bluuebunny/crossref_metadata_2025 huggingface dataset:
A Randomized Controlled Trial of Enteral Glutamine Supplementation in Very Low Birth Weight Infants: Plasma Amino Acid Concentrations
Authors: van den Berg Anemone , van Elburg Ruurd M , Teerlink T , Lafeber Harrie N , Twisk Jos W. R , Fetter Willem P. F
Published: July 2005

Objective:

Glutamine depletion has negative effects on the functional integrity of the gut and leads to immunosuppression. Very low birth weight (VLBW) infants are susceptible to glutamine depletion, as enteral nutrition is limited in the first weeks of life. Enteral glutamine supplementation may have a positive effect on feeding tolerance, infectious morbidity and short‐term outcome. The aim of the study was to determine the effect of enteral glutamine supplementation on plasma amino acid concentrations, reflecting one aspect of safety of enteral glutamine supplementation in VLBW infants.

Methods:

In a double‐blind placebo‐controlled randomized controlled trial, VLBW infants (gestational age <32 weeks or birth weight <1500 g) received enteral glutamine supplementation (0.3 g/kg per day) or isonitrogenous placebo supplementation (alanine) between day 3 and day 30 of life. Supplementation was added to breast milk or to preterm formula. Plasma amino acid concentrations were measured at four time points: before the start of the study and at days 7, 14 and 30 of life.

Results:

Baseline patient and nutritional characteristics were not different in glutamine (n = 52) and control (n = 50) groups. Plasma concentrations of most essential and non‐essential amino acids increased throughout the study period. There was no effect of enteral glutamine supplementation. In particular, the increase of plasma glutamine and glutamate concentrations was not different between the treatment groups (P = 0.49 and P = 0.34 respectively, day 30).

Conclusions:

Enteral glutamine supplementation in VLBW infants does not alter plasma concentrations of glutamine, glutamate or other amino acids. Enteral supplementation in a dose of 0.3 g/kg per day seems safe in VLBW infants.
Monte Carlo calibration of avalanches described as Coulomb fluid flows
Authors: Ancey Christophe
Published: July 2005

The idea that snow avalanches might behave as granular flows, and thus be described as Coulomb fluid flows, came up very early in the scientific study of avalanches, but it is not until recently that field evidence has been provided that demonstrates the reliability of this idea. This paper aims to specify the bulk frictional behaviour of snow avalanches by seeking a universal friction law. Since the bulk friction coefficient cannot be measured directly in the field, the friction coefficient must be calibrated by adjusting the model outputs to closely match the recorded data. Field data are readily available but are of poor quality and accuracy. We used Bayesian inference techniques to specify the model uncertainty relative to data uncertainty and to robustly and efficiently solve the inverse problem. A sample of 173 events taken from seven paths in the French Alps was used. The first analysis showed that the friction coefficient behaved as a random variable with a smooth and bell-shaped empirical distribution function. Evidence was provided that the friction coefficient varied with the avalanche volume, but any attempt to adjust a one-to-one relationship relating friction to volume produced residual errors that could be as large as three times the maximum uncertainty of field data. A tentative universal friction law is proposed: the friction coefficient is a random variable, the distribution of which can be approximated by a normal distribution with a volume-dependent mean.
The Savage–Hutter avalanche model: how far can it be pushed?
Authors: Hutter Kolumban , Wang Yongqi , Pudasaini Shiva P
Published: July 2005

The Savage–Hutter (SH) avalanche model is a depth-averaged dynamical model of a fluid-like continuum implementing the following simplifying assumptions: (i) density preserving, (ii) shallowness of the avalanche piles and small topographic curvatures, (iii) Coulomb-type sliding with bed friction angle
δ
and (iv) Mohr–Coulomb behaviour in the interior with internal angle of friction
ϕ
≥
δ
and an
ad hoc
assumption reducing the number of Mohr's circles in three-dimensional stress states to one. We scrutinize the available literature on information regarding these assumptions and thus delineate the ranges of validity of the proposed model equations. The discussion is limited to relatively large snow avalanches with negligible powder snow component and laboratory sand avalanches starting on steep slopes. The conclusion of the analysis is that the SH model is a valid model for sand avalanches, but its Mohr–Coulomb sliding law may have to be complemented for snow avalanches by a second velocity-dependent contribution. For very small snow avalanches and for laboratory avalanches starting on moderately steep and bumpy slopes it may not be adequate.
Rapid motions of free-surface avalanches down curved and twisted channels and their numerical simulation
Authors: Pudasaini Shiva P , Wang Yongqi , Hutter Kolumban
Published: July 2005

This paper presents a new model and discussions about the motion of avalanches from initiation to run-out over moderately curved and twisted channels of complicated topography and its numerical simulations. The model is a generalization of a well established and widely used depth-averaged avalanche model of Savage & Hutter and is published with all its details in Pudasaini & Hutter (Pudasaini & Hutter 2003
J. Fluid Mech.
495
, 193–208). The intention was to be able to describe the flow of a finite mass of snow, gravel, debris or mud, down a curved and twisted corrie of nearly arbitrary cross-sectional profile. The governing equations for the distribution of the avalanche thickness and the topography-parallel depth-averaged velocity components are a set of hyperbolic partial differential equations. They are solved for different topographic configurations, from simple to complex, by applying a high-resolution non-oscillatory central differencing scheme with total variation diminishing limiter. Here we apply the model to a channel with circular cross-section and helical talweg that merges into a horizontal channel which may or may not become flat in cross-section. We show that run-out position and geometry depend strongly on the curvature and twist of the talweg and cross-sectional geometry of the channel, and how the topography is shaped close to run-out zones.
Rotational flow in gravity current heads
Authors: McElwaine J.N
Published: July 2005

The structure of gravity currents and plumes, in an unbounded ambient, on a slope of arbitrary angle is analysed. Inviscid, rotational flow solutions in a wedge are used to study the flow near the front of a current, and used to show that the Froude number is

and the angle of the front to the slope is 60°. This extends the result of
von Kármán (1940)
to arbitrary slope angles and large internal current velocities. The predictions of the theory are briefly compared with experiments and used to explain the large negative (relative to ambient) pressures involved in avalanches.
Granular flow in the marginal ice zone
Authors: Feltham Daniel L
Published: July 2005

The region of sea ice near the edge of the sea ice pack is known as the marginal ice zone (MIZ), and its dynamics are complicated by ocean wave interaction with the ice cover, strong gradients in the atmosphere and ocean and variations in sea ice rheology. This paper focuses on the role of sea ice rheology in determining the dynamics of the MIZ. Here, sea ice is treated as a granular material with a composite rheology describing collisional ice floe interaction and plastic interaction. The collisional component of sea ice rheology depends upon the granular temperature, a measure of the kinetic energy of flow fluctuations. A simplified model of the MIZ is introduced consisting of the along and across momentum balance of the sea ice and the balance equation of fluctuation kinetic energy. The steady solution of these equations is found to leading order using elementary methods. This reveals a concentrated region of rapid ice flow parallel to the ice edge, which is in accordance with field observations, and previously called the
ice jet
. Previous explanations of the ice jet relied upon the existence of ocean currents beneath the ice cover. We show that an ice jet results as a natural consequence of the granular nature of sea ice.
Differential evolution algorithm for supply chain inventory planning
Authors: Routroy Srikanta , Kodali Rambabu
Published: July 2005

Purpose

This paper discusses the inventory planning of a supply chain, which consists of a manufacturer, distributor and retailer.

Design/methodology/approach

The differential evolution algorithm is developed to minimize the total system‐wide cost, which consists of supply chain inventory capital, supply chain ordering/set‐up cost and supply chain stock‐out cost.

Findings

The differential evolution algorithm helps in determining ordering/production quantity and inventory/service level that should be maintained by each member of the supply chain.

Originality/value

The algorithm developed is useful in increasing the customer service level and in decreasing the inventory level throughout the supply chain.
Design and control of a flexible order‐picking system (FOPS)
Authors: Manzini Riccardo , Gamberi Mauro , Regattieri Alberto
Published: July 2005

Purpose

To present an innovative approach to the design of a flexible order‐picking systems (OPS). The proposed conceptual framework is the first step to the development of an expert system created in a rapid and innovative manner, i.e. based on the integration of simulation, genetic algorithms and factorial analysis.

Design/methodology/approach

The impact of alternative policies and configurations of both picker‐to‐part and part‐to‐picker OPS is quantified, with the aim of designing and optimising robust facilities capable of minimising global costs and maximising their performances in terms of efficiency and customer service quality.

Findings

The importance of validation analysis and both virtual and on‐field data collection emerges.

Originality/value

Compared with the studies found in the literature, this article presents an innovative approach with original results that will be of use in the design and control of a flexible OPS.
Effect of fasting on resting metabolic rate and postprandial metabolic response in Silurus meridionalis
Authors: Fu S. J. , Xie X. J. , Cao Z. D.
Published: July 2005

Resting metabolic rate in southern catfish of 2 and 5 day fasting groups were significantly higher than that of the 15 day fasting group (P < 0·05). After feeding, peak metabolic rate of specific dynamic action (SDA) of the 15 day fasting group was significantly lower than that of the 2 and 5 day fasting groups (P < 0·05). The duration of the SDA of the 15 day fasting group was significantly longer than that of the 2 day fasting group (P < 0·05) and the SDA coefficient of the 15 day fasting group was significantly lower than that of the 2 day fasting group (P < 0·05).
Four rows of pharyngeal teeth in an aberrant specimen of the small African barb Barbus paludinosus(Cyprinidae): novelty or atavistic alteration?
Authors: Golubtsov A. S. , Dzerjinskii K. F. , Prokofiev A. M.
Published: July 2005

An extra fourth row of pharyngeal teeth was found on both pharyngeal arches in a specmen of the small African barb, Barbus paludinosus, a species normally exhibiting three rows of pharyngeal teeth. Possible phylogenetic significance of this alteration is discussed in connection with occurrence of extra fourth rows of pharyngeal teeth in other cyprinid lineages.
Air‐breathing behaviour of the African anabantoid fish Ctenopoma muriei
Authors: Randle A. M. , Chapman L. J.
Published: July 2005

Frequency of aerial respiration in Ctenopoma muriei increased as dissolved oxygen (DO) decreased; breathing behaviour was spatially synchronous, and there was no difference in air‐breathing frequency between populations from a high‐ and low‐DO site. Although C. muriei survived without access to the surface, its loss of buoyancy and equilibrium under these conditions suggested that it is a functionally obligatory air breather.
Fertilization mode, sperm characteristics, mate choice and parental care patterns in Artedius spp. (Cottidae)
Authors: Petersen C. W. , Mazzoldi C. , Zarrella K. A. , Hale R. E.
Published: July 2005

The reproductive biology of three species in the genus Artedius(A. harringtoni, A. lateralis and A. fenestralis) was studied, including parental behaviour, mate choice, fertilization mode, gamete morphology and behaviour, and gonad morphology to help understand the coevolution of reproductive characteristics with potentially different modes of fertilization. In all three species, males guard multiple clutches at oviposition sites. In laboratory mate‐choice experiments, males appearred to prefer to defend sites containing eggs and were better able to attract mates at these sites. There was evidence that internal gomete association, although more pronounced in A. harringtoni, existed in all three species. Sperm behaviour and morphology and histological analysis of gonads suggested that A. fenestralis and A. lateralis were more likely to engage in typical external fertilization. The adoption of eggs and their effect on female mate‐choice patterns appearred to reduce the importance of certainty of paternity in these species, and probably increased the evolutionary stability of male parental care.
Latitudinal variation in fecundity among Arctic charr populations in eastern North America
Authors: Power M. , Dempson J. B. , Reist J. D. , Schwarz C. J. , Power G.
Published: July 2005

Variation in fecundity was examined from 32 populations of Arctic charrSalvelinus alpinusin eastern North America covering a range of 37° latitude and extending from Maine, U.S.A., to northern Ellesmere Island in the Canadian Arctic. Populations were classed as dwarf, normal or anadromous and covered a suite of different habitat and climatic regimes. Fecundity varied with fork length (LF), withLFadjusted fecundity differing significantly among populations within each of the morphotypes implying that fecundity was a continuously responsive trait influenced by local environmental factors. Latitudinal variation in fecundity was also evident among morphotypes when the simultaneous effects of both latitude andLFwere controlled. There was a significant trade‐off between fecundity and egg size in two of five populations of anadromous Arctic charr, but no evidence in limited data from either normal or dwarf populations. In contrast with some other studies of fecundity in salmonids, there was no evidence for a latitudinal cline in egg size.
The end of regressive evolution: examining and interpreting the evidence from cave fishes
Authors: Romero A. , Green S. M.
Published: July 2005

The evolution of hypogean fauna in general and hypogean fishes in particular has been controversial. Explanations regarding the reduction or loss of phenotypic characters such as eyes and pigmentation range from neo‐Lamarckism to neutral mutations, with ‘regressive evolution’ being a catch‐all characterization for such processes. The assumptions required for special evolutionary mechanisms underlying the evolution of cave dwellers have been based on generalizations about the animals and their environments drawn from relatively few observations. The evidence offered for notions such as pre‐adaptation of colonizing fauna and the purported impoverished nutrients in all caves is examined and it appears that the generalizations cannot be supported. Some major accomplishments in field and laboratory studies of hypogean fishes are summarized, including work highlighting developmental phenotypic plasticity. At the end, it is argued that evolution of hypogean fauna can be explained by well‐known mechanisms within the current context of evolutionary biology.
Taming the neutrophil: calcium clearance and influx mechanisms as novel targets for pharmacological control
Authors: Tintinger G , Steel H C , Anderson R
Published: July 2005

Neutrophils are relatively insensitive to the anti-inflammatory actions of conventional chemotherapeutic agents, including corticosteroids, emphasizing the requirement for novel pharmacological strategies to control the potentially harmful proinflammatory activities of these cells. In the case of commonly-occurring inflammatory diseases of the airways, the neutrophil is the primary mediator of inflammation in conditions such as chronic obstructive pulmonary disease, cystic fibrosis, acute respiratory distress syndrome, bronchiectasis and non-eosinophilic bronchial asthma. Recent insights into the mechanisms utilized by neutrophils to restore Ca2+ homeostasis following activation with Ca2+-mobilizing, proinflammatory stimuli have facilitated the identification of novel targets for anti-inflammatory chemotherapy in these cells. The most amenable of these from a chemotherapeutic perspective, is the cyclic AMP-dependent protein kinase-modulated endomembrane Ca2+-ATPase which promotes clearance of the cation from the cytosol of activated neutrophils. Second generation type 4 phosphodiesterase inhibitors and adenosine receptor agonists operative at the level of subtype A2A adenosine receptors, which are currently undergoing clinical and preclinical assessment respectively, hold promise as pharmacologic modulators during the restoration of Ca2+ homeostasis. If this promise is realized, it may result in novel chemotherapeutic strategies for the control of hyperacute and chronic inflammatory conditions in which neutrophils are primary offenders. Alternative, potential future targets include the Na+, Ca2+-exchanger and store-operated Ca2+ channels, which cooperate in the refilling of intracellular Ca2+ stores.
Lymphocyte subset differences in patients with chronic fatigue syndrome, multiple sclerosis and major depression
Authors: Robertson M J , Schacterle R S , Mackin G A , Wilson S N , Bloomingdale K L , Ritz J , Komaroff A L
Published: July 2005

Chronic fatigue syndrome (CFS) is a heterogeneous disorder of unknown aetiology characterized by debilitating fatigue, along with other symptoms, for at least 6 months. Many studies demonstrate probable involvement of the central and autonomic nervous system, as well as a state of generalized immune activation and selective immune dysfunction in patients with CFS. The aim of this study was to compare the lymphocyte subsets of patients with chronic fatigue syndrome to those of patients with major depression and multiple sclerosis as well as those of healthy control subjects. No differences were found in total numbers of T cells, B cells or natural killer (NK) cells. However, differences were found in T, B and NK cell subsets. Patients with major depression had significantly fewer resting T (CD3+/CD25–) cells than the other groups. Patients with major depression also had significantly more CD20+/CD5+ B cells, a subset associated with the production of autoantibodies. Compared to patients with multiple sclerosis, patients with CFS had greater numbers of CD16+/CD3– NK cells. Further study will be required to determine whether these alterations in lymphocyte subsets are directly involved in the pathophysiology of these disorders, or are secondary effects of the causal agent(s).
Actinobacillus actinomycetemcomitansY4 capsular polysaccharide induces IL-1β mRNA expression through the JNK pathway in differentiated THP-1 cells
Authors: Iwata T , Mitani A , Ishihara Y , Tanaka S , Yamamoto G , Kikuchi T , Naganawa T , Matsumura Y , Suga T , Koide M , Sobue T , Suzuki T , Noguchi T
Published: July 2005

Capsular polysaccharide from Actinobacillus actinomycetemcomitans Y4 (Y4 CP) induces bone resorption in a mouse organ culture system and osteoclast formation in mouse bone marrow cultures, as reported in previous studies. We also found that Y4 CP inhibits the release of interleukin (IL)-6 and IL-8 from human gingival fibroblast (HGF). Thus Y4 CP induces various responses in localized tissue and leads to the secretion of several cytokines. However, the effects of Y4 CP on human monocytes/macrophages are still unclear. In this study, THP-1 cells, which are a human monocytic cell line, were stimulated with Y4 CP, and we measured gene expression in inflammatory cytokine and signal transduction pathways. IL-1β and tumour necrosis factor (TNF)-α mRNA were induced from Y4 CP-treated THP-1 cells. IL-1β mRNA expression was increased according to the dose of Y4 CP, and in a time-dependent manner. IL-1β mRNA expression induced by Y4 CP (100 µg/ml) was approximately 7- to 10-fold greater than that in the control by real-time PCR analysis. Furthermore, neither PD98059, a specific inhibitor of extracellular signal-regulated kinase nor SB203580, a specific inhibitor of p38 kinase prevented the IL-1β expression induced by Y4 CP. However, JNK Inhibitor II, a specific inhibitor of c-Jun N-terminal kinase (JNK) prevented the IL-1β mRNA expression induced by Y4 CP in a concentration-dependent manner. These results indicate that Y4 CP-mediated JNK pathways play an important role in the regulation of IL-1β mRNA. Therefore, Y4 CP-transduced signals for IL-1β induction in the antibacterial action of macrophages may provide a therapeutic strategy for periodontitis.
Possible role of autoantibodies against nephrin in an experimental model of chronic graft-versus-host disease
Authors: Nagahama K , Maru K , Kanzaki S , Chai H L , Nakai T , Miura S , Yamaguchi A , Yamanaka S , Nagashima Y , Aoki I
Published: July 2005

Nephrin, a product of the NPHS1 gene, is a component of the slit diaphragms that are found between glomerular foot processes and is a crucial element for glomerular filtration barrier. Recently, nephrin has been focused in a number of studies of proteinuria development including various types of acquired glomerular diseases including minimal change nephrotic syndrome and membranous nephropathy. However, the precise role of nephrin in such acquired glomerular diseases is still unknown. To analyse the role of nephrin further, two kinds of anti-nephrin antibodies were raised in the rabbits and applied to an experimental mouse model of chronic graft-versus-host disease, in which (C57BL/10 × DBA/2) F1 mice developed clinically apparent severe proteinuria with significant glomerular lesions 7 weeks after parental DBA/2 cell transfer. Antibody-sandwich ELISA detected anti-nephrin antibodies during week 2 to week 6, with the peak at week 2 or week 4. Colocalization of nephrin and IgG on week 4, week 6, and week 8 was revealed by confocal microscopic analysis, suggesting that in situ immune complex formation with nephrin in glomerular lesion. Taken together, it seems to be suggested nephrin and its autoantibody have a certain role in the development of glomerular lesion in our model mice.
Strain-specific differences in perivascular inflammation in lungs in two murine models of allergic airway inflammation
Authors: Singh B , Shinagawa K , Taube C , Gelfand E W , Pabst R
Published: July 2005

Histological data show perivascular recruitment of inflammatory cells in lung inflammation. However, the process of perivascular inflammation is yet-to-be characterized in any systematic manner at cell and molecular levels. Therefore, we investigated impact of genetic background on perivascular inflammation in acute or chronic airway inflammation in different strains of mice. Further, to address molecular mechanisms of perivascular inflammation, we examined immunohistochemical expression of vascular adhesion protein-1 (VAP-1) in chronic airway inflammation. Histological scoring revealed time and strain specific differences in perivascular recruitment of inflammatory cells in chronic and acute airway inflammation (P < 0·05). The data show that A/J strain is significantly more susceptible for perivascular inflammation followed by BALB/c and C57BL/6, while C3H/HeJ strain showed no perivascular accumulation of inflammatory cells. Of the two strains examined for perivascular inflammation in acute airway inflammation, BALB/c showed more accumulation of inflammatory cells compared to C57BL/c. VAP-1 expression occurred in the endothelium of pulmonary arteries but not in alveolar septa or airways in the control as well as challenged mice. In the inflamed lungs from A/J mice, the VAP-1 staining in pulmonary arteries was more intense compared to the other strains. VAP-1 staining was generally observed throughout the pulmonary arterial wall in chronic lung inflammation. These data show that periarterial inflammation is influenced by the genetic background, and may be partially regulated by VAP-1.
Oligoclonal T cells are infiltrating the brains of children with AIDS: sequence analysis reveals high proportions of identical β-chain T-cell receptor transcripts
Authors: Lin W L , Fincke J E , Sharer L R , Monos D S , Lu S , Gaughan J , Platsoucas C D , Oleszak E L
Published: July 2005

We have recently described the presence of perivascular CD3+ CD45RO+ T cells infiltrating the brains of children with AIDS. To determine whether these infiltrates contain oligoclonal populations of T cells, we amplified by PCR β-chain T-cell receptor (TCR) transcripts from autopsy brains of four paediatric patients with AIDS. The amplified transcripts were cloned and sequenced. Sequence analysis of the β-chain TCR transcripts from all four patients revealed multiple identical copies of TCR β-chain transcripts, suggesting the presence of oligoclonal populations of T-cells. These TCR transcripts were novel. The presence of oligoclonal populations of T cells in the brains of these four paediatric patients with AIDS suggests that these T cells have undergone antigen-driven proliferation and clonal expansion very likely in situ, in the brains of these AIDS patients, in response to viral or self-antigens. Although the specificity of the clonally expanded β-chain TCR transcripts remains to be elucidated, none of the β-chain TCR transcripts identified in this study were identical to those specific for HIV-1 antigens that are currently reported in the GENBANK/EMBL databases. Certain common CDR3 motifs were observed in brain-infiltrating T cells within and between certain patients. Large proportions (24 of 61; 39%) of β-chain TCR clones from one patient (NP95-73) and 2 of 27 (7%) of another patient (NP95-184-O) exhibited substantial CDR3 homology to myelin basic protein (MBP)-specific TCR derived from normal donors or TCR expressed in the brain of patients with multiple sclerosis (MS) or with viral encephalitis. These two patients (NP95-73 and NP95-184-O) also shared HLA class II with the normal donors and the MS patients who expressed these homologous TCR. Pathologic examination at autopsy of the brains revealed the presence of myelin pallor only in patient NP95-73. T-cell clones identified in the brain of patients NP95-73 and NP95-184-O may recognize MBP or another CNS self antigen and this recognition may be restricted by either DRB1*15 or DQB1*0602 specificities.
High levels of glucocorticoid receptors in patients with active Crohn's disease may predict steroid resistance
Authors: Towers R , Naftali T , Gabay G , Carlebach M , Klein A , Novis B
Published: July 2005

Up to 20% of Crohn's disease (CD) patients respond poorly to glucocorticoids (GC). A product of an alternative splicing of the glucocorticoid receptor (GR) premRNA, GRβ, may play a role as a dominant inhibitor of the glucocorticoid response. Increasing evidence suggests that inflammatory cytokines such as interleukin (IL)-18 alternate the splicing of the primary transcript between the two isoforms GRβ and GRα in hGR gene of CD patients. The aim of this study is to assess the expression of GRα and GRβ in patients with CD and to look for a possible correlation between these receptors and the response to glucocorticoid treatment. Forty-two CD patients and 17 healthy volunteers were studied. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was performed using real-time PCR techniques. Serum IL-18 protein levels were measured by enzyme-linked immunosorbent assay (ELISA). The amount of hGRα-mRNA in patients in remission was significantly lower than in controls (P < 0·05). The amount of hGRβ-mRNA was significantly higher in GC-resistant patients in the active stage of disease compared with all other groups (P < 0·05). Patients in the active stage of the disease had higher levels of IL-18 than patients in remission and both had higher levels than controls (P < 0·05). The amounts of IL-18 were directly correlated with the amount of hGRβ mRNA in GC-resistant patients with an active disease. High levels of hGRβ might be connected to GC resistance. IL-18 might participate in the alternative splicing of the hGR preliminary mRNA of CD patients. The results support the theory that augmented hGRβ mRNA expression level in PBMC is connected with GC-resistance of CD patients.
Modulation of the immune response in pristane-induced lupus by expression of activation and inhibitory Fc receptors
Authors: Clynes Raphael , Calvani Nicola , Croker Byron P , Richards Hanno B
Published: July 2005

Altered homeostasis in Fcγ receptor (FcγR) expression has been implicated in the induction of both immune complex-mediated glomerulonephritis and autoantibody production in systemic lupus erythematosus. FcγRI and III are required for immune complexes to activate inflammatory cells, thereby inciting tissue injury. In contrast, FcγRIIB functions as a negative regulator of immune complex-mediated inflammation and autoantibody production. We investigated the role of FcγRI/III versus FcγRIIB on pristane-induced lupus in mice. FcγRI/III and FcγRIIB-deficient (–/–) and control (+/+) BALB/c mice were injected with either pristane or PBS. Proteinuria and glomerular immune deposits were evaluated 9 months after treatment and serial sera were analysed for total IgG levels and lupus-specific autoantibodies. The incidence of nephritis was higher in pristane-treated FcγRIIB–/– mice than pristane-treated FcγRI/III–/– and +/+ mice. Hypergammaglobulinaemia and spontaneous anti-DNA/chromatin autoantibody production were associated with interleukin (IL)-6 over-expression in FcγRIIB–/– mice and were augmented further by pristane treatment when compared to both FcγRI/III–/– and +/+ mice. Lack of either FcγRIIB or FcγRI/III had little effect on both anti-nRNP/Sm and anti-Su production induced by pristane. Our results confirm that spontaneous autoimmunity occurs in the absence of FcγRIIB. Moreover, the lupus-like syndrome induced by pristane in BALB/c mice was regulated by opposing activating and inhibitory FcγRs. Activating FcγRs were required for significant proteinuria and unbridled activation in the absence of FcγRIIB dramatically exacerbated glomerular inflammatory responses. FcγRIIB may be a key modulator that suppresses cell activation in the inflammatory immune response in systemic lupus erythematosus in humans.
Bacterial lipopolysaccharide both renders resistant mice susceptible to mercury-induced autoimmunity and exacerbates such autoimmunity in susceptible mice
Authors: Abedi-Valugerdi M , Nilsson C , Zargari A , Gharibdoost F , DePierre J W , Hassan M
Published: July 2005

The initiation and severity of systemic autoimmune diseases are influenced by a variety of genetic and environmental factors, in particular bacterial infections and products. Here, we have employed bacterial lipopolysaccharide (LPS), which non-specifically activates the immune system, to explore the involvement of innate immunity in mercury-induced autoimmunity in mice. Following treatment of mouse strains resistant [DBA/2 (H-2d)] or susceptible [SJL(H-2s)] to such autoimmunity with mercuric chloride and/or LPS or with physiological saline alone (control), their immune/autoimmune responses were monitored. Resistant DBA/2 mice were rendered susceptible to mercury-induced autoimmunity by co-administration of LPS, exhibiting pronounced increases in the synthesis of IgG1 and IgE, high titres of IgG1 deposits in the kidneys and elevated circulating levels of IgG1 antibodies of different specificities. Furthermore, the percentages of the T cells isolated from the spleens of DBA/2 mice exposed to both mercury and LPS that produced pro-inflammatory cytokines were markedly increased by in vitro stimulation with phorbol myristate acetate (PMA) and ionomycin, which was not the case for splenic T cells isolated from mice receiving mercuric chloride, LPS or saline alone. In addition, exposure of susceptible SJL mice to mercury in combination with LPS aggravated the characteristic features of mercury-induced autoimmunity, including increased synthesis of IgG1 and IgE, the production of IgG1 anti-nucleolar antibodies (ANolA) and the formation of renal deposits of IgG1. In summary, our findings indicate that activation of the innate immune system plays a key role in both the induction and severity of chemically induced autoimmunity.
Accumulation of plasma cells expressing CXCR3 in the synovial sublining regions of early rheumatoid arthritis in association with production of Mig/CXCL9 by synovial fibroblasts
Authors: Tsubaki T , Takegawa S , Hanamoto H , Arita N , Kamogawa J , Yamamoto H , Takubo N , Nakata S , Yamada K , Yamamoto S , Yoshie O , Nose M
Published: July 2005

Accumulation of plasma cells in the synovium is one of the diagnostic hallmarks in the histopathological manifestations of rheumatoid arthritis (RA). This seems to be prominent even prior to significant B cell infiltration and/or formation of lymphoid follicles in the synovium. To clarify the mechanism of early plasma cell accumulation, we examined in situ expression of chemokines and their receptors using synovial targeting biopsy specimens, which were obtained under arthroscopy from early RA patients. By immunohistochemical staining, plasma cells were found to express a chemokine receptor CXCR3, while synovial fibroblasts in the synovial sublining regions expressed its ligand, Mig/CXCL9. By reverse transcription-polymerase chain reaction (RT-PCR), using targeted lesions of synovial tissues obtained by laser capture microdissection, expression levels of Mig/CXCL9 in the synovial sublining regions were remarkably high and were likely to be associated with interferon (IFN)-γ expression. Furthermore, cultured synovial fibroblasts were confirmed to produce Mig/CXCL9 upon stimulation with IFN-γ. Our results indicate that in the early stage of RA, plasma cells expressing CXCR3 may be recruited directly from the circulation into the synovial sublining regions by its ligand, Mig/CXCL9, produced by synovial fibroblasts.
A human oral keratinocyte cell line responds to human heat shock protein 60 through activation of ERK1/2 MAP kinases and up- regulation of IL-1β
Authors: Pleguezuelos O , Dainty S J , Kapas S , Taylor J J
Published: July 2005

Heat shock proteins (HSP) are released by cells in response to stress signals. It is hypothesized that pathogenic bacteria stimulate the cells in the periodontium to up-regulate the expression of HSP60, which would stimulate macrophages, and possibly other cells, to produce proinflammatory cytokines. We sought to determine whether oral keratinocytes responded to recombinant human HSP60 and to identify the signalling pathways involved. In addition, whether oral keratinocytes are a source of endogenous HSP60 was also investigated. RT-PCR revealed that rhHSP60 induced expression of the IL-1β gene in the Human Oral Keratinocyte (HOK-16B) cell line and it was highest at the lowest concentration used (0·1 µg/ml). These responses were mediated via activation of p44/42 MAP-kinases and to a lesser extend the MAP-kinase SAP/JNK. Similar data was obtained from analysis of intracellular signalling pathways in HOK-16B cells by rhHSP70 and LPS (from both E. coli and the oral pathogen Porphyromonas gingivalis). However, there was little activation of p38 by rhHSP60. Blocking of the p44/42 pathway decreased HSP60-induced IL-1β gene expression and protein secretion. In addition, we discovered that self-HSP60 proteins were constitutively secreted by HOK-16B cells. Secretion of self-HSP60 was up-regulated in cells treated with LPS from P. gingivalis, but down-regulated with LPS from E. coli. To summarize, oral keratinocytes respond to exogenous HSP60 by triggering expression of the inflammatory cytokine IL-1β through activation of p44/42 MAP kinase. Oral keratinocytes are also a source for self-HSP60 and the secretion of this protein may be differentially modified by LPS from different bacterial species. These results highlight the importance of oral keratinocytes and HSPs in the development of an immune response against bacterial infection.
Differential early mitogen‐activated protein kinase activation in hyperglycemic ischemic brain injury in the rat
Authors: Farrokhnia N. , Roos M. W. , Terént A. , Lennmyr F.
Published: July 2005

Background  Hyperglycemia aggravates brain injury induced by focal ischemia‐reperfusion. The mitogen‐activated protein kinase (MAPK) members extracellular‐signal regulated kinase (Erk) and c‐Jun N‐terminal kinase (JNK) have been proposed as mediators of ischemic brain injury, and Erk is strongly activated by combined hyperglycemia and transient global ischemia. It is unclear whether similar MAPK activation appears in focal brain ischemia with concomitant hyperglycemia.

Design  Hyperglycemia was induced in rats by an intraperitoneal bolus of glucose (2 g kg−1). The rats were then subjected to 90 min of transient middle cerebral artery occlusion (MCAO). Erk and JNK activation were investigated with immunofluorescence and Western blot along with infarct size measurement based on tetrazolium staining and neurological score.

Results  The hyperglycemic rats showed increased tissue damage and impaired neurological performance after 1 day compared with controls. The hyperglycemia was generally moderate (< 15 mM). Erk activation was increased after 30 min of reperfusion in the ischemic cortex of the hyperglycemic rats, while JNK activation was present on the contralateral side. Phospho‐Erk immunofluorescence revealed marked neuronal activation of Erk in the ischemic cortex of hyperglycemic rats compared with controls.

Conclusion  Besides confirming the detrimental effects of hyperglycemia on focal ischemia‐reperfusion, this study shows that hyperglycemia strongly activates the pathogenic mediator Erk in the ischemic brain in the early phase of reperfusion. JNK activation at this stage is present in the nonischemic hemisphere. The functional relevance of these findings needs further investigation.
News in gut‐brain communication: a role of peptide YY (PYY) in human obesity and following bariatric surgery?
Authors: Hanusch‐Enserer U. , Roden M.
Published: July 2005

Recent advances in obesity research focused on neuroendocrine control of food intake, appetite and body weight balance. Gut hormones, which are sequentially released from different regions of the gut, send signals to the areas of appetite control in the central nervous system causing a release of counter‐regulatory hormones also originating from the gastrointestinal system. Ghrelin, a peptide secreted from the gastric fundus is released just before meal intake and stimulates hunger and food intake. Recently, peptide YY has been suggested to counteract ghrelin by inducing satiety and reducing appetite and caloric intake. While the effects of PYY on various gastrointestinal functions are well described, its action on weight loss is less known. Controversial results on the effect of exogenous administration of PYY3–36 opened the discussion on the respective roles of PYY and/or PYY3–36 in body weight homeostasis in man.
Angiotensin converting enzyme gene, smoking and mortality in a population‐based study
Authors: Arias‐Vásquez A. , Sayed‐Tabatabaei F. A. , Schut A. F. C. , Hofman A. , Bertolli‐Avella A. M. , Vergeer J. M. , Aulchenko Y. S. , Witteman J. C. M. , Van Duijn C. M.
Published: July 2005

Background  The genetic and environmental risk factors, which may influence longevity and mortality, have received much attention during more than one decade. One of the major risks for mortality is cardiovascular disease and the renin angiotensin system (RAS) plays a major role in maintaining blood pressure homeostasis. In this system, the Angiotensin Converting Enzyme (ACE) is one of the key regulators and has been studied in relation to cardiovascular disease and mortality. We aimed to evaluate if the ACE I/D polymorphism is related to total mortality in the elderly.

Materials and methods  Some 6968 elderly individuals from the Rotterdam study were genotyped for this polymorphism. Smoking was studied as a possible covariable or effect modifier. To examine the effect of the ACE genotype on mortality, a Cox proportional hazards model was fitted.

Results  Our results show an increased risk of total mortality in subjects with age at death below 65 years carriers of the DD genotype (HR 1·8, 95% CI 1·1–2·9, P = 0·016). This association was significant in total and cause specific mortality only in those who smoke (P‐value < 0·001 for gene–age interaction). Our findings suggest that the ACE gene is rather associated with early mortality than with late.

Conclusions  Individuals who carry the DD genotype appear to be susceptible to early mortality if they smoke, suggesting a possible interaction between smoking and the ACE gene.
Delineation of a supernumerary marker chromosome utilizing a multimodal approach of G‐banding, fluorescent in situ hybridization, confirmatory P1 artificial chromosome fluorescent in situ hybridization, and high‐resolution comparative genomic hybridization
Authors: Mark HFL , Wyandt H , Huang XL , Milunsky JM
Published: July 2005

We describe the structure of a supernumerary marker in a child who presented with a right atretic ear and multiple congenital anomalies. Using G‐banding, fluorescent in situ hybridization (FISH), P1 artificial chromosome FISH and high‐resolution comparative genomic hybridization (CGH), the marker was demonstrated to be a derivative chromosome resulting from malsegregation of a paternal 8;22 translocation: 47,XY, +der(22)t(8;22)(q24.1; q11.2). This case is noteworthy because the marker, while sharing similarities to der(22) in the Cat Eye syndrome (CES), also contains chromosome 8q material. This partial 8q trisomy confounds the diagnosis of CES associated with pure trisomy or pure tetrasomy 22q. The paternal translocation is noted with prolonged infertility and oligospermia, which again highlights the utility and necessity of chromosome analysis in this setting.
Clinical and molecular characteristics of hereditary non‐polyposis colorectal cancer families in Southeast Asia
Authors: Lee S‐C , Guo J‐Y , Lim R , Soo R , Koay E , Salto‐Tellez M , Leong A , Goh B‐C
Published: July 2005

Hereditary non‐polyposis colorectal cancer (HNPCC), predominantly due to germline MLH1/MSH2 mutations, is the commonest form of hereditary colorectal cancer (CRC), but data in Asians are sparse. We sequenced the MLH1/MSH2 coding and promoter core regions in CRC patients diagnosed below age 40, and/or with multiple primary cancers or familial cancer clustering suggestive of HNPCC, and correlated deleterious mutations with clinical and tumour features. Forty‐six Chinese, Malay and Indian kindreds participated. Of the 153 cancers reported in the 46 kindreds, stomach (14%) and urogenital cancers (13%) were the most common extracolonic cancers, whereas endometrial cancer comprised only 7%. Eleven different MLH1 and 12 MSH2 mutations were identified, including nine novel and four recurring mutations in the Chinese. One Indian was a compound heterozygote for an MLH1 and MSH2 mutation. The MLH1/MSH2 mutation data in the Malays and the Indians represents the first in these ethnic groups. Factors strongly associated with deleterious mutations were the Amsterdam criteria, family history of stomach or multiple primary cancers, and MSI‐high tumours, whereas family history of endometrial cancer and young cancer age alone correlated poorly. Distinct clinical and molecular characteristics were identified among Asian HNPCC kindreds and may have important clinical implications.
Two novel CLN6 mutations in variant late‐infantile neuronal ceroid lipofuscinosis patients of Turkish origin
Authors: Siintola E , Topcu M , Kohlschütter A , Salonen T , Joensuu T , Anttonen A‐K , Lehesjoki A‐E
Published: July 2005

Neuronal ceroid lipofuscinoses (NCLs) are the most common neurodegenerative childhood‐onset disorders characterized by autosomal recessive inheritance, epileptic seizures, progressive psychomotor deterioration, visual failure, and premature death. At least seven subtypes of childhood‐onset NCLs have been identified of which the late‐infantile–onset forms (LINCLs) are genetically the most heterogeneous with four underlying genes identified. A variant form of LINCL (vLINCL) present in Turkish patients has been considered a distinct clinical and genetic entity (CLN7). However, we recently showed that mutations in the CLN8 gene account for a subset of Turkish vLINCL. Toward identifying the CLN7 gene we here screened the known NCL loci for homozygosity in nine Turkish vLINCL families. These loci were excluded in seven families that are likely to represent the ‘true’ Turkish vLINCL. In two families, we identified two novel homozygous mutations in the CLN6 gene: an intronic base substitution (c.542 + 5G > T) affecting the splicing of the transcript and a nonsense mutation (c.663C > G) creating a stop codon at tyrosine 221. These data indicate that CLN6 mutations, in addition to those of CLN8, should be considered a diagnostic alternative in Turkish vLINCL patients. The genetic background of the ‘true’ Turkish vLINCL, CLN7, remains to be defined.
How lay people respond to messages about genetics, health, and race
Authors: Condit C , Bates B
Published: July 2005

There is a growing movement in medical genetics to develop, implement, and promote a model of race‐based medicine. Although race‐based medicine may become a widely disseminated standard of care, messages that advocate race‐based selection for diagnosing, screening and prescribing drugs may exacerbate health disparities. These messages are present in clinical genetic counseling sessions, mass media, and everyday talk. Messages promoting linkages among genes, race, and health and messages emphasizing genetic causation may promote both general racism and genetically based racism. This mini‐review examines research in three areas: studies that address the effects of these messages about genetics on levels of genetic determinism and genetic discrimination; studies that address the effects of these messages on attitudes about race; and, studies of the impacts of race‐specific genetic messages on recipients. Following an integration of this research, this mini‐review suggests that the current literature appears fragmented because of methodological and measurement issues and offers strategies for future research. Finally, the authors offer a path model to help organize future research examining the effects of messages about genetics on socioculturally based racism, genetically based racism, and unaccounted for racism. Research in this area is needed to understand and mitigate the negative attitudinal effects of messages that link genes, race, and health and/or emphasize genetic causation.