PURPOSE: The house dust mite (HDM) is one of the most important sources of indoor allergens and a significant cause of allergic rhinitis and allergic asthma. Our previous studies demonstrated that Vibrio vulnificus flagellin B (FlaB) plus allergen as a co-treatment mixture improved lung function and inhibited eosinophilic airway inflammation through the Toll-like receptor 5 signaling pathway in an ovalbumin (OVA)- or HDM-induced mouse asthma model. In the present study, we fused the major mite allergen Derp2 to FlaB and compared the therapeutic effects of the Derp2-FlaB fusion protein with those of a mixture of Derp2 and FlaB in a Derp2-induced mouse asthma model. METHODS: BALB/c mice sensitized with Derp2 + HDM were treated with Derp2, a Derp2 plus FlaB (Derp2 + FlaB) mixture, or the Derp2-FlaB fusion protein 3 times at 1-week intervals. Seven days after the final treatment, the mice were challenged intranasally with Derp2, and airway responses and Derp2-specific immune responses were evaluated. RESULTS: The Derp2-FlaB fusion protein was significantly more efficacious in reducing airway hyperresponsiveness, lung eosinophil infiltration, and Derp2-specific IgE than the Derp2 + FlaB mixture. CONCLUSIONS: The Derp2-FlaB fusion protein showed a strong anti-asthma immunomodulatory capacity, leading to the prevention of airway inflammatory responses in a murine disease model through the inhibition of Th2 responses. These findings suggest that the Derp2-FlaB fusion protein would be a promising vaccine candidate for HDM-mediated allergic asthma therapy.
Allergens ; Animals ; Asthma ; Eosinophils ; Flagellin ; Immunoglobulin E ; Inflammation ; Lung ; Mice ; Mites ; Ovalbumin ; Pyroglyphidae ; Rhinitis, Allergic ; Therapeutic Uses ; Toll-Like Receptor 5 ; Vibrio vulnificus

BACKGROUND/AIMS: Patients with chronic kidney disease (CKD) have a high risk of gastrointestinal tract bleeding because of platelet dysfunction attributable to uremia, a poor blood supply, and frequent use of anticoagulant agents. We describe the colonoscopic characteristics of lower gastrointestinal tract bleeding (LGIB) in patients with CKD. METHODS: A total of 230 hospitalized patients with CKD who underwent colonoscopy because of suspected LGIB between January 2003 and August 2016 were reviewed retrospectively. We categorized CKD into five stages according to the estimated glomerular filtration rate and compared the colonoscopic findings and clinical manifestations among these five subgroups. RESULTS: Of the 230 patients with CKD suspected of LGIB, 73 (31.7%, 103 cases) were colonoscopically confirmed to exhibit LGIB. Their mean age was 65.7 ± 12.8 years, and 52.1% were female (n = 38). The most common causes of LGIB were hemorrhoidal bleeding (32 cases, 43.8%), followed by bleeding of colorectal ulcers (21 cases, 28.8%), diverticular bleeding (12 cases, 16.4%), colitis-related bleeding (12 cases, 16.4%), and angiodysplastic bleeding (12 cases, 16.4%). As the CKD stage progressed, the incidence of LGIB increased (p = 0.043). On multivariate logistic regression analysis, LGIB was more common in CKD patients with hemorrhoids (odds ratio [OR]: 4.349, 95% confidence interval [CI]: 2.043–9.256, p < 0.001) or colorectal ulcers (OR: 20.001, 95% CI: 4.780–83.686, p ℃ 0.001) and in those on hemodialysis (OR: 6.863, 95% CI: 1.140–41.308, p = 0.035). CONCLUSIONS In CKD patients, the risk of LGIB is significantly increased by hemorrhoids, colorectal ulcers, and a positive hemodialysis status.

BACKGROUND/AIMS: Patients with chronic kidney disease (CKD) have a high risk of gastrointestinal tract bleeding because of platelet dysfunction attributable to uremia, a poor blood supply, and frequent use of anticoagulant agents. We describe the colonoscopic characteristics of lower gastrointestinal tract bleeding (LGIB) in patients with CKD. METHODS: A total of 230 hospitalized patients with CKD who underwent colonoscopy because of suspected LGIB between January 2003 and August 2016 were reviewed retrospectively. We categorized CKD into five stages according to the estimated glomerular filtration rate and compared the colonoscopic findings and clinical manifestations among these five subgroups. RESULTS: Of the 230 patients with CKD suspected of LGIB, 73 (31.7%, 103 cases) were colonoscopically confirmed to exhibit LGIB. Their mean age was 65.7 ± 12.8 years, and 52.1% were female (n = 38). The most common causes of LGIB were hemorrhoidal bleeding (32 cases, 43.8%), followed by bleeding of colorectal ulcers (21 cases, 28.8%), diverticular bleeding (12 cases, 16.4%), colitis-related bleeding (12 cases, 16.4%), and angiodysplastic bleeding (12 cases, 16.4%). As the CKD stage progressed, the incidence of LGIB increased (p = 0.043). On multivariate logistic regression analysis, LGIB was more common in CKD patients with hemorrhoids (odds ratio [OR]: 4.349, 95% confidence interval [CI]: 2.043–9.256, p < 0.001) or colorectal ulcers (OR: 20.001, 95% CI: 4.780–83.686, p ℃ 0.001) and in those on hemodialysis (OR: 6.863, 95% CI: 1.140–41.308, p = 0.035). CONCLUSIONS: In CKD patients, the risk of LGIB is significantly increased by hemorrhoids, colorectal ulcers, and a positive hemodialysis status.
Anticoagulants ; Blood Platelets ; Colonoscopy ; Female ; Gastrointestinal Tract ; Glomerular Filtration Rate ; Hemorrhage ; Hemorrhoids ; Humans ; Incidence ; Logistic Models ; Lower Gastrointestinal Tract ; Renal Dialysis ; Renal Insufficiency, Chronic ; Retrospective Studies ; Ulcer ; Uremia

PURPOSE: Invariant natural killer T (iNKT) cells play a critical role in the pathogenesis of asthma. We previously reported the association between circulating Th2-like iNKT cells and lung function in asthma patients and the suppressive effect of Toll-like receptor 5 ligand flagellin B (FlaB) on asthmatic in a mouse model. Thus, we investigated whether FlaB modulates the function of circulating iNKT cells in asthmatic patients. METHODS: Peripheral blood mononuclear cells (PBMCs) were treated with FlaB, and the secreted and intracellular cytokines of iNKT cells were evaluated by using ELISA and flow cytometry, respectively, following stimulation with alpha-galactosylceramide. Foxp3+ iNKT cells were also measured. To determine the effect of FlaB-treated dendritic cells (DCs) on iNKT cells, we co-cultured CD14+ monocyte-derived DCs and T cells from patients with house dust mite-sensitive asthma and analyzed intracellular cytokines in iNKT cells. RESULTS: A reduction of IL-4 and IL-17 production by iNKT cells in PBMCs after FlaB treatment was alleviated following blocking of IL-10 signaling. A decrease in the frequencies of IL-4+ and IL-17+ iNKT cells by FlaB-treated DCs was reversed after blocking of IL-10 signaling. Simultaneously, an increase in Foxp3+ iNKT cells induced by FlaB treatment disappeared after blocking of IL-10. CONCLUSIONS: FlaB may inhibit Th2- and Th17-like iNKT cells and induce Foxp3+ iNKT cells by DCs via an IL-10-dependent mechanism in asthmatic patients. In patients with a specific asthma phenotype associated with iNKT cells, FlaB may be an effective immunomodulator for iNKT cell-targeted immunotherapy.
Animals ; Asthma* ; Cytokines ; Dendritic Cells* ; Dust ; Enzyme-Linked Immunosorbent Assay ; Flagellin* ; Flow Cytometry ; Humans ; Immunotherapy ; Interleukin-10 ; Interleukin-17 ; Interleukin-4 ; Lung ; Mice ; Natural Killer T-Cells* ; Phenotype ; T-Lymphocytes ; Toll-Like Receptor 5

BACKGROUND/AIMS: Various anatomical features of the biliary tree affect ability to remove difficult common bile duct (CBD) stones. In this study, we evaluated the clinical characteristics and outcomes of the endoscopic treatment of stones in stemware-shaped CBDs. METHODS: Thirty-four patients with a stone and a stemware-shaped CBD who were treated at different tertiary referral centers from January 2008 to December 2012 were studied retrospectively. When stone removal failed, percutaneous or direct peroral cholangioscopic lithotripsy, endoscopic retrograde biliary drainage, or surgery was performed as a second-line procedure. RESULTS: The overall success rate of the first-line procedure was 41.2%. Five of the 34 patients (14.7%) experienced procedure-related complications. No procedure-related mortality occurred. Mechanical lithotripsy was required to completely remove stones in 13 patients (38.2%). Conversion to a second-line procedure was required in 20 patients (58.8%). Mechanical lithotripsy was needed in 75% and 66.7% of those with a stone size of <1 cm or > or =1 cm, respectively. Stone recurrence occurred in two patients (9.1%) after 6 months and 27 months, respectively. CONCLUSIONS: The endoscopic treatment of stones in a stemware-shaped CBD is challenging. The careful assessment of difficult CBD stones is required before endoscopic procedures.
Adult ; Aged ; Aged, 80 and over ; Cholangiopancreatography, Endoscopic Retrograde/adverse effects/methods ; Choledocholithiasis/complications/*surgery ; Common Bile Duct/*anatomy & histology/surgery ; Endoscopy, Gastrointestinal/adverse effects/*methods ; Female ; Humans ; Lithotripsy/adverse effects/*methods ; Male ; Middle Aged ; Treatment Outcome

Incidence of renal involvement in mixed connective tissue disease (MCTD) is low. In the presence of glomerulonephritis, membranous nephropathy (MN) in MCTD is common. A 47-year-old woman presented with hypothyroidism. She developed Raynaud's phenomenon, arthralgia, and incomplete lupus erythematosus, diagnosed with MCTD. One year after then, the patient developed persistent proteinuria (1+) without hematuria. Following diagnosis with MCTD, her renal function began to deteriorate. The renal biopsy showed late stage MN. For the treatment of MN with mild proteinuria and MCTD, we prescribed an angiotensin II receptor blocker and 7.5 mg of methotrexate per week and 300 mg of hydroxychloroquine daily. The patient had a reduced estimated glomerular filtration rate of 55% for the subsequent eight years. The MN in MCTD is known to show good renal prognosis. Here, we report on a rare case of MN in MCTD in Korea with a bad prognosis.
Arthralgia ; Biopsy ; Diagnosis ; Female ; Glomerular Filtration Rate ; Glomerulonephritis ; Glomerulonephritis, Membranous* ; Hematuria ; Humans ; Hydroxychloroquine ; Hypothyroidism ; Incidence ; Korea ; Methotrexate ; Middle Aged ; Mixed Connective Tissue Disease* ; Prognosis* ; Proteinuria ; Receptors, Angiotensin

PURPOSE: Invariant natural killer T (iNKT) cells may play an important role in the pathogenesis of asthma in mice and humans. Thus, an agent that modulates the function of iNKT cells may have therapeutic potential to control asthma. We hypothesized that lipopolysaccharide (LPS)-, flagellin-, or CpG-induced changes in the cytokine milieu may modify and even inhibit the function of airway iNKT cells in asthma. METHODS: Because increased alpha-galactosylceramide (GalCer)-induced airway hyperreactivity (AHR) reflects the presence of airway iNKT cells, alpha-GalCer-induced AHR, as well as inflammatory cells and cytokines in bronchoalveolar lavage (BAL) fluid, were determined 24 hours after in vivo treatment with LPS, flagellin, or CpG in naive BALB/c mice. Intracellular IL-4 and IFN-gamma were measured in spleen iNKT cells after in vitro treatment with LPS, flagellin, or CpG. A role for IL-12 following the treatments was determined. RESULTS: Intranasal administration of LPS, flagellin, or CpG reduced development of alpha-GalCer-induced AHR, eosinophilic airway inflammation, and Th1 and Th2 cytokine responses in BAL fluid, while producing IL-12 in BAL fluid. Intraperitoneal administration of IL-12 mAb blocked the suppressive effect of LPS, flagellin, or CpG. In vitro treatment with LPS, flagellin, or CpG reduced production of IL-4 and IFN-gamma from alpha-GalCer-stimulated spleen iNKT cells; these effects were ameliorated by addition of anti-IL-12 mAb. CONCLUSIONS: TLR4, 5, and 9 agonists may suppress the function of airway and spleen iNKT cells via IL-12-dependent mechanisms. Anergy of iNKT cells by IL-12 might play a role in suppression by these TLR agonists.
Administration, Intranasal ; Animals ; Asthma ; Bronchoalveolar Lavage ; Cytokines ; Eosinophils ; Flagellin ; Galactosylceramides ; Humans ; Inflammation ; Interleukin-12 ; Interleukin-4 ; Mice ; Natural Killer T-Cells ; Spleen

Primary aldosteronism is present in approximately 1 percent of hypertensive patients, and is rarely associated with pregnancy. We report a case of unilateral aldosterone producing adenoma in a pregnant woman. A 29-year-old woman was referred to with hypertension and proteinuria at 14 weeks' gestation. She had known that she had unilateral aldosterone producing adenoma for 18 months and refused medical or surgical treatment. She was prescribed antihypertensive medication and preformed laparoscopic adrenalectomy in left adrenal gland at 22 weeks' gestation. After adrenalectomy, her blood pressure was normal. At 29 weeks' gestation, she complained headache, and her blood pressure was 200/100 mmHg with pitting edema. We thought preeclampsia and performed cesarean section. After the baby was delivered, she had uncontrolled hypertension, hypokalemia with persistent proteinuria. We checked plasma renin activitity, aldoterone and abdminopelvic computed tomography. We found remnant left adrenal adenoma and perfomed laparoscopic operation. After reoperation, her blood pressure was normal and no proteinuria.
Adenoma ; Adrenal Glands ; Adrenalectomy ; Adrenocortical Adenoma ; Adult ; Aldosterone ; Blood Pressure ; Cesarean Section ; Edema ; Female ; Headache ; Humans ; Hyperaldosteronism ; Hypertension ; Hypokalemia ; Plasma ; Pre-Eclampsia ; Pregnancy ; Pregnant Women ; Proteinuria ; Renin ; Reoperation

Recently, the incidence of fungal infection increases because of immunosuppressive therapy and chemotherapy. In immunosuppressed transplant recipients, Aspergillus can be a dangerous pathogen, capable of inducing fulminant clinical disease. Invasive fungal infections are life-threatening complications in solid-organ transplantation. Although the rate of fungal infections in transplant recipients is lower than that of other infections, the mortality rate is higher. A 34 year-old male was admitted to our hospital with fever and gross hematuria. He had received renal transplantation 2 years ago and had been transferred the other hospital 1 month ago. Initial laboratory data evaluation showed a pancytopenia and azotemia. We thought that pancytopenia was caused by immunosuppressive agents and infection. The patient was treated with antibiotics but fever was not subsided. After 4 days, he complained of transplant site pain and tenderness to percussion. A percutaneous renal biopsy was performed. Microscopic examination showed invasive aspergillosis in transplanted kidney and perirenal area. We removed the transplanted kidney and perirenal tissue, and prescribed antifungal agents for 3 months.
Anti-Bacterial Agents ; Antifungal Agents ; Aspergillosis ; Aspergillus ; Azotemia ; Biopsy ; Fever ; Hematuria ; Humans ; Immunosuppressive Agents ; Incidence ; Kidney ; Kidney Transplantation ; Male ; Pancytopenia ; Percussion ; Transplants

Transfusion free surgery is of increasing interest as more patients are refusing a blood transfusion because of religious belief, infection or fear of a blood-transmitted disease such as AIDS. Patients of the Jehovah's Witness faith generally do not accept transfusions of blood or blood products but some will accept cadaveric organs for transplantation. Recently, it is possible to perform 'bloodless' autologous or reduced-intensity allogeneic transplants in properly selected patients. The success of these procedures depends on the transplantation technique and on meticulous attention to blood conservation and supportive care. In our center, nine Jehovah's Witness received a kidney transplantations and transfusion free surgery. All the patients received erythropoietin injection and iron supplement before kidney transplantation. They were not serious bleeding in surgery and graft dysfunction after surgery. All the recipients are alive and have well functioning grafts. Elective living donor kidney transplantation allows implementation of a transfusion free strategy. We think that various methods replaced blood transfusion reduced risk of postoperative anemia and unnecessary transfusion.
Anemia ; Blood Transfusion ; Bloodless Medical and Surgical Procedures ; Cadaver ; Erythropoietin ; Hemorrhage ; Humans ; Iron ; Kidney ; Kidney Transplantation ; Living Donors ; Religion ; Transplants ; Wit and Humor as Topic