bluuebunny/crossref_metadata_2025 huggingface dataset:
Cytokines and Reperfusion in Ischemic Stroke
Authors: Garcia Julio H. , Liu Kai‐Feng , Ye Zhu‐Rong
Published: January 2008

The clinical syndrome known as ischemic stroke, secondary to the occlusion of an intracranial artery, once considered an ineluctably catastrophic event, may be susceptible of being improved through the application of newly developed therapeutic interventions. The evidence favoring this optimistic outlook is based on three separate but probably interrelated observations: (1) There exists a lapse of hours, perhaps days, between the ictus (i.e., the appearance of a focal neurologic deficit or stroke) and the time when irreversible tissue injury (i.e., widespread pannecrosis) becomes demonstrable. This time interval, generally known as the therapeutic window, may be measured in hours or days depending on the degree or severity of the post occlusive ischemia. (2) Reopening the artery, within a reasonable period of time, has beneficial effects in terms of: (a) improving the neurologic function, and (b) decreasing the numbers of necrotic neurons as well as preventing the appearance of pannecrosis or infarction. (3) The progression from the early ischemic changes (potentially reversible) to the development of an infarct may be influenced by the effects of selected cytokines, in particular those of interleukin 1 (IL‐1).

In this review we illustrate selected structural features of the various brain lesions induced by either permanent or transient arterial occlusions. Moreover, we discuss the possible Involvement of interleukins in the progression of the brain lesion based on experiments utilizing the administration of a human recombinant IL‐1 receptor antagonist. Combined with the efforts aimed at restoring the normal circulatory conditions, therapeutic interventions that inhibit specific cytokines may contribute to improve the outcome of ischemic strokes.
The Role of Macrophages in Wallerian Degeneration
Authors: Brück Wolfgang
Published: January 2008

The present review focuses on macrophage properties in Wallerian degeneration. The identification of hematogenous phagocytes, the involvement of cell surface receptors and soluble factors, the state of activation during myelin removal and the signals and factors leading to macrophage recruitment into degenerating peripheral nerves after nerve transection are reviewed. The main effector cells in Wallerian degeneration are hematogenous phagocytes. Resident macrophages and Schwann cells play a minor role in myelin removal. The macrophage complement receptor type 3 is the main surface receptor involved in myelin recognition and uptake. The signals leading to macrophage recruitment are heterogenous and not yet defined in detail. Degenerating myelin and axons are suggested to participate. The relevance of these findings for immune‐mediated demyelination are discussed since the definition of the role of macrophages might lead to a better understanding of the pathogenesis of demyelination.
Primitive Neuroectodermal Tumors of the Central Nervous System
Authors: Rorke Lucy Balian , Trojanowski John Q. , Lee Virginia MY , Zimmerman Robert A. , Sutton Leslie N. , Biegel Jaclyn A. , Goldwein Joel W. , Packer Roger J.
Published: January 2008

Controversial issues relating to the pathobiology and classification of central nervous system primitive neuroectodermal tumors (PNETs) have plagued neuropathologists for more than 70 years. Hypotheses advanced in the mid‐1920's have remained as fixed concepts in contemporary literature, largely consequent to repetitious support by a small number of neuropathologists despite a growing body of information discrediting these ideas from neuroembryologists, oncologists, neuroscien‐tists and pathologists.

Attention has largely focused upon PNETs arising in the cerebellum (commonly known as medul‐loblastomas [MBs]), because about 80% of central nervous system (CNS) PNETs originate in this site. It has been asserted that the 20% which do not are biologically different, although most individuals agree that the histological features of PNETs that occur in different sites throughout the CNS are indistinguishable from those growing in the cerebellum.

The historical aspects of this controversy are examined in the face of evidence that there is, in fact, a unique class of CNS tumors which should appropriately be regarded as primitive neuroectodermal in nature. Specifically, a number of different approaches to the problem have yielded data supporting this hypothesis. These approaches include the identification of patterns of expression among a variety of cellular antigens (demonstrated by the use of immunopathological techniques), molecular analyses of cell lines derived from these tumors, experimental production of PNETs and molecular genetic analyses.

Differences of opinion among surgeons, oncologists and radiotherapists are typically resolved by conducting cooperative studies of patients with these tumors who are diagnosed and treated at multiple centers.
The Molecular Biology of Ependymomas
Authors: Hamilton Ronald L. , Pollack Ian F.
Published: January 2008

Intracranial ependymomas are the third most common primary brain tumor in the pediatric population. Although an anaplastic variant is recognized, numerous studies examining the prognostic implications of histological features, such as necrosis, endothelial proliferation and mitoses, have yielded contradictory results. In order to improve outcome prediction in affected patients and to refine therapeutic decision‐making, there is a strong need for identifying relevant biological correlates of tumor behavior. The molecular biology of tumors is a rapidly expanding field and includes investigations into cytogenetics, oncogenes, growth factors, growth factor receptors, hormonal receptors, proliferation markers, apoptosis, cell cycle genes and cell adhesion molecules, as well as factors potentially related to therapeutic resistance, such as the multidrug resistance gene. The molecular biology of astrocytic tumors in adults has been the subject of many studies; however, relatively few studies have been focused on ependymomas. Herein we review potential oncological markers in ependymomas that have been identified to date and highlight the limitations of our current knowledge as a basis for defining areas for future investigation.
Neurofibromatosis 1 and 2
Authors: Pollack Ian F. , Mulvihill Jonn J.
Published: January 2008

Neurofibromatosis (NF) 1 and 2 are multisystem disorders associated with a variety of neoplastic and non‐neoplastic manifestations that typically progress in severity during the lifetime of the affected patient. The importance of appropriately diagnosing these disorders stems from the fact that the natural history of an associated neoplasm, such as a peripheral nerve tumor or an optic glioma, may be significantly different depending on whether or not the lesion arises in a person with NF. In addition, the indications for therapeutic intervention, hierarchy of treatment options and long‐term management goals may differ substantially for patients with NF‐related versus sporadic tumors. Finally, recognition of the diagnosis comprises an essential step for providing appropriate multidisciplinary evaluation and counseling to affected patients and their families. This article addresses the principal manifestations of these disorders and provides a contemporary review of the diagnostic and therapeutic issues that arise in children with NF1 and NF2.
November 1996 — Premature Baby with Lethargy and Coma
Authors: Hevner Robert , Sobel Raymond A.
Published: January 2008

Case Abstract

A premature male baby (28 weeks gestational age) was delivered by Cesarean section and required ventilation for respiratory distress syndrome during the first postnatal week. Four weeks postnatally, he had an episode of transient renal failure followed by lethargy leading to coma. Ultrasound changes were interpreted as intraventricular hemorrhage, grade 2. The baby died 31 days after birth. Autopsy showed bilateral thrombosis of the deep cerebral veins.
December 1996 — Cervicomedullary Tumor
Authors: Hamilton Ronald L.
Published: January 2008

Case Abstract

A cervicomedullary tumor in a 22‐month‐old female with an eight‐month history of symptoms showed the histological features of a pilocytic astrocytoma but had many areas of palisading cells identical to those described in polar spongioblastomas. The tumor recurred 18 months later and showed predominately pilocytic features. The case is used to discuss polar spongioblastomas and tumors which can histologically simulate them.
Pathology and Immunocytochemistry of a Kuru Brain
Authors: Hainfellner Johannes A. , Liberski Pawel P. , Guiroy Don C. , Cervénaková Larisa , Brown Paul , Gajdusek D. Carleton , Budka Herbert
Published: January 2008

We report here results of modern staining techniques including anti‐prion protein (PrP) immunocytochemistry to a set of archival brain specimens of a 16 year‐old male who died from kuru in 1967. Brain suspensions transmitted disease to chimpanzees and New World monkeys. The PrP gene is homozygous for valine at the polymorphic codon 129. Histology shows neuronal loss, spongiform change, and astrogliosis. Lesions are maximal in parasagittal and interhemispheric areas of frontal, central and parietal cortex, cingulate cortex, striatum, and thalamus, and are accentuated in middle and deep cerebral cortical layers. PrP accumulates as diffuse synaptic type deposits and mostly unicentric plaques. PrP deposition is maximal in parasagittal and interhemispheric areas of frontal, central and parietal cortex, cingulate cortex, basal ganglia, and cerebellar cortex. Plaques are prominent in the striatum, thalamus, and granular layer of cerebellar cortex. Meticulous examination reveals only rare “florid” plaques with surrounding vacuolation.

We conclude that 1) pathology including immunomorphology of PrP deposition in this kuru brain is within the lesion spectrum of Creutzfeldt‐Jakob disease although plaques are unusually prominent and widespread; 2) kuru does not share the neuropathological hallmarks of the new Creutzfeldt‐Jakob disease variant recently reported in the UK and France; 3) topographic prominence of PrP deposition parallels that of spongiform change and/or astrogliosis.
Trichinosis
Authors: Taratuto Ana Lia , Venturiello Stella M.
Published: January 2008

Trichinosis is a worldwide zoonotic disease closely related to cultural and dietary habits caused by a nematode Trichinella spp. Human infection is acquired through ingestion of undercooked meat containing infective encysted larvae. There are two cycles of transmission, one domestic and the other wild. A complete life cycle develops in a single host harboring adult worms in the small intestine, from which newborn larvae migrate and finally encyst in striated muscle. Traumatic and immunological alterations are responsible for the main clinical features, including diarrhea, febrile syndrome, myalgias, oculopalpebral signs and eosinophilia. Cardiovascular, lung and CNS involvement characterize severe trichinosis. CNS inflammatory infiltration and damage may result from larval migration and vascular obstruction, or from the effect of toxic parasite antigens, or eosinophil infiltration. Humoral and cellular immune host response are relevant both to protect against re‐infection and for immun‐odiagnosis. DNA probes and PCR technology may help to identify Trichinella spp. Muscle biopsy may disclose T spiralis larvae coiled within a muscle fibre host nurse cell surrounded by a capsule. Inflammatory infiltration includes monocytes, plasma cells, eosinophils and T lymphocytes mainly of the suppressor/cytotoxic phenotype. Histological appearance and histochemical profile of the host nurse cell differ from that of striated muscle fibre and are partly indicative of regeneration. Our own histological and histochemical findings in experimental studies of infected mouse muscle support the concept that changes induced by the larva encysting within a single host skeletal muscle fibre which becomes a nurse cell are unique of Trichinella infection. Interestingly, no dystrophin could be detected within the host nurse cell‐capsule interface. It has been advanced that larva‐induced host muscle fibre changes may be regulated at muscle gene transcription level whilst host regulatory pathways governed by cell cycle phase may also contribute to larval development.
Neurocysticercosis
Authors: Pittella José E. H.
Published: January 2008

Cysticercosis is an infection caused by Taenia solium larvae (cysticerci). When the cysticercus is lodged in the central nervous system (CNS), the disease is known as neurocysticercosis (NCC). NCC is the most frequent and most widely disseminated human neuroparasitosis. It is endemic in many parts of the world, particularly Latin America, Africa, and Asia, and still relatively frequent in Portugal, Spain and Eastern European countries. It is also endemic in developed countries with high rates of immigration from endemic areas. Man may act as an intermediate host after ingestion of mature, viable T. solium eggs via the fecal‐oral route. The development of lesions in the brain and leptomeninges, and the consequent onset of symptoms associated with NCC are mainly due to the host immune‐inflammatory response. As long as the cysticercus remains viable, there is relative host immune tolerance. It is only when the parasite dies that massive antigen exposure occurs, with intensification of the immune response/inflammatory reaction and the appearance or worsening of symptoms. NCC can be asymptomatic or cause widely varied clinical manifestations, such as seizures, increased intracranial pressure, ischemic cerebrovascular disease, dementia, and signs of compression of the spinal roots/cord. The combination of two or more symptoms is common. Such clinical polymorphism is determined by 1) the number of lesions (single or multiple cysticerci); 2) the location of CNS lesions (subarachnoid, intracerebral, intraventricular, intramedullary); 3) the type of cysticercus (Cysticercus cellulosae, Cysticercus racemosus); 4) the stage of development and involution of the parasite (vesicular or viable, necrotic, fibrocalcified nodule); and 5) the intensity of the host immune‐inflammatory response (no inflammatory reaction, leptomeningitis, encephalitis, granular ependymitis, arteritis).
July 1996 — Precocious Puberty
Authors: Hamilton Ronald L.
Published: January 2008

Case Abstract

A 4 year old girl presented with precocious puberty. She had pubic hair, breast buds and showed a height and weight well above the 95th percentile. An MRI scan of the head revealed a discrete mass in the tuber cinereum which was surgically removed. Microscopic examination showed a hypothalamic hamartoma. The clinical, radiologic and microscopic findings in this case are “classic” for hypothalamic hamartoma Other clinical presentations are discussed. The patient's symptoms have regressed following surgery and there has been no regrowth in six months.
Virulence and resistance in a mosquito–microsporidium interaction
Authors: Michalakis Yannis , Bédhomme Stéphanie , Biron David G. , Rivero Ana , Sidobre Christine , Agnew Philip
Published: January 2008

We review the results of a series of experiments involving Aedes aegypti and its microsporidian parasite Vavraia culicis to illustrate how intra‐specific competition and parasitism shape life history traits. More specifically these experiments showed that some major components of virulence are host condition‐dependent in this system, while others are not. We also briefly discuss the ways through which V. culicis modifies the physiological functioning of its host. We discuss the implications of these results for studies of host – parasite interactions in general and propose ways through which our studies could contribute to vector control and management programs.
Multilaboratory Testing of Antifungal Combinations against a Quality Control Isolate of
Candida krusei
Authors: Chaturvedi Vishnu , Ramani Rama , Ghannoum Mahmoud A. , Killian Scott B. , Holliday Nicole , Knapp Cindy , Ostrosky-Zeichner Luis , Messer Shawn A. , Pfaller Michael A. , Iqbal Naureen J. , Arthington-Skaggs Beth A. , Vazquez Jose A. , Sein Tin , Rex John H. , Walsh Thomas J.
Published: January 2008

Candida krusei
ATCC 6258 was tested by eight laboratories using 96-well plates containing checkerboard pairwise combinations of amphotericin B (AMB), posaconazole (PSC), caspofungin (CSP), and voriconazole (VRC). The methodology led to reproducible results across the laboratories. All drug combinations yielded MICs lower than the MICs of any two drugs tested singly, and combinations of AMB, PSC, CSP, and VRC were indifferent (no antagonism) by summations of fractional inhibitory concentration.
In Vitro Model of Colonization Resistance by the Enteric Microbiota: Effects of Antimicrobial Agents Used in Food-Producing Animals
Authors: Wagner R. Doug , Johnson Shemedia J. , Cerniglia Carl E.
Published: January 2008

A bioassay was developed to measure the minimum concentration of an antimicrobial drug that disrupts the colonization resistance mediated by model human intestinal microbiota against
Salmonella
invasion of Caco-2 intestinal cells. The bioassay was used to measure the minimum disruptive concentrations (MDCs) of drugs used in animal agriculture. The MDCs varied from 0.125 μg/ml for some broad-spectrum antimicrobial drugs (e.g., streptomycin) to 16 μg/ml for drugs with limited spectra of antimicrobial activity (e.g., lincomycin). The acceptable daily intake (ADI) residue concentration calculated on the basis of the MDCs were higher for erythromycin, lincomycin, and tylosin than the ADI residue concentrations calculated on the basis of the MICs. The MDC-based ADI values for apramycin, bacitracin, neomycin, novobiocin, penicillin G, streptomycin, tetracycline, and vancomycin were lower than the reported MIC-based ADI values. The effects of antimicrobial drugs at their MDCs on the bacterial composition of the microbiota were observed by denaturing gradient gel electrophoresis of 16S rRNA sequences amplified by PCR. Changes in the population composition of the model colonization resistance microbiota occurred simultaneously with reduced colonization resistance. The results of this study suggest that direct assessment of the effects of antimicrobial drugs on colonization resistance in an in vitro model can be useful in determining ADI values.
In Vitro Interactions of Micafungin with Amphotericin B against Clinical Isolates of
Candida
spp
Authors: Serena Carolina , Mariné Marçal , Quindós Guillermo , Carrillo Alfonso J. , Cano J. F. , Pastor F. Javier , Guarro Josep
Published: January 2008

The in vitro activity of amphotericin B in combination with micafungin was evaluated against 115 isolates representing seven species of
Candida
. Overall, the percentages of synergistic interactions were 50% and 20% when the MIC-2 (lowest drug concentration to cause a prominent reduction in growth) and MIC-0 (lowest drug concentration to cause 100% growth inhibition) end point criteria, respectively, were used. Antagonism was not observed. Some of the interactions were confirmed by time-kill assays.
Isolation of Imipenem-Resistant
Enterobacter
Species: Emergence of KPC-2 Carbapenemase, Molecular Characterization, Epidemiology, and Outcomes
Authors: Marchaim Dror , Navon-Venezia Shiri , Schwaber Mitchell J. , Carmeli Yehuda
Published: January 2008

The prevalence of isolation of imipenem-resistant
Enterobacter
(IRE) strains is rising, with potential serious consequences in terms of patients' outcomes and general care. The study objective was to define the various epidemiological aspects of the isolation of these strains in comparison to cases of isolation of imipenem-susceptible
Enterobacter
(ISE) strains. Molecular analysis of IRE strains included genotyping and defining the presence of carbapenemases. We conducted a matched retrospective case-control study of patients hospitalized from April 2003 to December 2006. Each IRE case was matched with an ISE case by age and source of isolation. A multivariate analysis using conditional logistic regression was performed to compare the two patient groups. There were 33 cases of IRE isolations during the study period. Twenty isolates were analyzed and found to belong to three distinct pulsotypes. Cell extracts of all of these isolates hydrolyzed imipenem. PCR and sequencing revealed that these isolates harbored a KPC-2 gene. In multivariate analysis, a high invasive-device score (
P
= 0.02) remained a predictor of IRE isolation. The mortality in the IRE group was 33%, compared to 9% among controls. Being an IRE case was significantly associated with increased mortality after controlling for confounders in a multivariate model (odds ratio, 8.3 ± 8.6; 95% confidence interval, 1.07 to 64;
P
= 0.043). Resistance to imipenem due to
bla
KPC-2
among
Enterobacter
isolates has occurred in several clones in Tel Aviv, affecting particularly patients with multiple invasive devices compared to ISE controls. IRE infections are associated with increased mortality. Enhanced measures to control the hospital spread of IRE are warranted.
Activity of Tigecycline against Coryneform Bacteria of Clinical Interest and
Listeria monocytogenes
Authors: Salas Carlos , Calvo Jorge , Martínez-Martínez Luis
Published: January 2008

The activities of tigecycline and eight other agents were evaluated against 220 coryneform bacteria and 42
Listeria monocytogenes
isolates. All strains were inhibited by tigecycline at 0.5 μg/ml, except for 11
Corynebacterium striatum
strains that were inhibited at 1 μg/ml. Tigecycline shows good in vitro activity against coryneform bacteria and
L. monocytogenes
.
Diversity of Extended-Spectrum β-Lactamases and Class C β-Lactamases among Cloacal
Escherichia coli
Isolates in Belgian Broiler Farms
Authors: Smet Annemieke , Martel An , Persoons Davy , Dewulf Jeroen , Heyndrickx Marc , Catry Boudewijn , Herman Lieve , Haesebrouck Freddy , Butaye Patrick
Published: January 2008

A total of 295 ceftiofur-resistant
Escherichia coli
isolates were obtained from 489 cloacal samples collected at five different Belgian broiler farms with the aim to evaluate the diversity of this resistance at the farm level. Strains were examined for resistance against β-lactam antibiotics and other antimicrobial agents by using disk diffusion tests. Three different β-lactam resistance phenotypes suggested the presence of an extended-spectrum β-lactamase (ESBL), a class C β-lactamase, or the combination of an ESBL with a class C β-lactamase. Seventy-six percent of these isolates also showed acquired resistance to other antimicrobial agents. After genotyping by repetitive extragenic palindromic-PCR, 51 unrelated
E. coli
strains were selected for further analyses. Isoelectric focusing and sequencing of the amplicons obtained in PCRs for the detection of genes encoding broad-spectrum β-lactamase enzymes revealed the following ESBLs: TEM-52 (13.2%), TEM-106 (2%), CTX-M-1 (27.4%), CTX-M-2 (7.8%), CTX-M-14 (5.9%), and CTX-M-15 (2%). The only plasmidic AmpC β-lactamase found in this study was the CMY-2 enzyme (49%). Mutations in the promoter and attenuator regions of the chromosomal
ampC
gene were found only in association with
bla
CMY-2
genes and ESBL genes. The combination of an ESBL (CTX-M-1) with a plasmidic AmpC β-lactamase (CMY-2) was found in 7.8% of the isolates. These data show that ceftiofur-resistant
E. coli
strains are often present in cloacal samples of broilers at the farm level in Belgium. The diversity of broad-spectrum β-lactamases among these isolates is high, and they may act as a reservoir of ESBL and
ampC
genes.
NK Cells and Gamma Interferon Coordinate the Formation and Function of Hepatic Granulomas in Mice Infected with theFrancisella tularensisLive Vaccine Strain
Authors: Bokhari Sirosh M. , Kim Kee-Jun , Pinson David M. , Slusser Joyce , Yeh Hung-Wen , Parmely Michael J.
Published: January 2008

Host innate immune responses to many intracellular pathogens include the formation of inflammatory granulomas that are thought to provide a physical barrier between the microbe and host. Because two common features of infections with the live vaccine strain (LVS) ofFrancisella tularensiswithin the mouse liver are the formation of granulomas and the production of gamma interferon (IFN-γ), we have asked what role IFN-γ plays in hepatic granuloma formation and function.Francisellaantigens were predominantly localized within granulomas of the livers of mice infected withF. tularensisLVS 4 days postinfection. Hepatic granulomas also contained large numbers of dying cells, some of which coexpressed the F4/80 macrophage antigen and activated caspase-3. IFN-γ-deficient mice did not form normal numbers of hepatic granulomas and showed widely disseminatedFrancisellaantigens within the liver. The incidence of cell death within hepatic granulomas also decreased significantly in the absence of IFN-γ. Inducible NO synthase (iNOS) expression was restricted to the granulomas of wild-type mice but was not seen for IFN-γ-deficient mice. Cell death within granulomas was also significantly decreased for iNOS-deficient mice. The predominant IFN-γ-expressing cells in the liver were NK cells. Depleting NK cells resulted in the expression of bacterial antigens and iNOS outside the granulomas and the appearance of extensive hepatic focal necrosis. These findings indicate that IFN-γ and hepatic NK cells that are activated duringF. tularensisLVS infections regulate hepatic granuloma formation, the spatial containment of infection, the expression of iNOS, and the induction of cell death within the liver.
Flagellin-Dependent and -Independent Inflammatory Responses following Infection by EnteropathogenicEscherichia coliandCitrobacter rodentium
Authors: Khan Mohammed A. , Bouzari Saeid , Ma Caixia , Rosenberger Carrie M. , Bergstrom Kirk S. B. , Gibson Deanna L. , Steiner Theodore S. , Vallance Bruce A.
Published: January 2008

EnteropathogenicEscherichia coli(EPEC) and the murine pathogenCitrobacter rodentiumbelong to the attaching and effacing (A/E) family of bacterial pathogens. These noninvasive bacteria infect intestinal enterocytes using a type 3 secretion system (T3SS), leading to diarrheal disease and intestinal inflammation. While flagellin, the secreted product of the EPECfliCgene, causes the release of interleukin 8 (IL-8) from epithelial cells, it is unclear whether A/E bacteria also trigger epithelial inflammatory responses that are FliC independent. The aims of this study were to characterize the FliC dependence or independence of epithelial inflammatory responses to direct infection by EPEC orC. rodentium. Following infection of Caco-2 intestinal epithelial cells by wild-type and ΔfliCEPEC, a rapid activation of several proinflammatory genes, including those encoding IL-8, monocyte chemoattractant protein 1, macrophage inflammatory protein 3α (MIP3α), and β-defensin 2, occurred in a FliC-dependent manner. These responses were accompanied by mitogen-activated protein kinase activation, as well as the Toll-like receptor 5 (TLR5)-dependent activation of NF-κB. At later infection time points, a subset of these proinflammatory genes (IL-8 and MIP3α) was also induced in cells infected with ΔfliCEPEC. The nonmotile A/E pathogenC. rodentiumalso triggered similar innate responses through a TLR5-independent but partially NF-κB-dependent mechanism. Moreover, the EPEC FliC-independent responses were increased in the absence of the locus of enterocyte effacement-encoded T3SS, suggesting that translocated bacterial effectors suppress rather than cause the FliC-independent inflammatory response. Thus, we demonstrate that infection of intestinal epithelial cells by A/E pathogens can trigger an array of proinflammatory responses from epithelial cells through both FliC-dependent and -independent pathways, expanding our understanding of the innate epithelial response to infection by these pathogens.
Activation of the Cpx Envelope Stress Response Down-Regulates Expression of Several Locus of Enterocyte Effacement-Encoded Genes in Enteropathogenic
Escherichia coli
Authors: MacRitchie Dawn M. , Ward Jordan D. , Nevesinjac Anna Z. , Raivio Tracy L.
Published: January 2008

The Cpx two-component system regulates an extracytoplasmic stress response that functions to rid the envelope of misfolded and mislocalized proteins that may interfere with normal cellular processes. The Cpx pathway is also involved in pathogenesis. This study investigated the role of the Cpx response in enteropathogenic
Escherichia coli
(EPEC) type III secretion (T3S). It was determined that a functional Cpx pathway is not required for T3S but that pathway activation inhibits secretion by reducing the cellular pools of T3S substrates. The EPEC T3S system structural components, as well as a number of its substrates, are encoded on the locus of enterocyte effacement (LEE) pathogenicity island. Transcriptional fusions to the five major operons of the LEE were constructed and examined under Cpx pathway-activating conditions. Induction of the Cpx response caused a decrease in the transcription of several LEE operons, with the most pronounced effect on LEE4 and LEE5. Collectively, these two operons encode components of the T3S translocation apparatus, the bacterial adhesin intimin, and the translocated bacterial receptor Tir. These data show for the first time that activation of the Cpx envelope stress response in EPEC inhibits T3S of both translocators and effectors, likely through down regulation of LEE transcription. Coupled with recent findings, our results suggest that Cpx-mediated down regulation of virulence is a conserved theme in a number of bacterial pathogens.
Role of Cyclic Di-GMP during El Tor Biotype
Vibrio cholerae
Infection: Characterization of the In Vivo-Induced Cyclic Di-GMP Phosphodiesterase CdpA
Authors: Tamayo Rita , Schild Stefan , Pratt Jason T. , Camilli Andrew
Published: January 2008

In
Vibrio cholerae
, the second messenger cyclic di-GMP (c-di-GMP) positively regulates biofilm formation and negatively regulates virulence and is proposed to play an important role in the transition from persistence in the environment to survival in the host. Herein we describe a characterization of the infection-induced gene
cdpA
, which encodes both GGDEF and EAL domains, which are known to mediate diguanylate cyclase and c-di-GMP phosphodiesterase (PDE) activities, respectively. CdpA is shown to possess PDE activity, and this activity is regulated by its inactive degenerate GGDEF domain. CdpA inhibits biofilm formation but has no effect on colonization of the infant mouse small intestine. Consistent with these observations,
cdpA
is expressed during in vitro growth in a biofilm but is not expressed in vivo until the late stage of infection, after colonization has occurred. To test for a role of c-di-GMP in the early stages of infection, we artificially increased c-di-GMP and observed reduced colonization. This was attributed to a significant reduction in
toxT
transcription during infection. Cumulatively, these results support a model of the
V. cholerae
life cycle in which c-di-GMP must be down-regulated early after entering the small intestine and maintained at a low level to allow virulence gene expression, colonization, and motility at appropriate stages of infection.
Fcγ Receptor Regulation of
Citrobacter rodentium
Infection
Authors: Masuda Atsuhiro , Yoshida Masaru , Shiomi Hideyuki , Ikezawa Satoshi , Takagawa Tetsuya , Tanaka Hiroshi , Chinzei Ryo , Ishida Tsukasa , Morita Yoshinori , Kutsumi Hiromu , Inokuchi Hideto , Wang Shuo , Kobayashi Kanna , Mizuno Shigeto , Nakamura Akira , Takai Toshiyuki , Blumberg Richard S. , Azuma Takeshi
Published: January 2008

Citrobacter rodentium
, a murine model pathogen for enteropathogenic
Escherichia coli
, colonizes the colon utilizing attaching and effacing lesions to adhere specifically to the surfaces of intestinal epithelial cells and cause mucosal inflammation. CD4
+
T cells, B cells, and immunoglobulin G (IgG), but not secretory IgA or IgM, play a critical role in eradicating this pathogen. Consistent with the importance of IgG in
C
.
rodentium
eradication, IgG transport by the neonatal Fc receptor for IgG within the intestinal epithelium also has a critical role in the regulation of
C
.
rodentium
infection. It remains to be determined, however, whether Fcγ receptors (FcγRs), the receptors for the Fc portion of IgG, regulate this bacterial infection within mucosal tissues. Therefore, we investigated the roles of FcγRs during
C
.
rodentium
infection. Fc receptor common gamma chain (FcRγ)-deficient mice were more susceptible to
C
.
rodentium
-induced colitis. This occurred through decreased efficiency of FcR-mediated endocytosis and maturation of dendritic cells and consequently T-cell activation of antigen-specific T cells. Moreover, in the absence of FcγRs, phagocytosis by macrophages was significantly diminished. Therefore, activating FcγRs play an important role in defending against
C
.
rodentium
infection, indicating that the critical role played by IgG in this infection is not mediated by IgG alone but is dependent upon this class of receptors.
The
Listeria monocytogenes
Virulence Factor InlJ Is Specifically Expressed In Vivo and Behaves as an Adhesin
Authors: Sabet Christophe , Toledo-Arana Alejandro , Personnic Nicolas , Lecuit Marc , Dubrac Sarah , Poupel Olivier , Gouin Edith , Nahori Marie-Anne , Cossart Pascale , Bierne Hélène
Published: January 2008

The food-borne pathogen
Listeria monocytogenes
is adapted to a diversity of environments, such as soil, food, body fluids, and the cytosol of eukaryotic cells. The transition between saprophytic and pathogenic life is mediated through complex regulatory pathways that modulate the expression of virulence factors. Here we examined the expression of
inlJ
, a recently identified gene encoding a protein of the LPXTG-internalin family and involved in pathogenesis. We show that
inlJ
expression is controlled neither by the major listerial regulator of virulence genes, PrfA, nor by AxyR, a putative AraC regulator encoded by a gene adjacent to
inlJ
and divergently transcribed. The InlJ protein is not produced by bacteria grown in vitro in brain heart infusion medium or replicating in the cytosol of tissue-cultured cells. In contrast, it is efficiently produced and localized at the surface of bacteria present in the liver and blood of infected animals. Strikingly, the expression of
inlJ
by a heterologous promoter in
L
.
monocytogenes
or
L
.
innocua
promotes bacterial adherence to human cells in vitro. Taken together, these results strongly suggest that InlJ acts as a novel
L
.
monocytogenes
sortase-anchored adhesin specifically expressed during infection in vivo.
A New Linker for Solid-Phase Synthesis of Oligonucleotides with Terminal Phosphate Group
Authors: Pačes Ondřej , Točík Zdeněk , Rosenberg Ivan
Published: January 2008

Synthesis of a novel cyanoethyl-type linker suitable for the solid-phase synthesis of oligodeoxynucleotides possessing terminal 3'-phosphate group is described. Since the linker is a 2-substituted 2-cyanoethanol, the release of the synthesized oligonucleotide from the solid support is accomplished by β-elimination in the ammonia deprotection step.
Pitfalls in the performance and interpretation of clinical immunology tests
Authors: Lock R J , Virgo P F , Unsworth D J
Published: January 2008

A broad overview, with examples, of the potential pitfalls encountered in the clinical immunology laboratory is presented. Illustrative examples and case scenarios are provided from autoimmunity, immunochemistry and cellular immunology, looking at both technical and interpretative pitfalls.
Role of age stratification for colposcopy referral following initial diagnosis of mild dyskaryosis
Authors: Crowther S , Turner L , Magee D , Gibbons D
Published: January 2008

Introduction:

Referral to colposcopy following a single mildly dyskaryotic smear is becoming more widely recommended in the developed world. This has workload and cost implications.

Aim:

To investigate if stratification of mildly dyskaryotic smears by age group might allow selection of populations that could be followed by repeat cytology initially.

Methods:

The study set was of all women with a diagnosis of dyskaryosis between July 2004 and June 2005 in an opportunistic screening programme. The dyskaryosis was divided into high grade (moderate and severe) and low grade and ratios of high to low grade were calculated for age groups. The age intervals were under 20 years, and every 5 years from 20 to 54 years.

Results:

In the study period, a total of 34 180 cervical smears were examined. Of these, 2326 women were diagnosed with dyskaryosis, (1566 (67%) low grade, 760 (33%) high grade) in the given age groups. This gave an overall ratio of high grade to low grade of 1:2. Ratios of high-grade dyskaryosis to low-grade dyskaryosis stayed relatively constant throughout the age intervals from 20 to 54 years of age, Pearson correlation coefficient 0.91, p = 0.0014.

Conclusion:

The ratios of incidences of grades of dyskaryosis remained constant throughout the age intervals suggesting that selective patterns of referral to colposcopy based on patient’s age at diagnosis of mild dyskaryosis are not applicable.
Cervical cytology biobanking: quality of DNA from archival cervical Pap-stained smears
Authors: Boulet G A V , Horvath C A J , Berghmans S , Moeneclaey L M , Duys I S M , Arbyn M , Depuydt C E , Vereecken A J , Sahebali S , Bogers J J
Published: January 2008

Aims:

Cervical cytology biobanking is a feasible concept in cervical pathology and could be an indispensable tool for fundamental and applied molecular biological research. PCR is a powerful molecular technique that can be performed on a variety of cervical sample types including Pap-stained cervical smears. However, since the quality of DNA from such specimens is inferior to that from fresh tissue, the correct processing methods are required. This study evaluates three commercial isolation methods and one digestion procedure for their ability to obtain DNA suitable for PCR from fixed and stained Pap smears.

Methods:

The High Pure PCR Template Preparation kit, the NucliSENS easyMAG system, the QIAamp DNA Mini Kit and crude proteinase K digestion were used to obtain DNA for subsequent PCR applications. Amplification of β-globin was performed to verify the presence and integrity of target DNA. The influence of PCR inhibitors and extent of DNA fragmentation were analysed.

Results:

All commercial DNA isolation techniques provided DNA suitable for PCR amplification, and DNA isolated from 10-year-old archival smears yielded amplicons up to 400 base pairs. Conversely, crude proteinase K digestion limited the amplicon size to 300 bp and did not consistently yield amplifiable digests, as these were contaminated with PCR-inhibiting factors and debris.

Conclusion:

The study indicates that commercial DNA isolation techniques are suitable for PCR amplification of DNA isolated from archival smears, yielding amplicons up to 400 base pairs. Proteinase K digestion is not suitable to obtain amplifiable DNA from fixed and stained Pap-stained smears.
Transition from CK-MB to troponin did not improve the 1 year mortality of non-ST elevation acute coronary syndromes
Authors: Novack V , Jotkowitz A B , Cutlip D , Amit G , Liebermann N , Porath A
Published: January 2008

Objective

To examine the hypothesis that transition from creatine kinase MB subunits (CK-MB) to troponin as a more sensitive biomarker of myocardial necrosis reduced the 1 year mortality of non-ST elevation acute coronary syndrome (ACS) patients.

Design

Retrospective population based cohort study performed in seven tertiary care hospitals in Israel. The patient population comprised all non-ST elevation ACS admissions during a 5 year period (1999–2004). CK-MB was the biomarker for the diagnosis of myocardial infarction (MI) at the time of admission in 14 037 patients (group 1), while 11 643 patients were admitted after the individual hospital laboratory switched to troponin (group 2). Incidence of ACS types, in-hospital management and 1 year survival was assessed.

Results

Group 2 patients had a higher frequency of non-ST elevation MI diagnosis (27.9% vs 17.7%, p<0.001) and were more likely to undergo coronary catheterisation during hospitalisation (44.5% vs 37.5%, p<0.001). One year mortality in non-ST elevation MI was lower in group 2 compared to group 1 (24.6% vs 28.1%, p = 0.002). Similarly, the 1 year death rate in the unstable angina group decreased in group 2 compared to group 1 (7.7% vs 8.5%, p = 0.04). However, the overall non-ST elevation ACS 1 year mortality rate did not change (12.4% vs 11.9%, p = 0.27). In multivariate Cox proportional hazard analysis the transition from CK-MB to troponin had no significant effect on overall 1 year mortality (hazard ratio 0.95, 95% confidence interval 0.89 to 1.03).

Conclusions

Transition to troponin as a diagnostic marker of MI led to an increase in the incidence of non-ST elevation MI. This transition was not associated with a decrease in the 1 year non-ST elevation ACS mortality rate.
Neurogenic orthostatic hypotension: chasing “the fall”
Authors: Gupta D , Nair M D
Published: January 2008

Orthostatic hypotension (OH) is a frequently encountered problem affecting nearly 30% of the population aged more than 60 years. It can result from neurological and non-neurological derangements which compromise the perfusion of the brain in an erect posture. Neurogenic OH is a manifestation of autonomic failure. It is an important cause of recurrent falls in the elderly, syncopal events and also has been shown to be associated with increased long term mortality from vascular and non-vascular causes. This review will discuss the pathophysiology, aetiology, clinical features and management of neurogenic OH and its differentiation from OH caused by non-neurological causes at each step. A clinician should primarily look for any reversible causes in a patient with neurogenic OH and should not forget that treatment is aimed at restoring the functioning capability of the patient rather than normotension. Co-existent supine hypertension in some patients should be taken into account while treating them.
Estimation of mating system parameters in two Italian natural populations of Fagussylvatica
Authors: Rossi Patrizia , Vendramin Giovanni Giuseppe , Giannini Raffaello
Published: January 2008

Mating system parameters were estimated in two Italian natural populations of European beech (Fagussylvatica L.) using a mixed mating model and considering seven allozyme loci (Idh-A, Lap-A, Mdh-B, Pgd-A, Pgd-B, Pgd-C, Skd-A). High values of multilocus estimates of the outcrossing rate were found in both populations, ranging from 94 to 98%. Comparison of single- and multi-locus estimates of outcrossing rates seems to indicate the presence of consanguineous matings, probably because the populations are substructured. This hypothesis seems to be confirmed by the presence of a heterogeneity of the pollen allele frequencies across female parent trees and by the significant coefficient of the regression of pollen allele frequencies on ovule genotype. Variation in the fixation indices in different life-cycle phases was observed, indicating possible presence of selective processes between seed set and sexual maturity. Possible explanations of these results are presented.
Biodegradation of thujaplicins in living western red cedar
Authors: Jin Lehong , Kamp Bart J. Van Der , Wilson Jack , Swan Eric P.
Published: January 2008

The role of three common fungal isolates from the heartwood of mature coastal western red cedar (Thujaplicata Donn) in the detoxification of thujaplicins was investigated. A Sporothrix species, Kirschsteiniellathujina (Peck) Pomerleau & Etheridge, and a Phialophora species are shown to form a succession of fungi, in that order, which invade red cedar heartwood from within and cause discolouration of the heartwood from light straw to red and various shades of brown. Thujin, a recently described lactone compound in red cedar heartwood extractives, is shown to be present in discoloured wood only. It is formed by the oxidative dimerization and isomerization of thujaplicins by the Sporothrix isolate. The other two fungi may play a minor role in thujaplicin degradation. Thujin is shown to lack toxicity to Poriarivulosa (B. & C.) Cooke, the common decay fungus of coastal western red cedar.
ERRATA: "NONCOMMUTATIVE KdV HIERARCHY"
Authors: TREVES FRANÇOIS
Published: January 2008

The proof of Lemma 2.20 in the article "Noncommutative KdV Hierarchy" is corrected.
Finite Unified Theories and the prediction of the Higgs mass
Authors: MONDRAGON MYRIAM , ZOUPANOS GEORGE
Published: January 2008

Finite Unified Theories (FUTs) are N =1 supersymmetric Grand Unified Theories, which can be made all-loop finite, both in the gauge and Yukawa couplings and in the soft supersymmetry breaking sector. This remarkable property, based on the reduction of couplings at the quantum level, provides a drastic reduction in the number of free parameters, which in turn leads to predictions for the top and bottom quark masses, as well as predictions for the Higgs boson mass and the supersymmetric spectrum. Here we examine the predictions of two SU(5) FUTs, taking into account a number of theoretical and experimental constraints. We show how the phenomenological constraints can discriminate among the two models, and we give also the above mentioned predictions for the model that complies with all the constraints.
LHC DATA CLASSIFICATION USING A NEW MORPHOLOGICAL BOUNDARY DETECTION
Authors: MJAHED MOSTAFA
Published: January 2008

A new morphological boundary detection approach is used to separate the signal from the background in the Standard Model Higgs boson search at LHC. Based on mathematical concepts, this method consists of a fast computation of probabilistic density functions of events and a smoothing using a combination of dilatation and erosion operators. In a binary search approach, the performances are improved and the results compare favourably with other multivariate analysis.
DETERMINING THE VALUE OF INTANGIBLE ASSETS — A STUDY AND AN EMPIRICAL APPLICATION
Authors: CHIESA VITTORIO , GILARDONI ELENA , MANZINI RAFFAELLA , PIZZURNO EMANUELE
Published: January 2008

It is widely recognized nowadays that intangible assets represent the crucial base for business development and companies are often required to value them. The paper aims to analyze the critical problems emerging from the empirical application of available valuation approaches through a case study on a medical device patent pending.
Enhanced β-cell mass without increased proliferation following chronic mild glucose infusion
Authors: Jetton Thomas L. , Everill Brian , Lausier James , Roskens Violet , Habibovic Aida , LaRock Kyla , Gokin Alexander , Peshavaria Mina , Leahy Jack L.
Published: January 2008

The physiological mechanisms underlying pancreatic β-cell mass (BCM) homeostasis are complex and not fully resolved. Here we examined the factors contributing to the increased BCM following a mild glucose infusion (GI) whereby normoglycemia was maintained through 96 h. We used morphometric and immunochemical methods to investigate enhanced β-cell growth and survival in Sprague-Dawley rats. BCM was elevated >2.5-fold over saline-infused control rats by 48 h and increased modestly thereafter. Unexpectedly, increases in β-cell proliferation were not observed at any time point through 4 days. Instead, enhanced numbers of insulin+ cell clusters and small islets (400–12,000 μm2; ∼23- to 124-μm diameter), mostly scattered among the acini, were observed in the GI rats by 48 h despite no difference in the numbers of medium to large islets. We previously showed that increased β-cell growth in rodent models of insulin resistance and pancreatic regeneration involves increased activated Akt/PKB, a key β-cell signaling intermediate, in both islets and endocrine cell clusters. GI in normal rats also leads to increased Akt activation in islet β-cells, as well as in insulin+ and insulin− cells in the common duct epithelium and endocrine clusters. This correlated with strong Pdx1 expression in these same cells. These results suggest that mechanisms other than proliferation underlie the rapid β-cell growth response following a mild GI in the normal rat and involve Akt-regulated enhanced β-cell survival potential and neogenesis from epithelial precursors.