The purpose of this study was to compare the clinical efficacy and safety of vancomycin to those of teicoplanin for the treatment of adult patients with health care-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) bacteremia. A multicenter observational study was prospectively conducted in 15 teaching hospitals in Korea between February 2010 and July 2011. Adult patients (≥18 years old) with HA-MRSA bacteremia who were initially treated with vancomycin (VAN) (n = 134) or teicoplanin (TEC) (n = 56) were enrolled. Clinical and microbiological responses and drug-related adverse events were compared between the two treatment groups using univariate and multivariate logistic regression analyses. The vancomycin and teicoplanin MICs were determined by Etest. The MRSA-related mortality, duration of fever, and duration of MRSA bacteremia in the treatment groups were not significantly different. There was no significant difference in the occurrence of drug-related adverse events. Among the 190 MRSA isolates, the VAN MICs ranged from 0.5 to 2 μg/ml (MIC50 and MIC90, 1.5 μg/ml), and the TEC MIC ranged from 0.5 to 8 μg/ml (MIC50, 3 μg/ml; MIC90, 6 μg/ml). In multivariate analyses, the antibiotic type (vancomycin or teicoplanin) was not associated with treatment outcomes. This study indicates that teicoplanin is an effective and safe alternative to vancomycin for the treatment of HA-MRSA bacteremia.
Osterix (Osx) is essential for osteoblast differentiation and bone formation, because mice lacking Osx die within 1 h of birth with a complete absence of intramembranous and endochondral bone formation. Perinatal lethality caused by the disruption of the Osx gene prevents studies of the role of Osx in bones that are growing or already formed. Here, the function of Osx was examined in adult bones using the time- and site-specific Cre/loxP system. Osx was inactivated in all osteoblasts by Col1a1-Cre with the activity of Cre recombinase under the control of the 2.3-kb collagen promoter. Even though no bone defects were observed in newborn mice, Osx inactivation with 2.3-kb Col1a1-Cre exhibited osteopenia phenotypes in growing mice. BMD and bone-forming rate were decreased in lumbar vertebra, and the cortical bone of the long bones was thinner and more porous with reduced bone length. The trabecular bones were increased, but they were immature or premature. The expression of early marker genes for osteoblast differentiation such as Runx2, osteopontin, and alkaline phosphatase was markedly increased, but the late marker gene, osteocalcin, was decreased. However, no functional defects were found in osteoclasts. In summary, Osx inactivation in growing bones delayed osteoblast maturation, causing an accumulation of immature osteoblasts and reducing osteoblast function for bone formation, without apparent defects in bone resorption. These findings suggest a significant role of Osx in positively regulating osteoblast differentiation and bone formation in adult bone.
Osterix; Col1a1-Cre; osteopenia; osteoblast differentiation; adult bone formation
Despite remarkable progression in the treatment and classification system of neuroendocrine tumor (NET), some questions have remained unanswered. The lack of an established treatment strategy for gastric NET is one of the problems. Because of its paucity, gastric NET is not discussed in independent, large-scaled prospective studies and tends to be excluded from clinical trials. Moreover, a separate classification system and some distinguished clinical features render the treatment of gastric NET more complicated. Here, we present a case of a female gastric NET patient with G2 proliferation index and multiple liver metastases. Based on the histologic grade and a high serum gastrin level, we initially treated her with somatostatin analogue. However, the patient did not respond. After that, cytotoxic chemotherapy with the etoposide plus cisplatin regimen only showed response in the short-term period. However, combination therapy with octreotide and interferon brought about significant regression of the tumor. Herein, we present our case together with a literature review of the treatment of metastatic gastric NET.
Stomach; Neuroendocrine tumor; Therapy
Rett syndrome (RTT), associated with mutations in methyl-CpG-binding protein 2 (Mecp2), is linked to diverse neurological symptoms such as seizures, motor disabilities, and cognitive impairments. An altered GABAergic system has been proposed as one of many underlying pathologies of progressive neurodegeneration in several RTT studies. This study for the first time investigated the temporal- and location-specific alterations in the expression of γ-amino butyric acid (GABA) transporter 1 (GAT-1), vesicular GABA transporter (vGAT), and glutamic acid decarboxylase 67kD (GAD67) in wild type (WT) and knockout (KO) mice in the Mecp2tm1.1Bird/y mouse model of RTT. Immunohistochemistry (IHC) co-labeling of GAT-1 with vGAT identified GABAergic synapses that were quantitated for mid-sagittal sections in the frontal cortex (FC), hippocampal dentate gyrus (DG), and striatum (Str). An age-dependent increase in the expression of synaptic GABA transporters, GAT-1, and vGAT, was observed in the FC and DG in WT brains. Mecp2 KO mice showed a significant alteration in this temporal profile that was location-specific, only in the FC. GAD67-positive cell densities also showed an age-dependent increase in the FC, but a decrease in the DG in WT mice. However, these densities were not significantly altered in the KO mice in the regions examined in this study. Therefore, the significant location-specific downregulation of synaptic GABA transporters in Mecp2 KO brains with unaltered densities of GAD67-positive interneurons may highlight the location-specific synaptic pathophysiology in this model of RTT.
Rett syndrome; MeCP2 mutation; GABAergic neurons; synapse; lipofuscin; GAT-1
Mild traumatic brain injury (mTBI) is frequently associated with psychiatric symptoms and cognitive dysfunction, as well as with the receipt of workers' compensation, as many mTBIs occur due to work-related accidents. We hypothesized that depression and insufficient cognitive effort mediate the relationship between sociodemographic variables and cognitive dysfunction in mTBI.
A retrospective chart review study was conducted using 115 records of patients with mTBI. Cognitive effort was measured based on scores on the Rey 15-Item Test. Multivariate linear regression analysis was performed to examine factors predictive of cognitive functions. Path analysis was subsequently performed to investigate the mediating effects of depression and cognitive effort in relation to receipt of workers' compensation and demographic variables.
Fifteen of the 115 participants (13.0%) received failing scores on the Rey 15-Item Test, which indicated insufficient cognitive effort. Path analysis indicated that cognitive effort mediated the effects of age and workers' compensation on cognitive functions.
Given the significant mediating effects of cognitive effort on cognitive performance, it is important to address patient motivation and encourage mTBI patients covered by workers' compensation to perform tests with authentic effort.
Neuropsychological test; Brain concussion; Depression; Mental process; Compensation
Central hyperthermia is a very rare disease; however, once it happens, it is associated with a poor prognosis and high mortality for patients with severe brainstem strokes. Following a pontine hemorrhage, a 46-years-old female developed prolonged hyperthermia. Work-ups to the fever gave no significant clues for the origin of fever, and hyperthermia did not respond to any empirical antibiotics or antipyretic agents. The patient's body temperature still fluctuated in a range of 37.5℃ to 39.2℃. Considering the lesion of hemorrhage, we suspected central hyperthermia rather than infectious diseases. We started with baclofen administration at a dose of 30 mg/day. The body temperature changed to a range of 36.6℃ to 38.2℃. We raised the dose of baclofen to 60 mg/day. The patient's body temperature finally dropped to a normal range. Central hyperthermia, caused by failures of thermoregulatory pathways in brainstem, following the pontine hemorrhage rarely occurs. Baclofen can be used to treat suspected central hyperthermia in a patient with pontine hemorrhage.
Fever; Pons; Hemorrhage; Baclofen
Primary mediastinal large B-cell lymphoma (PMBL) is a distinct subtype of non-Hodgkin lymphoma, which has no consensus for its ideal treatment or prognosis.
We reviewed the clinicopathologic features and clinical outcomes of 25 PMBL cases diagnosed at a single institution between 1993 and 2009 and compared them with 588 cases of non-mediastinal, diffuse large B-cell lymphoma (DLBCL, control group) diagnosed during the same period.
Thirteen (52.0%) PMBL patients had Ann Arbor stage III or IV disease, and 10 (40.0%) had B symptoms. Thirteen (52%) PMBL patients were classified as high-intermediate/high-risk according to the International Prognostic Index. There was a significant prevalence of young (median: 31 years; range, 15-78 years; P<0.001), female (68%; P=0.014) patients in the PMBL group compared to the control group (median: 56 years; range, 15-85 years; 43.2% female). Bulky disease and elevated levels of lactate dehydrogenase (LDH) were more frequent in the PMBL group (P<0.001 and P=0.003, respectively). Nineteen (76%) PBML patients achieved complete remission, and 18 were alive at the last follow-up (median: 43 months; range, 1-92 months). There was no difference in the 3-year, overall survival rate (72%, 95% confidence interval [CI]: 54.0-83.0 versus 70.1%, 95% CI, 109.0-126.0; P=0.686) between PMBL and control patients, respectively.
Compared to patients with non-mediastinal DLBCL, Korean patients with PMBL are predominantly young women with bulky disease and high LDH levels but with no significant difference in survival.
Lymphoma; B cell; PMBL; Prognosis; Treatment
POEMS syndrome is a rare paraneoplastic syndrome associated with plasma cell dyscrasia. High-dose chemotherapy followed by autologous stem cell transplantation has shown encouraging efficacy in the treatment of patients with POEMS syndrome. However, there are minimal reports on clinical outcomes after autologous stem cell transplantation for patients with advanced disease and very poor performance status.
We retrospectively evaluated 9 advanced POEMS syndrome patients, who had an Eastern Cooperative Oncology Group performance status score of 3 or 4, and were treated with high-dose melphalan therapy followed by autologous stem cell transplantation from 2004 to 2011.
Eight patients achieved initial hematologic response, 4 of whom had complete responses. At a median follow-up of 44 months (range, 8-94 months), 7 patients were alive, with 3-year overall survival rate of 77.8%. There were no hematologic relapses in the survivors. One patient died of disease progression; the other died of pneumonia despite a hematologic response 3 months after autologous stem cell transplantation. All survivors achieved improvement in general performance status and in clinical response.
High-dose melphalan followed by autologous stem cell transplantation can be considered a valid treatment option even for patients with advanced POEMS syndrome.
POEMS syndrome; Stem cell transplantation; Chemotherapy; Severity; Illness index
To assess the effectiveness of a comprehensive workplace stress management program consisting of participatory action-oriented training (PAOT) and individual management.
A comprehensive workplace stress management program was conducted in a medium-sized enterprise. The baseline survey was conducted in September 2011, using the Korean Occupational Stress Scale (KOSS) and Worker’s Stress Response Inventory (WSRI). After implementing both organizational and individual level interventions, the follow up evaluation was conducted in November 2011.
Most of the workers participated in the organizational level PAOT and made Team-based improvement plans. Based on the stress survey, 24 workers were interviewed by a researcher. After the organizational and individual level interventions, there was a reduction of several adverse psychosocial factors and stress responses. In the case of blue-collar workers, psychosocial factors such as the physical environment, job demands, organizational system, lack of rewards, and occupational climate were significantly improved; in the case of white-collar workers, the occupational climate was improved.
In light of these results, we concluded that the comprehensive stress management program was effective in reducing work-related stress in a short-term period. A persistent long-term follow up is necessary to determine whether the observed effects are maintained over time. Both team-based improvement activities and individual interviews have to be sustainable and complementary to each other under the long-term plan.
Health promotion; Stress/psychological; Workplace; Intervention studies; Participatory action-oriented training
The purpose of this study was to explore the effect of demographic variables on Digit Span test (DS) performance in an educationally diverse elderly population and to provide normative information.
The DS was administered to 784 community-dwelling volunteers aged 60-90 years with an educational history of from zero to 25 years of full-time education. People with serious neurological, medical and psychiatric disorders (including dementia) were excluded.
Age, education and gender were found to be significantly associated with performance on the DS. Based on the results obtained, DS norms were stratified by age (2 strata), education (3 strata), and gender (2 strata).
Our results on DS performance suggest that both attention and working memory are influenced by age, education and gender. The present study provides reasonably comprehensive normative information on the DS for an educationally diverse elderly population.
Neuropsychological tests; Reference standards; Age factors; Education; Sex; Koreans
This study aimed to investigate whether the supplementation of Verbal Fluency: Animal category test (VF) performance can improve the screening ability of Mini-Mental State Examination (MMSE) for mild cognitive impairment (MCI), dementia and their major subtypes.
Six hundred fifty-five cognitively normal (CN), 366 MCI [282 amnestic MCI (aMCI); 84 non-amnestic MCI (naMCI)] and 494 dementia [346 Alzheimer's disease (AD); and 148 non-Alzheimer's disease dementia (NAD)] individuals living in the community were included (all aged 50 years and older) in the study.
The VF-supplemented MMSE (MMSE+VF) score had a significantly better screening ability for MCI, dementia and overall cognitive impairment (MCI plus dementia) than the MMSE raw score alone. MMSE+VF showed a significantly better ability than MMSE for both MCI subtypes, i.e., aMCI and naMCI. In the case of dementia subtypes, MMSE+VF was better than the MMSE alone for NAD screening, but not for AD screening.
The results support the usefulness of VF-supplementation to improve the screening performance of MMSE for MCI and NAD.
Mini-Mental State Examination; Verbal fluency; Screening accuracy; Mild cognitive impairment; Non-Alzheimer's disease dementia
The causative pathogens of and prevalence of antibiotic resistance in community-acquired pneumonia (CAP) varies across countries. We evaluated the patterns of antibiotic prescriptions for adult CAP patients, and physician satisfaction with the form and content of the 2009 Korean CAP treatment guidelines.
Materials and Methods
We designed an online survey for clinical physicians who treat CAP (infectious disease specialists, pulmonologists, and other physicians). We e-mailed the online survey to physicians and gathered results from December 2011 to January 2012, and then analyzed their responses.
A total of 157 physicians responded to our survey: 61 (38.9%) infectious disease specialists, 33 (21.0%) pulmonologists, and 63 (40.1%) other physicians. Two-thirds (96/157, 61.2%) had positions in tertiary and secondary hospitals; the others (61, 38.8%) worked in primary clinics (hospitals and private clinics). One hundred and eight (68.8%) were aware of the Korean CAP clinical guidelines; of these, 98 (62.4%) applied the guidelines to their practice. Among physicians using them, 86.7% (85/98) reported the guidelines to be most useful for empirical selection of antibiotics, and 75.2% (118/157) said the guidelines were useful and satisfactory. Sixty-eight (43.3%) respondents indicated that they had not used aminoglycosides as an initial empirical CAP treatment, while 51 (32.5%) had combined aminoglycosides with other antibiotics to treat patients with CAP. Seventy-three (46.5%) physicians often combined macrolides with β-lactam antibiotics for empirical treatment of CAP, and 21 (13.4%) reported using macrolide monotherapy (which is not recommended in the 2009 Korean CAP treatment guidelines) for CAP patients. The most commonly used β-lactams were third-generation cephalosporins (72, 45.9%) and ampicillin/sulbactam or amoxicillin/clavulanate (28, 17.8%).
Some physicians remain unaware of the 2009 Korean treatment guidelines for CAP and do not use them in clinical practice. In addition, aminoglycoside combination therapy is frequently and inappropriately used in practice. In some cases, CAP is treated with macrolide monotherapy. Thus, the Korean CAP clinical guidelines must be more aggressively and continuously publicized.
Pneumonia; Guidelines; Antibiotics
Quantification of cell-free fetal DNA by methylation-based DNA discrimination has been used in non-invasive prenatal testing of fetal chromosomal aneuploidy. The maspin (Serpin peptidase inhibitor, clade B (ovalbumin), member 5; SERPINB5) gene, located on chromosome 18q21.33, is hypomethylated in the placenta and completely methylated in maternal blood cells. The objective of this study was to evaluate the accuracy of non-invasive detection of fetal trisomy 18 using the unmethylated-maspin (U-maspin) gene as a cell-free fetal DNA marker and the methylated-maspin (M-maspin) gene as a cell-free total DNA marker in the first trimester of pregnancy.
A nested case-control study was conducted using maternal plasma collected from 66 pregnant women, 11 carrying fetuses with trisomy 18 and 55 carrying normal fetuses. Median U-maspin concentrations were significantly elevated in women with trisomy 18 fetuses compared with controls (27.2 vs. 6.7 copies/mL; P<0.001). Median M-maspin concentrations were also significantly higher in women with trisomy 18 fetuses than in controls (96.9 vs. 19.5 copies/mL, P<0.001). The specificities of U-maspin and M-maspin concentrations for non-invasive fetal trisomy 18 detection were 96.4% and 74.5%, respectively, with a sensitivity of 90.9%.
Our results suggest that U-maspin and M-maspin concentrations may be useful as potential biomarkers for non-invasive detection of fetal trisomy 18 in the first trimester of pregnancy, irrespective of the sex and genetic variations of the fetus.
Avian paramyxoviruses (APMV) serotypes 1–9 are frequently isolated from domestic and wild birds worldwide. APMV-1 (also called Newcastle disease virus, NDV) is attenuated in non-human primates and is being developed as a candidate human vaccine vector. The vector potential of the other serotypes was unknown. In the present study, we evaluated nine different biologically- or recombinantly-derived APMV strains for the ability to replicate and cause disease in rhesus macaque model. Five of the viruses were: biologically-derived wild type (wt) APMV-2, -3, -5, -7 and -9. Another virus was a recombinant (r) version of wt APMV-4. The remaining three viruses were versions of wt rAPMV-2, -4 and -7 in which the F cleavage site had been modified to be multi-basic. Rhesus macaques were inoculated intranasally and intratracheally and monitored for clinical disease, virus shedding from the upper and lower respiratory tract, and seroconversion. Virus shedding was not detected for wt APMV-5. Very limited shedding was detected for wt rAPMV-4 and modified rAPMV-4, and only in a subset of animals. Shedding by the other viruses was detected in every infected animal, and usually from both the upper and lower respiratory tract. In particular, shedding over a number of days in every animal was observed for modified rAPMV-2, wt APMV-7, and modified rAPMV-7. Modification of the F protein cleavage site appeared to increase shedding by wt rAPMV-2 and marginally by wt rAPMV-4. All APMVs except wt APMV-5 induced a virus-specific serum antibody response in all infected animals. None of the animals exhibited any clinical disease signs. These results indicate that APMVs 2, 3, 4, 7, and 9 are competent to infect non-human primates, but are moderately-to-highly restricted, depending on the serotype. This suggests that they are not likely to significantly infect primates in nature, and represent promising attenuated candidates for vector development.
Opioid-based intravenous patient-controlled analgesia (IV PCA) is popular method of postoperative pain control, but many patients suffer from IV PCA-related postoperative nausea and vomiting (PONV). In this retrospective observational study, we have determined independent predictors of IV PCA-related PONV and predictive values of the Apfel's simplified risk score in pursuance of identifying high-risk patients.
Materials and Methods
We analyzed 7000 patients who received IV PCA with background infusion after elective surgery. Patients who maintained IV PCA for a postoperative period of 48 hr (completion group, n=6128) were compared with those who have discontinued IV PCA within 48 hr of surgery due to intractable PONV (cessation group, n=872). Patients, anesthetics, and surgical factors known for predicting PONV were evaluated by logistic regression analysis to identify independent predictors of IV PCA related intractable PONV.
In a stepwise multivariate analysis, weight, background infusion dose of fentanyl, addition of ketolorac to PCA, duration of anesthesia, general anesthesia, head and neck surgery, and Apfel's simplified risk score were revealed as independent risk factors for intractable PONV followed by the cessation of IV PCA. In addition, Apfel's simplified risk score, which demonstrated the highest odds ratio among the predictors, was strongly correlated with the cessation rate of IV PCA.
Multimodal prophylactic antiemetic strategies and dose reduction of opioids may be considered as strategies for the prevention of PONV with the use of IV PCA, especially in patients with high Apfel's simplified risk scores.
Apfel's simplified risk score; patient-controlled analgesia; postoperative nausea and vomiting
The pneumonia severity index (PSI) and CURB-65 are widely used tools for the prediction of community-acquired pneumonia (CAP). This study was conducted to evaluate validation of severity scoring system including the PSI and CURB-65 scores of Korean CAP patients. In the prospective CAP cohort (participated in by 14 hospitals in Korea from January 2009 to September 2011), 883 patients aged over 18 yr were studied. The 30-day mortalities of all patients were calculated with their PSI index classes and CURB scores. The overall mortality rate was 4.5% (40/883). The mortality rates per CURB-65 score were as follows: score 0, 2.3% (6/260); score 1, 4.0% (12/300); score 2, 6.0% (13/216); score 3, 5.7% (5/88); score 4, 23.5% (4/17); and score 5, 0% (0/2). Mortality rate with PSI risk class were as follows: I, 2.3% (4/174); II, 2.7% (5/182); III, 2.3% (5/213); IV, 4.5% (11/245); and V, 21.7% (15/69). The subgroup mortality rate of Korean CAP patients varies based on the severity scores and CURB-65 is more valid for the lower scores, and PSI, for the higher scores. Thus, these variations must be considered when using PSI and CURB-65 for CAP in Korean patients.
Pneumonia; Prognosis; Severity Index
The optical neural recording techniques are promising tools in recent years. Compared to the traditional electrophysiological recording, the optical means offer several advantages including no inclusion of electrical noise, simultaneous imaging of a large number of neurons, or selective recording from genetically-targeted neurons. Overall the optical neural recording technique comprises the intrinsic and the extrinsic optical recordings. The methods for intrinsic neural recording employ the change of optical properties in brains such as blood flow/oxygenation, cellular volume change, or refractive index change without addition of external indicators. Those properties can be detected using various optical techniques including laser Doppler flowmetry (LDF), near-infrared (NIR) spectrometer, functional optical coherence tomography (fOCT), and surface plasmon resonance (SPR). The extrinsic monitoring techniques use fluorescence signals reflecting neuronal activity via chemical or genetic modification of the neuronal cells. Two most popular activity-dependent fluorescent probes, calcium indicators and voltage-sensitive fluorescent proteins will be examined in this review. The principles, the instrumentations and in vivo applications of those optical signal measurements are described.
optical neural recording; intrinsic optical recording; extrinsic optical recording; calcium indicators; voltage-sensitive fluorescent protein (VSFP)
Previous reports show an association between high serum ferritin levels and metabolic syndrome (MS) in adults. In adolescents, little information is available with obesity and serum ferritin levels.
This is a cross-sectional study. Data were obtained from the 5th Korean National Health and Nutrition Examination Survey (K-NHANES) conducted during 2010 by the Korean Ministry of Health and Welfare. A total of 849 subjects aged 10-18 years participated in the 2010 survey. A body mass index (BMI) ≥95th percentile for age and sex or a BMI ≥25 was used to diagnose as obesity.
The weighted prevalence of obesity was 13.4% (62/462) in male and 8.5% (33/387) in female. We observed significantly higher serum ferritin in male than in female (mean±standard error [SE], 50.5±2.3 µU/L vs. 30.6±1.3 µU/L; P<0.0001). In male, serum ferritin is positively correlated with age (P<0.0001). White blood cell (WBC) count, serum fasting blood sugar, triglyceride (TG), total cholesterol, low-density lipoprotein, insulin, homeostasis model assessment-insulin resistance (HOMA-IR), systolic and diastolic blood pressure, and ferritin levels were higher and high-density lipoprotein (HDL) were lower in the obesity than in the normal group. In female adolescents, WBC count, TG, insulin, and HOMA-IR were higher and HDL were lower in the obesity than in the normal group. In male, serum ferritin levels showed positive association with obesity (β=21.196, P=0.016).
Serum ferritin levels appear to be associated with obesity in Korean male adolescents.
Ferritins; Adolescent; Obesity; Male; Korean
Virulent strains of Newcastle disease virus (NDV) can cause devastating disease in chickens worldwide. Although the current vaccines are substantially effective, they do not completely prevent infection, virus shedding and disease. To produce genotype-matched vaccines, a full-genome reverse genetics system has been used to generate a recombinant virus in which the F protein cleavage site has been changed to that of avirulent vaccine virus. In the other strategy, the vaccines have been generated by replacing the F and HN genes of a commercial vaccine strain with those from a genotype-matched virus. However, the protective efficacy of a chimeric virus vaccine has not been directly compared with that of a full-genome virus vaccine developed by reverse genetics. Therefore, in this study, we evaluated the protective efficacy of genotype VII matched chimeric vaccines by generating three recombinant viruses based on avirulent LaSota (genotype II) strain in which the open reading frames (ORFs) encoding the F and HN proteins were replaced, individually or together, with those of the circulating and highly virulent Indonesian NDV strain Ban/010. The cleavage site of the Ban/010 F protein was mutated to the avirulent motif found in strain LaSota. In vitro growth characteristics and a pathogenicity test indicated that all three chimeric viruses retained the highly attenuated phenotype of the parental viruses. Immunization of chickens with chimeric and full-length genome VII vaccines followed by challenge with virulent Ban/010 or Texas GB (genotype II) virus demonstrated protection against clinical disease and death. However, only those chickens immunized with chimeric rLaSota expressing the F or F plus HN proteins of the Indonesian strain were efficiently protected against shedding of Ban/010 virus. Our findings showed that genotype-matched vaccines can provide protection to chickens by efficiently preventing spread of virus, primarily due to the F protein.
c-Src and Lyn are the only Src family kinases (SFKs) with established activity in osteoclasts (OCs). c-Src promotes function via cytoskeletal organization of the mature resorptive cell while Lyn is a negative regulator of osteoclastogenesis. We establish that Fyn, another SFK, also impacts the OC, but in a manner distinctly different than c-Src and Lyn. Fyn deficiency principally alters cells throughout the osteoclastogenic process, resulting in diminished numbers of resorptive polykaryons. Arrested OC formation in the face of insufficient Fyn reflects reduced proliferation of precursors, in response to M-CSF and retarded RANK ligand (RANKL)-induced differentiation, attended by suppressed activation of the osteoclastogenic signaling molecules, c-Jun and NF-κB. The anti-apoptotic properties of RANKL are also compromised in cells deleted of Fyn, an event mediated by increased Bim expression and failed activation of Akt. The defective osteoclastogenesis of Fyn-/- OCs dampens bone resorption, in vitro. Finally, while Fyn deficiency does not regulate basal osteoclastogenesis, in vivo, it reduces that stimulated by RANKL by approximately 2/3. Thus, Fyn is a pro-resorptive SFK, which exerts its effects by prompting proliferation and differentiation while attenuating apoptosis of OC lineage cells.
Osteoclasts; Fyn; Src family kinase (SFK); M-CSF; RANK ligand