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Siavash H Lopes M Norris K Hebert C Nikitakis N Sauk JJ 《Connective tissue research》2002,43(4):589-594
CBP2/Hsp47 is a glycoprotein normally limited to the ER-Golgi where it is first associated with procollagen chains at a very early point during translation of nascent chains and later with properly folded procollagen. Although CBP2/Hsp47 is regarded as a molecular chaperone belonging to the serpin superfamily, this protein does not appear to inhibit serine proteinases. Here we demonstrate that CBP2/Hsp47 functions in a manner similar to other serpin superfamily members by cross class inhibiting cysteine proteinases. A CBP2/Hsp47 to cathepsin L inactivation stoichiometery of approximately 1.5 revealed concurrent cleavage of CBP2/Hsp47 with proteinase inactivation. Cleavage of the CBP2/Hsp47 was shown to occur outside the P1-P1' at the P16-P15 and P2'-P3' bonds. In addition, the proteinase bands in SDS/PAGE diminished on reaction of the enzyme with CBP2/Hsp47. These results sustain a mechanism advocated by Bjork et al. (1998), in which cysteine proteinases assault a peptide bond in the reactive site loop of serpins, (CBP2/Hsp47) adjacent to the P1-P1' bonds involved in serine proteinase inhibition. The reaction proceeds with the substrate pathway dominating in the cysteine proteinase reaction. In these complexes the cysteine proteinases, papain and cathepsin L, are rendered more susceptible to proteolysis and are degraded by active enzyme. These properties help explain the mechanism by which CBP2/Hsp47 increases the fidelity of collagen production. Moreover, if CBP2/Hsp47 is shown to involve the multiplexin subclass of collagens, it may further provide a mechanism by which the motogen and angiogenic properties during development and/or neoplasia are regulated. 相似文献
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Kitty Pavlakis Panteleimon Kountourakis Efstathios Stathopoulos Amanda Psyrri Dimitra Rontogianni Maria Kafousi Maria Derivianaki Nikolaos Xiros Dimitrios Pectasides Theofanis Economopoulos 《Applied immunohistochemistry & molecular morphology》2007,15(4):441-445
This study was sought to evaluate the relationship between Her-2 protein expression, cellular localization, gene amplification, and other clinicopathologic parameters in colorectal carcinomas. Her-2 protein expression and gene amplification were assessed in paraffin sections from 106 primary colorectal adenocarcinoma cases using immunohistochemistry and fluorescence in situ hybridization. Both membranous and cytoplasmic immunostaining was evaluated. The results were correlated with each other and with tumor grade, stage, and overall survival. Membranous and cytoplasmic protein expression was identified in 6 (5.6%) and 13 (12.26%) cases, respectively. Gene amplification was detected in 4 (3.7%) cases. There was a high concordance between membranous protein expression and gene amplification (kappa=0.791). No apparent association with any of the clinicopathologic parameters was identified. Membranous Her-2 protein expression and gene amplification are encountered in a small subset of colorectal carcinomas and are highly concordant events. Cytoplasmic protein expression might be either artifactual or it might represent a cross-reacting protein or a precursor form of the mature protein. 相似文献
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Somasundaram P Ren G Nagar H Kraemer D Mendoza L Michael LH Caughey GH Entman ML Frangogiannis NG 《The Journal of pathology》2005,205(1):102-111
Mast cells and macrophages infiltrate healing myocardial infarcts and may play an important role in regulating fibrous tissue deposition and extracellular matrix remodelling. This study examined the time-course of macrophage and mast cell accumulation in healing infarcts and studied the histological characteristics and protease expression profile of mast cells in a canine model of experimental infarction. Although macrophages were more numerous than mast cells in infarct granulation tissue, macrophage density decreased during maturation of the scar, whereas mast cell numbers remained persistently elevated. During the inflammatory phase of infarction, newly recruited leucocytes infiltrated the injured myocardium and appeared to be clustered in close proximity to degranulating cardiac mast cells. During the proliferative phase of healing, mast cells had decreased granular content and were localized close to infarct neovessels. In contrast, macrophages showed no selective localization. Mast cells in healing canine infarcts were alcian blue/safranin-positive cells that expressed both tryptase and chymase. In order to explain the pro-inflammatory and angiogenic actions of tryptase--the major secretory protein of mast cells--its effects on endothelial chemokine expression were examined. Chemokines are chemotactic cytokines that play an important role in leucocyte trafficking and angiogenesis and are highly induced in infarcts. Tryptase, a proteinase-activated receptor (PAR)-2 agonist, induced endothelial expression of the angiogenic chemokines CCL2/MCP-1 and CXCL8/IL-8, but not the angiostatic chemokine CXCL10/IP-10. Endothelial PAR-2 stimulation with the agonist peptide SLIGKV induced a similar chemokine expression profile. Mast cell tryptase may exert its angiogenic effects in part through selective stimulation of angiogenic chemokines. 相似文献
25.
Andrew M Passam Alexandros Zafiropoulos Spiros Miyakis Ioannis Zagoreos Nikolaos G Stavrianeas Elias Krambovitis Demetrios A Spandidos 《Journal of clinical virology》2005,34(4):302-309
BACKGROUND: The chemokine receptor polymorphisms CCR5Delta32, CXCL12 3'A, CCR2-64I and CCR5-59029 G/A have been demonstrated to affect HIV-1 infection and progression. OBJECTIVE: We studied the impact of the above polymorphisms on the effectiveness of a 30-month treatment with highly active antiretroviral therapy (HAART) in 149 HIV-1 patients. STUDY DESIGN: We stratified the patients according to CD4 CDC criteria and applied Kaplan-Meier analysis using the following end-point criteria: (a) the time from HAART initiation to undetectable viral load (VL) counts (VL<50 copies/ml), (b) the duration of undetectable VL status and (c) the time required for CD4+ T-cell counts to pass over the 500 cells/ml threshold. RESULTS: Our results in the second group (CD4 201-500) revealed that patients with the CCR2-64I allele achieved undetectable VL counts at 3.5+/-0.48 months as compared to 10.26+/-1.42 months in the control group (p=0.018). The VL remained undetectable for 28+/-2 months, in contrast to 20+/-2 months in the control group (p=0.048). Patients carrying CXCL12 3'A restored the CD4 population faster than the control group (9+/-2 and 14+/-2 months, respectively, p=0.023). The CCR5Delta32 and CCR5-59029 G/A alleles did not appear to affect the parameters studied. CONCLUSIONS: Our results suggest that patients carrying either CCR2-64I or CXCL12 3'A have a more favorable prognosis during HAART treatment. 相似文献
26.
Nikolaos Karamanis Georgia Stamatiou Dionysia Vasdeki Nikolaos Sakellaridis Konstantinos C. Xarchas Sokratis Varitimidis Zoe H. Dailiana 《Journal of hand and microsurgery》2021,13(2):95
Introduction Wide awake open carpal tunnel decompression is a procedure performed under local anesthesia. This study aimed to present the effect of various local anesthetics in peri and postoperative analgesia in patients undergoing this procedure. Materials and Methods A total of 140 patients, with 150 hands involved, underwent carpal tunnel release under local anesthesia. Patients were divided in five groups according to local anesthetic administered: lidocaine 2%, ropivacaine 0.75%, ropivacaine 0.375%, chirocaine 0.5%, and chirocaine 0.25%. Total 400 mg of gabapentin were administered to a subgroup of 10 cases from each group (50 cases totally), 12 hours before surgery. Patients were evaluated immediately, 2 weeks and 2 months after surgery according to VAS pain score, grip strength, and two-point discrimination. Results In all patients, pain and paresthesia improved significantly postoperatively, while the use of gabapentin did not affect outcomes. Grip strength recovered and exceeded the preoperative value 2 months after surgery, without any difference between the groups. No case of infection, hematoma, or revision surgery was reported. Conclusion Recovery after open carpal tunnel release appears to be irrelevant of the type of local anesthetic used during the procedure. Solutions of low local anesthetic concentration (lidocaine 2%, ropivacaine 0.375%, and chirocaine 0.25%) provide adequate intraoperative analgesia without affecting the postoperative course. 相似文献
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Nikolaos Athanasiou Katerina Baou Eleni Papandreou Georgia Varsou Anastasia Amfilochiou Elisavet Kontou Athanasia Pataka Konstantinos Porpodis Ioanna Tsiouprou Evangelos Kaimakamis Serafeim-Chrysovalantis Kotoulas Evgenia Katsibourlia Christina Alexopoulou Izolde Bouloukaki Meropi Panagiotarakou Aspasia Dermitzaki Nikolaos Charokopos Kyriakh Pagdatoglou Kallirroi Lamprou Sofia Pouriki Foteini Chatzivasiloglou Zoi Nouvaki Alexandra Tsirogianni Ioannis Kalomenidis Paraskevi Katsaounou Emmanouil Vagiakis 《Journal of sleep research》2023,32(1):e13656
Growing evidence suggests that sleep could affect the immunological response after vaccination. The aim of this prospective study was to investigate possible associations between regular sleep disruption and immunity response after vaccination against coronavirus disease 2019 (COVID-19). In total, 592 healthcare workers, with no previous history of COVID-19, from eight major Greek hospitals were enrolled in this study. All subjects underwent two Pfizer–BioNTech messenger ribonucleic acid (mRNA) COVID-19 vaccine BNT162b2 inoculations with an interval of 21 days between the doses. Furthermore, a questionnaire was completed 2 days after each vaccination and clinical characteristics, demographics, sleep duration, and habits were recorded. Blood samples were collected and anti-spike immunoglobulin G antibodies were measured at 20 ± 1 days after the first dose and 21 ± 2 days after the second dose. A total of 544 subjects (30% males), with median (interquartile range [IQR]) age of 46 (38–54) years and body mass index of 24·84 (22.6–28.51) kg/m2 were eligible for the study. The median (IQR) habitual duration of sleep was 6 (6–7) h/night. In all, 283 participants (52%) had a short daytime nap. In 214 (39.3%) participants the Pittsburgh Sleep Quality Index score was >5, with a higher percentage in women (74·3%, p < 0.05). Antibody levels were associated with age (r = −0.178, p < 0.001), poor sleep quality (r = −0.094, p < 0.05), insomnia (r = −0.098, p < 0.05), and nap frequency per week (r = −0.098, p < 0.05), but after adjusting for confounders, only insomnia, gender, and age were independent determinants of antibody levels. It is important to emphasise that insomnia is associated with lower antibody levels against COVID-19 after vaccination. 相似文献
30.
In this paper we use nonparametric mathematical programming models to compute and decompose Malmquist indices of productivity and quality change, which are used to evaluate the reforms in the UK National Health Service in the early nineties. We focus on acute hospitals and we study them over the first five years of the reforms. The findings of the study indicate that there was a productivity slowdown in the first year after the reforms but productivity progress in the subsequent years and thus, overall there was a net gain in productivity over the entire period considered. Productivity trends were dominated by technical change rather than hospital relative efficiency changes, as hospitals were already largely relatively efficient at the time of the introduction of the reforms. In fact, over the last four years in the period studied there was small relative efficiency regress and this does not bear out the argument that the reforms would increase hospital efficiency. The productivity changes are similar when service quality is incorporated in the analysis but the magnitude of these changes diminishes. Quality of service followed different trends to productivity change and this may have been the price for the productivity gains achieved. 相似文献