Effects of human parvovirus B19 VP1 unique region protein on macrophage responses

<p>Abstract</p> <p>Background</p> <p>Activity of secreted phospholipase A (sPLA2) has been implicated in a wide range of cellular responses. However, little is known about the function of human parvovirus B19-VP1 unique region (VP1u) with sPLA2 activity on macrophage.</p> <p>Methods</p> <p>To investigate the roles of B19-VP1u in response to macrophage, phospholipase A2 activity, cell migration assay, phagocytosis activity, metalloproteinase assay, RT-PCR and immunoblotting were performed.</p> <p>Results</p> <p>In the present study, we report that migration, phagocytosis, IL-6, IL-1β mRNA, and MMP9 activity are significantly increased in RAW264.7 cells by B19-VP1u protein with sPLA2 activity, but not by B19-VP1uD175A protein that is mutated and lacks sPLA2 activity. Additionally, significant increases of phosphorylated ERK1/2 and JNK proteins were detected in macrophages that were treated with B19-VP1u protein, but not when they were treated with B19-VP1uD175A protein.</p> <p>Conclusion</p> <p>Taken together, our experimental results suggest that B19-VP1u with sPLA2 activity affects production of IL-6, IL-1β mRNA, and MMP9 activity, possibly through the involvement of ERK1/2 and JNK signaling pathways. These findings could provide clues in understanding the role of B19-VP1u and its sPLA2 enzymatic activity in B19 infection and B19-related diseases.</p

Human parvovirus B19 nonstructural protein NS1 enhanced the expression of cleavage of 70 kDa U1-snRNP autoantigen

<p>Abstract</p> <p>Background</p> <p>Human parvovirus B19 (B19) is known to induce apoptosis that has been associated with a variety of autoimmune disorders. Although we have previously reported that B19 non-structural protein (NS1) induces mitochondrial-dependent apoptosis in COS-7 cells, the precise mechanism of B19-NS1 in developing autoimmunity is still obscure.</p> <p>Methods</p> <p>To further examine the effect of B19-NS1 in presence of autoantigens, COS-7 cells were transfected with pEGFP, pEGFP-B19-NS1 and pEGFP-NS1K334E, a mutant form of B19-NS1, and detected the expressions of autoantigens by various autoantibodies against Sm, U1 small nuclear ribonucleoprotein (U1-snRNP), SSA/Ro, SSB/La, Scl-70, Jo-1, Ku, and centromere protein (CENP) A/B by using Immunoblotting.</p> <p>Results</p> <p>Significantly increased apoptosis was detected in COS-7 cells transfected with pEGFP-B19-NS1 compared to those transfected with pEGFP. Meanwhile, the apoptotic 70 kDa U1-snRNP protein in COS-7 cells transfected with pEGFP-B19-NS1 is cleaved by caspase-3 and converted into a specific 40 kDa product, which were recognized by anti-U1-snRNP autoantibody. In contrast, significantly decreased apoptosis and cleaved 40 kDa product were observed in COS-7 cells transfected with pEGFP-NS1K334E compared to those transfected with pEGFP-B19-NS1.</p> <p>Conclusions</p> <p>These findings suggested crucial association of B19-NS1 in development of autoimmunity by inducing apoptosis and specific cleavage of 70 kDa U1-snRNP.</p

Longitudinal Changes in Retinal Nerve Fiber Layer Thickness after Acute Primary Angle Closure Measured with Optical Coherence Tomography

PURPOSE. Longitudinal follow-up of peripapillary retinal nerve fiber layer (RNFL) thickness after an episode of acute primary angle closure (APAC) using Stratus optical coherence tomography (OCT). METHODS. Seventeen patients who had experienced a single unilateral APAC episode (intraocular pressure, Ͼ50 mm Hg) were enrolled. The average and superior, temporal, inferior, and nasal quadrant RNFL thicknesses of the affected and fellow eyes at 1, 4, and 12 weeks after remission were compared by using StratusOCT. The relationship between average RNFL thickness and interval of follow-up were evaluated with regression analysis. RESULTS. The mean duration of the APAC episode was 13.8 hours (range, 3-40). Comparison of the average and four quadrant RNFL thicknesses in the affected eyes longitudinally showed significant differences between 1 and 4, and 1 and 12 weeks, but not between 4 and 12 weeks. The average and four-quadrant RNFL thicknesses for the affected eyes were greater than the analogous values for fellow eyes at 1 week. In contrast, the inferior-and superior-quadrant RNFL thicknesses for the affected eyes were lower at 4 and 12 weeks, whereas the average and nasal quadrant values for the affected eyes were lower than those in fellow eyes at 12 weeks. Average RNFL thickness for the affected eyes was correlated with the interval of follow-up by using inverse regression analysis (P Ͻ 0.001; R 2 ϭ 0.60). Controlling for duration of APAC episode, the interval of follow-up on RNFL thickness reduction remained significant (P Ͻ 0.001, r ϭ Ϫ0.69). CONCLUSIONS. This study demonstrated an initial increase in diffuse RNFL thickness after a single APAC episode, followed by a subsequent decrease. (Invest Ophthalmol Vis Sci. 2007; 48:1659 -1664) DOI:10.1167/iovs.06-0950 A cute primary angle closure (APAC) is an ophthalmic emergency and a potentially blinding disease. Optic nerve damage can occur after the sudden rise in intraocular pressure (IOP) associated with an APAC episode. The optic disc appears edematous during this episode, and pallor with or without cupping may develop after remission. When treatment is delayed, vision may be markedly reduced to hand movement or light perception. 1 Perimetric examination during acute episodes is difficult and usually unreliable. After remission, visual field defects vary greatly in severity and type. 2 Measurement of retinal nerve fiber layer (RNFL) thickness loss after APAC is very important, as it is both objective and sensitive in terms of detection of the optic disc damage with either normal or unreliable visual fields. Scanning laser polarimetry with fixed corneal compensator (SLP-FCC) has been used for quantification of RNFL thickness change after APAC in cross-sectional study, 5 However, the latter investigation included several patients with poor IOP control after an APAC episode, as determined by RNFL measurement at follow-up. Moreover, SLP-FCC has limited functionality in measurement of RNFL thickness because of the lack of correction for variation in corneal polarization axis and corneal curvature. StratusOCT is a powerful imaging technology that can measure RNFL thickness and image tissue structure to an axial resolution of Ͻ10 m. 7 The stronger association with function in StratusOCT RNFL measurement compared with SLP-VCC suggests that the former may be superior for evaluation of glaucoma progression. 8 Therefore, the purpose of this study was to use StratusOCT to detect longitudinal change (1-12 weeks) in RNFL thickness after remission from a single APAC episode. MATERIALS AND METHODS In this prospective study, longitudinal observations were made using RNFL measurements obtained from StratusOCT at 1, 4, and 12 weeks after a single episode of unilateral APAC. Seventeen consecutive patients were recruited while undergoing treatment in the emergency or the ophthalmology outpatient departments of the Chang Gung Memorial Hospital-Kaohsiung Medical Center over a 1-year period. The study and data accumulation were in conformity with all relevant Taiwanese laws, and the investigation was conducted in accordance with the tenets of the Declaration of Helsinki. The APAC definition used for the study consisted of: The inclusion criteria were: (1) duration of episode less than 48 hours (interval from onset of acute symptoms to first hospital presentation); (2) resolution of acute episode and IOP control (Ͻ21 mm Hg) after antiglaucoma medication prescribed on first presentation, with interval between presentation and resolution under 2 hours (patients were treated with intravenous mannitol drip, oral acetazolamide, topical ␤-blocker and pilocarpine; the IOP was then rechecked 30 to 60 minutes after treatment); (3) subsequent laser iridotomy (LI) performed within 2 days of presentation on both affected and fellow eyes; and, (4) IOP Ͻ 21 mm Hg in both eyes for up to 12 weeks after treatment. Antiglaucoma medication was used to control IOP before and after LI in both eyes to prevent elevation (IOP Ͼ 21 mm Hg). The exclusion criteria were: (1) history of previous APAC in the affected or fellow eyes; (2) previous intraocular surgery, coexisting From th

Healthcare costs associated with progressive diabetic retinopathy among National Health Insurance enrollees in Taiwan, 2000-2004

<p>Abstract</p> <p>Background</p> <p>Diabetic retinopathy is one of the most common microvascular complications of diabetes and one of the major causes of adult visual impairment in national surveys in Taiwan. This study aimed to identify the healthcare costs of Taiwan's National Health Insurance program on behalf of diabetic patients with stable or progressive retinopathy.</p> <p>Methods</p> <p>A retrospective cohort study was conducted with 4,988 medication-using diabetic retinopathy subjects ≥ 40 years of age under National Health Insurance Program coverage between 2000 and 2004. Study cohort subjects were recorded as having diabetic retinopathy according to ICD-9-CM codes. States of diabetic retinopathy were strategically divided into stable and progressive categories according to subjects' conditions at follow-up in 2004. Expenditures were calculated and compared for the years 2000 and 2004.</p> <p>Results</p> <p>During the 4-year follow-up (2000 through 2004), 4,116 subjects (82.5%) of 4,988 diabetic subjects were in the stable category, and 872 (17.5%) were in the progressive category. Average costs of those in the normal category increased by US $48 from US$1921 in 2000 to US $1969 in 2004 (p = 0.594), whereas costs for those progressing from normal to non-proliferative diabetic retinopathy (NPDR) or proliferative diabetic retinopathy (PDR) increased by US$1760, from US $1566 in 2000 to US$3326 in 2004 (p < 0.001). The PDR category had the highest average costs at US $3632 in 2000. The NPDR-to-PDR category experienced the greatest increase in costs at US$3482, from US $2723 in 2000 to US$6204 in 2004 (p = 0.042), and the greatest percentage of increase at 2.3% (2.2% when adjusted by comparing to normal category).</p> <p>Conclusions</p> <p>This large-scale longitudinal study provides evidence that increased healthcare costs are associated with progressive diabetic retinopathy among diabetic NHI enrollees in Taiwan.</p

Efficacy of Femarelle for the treatment of climacteric syndrome in postmenopausal women: An open label trial

AbstractObjectiveTo assess the effects of 2 months of treatment with Femarelle for climacteric syndrome in Taiwanese postmenopausal women.Materials and methodsA multi-center, open-label trial of 260 postmenopausal women, age ≥ 45 years with vasomotor symptoms. Women were enrolled after obtaining a detailed medical history and a thorough physical examination. They then received Femarelle (640 mg/d) twice daily for 8 weeks. The primary outcome was the changes in the frequency and severity of hot flushes from baseline to 4 weeks (1 month) and 8 weeks (2 months). Changes of general climacteric syndrome were assessed using a modified climacteric scale designed by Greene.ResultsThe frequency and severity of hot flushes were significantly improved with Femarelle use (p < 0.001). After 8 weeks of treatment, the percentage of women with various climacteric syndromes was reduced (from 100% to 20.9% for hot flushes, from 97.7% to 87.9% for psychological symptoms, from 93.8% to 78.8% for somatic symptoms, and from 87.8% to 74.9% for sexual symptoms). General climacteric syndrome scores also significantly decreased, from 20.8 ± 0.7 at the time of enrollment to 12.9 ± 0.7 after 8 weeks of Femarelle treatment (p < 0.0001). Participants experienced improvement of various climacteric symptoms and signs after 8 weeks of treatment (75.1% for hot flushes, 68.7% for psychological symptoms, 70.6% for somatic symptoms, and 69.0% for sexual problems respectively). After 4 weeks and 8 weeks of treatment with Femarelle, patients showed statistically significant improvement in climacteric symptoms (p < 0.0001). Three women (1.2%) withdrew from the study after 4 weeks of treatment due to adverse effects.ConclusionFemarelle significantly improved climacteric symptoms in Taiwanese postmenopausal women. However, further evaluation is needed regarding the safety of long-term consumption

Comparative Geochemistry of 234Th, 210Pb, and 210Po: A Case Study in the Hung-Tsai Trough off Southwestern Taiwan

Detailed profiles of dissolved and particulate 234Th, 210Pb, and 210Po activities at three stations in the Hung-Tsai Trough off south western Taiwan were determined. The total 234Th activ ity is 20 ~ 25% deficientfrom its secular equilibrium in the entire water column. Except for an evident excess of 210Po at some depths in the mixed layer and in the pycnocline layer, total 210Po activity is also lower than total 210Pb activity. As a result of atmospheric deposition, 210Pb is about 25% in excess of its parent, 226Ra, through out the water column of the Hung-Tsai Trough. The ratios of the distribution coefficients of 234Th, 210Pb, and 210Po show that the order of particle affinity is Po > Th ~ Pb in the mixed layer and bottom layer, whereas the order changes, due to particlere generation, into Th > Pb > Po in the pycnocline layer of the Hung-Tsai Trough

Effects of Growth Hormone Treatment on Height, Weight, and Obesity in Taiwanese Patients with Prader-Willi Syndrome

BackgroundInformation regarding the efficacy of growth hormone (GH) therapy in Asian Prader-Willi syndrome (PWS) patients is lacking. We report our experience with GH treatment in children with PWS in Taiwan.MethodsForty-six PWS patients (27 males, 19 females; age range, 1 year 4 months to 13 years 7 months) who received and/or who are currently receiving GH treatment (0.1 IU/kg/day subcutaneously) for a period from 1 year to 3 years were retro-spectively analyzed. We evaluated height, weight, body mass index (BMI) and Rohrer index, before and after GH treatment.ResultsAfter patients had received GH for 1, 2 and 3 years, a significant improvement in mean height standard deviation score (SDS) was noted from −1.24 to −0.31 (p <0.01), 0.00 (p <0.001) and −0.26 (p <0.001), respectively. Mean BMI SDS decreased significantly from 1.93 to 1.13 (p <0.05) after 1 year of treatment; however, no significant changes were observed afterward. Mean Rohrer index decreased significantly, from 224.2 to 186.6 (p <0.001), 178.9 (p <0.001) and 169.3 (p <0.001). No significant gender or genotype pattern differences were noted among the 4 parameters examined.ConclusionThis 3-year, retrospective study indicates that PWS patients benefit from GH therapy in height increase and improved body composition