Antigen-driven clonal proliferation of B cells within the target tissue of an autoimmune disease: the salivary glands of patients with Sjögren's syndrome

Structures resembling germinal centers are seen in the salivary glands of patients with Sjögren's syndrome, but it is not known whether the microenvironment of these cell clusters is sufficient for the induction of a germinal center response. Therefore, we cloned and sequenced rearranged Ig V genes expressed by B cells isolated from sections of labial salivary gland biopsies from two Sjögren's syndrome patients. Rearranged V genes from B cells within one cell cluster were polyclonal and most had few somatic mutations. Two adjacent clusters from another patient each contained one dominant B cell clone expressing hypermutated V genes. None of the rearranged V genes was found in both clusters, suggesting that cells are unable to migrate out into the surrounding tissue and seed new clusters. The ratios of replacement to silent mutations in the framework and complementarity determining regions suggest antigen selection of high-affinity mutants. These results show that an antigen-driven, germinal center-type B cell response is taking place within the salivary glands of Sjögren's syndrome patients. In view of the recent demonstration of a germinal center response within the rheumatoid synovial membrane and the existence of similar structures in the target tissues of other autoimmune. diseases, we propose that germinal center- type responses can be induced in the nonlymphoid target tissues of a variety of autoimmune diseases

Molecular Beam Measurements Of Total Collision Cross Sections Of H 22O

The total cross section for H22O-H22O scattering is measured with a supersonic nozzle beam system. The primary beam has a narrow velocity distribution, and the velocity is varied by control of the nozzle temperature. Velocities are determined by time-of-flight techniques. Cross sections obtained are averages over a Maxwellian distribution of the target molecules. Data at three velocities are presented. The cross sections for H2O are surprisingly small, for example, 3.07 x10-14 cm2 at 1x105 cm/sec, indicating little contribution from the dipole-dipole interaction

Root-Colonizing Endophytic Fungi of the Dominant Grass Stipa krylovii From a Mongolian Steppe Grassland

In several terrestrial ecosystems such as grasslands, plants live together with various root-colonizing dark septate endophytes (DSEs), fungi that are relatively frequent colonizers of healthy belowground tissues of plants in these environments. They are important members of the plant microbiota and may have various effects on plant survival under different stress conditions; however, their general functions in relation to plants and the greater ecosystem remain elusive. Although an increasing number of studies has been published focusing on DSEs in Asian grasslands, our knowledge is limited. Especially in Mongolia, where the steppe region represents a significant area, information is not available on these root colonizers. In this study, we aimed to characterize DSEs of a common dominant gramineous plant species, Stipa krylovii in a semiarid grassland of Mongolia. Root samples were collected in a natural steppe and were processed for isolation of fungal endophytes. For molecular identification of the isolates, the internal transcribed spacer (ITS) region of the nrDNA was obtained for all the isolates investigated; furthermore, the partial translation elongation factor 1-a (TEF) gene and large subunit (LSU) and small subunit (SSU) of rDNA were also amplified and sequenced in case of representative isolates. In vitro tests were used to examine the rough symbiotic nature of the fungi, and root colonization was visualized. A majority of the 135 isolates examined in detail was found to belong to several orders of Ascomycota (110 isolates) and some to Basidiomycota (25 isolates). A significant number of the isolates represented presumably novel taxa, and dominant similarities of the lineages have been found with relatively frequent and known grass root endophytes of semiarid areas in other geographic regions. These endophytes included Periconia macrospinosa, Microdochium bolley, and Darksidea, the genus of which comprised one fourth of the isolates. We found numerous lineages, which have been detected not only from Asian steppe ecosystems, but also from prairies in North America and sandy grasslands in Europe. Therefore, our results strengthen the hypothesized worldwide presence of a common and dominant core group of a DSE community in arid and semiarid grasslands

Atípusos aortacoarctatiók sebészi kezelésének hosszú távú eredményei

Absztrakt Bevezetés: Az aortacoarctatio a leggyakoribb congenitalis cardiovascularis elváltozások egyike, azok 5–8%-ában fordul elő. Típusos előfordulási helye az isthmicus szakasz. Atípusos helyen kialakuló coarctatio az esetek mintegy 1%-ában fordul elő és többnyire súlyos hypertoniával szövődik. Célkitűzés: A szerzők célul tűzték ki a kórkép sebészi kezelési lehetőségeinek és azok hosszú távú eredményeinek ismertetését 27 beteg műtéti kezelésével szerzett tapasztalataik alapján. Módszer: A 35 évet felölelő utánkövetés során a diagnosztika és a kezelési módszerek változtak. Napjainkban a morfológiai diagnózis legáltalánosabb módszerei a komputertomográfiás angiográfia és a mágneses rezonanciás angiográfia. Az aortarekonstrukció lehetőségei az endovascularis technikák bevezetésével gazdagodtak, de atípusos aortacoartatio esetében a szerzők ma is túlnyomóan változatos sebészi megoldásokat alkalmaznak. Eredmények: A műtétek után nem veszítettek el beteget. A hypertonia minden esetben jelentősen csökkent. Gyermekkorban operált esetekben a növekedés okozta testméretváltozások 3 esetben újabb rekonstrukciós műtétet indokoltak. Következtetések: Az atípusos aortacoarctatio individuális sebészi módszerekkel eredményesen kezelhető. Gyermekkorban operált esetekben a testméret-növekedés a rekonstruált aortaszakasz revízióját teheti szükségessé. Orv. Hetil., 2016, 157(26), 1043–1051

The grass root endophytic fungus Flavomyces fulophazii: An abundant source of tetramic acid and chlorinated azaphilone derivatives

Fungal endophytes are remarkable sources of biologically active metabolites of ecological and pharmacological significance. In this study, fungal isolates producing yellow pigments and originating from grass roots, were identified as the recently described grass root colonizing dark septate endophyte (DSE), Flavomyces fulophazii (Periconiaceae, Pleosporales). While analyzing the metabolite composition of 17 isolates of this fungus, 11 previously undescribed compounds, including four tetramic acids (dihydroxyvermelhotin, hydroxyvermelhotin, methoxyvermelhotin, oxovermelhotin), and seven chlorinated azaphilones (flavochlorines A–G), together with the known tetramic acid vermelhotin, were tentatively identified by high performance liquid chromatography (HPLC)-tandem mass spectrometry (MS/MS). Among them, flavochlorine A, flavochlorine G, hydroxyvermelhotin and vermelhotin could be isolated by preparative HPLC, thus their structures were also confirmed by nuclear magnetic resonance (NMR) spectroscopy. Vermelhotin was found to be the main compound, reaching its maximum level of 5.5 mg/g in the in vitro cultures of a selected F. fulophazii isolate. A significant amount of vermelhotin was isolated by preparative HPLC from these cultures (4.8 mg from 1.0 g lyophilized culture), confirming the practical utility of F. fulophazii in high-yield vermelhotin production. The main compounds of this endophyte expressed no activity in standardized plant bioassays (i.e., in the Lactuca sativa seed germination and Lemna minor growth tests). An antiproliferative study of the isolated compounds confirmed moderate activity of vermelhotin against a panel of twelve cancer cell lines, with IC50 ranges of 10.1–37.0 μM, without inhibiting the non-cancer Vero cells, suggesting its selectivity towards cancers

Co-Evolution of quasispecies: B-cell mutation rates maximize viral error catastrophes

Co-evolution of two coupled quasispecies is studied, motivated by the competition between viral evolution and adapting immune response. In this co-adaptive model, besides the classical error catastrophe for high virus mutation rates, a second ``adaptation-'' catastrophe occurs, when virus mutation rates are too small to escape immune attack. Maximizing both regimes of viral error catastrophes is a possible strategy for an optimal immune response, reducing the range of allowed viral mutation rates to a minimum. From this requirement one obtains constraints on B-cell mutation rates and receptor lengths, yielding an estimate of somatic hypermutation rates in the germinal center in accordance with observation.Comment: 4 pages RevTeX including 2 figure

Optimality of mutation and selection in germinal centers

The population dynamics theory of B cells in a typical germinal center could play an important role in revealing how affinity maturation is achieved. However, the existing models encountered some conflicts with experiments. To resolve these conflicts, we present a coarse-grained model to calculate the B cell population development in affinity maturation, which allows a comprehensive analysis of its parameter space to look for optimal values of mutation rate, selection strength, and initial antibody-antigen binding level that maximize the affinity improvement. With these optimized parameters, the model is compatible with the experimental observations such as the ~100-fold affinity improvements, the number of mutations, the hypermutation rate, and the "all or none" phenomenon. Moreover, we study the reasons behind the optimal parameters. The optimal mutation rate, in agreement with the hypermutation rate in vivo, results from a tradeoff between accumulating enough beneficial mutations and avoiding too many deleterious or lethal mutations. The optimal selection strength evolves as a balance between the need for affinity improvement and the requirement to pass the population bottleneck. These findings point to the conclusion that germinal centers have been optimized by evolution to generate strong affinity antibodies effectively and rapidly. In addition, we study the enhancement of affinity improvement due to B cell migration between germinal centers. These results could enhance our understandings to the functions of germinal centers.Comment: 5 figures in main text, and 4 figures in Supplementary Informatio

Ovarian cancer in younger vs older women: a population-based analysis

To compare the clinico-pathologic prognostic factors and survival of younger vs older women diagnosed with epithelial ovarian cancer. Demographic, clinico-pathologic, treatment, and surgery information were obtained from patients with ovarian cancer from the Surveillance, Epidemiology, and End Results Program from 1988 to 2001 and analysed using Kaplan–Meier estimates. Of 28 165 patients, 400 were <30 years (very young), 11 601 were 30–60 (young), and 16 164 were >60 (older) years of age. Of the very young, young, and older patients, 261 (65.3%), 4664 (40.2%), and 3643 (22.5%) had stage I–II disease, respectively (P<0.001). Across all stages, very young women had a significant survival advantage over the young and older groups with 5-year disease-specific survival estimates at 78.8% vs 58.8 and 35.3%, respectively (P<0.001). This survival difference between the age groups persists even after adjusting for race, stage, grade, and surgical treatment. Reproductive age (16–40 years) women with stage I–II epithelial ovarian cancer who received uterine-sparing procedures had similar survivals compared to those who underwent standard surgery (93.3% vs 91.5%, P=0.26). Younger women with epithelial ovarian cancer have a survival advantage compared to older patients