bluuebunny/crossref_metadata_2025_split huggingface dataset:
New Rat Model ofPneumocystisPneumonia Induced by Anti-CD4+T-Lymphocyte Antibodies
Authors: Thullen Timothy D. , Ashbaugh Alan D. , Daly Kieran R. , Linke Michael J. , Steele Paul E. , Walzer Peter D. 
Published: October 2003

ABSTRACTThe CD4+T lymphocyte plays a central role in host defense againstPneumocystispneumonia but has received only limited attention in rats. CD4+T-cell-depleting (OX-38) and nondepleting (W3/25) monoclonal antibodies, which recognize an identical or adjacent epitope, were administered for up to 14 weeks to Lewis rats that had been exposed toPneumocystis. While OX-38 produced a greater decrease in circulating CD4+cells than W3/25, both antibody treatments resulted in similar effects on the health of the rats and the levels ofPneumocystispneumonia, which were milder than those found with corticosteroids. W3/25 also did not enhance the severity ofPneumocystispneumonia achieved with corticosteroids alone. We conclude that CD4+cell function is more important than CD4+cell number in host defense againstPneumocystisin the rat and that this new model permits study of opportunistic infections in the rat without the confounding effects of corticosteroids.
Role of Cytokines and Major Histocompatibility Complex Restriction in Mouse Resistance to Infection with a Natural Recombinant Strain (Type I-III) ofToxoplasma gondii
Authors: Fux Blima , Rodrigues Cibele V. , Portela Ricardo W. , Silva Neide M. , Su Chunlei , Sibley David , Vitor Ricardo W. A. , Gazzinelli Ricardo T. 
Published: October 2003

ABSTRACTHerein we characterized various genetic markers and the biological behavior of a natural recombinant strain ofToxoplasma gondii(P-Br). From nine genetic markers analyzed, three (B1,ROP1, andSAG1) and three (cS10-A6,GRA6, andSAG3) markers belong to parasites from the type I and type III lineages, respectively. TheSAG2andL363loci were shown to be type I-III chimera alleles. The cB2l-4 microsatellite marker showed a unique haplotype. The P-Br strain presented low virulence in the acute phase of infection and was cystogenic during the chronic infection. The interleukin 12/gamma interferon axis and inducible nitric oxide synthase were main determinants of resistance during the acute infection with the P-Br strain. As opposed to infection with the type II strain ofT. gondii(ME-49), peroral infection with the P-Br strain led only to a light inflammatory infiltrate and no major lesions in the intestine of the C57BL/6 mice. In addition, the BALB/c (resistant to ME-49) and C57BL/6 (susceptible to ME-49) mice were shown, respectively, to be more susceptible and more resistant to cyst formation and toxoplasmic encephalitis when infected with the P-Br strain. Further, the C57BL/KsJ and DBA2/J congenic strains containing major histocompatibility complex (MHC) haplotype “d” were more resistant than the parental strains (C57BL/6 and DBA1/J), when infected with the ME-49 but not with the P-Br strain. Together, our results indicate that resistance to cyst formation and toxoplasmic encephalitis induced during infection with P-Br is not primarily controlled by the MHC haplotype d, as previously reported for type II strains ofT. gondii.
Modulation of the Bovine Delayed-Type Hypersensitivity Responses to Defined Mycobacterial Antigens by a Synthetic Bacterial Lipopeptide
Authors: Whelan A. O. , Hope J. C. , Howard C. J. , Clifford D. , Hewinson R. G. , Vordermeier H. M. 
Published: October 2003

ABSTRACT

The use of defined protein and peptide antigens can overcome specificity limitations of purified protein derivatives in the detection of bovine tuberculosis when the antigens are used in blood-based tests. Since the use of these specific antigens as skin test reagents could have practical advantages, we investigated the potential of
Mycobacterium bovis
-specific antigens to stimulate delayed-type hypersensitivity (DTH) responses in cattle experimentally infected with
M. bovis
. A cocktail of the recombinant antigens ESAT-6, MPB83, and MPB64 failed to stimulate in vivo DTH in cattle that had been experimentally infected with
M. bovis
despite the fact that the antigens were recognized in vitro by the same animals. However, it was possible to stimulate antigen-specific bovine DTH responses by using ESAT-6 in combination with a synthetic bacterial lipopeptide. This lipopeptide stimulated the release of the proinflammatory cytokine tumor necrosis factor alpha from monocyte-derived bovine dendritic cells in vitro, thereby providing a possible mechanism for its DTH-enhancing properties.
Lung Epithelial Cells and Extracellular Matrix Components Induce Expression of
Pneumocystis carinii STE20
, a Gene Complementing the Mating and Pseudohyphal Growth Defects of
ste20
Mutant Yeast
Authors: Kottom Theodore J. , Köhler Julia R. , Thomas Charles F. , Fink Gerald R. , Limper Andrew H. 
Published: October 2003

ABSTRACT

Pneumocystis carinii
causes severe pneumonia in immunocompromised hosts. The binding of
P. carinii
to alveolar epithelial cells and extracellular matrix constituents such as fibronectin and vitronectin is a central feature of infection, which initiates proliferation of the organism. Herein, we demonstrate that
P. carinii
binding to lung cells specifically alters the gene expression of the organism, regulating fungal growth. Subtractive hybridization was performed to isolate
P. carinii
genes expressed following binding to mammalian extracellular matrix constituents.
P. carinii STE20
(
PCSTE20
), a gene participating in mating and pseudohyphal growth of other fungi, was identified following adherence to the extracellular matrix constituents fibronectin, vitronectin, collagen, and lung epithelial cells. The expression of
PCSTE20
and a related
P. carinii
mitogen-activated protein kinase (MAPK) kinase gene, also implicated in signaling of mating, were both specifically upregulated by binding to matrix protein. The expression of general cyclin-dependent kinases and other MAPKs not involved in mating pathways were not altered by organism binding.
PCSTE20
expression was also strongly enhanced following organism attachment to A549 lung epithelial cells. When expressed in a
Saccharomyces cerevisiae ste20Δ
mutant,
PCSTE20
suppressed defects in both mating and pseudohyphal growth. These findings are consistent with the observed proliferation and filopodial extension of
Pneumocystis
organisms adherent to the epithelium in the lungs of immunocompromised hosts.
PCSTE20
expression appears to represent a significant component in the regulation of the life cycle of this intractable opportunistic pathogen.
Comparative Pathogenicity ofEscherichia coliO157 and Intimin-Negative Non-O157 Shiga Toxin-ProducingE. coliStrains in Neonatal Pigs
Authors: Dean-Nystrom Evelyn A. , Melton-Celsa Angela R. , Pohlenz Joachim F. L. , Moon Harley W. , O'Brien Alison D. 
Published: October 2003

ABSTRACTWe compared the pathogenicity of intimin-negative non-O157:H7 Shiga toxin (Stx)-producingEscherichia coli(STEC) O91:H21 and O104:H21 strains with the pathogenicity of intimin-positive O157:H7 and O157:H−strains in neonatal pigs. We also examined the role of Stx2d-activatable genes and the large hemolysin-encoding plasmid of O91:H21 strain B2F1 in the pathogenesis of STEC disease in pigs. We found that allE. colistrains that made wild-type levels of Stx caused systemic illness and histological lesions in the brain and intestinal crypts, whereas none of the control Stx-negativeE. colistrains evoked comparable central nervous system signs or intestinal lesions. By contrast, the absence of intimin, hemolysin, or motility had little impact on the overall pathogenesis of systemic disease during STEC infection. The most striking differences between pigs inoculated with non-O157 STEC strains and pigs inoculated with O157 STEC strains were the absence of attaching and effacing intestinal lesions in pigs inoculated with non-O157:H7 strains and the apparent association between the level of Stx2d-activatable toxin produced by an STEC strain and the severity of lesions.
Inhibition of Platelet Adherence to Brain Microvasculature Protects against SeverePlasmodium bergheiMalaria
Authors: Sun Guang , Chang Wun-Ling , Li Jie , Berney Seth Mark , Kimpel Donald , van der Heyde Henri C. 
Published: October 2003

ABSTRACTSome patients withPlasmodium falciparuminfections develop cerebral malaria, acute respiratory distress, and shock and ultimately die even though drug therapy has eliminated the parasite from the blood, suggesting that a systemic inflammatory response contributes to malarial pathogenesis.Plasmodium berghei-infected mice are a well-recognized model of severe malaria (experimental severe malaria [ESM]), and infected mice exhibit a systemic inflammatory response. Because platelets are proposed to contribute to ESM and other systemic inflammatory responses, we determined whether platelet adherence contributes to experimental malarial pathogenesis. Indeed, a significant (P< 0.005) increase in the number of rolling and adherent platelets was observed by intravital microscopy in brain venules ofP. berghei-infected mice compared with the number in uninfected controls. P-selectin- or ICAM-1-deficient mice exhibit increased survival afterP. bergheiinfection. We observed a significant (P< 0.0001) reduction in the morbidity of mice injected with anti-CD41 (αIIbor gpIIb) monoclonal antibody on day 1 ofP. bergheiinfection compared with the morbidity of infected controls injected with rat immunoglobulin G. Additionally, platelet rolling and adhesion in brain venules were reduced inP. bergheimice lacking either P-selectin or ICAM-1 or when the platelets were coated with anti-CD41 monoclonal antibody. Unlike other inflammatory conditions, we did not detect platelet-leukocyte interactions duringP. bergheimalaria. Because (i) leukocyte adhesion is not markedly altered in the absence of P-selectin or ICAM-1 and (ii) CD41 is not an adhesion molecule for parasitized erythrocytes, these findings support the hypothesis that inhibition of platelet adhesion to the brain microvasculature protects against development of malarial pathogenesis.
Antibodies That Inhibit
Plasmodium falciparum
Adhesion to Chondroitin Sulfate A Are Associated with Increased Birth Weight and the Gestational Age of Newborns
Authors: Duffy Patrick E. , Fried Michal 
Published: October 2003

ABSTRACT

Antibodies that inhibit
Plasmodium falciparum
adhesion to the placental receptor chondroitin sulfate A are associated with a reduced risk of placental malaria, but whether these antibodies lead to improved pregnancy outcomes is unknown. We measured antiadhesion antibody levels in parturient women in western Kenya, where malaria transmission is intense. Secundigravid women with antiadhesion activity in their plasma delivered babies that were on average 398 g heavier (
P
= 0.019) and 2 weeks more mature (
P
= 0.002) than babies delivered to secundigravidas without antiadhesion activity. Our findings support the development of antiadhesion vaccines to prevent poor fetal outcomes due to pregnancy malaria.
Novel Role for Albumin in Innate Immunity: Serum Albumin Inhibits the Growth ofBlastomyces dermatitidisYeast Form In Vitro
Authors: Giles Steven , Czuprynski Charles 
Published: October 2003

ABSTRACTIn this study we found that serum inhibitory activity againstBlastomyces dermatitidiswas principally mediated by albumin. This was confirmed in experiments using albumin from several mammalian species. Analbuminemic rat serum did not inhibitB.dermatitidisgrowth in vivo; however, the addition of albumin restored inhibitory activity. Inhibitory activity does not require albumin domain III and appears to involve binding of a low-molecular-weight yeast-derived growth factor.
Secretion of theorgCGene Product bySalmonella entericaSerovar Typhimurium
Authors: Day James B. , Lee Catherine A. 
Published: October 2003

ABSTRACTHilA activates the transcription of genes onSalmonellapathogenicity island 1 (SPI1), which encodes a type III secretion system (TTSS). Previous studies showed that transposon insertions inorgC, a gene located on SPI1, increasehilAexpression. We characterize theorgCgene product and show that it is secreted via the SPI1 TTSS. We propose a model whereby OrgC functions as a secreted repressor of the SPI1 virulence genes.
Direct Restorative Material Use of Selected Practitioners in the United Kingdom
Authors: Brunton Paul A , Hickel Reinhard , Wilson Nairn HF 
Published: October 2003

Purpose of the Investigation To investigate, by questionnaire, the direct restorative materials used by a sample of practitioners from the Unite d Kingdom. Basic Procedures A postal questionnaire was distributed to a group of self-selected practitioners, who volunteered to participate in the study. In all 110 practitioners participated in the study. Main Findings The most used material for the restoration of occlusal (Class I) and approximal (Class II) lesions was amalgam with 61% and 73% of practitioners indicating that they used amalgam in this situation. Adhesive tooth-coloured materials, specifically composites and compomers, were preferred by the majority of practitioners for anterior approximal (Class III) and incisal (Class IV) restorations with compomer preferred for Class V restorations including non-carious cervical lesions and for the restoration of primary teeth. Principal Conclusions It is concluded that the general practitioners surveyed in this study tend to use amalgam for the restoration of Class I and II lesions as opposed to resin composite. The majority of practitioners in this study used compomers, a relatively new group of restorative materials, with little evidence of traditional glass-ionomer cements being used routinely.
Stress in Dental Specialists: A Comparison of Six Clinical Dental Specialties
Authors: Newton Jonathon T , Mistry Kamini , Patel Akit , Patel Priya , Perkins Matthew , Saeed Kashif , Smith Christoper 
Published: October 2003

Objective To describe and compare the levels of stress reported by dental practitioners working within clinical dental specialties. Method Questionnaire survey of 220 dental practitioners identified from the General Dental Council lists of specialist practitioners in the following clinical specialties: orthodontics, paediatric dentistry, restorative dentistry, endo-dontics, periodontology, prosthetic dentistry. Findings The clinical specialties did not differ in their reported levels of stress. Practitioners working in the field of paediatric dentistry reported the highest median levels of reported stress for three of the four scales, though this trend was not significant. Conclusions The practitioners surveyed from six clinical specialties did not experience significantly different sources of stress.
Ischemia triggered by spreading neuronal activation is induced by endothelin‐1 and hemoglobin in the subarachnoid space
Authors: Petzold Gabor C. , Einhäupl Karl M. , Dirnagl Ulrich , Dreier Jens P. 
Published: October 2003

AbstractDelayed cerebral vasospasm has a major impact on the outcome of subarachnoid hemorrhage. Two important candidates to cause the arterial spasm are the red blood cell product oxyhemoglobin and the vasoconstrictor endothelin‐1, although oxyhemoglobin alone is not sufficient to induce cerebral ischemia and endothelin‐1 leads to ischemia only at relatively high concentrations. In this study, we demonstrated that the combination of oxyhemoglobin and endothelin‐1 triggered spreading neuronal activation in rat cortex in vivo. In contrast with the expected transient increase of regional cerebral blood flow during spreading depression, however, cerebral blood flow decreased profoundly and was long‐lasting, paralleled by delayed repolarization of the steady (direct current) potential. These changes are characteristic of cortical spreading ischemia. Replacing oxyhemoglobin for the nitric oxide synthase inhibitor Nω‐nitro‐L‐arginine mimicked these effects, implicating nitric oxide scavenging functions of oxyhemoglobin. Furthermore, the effect of endothelin‐1 was related to a reduction of Na+‐/K+‐ATPase activity rather than solely to its vasoconstrictive properties. In conclusion, the threshold concentration of endothelin‐1 that induces cerebral ischemia is profoundly reduced via a complex interaction between the neuronal/astroglial network and the cortical microcirculation if nitric oxide availability declines. The results may have implications for the understanding of subarachnoid hemorrhage–related cortical lesions.
Growth hormone prevents human immunodeficiency virus–induced neuronal p53 expression
Authors: Silva Claudia , Zhang Kunyan , Tsutsui Shigeki , Holden Janet K. , Gill M. John , Power Christopher 
Published: October 2003

AbstractGrowth hormone (GH) is neuroprotective, presumably through its actions on GH receptor–mediated pathways. Here, we examined the effects of GH using in vitro and in vivo assays of human immunodeficiency virus (HIV)–induced neuronal injury. Neuronal cultures were in assays of neurotoxicity induced by supernatants from HIV‐1 tat‐transfected monocytoid cells (Tat supernatant). GH treatment reduced neuronal death compared with untreated cultures (p < 0.001), which was blocked by a GH receptor antagonist, B2036. Tat supernatant–induced p53 expression in neurons was also reduced by GH treatment. Expression of both p53 and GH receptor were increased in brain tissue from HIV‐infected persons compared with controls (p < 0.05). Mice receiving intrastriatal implants of Tat supernatant and treated with GH showed less neurobehavioral abnormalities together with reduced neuroinflammation and neuronal injury compared with untreated animals (p < 0.01). Three acquired immunodeficiency syndrome–defined patients with neurocognitive impairment were serially evaluated during daily GH treatment showing a sustained improvement in neuropsychological performance (p < 0.01). GH prevents neuronal death through its actions on neurons involving a p53‐mediated pathway and also improved in vivo neurological function, indicating that GH may have a role in the treatment of HIV‐induced neurodegeneration. Ann Neurol 2003;54:605–614
An English kindred with a novel recessive tauopathy and respiratory failure
Authors: Nicholl David J. , Greenstone Michael A. , Clarke Carl E. , Rizzu Patrizia , Crooks Daniel , Crowe Alex , Trojanowski John Q. , Lee Virginia M.‐Y. , Heutink Peter 
Published: October 2003

AbstractWe present the clinicopathological features of two siblings from a consanguineous marriage who presented with respiratory hypoventilation and died 10 days and 4 years later, respectively. This disorder showed extensive tau neuropathology, and both had a novel homozygous S352L tau gene mutation. This is the first description of a pathologically proved young‐onset tauopathy with apparent recessive inheritance. Ann Neurol 2003;54:682–686
Experimental studies on reproductive toxicologic effects of lamotrigine in mice
Authors: Padmanabhan R. , Abdulrazzaq Y.M. , Bastaki S.M.A. , Shafiullah M. , Chandranath S.I. 
Published: October 2003

AbstractBACKGROUND: Virtually all antiepileptic drugs (AED) tested so far have been found to be teratogenic. The second generation AED possess a number of therapeutic advantages over the older ones. There are, however, very little data on their effects on embryonic development. A recent report suggests that lamotrigine (LTG) can be teratogenic to human fetuses. With only a few cases of prenatal exposure to LTG in the record, however, it has not been possible to establish a recognizable pattern of malformations in the infants of LTG‐treated mothers.OBJECTIVES: The objectives of the present study were to evaluate the reproductive toxic effects of LTG RESULTS: Single (50–200 mg/kg) or multiple doses (25, 50, 75 mg/kg) of LTG were administered by intraperitoneal (i.p.) injection (note that the therapeutic administration is oral) to groups of TO mice on gestation day (GD) 7 or 8. Fetuses were collected on GD 18. Maternal toxic effects including a dose‐related mortality, a high incidence of abortion, embryo lethality, congenital malformations and intrauterine growth retardation (IUGR) were observed in the LTG‐treated group. Administration of LTG in multiple low doses resulted in a better maternal survival and increased incidence of embryonic resorption and malformations with increasing dose; IUGR was significant but not dose‐dependent. The malformations characteristic of the LTG multiple low dose group fetuses included maxillary‐mandibular hypoplasia, exencephaly, cleft palate, median facial cleft, urogenital anomalies and varying degrees of caudal regression. Skeletal malformations and developmental delay of the skeleton were observed both in single and multiple dose groups.CONCLUSIONS: The results of this study indicate that LTG administered i.p. at high doses can induce intrauterine growth retardation and at low multiple doses causes a dose‐dependent increase in embryonic resorption, craniofacial and caudal malformations as well as maternal toxicity in the mouse. Previous studies in other laboratories have used oral route of exposure and concluded that there are no teratogenic effects of LTG at dose levels that are not maternally toxic. Birth Defects Res B 68:428–438, 2003. © 2003 Wiley‐Liss, Inc.
The molecular biology of Euglena gracilis. XV. Recovery from centrifugation‐induced stratification
Authors: Kempner E. S. , Miller J. H. 
Published: October 2003

AbstractThe contents of Euglena gracilis cells can be separated in vivo by ultracentrifugation. Within the unbroken cell, each set of components forms a distinct layer according to their respective densities. The degree of segregation increases with both the g‐force and the time of centrifugation, up to a maximum at 100,000 × g for 1 h, when six distinct strata can be observed. When returned to normal growth conditions, essentially all the cells return to the normal state and growth pattern. Greater g‐forces or longer exposures do not alter the observable strata, but the ability of the cells to recover is diminished. Smaller g‐forces result in less separation of cellular contents and all cells recover, even after 18 h of exposure. Euglena cells stratified at 100,000 × g for 1 h were returned to normal growth conditions; recovery was followed microscopically and by the rate of utilization of oxygen as well as that of the single carbon source. The cells recovered their normal state within 1 to 2 h, which is only a tenth of the normal doubling time. The mechanism for this recovery involves a natural process of change in cell shape caused by contraction and relaxation of the pellicle, a cell surface structure. Cell Motil. Cytoskeleton 56:219–224, 2003. Published 2003 Wiley‐Liss, Inc.