BACKGROUND: The expression of the SOCS genes in cytomegalovirus (CMV) viremia after hematopoietic stem cell transplantation (HSCT) remains largely unexplored. METHODS: Using quantitative RT-PCR of mononuclear cells, we conducted pairwise comparison of SOCS1 and SOCS3 expression levels among a healthy donor group (N=55), a pre-HSCT group (N=17), and the recipient subgroup (N=107), which were divided according to the occurrence of CMV viremia and acute graft-versus-host disease (aGVHD). RESULTS: Compared to that in the healthy donor group, SOCS1 expression was higher in the CMV+ subgroup, especially in the CMV+GVHD- group, but decreased in the other subgroups. When compared to the expression in the pre-HSCT group, SOCS1 expression was significantly higher in the CMV+ subgroup, especially in the CMV+GVHD+ subgroup. Meanwhile, compared to that in the healthy donor group, SOCS3 expression was significantly lower in all other groups. The CMV-GVHD- subgroup showed significantly lower SOCS3 expression compared to the CMV+ subgroup, the CMV+GVHD+ subgroup, and the CMV+GVHD- subgroup. CONCLUSION: We report differential expression of SOCS genes according to CMV viremia with acute GVHD occurrence after HSCT, suggesting that regulation of SOCS expression is associated with CMV viremia.
Cytomegalovirus* ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation* ; Humans ; Tissue Donors ; Viremia*

BACKGROUND: Suppressor of cytokine signaling genes (SOCS) are regarded as pivotal negative feedback regulators of cytokine signals, including the interferon-gamma (IFN-gamma), granulocyte-colony stimulating factor, and interleukin families, released by T cells. A detailed understanding of the involvement of SOCS genes in graft-versus-host disease (GVHD) is critical to effectively manage GVHD, yet their expression patterns among recipients remain largely unexplored. METHODS: Expression levels of SOCS1 and SOCS3 were determined by real-time quantitative reverse transcription PCR (qRT-PCR) in patients with acute GVHD (aGVHD) and chronic GVHD (cGVHD), in a severity-dependent manner, after allogeneic hematopoietic stem cell transplantation (HSCT). A total of 71 recipients with AML (N=40), ALL (N=12), myelodysplastic syndromes (MDS; N=10), chronic myelogenous leukemia (CML; N=2), severe aplastic anemia (SAA; N=5), or others (N=2), who received allogeneic HSCT from human leukocyte antigen-identical siblings or unrelated donors between 2009 and 2011, were included in the present study. RESULTS: Overall, the expression levels of SOCS1 decreased in recipients with grade II to IV aGVHD and cGVHD when compared to normal donors and non-GVHD recipients. Interestingly, the expressions of SOCS1 decreased significantly more in cGVHD than in aGVHD recipients (P=0.0091). In contrast, SOCS3 expressions were similarly reduced in all the recipients. CONCLUSION: This is the first study to show that SOCS1 and SOCS3 are differentially expressed in recipients following allogeneic HSCT, suggesting a prognostic correlation between SOCS genes and the development of GVHD. This result provides a new platform to study GVHD immunobiology and potential diagnostic and therapeutic targets for GVHD.
Anemia, Aplastic ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; Humans ; Interferon-gamma ; Interleukins ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Leukocytes ; Myelodysplastic Syndromes ; Polymerase Chain Reaction ; Real-Time Polymerase Chain Reaction ; Reverse Transcription ; Siblings ; Suppressor of Cytokine Signaling Proteins ; T-Lymphocytes ; Tissue Donors ; Transplantation, Homologous ; Unrelated Donors

BACKGROUND: Suppressor of cytokine signaling genes (SOCS) are regarded as pivotal negative feedback regulators of cytokine signals, including the interferon-gamma (IFN-gamma), granulocyte-colony stimulating factor, and interleukin families, released by T cells. A detailed understanding of the involvement of SOCS genes in graft-versus-host disease (GVHD) is critical to effectively manage GVHD, yet their expression patterns among recipients remain largely unexplored. METHODS: Expression levels of SOCS1 and SOCS3 were determined by real-time quantitative reverse transcription PCR (qRT-PCR) in patients with acute GVHD (aGVHD) and chronic GVHD (cGVHD), in a severity-dependent manner, after allogeneic hematopoietic stem cell transplantation (HSCT). A total of 71 recipients with AML (N=40), ALL (N=12), myelodysplastic syndromes (MDS; N=10), chronic myelogenous leukemia (CML; N=2), severe aplastic anemia (SAA; N=5), or others (N=2), who received allogeneic HSCT from human leukocyte antigen-identical siblings or unrelated donors between 2009 and 2011, were included in the present study. RESULTS: Overall, the expression levels of SOCS1 decreased in recipients with grade II to IV aGVHD and cGVHD when compared to normal donors and non-GVHD recipients. Interestingly, the expressions of SOCS1 decreased significantly more in cGVHD than in aGVHD recipients (P=0.0091). In contrast, SOCS3 expressions were similarly reduced in all the recipients. CONCLUSION: This is the first study to show that SOCS1 and SOCS3 are differentially expressed in recipients following allogeneic HSCT, suggesting a prognostic correlation between SOCS genes and the development of GVHD. This result provides a new platform to study GVHD immunobiology and potential diagnostic and therapeutic targets for GVHD.
Anemia, Aplastic ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; Humans ; Interferon-gamma ; Interleukins ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Leukocytes ; Myelodysplastic Syndromes ; Polymerase Chain Reaction ; Real-Time Polymerase Chain Reaction ; Reverse Transcription ; Siblings ; Suppressor of Cytokine Signaling Proteins ; T-Lymphocytes ; Tissue Donors ; Transplantation, Homologous ; Unrelated Donors

BACKGROUND: Biodegradable polymers have increasingly been recognized for various biological applications in recent years. Here we examined the immunostimulatory activities of the novel poly(aspartic acid) conjugated with L-lysine (PLA). METHODS: PLA was synthesized by conjugating L-lysine to aspartic acid polymer. PLA-nanoliposomes (PLA-NLs) were prepared from PLA using a microfluidizer. The immunostimulatory activities of PLA-NLs were examined in mouse bone marrow-derived dendritic cells (BM-DCs). RESULTS: PLA-NLs increased the number of BM-DCs when added to cultures of GM-CSF-induced DC generation on day 4 after the initiation of cultures. Examination of the phenotypic properties showed that BM-DCs generated in the presence of PLA-NLs are more mature in terms of the expression of MHC class II molecules and major co-stimulatory molecules than BM-DCs generated in the absence of PLA-NLs. In addition, the BM-DCs exhibited enhanced capability to produce cytokines, such as IL-6, IL-12, TNF-alpha and IL-1beta. Allogeneic mixed lymphocyte reactions also confirmed that the BMDCs were more stimulatory on allogeneic T cells. PLA- NL also induced further growth of immature BM-DCs that were harvested on day 8. CONCLUSION: These results show that PLA-NLs induce the generation and functional activities of BM-DCs, and suggest that PLA-NLs could be immunostimulating agents that target DCs.
Animals ; Aspartic Acid ; Cytokines ; Dendritic Cells ; Immunomodulation ; Interleukin-12 ; Interleukin-6 ; Lymphocyte Culture Test, Mixed ; Lysine ; Mice ; Polymers ; T-Lymphocytes ; Tumor Necrosis Factor-alpha

BACKGROUND: Biodegradable polymers have increasingly been recognized for various biological applications in recent years. Here we examined the immunostimulatory activities of the novel poly(aspartic acid) conjugated with L-lysine (PLA). METHODS: PLA was synthesized by conjugating L-lysine to aspartic acid polymer. PLA-nanoliposomes (PLA-NLs) were prepared from PLA using a microfluidizer. The immunostimulatory activities of PLA-NLs were examined in mouse bone marrow-derived dendritic cells (BM-DCs). RESULTS: PLA-NLs increased the number of BM-DCs when added to cultures of GM-CSF-induced DC generation on day 4 after the initiation of cultures. Examination of the phenotypic properties showed that BM-DCs generated in the presence of PLA-NLs are more mature in terms of the expression of MHC class II molecules and major co-stimulatory molecules than BM-DCs generated in the absence of PLA-NLs. In addition, the BM-DCs exhibited enhanced capability to produce cytokines, such as IL-6, IL-12, TNF-alpha and IL-1beta. Allogeneic mixed lymphocyte reactions also confirmed that the BMDCs were more stimulatory on allogeneic T cells. PLA- NL also induced further growth of immature BM-DCs that were harvested on day 8. CONCLUSION: These results show that PLA-NLs induce the generation and functional activities of BM-DCs, and suggest that PLA-NLs could be immunostimulating agents that target DCs.
Animals ; Aspartic Acid ; Cytokines ; Dendritic Cells ; Immunomodulation ; Interleukin-12 ; Interleukin-6 ; Lymphocyte Culture Test, Mixed ; Lysine ; Mice ; Polymers ; T-Lymphocytes ; Tumor Necrosis Factor-alpha

BACKGROUND: The purpose of this study is to know the healthcare-associated infection (HAI)s in small and medium sized hospitals, less than 400 beds. METHODS: We had web based surveillance for HAIs in 27 hospitals from August to October 2010. The surveillance performed in 1-2 ICUs and 1 general ward in each hospitals by CDC definition. And for the multi-drug resistant organisms (MDROs), we reviewed all of blood culture results. RESULTS: We identified 319 HAIs among 269,436 patients days. The HAIs rate was 1.18 (CI 1.05-1.32)/1,000 patient-days. Urinary tract infection was the most common HAI (52.4%) in this study followed by pneumonia (18.9%), blood-stream infections (14.2%), surgical site infection (7.9%), and others (6.6%). There were 76.5% of device associated infections in UTI, 46.7% in BSI, and 18.3% in pneumonia. The rate of HAIs in ICU was higher than that of in general ward (4.6 vs 0.9/1,000 patient-days). However, the indwelling catheter associated urinary tract infection rate was lower in ICU (2.6 vs 4.4/1,000 device days). There were no significant differences in central line-associated blood stream infection rate (1.5 vs 1.8) and ventilator-associated pneumonia rate (3.0 vs 0.0). The common microorganisms found in HAIs were Escherichia coli (19.8%), Staphylococcus aureus (13.1%), and Pseudomonas aeruginosa (12.7%). Moreover, 90.9% of S. aureus were resistant to methicillin, and 38.2% of P. aeruginosa and 44.4% of Acinetobacter baumannii were resistant to imipenem. Total of 66 MDROs were isolated from blood culture and the result shows that the MRSA was 84.6% (56 case), carbapenmen-resistant Acinetobacter spp. was 10.6% (7 case), and vancomycin-resistant enterococci was 4.6% (3 case). CONCLUSION: The characteristics of HAIs in small and medium sized hospitals will be contributed to the decision making of governance policy for infection control and to provide comparable data for these hospitals.
Acinetobacter ; Acinetobacter baumannii ; Catheters, Indwelling ; Centers for Disease Control and Prevention (U.S.) ; Decision Making ; Escherichia coli ; Humans ; Imipenem ; Infection Control ; Methicillin ; Methicillin-Resistant Staphylococcus aureus ; Patients' Rooms ; Pneumonia ; Pneumonia, Ventilator-Associated ; Pseudomonas aeruginosa ; Rivers ; Staphylococcus aureus ; Urinary Tract Infections

PURPOSE: To validate the Dinamap ProCare 200 blood pressure (BP) monitor against a mercury sphygmomanometer in children 7 to 18 years old in accordance with the 2010 International Protocol of European Society of Hypertension (ESH-IP2) and the British Hypertension Society (BHS) protocol. METHODS: Forty-five children were recruited for the study. A validation procedure was performed following the protocol based on the ESH-IP2 and BHS protocols for children and adolescents. Each subject underwent 7 sequential BP measurements alternatively with a mercury sphygmomanometer and the test device by trained nurses. The results were analyzed according to the validation criteria of ESH-IP2. RESULTS: The mean (+/-SD) difference in the absolute BP values between test device and mercury sphygmomanometer readings was 1.85+/-1.65 mmHg for systolic BP (SBP) and 4.41+/-3.53 mmHg for diastolic BP (DBP). These results fulfilled the Association for the Advancement of Medical Instrumentation criterion of a mean+/-SD below 5+/-8 mmHg for both SBP and DBP. The percentages of test device-observer mercury sphygmomanometer BP differences within 5, 10, and 15 mmHg were 96%, 100%, and 100% for SBP, and 69%, 92%, and 100% for DBP, respectively, in the part 1 analysis; both SBP and DBP passed the part 1 criteria. In the part 2 analysis, SBP passed the criteria but DBP failed. CONCLUSION: Although the Dinamap ProCare 200 BP monitor failed an adapted ESH-IP2, SBP passed. When comparing BP readings measured by oscillometers and mercury sphygmomanometers, one has to consider the differences between them, particularly in DBP, because DBP can be underestimated.
Adolescent ; Arm ; Blood Pressure ; Blood Pressure Monitors ; Child ; Humans ; Hypertension ; Organothiophosphorus Compounds ; Reading ; Sphygmomanometers

PURPOSE: To validate the Dinamap ProCare 200 blood pressure (BP) monitor against a mercury sphygmomanometer in children 7 to 18 years old in accordance with the 2010 International Protocol of European Society of Hypertension (ESH-IP2) and the British Hypertension Society (BHS) protocol. METHODS: Forty-five children were recruited for the study. A validation procedure was performed following the protocol based on the ESH-IP2 and BHS protocols for children and adolescents. Each subject underwent 7 sequential BP measurements alternatively with a mercury sphygmomanometer and the test device by trained nurses. The results were analyzed according to the validation criteria of ESH-IP2. RESULTS: The mean (+/-SD) difference in the absolute BP values between test device and mercury sphygmomanometer readings was 1.85+/-1.65 mmHg for systolic BP (SBP) and 4.41+/-3.53 mmHg for diastolic BP (DBP). These results fulfilled the Association for the Advancement of Medical Instrumentation criterion of a mean+/-SD below 5+/-8 mmHg for both SBP and DBP. The percentages of test device-observer mercury sphygmomanometer BP differences within 5, 10, and 15 mmHg were 96%, 100%, and 100% for SBP, and 69%, 92%, and 100% for DBP, respectively, in the part 1 analysis; both SBP and DBP passed the part 1 criteria. In the part 2 analysis, SBP passed the criteria but DBP failed. CONCLUSION: Although the Dinamap ProCare 200 BP monitor failed an adapted ESH-IP2, SBP passed. When comparing BP readings measured by oscillometers and mercury sphygmomanometers, one has to consider the differences between them, particularly in DBP, because DBP can be underestimated.
Adolescent ; Arm ; Blood Pressure ; Blood Pressure Monitors ; Child ; Humans ; Hypertension ; Organothiophosphorus Compounds ; Reading ; Sphygmomanometers

Hypocrellin A has gained much attention in recent years due to its light-induced antitumor, antifungal and antiviral activities. Here we report that hypocrellin A exerts immunomodulatory effects on MHC-restricted presentation of antigen. Hypocrellin A inhibited class II-MHC restricted presentation of exogenous antigen, but not class I MHC-restricted presentation of exogenous antigen, in dendritic cells. Hypocrellin A also inhibited the cytosolic pathway of endogenous antigen presentation. However, hypocrellin A did not inhibit the expression of class I and class II MHC molecules on dendritic cells (DCs), the phagocytic activity of DCs, or the H-2K(b)-restricted presentation of a synthetic peptide, SIINFEKL. These results show that hypocrellin A differentially modulates the MHC-restricted antigen presentation pathways.
Antigen Presentation ; Cytosol ; Dendritic Cells ; Perylene ; Quinones

PURPOSE: Clinical treatment for lupus nephritis largely depends upon histological renal biopsy classification. But it has been reported that serologic biochemical markers are not strongly associated with pathologic classification. The aim of this study is to see whether serologic markers could predict pathologic class of lupus nephritis for appropriate treatment. METHODS: We investigated 67 patients, who underwent renal biopsy with lupus nephritis at Hanyang University Hospital between January, 2005 and August, 2007. Biological markers for this study are hematuria, proteinuria, serologic data of lupus activity and azotemia. They were retrospectively analyzed from patients grouped by ISN/RPS 2003 lupus nephritis classification. RESULTS: Total 67 patients (men 5, women 62) were enrolled and the mean age of the patients was 30.6+/-9 years. The number of patient group by pathologic classification was 4 cases for class II, 15 cases for class III, 30 cases for class IV and 15 cases for class V. Spot urine protein to creatinine ratio more than 3 increased in class IV group statistically (p=.007). C3 level decreased more in class IV group than class III, V groups. Ten patients showed azotemia, and 9 of them were class IV group (p=.048). CONCLUSION: The patients with more increased proteinuria, decreased C3 level and azotemia showed more frequently in class IV group. Hence those three biological markers may be a clinical clue to pathologic diagnosis.
Azotemia ; Biomarkers ; Biopsy ; Creatinine ; Female ; Hematuria ; Humans ; Lupus Nephritis ; Proteinuria ; Retrospective Studies