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191.
Danias PG; McConnell MV; Khasgiwala VC; Chuang ML; Edelman RR; Manning WJ 《Radiology》1997,203(3):733
192.
JP Zappulla L Wickham W Bawab XF Yang MV Storozhuk VF Castellucci L DesGroseillers 《The Journal of neuroscience》1999,19(11):4280-4292
Cell surface metallo-endopeptidases play important roles in cell communication by controlling the levels of bioactive peptides around peptide receptors. To understand the relative relevance of these enzymes in the CNS, we characterized a metallo-endopeptidase in the CNS of Aplysia californica, whose peptidergic pathways are well described at the molecular, cellular, and physiological levels. The membrane-bound activity cleaved Leu-enkephalin at the Gly3-Phe4 bond with an inhibitor profile similar to that of the mammalian neutral endopeptidase (NEP). This functional homology was supported by the molecular cloning of cDNAs from the CNS, which demonstrated that the Aplysia and mammalian NEPs share all the same amino acids that are essential for the enzymatic activity. The protein is recognized both by specific anti-Aplysia NEP (apNEP) antibodies and by the [125I]-labeled NEP-specific inhibitor RB104, demonstrating that the apNEP gene codes for the RB104-binding protein. In situ hybridization experiments on sections of the ganglia of the CNS revealed that apNEP is expressed in neurons and that the mRNA is present both in the cell bodies and in neurites that travel along the neuropil and peripheral nerves. When incubated in the presence of a specific NEP inhibitor, many neurons of the buccal ganglion showed a greatly prolonged physiological response to stimulation, suggesting that NEP-like metallo-endopeptidases may play a critical role in the regulation of the feeding behavior in Aplysia. One of the putative targets of apNEP in this behavior is the small cardioactive peptide, as suggested by RP-HPLC experiments. More generally, the presence of apNEP in the CNS and periphery may indicate that it could play a major role in the modulation of synaptic transmission in Aplysia and in the metabolism of neuropeptides close to their point of release. 相似文献
193.
Anab R Lehr Martha L McKinney Serge Gouin Jean-Guy Blais MV Pusic Francine M Ducharme 《Canadian respiratory journal》2013,20(6):435-441
BACKGROUND:
Severity-specific guidelines based on the Pediatric Respiratory Assessment Measure (PRAM), a validated clinical score, reduce pediatric asthma hospitalization rates.OBJECTIVE:
To develop, pretest the educational value of and revise an electronic learning module to train health care professionals on the use of the PRAM.METHODS:
The respiratory efforts of 32 children with acute asthma were videotaped and pulmonary auscultation was recorded. A pilot module, composed of a tutorial and 18 clinical cases, was developed in French and English. Health care professionals completed the module and provided feedback. The performance of participants, case quality and difficulty, and learning curve were assessed using the Rasch test; quantitative and qualitative feedback served to revise the module.RESULTS:
Seventy-two participants (19 physicians, 22 nurses, four respiratory therapists and 27 health care trainees) with a balanced distribution across self-declared expertise (26% beginner, 35% competent and 39% expert) were included. The accuracy of experts was superior to beginners (OR 1.79, 1.15 and 2.79, respectively). Overall performance significantly improved between the first and latter half of cases (P<0.001). Participants assessed the module to be clear (96%), relevant (98%), realistic (94%) and useful (99%) to learn the PRAM. The qualitative/quantitative analysis led to the deletion of three cases, modification of remaining cases to further enhance quality and reordering within three levels of difficulty.DISCUSSION:
Using rigorous educational methods, an electronic module was developed to teach health care professionals on use of the PRAM score. Using the back-translation technique, both French and English versions were developed and validated simultaneously. The pilot module comprised a tutorial and three case-scenario sections, and was tested on a target audience of physicians, nurses, respiratory therapists and medical trainees.CONCLUSION:
The final electronic learning module met the clarity and quality requirements of a good teaching tool, with a demonstrated learning effect and high appreciation by health care professionals. Available in French and English, it is offered to facilitate implementation of PRAM-based acute pediatric asthma guidelines. 相似文献194.
195.
In the clinical setting, antidotes are generally administered after the occurrence of a drug overdose. Therefore, the most pertinent evaluation of any new agent should model human exposure. This study tested whether acetaminophen (APAP) hepatotoxicity was reversed when S-adenosyl-L-methionine (SAMe) was administered after APAP exposure, similar to what occurs in clinical situations. Comparisons were made for potency between SAMe and N-acetylcysteine (NAC), the current treatment for APAP toxicity. Male C57BL/6 mice were fasted overnight and divided into groups: control (VEH), SAMe treated (SAMe), APAP treated (APAP), N-acetylcysteine treated (NAC), SAMe or NAC administered 1h after APAP (SAMe+APAP) and (NAC+APAP), respectively. Mice were injected intraperitoneal (i.p.) with water (VEH) or 250 mg/kg APAP (15 ml/kg). One hour later, mice were injected (i.p.) with 1.25 mmol/kg SAMe (SAMe+APAP) or NAC (NAC+APAP). Hepatotoxicity was evaluated 4h after APAP or VEH treatment. APAP induced centrilobular necrosis, increased liver weight and alanine transaminase (ALT) levels, depressed total hepatic glutathione (GSH), increased protein carbonyls and 4-hydroxynonenal (4-HNE) adducted proteins. Treatment with SAMe 1h after APAP overdose (SAMe+APAP) was hepatoprotective and was comparable to NAC+APAP. Treatment with SAMe or NAC 1h after APAP was sufficient to return total hepatic glutathione (GSH) to levels comparable to the VEH group. Western blot showed reversal of APAP mediated effects in the SAMe+APAP and NAC+APAP groups. In summary, SAMe was protective when given 1h after APAP and was comparable to NAC. 相似文献
196.
197.
Clinical spectrum of clonal proliferations of T-large granular lymphocytes: a T-cell clonopathy of undetermined significance? 总被引:5,自引:4,他引:5
We identified 68 patients with clonal T-large granular lymphocyte (T- LGL) proliferations who were seen at the Mayo Clinic between 1984 and 1992. Nineteen (28%) were asymptomatic at diagnosis, while the rest experienced fatigue (60%), B-symptoms (12%), and recurrent infections (15%). Associated comorbid conditions included rheumatoid arthritis (RA) in 26%. Severe anemia (hemoglobin [Hb] < 8g/dL) and neutopenia (absolute neutrophil count [ANC] < 500/microL) were seen in 19% and 40% of patients, respectively. Immunophenotypic studies showed CD3+, CD8+ phenotype in the majority (72%). Twenty-one patients (31%) have required no therapy, and remain relatively stable with a median follow- up period of 50 months. Treatment was required at either diagnosis (36 patients) or at subsequent follow-up (11 patients). Initial response rates were similar in patients treated with cyclophosphamide (CTX) with or without prednisone (69%), or prednisone alone (73%). Overall, 61 patients (90%) are alive with a median follow-up of 44 months. Actuarial median survival of this entire cohort is 161 months. The presence of anemia or symptoms does not appear to correlate with the tumor burden. In patients requiring therapy, a lower ANC and the presence of B-symptoms/infection were independently associated with a significantly lower probability of achieving a molecular or hematologic complete remission (H-CR). Intermittent immunosuppressive therapy is effective in achieving durable responses in a number of patients. T-LGL proliferations are associated with a favorable prognosis and response to therapy. However, significant heterogeneity exists in clinical presentation and associated comorbid conditions. These disorders should be included in the differential diagnosis of patients with unexplained cytopenias, particularly in the setting of RA and other autoimmune disorders. Analogous to the situation with monoclonal gammopathies, a term such as T-cell clonopathy of undetermined significance (TCUS) may be more appropriate to describe these patients. 相似文献
198.
FN Engsig LH Omland MV Larsen LD Rasmussen T Qvist J Gerstoft N Obel 《HIV medicine》2010,11(7):457-461
Objectives
According to the Swiss Federal Commission for HIV/AIDS, HIV‐infected patients on successful antiretroviral treatment have a negligible risk of transmitting HIV sexually. We estimated the risk that patients considered to have an undetectable viral load (VL) are actually viraemic.Methods
A Danish, population‐based nationwide cohort study of HIV‐infected patients with VL <51 HIV‐1 RNA copies/mL for more than 6 months was carried out for the study period 2000–2008. The observation time was calculated from 6 months after the first VL <51 copies/mL to the last measurement of VL or the first VL >50 copies/mL. The time at risk of transmitting HIV sexually was calculated as 50% of the time from the last VL <51 copies/mL to the subsequent VL if it was >1000 copies/mL. The outcome was the time at risk of transmitting HIV sexually divided by the observation time.Results
We identified 2680 study subjects contributing 9347.7 years of observation time and 56.4 years of risk of transmitting HIV (VL>1000 copies/mL). In 0.6% [95% confidence interval (CI) 0.5–0.8%] of the overall observation time the patients had VL >1000 copies/mL. In the first 6 months this risk was substantially higher (7.9%; 95% CI 4.5–11.0%), but thereafter decreased and was almost negligible after 5 years (0.03%; 95% CI 0.0–0.2%). The risk was higher in injecting drug users, but otherwise did not differ between subgroups of patients.Conclusion
The risk of viraemia and therefore the risk of transmitting HIV sexually are high in the first 12 months of successful antiretroviral treatment, but thereafter are low. 相似文献199.
P Rao MV Schaverien KJ Stewart 《Annals of the Royal College of Surgeons of England》2010,92(4):320-325