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21.
Nilana MT Barros Raquel L Neves William N Addison Diego M Assis Monzur Murshed Adriana K Carmona Marc D McKee 《Journal of bone and mineral research》2013,28(3):688-699
X‐linked hypophosphatemia (XLH/HYP)—with renal phosphate wasting, hypophosphatemia, osteomalacia, and tooth abscesses—is caused by mutations in the zinc‐metallopeptidase PHEX gene (phosphate‐regulating gene with homologies to endopeptidase on the X chromosome). PHEX is highly expressed by mineralized tissue cells. Inactivating mutations in PHEX lead to distal renal effects (implying accumulation of a secreted, circulating phosphaturic factor) and accumulation in bone and teeth of mineralization‐inhibiting, acidic serine‐ and aspartate‐rich motif (ASARM)‐containing peptides, which are proteolytically derived from the mineral‐binding matrix proteins of the SIBLING family (small, integrin‐binding ligand N‐linked glycoproteins). Although the latter observation suggests a local, direct matrix effect for PHEX, its physiologically relevant substrate protein(s) have not been identified. Here, we investigated two SIBLING proteins containing the ASARM motif—osteopontin (OPN) and bone sialoprotein (BSP)—as potential substrates for PHEX. Using cleavage assays, gel electrophoresis, and mass spectrometry, we report that OPN is a full‐length protein substrate for PHEX. Degradation of OPN was essentially complete, including hydrolysis of the ASARM motif, resulting in only very small residual fragments. Western blotting of Hyp (the murine homolog of human XLH) mouse bone extracts having no PHEX activity clearly showed accumulation of an ~35 kDa OPN fragment that was not present in wild‐type mouse bone. Immunohistochemistry and immunogold labeling (electron microscopy) for OPN in Hyp bone likewise showed an accumulation of OPN and/or its fragments compared with normal wild‐type bone. Incubation of Hyp mouse bone extracts with PHEX resulted in the complete degradation of these fragments. In conclusion, these results identify full‐length OPN and its fragments as novel, physiologically relevant substrates for PHEX, suggesting that accumulation of mineralization‐inhibiting OPN fragments may contribute to the mineralization defect seen in the osteomalacic bone characteristic of XLH/HYP. © 2013 American Society for Bone and Mineral Research. 相似文献
22.
Gina Shetty BS Georgia M. Beasley MD Sara Sparks BS MT ASCP Michael Barfield MD Melanie Masoud BS Paul J. Mosca MD PhD Scott K. Pruitt MD PhD April K. S. Salama MD Cliburn Chan MD PhD Douglas S. Tyler MD Kent J. Weinhold PhD 《Annals of surgical oncology》2013,20(4):1128-1135
Background
Preprocedure clinical and pathologic factors have failed to consistently differentiate complete response (CR) from progressive disease (PD) in patients after isolated limb infusion (ILI) with melphalan for unresectable in-transit extremity melanoma.Methods
Multiplex immunobead assay technology (Milliplex MAP Human Cytokine/Chemokine Magnetic Bead Panel, Millipore Corp., Billerica, MA; and Magpix analytical test instrument, Luminex Corp., Austin, TX) was performed on pre-ILI plasma to determine concentrations of selected cytokines (MIP-1α, IL-1Rα, IP-10, IL-1β, IL-1α, MCP-1, IL-6, IL-17, EGF, IL-12p40, VEGF, GM-CSF, and MIP-1β) on a subset of patients (n = 180) who experienced CR (n = 23) or PD (n = 24) after ILI. Plasma from normal donors (n = 12) was also evaluated.Results
Of 180 ILIs performed, 28 % (95 % confidence interval 22–35, n = 50) experienced a CR, 14 % (n = 25) experienced a partial response, 11 % (n = 21) had stable disease, 34 % (n = 61) had PD, and 13 % (n = 23) were not evaluable for response. Tumor characteristics and pharmacokinetics appeared similar between CR (n = 23) and PD (n = 24) patients who underwent cytokine analysis. Although there were no differences in cytokine levels between CR and PD patients, there were differences between the melanoma patients and controls. MIP-1α, IL-1Rα, IL-1β, IL-1α, IL-17, EGF, IL-12p40, VEGF, GM-CSF, and MIP-1β were significantly higher in normal controls compared to melanoma patients, while IP-10 was lower (p < 0.001) in controls compared to melanoma patients.Conclusions
Patients with unresectable in-transit melanoma appear to have markedly decreased levels of immune activating cytokines compared to normal healthy controls. This further supports a potential role for immune-targeted therapies and immune monitoring in patients with regionally advanced melanoma. 相似文献23.
Yu Ueda PhD Satoru Takahashi MD PhD Naoki Ohno PhD Katsusuke Kyotani RT Hideaki Kawamitu MS Tosiaki Miyati PhD Nobukazu Aoyama RT Yoshiko Ueno MD PhD Kazuhiro Kitajima MD PhD Fumi Kawakami MD Tomoyuki Okuaki MS Ryuko Tsukamoto MT Emmy Yanagita MT Kazuro Sugimura MD PhD 《Journal of magnetic resonance imaging : JMRI》2016,43(1):138-148
24.
25.
JL Adams M Murray N Patel MT Sawkin RC Boardman C Pham H Kaur D Patel JL Yager L Pontiggia J Baxter 《HIV medicine》2021,22(1):28-36
26.
Gastroesophageal pH step-up inaccurately locates proximal border of lower esophageal sphincter 总被引:3,自引:0,他引:3
Huitt E. Mattox III MD Dr. Joel E. Richter MD Jane W. Sinclair PA-C Jean E. Price MT L. Douglas Case PhD 《Digestive diseases and sciences》1992,37(8):1185-1191
Limiting the widespread use of 24-hr pH monitoring is the necessity of manometrically placing the pH probe 5 cm above the proximal lower esophageal sphincter (LES) border. Therefore, we prospectively compared LES localization by gastroesophageal pH step-up with manometry in 71 patients and 14 asymptomatic volunteers. The gastroesophageal pH step-up significantly correlated with the proximal LES border in patients (r=0.53, P<0.0001) and volunteers (r=0.91, P<0.0001). Based on previously published criteria, the pH step-up value was considered acceptably accurate if it was within ±3 cm (6 cm total span) of the manometrically determined proximal LES border. In 58% of patients and 29% of volunteers the pH step-up occurred outside this accuracy range. Esophagitis (P=0.015) and abnormal reflux parameters (P=0.002) were variables contributing to this error. Subsequent analysis found that the pH step-up overestimated the proximal LES border and occurred at the midportion of the sphincter. The pH step-up still inaccurately located the mid LES in 34% of patients. Therefore, manometry should remain the standard for accurate LES localization prior to placing the pH probe. 相似文献
27.
Dr J. Donald Ostrow MD Carl A. Mulvaney John R. Hansell Robert S. Rhodes Patricia Weigand MT 《Digestive diseases and sciences》1973,18(11):930-940
In 20 healthy volunteers ingesting 5 to 50 ml of51Cr-red cells, reaction intensities obtained with four chemical methods for fecal occult blood were compared with the “true” blood loss simultaneously determined by radioassay of each stool. Dilute tincture of guaiac reagent was found to have the same sensitivity and high frequency of false-positive reactions as the saturated guaiac reagent, but was more reproducible. HematestTM was slightly less sensitive but was poorly reproducible and yielded frequent false-negative as well as false-positive reactions. False-positive reactions by both methods were not eliminated by a meat-free diet; they were increased with guaiac reagents if stools were stored for 3 or more days. A new guaiac method (HemoccultTM) was found to be one-fourth as sensitive as the older tests, but was virtually free from false-positive reactions, even on an unrestricted diet and after storage of the stool specimens. It is recommended that the use of Hematest be abandoned and that Hemoccult be used preferentially if future studies confirm that its sensitivity is sufficient to detect most gastrointestinal lesions which are yielding occult blood. 相似文献
28.
Y.H. Chung MD W.H. Kim MD J.J. Lee MD PhD S.-I. Yang MD S.H. Lim MT D.W. Seo MD PhD K. Park MD PhD I.S. Chung MD PhD 《Der Anaesthesist》2014,63(2):122-128
Aim
The aim of the present study was to determine (1) whether successful intraoperative electromyography monitoring for lateral spread response (LSR) is possible with partial neuromuscular blockade (NMB) in subjects undergoing microvascular decompression (MVD) for hemifacial spasm and (2) the adequate level of NMB to achieve that goal.Material and methods
A total of 61 patients in whom LSR was monitored during MVD were enrolled in the study. Patients were randomly allocated to two groups: group TOF in which the NMB target was maintenance of two train-of-four (TOF) counts and group T1 in which the NMB target was maintenance of a T1/Tc ratio of 50?% (T1: first twitch height of TOF and Tc: control twitch height). The adductor pollicis brevis muscle was used to monitor TOF responses. The frequency of successful LSR monitoring, defined as successful baseline establishment and maintenance of LSR until surgical decompression, was compared between the two groups.Results
Of the 61 patients 2 were excluded from the study so that 30 patients in group TOF and 29 patients in group T1 were analyzed. The success rate of LSR monitoring was clinically acceptable and significantly higher in group T1 than in group TOF, i.e. n?=?15 (50.0?%) in group TOF versus n?=?24 (82.8?%) in group T1 (P?=?0.008), corresponding to a 32.8?% higher success rate in group T1 than group TOF (95?% CI: 13.9–51.7?%). Mean vecuronium infusion dose was smaller and mean TOF count was higher in group T1 than group TOF with a TOF count =?2 (1) in group TOF versus 3 (1) in group T1 (P?=?0.003). Mean sevoflurane and remifentanil infusion doses were not different between groups. There was no incidence of spontaneous movement during microscopy in either group.Conclusion
Maintenance of partial NMB with a target T1/Tc ratio of 50?% resulted in a clinically acceptable success rate of LSR monitoring and surgical condition during MVD. Maintenance of partial NMB with a target T1/Tc ratio of 50?% rather than TOF count of two during LSR monitoring for MVD can therefore be recommended. 相似文献29.
Strenuous exercise promotes changes in salivary IgA and can be associated with a high incidence of upper respiratory tract Infections. However, moderate exercise enhances immune function. The effect of exercise on salivary IgA has been well studied, but its effect on other immunological parameters is poorly studied. Thus, this study determined the effect of moderate acute exercise on immunological salivary parameters, such as the levels of cytokines (TGF‐β and IL‐5), IgA, α‐amylase and total protein, over 24 h. Ten male adult subjects exercised for 60 min at an intensity of 70% VO2 peak. Saliva samples were collected before (‘basal’) and 0, 12 and 24 h after an exercise session. The total salivary protein was lower after 12 and 24 h than immediately after exercise, whereas α‐amylase increased at 12 and 24 h after exercise compared with basal levels. The IgA concentration was increased at 24 h after exercise relative to immediately after exercise, and there was no difference in the IL‐5 while TGF‐β concentration increased in recovery. In conclusion, 70% VO2 peak exercise does not induce changes immediately after exercise, but after 24 h, it produces an increase in salivary TGF‐β without changing IL‐5. 相似文献
30.
APIC Research Committee Deborah Coleman M.S. R.N. C.S. Chairman Brian Cooper M.D. Joseph Gadsberry Ph.D. Eddie Hedrick B.S. MT CIC Elaine Larson R.N. Ph.D. FAAN Barbara Terry R.N. B.S.N. 《American journal of infection control》1987,15(6)
The JCAH move to evaluate clinical outcomes as part of its ongoing accreditation process has significant implications for infection control, APIC, and research. Through a concerted, progressive plan to address this issue, APIC can be a pathfinder in helping to prepare its members for this change. A proactive approach to both continued input into the process and the initiation of research to establish the groundwork are clearly indicated. 相似文献