bluuebunny/crossref_metadata_2025_split huggingface dataset:
The antibacterial activity of peptides derived from human beta‐2 glycoprotein I is inhibited by protein H and M1 protein from Streptococcus pyogenes
Authors: Nilsson Maria , Wasylik Sylwia , Mörgelin Matthias , Olin Anders I. , Meijers Joost C. M. , Derksen Ronald H. W. M. , De Groot Philip G. , Herwald Heiko 
Published: September 2009

SummaryDuring the last years, the importance of antibacterial peptides has attracted considerable attention. We report here that peptides derived from the fifth domain of beta‐2 glycoprotein I (β2GPI), a human heparin binding plasma protein, have antibacterial activities against Gram‐positive and Gram‐negative bacteria. Streptococcus pyogenes, an important human pathogen that can survive and grow in human blood, has developed mechanisms to escape the attack by these peptides. Thus, protein H and M1 protein, two surface proteins of the highly pathogenic S. pyogenes AP1 strain, bind full‐length β2GPI and thereby prevent the processing of β2GPI by proteases from polymorphonuclear neutrophils (PMNs) into antibacterial peptides. In addition, protein H and M1 protein, released from the bacterial cell wall by PMN‐derived proteases, bind to, and inhibit the activity of, β2GPI‐derived antibacterial peptides. Taken together, the data suggest that the interaction between the streptococcal proteins and β2GPI or β2GPI‐derived peptides presents a novel mechanism to resist an antibacterial attack by β2GPI‐cleavage products.
A bifunctional DNA binding region in Tn5 transposase
Authors: Gradman Richard J. , Ptacin Jerod L. , Bhasin Archna , Reznikoff William S. , Goryshin Igor Y. 
Published: September 2009

SummaryTn5 transposition is a complicated process that requires the formation of a highly ordered protein–DNA structure, a synaptic complex, to catalyse the movement of a sequence of DNA (transposon) into a target DNA. Much is known about the structure of the synaptic complex and the positioning of protein–DNA contacts, although many protein–DNA contacts remain largely unstudied. In particular, there is little evidence for the positioning of donor DNA and target DNA. In this communication, we describe the isolation and analysis of mutant transposases that have, for the first time, provided genetic and biochemical evidence for the stage‐specific positioning of both donor and target DNAs within the synaptic complex. Furthermore, we have provided evidence that some of the amino acids that contact donor DNA also contact target DNA, and therefore suggest that these amino acids help define a bifunctional DNA binding region responsible for these two transposase–DNA binding events.
Rhizobium common nod genes are required for biofilm formation
Authors: Fujishige Nancy A. , Lum Michelle R. , De Hoff Peter L. , Whitelegge Julian P. , Faull Kym F. , Hirsch Ann M. 
Published: September 2009

SummaryIn legume nitrogen‐fixing symbioses, rhizobial nod genes are obligatory for initiating infection thread formation and root nodule development. Here we show that the common nod genes, nodD1ABC, whose products synthesize core Nod factor, a chitin‐like oligomer, are also required for the establishment of the three‐dimensional architecture of the biofilm of Sinorhizobium meliloti. Common nod gene mutants form a biofilm that is a monolayer. Moreover, adding Nod Factor antibody to S. meliloti cells inhibits biofilm formation, while chitinase treatment disrupts pre‐formed biofilms. These results attest to the involvement of core Nod factor in rhizobial biofilm establishment. However, luteolin, the plant‐derived inducer of S. meliloti's nod genes, is not required for mature biofilm formation, although biofilm establishment is enhanced in the presence of this flavonoid inducer. Because biofilm formation is plant‐inducer‐independent and because all nodulating rhizobia, both alpha‐ and beta‐proteobacteria have common nod genes, the role of core Nod factor in biofilm formation is likely to be an ancestral and evolutionarily conserved function of these genes.
Maturation of Streptococcus pneumoniae lipoproteins by a type II signal peptidase is required for ABC transporter function and full virulence
Authors: Khandavilli Suneeta , Homer Karen A. , Yuste Jose , Basavanna Shilpa , Mitchell Timothy , Brown Jeremy S. 
Published: September 2009

SummaryCell surface lipoproteins are important for the full virulence of several bacterial pathogens, including Streptococcus pneumoniae. Processing of prolipoproteins seems to be conserved among different bacterial species, and requires type II signal peptidase (Lsp) mediated cleavage of the N‐terminal signal peptide to form the mature lipoprotein. Lsp has been suggested as a target for new antibiotic therapies, but at present there are only limited data on the function of Lsp for Gram‐positive bacterial pathogens. We have investigated the function and role during disease pathogenesis of the S. pneumoniae Lsp, which, blast searches suggest, is encoded by the gene Sp0928. Expression of Sp0928 protected Escherichia coli against the Lsp antagonist globomycin, and proteomics and immunoblot analysis demonstrated that deletion of Sp0928 prevented processing of S. pneumoniae prolipoproteins to mature lipoproteins. These data strongly suggest that Sp0928 encodes the S. pneumoniae Lsp. However, immunoblots of membrane‐associated proteins, immunoelectron microscopy and flow cytometry assays all confirmed that in the absence of Lsp, immature lipoproteins were still attached to the cell surface. Despite preservation of lipoprotein attachment to the cell membrane, loss of S. pneumoniae Lsp resulted in several phenotypes associated with impaired lipoprotein function and reduced S. pneumoniae replication in animal models of infection.
The Scl1 protein of M6‐type group A Streptococcus binds the human complement regulatory protein, factor H, and inhibits the alternative pathway of complement
Authors: Caswell Clayton C. , Han Runlin , Hovis Kelley M. , Ciborowski Pawel , Keene Douglas R. , Marconi Richard T. , Lukomski Slawomir 
Published: September 2009

SummaryNon‐specific activation of the complement system is regulated by the plasma glycoprotein factor H (FH). Bacteria can avoid complement‐mediated opsonization and phagocytosis through acquiring FH to the cell surface. Here, we characterize an interaction between the streptococcal collagen‐like protein Scl1.6 of M6‐type group A Streptococcus (GAS) and FH. Using affinity chromatography with immobilized recombinant Scl1.6 protein, we co‐eluted human plasma proteins with molecular weight of 155 kDa, 43 kDa and 38 kDa. Mass spectrometry identified the 155 kDa band as FH and two other bands as isoforms of the FH‐related protein‐1. The identities of all three bands were confirmed by Western immunoblotting with specific antibodies. Structure–function relation studies determined that the globular domain of the Scl1.6 variant specifically binds FH while fused to collagenous tails of various lengths. This binding is not restricted to Scl1.6 as the phylogenetically linked Scl1.55 variant also binds FH. Functional analyses demonstrated the cofactor activity of the rScl1.6‐bound FH for factor I‐mediated cleavage of C3b. Finally, purified FH bound to the Scl1.6 protein present in the cell wall material obtained from M6‐type GAS. In conclusion, we have identified a functional interaction between Scl1 and plasma FH, which may contribute to GAS evasion of complement‐mediated opsonization and phagocytosis.
An atypical orthologue of 6‐pyruvoyltetrahydropterin synthase can provide the missing link in the folate biosynthesis pathway of malaria parasites
Authors: Dittrich Sabine , Mitchell Sarah L. , Blagborough Andrew M. , Wang Qi , Wang Ping , Sims Paul F. G. , Hyde John E. 
Published: September 2009

SummaryFolate metabolism in malaria parasites is a long‐standing, clinical target for chemotherapy and prophylaxis. However, despite determination of the complete genome sequence of the lethal species Plasmodium falciparum, the pathway of de novo folate biosynthesis remains incomplete, as no candidate gene for dihydroneopterin aldolase (DHNA) could be identified. This enzyme catalyses the third step in the well‐characterized pathway of plants, bacteria, and those eukaryotic microorganisms capable of synthesizing their own folate. Utilizing bioinformatics searches based on both primary and higher protein structures, together with biochemical assays, we demonstrate that P. falciparum cell extracts lack detectable DHNA activity, but that the parasite possesses an unusual orthologue of 6‐pyruvoyltetrahydropterin synthase (PTPS), which simultaneously gives rise to two products in comparable amounts, the predominant of which is 6‐hydroxymethyl‐7,8‐dihydropterin, the substrate for the fourth step in folate biosynthesis (catalysed by 6‐hydroxymethyl‐7,8‐dihydropterin pyrophosphokinase; PPPK). This can provide a bypass for the missing DHNA activity and thus a means of completing the biosynthetic pathway from GTP to dihydrofolate. Supported by site‐directed mutagenesis experiments, we ascribe the novel catalytic activity of the malarial PTPS to a Cys to Glu change at its active site relative to all previously characterized PTPS molecules, including that of the human host.
Distinct regulators control the expression of methanol methyltransferase isozymes in Methanosarcina acetivorans C2A
Authors: Bose Arpita , Metcalf William W. 
Published: September 2009

SummaryThe mtaCB1, mtaCB2 and mtaCB3 operons encode isozymes of methanol methyltransferases in Methanosarcina acetivorans C2A and are among the most highly regulated genes known in Archaea. Here we identify cis and trans acting elements that affect the expression of these operons. In vivo reporter gene constructs expressed from sequentially truncated promoters show that the mRNA transcripts for these operons have large 5′ untranslated regions. Regions upstream of the transcription start site (TSS) are important for induction of the mtaCB1 and mtaCB2 operons and for repression of the mtaCB3. Regions downstream of the TSS are important for expression of the mtaCB2 and mtaCB3 operons, but are dispensable for mtaCB1 expression. Proteins encoded by the MA0459 and MA0460 loci are required for induction of the mtaCB1 operon, while those encoded by MA4383, MA4397 and MA4398 are required for induction of mtaCB2. Proteins encoded by MA4397 and MA4398 are also required for methanol‐specific repression of the mtaCB3 operon and, thus, are the first archaeal examples of regulatory proteins that simultaneously act in both repression and activation. We refer to these genes as methanol‐specific regulators and designate MA0459, MA0460, MA4383, MA4397 and MA4398 as msrA, msrB, msrC, msrD and msrE respectively.
Identification of Rv2041c, a Novel Immunogenic Antigen from Mycobacterium tuberculosis with Serodiagnostic Potential
Authors: Kim S.‐Y. , Shin A.‐R. , Kim H.‐J. , Cho S.‐N. , Park J.‐K. , Shin S. J. 
Published: September 2009

AbstractNovel immunogenic antigens are continually required for the improvement of diagnostic techniques for Mycobacterium tuberculosis infection. Some proteins with serodiagnostic value are not expressed under normal culture conditions, but may be induced under specific conditions such as gradual oxygen depletion and low pH, and from inside macrophages. Using a customized amplification library, we previously found that Rv2041c from M. tuberculosis H37Rv was highly expressed in vitro under conditions of low pH and hypoxia. In this study, recombinant (r)Rv2041c was produced in Escherichia coli to examine its role in immune responses. Increased Rv2041c expression in vitro during dormancy and during infection in human macrophages was confirmed by Western blotting and reverse transcription polymerase chain reaction, respectively. Interestingly, positive antibody responses to rRv2041c were detected only in those patients with active tuberculosis (TB) and in mice infected with M. tuberculosis H37Rv. Finally, Rv2041c was used successfully in the serodiagnosis of active M. tuberculosis infection in Korean patients in conjunction with other M. tuberculosis proteins, including Ag85 complex, 38 kDa, rESAT‐6, rHSP‐X and rCFP‐10. Our Rv2041c–ELISA had comparable diagnostic sensitivity and equivalent specificity to the use of an M. tuberculosis H37Rv cellular extract. In addition, seven of 46 serum samples collected from TB patients (15.28%) showed positive antibody responses to Rv2041c, but not to the other proteins. These results suggest that Rv2041c can be used to increase assay sensitivity alongside well‐known antigens for the serodiagnosis of M. tuberculosis infection.
The predominance of IgG4 in prodromal bullous pemphigoid
Authors: Lamb Philina M. , Patton Timothy , Deng Jau‐Shyong 
Published: September 2009

Ab stractBackground  Prodromal bullous pemphigoid (PBP) and bullous pemphigoid (BP) demonstrate immunoglobulin G (IgG) and/or C3 deposition at the basement membrane zone (BMZ) on direct immunofluorescence. BP‐180‐specific IgG1, IgG4, and IgE antibodies have been detected in BP. However, the distribution of IgG subclasses is unknown in PBP.Objectives  We will describe the role of anti‐BMZ IgG subclasses in PBP and we will correlate these findings to better understand the pathogenesis of PBP.Methods  Skin biopsies and serum samples were obtained from 45 patients who had PBP. The skin tissue was processed for direct immunofluorescence studies. Sera were analyzed by indirect immunofluorescence for the presence of circulating anti‐BMZ IgG antibodies (by standard IIF) and IgG subclasses antibodies (by sandwich double antibody immunofluorescence [SDAI]). Sera were also analyzed for antibodies against BP‐180 and BP‐230 antigens by enzyme‐linked immunosorbent assay (ELISA).Results  Thirty‐two patients (71%) had IgG and C3 staining at the BMZ, while 13 patients (29%) had isolated C3 staining at the BMZ on direct immunofluorescence. All patients demonstrated staining on the epidermal side of the salt‐split skin. Of the seven skin specimens that were available for C5‐9 SDAI testing, all were found to be positive along BMZ area. Standard IIF studies demonstrated the presence of circulating BMZ antibodies in 11 of the 30 patients (36.6%). When SDAI for IgG subclass differentiation was utilized, 17 of 30 (56.6%) patients were found to have circulating anti‐BMZ antibodies. All of these 17 patients had IgG4 subclass antibodies. Thirteen patients did not have detectable IgG subclass anti‐BMZ antibody on SDAI. Sixteen of 30 patients had detectable anti‐BP‐180 or anti‐BP‐230 antibodies, while 12 (40%) did not have detectable antibody against BP antigens on ELISA.Conclusions  IgG4 is the initial and predominant anti‐BMZ antibody subclass detected in PBP. Demonstration of linear C5‐9 at the BMZ enhances the early diagnosis of PBP. Predominance of IgG4 and the initial presence of IgG4 on skin lesions as well as the presence of only IgG4 subclass anti‐BMZ antibody suggest that IgG4 subclass antibody could be the initial immunologic event encountered in patients with PBP.
Cutaneous diffuse large B‐cell lymphoma of the leg associated with chronic lymphedema
Authors: González‐Vela M. Carmen , González‐López Marcos A. , Val‐Bernal J. Fernando , Fernández‐Llaca Héctor 
Published: September 2009

AbstractDevelopment of malignant tumors is a rare but well known complication in chronic lymphedema (CL). We report herein a cutaneous diffuse large B‐cell lymphoma of the leg associated with CL. An 89‐year‐old man presented with multiple cutaneous lesions on his right limb that showed a CL. Dermatological examination disclosed multiple violaceous, firm, slightly infiltrated nodules on the anterior aspect of the leg and the dorsum and sole of the foot. A biopsy of one nodule of the leg disclosed a diffuse large B‐cell lymphoma, type of the legs. There was no evidence of lymphadenopathy on computed tomography (CT) scans of the chest, abdomen, and pelvis. A bone marrow aspiration and biopsy showed normal results. The patient was treated with local radiotherapy at a dose of 40 Gy, obtaining a highly significant, almost complete, clinical remission. A literature search identified 11 additional cases of primary cutaneous lymphoma associated with CL. An inadequate lymphatic drainage may make the lymphedematous region an immunologically vulnerable area, predisposing to neoplasia.
Two cases of Zoon's balanitis treated with pimecrolimus 1% cream
Authors: Bardazzi F. , Antonucci Angela , Savoia F. , Balestri R. 
Published: September 2009

AbstractBackground  Plasma cell balanitis is a disorder of the middle‐aged and older uncircumcised male. Several treatments have been proposed to treat this disease, but plasma cell balanitis is often resistant to conventional therapy.Methods  We decided to evaluate the efficacy and tolerability of pimecrolimus 1% cream in resistant Zoon's balanitis. We report two cases of resistant Zoon's balanitis treated with topical pimecrolimus 1% cream.Results  One of the two patients had a complete regression of the lesion after 2 months of therapy. The other one had a great improvement of the lesion, but a hyperpigmented patch persisted on the glans.Conclusion  Pimecrolimus 1% cream may be a valuable second‐line treatment for patients with steroid related side effects or with steroid and other conventional therapy resistant Zoon's balanitis, as well as for those rejecting circumcision.
Pyoderma gangrenosum – rebel without a cure?
Authors: Jacob Sharon E. , Weisman Robyn S. , Kerdel Francisco A. 
Published: September 2009

Abst ractBackground  Pyoderma gangrenosum (PG) is a rare neutrophilic, ulcerating dermatosis that is frequently difficult to diagnose and often a diagnosis of exclusion. It is hypothesized that PG may be caused by an abnormal T‐cell and neutrophil response, which correlates with its common link to other disorders, such as inflammatory bowel disease, rheumatoid arthritis, and malignancies. Several treatments have been used successfully for PG, but none has proven to be universally effective.Methods  We present three cases of PG treated with adalimumab after failed courses of steroids (orally and parenterally), thalidomide, cyclosporine, and mycophenolate mofetil.Results  Patients 2 and 3, who had previously responded to infliximab, albeit with recurrence, were successfully treated with adalimumab at a dose of 40 mg once a week. Patient 1 initially responded to adalimumab, but after 7.5 months failed to show wound bed improvement at a dose of 80 mg/week subcutaneously. This patient had not previously been treated with infliximab.Conclusion  We believe adalimumab to be a valuable alternative for the treatment of PG, with comparable efficacy to infliximab.
Effects of interferon‐α2b on keloid treatment with triamcinolone acetonide intralesional injection
Authors: Lee June Hyunkyung , Kim Seong Eon , Lee Ai‐Young 
Published: September 2009

AbstractBackground  Triamcinolone acetonide intralesional injection (TAIL) has been used for the treatment of keloids, but only with limited success. Interferon‐α (IFN‐α) is the most widely used IFN, and has mainly antiviral, antiproliferative, and antitumoral functions. A few studies have evaluated the efficacy of IFN‐α2b in controlled trials for the treatment of keloids.Objective  To compare the efficacy and side‐effects of keloid treatment using IFN‐α2b and TAIL, and TAIL only.Methods  Twenty lesions (combined TAIL + IFN‐α2b group) and 20 control lesions (TAIL‐only group) were studied in 19 patients (14 women and five men). The age range was 7–51 years (mean age, 24.6 years). Both groups were treated with TAIL every 2 weeks. The combined TAIL + IFN‐α2b group was treated with intralesional injection of IFN‐α2b, twice a week. Lesion measurements were made using thread, glue, and alginate.Results  Statistically significant decreases in depth (81.6%, P = 0.005) and volume (86.6%, P = 0.002) were observed in lesions of the combined TAIL + IFN‐α2b group. In the TAIL‐only group, the decreases in depth (66.0%, P = 0.281) and volume (73.4%, P = 0.245) were less statistically significant. The main side‐effects were fever and flu‐like symptoms, mild pain, and inflammation at the injection site.Conclusions  Intralesional IFN‐α2b is an effective and safe treatment for keloids. Although the recurrence rate is as yet unknown, more than 80% improvement was noted in the majority of cases. Hence, adjuvant intralesional IFN‐α2b should be considered, particularly for patients who have a history of failed corticosteroid injections.
“The Laundry Bag Project”– unequal distribution of dermatological healthcare resources for male and female psoriatic patients in Sweden
Authors: Nyberg Filippa , Osika Ingrid , Evengård Birgitta 
Published: September 2009

AbstractBackground  Psoriasis and eczema are common dermatological diseases that occur with approximately equal frequency in men and in women. The aim of this study was to determine whether men and women with dermatological diseases in need of ultra‐violet radiation (UV) treatment receive equal care.Methods  We conducted a retrospective analysis of records of all patients referred to and seen at our clinic during 2003 with diagnoses of psoriasis or eczema. We performed a gender‐based analysis of the number, type, and estimated cost of the treatments given to each patient. We evaluated similar data from a Swedish Psoriasis Association (SPA) treatment center and from the state pharmacy monopoly (Apoteksstatistiken).Results  Men with eczema or psoriasis received more help with emollients than did women and were given a greater number of UV treatments. At our clinic and at the SPA center, women constituted 37 and 42%, respectively, of the individuals who received UV treatment; yet, they received only 34 and 36% of the treatments, respectively. Women were prescribed self‐care more often than men, with 61% of prescriptions for emollients and 48% of specific topical treatments for psoriasis dispensed to women.Conclusions  We discovered previously unrecognized gender differences in standard dermatological treatment for common diagnoses at our hospital. To ensure optimal care for each patient, treatment disparity should be recognized and gender‐based analyzes be carried out when planning dermatological health care.
Immunohistochemistry and polymerase chain reaction on paraffin‐embedded material improve the diagnosis of cutaneous leishmaniasis in the Amazon region
Authors: Amato Valdir Sabbaga , Tuon Felipe Francisco , De Andrade, Jr Heitor Franco , Bacha Helio , Pagliari Carla , Fernandes Elaine Raniero , Duarte Maria Irma Seixas , Neto Vicente Amato , Zampieri Ricardo Andrade , Floeter‐Winter Lucile Maria , Celeste Beatriz J. , Oliveira Juliane , Quiroga Mariana Martinez , Mascheretti Melissa , Boulos Marcos 
Published: September 2009

AbstractBackground  Recently, there has been an increase in the incidence of cutaneous leishmaniasis (CL), which represents an important health problem. This increase may be related to the epidemiologic expansion of the infective agent and the increase in tourism in tropical areas. The difficulty in clinical diagnosis, mainly in areas in which CL is not the first consideration of local physicians, has intensified efforts to describe diagnostic tests, which should be specific, sensitive, and practical. Amongst the new tests described are those including nucleic acid amplification (polymerase chain reaction, PCR) and immunohistochemistry (IHC).Methods  In this study, we evaluated the sensitivity of a PCR based on small subunit (SSU) ribosomal DNA, in comparison with IHC using Leishmania spp. antibodies, in biopsies embedded in paraffin.Result  The results indicated a total sensitivity of 96% (90.9% with PCR and 68.8% with IHC), showing the possibility of using paraffin‐embedded biopsies to diagnose CL.Conclusion  We propose the use of the two tests together as a routine protocol for diagnosis. This would require the provision of local medical services to perform molecular biology techniques and adequate Leishmania antibodies.