Phosphorylation of cytosolic proteins by resting and activated human neutrophils

A study was conducted on the phosphorylation of proteins in the neutrophil cytosol in response to phorbol myristate acetate (PMA) and N- formyl-methionyl-leucyl-phenylalanine (fMLP). Autoradiography of gel electrophoretograms prepared from neutrophils incubated with 32Pi in the presence and absence of the activators showed nine proteins whose state of phosphorylation was affected by neutrophil activation. 32P was gained by eight of these proteins and was lost by the ninth. For all but one of these proteins, the change in the extent of labeling appeared to reach completion by one to two minutes. It was possible to quantitate the changes in 32P content of three of the nine proteins. One of these was the 20-kD protein that lost label when the neutrophils were activated. Quantitation showed that over half the 32P present in this protein in the resting state was gone within 0.2 minutes after activation. The other two were proteins weighing 11 and 69 kD. The phosphorylation characteristics of these two proteins differed, depending on whether activation had been carried out with PMA or fMLP. These differences in protein phosphorylation support other evidence suggesting that PMA and fMLP do not activate neutrophils by identical biochemical pathways. Differences in phosphorylation between resting and activated cells were not affected by dibutyryl cyclic guanosine monophosphate (cGMP), dibutyryl cyclic adenosine monophosphate (cAMP), theophylline, aspirin, hydrocortisone, or colchicine. The differences were abolished, however, by 30 mumol/L trifluoperazine. This finding is consistent with the hypothesis that the calcium/calmodulin system plays a biochemical role in the activation of neutrophils.     

COMP-Ang1: a designed angiopoietin-1 variant with nonleaky angiogenic activity

Angiopoietin-1 (Ang1) has potential therapeutic applications in inducing angiogenesis, enhancing endothelial cell survival, and preventing vascular leakage. However, production of Ang1 is hindered by aggregation and insolubility resulting from disulfide-linked higher-order structures. Here, by replacing the N-terminal portion of Ang1 with the short coiled-coil domain of cartilage oligomeric matrix protein (COMP), we have generated a soluble, stable, and potent Ang1 variant, COMP-Ang1. This variant is more potent than native Ang1 in phosphorylating the tyrosine kinase with Ig and epidermal growth factor homology domain 2 (Tie2) receptor and Akt in primary cultured endothelial cells, enhancing angiogenesis in vitro and increasing adult angiogenesis in vivo. Thus, COMP-Ang1 is an effective alternative to native Ang1 for therapeutic angiogenesis in vivo.     

Effect of remifentanil during drug-induced sleep endoscopy in patients with obstructive sleep apnea

Purpose

During drug-induced sleep endoscopy (DISE) in patients with obstructive sleep apnea, the increased depth of propofol anesthesia is related to the increased collapsibility of the upper airway with dose-dependent. We examined the effect of remifentanil on propofol concentration during DISE.

Methods

In a prospective randomized trial, 56 adult patients were divided into remifentanil-propofol (n?=?28) and propofol alone (n?=?28) groups. Anesthesia was administered using a target-controlled infusion system. In the remifentanil-propofol group, 0.5 ng/ml remifentanil was administered prior to propofol infusion and its concentration maintained; thereafter, in the propofol alone group, normal saline was injected instead of remifentanil. Propofol was infused at a concentration of 1.5 μg/ml after the target concentration of remifentanil was reached. In both groups, the concentration of propofol was increased by 0.5 μg/ml if the degree of sedation was not sufficient. The sedation level was targeted at observer’s assessment of alertness/sedation (OAA/S) scale 3.

Results

The mean propofol concentration was 2.87?±?0.60 μg/ml in the remifentanil-propofol group, which was lower than that in the propofol alone group (3.38?±?0.72 μg/ml, P?<?0.001). The time until sufficient sedation to perform DISE was shorter in the remifentanil-propofol group (P?<?0.001). Apnea-hypopnea index and the lowest peripheral capillary oxygen saturation (SpO₂) during polysomnography showed no statistical difference between groups (P?>?0.05). The lowest SpO₂ and VOTE classification during DISE were also not statistically different (P?>?0.05).

Conclusions

Use of remifentanil during DISE reduces the target concentration of propofol required for patient sedation to perform DISE without respiratory depression.

     

Role of adenosine receptors in regulating chemotaxis and cytokine production of plasmacytoid dendritic cells

Plasmacytoid dendritic cells (PDCs) are potent regulators of immune function and the major source of type I interferon (IFN) following viral infection. PDCs are found at sites of inflammation in allergic reactions, autoimmune disorders, and cancer, but the mechanisms leading to the recruitment of PDCs to these sites remain elusive. During inflammation, adenosine is released and functions as a signaling molecule via adenosine receptors. This study analyzes adenosine receptor expression and function in human PDCs. Adenosine was found to be a potent chemotactic stimulus for immature PDCs via an A(1) receptor-mediated mechanism. The migratory response toward adenosine was comparable to that seen with CXCL12 (stromal-derived factor-1 alpha [SDF-1 alpha), the most potent chemotactic stimulus identified thus far for immature PDCs. Upon maturation, PDCs down-regulate the A(1) receptor, resulting in a loss of migratory function. In contrast, mature PDCs up-regulate the A(2a) receptor, which is positively coupled to adenylyl cyclase and has been implicated in the down-regulation of DC cytokine-producing capacity. We show that in mature PDCs adenosine reduces interleukin-6 (IL-6), IL-12, and IFN-alpha production in response to CpG oligodeoxynucleotides (ODN). These findings indicate that adenosine may play a dual role in PDC-mediated immunity by initially recruiting immature PDCs to sites of inflammation and by subsequently limiting the extent of the inflammatory response induced by mature PDCs by inhibiting their cytokine-producing capacity.     

Physiologic Characteristics and Clinical Outcomes of Patients With Discordance Between FFR and iFR

ObjectivesThis study evaluated the physiologic characteristics of discordant lesions between instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR) and the prognosis at 5 years.BackgroundFFR or iFR have been standard methods for assessing the functional significance of coronary artery stenosis. However, limited data exist about the physiologic characteristics of discordant lesions and the prognostic implications resulting from these lesions.MethodsA total of 840 vessels from 596 patients were classified according to iFR and FFR; high iFR–high FFR (n = 580), low iFR–high FFR (n = 40), high iFR–low FFR (n = 69), and low iFR–low FFR (n = 128) groups, which were compared with a control group (n = 23). The differences in coronary circulatory indices including the coronary flow reserve (CFR), index of microcirculatory resistance (IMR), and resistance reserve ratio (RRR) (resting distal arterial pressure × mean transit time / hyperemic distal arterial pressure × hyperemic mean transit time), which reflect the vasodilatory capacity of coronary microcirculation, were compared. Patient-oriented composite outcomes (POCO) at 5 years including all-cause death, any myocardial infarction, and any revascularization were compared among patients with deferred lesions.ResultsIn the low iFR–high FFR group, CFR, RRR, and IMR measurements were similar to the low iFR–low FFR group: CFR 2.71 versus 2.43 (p = 0.144), RRR 3.36 versus 3.68 (p = 0.241), and IMR 18.51 versus 17.38 (p = 0.476). In the high iFR–low FFR group, the CFR, RRR, and IMR measurements were similar to the control group: CFR 2.95 versus 3.29 (p = 0.160), RRR 4.28 versus 4.00 (p = 0.414), and IMR 17.44 versus 17.06 (p = 0.818). Among the 4 groups, classified by iFR and FFR, CFR and RRR were all significantly different, except for IMR. However, there were no significant differences in the rates of POCO, regardless of discordance between the iFR and FFR. Only the low iFR–low FFR group had a higher POCO rate compared with the high iFR–high FFR group (adjusted hazard ratio: 2.46; 95% confidence interval: 1.17 to 5.16; p = 0.018).ConclusionsDifferences in coronary circulatory function were found, especially in the vasodilatory capacity between the low iFR–high FFR and high iFR–low FFR groups. FFR–iFR discordance was not related to an increased risk of POCO among patients with deferred lesions at 5 years. (Clinical, Physiological and Prognostic Implication of Microvascular Status; NCT02186093; Physiologic Assessment of Microvascular Function in Heart Transplant Patients; NCT02798731)     

Prevalence, awareness, treatment, control and risk factors of hypertension in Korea: the Ansan study

OBJECTIVES: To determine prevalence, awareness, treatment, and control of hypertension, and its risk factors in an urban Korean population. DESIGN AND SETTING: A cross-sectional survey in Ansan-city, Korea. SUBJECTS AND METHODS: Population-based samples of people aged 18-92 years in Ansan-city, Korea, were selected, yielding 2278 men and 1948 women, and their blood pressures were measured using a highly standardized protocol. Hypertension was defined as a systolic BP > or = 140 mmHg or diastolic BP > or = 90 mmHg or reported treatment with antihypertensive medications, and subclassified according to 1999 WHO-ISH guidelines. Isolated systolic hypertension (ISH) defined as a systolic BP > or = 140 mmHg and diastolic BP < 90 mmHg was also examined. Data were stratified by age and sex. RESULTS: The overall prevalence of hypertension in this study was 33.7%. Among these, 64.9% had Grade 1 hypertension, 22.5% Grade 2, and 12.5% Grade 3. Age-specific prevalence of hypertension increased progressively with age, from 14.19% in 18 to 24 year-olds to 71.39% in those 75 years or older. Hypertension prevalence was significantly higher in men (41.5%) than in women (24.5%) (P < 0.001). Isolated systolic hypertension had significantly lower prevalence (4.33%) within the population, although in the elderly aged 55 years or more it rose by 11.13%. Overall, 24.6% of hypertensive individuals were aware that they had high blood pressure, as much as 78.6% were being treated with antihypertensive medications, and 24.3% were under control. Hypertension awareness as well as treatment and control rates varied by sex, with women higher in all three rates. Multivariate analysis revealed that age, body mass index and abdomen circumference were significantly associated with prevalence of hypertension both in men and women. CONCLUSIONS: Hypertension is highly prevalent in Korea. Despite the high rate of treatment, the rates of awareness and control are relatively low, suggesting the nationwide demand for preventing and controlling high blood pressure in Korea in order to avert an epidemic of cardiovascular disease.     

Oncogenic osteomalacia associated with mesenchymal tumour detected by indium-111 octreotide scintigraphy

In a 40-year-old man who had suffered from vague and generalized bone pains for 7 years due to oncogenic osteomalacia, the causative tumour was finally detected by Indium-111 octreotide scintigraphy. Some characteristics of the tumour associated with oncogenic osteomalacia, such as its size, growth rate, location and origin, often make the diagnosis difficult. However, the recent discovery of somatostatin receptors in mesenchymal tumours, which are the most common cause of oncogenic osteomalacia, has raised the possibility of early detection of this devastating disorder. Here, we report that radiolabelled octreotide scintigraphy has a potential role as a diagnostic tool in oncogenic osteomalacia. However, the exact role of somatostatin receptors in tumours associated with oncogenic osteomalacia still remains elusive.     

The effect of psychosocial factors on outcomes of cochlear implantation

Conclusion: Psychosocial factors should be considered during cochlear implantation (CI). There were differences in psychosocial characteristics according to the etiology of deafness. The outcomes may be affected by psychosocial variables such as the severity of mental distress and social problems as well as duration of deafness. Objective: To evaluate the psychosocial characteristics of deaf people undergoing CI and to determine which psychosocial factors affect performance after CI. Methods: A total of 289 subjects who underwent CI were enrolled. The participants were classified into prelingually deaf (pre-LD) and postlingually deaf groups (post-LD), including progressive and sudden deafness subgroups. The Minnesota Multiphasic Personality Inventory (MMPI) was administered before CI to measure psychosocial and emotional problems. To measure CI outcomes, speech perception ability was assessed by the open-set Korean version of the Central Institute of Deafness (K-CID) test and categories of auditory performance (CAP) scores before and after CI. Results: Approximately 45% of subjects experienced psychological problems before undergoing CI. Subjects in the Pre-LD group had more psychosocial distress and were more likely to be oversensitive in interpersonal situations, while those in the post-LD group were more depressed. Deafness duration and psychosocial factors significantly predicted hearing ability after CI. Deafness duration directly and indirectly affected the outcome of CI. That is, duration of deafness caused psychosocial problems, which may have resulted in negative effects on outcomes of CI.