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101.
Regulation of Rat Liver Glutamine Synthetase: Activation by α-Ketoglutarate and Inhibition by Glycine, Alanine, and Carbamyl Phosphate
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Suresh S. Tate Alton Meister 《Proceedings of the National Academy of Sciences of the United States of America》1971,68(4):781-785
Rat liver glutamine synthetase (s(20,w) 15.0 S; MW about 352,000) resembles ovine brain glutamine synthetase in that it (a) has 8 subunits, (b) acts on both L- and D-glutamate and certain glutamate analogs (e.g., beta-glutamate, cis-cycloglutamate, and alpha-methyl-L-glutamate), and (c) is irreversibly inhibited by L-methionine-S-sulfoximine. The liver enzyme (but not the brain enzyme) is (a) markedly activated by alpha-ketoglutarate and less so by citrate, and (b) inhibited noncumulatively by glycine and alanine, in the presence of Mn(++) but not Mg(++); inhibition increases with increasing concentrations of glutamate. These regulatory phenomena seem to be correlated with metabolically related enzymes, e.g., glutamine transaminase. Both liver and brain glutamine synthetases are inhibited by carbamyl phosphate (with Mn(++) but not with Mg(++)), which provides a means for controlling glutamine for pyrimidine biosynthesis. Addition of Mn(++) to the Mg(++)-synthetase system, even at Mg(++): Mn(++) ratios of 1000, markedly inhibits synthesis by both brain and liver enzymes. This finding, and the fact that Mn(++) promotes sensitivity to the negative effectors, indicates that Mn(++) plays a central role in the regulation of glutamine synthetase. Properties of the glutamine synthetases that have been isolated from mammalian, plant, and bacterial cells are compared. They are similar with respect to subunit size, substrate specificity, inhibition by methionine sulfoximine, and Mn(++)-sensitive inhibition by glycine, alanine, and carbamyl phosphate, but differ in certain other regulatory phenomena and in subunit structure. 相似文献
102.
Kath Padgett BSc MA PGDip Cert Ed RMN Christine Rhodes BSc MSc RGN RM RN Child RHV Maureen Lumb Penny Morris BA Sue Sherwin BA MA PGCHE RMN Jools Symons BA MA Joannie Tate Ken Townend 《Health expectations》2014,17(3):418-428
Background Involving service users and carers in decisions about their health care is a key feature of health‐care practice. Professional health and social care students need to develop skills and attributes to best enable this to happen. Aims The aims were to explore service user and carer perceptions of behaviours, attributes and context required to enable shared decision making; to compare these perceptions to those of students and academic staff with a view to utilizing the findings to inform the development of student assessment tools. Methods A mixed methods approach was used including action learning groups (ALG) and an iterative process alongside a modified Delphi survey. Participants The ALGs were from an existing service user and carer network. The survey was sent to sixty students, sixty academics and 30 service users from 16 different professional disciplines, spanning four Universities in England. Results The collaborative enquiry process and survey identified general agreement that being open and honest, listening, showing respect, giving time and being up to date were important. The qualitative findings identified that individual interpretation was a key factor. An unexpected result was an insight into possible insecurities of students. Conclusions The findings indicate that distilling rich qualitative information into a format for student assessment tools could be problematic as the individual context could be lost, it is therefore proposed that the information could be better used as a learning rather than assessment tool. Several of those involved identified how they valued the process and found it beneficial. 相似文献
103.
D. F. Tate G. E. York M. W. Reid D. B. Cooper L. Jones D. A. Robin J. E. Kennedy J. Lewis 《Brain imaging and behavior》2014,8(1):102-109
Though cortical abnormalities have been demonstrated in moderate and severe traumatic brain injured (TBI) patients, there have been no studies examining cortical changes following blast related mild TBI (mTBI). The purpose of this study was to determine the effects and functional relevance of blast mTBI on cortical thickness in a small cohort of carefully screened blast injured US Service Members (SM). Twelve SM with mTBI acquired through blast injury were compared to 11 demographically matched control SM without TBI. Both mTBI and control participants were active duty and had completed a combat deployment. Subjects underwent MRI examination and the T1 weighted anatomic images were processed using the FreeSurfer suite of tools. Cortical thickness maps were compared between groups and examined for relationships with time since injury (TSI). Utilizing a large database of functional imaging results (BrainMap), significant regions of interest (ROI) were used to determine the behavioral profiles most consistently associated with the specific ROI. In addition, clinical variables were examined as part of post-hoc analysis of functional relevance. Group comparisons controlling for age demonstrated several significant clusters of cortical thinning for the blast injured SM. After multiple comparisons correction (False Discovery Rate (FDR)), two left hemisphere clusters remained significant (left superior temporal (STG) and frontal (SFG) gyri). No clusters were significantly correlated with TSI after FDR correction. Behavioral analysis for the STG and SFG clusters demonstrated three significant behavioral/cognitive sub-domains, each associated with audition and language. Blast injured SMs demonstrated distinct areas of cortical thinning in the STG and SFG. These areas have been previously shown to be associated with audition and language. Post-hoc analyses of clinical records demonstrated significant abnormal audiology reports for the blast injured SM suggesting that the thinning in these ROIs might be related to injury to the external auditory system rather than direct injury to the brain from the blast. It is clear that additional replication is needed in much larger cohorts. Importantly, the combination of imaging tools and methods in this study successfully demonstrated the potential to define unique ROIs and functional correlates that can be used to design future studies. 相似文献
104.
Mary Beth Happ Kathryn L. Garrett Judith A. Tate Dana DiVirgilio Martin P. Houze Jill R. Demirci Elisabeth George Susan M. Sereika 《Heart & lung : the journal of critical care》2014
Objective
To test the impact of two levels of intervention on communication frequency, quality, success, and ease between nurses and intubated intensive care unit (ICU) patients.Design
Quasi-experimental, 3-phase sequential cohort study: (1) usual care, (2) basic communication skills training (BCST) for nurses, (3) additional training in augmentative and alternative communication devices and speech language pathologist consultation (AAC + SLP). Trained observers rated four 3-min video-recordings for each nurse–patient dyad for communication frequency, quality and success. Patients self-rated communication ease.Setting
Two ICUs in a university-affiliated medical center.Participants
89 intubated patients awake, responsive and unable to speak and 30 ICU nurses.Main results
Communication frequency (mean number of communication acts within a communication exchange) and positive nurse communication behaviors increased significantly in one ICU only. Percentage of successful communication exchanges about pain were greater for the two intervention groups than the usual care/control group across both ICUs (p = .03) with more successful sessions about pain and other symptoms in the AAC + SLP group (p = .07). Patients in the AAC + SLP intervention group used significantly more AAC methods (p = .002) and rated communication at high difficulty less often (p < .01).Conclusions
This study provides support for the feasibility, utility and efficacy of a multi-level communication skills training, materials and SLP consultation intervention in the ICU. 相似文献105.
Ellen C. Caniglia Elizabeth R. Stevens Maria Khan Kailyn E. Young Kaoon Ban Brandon D.L. Marshall Natalie E. Chichetto Julie R. Gaither Stephen Crystal Eva Jennifer Edelman David A. Fiellin Adam J. Gordon Kendall J. Bryant Janet Tate Amy C. Justice Ronald Scott Braithwaite 《Alcoholism, clinical and experimental research》2020,44(11):2257-2265
106.
Viviane M. Gonçalves Waldely O. Dias Ivana B. Campos Celia Liberman Maria E. Sbrogio-Almeida Eliane P. Silva Celso P. Cardoso Jr. Mark Alderson George Robertson Jean-François Maisonneuve Andrea Tate Porter Anderson Richard Malley Fernando Fratelli Luciana C.C. Leite 《Vaccine》2014
Pneumococcal infections impose a large burden of disease on the human population, mainly in developing countries, and the current pneumococcal vaccines offer serotype-specific protection, but do not cover all pathogenic strains, leaving populations vulnerable to disease caused by non-vaccine serotypes. The pneumococcal whole cell vaccine is a low-cost strategy based on non-capsular antigens common to all strains, inducing serotype-independent immunity. Therefore, we developed the process for the cGMP production of this cellular vaccine. Initially, three engineering runs and two cGMP runs were performed in 60-L bioreactors, demonstrating the consistency of the production process, as evaluated by the growth curves, glucose consumption and metabolite formation (lactate and acetate). Cell recovery by tangential filtration was 92 ± 13%. We optimized the conditions for beta-propiolactone (BPL) inactivation of the bacterial suspensions, establishing a maximum cell density of OD600 between 27 and 30, with a BPL concentration of 1:4000 (v/v) at 150 rpm and 4 °C for 30 h. BPL was hydrolyzed by heating for 2 h at 37 °C. The criteria and methods for quality control were defined using the engineering runs and the cGMP Lots passed all specifications. cGMP vaccine Lots displayed high potency, inducing between 80 and 90% survival in immunized mice when challenged with virulent pneumococci. Sera from mice immunized with the cGMP Lots recognized several pneumococcal proteins in the extract of encapsulated strains by Western blot. The cGMP whole cell antigen bulk and whole cell vaccine product lots were shown to be stable for up to 12 and 18 months, respectively, based upon survival assays following i.p. challenge. Our results show the consistency and stability of the cGMP whole cell pneumococcal vaccine lots and demonstrate the feasibility of production in a developing country setting. 相似文献
107.
David Anthony Provenzano MD Nicholas Park MD Deborah Edgar PhD Chris Bovinet DO Jordan Tate MD 《Pain practice》2023,23(3):301-312
Introduction
Traditional spinal cord stimulation (t-SCS) has been used to treat chronic pain for over 50 years. However, up to 30% of patients undergo explant, with the main indication being loss of efficacy (LoE), and few alternative treatment options exist for these patients. Strategies to mitigate LoE commonly include conversion to another type of SCS (termed ‘salvage’ or ‘rescue’). This review summarizes the existing literature concerning the efficacy and safety of 10 kHz SCS as a salvage therapy.Methods
We searched PubMed, the Cochrane Library, ClinicalTrials.gov , and other sources between January 2009 and April 2021. Records were retained if the authors reported clinical outcomes with a minimum of ≥ 3 months of follow-up in patients implanted with a Senza® 10 kHz SCS system in an effort to treat t-SCS LoE.Results
Ten articles were eligible for inclusion, reporting 3 prospective studies and 7 retrospective reviews. In the single study that salvaged patients without a repeat trial prior to surgery, 81% of patients were responders (≥ 50% pain relief from baseline), with mean pain relief of 60%. Among repeat-trial studies, the responder rate ranged from 46% to 80%, and mean pain relief from 47% to 68%. No unanticipated therapy-related safety issues were reported among the included articles.Conclusion
Preliminary data suggest that chronic back and/or leg pain patients with t-SCS LoE can experience improved and durable pain relief after conversion to 10 kHz SCS. However, additional research is needed to define predictors of success and establish whether salvage without a repeat trial is a viable conversion method. 相似文献108.
109.
110.
Modesitt SC Tian C Kryscio R Thigpen JT Randall ME Gallion HH Fleming GF;Gynecologic Oncology Group 《Gynecologic oncology》2007,105(1):59-65
OBJECTIVES: To evaluate the association between body mass index (BMI) and outcomes in women with advanced or recurrent endometrial cancer treated with doxorubicin/cisplatin. METHODS: Data from patients treated on five Gynecologic Oncology Group trials were retrospectively reviewed. BMI was categorized as normal (< 25), overweight (> or = 25 to < 30), obese (> or = 30 to < 40), and morbidly obese (> or = 40). BMI was analyzed for associations with demographics, clinical characteristics, toxicity, progression-free survival (PFS), and overall survival (OS). RESULTS: Among 949 patients, 533 (56%) had recurrent disease, 227 (23.9%) had Stage IV disease, and 189 (19.9%) had Stage III disease. Mean BMI was 29.8; 29.6%, 27.0%, 33.2% and 10.2% of patients, respectively, were categorized as normal, overweight, obese, and morbidly obese. The mean BMI was significantly different when compared by age group (p<0.001), stage (p=0.047), histologic type (p=0.024), and tumor grade (p=0.014). Older patients and those with clear cell, poorly differentiated tumors, or stage IV disease had a lower BMI. No significant associations between PFS and BMI were detected. Increasing BMI was significantly associated with an increased risk of death in Stage III/IV (HR=1.86, 95% CI 1.16-2.99 for BMI > or = 40 vs. BMI < 25) but not recurrent patients. Higher BMI patients had less Grade 3/4 toxicities than normal patients (p<0.001) but this difference disappeared for obese patients receiving > or = 95% of the calculated dose. CONCLUSIONS: BMI was not predictive of PFS in this endometrial cancer population although morbidly obese patients had decreased OS in primary Stage III/IV patients. Toxicities decreased with increasing BMI, perhaps secondary to capped dosing. 相似文献