection according to Billroth-I in combination with truncal vagotomy in case of hypersecretory syndrome. 相似文献
80.
Neuronal bungarotoxin (NBT) is a highly selective, slowly reversible, competitive antagonist of the alpha3beta2 neuronal nicotinic receptor. Contributions to NBT sensitivity are made by both the alpha3 and beta2 subunits. We used a chimeric alpha subunit to demonstrate that the entire alpha3 contribution lies within sequence segment 84-215. Construction and analysis of a series of mutant alpha3 subunits identified seven amino acid residues (Thr143, Tyr184, Lys185, His186, Ile188, Gln198, Ser203) within this region that contribute to NBT sensitivity. Changing Thr143 to lysine, as in alpha2, resulted in a approximately 1000-fold loss of NBT sensitivity. The effect on NBT sensitivity of changing each of the other six residues ranged from 1.8- to 40.5-fold. More extensive mutagenesis demonstrated that Thr143 serves as part of the consensus sequence for glycosylation at N141, and it is this glycosylation that is the determinant of NBT sensitivity. Only serine could substitute for threonine to maintain full NBT sensitivity, and changing Asn141 to alanine resulted in a approximately 300-fold loss of NBT sensitivity. The chimera alpha2-181-alpha3, containing all identified determinants except the glycosylation site, formed receptors insensitive to 300 nM NBT. Installation of threonine to complete the glycosylation consensus site in this chimera conferred NBT sensitivity only 10-fold less than that of wild-type alpha3beta2. These seven determinants of NBT sensitivity are located in close proximity to a series of conserved residues that are common features of all nicotinic receptor binding sites. 相似文献