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91.
We have identified the human papillomavirus (HPV) DNA replication initiation protein E1 as a tight-binding substrate of cyclin E/cyclin-dependent kinase (Cdk) complexes by using expression cloning. E1, a DNA helicase, collaborates with the HPV E2 protein in ori-dependent replication. E1 formed complexes with cyclin E in insect and mammalian cells, independent of Cdks and E2. Additional cyclins, including A-, B-, and F-type (but not D-type), interacted with the E1/E2 complex, and A- and E-type cyclin kinases were capable of phosphorylating E1 and E2 in vitro. Association with cyclins and efficient phosphorylation of E1 required the presence of a cyclin interaction motif (the RXL motif). E1 lacking the RXL motif displayed defects in E2-dependent HPV ori replication in vivo. Consistent with a role for Cdk-mediated phosphorylation in E1 function, an E1 protein lacking all four candidate Cdk phosphorylation sites still associated with E2 and cyclin E but was impaired in HPV replication in vitro and in vivo. Our data reveal a link between cyclin/Cdk function and activation of HPV DNA replication through targeting of Cdk complexes to the E1 replication-initiation protein and suggest a functional role for E1 phosphorylation by Cdks. The use of cyclin-binding RXL motifs is now emerging as a major mechanism by which cyclins are targeted to key substrates.  相似文献   
92.
This study examined risk factors associated with incisor injury in 3396 third and fourth grade school children in Alachua County, Florida. One of six orthodontists completed a standardized examination form for each child to assess severity of incisor injury, gender, age, race, skeletal relationships, morphologic malocclusion, incisor exposure, interlabial gap, TMJ sounds, chin trauma, and history of lower facial trauma. One in five (19.2%) exhibited some degree of incisor injury. This was limited to a single tooth in 73.1% of those with injury, while enamel injury predominated (89.4%). The majority of the injuries (75.4%) were localized in the maxillary arch, with central incisors the most frequently traumatized. Chi-square tests of association indicated that gender, race, school, orthodontist, history of lower facial trauma, chin trauma, profile, and maxillary and mandibular horizontal positions were associated with incisor injury (P < 0.05). Wilcoxon rank sum tests identified differences in age, overjet, time of screening, and interlabial gap between those with and without injury (P < 0.05). Results of logistic regression analyses indicated risk of incisor injury was greater for children who had a prognathic maxilla, a history of trauma, were older, were male, and had greater overjet and mandibular anterior spacing.  相似文献   
93.
OBJECTIVES/HYPOTHESIS: To compare early (<1 y) and longer-term (1.0-7.5 y; mean follow-up, 2.8 y) hearing results following surgery for congenital aural atresia and to analyze revision cases for cause of failure, time of occurrence, and outcome. STUDY DESIGN: Retrospective study of 55 consecutive patients (59 ears) undergoing surgery during an 11-year period for congenital aural atresia. METHODS: The best speech reception threshold (SRT) during the first postoperative year was compared with the most recent SRT beyond the first postoperative year. The complication rate and long-term hearing results (>1 y) for initial and revision surgeries were compared. RESULTS: In the early postoperative period, an SRT of < or =25 dB was achieved in 60% and an SRT of < or =30 dB in 70%. With longer follow-up (mean, 2.8 y), 46% of patients maintained an SRT < or =25 dB. Revision surgery was necessary in approximately one third of patients. Longer-term hearing results following initial surgery only or after revision surgery showed an SRT < or =25 dB in 53% and an SRT < or =30 dB in 64%. For primary and revisions surgeries the incidence of temporary facial paralysis was 1.5% and for significant hearing loss, 3.0%. CONCLUSIONS: Some degradation in hearing does occur as patients are followed beyond the first postoperative year. Revision surgery will be necessary in approximately one third of cases. With revisions, an SRT < or =25 dB can be expected in half of cases and an SRT < or =30 dB in two thirds of cases. The ability to provide these hearing results supports this surgery in unilateral cases.  相似文献   
94.
The purpose of this study was to evaluate accuracy of dynamic gadolinium-enhanced MR angiography (MRA) of the celiac, superior, and inferior mesenteric arteries in patients with suspected mesenteric ischemia compared with catheter angiography or surgery. Sixty-five patients with suspected mesenteric ischemia underwent three-dimensional spoiled gradient-recalled acquisition in the steady state (GRASS) gadolinium-enhanced MRA. Correlative studies were performed on 14 patients, catheter angiography alone was performed on 12 patients, and surgery alone was performed on two patients. Six patients had mesenteric ischemia. In all patients, the celiac artery (CA) and superior mesenteric artery (SMA) were seen well enough to evaluate; however, the inferior mesenteric artery (IMA) could be evaluated in only 9 of the 14 patients. MRA showed severe stenosis (> 75%) or occlusion of the celiac axis in seven patients, of the SMA in six patients, and of the IMA in four patients. The overall sensitivity and specificity were 100% and 95%, respectively, compared with catheter angiography and surgery. The two errors were caused by overgrading the severity of IMA disease. Three-dimensional gadolinium-enhanced MRA can accurately demonstrate the origins of the CA and SMA and is useful in evaluation of patients with suspected mesenteric ischemia.  相似文献   
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Adenylosuccinate lyase of Bacillus subtilis is inactivated by 2-[(4-bromo-2,3-dioxobutyl)thio]adenosine 5'-monophosphate (2-BDB-TAMP) at pH 7.0. As the reagent concentration is increased, a maximum rate constant is approached, indicative of reversible enzyme-reagent complex formation (KR = 68 +/- 9 microM) prior to irreversible modification (kmax = 0.081 +/- 0.004 min-1). Complete inactivation occurs concomitant with about 1 mol of 2-BDB-[14C]TAMP incorporated/mol of enzyme subunit. Adenylosuccinate, or a combination of AMP and fumarate, decreases the inactivation rate and reduces incorporation of [14C] reagent, whereas either AMP or fumarate alone is much less effective. These observations suggest that 2-BDB-TAMP attacks the adenylosuccinate binding site. Proteolytic digestion of inactivated enzyme, followed by purification of the digest by HPLC, yields the radioactive peptide Ile62-Ala72, in which Arg67 and His68 are the most likely targets. Thus 2-BDB-TAMP reacts with adenylosuccinate lyase at a site distinct from the His141 attacked by 6-BDB-TAMP (Lee, Worby, Dixon, and Colman (1997) J. Biol. Chem. 272, 458-465). Site-directed mutagenesis was used to construct mutant enzymes with replacements for both Arg67 and His68, and either Arg67 or His68. The R67M mutant enzyme has almost the same specific activity as the wild-type enzyme under standard assay conditions, whereas the single mutant H68Q and double mutant R67M-H68Q enzymes exhibit specific activities that are decreased more than 100-fold. These results indicate that while Arg67 and His68 may both be in the region of the substrate site, only His68 is important for the catalytic activity of B. subtilis adenylosuccinate lyase. A role is proposed for His68 as a general acid-base catalyst.  相似文献   
98.
Twelve neurologically normal infants (age 2.9+/-0.9 months) with peptic esophagitis (grade 2) who did not respond to cimetidine (in addition to positioning, cisapride, and Gaviscon) were treated with omeprazole, 0.5 mg/kg once a day, for 6 weeks. The effectiveness of omeprazole was evaluated in all infants by clinical assessment and endoscopy before and after treatment and by 24-hour gastric pH monitoring during treatment in seven infants. Omeprazole therapy led to a marked decrease in symptoms, endoscopic and histologic signs of esophagitis, and intragastric acidity.  相似文献   
99.
Strongyloides stercoralis infection is of low prevalence in Malaysia. We report an unusual case presenting primarily with gastric symptoms. The patient was a 72 years old Chinese male admitted for progressive weight loss and abdominal bloating. Gastroscopic examination revealed mucosal prepyloric elevations in the gastric mucosa. Gastric strongyloidiasis was confirmed by the presence of adult forms, as well as ova and larval rhabditiform stages of the worm in the gastric mucosal crypts. We believe that this is the first histologically documented case of gastric strongyloidiasis in Malaysia.  相似文献   
100.
The study was concerned with immune response in the workers engaged in rubber manufacture which is a cancer hazard. A group of healthy donors were in control. The study group was divided into those free from carcinogen-protein adducts (CPA) and those who revealed them and, therefore, are considered at high risk for cancer. CPAs containing benzidine, 2-naphtylamine or 3-oxyanthranyl acid were assayed in blood serum. B- and T-immunity inhibition was shown to be present in both study sub-groups. A significant difference in immune response indices was established between the CPA-free and CPA-containing groups of the rubber workers. The latter group had relatively higher levels of IgA, IgM and globulins of immunocomplexes, and revealed inhibition of formation of antibody-forming cells to ovine erythrocytes following injection of CPA-containing blood serum into mice as well as relatively higher suppression of T-cell immunity in the workers at high risk.  相似文献   
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