This still begs the question of precisely how IL-23 fits in the Th17 model. Naive T cells do not express the IL-23 receptor (IL-23R); however, when exposed to IL-6, IL-23R expression is up-regulated in a STAT3-dependent manner.[49] Over-expression of a hyperactive variant of STAT3 potentiated T-cell production of IL-17

and increased expression of Th17-associated genes, such as IL-23 and RORγt. Conversely, conditional knockout of STAT3 abolished Th17 differentiation, providing a partial explanation as to why IL-23 itself, in the absence of IL-6 or STAT3 signalling, did not have biological activity on Th17. Gene expression analysis of naive T cells stimulated IWR-1 in vitro with Th17 polarizing cytokines found that IL-21 and IL-23R were highly up-regulated in response to IL-6.[50] Forced expression of IL-23R overcame the requirement for IL-6 in Th17 polarization, though this still depended upon activation of RORγt, the expression

of which is inducible via IL-23/IL-23R signalling. Curiously, signalling through IL-21/IL-21R could also replace IL-6 in polarizing assays, suggesting that IL-6 functions as an upstream signal to IL-21. The IL-21-mediated Th17 induction also depended on STAT3 activation. Although in vitro studies using IL-21R−/− cells exhibited click here an inhibition to induce IL-17 production in response to IL-6 and TGF-β, however, clear defects in Th17 induction were not observed in vivo in IL-21R−/− mice. Collectively, these data indicate that IL-6 functions

as an instructive cue to induce buy Sirolimus T-cell expression of IL-21, which both signals through STAT3 and increases its expression. This leads to feed-forward STAT3 activation and sensitization of cells to IL-23 by promoting expression of IL-23R. The TGF-β and IL-6 signals induce expression of RORγt, which in combination with STAT3, synergistically drives the Th17 programme. The requirement for TGF-β in programming Th17 is intriguing because TGF-β can also induce Treg cell development.[51] The decision between Treg and Th17 appears to be dictated by levels of TGF-β and IL-6:[44, 52] IL-6 signalling can block Treg cell differentiation, presumably through STAT3 activation. Since S1P1 signalling may activate STAT3[39] in tumour cells, it would be interesting to know if cells from S1P1 over-expressing transgenic animals, particularly T cells, have enhanced STAT3 activation. One hypothesis for how S1P1 inhibits Treg cell development is interference with the TGF-β signalling pathway.[53] The TGF-β signalling can induce the expression of both the RORγt (Th17-driving) and Foxp3 (Treg-driving) transcription factors, and these factors can be co-expressed.[52] There is cross-talk between the two programmes, as Foxp3 is known to inhibit RORγt function and hence Th17 differentiation. If the S1P1 transgenic animals used by Liu et al.

The significance TNF-α-TNFR1 interaction is also underscored in SLE. Zhu et al. have observed that SLE patients have increased levels of TNFRI, TNFRII and TRAF2 and decreased levels of RIP [170]. However, no correlation was found among soluble TNFR1/2 and serum TNF-α levels or their RNA expression [170]. It is important to note that lupus-prone NZB/F1 mice deficient in both TNFR1 and TNFR2 showed accelerated course of disease [171]. Conversely, NZB/F1 mice deficient in https://www.selleckchem.com/products/Trichostatin-A.html TNFR1 or TNFR2 had a comparable phenotype [171]. TNFR1, but not TNFR2, was expressed dominantly in skin lesions of MRL/lpr mice [172]. Taken together, these data indicate that TNF-α is a critical parameter

of several autoimmune diseases and its blockade ameliorates as well as exacerbates autoimmune disease pathology (Table 1, Fig. 1g). The TNF-α-related apoptosis-inducing ligand (TRAIL; Apo2L) is a type II membrane protein and plays an important role in immune regulation [173,174]. In humans, TRAIL expression is inducible on IFN-γ activated fibroblasts [175], peripheral blood monocytes [176], monocyte-derived DCs

[177], immature NK cells [178], T cells [179–181] and NK T cells [182]. In the case of mice, TRAIL is expressed by activated NK [183] and liver NK cells [184,185]. TRAIL binds to two death receptors: death receptor (DR) 4 and DR5 and two decoy receptors: decoy receptor (DcR1) 1 and DcR2, and following binding to its death receptors DR4 and DR5 TRAIL can induce apoptosis, as they contain intracellular ABT-263 in vitro death domains [186–188]. Incidentally, the binding of TRAIL to DR5 can also activate the transcription factor NF-κB, which is known to control cell proliferation [189]. Thus, depending on the cellular system, TRAIL is capable of initiating apoptosis or cell survival. Importance of the TRAIL pathway in autoimmune diseases is revealed by

a number of studies. Chronic in vivo blockade of TRAIL–DR5 interaction by soluble DR5 has been shown to induce hyperproliferation of synovial cells and arthritogenic lymphocytes, resulting in increased production of proinflammatory cytokines and autoantibodies leading to exacerbation of arthritis [190]. That the TRAIL pathway Phloretin plays critical roles in arthritis is also corroborated by amelioration of disease by intra-articular transfer of the TRAIL gene [190,191] and by intraarticular transfer of recombinant TRAIL [192]. Further proof that the TRAIL signal is important in arthritis pathogenesis came from gene knock-out studies which showed that TRAIL deficiency increases the susceptibility of mice to autoimmune arthritis [193]. Interestingly, Liu et al. have reported that adoptive transfer of TRAIL-transfected DCs pulsed with collagen into susceptible mice suppressed disease pathology [194].

The following antimouse antibodies were used for staining from BD Biosciences (San Jose, CA, USA): CD3-fluorescein isothiocyanate (FITC), CD4-PerCP, IFN-γ-PE, CD11c-PE, PDCA-1-PE, MHC II-FITC, CD80-Alexa647, CD86-Alexa647, CD11b-PerCP-Cy5.5, B220-PerCP, Langerin-allophycocyanin, Ly6C-FITC, and isotype

controls. Flow cytometry analysis was performed on a FACS Canto II cytometer (BD Biosciences). Isolation of dermal single cells was performed as previously described [22]. Isolation of immune cells using Percoll gradient from spinal cords was performed as presiously described [23]. In the present EAE model, almost all infiltrates are located in the spinal cord [13]. Therefore, spinal cords from three mice per group were pooled

to obtain detectable amounts of cells for flow cytometry. To assess the number of IL-17A-secreting splenocytes from MOG immunized or unimmunized mice, an ELISPOT method was used as previously this website described [13]. Differences between mean daily EAE scores for individual mice, gene expression, and cytokine levels were analyzed with Mann–Whitney’s U-test. p-values lower than 0.05 were considered significant. All analyses were performed using Graphpad Prism™ 4.0 software. We would like to thank Dr. Dan Kaplan and Dr. Botond Igyarto, Minnesota University, for sharing their protocol of isolation of dermal DCs; and Dr. Jenny H. Martinsson, Uppsala University, for sharing her protocol of generation of bone marrow

chimeras. We would also like to thank Rakan Naboulsi for excellent technical assistance. This work was supported by a grant from Dabrafenib datasheet The Swedish Research Council, The Swedish Research Council Formas, Petrus and Augusta Hedlund’s why Foundation, Tornspiran foundation, The Hoff family (via The Swedish Brain Foundation), The Swedish Association for the Neurologically Disabled, Torsten and Ragnar Söderbergs Foundation, The Lars Hierta Memorial Foundation, and Magnus Bergvall’s Foundation. No funding source had any involvement in study design, collection, analysis, or interpretation of the data. Further, no funding source had any involvement in writing or submitting the paper. The authors declare no financial or commercial conflict of interest. Disclaimer: Supplementary materials have been peer-reviewed but not copyedited. Table S1. Percent depletion of CD11chi MHC II+ mDC after DTx injection of CD11c-DTR mice or BM chimeras- before or after MOG immunization Table S2. Percent depletion of CD11cintermediate MHC II+ CD11b+ inflDC after DTx injection of BM chimeras- before or after MOG immunization Figure S. DTx-treatment of CD11c-DTR mice do not lead to ablation of T cells, CD11b+ cells, B220+ cells or Ly6Chi CD11b+ monocytes in the spleen. “
“Radiotherapy is an efficient remedy in the treatment for bladder carcinoma (BCa); still, some cancer cells can survive from the radiation; the therapeutic effect is to be improved.

13 Although incompletely documented, non-human primates appear to possess subpopulations of dendritic cells (DCs) and B cells that are similar

to those present in humans.14,15 Non-human primates are therefore valuable for studies aimed at investigating immune responses induced by human pathogens and vaccine components aimed for human use.16,17 Several reports indicate that TLR ligands show potency as vaccine adjuvants when tested in rhesus macaques18–20 or in human clinical trials.21–23 Subsets of human DCs and B cells express distinct repertoires of TLRs and they respond to TLR stimulation accordingly.2,24,25 Unlike rodents, rhesus macaques express a similar repertoire of TLRs on immune cells such as DCs and B cells as humans.26 Some differences between the human and rhesus macaque immune systems have been reported.17 An improved understanding about similarities check details and disparities between human and non-human primate immune functions is therefore important and would provide valuable information for translating non-human

primate studies for the design of clinical trials aimed at testing new vaccine and treatment strategies. In this study, we performed a side-by side comparison of the phenotypes of human and rhesus DCs and B cells and we examined their responsiveness to well-defined ligands targeting TLR3, 7/8, and 9. We further asked if IFN-α comparably enhanced B-cell functions such as proliferation and differentiation into antibody-producing cells as EMD 1214063 molecular weight observed in culture systems of human cells. We found similar responses in human and rhesus primary cell cultures to TLR ligand stimulation in terms of B-cell proliferation and induction of IFN-α production by pDCs. In both species, B-cell proliferation to the TLR7/8 ligand (-L) and CpG class C showed a significant increase in the presence of IFN-α. Some phenotypic differences between human and rhesus B cells were observed as the cells differentiated

DNA Synthesis inhibitor into antibody-producing cells, although in both species TLR stimulation promoted maturation of B cells into IgM-producing cells and this effect was enhanced in the presence of IFN-α. Untreated and healthy rhesus macaques of Chinese origin, 5–6 years old, were housed in the Astrid Fagraeus laboratory at the Swedish Institute for Infectious Disease Control. Housing and care procedures were in compliance with the provisions and general guidelines of the Swedish Animal Welfare Agency. All procedures were approved by the Local Ethical Committee on Animal Experiments. The animals were housed in pairs in 4-m3 cages and enriched daily. All blood samplings were performed under sedation with ketamine at 10 mg/kg (100 mg/ml Ketaminol; Intervet, Sollentuna, Sweden). All animals were confirmed negative for simian immunodeficiency virus, simian T-cell lymphotropic virus, and simian retrovirus type D.

Using the Pressure-Specified Sensory Device epicritic, proprioceptive, and protopathic sensitivities Cabozantinib order were tested. Outcomes were compared with those of a control group of 5 patients addressed to reconstruction with perforator flaps (3 anterolateral thigh flap, 2 vertical deep inferior perforator flap). At mean 21-month follow-up all flaps healed uneventfully without need for revisions, all developing more satisfactory results in terms of skin color (P = 0.028) and texture (P = 0.021) match, shape (P = 0.047) and bulkiness (P =

0.012) compared with perforator flaps. No differences in epicritic, proprioceptive, and protopathic sensitivities were observed (P > 0.05) between the two groups. Skin-grafted LD flap may be a suitable option for reconstruction of wide defects of the lateral aesthetic units of the face. © 2014 Wiley Periodicals, Inc. Microsurgery, 2014. “
“The objective of this study was to determine precise localization and external diameter of the lower abdominal wall perforators as well as to investigate some vascularity differences between the same parts of perfusion zones II and III according to Hartrampf perfusion MK-2206 in vitro zones. The study was performed

on 10 fresh cadavers (20 hemiabdomens) using the gelatin injection technique. All perforators were identified, and their localization and diameter were noted. Measurements were made at the level of the fascia. We noted localization and diameter of arteries on cross-sectional planes of either part of the flap. The median sum of the external diameter of all arteries in zone I was 17.01 mm. The median sum of the external diameter of all arteries in the medial 1/3 part of zone III was 4.17 mm, and in the medial 1/3

part of zone II, it was 0.96 mm. The median sum of the external diameter of all arteries in the intermediary 1/3 ID-8 part of zone III was 2.16 mm, whereas in the intermediary 1/3 part of zone II, it was 0.81 mm. Significant differences were recorded between proximal and middle horizontal regions of zones II and III and between medial vertical part of zone III and medial vertical part of zone II. Anastomoses between zones I and II are considerably smaller compared with anastomoses between zones I and III. The best vascularized parts of the lower abdominal wall were perfusion zone I, then the inner 2/3 of zone III and medial 1/3 of zone II. © 2011 Wiley Periodicals, Inc. Microsurgery, 2012. “
“Controversy exists over how long a free flap is dependent on its pedicle and if neovascularization is different between flap types, recipient sites, and irradiated and nonirradiated patients. An understanding of the timing of this process should optimize the safety of secondary procedures involving the flap. In a prospective clinical study, hemoglobin oxygenation and capillary flow were measured in 50 flaps (25 forearm flaps, 15 osteocutaneous fibula flaps, and 10 anterolateral thigh flaps) 4 and 12 weeks postoperatively.

281 ATYPICAL PRESENTATION OF ANTI-GLOMERULAR BASEMENT MEMBRANE DISEASE WITH CO-EXISTING IgA NEPHROPATHY A LECAMWASAM1, A SKENE2, D LEE1, L MCMAHON1 1Department of Renal Medicine, Eastern Health, Melbourne, Victoria; 2Department of Anatomical Pathology, Austin Health,

Melbourne, Victoria, Australia Background: We report a case of atypical presentation of anti-glomerular basement membrane (anti-GBM) 3-MA datasheet disease co-existing with IgA nephropathy. Case Report: A 56-year-old Caucasian normotensive man presented with prodromal symptoms for a month. Kidney function deteriorated over 3 weeks with serum creatinine from 134 to 194 μmol/L, while it was normal 14 months prior. Urine microscopy revealed microscopic haematuria but no red cell casts, and spot urine protein-to-creatinine ratio was 0.057 mg/mmol. Anti-GBM antibody titre was 57 units/mL (<20), and anti-neutrophil cytoplasmic antibody was negative. Urgent treatment was commenced consisting of intravenous methylprednisolone, oral cyclophosphamide and plasmapheresis.

Renal biopsy showed 20% crescents. Immunohistochemical studies (IHC) were performed as there was inadequate renal cortex for immunofluorescence selleck inhibitor (IF) studies. IHC showed mesangial IgA deposits and weak IgG but no observable linear staining, favouring IgA nephropathy

with occasional crescents, and plasmapheresis was ceased. His kidney function worsened, and a second renal biopsy was performed 5 days later showing 41% crescents. Repeat IHC studies identified no IgG deposits and weak mesangial IgA staining. Interestingly, IF studies revealed patchy but linear IgG and mesangial IgA staining consistent with anti-GBM disease with mild IgA nephropathy. Plasmapheresis Farnesyltransferase was reinstituted followed by undetectable circulating anti-GBM antibody, normalisation of kidney function, proteinuria and haematuria at 5 months follow-up. Conclusions: Our case reinforces the importance of strong clinical suspicion for atypical presentation of anti-GBM disease in the context of acute kidney injury and circulating anti-GBM antibody, as early initiation of treatment is paramount for favourable outcomes. Co-existing glomerulonephritis, prodromal symptoms and less rapid deterioration in kidney function are not uncommon. Linear IgG deposits may be more sensitive by IF compared to IHC.

This systematic review examines the safety and efficacy of this monoclonal antibody. Methods: MEDLINE and EMBASE databases were searched. Only randomized controlled trials where campath was used as an induction agent with a minimum sample size of 20 patients were included. Studies which did not directly compare campath with another induction agent were excluded. Primary outcomes measured were acute Paclitaxel nmr rejection rate, CMV infection rate, graft and patient survival. Results: Five studies fulfilled the inclusion criteria. Meta-analysis reveals the overall odd ratios for acute rejection, CMV infection and graft survival at 12 months

were 0.65(0.39 to 1.08), 0.69(0.36 to 1.34) and 0.59(0.31 to 1.12) respectively in favour of campath. Further subgroup analysis shown on Figure 1 PLX4032 ic50 comparing the efficacy between this antibody with antithymocyte globulin(ATG) found that campath is non inferior in the incidence of acute rejection. Summary: This systematic review demonstrates induction of renal transplantation with campath is not inferior to ATG at 12 months. Larger trials with longer study period would be useful to further ascertain its future

as a definitive effective and safe agent in transplantation. SOFUE TADASHI1, INUI MASASHI2, HARA TAIGA1, NISHIJIMA YOKO1, MORIWAKI KUMIKO1, HAYASHIDA YUSHI3, UEDA NOBUFUMI3, NISHIYAMA AKIRA4, KAKEHI YOSHIYUKI3, KOHNO MASAKAZU1 1Division of Nephrology and Dialysis, Department of CardioRenal and Cerebrovascular Medicine, Kagawa University, Kagawa, Japan; 2Department of Urology, Tokyo Women’s Medical University Yachiyo Medical Center, Chiba, Japan; 3Department of Urology, Kagawa University, Kagawa, Japan; 4Department of Pharmacology, Kagawa University, Kagawa, Japan Introduction: Post-transplant hyperuricemia (PTHU), defined as serum uric acid (UA) concentration ≥7.0 mg/dl or treatment with conventional treatment, reduces

long-term allograft survival in kidney transplant recipients. Febuxostat, a new non-purine selective xanthine oxidase inhibitor, is well tolerated in patients with moderate renal impairment. However, its efficacy and safety Rutecarpine in kidney recipients with PTHU is unclear. We therefore assessed the efficacy and safety of febuxostat in stable kidney transplant recipients with PTHU. Methods: Of 93 adult stable kidney transplant recipients, 51 were diagnosed with PTHU and 42 were not (NPTHU group). Of the 51 patients with PTHU, 26 were treated with febuxostat (FX group) and 25 were not (NFX group), at the discretion of each attending physician. One-year changes in serum UA concentrations, rates of achievement of target UA. Results: The FX group showed significantly greater decreases in serum UA (−2.0 ± 1.1 vs. 0.0 ± 0.8 mg/dl/year, p < 0.01) and tended to show a higher rate of achievement of target UA level (50% vs. 24%: odds ratio = 3.17 [95% confidential interval = 0.96−10.5], p = 0.08) than the NFX group.

11). Studies which recruited

mainly Asian participants reported find more an almost two-fold risk of stroke compared to studies recruiting mainly white participants (RR1.93, 95%CI1.19 to 3.13). When GFR and proteinuria were both present, their combined effects were additive. All of our observations were consistent across different subtypes of stroke. Conclusions: Risk of stroke increases with declining GFR and increasing quantities of proteinuria with variation in the effect of proteinuria by ethnicity. Assessing risk of stroke requires measurement of both GFR and proteinuria and recognition of subgroups of people at particular risk. ISEKI KUNITOSHI Dialysis Unit, University Hospital of the Ryukyus Introduction: According to the

Japanese Society for Dialysis Therapy (JSDT), the number of chronic dialysis (HD) patients is still increasing. Okinawa prefecture is known as a highest incidence and prevalence of HD. However, the reasons are not entirely clear as the Neratinib natural courses of CKD progression is difficult to ascertain. Methods: We have been registered all HD patients since 1971 when the dialysis therapy was stared in Okinawa. By 2010, the total number of HD patients is about 10,000. We are able to determine the outcomes such as death, renal transplantation and transfer outside Okinawa with the full collaboration of the Okinawa Dialysis and Transplant Association (ODTA) and Okinawa Dialysis Physicians Association (ODPA). Also, we used the date of start of HD as an outcome of the general screening Pregnenolone program subjects which have been performed annually by the Okinawa General Health Association (OGHMA). Moreover, we compared the results of the Specific Health Check and Guidance (Tokutei-Kenshin) which was done 2008 throughout Japan. Results: Prevalence of HD was similar at around 500 per million populations (pmp) in 1983; however since then that of Okinawa is increased faster than national

average. In 2012, the prevalence of HD was 3018 in Okinawa and that of 2430 in Japan. For the past three OGHMA screening, the prevalence of obesity, body mass index ≥30 kg/m2 is increase from 3.5% in 1983, 4.7% in 1993, and 6.2% in 2003. Conclusion: Possible reasons for increasing HD prevalence are 1) high incidence and prevalence of CKD, 2) better survival after starting HD, 3) or both. Increasing prevalence of obesity may underlie the former reason, but we have not yet clear explanation. We are currently examining whether the presence of metabolic syndrome does increase mortality rate and/or CKD incidence by using Tokutei-Kenshin database. OKIDS registry provides the clues to determine the natural course of CKD progression and also the outcomes after starting HD therapy. Further studies are necessary to compare the geographic and racial differences in HD incidence and survival of HD patients.

These data suggested that young and mature biofilms show a rapid and antifungal-specific transcriptional response to exposure

to antifungal agents. This Wnt inhibitor drug-specific molecular adaptation could help to explain the high resistance of C. albicans biofilms toward antifungal agents (Nailis et al., 2010). Overexpression of phage-related genes in sessile cells compared with planktonic cells and/or increased expression in response to stress has been observed in several species. The most highly overexpressed P. aeruginosa PAO1 genes in the study of Whiteley et al. (2001) were proteins from a Pf1-like bacteriophage (now designated Pf4; Webb et al., 2004), and this was confirmed by a 100–1000-fold greater abundance of phage particles in the biofilm reactor compared with planktonic cultures. In Bacillus subtilis, 17 genes involved in the production of the defective prophage PBSX are overexpressed in biofilms (Stanley et al., 2003). In B. cenocepacia biofilms, a prolonged treatment (30 or 60 min) with H2O2 resulted in an increased buy Carfilzomib transcription of genes belonging to a BcepMu prophage (BCAS0540–BCAS0554), located on one of the B. cenocepacia genomic islands (genomic island 14) (Peeters et al., 2010). One of these genes (BCAS0547, encoding a putative DNA-binding phage protein)

was also found to be upregulated during growth in cystic fibrosis sputum (Drevinek et al., 2008). Bacterial stress responses can increase the mobility of bacteriophages (reviewed by Miller, 2001), and it has been proposed that prophage production may play a role in generating genetic diversity in the biofilm (e.g. the production of Pf4 in P. aeruginosa biofilms is correlated with the emergence of small-colony variants) (Webb et al., 2004). When faced with unstable

environmental conditions, communities are protected by diversity, SPTLC1 a principle known as the ‘insurance hypothesis’ (Boles et al., 2004); and the diversity generated by the induction of prophages may contribute to biofilm resilience. From the above examples, it is clear that sessile cells have various ways of coping with the stress imposed on them by treatment with antibiotics or disinfectants. A first defense mechanism is the upregulation of genes encoding efflux pumps, resulting in an increased efflux of the antimicrobial agent. In some organisms, particular efflux pumps appear to be biofilm specific. The increased production of enzymes that can degrade antibiotics or reactive oxygen species is an important defense mechanism in various bacteria. While some of these enzymes appear to be equally important for protecting planktonic and sessile cells (e.g. katB in B. cenocepacia), some appear to be biofilm specific (e.g. ahpCF in P. aeruginosa). Phenotypic adaptations resulting in reduced transport of antimicrobial agents in biofilms and/or reduced permeability of the cell have also been reported.

Meanwhile, between July 2009

and March 2010, only 6 (8%) of 75 viruses isolated in Nagasaki, in the southern part of Japan, possessed both S203T and A197T (12). Through surveillance in several PLX-4720 cell line areas in Japan between May 2009 and January 2010, Morlighem et al. also demonstrated that less than 20% (47 or 48/253 isolates) had both these substitutions (13). BLAST analysis showed that, out of the 563 A(H1N1)pdm09 with S203T isolated by May 2010, only 123 (22%) had both the S203T and A197T substitutions. These findings indicate that the ratio of the epidemic strains in the university students is different from those in other areas. In addition to the Q293H, S203T, and A197T mutations, we observed several unique and fixed amino acid changes in

the HA1 region of the isolates examined in this study. Substitutions of S69L, P137L, A186T and D187N occurred in the antigenic sites Cb, Ca, Sb and Sb, respectively (10). We postulate that these substitutions affect antigenicity and that Sapporo- and Texas-like viruses may therefore vary in antigenicity. We found BIBW2992 substitution of A134T in Sapporo-like T38 and T44, and of D187N in Sapporo-like T52. Since these amino acid positions are located in the receptor-binding site (14), these substitutions may affect the binding of virus to host calls. The substitutions of D187E and D222G could shift receptor specificity from α2,6- to α2,3-linked sialic acid (15). Substitutions of D222G/N possibly also alter the virulence of the virus; isolates possessing this substitution have been detected in fatal cases in several countries (16–18). We observed none of these substitutions among the isolates in this study. The A(H1N1)pdm09 genome has been Tenofovir found to have an extremely

high evolutionary rate (19). Based on the ratio of dN/dS, Karoline et al. demonstrated that the seasonal H3N2 and H1N1 virus genes show stochastic variation (dN/dS < 1) (Table 1). On the other hand, the A(H1N1)pdm 09 of the 70 isolates demonstrated positive evolution (dN/dS > 1). In particular, Texas-like viruses showed the highest dN/dS value of the three groups and had significantly higher rates of missense mutation than Sapporo-like viruses. The high proportion of Texas-like viruses in this study possibly reflects these higher values, which denote more positive evolution. These findings may indicate that A(H1N1)pdm09 is more influenced than the other viruses by immune selection pressure. Although elderly people exposed to the 1918 “Spanish flu” had antibodies that cross-neutralized A(H1N1)pdm09 (21, 22), they may be also have been affected by A(H1N1)pdm09 due to antigenic drift. In conclusion, our phylogenetic analysis of the HA genes of the isolates shows that different virus populations, which might also vary in antigenicity, were responsible for the two student epidemics.