Nomenclature for the chromosomes of the common shrew (Sorex araneus)

A G-band composite karyotype has been prepared for the common shrew (Sorex araneus Linnaeus, 1758). This includes multiple cut-outs of each chromosome arm (in different stages of contraction) derived from chromosome spreads prepared by a variety of methods by the different authors. The important features of each chromosome arm are described. The nomenclature for the chromosome arms follows that of Halkka et al. (1974) as clarified by Fredga, Nawrin (1977) and subsequent authors, i.e. italicised letters of the alphabet are used with a as the largest chromosome arm. Different authors have used a variety of methods to describe the karyotype of (a) individuals and (b) the pattern of variation within populations. Also, definitions of chromosomal ‘race’ differ. We suggest a standardised scheme for the description of individuals, populations and chromosomal race

The DNA Glycosylases Ogg1 and Nth1 Do Not Contribute to Ig Class Switching in Activated Mouse Splenic B Cells

During activation of B cells to undergo class switching, B cell metabolism is increased, and levels of reactive oxygen species (ROS) are increased. ROS can oxidize DNA bases resulting in substrates for the DNA glycosylases Ogg1 and Nth1. Ogg1 and Nth1 excise oxidized bases, and nick the resulting abasic sites, forming single-strand DNA breaks (SSBs) as intermediates during the repair process. In this study, we asked whether splenic B cells from mice deficient in these two enzymes would show altered class switching and decreased DNA breaks in comparison with wild-type mice. As the c-myc gene frequently recombines with the IgH S region in B cells induced to undergo class switching, we also analyzed the effect of deletion of these two glycosylases on DSBs in the c-myc gene. We did not detect a reduction in S region or c-myc DSBs or in class switching in splenic B cells from Ogg1- or Nth1-deficient mice or from mice deficient in both enzymes

Ogólnopolski program oceny diagnostyki, leczenia i kosztów u chorych z niewydolnością serca w losowo wybranych jednostkach lecznictwa otwartego i zamkniętego na poziomie podstawowym, wojewódzkim i specjalistycznym. Założenia i metodyka projektu realizowanego w ramach Narodowego Programu Profilaktyki i Leczenia Chorób Układu Krążenia: PolKARD 2003-2005

Wstęp: W dużych badaniach epidemiologicznych, takich jak Improvement czy EuroHeart Survey, realizowane także w Polsce w latach 1999-2001, wykazano niedostateczne przestrzeganie wytycznych sformułowanych przez Europejskie Towarzystwo Kardiologiczne, dotyczących postępowania w niewydolności serca. Celem ostatnio zakończonego badania była aktualna ocena postępowania diagnostyczno-terapeutycznego, kosztów opieki oraz określenie dostępności do badań diagnostycznych i metod leczniczych w ośrodkach o różnym poziomie referencyjności. Celem niniejszej pracy jest przedstawienie założeń i sposobu realizacji programu. Materiał i metody: Program realizowano w 2005 r. w ramach Narodowego Programu Profilaktyki i Leczenia Chorób Układu Krążenia (PolKARD). Badaniem objęto losowo dobraną próbę ośrodków podstawowej opieki zdrowotnej, poradni specjalistycznych, szpitali oraz wszystkie ośrodki kliniczne (akademickie). W każdym z ośrodków lekarz wypełniał ankietę dotyczącą postępowania diagnostyczno-terapeutycznego (na podstawie dokumentacji medycznej) u ostatnich 5 pacjentów z rozpoznaną niewydolnością serca, przyjętych podczas wizyty w gabinecie lub hospitalizowanych. Ponadto z jednym losowo wybranym pacjentem z danego ośrodka przeprowadzono wywiad, podczas rozmowy telefonicznej lub wizyty domowej. Badanie zrealizowano przy udziale pielęgniarek zatrudnionych w charakterze ankieterów przez Pracownię Badań Społecznych w Sopocie. Wyniki: Ogółem uzyskano 5275 ankiet na temat postępowania diagnostyczno-terapeutycznego od lekarzy podstawowej opieki zdrowotnej, specjalistów (kardiologów i internistów) oraz z oddziałów kardiologicznych i internistycznych z terenu całej Polski (efektywność: dane uzyskano z 99,5% ośrodków spośród rekrutowanych). Ponadto uzyskano dane bezpośrednio od 1024 pacjentów. Wnioski: Wyniki analiz z zakresu diagnostyki i leczenia pacjentów z niewydolnością serca posłużą do przedstawienia rozwiązań mających na celu poprawę obecnego modelu opieki w Polsce

A microsatellite study in the Łęgucki Młyn/Popielno hybrid zone reveals no genetic differentiation between two chromosome races of the common shrew (Sorex araneus)

This study investigated a chromosome hybrid zone between two chromosomal races of the common shrew (Sorex araneus). Gene flow and genetic structure of the hybrid zone, located in the northeast of Poland, were studied using seven polymorphic autosomal microsatellite loci (L9, L14, L33, L45, L67, L68, L97) and a Y-linked microsatellite locus (L8Y). Seventy-five animals (46 of the Łęgucki Młyn race and 29 of the Popielno race) from nine different localities were examined and the data were analyzed using hierarchical AMOVA and F-statistic. The studied microsatellite loci and races (divided into nine geographical populations) were characterized by observed heterozygosity (HO), expected heterozygosities within (HS), and between (HT) populations, inbreeding coefficient (FIS), fixation index (FST), and average allelic richness (A). We found that genetic structuring within and between the two chromosome races were weak and non-significant. This finding and unconstrained gene flow between the races indicates a high level of migration within the Łęgucki Młyn/Popielno hybrid zone, suggesting that evolutionarily important genetic structuring does not occur in interracial zones where races which are not genetically distinct come into contact

Ogólnopolski program oceny diagnostyki, leczenia i kosztów u chorych z niewydolnością serca w losowo wybranych jednostkach lecznictwa otwartego i zamkniętego na poziomie podstawowym, wojewódzkim i specjalistycznym. Założenia i metodyka projektu realizowanego w ramach Narodowego Programu Profilaktyki i Leczenia Chorób Układu Krążenia: PolKARD 2003-2005

Wstęp: W dużych badaniach epidemiologicznych, takich jak Improvement czy EuroHeart Survey, realizowane także w Polsce w latach 1999-2001, wykazano niedostateczne przestrzeganie wytycznych sformułowanych przez Europejskie Towarzystwo Kardiologiczne, dotyczących postępowania w niewydolności serca. Celem ostatnio zakończonego badania była aktualna ocena postępowania diagnostyczno-terapeutycznego, kosztów opieki oraz określenie dostępności do badań diagnostycznych i metod leczniczych w ośrodkach o różnym poziomie referencyjności. Celem niniejszej pracy jest przedstawienie założeń i sposobu realizacji programu. Materiał i metody: Program realizowano w 2005 r. w ramach Narodowego Programu Profilaktyki i Leczenia Chorób Układu Krążenia (PolKARD). Badaniem objęto losowo dobraną próbę ośrodków podstawowej opieki zdrowotnej, poradni specjalistycznych, szpitali oraz wszystkie ośrodki kliniczne (akademickie). W każdym z ośrodków lekarz wypełniał ankietę dotyczącą postępowania diagnostyczno-terapeutycznego (na podstawie dokumentacji medycznej) u ostatnich 5 pacjentów z rozpoznaną niewydolnością serca, przyjętych podczas wizyty w gabinecie lub hospitalizowanych. Ponadto z jednym losowo wybranym pacjentem z danego ośrodka przeprowadzono wywiad, podczas rozmowy telefonicznej lub wizyty domowej. Badanie zrealizowano przy udziale pielęgniarek zatrudnionych w charakterze ankieterów przez Pracownię Badań Społecznych w Sopocie. Wyniki: Ogółem uzyskano 5275 ankiet na temat postępowania diagnostyczno-terapeutycznego od lekarzy podstawowej opieki zdrowotnej, specjalistów (kardiologów i internistów) oraz z oddziałów kardiologicznych i internistycznych z terenu całej Polski (efektywność: dane uzyskano z 99,5% ośrodków spośród rekrutowanych). Ponadto uzyskano dane bezpośrednio od 1024 pacjentów. Wnioski: Wyniki analiz z zakresu diagnostyki i leczenia pacjentów z niewydolnością serca posłużą do przedstawienia rozwiązań mających na celu poprawę obecnego modelu opieki w Polsce

Stromal‐Derived Factor‐1α (CXCL12) Levels Increase in Periodontal Disease

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142300/1/jper0845.pd

Cyclophosphamide-Induced Cystitis Increases Bladder CXCR4 Expression and CXCR4-Macrophage Migration Inhibitory Factor Association

BACKGROUND: Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine involved in cystitis and a non-cognate ligand of the chemokine receptor CXCR4 in vitro. We studied whether CXCR4-MIF associations occur in rat bladder and the effect of experimental cystitis. METHODS AND FINDINGS: Twenty male rats received saline or cyclophosphamide (40 mg/kg; i.p.; every 3(rd) day) to induce persistent cystitis. After eight days, urine was collected and bladders excised under anesthesia. Bladder CXCR4 and CXCR4-MIF co-localization were examined with immunhistochemistry. ELISA determined MIF and stromal derived factor-1 (SDF-1; cognate ligand for CXCR4) levels. Bladder CXCR4 expression (real-time RTC-PCR) and protein levels (Western blotting) were examined. Co-immunoprecipitations studied MIF-CXCR4 associations.Urothelial basal and intermediate (but not superficial) cells in saline-treated rats contained CXCR4, co-localized with MIF. Cyclophosphamide treatment caused: 1) significant redistribution of CXCR4 immunostaining to all urothelial layers (especially apical surface of superficial cells) and increased bladder CXCR4 expression; 2) increased urine MIF with decreased bladder MIF; 3) increased bladder SDF-1; 4) increased CXCR4-MIF associations. CONCLUSIONS: These data demonstrate CXCR4-MIF associations occur in vivo in rat bladder and increase in experimental cystitis. Thus, CXCR4 represents an alternative pathway for MIF-mediated signal transduction during bladder inflammation. In the bladder, MIF may compete with SDF-1 (cognate ligand) to activate signal transduction mediated by CXCR4

The extract of syngeneic keratinocytes enhances IgE production from BALB/c mouse splenic lymphocytes in vitro.

Background: The increase of serum IgE levels is closely associated with atopic dermatitis. We have previously revealed that cellular extract of PAM212 cells (PAM-extract), BALB/c mouse keratinocyte cell line, induced a remarkable increase of serum IgE levels, in vivo, when subcutaneously injected into BALB/c mice. However, precise mechanism of IgE-increasing activity was unclear. Objective: To elucidate the mechanism of IgE-increase in sera of BALB/c mice induced by PAM-extract, we explored the direct influence of PAM-extract on immunoglobulin production and class-switching in the culture of splenic lymphocytes and purified B-cells, in vitro. Methods: Splenic lymphocytes or purified B-cells obtained from BALB/c mice were cultured with various combinations of IL-4, anti-CD40 antibody, and PAM-extract for seven days. IgE and IgG concentrations of culture supernatants were measured by ELISA. Epsilon germ-line transcriptions were assessed by RT-PCR from the cultured cells. Results: IgE and IgG concentrations in culture supernatant of splenic lymphocytes were increased by an addition of PAM-extract in the presence of both IL-4 and anti-CD40 antibody. Epsilon germ-line transcript was also induced in parallel to the increase of IgE production. Similar results were obtained when purified B-cells were employed in stead of whole splenic lymphocytes. Conclusion: The cellular extract of keratinocyte promotes immunoglobulin class-switching to IgE and IgE production from mouse splenic B-cells in an IL-4- and CD40-stimuli-dependent manner. Such enhancement may account for the increase of serum IgE in patients with dermatitis in association with a Th2 microenvironment

CD152 (CTLA-4) Determines CD4 T Cell Migration In Vitro and In Vivo

BACKGROUND:Migration of antigen-experienced T cells to secondary lymphoid organs and the site of antigenic-challenge is a mandatory prerequisite for the precise functioning of adaptive immune responses. The surface molecule CD152 (CTLA-4) is mostly considered as a negative regulator of T cell activation during immune responses. It is currently unknown whether CD152 can also influence chemokine-driven T cell migration. METHODOLOGY/PRINCIPAL FINDINGS:We analyzed the consequences of CD152 signaling on Th cell migration using chemotaxis assays in vitro and radioactive cell tracking in vivo. We show here that the genetic and serological inactivation of CD152 in Th1 cells reduced migration towards CCL4, CXCL12 and CCL19, but not CXCL9, in a G-protein dependent manner. In addition, retroviral transduction of CD152 cDNA into CD152 negative cells restored Th1 cell migration. Crosslinking of CD152 together with CD3 and CD28 stimulation on activated Th1 cells increased expression of the chemokine receptors CCR5 and CCR7, which in turn enhanced cell migration. Using sensitive liposome technology, we show that mature dendritic cells but not activated B cells were potent at inducing surface CD152 expression and the CD152-mediated migration-enhancing signals. Importantly, migration of CD152 positive Th1 lymphocytes in in vivo experiments increased more than 200% as compared to CD152 negative counterparts showing that indeed CD152 orchestrates specific migration of selected Th1 cells to sites of inflammation and antigenic challenge in vivo. CONCLUSIONS/SIGNIFICANCE:We show here, that CD152 signaling does not just silence cells, but selects individual ones for migration. This novel activity of CD152 adds to the already significant role of CD152 in controlling peripheral immune responses by allowing T cells to localize correctly during infection. It also suggests that interference with CD152 signaling provides a tool for altering the cellular composition at sites of inflammation and antigenic challenge

What is the risk of progressive multifocal leukoencephalopathy in patients with ulcerative colitis or Crohn’s Disease treated with vedolizumab?

Background: Progressive multifocal leukoencephalopathy is a serious condition linked to certain diseases and immunosuppressant therapies, including the α4 integrin antagonist natalizumab. No cases have been reported to date with vedolizumab, a selective antagonist of the α4β7 integrin expressed on gut-homing lymphocytes. This analysis aimed to describe the current and future expected occurrence of progressive multifocal leukoencephalopathy with vedolizumab use, were the risk the same as in other populations in which this disease has been studied. Methods: The expected number of vedolizumab-associated progressive multifocal leukoencephalopathy cases was estimated up to May 19, 2016 and modelled up to 2034. These estimates were based on the cumulative exposure to the drug, assuming an equivalent risk to that of patients treated with natalizumab or those from other reference populations where progressive multifocal leukoencephalopathy has been examined. Future cases were modelled based on similar risks and projected sales. Results: The cumulative vedolizumab exposure was estimated at 54,619 patient-years, with a 95% confidence interval of 0.0–6.75 cases per 100,000 patient-years. An estimated 30.2 (95% confidence interval 19.4–40.9) cases of progressive multifocal leukoencephalopathy would have occurred if vedolizumab had the same risk as that of natalizumab. There would be a 50% chance of the first case occurring by 2018, assuming an equivalent risk to the general population. Conclusions: These analyses indicate the risk of progressive multifocal leukoencephalopathy with vedolizumab is small, and unlikely to be above 6.75 cases per 100,000 patient-years