Rheumatoid arthritis (RA) is a multifactorial immune-mediated disease, the pathogenesis of which involves different cell types. T-cell activation plays an important role in RA. Therefore, inhibiting T-cell activation is one of the current therapeutic strategies.Cytotoxic T-lymphocyte antigen 4-immunoglobulin (CTLA4-Ig), also known as abatacept, reduces cytokine secretion by inhibiting T-cell activation. To achieve a homeostatic therapeutic effect, CTLA4-Ig has to be administered repeatedly over several weeks, which limits its applicability in RA treatment. To overcome this limitation, we increased the number of sialic acid-capped antennas by genetically engineering the CTLA4 region to increase the therapeutic effect of CTLA4-Ig. N-acetylglucosaminyltransferase (GnT) and α2,6-sialyltransferase (α2,6-ST) were co-overexpressed in Chinese hamster ovary (CHO) cells to generate a highly sialylated CTLA4-Ig fusion protein, named ST6. The therapeutic and immunogenic effects of ST6 and CTLA4-Ig were compared. ST6 dose-dependently decreased paw edema in a mouse model of collagen-induced arthritis and reduced cytokine levels in a co-culture cell assay in a similar manner to CTLA4-Ig. ST6- and CTLA4-Ig-induced T cell-derived cytokines were examined in CD4 T cells isolated from peripheral blood mononuclear cells after cell killing through irradiation followed by flow- and magnetic-beadassisted separation. Interestingly, compared to CTLA4-Ig, ST6 was substantially less immunogenic and more stable and durable. Our data suggest that ST6 can serve as a novel, less immunogenic therapeutic strategy for patients with RA.

Ceramide metabolism is known to be an essential etiology for various diseases, such as atopic dermatitis and Gaucher disease. Glucosylceramide synthase (GCS) is a key enzyme for the synthesis of glucosylceramide (GlcCer), which is a main ceramide metabolism pathway in mammalian cells. In this article, we developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to determine GCS activity using synthetic non-natural sphingolipid C8-ceramide as a substrate. The reaction products, C8-GlcCer for GCS, could be separated on a C18 column by reverse-phase high-performance liquid chromatography (HPLC). Quantification was conducted using the multiple reaction monitoring (MRM) mode to monitor the precursor-to-product ion transitions of m/z 588.6 → 264.4 for C8-GlcCer at positive ionization mode. The calibration curve was established over the range of 0.625–160 ng/mL, and the correlation coefficient was larger than 0.999. This method was successfully applied to detect GCS in the human hepatocellular carcinoma cell line (HepG2 cells) and mouse peripheral blood mononuclear cells. We also evaluated the inhibition degree of a known GCS inhibitor 1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) on GCS enzymatic activity and proved that this method could be successfully applied to GCS inhibitor screening of preventive and therapeutic drugs for ceramide metabolism diseases, such as atopic dermatitis and Gaucher disease.
Animals ; Calibration ; Carcinoma, Hepatocellular ; Cell Line ; Chromatography, Liquid ; Dermatitis, Atopic ; Gaucher Disease ; Humans ; Mass Screening ; Mass Spectrometry ; Metabolism ; Methods ; Mice

PURPOSE: It has been studied prognostic factors about secondary displacement after conservative treatment of the distal radius fracture, but each study showed different results. Authors retrospectively evaluated factors known to be involved secondary displacement of the distal radius fracture to determine its significance. METHODS: One hundred eighteen cases of the radiographically unstable distal radius fractures that closed reduction was adequately performed were retrospectively studied and the radiographic images were taken at 1, 2, 3, 4, 6 weeks after closed reduction. During follow-up, dorsal tilt more than 15°, volar tilt more than 20°, ulnar positive variance more than 4 mm, radial length less than 6 mm, radial inclination less than 10° were thought of the loss of reduction. RESULTS: In 41 cases (34.7%), the loss of reduction occurred. Sex, intra-articular fracture, dorsal and volar comminution, concomitant ulnar fracture and involvement of the distal radio-ulnar joint were statistically not significant. Analysis results of the binomial logistic regression model were as follows: age (p=0.003), radial shortening (p=0.010) and ulnar positive variance (p=0.010) were statistically significant as the predictive prognostic factors. Analysis results of the multinomial logistic regression model showed age (p=0.006) as an only statistically significant factor. CONCLUSION: As the predictive prognostic factors for development of secondary displacement after conservative treatment of the unstable distal radius fracture, age was determined as most significant factor. Also radial shortening and ulnar positive variance were thought of the predictive factors for secondary displacement.
Colles' Fracture ; Follow-Up Studies ; Intra-Articular Fractures ; Joints ; Logistic Models ; Radius Fractures* ; Radius* ; Retrospective Studies

The immune correlate of host resistance induced by reinfection of Trichinella spiralis remains unclear. In this study, we investigated immune correlates between the resistance and serum IgG antibody level, CD23⁺ IgM⁺ B cells, and eosinophil responses induced by T. spiralis reinfection. Mice were primarily infected with 10 or 100 T. spiralis larvae (10 TS, 100 TS), respectively, and after 4 weeks, they were challenge infected with 100 T. spiralis larvae (10–100 TS, 100-100 TS). Upon challenge infections, 10–100 TS mice induced significantly higher levels of T. spiralis-specific total IgG antibody responses in sera and antibody secreting cell responses in spleens compared to 100-100 TS mice, resulting in significantly reduced worm burdens in 10–100 TS mice (60% and 70% reductions for adult and larvae, respectively). Higher levels of eosinophils were found in mice primarily infected with 10 TS compared to those of 100 TS at week 8 upon challenge. CD23+ IgM+ B cells were found to be increased significantly in mice primarily infected with 10 TS. These results indicate that primary infection of 10 larvae of T. spiralis, rather than 100 larvae, induces significant resistance against reinfection which closely correlated with T. spiralis-specific IgG, eosinophil, and CD23+ IgM+ B cell responses.
Adult ; Animals ; Antibody Formation ; B-Lymphocytes ; Eosinophils ; Humans ; Immunoglobulin G ; Larva ; Mice* ; Spleen ; Trichinella spiralis* ; Trichinella*

A case of successful correction of subclavian steal syndrome by percutaneous transluminal angioplasty with stenting in a male patient who found incidentally significant interarm blood pressure difference. Small difference in blood pressure (BP) between two arms is a relatively common. Significant interarm BP difference is a potential marker of peripheral vascular disease such as subclavian artery stenosis and a predictor of cardiovascular disease. The subclavian steal syndrome is a condition that results from stenosis of subclavian artery proximal to the vertebral artery. The resulting symptoms are vertebrobasilar insufficiency symptoms due to reversal of blood flow from the contralateral vertebral and basilar artery into the ipsilateral upper extremity vessels and arm ischemic symptoms. Stenotic lesion of subclavian artery has traditionally been treated surgically. However recent trends are undergoing a paradigm shift from open surgery to endovascular approach. We report a patient with subclavian steal syndrome who found incidentally 35 mmHg interarm systolic BP difference. It was successfully treated by percutaneus transradial angioplasty with stenting on stenotic lesion of the subclavian artery.
Angioplasty ; Arm ; Basilar Artery ; Blood Pressure ; Cardiovascular Diseases ; Constriction, Pathologic ; Humans ; Male ; Peripheral Vascular Diseases ; Stents ; Subclavian Artery ; Subclavian Steal Syndrome ; Upper Extremity ; Vertebral Artery ; Vertebrobasilar Insufficiency

Background and Purpose: Elevation of serum cardiac troponin T (cTnT) is regarded as a specific marker of acute coronary syndrome. Serum cTnT can be increased in patients with acute ischemic stroke, but its clinical implications remain unclear. The aim of this study was to identify the relationships between elevated cTnT and stroke severity, location, and prognosis. Methods: From January 2005 to December 2006, this study recruited 455 consecutive patients who were admitted to Kangbuk Samsung Hospital due to acute ischemic stroke within 3 days of onset, which was confirmed by diffusion magnetic resonance imaging. A total of 416 patients was finally included and divided into 2 groups: an elevated cTnT group (n=45) and a normal cTnT group (n=371). The short-term prognosis was assessed by 30-day modified Rankin Scale responder analysis was compared between the two groups. Results: Serum cTnT was elevated in 10.8% of cases, with elevated cTnT associated with greater stroke severity, as assessed by the National Institutes of Health Stroke Scale score, Insular-lobe involvement was more common in patients with elevated cTnT than in the normal cTnT group. Short-term prognosis was more unfavorable in the elevated cTnT group than in the normal cTnT group. Multivariate regression analysis indicated that elevated cTnT was independently related to insular involvement, cardioembolism, and unfavorable outcome. Conclusions: Elevated cTnT in acute ischemic stroke was associated with severe neurological deficits at stroke onset and damages to the insular lobe. The outcome of acute ischemic stroke was worse for patients with elevated cTnT than for those with normal cTnT. The pathomechanism underlying acute ischemic stroke and subclinical myocardial damage warrants further study.
Acute Coronary Syndrome ; Diffusion Magnetic Resonance Imaging ; Humans ; National Institutes of Health (U.S.) ; Prognosis ; Stroke ; Troponin ; Troponin T

PURPOSE: To evaluate the diagnostic capabilities of the low-field (0.2T) magnetic resonance (MR) system in the detection of the superior labrum anterior to posterior (SLAP) lesion. MATERIALS AND METHODS: One hundred fifty patients underwent magnetic resonance imaging of the shoulder over a 7-month period. Forty-six patients underwent arthroscopic surgery, and the surgical results were correlated with the findings of the MR imaging. Arthroscopic procedures were performed within a mean of 8 days after MR imaging. MR imaging of the shoulder was conducted as follows: shoulder coil; T1-weighted spin echo, coronal-oblique images; T2-weighted gradient echo, coronal-oblique and axial images; and T2-weighted spin echo, coronal-oblique and sagittal-oblique images. Prospectively, one radiologist interpreted the MR images. RESULTS: The results of surgery were as follows: SLAP II in 26 shoulders, SLAP III in 1 shoulder, SLAP IV in 1 shoulder, normal labrum in 6 shoulders. For SLAP lesions with a higher grade than type 2, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the low-field MRI were 85.7%, 55.5%, 75%, 71%, and 74%, respectively. CONCLUSION: There was relatively good agreement for the comparison of the MR results obtained using a low-field MR system with the surgical findings for identifying SLAP lesions.
Arthroscopy ; Humans ; Magnetic Resonance Imaging ; Prospective Studies ; Sensitivity and Specificity ; Shoulder

PURPOSE: We wished to compare the ability of ultrasonography and radiography performed on the same day to detect rib fractures in minor chest injuries. MATERIALS AND METHODS: Two hundred and fifteen patients with minor chest injuries were selected. Radiography and ultrasonography were performed on the same day with these patients. Chest wall pain was the only presenting symptom. Two radiologists performed ultrasonography. Fractures were identified by a disruption of the anterior margin of the rib and costal cartilage. The incidence and location of fractures and complications revealed by radiography and ultrasonography were compared. RESULTS: Radiographs revealed the presence of 70 rib fractures in 50 (23%) of 215 patients and ultrasonography revealed the presence of 203 rib fractures in 133 (62%) of 215 patients. Ultrasonography uniquely identified 133 rib fractures in 83 patients. Ultrasonography identified a 2.9 fold increase in the number of fractures in a 2.6 fold number of subjects as compared to radiography. Of the 203 sonographically detected fractures, 201 were located in the rib, one was located at the costochondral junction, and one in the costal cartilage. There were no complications seen by either radiography or ultrasonography. CONCLUSION: Ultrasonography reveals more fractures than those that may be overlooked on radiography for minor chest injuries.
Cartilage ; Humans ; Incidence ; Radiography* ; Rib Fractures* ; Ribs* ; Thoracic Injuries* ; Thoracic Wall ; Thorax* ; Ultrasonography*

PURPOSE: Popular use of fetal ultrasonography has increased to detect congenital hydronephrosis(CH) which is the most common anomaly prenatally detected. We'd like to determine the frequency and clinical characteristics of prenatally diagnosed CH and outcome of ureteropelvic junction stenosis(UPJS). METHODS: The records of births between January 1994 and June 2003 in Chonnam National University Hospital(CNUH), and the records of children who were diagnosed with CH in the Department of Pediatrics of CNUH during the above period, were retrospectively analyzed. In the patients with UPJS, the initial anterior posterior diameters of renal pelvis(APD) were compared between the spontaneous regression (SR) and operation group(OP). In the SR group, sequential regression rates of APD were estimated. RESULTS: Among a total 9,076 births, 231(2.54 percent) patients with 293 renal units were diagnosed as CH and 19(6.78 percent) renal units spontaneously regressed 3 days after birth. In 228 children(56 bilateral; 172 unilateral; total 284 renal units) diagnosed with CH in the department of pediatrics of CNUH, male(71.9 percent) and left kidney(69.2 percent) predilection were found and 78.1 percent of CH were caused by UPJS. The initial APD of the SR group(121 units) in UPJS was 7.8+/-6.28 mm, which was significantly smaller than the APD(26.8+/-12.14 mm) of the OP group(25 unit)(P<0.05). In the SR group, 81 percent spontaneously regressed within one year. CONCLUSIONS: In CH, male and left kidney predilection were found. UPJS was the most common cause of CH and initial APD in UPJS at 3 days of age was a good prognostic indicator. Close monitoring should be done for at least one year because most SR in UPJS regressed spontaneously within one year.
Child ; Constriction, Pathologic* ; Humans ; Hydronephrosis* ; Jeollanam-do ; Kidney ; Male ; Parturition ; Pediatrics ; Retrospective Studies ; Ultrasonography, Prenatal

PURPOSE: The improved availability of breast cancer screening, including mammography, has dramatically increased the detection rate of DCIS (ductal carcinoma in situ). However, there has been controversy regarding the clinico-pathological characteristics and optimal management of DCIS. This analysis was conducted in order to evaluate the clinico- pathological findings of DCIS, and any possible correlations between the known prognostic factors. METHODS: We analyzed 58 consecutive cases of DCIS, from 1990 to 1995, including data on the annual proportion of DCIS to total breast cancer cases, the clinico-pathological characteristics and the expressions of ER, PR, c-erbB-2 and p53. The median length of follow-up was 98.5 months. RESULTS: The proportion of DCIS was 8.8%, with progressive increases from 1990 to 1995. The mean age at diagnosis was 47.1 years, with the peak of prevalence seen in women aged 40~49 years. The most common presentation was a palpable breast mass in 28 (48.3%) cases, but 18 (31%) patients were asymptomatic. The mammographic findings demonstrated calcification in 75% and mass density in 59.6%. There was only 1 (1.8%) case of a bilateral lesion, and 5 (8.6%) of multifocal or multicentric lesions. Axillary lymph nodes were positive in 5.5% of the patients who underwent an axillary dissection. Breast conserving operations were performed in 8 (13.8%) cases. The frequencies of ER, PR, c-erbB-2 and p53, positivity, by immunohistochemistry were 52, 50, 55.1 and 30.6%, respectively. c-erbB- 2 immunoreactivity was found more often in DCIS with larger size, higher nuclear grade and negative ER and PR (P= 0.011, P=0.001, P=0.002, and P=0.006, respectively). There was a significant association between higher nuclear grade and negative ER and PR, and comedotype (P=0.001, P= 0.000, and 0.008, respectively). Although an invasive ductal carcinoma had developed in 5.4% of the contralateral breasts, there were no cases of systemic relapse, or disease-specific mortality, at the last follow-up.
Breast Neoplasms ; Breast* ; Carcinoma, Ductal* ; Carcinoma, Intraductal, Noninfiltrating* ; Diagnosis ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Lymph Nodes ; Mammography ; Mass Screening ; Mortality ; Prevalence ; Recurrence