Objective This study has explored the role of antibody against annexin A2 in patients with antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). Methods Using purified recombinant annexin A2, IgG anti-annexin A2 antibody was measured by ELISA in 101 APS patients, 41 SLE patients with thrombosis, 124 SLE patients without thrombosis and 120 healthy controls. Results The positive rate of IgG anti-annexin A2 antibody in APS patients and SLE patients with thrombosis was 21.8%, 26.8%, respectively, they were all significantly higher than in SLE patients without thrombosis (6.5%). IgG anti-annexin A2 antibody was associated with thrombosis and/or pregnancy morbidity (P<0.01). Conclusion Anti-annexin A2 antibody is associated with thrombosis and/or pregnancy mnrbidity. It suggests that anti-annexin A2 antibody may be helpful in identifying in some potential AIRS.

Objective To compare the efficacy and predictability of sphere-cylinder-combined LASIK and two-zone cross-cylinder LASIK for the correction of moderate and high astigmatism.Design Prospective,comparative case series.Participants 40 eyes of 35 patients with mixed astigmatism undergoing LASIK.Methods All patients were treated with Visx Star IV LASIK system.20 eyes of 19 cases were used for sphere-cylinder combined LASIK mode and 20 eyes of 16 cases for two-zone-cross-cylinder LASIK mode.All sub- jects were followed more than 6 months.Main Outcome Measures Uncorrected visual acuity (UCVA),best spectacle-corrected visual acuity (BSCVA),spherical diopter,residual astigmatism and corneal thickness.Results For the patients who received two-zone-cross-cylinder LASIK mode,the UCVA at 6 months after surgery was 0.5 or above,and 13 eyes (65.0%) were 1.0 or above. For the patients who received sphere-cylinder-combined LASIK mode,the UCVA at 6 months after surgery was 0.5 or above,and 11 eyes (55.0%) was 1.0 or above (P=0.683).The residual astigmatism for the patients received sphere-cylinder-combined LASIK mode was (1.15?1.00)D,while for the patients received cross-cylinder LASIK mode was (1.13?0.62)D(P=0.045).The remotion depth of cornea for sphere-cylinder-combined LASIK mode and cross-cylinder LASIK mode was (36.73?13.12)?m and (15.60?6.85)?m,respectively (P= 0.031).Condusion The UCVA,residual astigmatism and corneal thickness after surgery in two-zone-cross-cylinder LASIK mode were better than that in sphere-cylinder-combined LASIK mode for the correction of moderate and high astigmatism.

IgA nephropathy is one of the most common forms of primary glomerulonephritis in adults, and the pathogenetic mechanisms seem to be diverse. Proinflammatory cytokines, Th1/Th2 cytokines, and chemokines would be involved in the pathogenetic pathways and would affect the functional and histologic consequences. To evaluate this hypothesis, we tried to quantify the magnitude of intrarenal gene expression of various cytokines(TNF-alpha, IL-1beta, IL- 6, IL-15, IFN-gamma, IL-2, IL-10) and chemokines(IL-8, RANTES) in 61 renal core biopsy specimens confirmed as IgA nephropathy by immunofluorescent microscopy. Semiquantitative reverse-transcriptase polymerase chain reactions(RT-PCR) using the internal competitors were done for the quantification of gene transcripts. And using the immunohistochemistry (IHC), we tried to determine the degree of expression and the location of various cytokines and chemokines in renal tissues in 29 patients among the above patients. The IFN-gamma/IL-10 ratio was higher in patients with renal dysfunction than that in patients with normal renal function(p=0.0483). Gene transcript levels of proinflammatory cytokines(TNF-alpha, IL-1beta) were high in patients with significant proteinuria. In patients with severe glomerular sclerosis, the ratio of IFN-gamma/IL-10 gene transcripts was high(p=0.0363). IL-10 gene transcript level was related to the severity of tubulointerstitial damage. The levels of gene expression of TNF-alpha(p=0.0026), IL-10(p=0.0092) and IFN-gamma(p=0.0188) were related to the degree of mesangial matrix expansion, and the extent of intrarenal arteriolar lesions correlated with the expression of the IL-8 genetranscript(r=0.3828, p=0.0033). The cellular infiltration in glomeruli was related with chemokine(IL-8) gene expression, but the relation was not significant statistically. The degree of IgA deposition in glomeruli was related with the expression of IL-6 and IL-15. The expression of intrarenal gene transcripts of various cytokines and chemokines were closely interrelated. Th1 or Th2 cytokine polarization was not present in IgA nephropathy. In IHC, TNF-alpha, IFN-gamma and IL-2 were immunostained dominantly in mesangial region, but not in tubulointerstitial region. In contrast, positive reactions for IL-10 were observed mainly in tubules. The significant reactions for IL-8 were noted in the periarteriolar and arteriolar areas. The results of RT- PCR and IHC showed positive relationships, but those were not significant statistically. This study suggests that proinflammatory, Th1/ Th2 cytokines and chemokines are involved in the specific processes of inflammation and immunologic injury, and their predominance and the level of expression could determine the pathogenetic processes and the severity of the clinical manifestations in IgA nephropathy.
Adult ; Biopsy ; Chemokines* ; Cytokines* ; Gene Expression ; Glomerulonephritis ; Glomerulonephritis, IGA* ; Humans ; Immunoglobulin A* ; Immunohistochemistry ; Inflammation ; Interleukin-10 ; Interleukin-15 ; Interleukin-2 ; Interleukin-6 ; Interleukin-8 ; Microscopy ; Polymerase Chain Reaction ; Proteinuria ; Sclerosis ; Tumor Necrosis Factor-alpha

Uteroglobin(UG) is an anti-inflammatory/immunomodulatory protein secreted by the epithelial cells of vertebrates. Targeted disruption of UG rendered mouse glomerulonephritis resembling IgA nephropathy(IgAN). Sequence analysis on exon 1 of UG showed several putative binding sites for transcription factors, and genetic polymorphisms in this site might influence the expression level of UG as a competitive protein. We speculated that the single nucleotide polymorphism at the 38th nucleotide from the transcription initiation site of UG exon 1 would impact the progression of IgAN. PCR-RFLP was instituted to determine the genetic polymorphism in 60 patients with IgAN. Other measures like SSCP and direct sequencing were also adopted for the verification of polymorphic sites. Seventeen patients with IgAN(28%) were homozygous for adenine at position 38(38AA), 26 patients(43%) were heterozygous(38AG), and 17 patients(28%) were homozygous for the polymorphism(38GG), which was similar to the pattern obtained from the 60 normal controls. The amount of daily proteinuria, presence of hypertension, the level of IgA, and the amount of IgA-fibronectin(FN) complexes was similar between the genotypes. Serum IgA-FN level did not influence the progression of disease. However, 8 out of 17 patients (47%) with the AA genotype had progressive disease(PD), 10 of 26 patients(38%) with the AG genotype had PD, and only 1 of 17 patients(6%) with GG homozygocity had PD after 94+/-30.1 months of follow-up(mean+/-S.D.). The odds ratio for the progression of renal disease in patients with the AA genotype was 14.93(p=0.0355) and in patients with AG genotype was 12.94(p=0.0496) compared with patients have the GG genotype. Moreover, serum creatinine at the time of kidney biopsy was higher in patients with AA and AG genotypes than in patients with the GG genotype(1.5+/-0.69 : 1.3+/-0.53 : 1.0+/-0.31mg/dL; AA : AG : GG; p=0.0137 AA vs. GG; p=0.0269 AG vs. GG). Our results suggest that polymorphism at the 5' UTR region of UG exon 1 is an important marker for the progression of IgAN.
5' Untranslated Regions* ; Adenine ; Animals ; Binding Sites ; Biopsy ; Creatinine ; Epithelial Cells ; Exons* ; Genotype ; Glomerulonephritis ; Glomerulonephritis, IGA* ; Humans ; Hypertension ; Immunoglobulin A* ; Kidney ; Mice ; Odds Ratio ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; Polymorphism, Single-Stranded Conformational ; Proteinuria ; Sequence Analysis ; Transcription Factors ; Transcription Initiation Site ; Uteroglobin* ; Vertebrates

IgA nephropathy(IgAN) is the most common glomerulonephritis(GN) in worldwide, and accounts for 20% to 40% of all patients with primary GN in Korea. IgAN has diverse clinical courses, but the risk factors affecting the deterioration of renal function are not established. Recently, there were some suggestions that systemic or local expression of peptides of angiotensin system exerts several effects on the progression of renal disease, and the genetic polymorphisms may associated with peptide expression. To evaluate the role of genetic polymorphism of angiotensin I converting enzyme(ACE) polymorphism in the progression of IgAN, the genotypic distributions in 278 biopsy-proven cases of IgAN were studied, which had undergone a renal biopsy at Seoul National University Hospital, between 1979 and 2000. We also compared the genotypes with clinical manifestations to evaluate the clinical implications of genetic polymorphism. The study shows that there was no difference in the ACE genotype frequencies between the patients (II : 26.6%, ID : 55.0%, DD : 18.4%) and normal controls(II : 31.4%, ID : 57.4%, and DD : 11.2%). Seventy- two percent and 48% of patients maintained renal function for 10 years and 20 years after the initial diagnosis in 278 patients, respectively. However, in 153 patients who were followed more than 5 years, the DD genotype was more prevalent in patients with deteriorating renal function than in those with stable renal function(31.8% vs. 13.8%; p=0.0146). Presence of systemic hypertension increased the risk of renal disease progression(OR=3.3), and it was showed 7.4 fold risk whenever the creatinine was increased by 1 mg/dL. Renal disease progression is not associated with DD genotype among normotensive patients at the biopsy. But, in patients with hypertension, II and DD/ID genotypes have an increased risk for disease progression when compared with II genotype of normotensive patients(OR=1.4, OR=7.8; respectively). ACE polymorphisms did not have any interaction with the levels of serum creatinine at the time of biopsy in our patients. Our results suggested that ACE genotypes(D allele) affected the progression of IgAN, especially in hypertensive patients. One of the prospects of the present study is the potential for screening high risk individuals, thus helping to develop a practical application of the molecular findings in clinical practice.
Angiotensin I* ; Angiotensins* ; Biopsy ; Creatinine ; Diagnosis ; Disease Progression ; Genotype ; Glomerulonephritis, IGA* ; Humans ; Hypertension ; Immunoglobulin A* ; Korea ; Mass Screening ; Peptides ; Peptidyl-Dipeptidase A* ; Polymorphism, Genetic ; Risk Factors ; Seoul