bluuebunny/crossref_metadata_2025 huggingface dataset:
How useful are the rodent animal models of gastric adenocarcinoma?
Authors: Pritchard D. M. , Przemeck S. M. C.
Published: April 2004

Gastric cancer is the second most common cause of cancer‐related mortality world‐wide. In most cases, it develops via the pre‐malignant stages of atrophic gastritis, intestinal metaplasia and dysplasia, following Helicobacter pylori infection of susceptible individuals. A number of rodent models have recently provided valuable insights into the host, bacterial and environmental factors involved in gastric carcinogenesis. Wild‐type rodents do not develop gastric adenocarcinoma, but early studies showed that the disease could be induced in several rodent species by chemical carcinogens. More recently, it has been demonstrated that gastric adenocarcinoma can be induced in Mongolian gerbils by H. pylori infection and in C57BL/6 mice by long‐term H. felis infection. These models have allowed the importance of Helicobacter virulence genes, host factors, such as gender, strain and immune response, and environmental factors, such as dietary salt, to be explored. A number of transgenic mice with alterations in various pathways, including the immune response, gastrin biosynthesis, parietal cell development, growth factors and tumour suppressors, have also provided models of various stages of gastric carcinogenesis. One model that has proved to be particularly valuable is the hypergastrinaemic INS‐GAS mouse, in which gastric carcinoma develops spontaneously in old animals, but the process is greatly accelerated by Helicobacter infection.
Adenomatous colonic polyps are rare in ulcerative colitis
Authors: Kitiyakara T. , Bailey D. M. , McIntyre A. S. , Gorard D. A.
Published: April 2004

Background : Uncertainty exists as to whether dysplastic polyps in ulcerative colitis should always be managed as dysplasia‐associated lesions/masses requiring colectomy, or whether some can be managed by polypectomy. The prevalence of non‐inflammatory polyps in ulcerative colitis is unknown.

Aim : To compare dysplastic polyp occurrence in patients with ulcerative colitis and in patients without inflammatory bowel disease.

Methods : The clinical, endoscopic and histological records of 150 ulcerative colitis patients (median disease duration, 10 years; 57% with pancolitis) undergoing colonoscopy were scrutinized for any polyp history. Two hundred and five patients undergoing colonoscopy for altered bowel habit, but without features suggestive of polyp presence, were used as a control group. Immunohistochemical staining of flat and polypoid mucosa for p16, β‐catenin, p53 and cyclo‐oxygenase‐2 was compared in the two groups.

Results : Only six (4%) ulcerative colitis patients had ever had dysplastic polyps. Two had single adenomatous polyps proximal to the colitis segment. Of the four patients with dysplastic polyps within colitic mucosa, two were treated endoscopically, but in two the lesions were considered to be dysplasia‐associated lesions/masses and colectomy was advised. In contrast, 24 controls had at least one adenomatous polyp (χ2 = 6.7, P < 0.01). Ten (6.7%) ulcerative colitis patients and 24 (12%) control patients had metaplastic polyps (N.S.). Immunohistochemical staining was not discriminatory.

Conclusion : Despite the increased cancer risk in long‐standing ulcerative colitis, adenomatous polyps arise less frequently in ulcerative colitis patients than in patients without ulcerative colitis.
Costs and efficacy of three different esomeprazole treatment strategies for long‐term management of gastro‐oesophageal reflux symptoms in primary care
Authors: Meineche‐Schmidt V. , Hauschildt Juhl H. , Østergaard J. E. , Luckow A. , Hvenegaard A.
Published: April 2004

Background: A prospective, open, randomized multi‐centre study with parallel group design was conducted in 155 general practice clinics, and included 1357 endoscopically uninvestigated patients with symptoms suggestive of gastro‐oesophageal reflux disease.

Aim: To assess the differences in direct medical costs between a patient‐controlled on‐demand treatment strategy with esomeprazole, 20 mg daily, and general practitioner‐controlled intermittent treatment strategies with esomeprazole, 40 mg daily, for either 2 or 4 weeks. Secondary objectives were to measure other costs, total costs, patient satisfaction and time to first relapse.

Methods: The primary cost analysis was carried out as a cost minimization analysis, comparing the direct medical costs in patients allocated to on‐demand treatment vs. those in patients allocated to either of the intermittent treatment strategies.

Results: The mean direct medical costs were 182, 221 and 195 euros for patient‐controlled on‐demand treatment and 2 weeks and 4 weeks of general practitioner‐controlled intermittent treatment, respectively, showing no statistically significant difference. The comparable mean total costs were 211, 344 and 300 euros, i.e. significantly lower for patients treated on‐demand compared with either of the general practitioner‐controlled intermittent treatment strategies.

Conclusions: The mean total costs, but not the mean direct medical costs, were higher in general practitioner‐controlled intermittent treatment strategies with esomeprazole compared with a patient‐controlled on‐demand treatment strategy.
Prospective, randomized, parallel‐group trial to evaluate the effects of lactulose and polyethylene glycol‐4000 on colonic flora in chronic idiopathic constipation
Authors: Bouhnik Y. , Neut C. , Raskine L. , Michel C. , Riottot M. , Andrieux C. , Guillemot F. , Dyard F. , Flourié B.
Published: April 2004

Background : Although lactulose and polyethylene glycol are osmotic laxatives widely used in the treatment of chronic constipation, no study has been conducted to compare their actions on the colonic bacterial ecosystem, which has an important influence on host health.

Aim : To assess the effects of lactulose and polyethylene glycol on the composition and metabolic indices of the faecal flora in patients with chronic idiopathic constipation.

Methods : Sixty‐five patients with chronic idiopathic constipation were included in this controlled, multi‐centre, randomized, parallel‐group study. Participants received lactulose (Duphalac) or polyethylene glycol‐4000 (Forlax) powders for the first week at a fixed dosage at night (20 g/day); in the second week, patients were given the option to vary the dose according to efficacy and tolerance (10–30 g/day); for the last 2 weeks, treatment was administered at a fixed dosage based on the results of the second week (10–30 g/day). Stools were recovered for bacteriological analysis at days − 1, 21 and 28.

Results : Clinical efficacy and tolerance were similar with both treatments. In the lactulose group, an increase in faecal bifidobacteria counts (P = 0.04) and β‐galactosidase activity (P < 0.001) was observed from day − 1 to day 28, whereas, in the polyethylene glycol group, there was a decrease in total short‐chain fatty acids (P = 0.02), butyrate (P = 0.04), acetate (P = 0.02) and faecal bacterial mass (P = 0.001). No differences were observed in stools with regard to the following parameters: counts of Lactobacillus, clostridial spores, Bacteroides and enterobacteria, pH, biliary acids and neutral sterol concentrations.

Conclusions : Both lactulose and polyethylene glycol are efficacious and well tolerated. However, although lactulose can be considered as a pre‐biotic in constipated patients, polyethylene glycol produces signs of decreased colonic fermentation in the stool.
Low molecular weight heparin (tinzaparin) vs. placebo in the treatment of mild to moderately active ulcerative colitis
Authors: Bloom S. , Kiilerich S. , Lassen M. R. , Forbes A. , Leiper K. , Langholz E. , Irvine E. J. , O'Morain C. , Lowson D. , Orm S.
Published: April 2004

Background : Heparin has anti‐inflammatory and immunomodulatory activity which may be of therapeutic benefit in the treatment of ulcerative colitis.

Aim : To test whether low molecular weight heparin, given subcutaneously, would provide a significant therapeutic response compared with placebo in the treatment of mild to moderate ulcerative colitis.

Study design : A prospective, double‐blind, randomized, placebo‐controlled, multi‐centre trial comparing tinzaparin 175 anti‐Xa IU/kg/day (innohep, LEO Pharma) subcutaneously for 14 days followed by tinzaparin 4500 anti‐Xa IU/day subcutaneously for 28 days with placebo, administered subcutaneously once daily for up to 42 days. The primary outcome measure was the mean change in colitis activity from baseline to the end of study treatment assessed by the sum of scores of stool frequency, rectal bleeding, sigmoidoscopic appearance and histology. Secondary outcome measures included changes in individual activity indices and laboratory parameters. Patients were assessed at weekly intervals for 6 weeks and within 1 week of completing treatment.

Results : One hundred patients with active ulcerative colitis (up to six bloody stools per day, no fever, no tachycardia or systemic disturbances) were randomized. Forty‐eight received tinzaparin and 52 received placebo. The difference in the mean percentage change in colitis activity from baseline to end of treatment (tinzaparin‐placebo) was not statistically significant (P = 0.84). There was no difference between tinzaparin and placebo in any secondary outcome measure. One major bleed (rectal), occurred in a patient receiving placebo.

Conclusion : This is the largest trial to date of heparin in ulcerative colitis. The results show no benefit of low molecular weight heparin over placebo in mild to moderately active ulcerative colitis.
Patient‐directed strategy to reduce prescribing for patients with dyspepsia in general practice: a randomized trial
Authors: Krol N. , Wensing M. , Haaijer‐Ruskamp F. , Muris J. W. M. , Numans M. E. , Schattenberg G. , van Balen J. , Grol R.
Published: April 2004

Background : The percentage of patients receiving long‐term treatment with acid suppressive drugs, mainly proton pump inhibitors, is higher than the prevalence of diseases that are commonly accepted as the proper indication for long‐term proton pump inhibitor use.

Aim : To evaluate whether a patient‐directed intervention (direct mail) reduced the prescription of antisecretory medication for dyspepsia in general practice.

Methods : A cluster‐randomized trial was performed. One hundred and thirteen chronic users of proton pump inhibitors were recruited by 20 general practitioners. An unsolicited information leaflet was sent to patients that suggested stopping or reducing the use of proton pump inhibitors. The number of patients who stopped or reduced proton pump inhibitor use was measured at 12 and 20 weeks after the intervention. Secondary outcome measures were dyspepsia symptom severity and perceived quality of life measured at 12 weeks after the intervention.

Results : Fourteen of the 59 (24%) intervention group patients stopped or reduced their use of proton pump inhibitors, compared with three of the 45 (7%) control group patients (relative risk ratio 3.56; CI 95%: 1.088–11.642). Dyspepsia symptom severity and quality of life did not change.

Conclusions : A simple patient‐directed intervention reduced the volume of long‐term prescriptions of proton pump inhibitors in patients with dyspepsia.
Natural history of irritable bowel syndrome
Authors: El‐Serag H. B. , Pilgrim P. , Schoenfeld P.
Published: April 2004

Background:  The natural history of irritable bowel syndrome is unclear, including the likelihood that these patients will be diagnosed with an alternative organic or functional gastrointestinal disorder. Understanding the stability of an irritable bowel syndrome diagnosis may limit repeated diagnostic evaluation among these patients.

Methods:  The inclusion criteria included observational longitudinal studies of clinic‐based samples of adult patients with irritable bowel syndrome. Only studies published in the English language in full manuscript form were included. Literature searches, selection and review of eligible articles, and data abstraction were performed in a duplicate, independent manner.

Results:  Fourteen studies met study selection criteria. In six studies with relevant information, 2–5% of irritable bowel syndrome patients were diagnosed with an alternative organic GI disorder after 6 months to 6 years of follow‐up. Long‐term follow‐up indicated that 2–18% of patients developed worse irritable bowel syndrome symptoms, approximately 30–50% of patients had unchanged symptoms, and the rest either improved or had symptoms disappear. Prior surgery (one study), higher somatic scores (one study), higher baseline anxiety (two studies), depression scores (one study) were predictive of worsening of symptoms during long‐term follow‐up.

Conclusions:  Irritable bowel syndrome, a chronic disorder, is a stable diagnosis. Once initial investigations are negative, fewer than 5% are diagnosed with an alternative organic GI disorder. Repeated diagnostic evaluations of patients with recurrent or persistent symptoms similar to their baseline symptoms are not warranted.
Antigen specific correlations of cellular immune responses in human leishmaniasis suggests mechanisms for immunoregulation
Authors: ANTONELLI L R V , DUTRA W O , ALMEIDA R P , BACELLAR O , GOLLOB K J
Published: April 2004

Regulation of the immune response directed against Leishmania is critical for the establishment of effective control of the disease. It is likely that some types of immune responses directed against Leishmania can lead to more severe clinical forms of leishmaniasis causing a poor control of the pathogen and/or pathology, while others lead to resolution of the infection with little pathology as in cutaneous leishmaniasis. To gain a better understanding of the possible role that subpopulations of T cells, and their associated cytokines have on disease progression and/or protective immune responses to L. braziliensis infection, a detailed study of the frequency of activated and memory T cells, as well as antigen specific, cytokine producing T cells was carried out. Following the determination of cytokine producing mononuclear cell populations in response to total Leishmania antigen (SLA), and to the recombinant antigen LACK, correlation analysis were performed between specific cytokine producing populations to identify models for cellular mechanisms of immunoregulation in human cutaneous leishmaniasis. These studies have shown: (1) a positive correlation between ex vivo CD45RO frequencies and antigen specific cytokine (IFN-gamma or IL-10) producing cells; (2) a negative correlation between ex vivo CD69 expression and the frequency of IFN-gamma producing cells; (3) a positive correlation amongst SLA specific, IFN-gamma or TNF-alpha and IL-10 producing lymphocytes with one another; and (4) a higher frequency of IL-10 producing, parasite specific (anti-SLA or anti-LACK), lymphocytes are correlated with a lower frequency of TNF-alpha producing monocytes, demonstrating an antigen specific delivery of IL-10 inducing negative regulation of monocyte activity.
High expression of interleukin-1βin the corneal epithelium of MRL/lpr mice is under the control of their genetic background
Authors: OKAMOTO M , TAKAGI M , KUTSUNA M , HARA Y , NISHIHARA M , ZHANG M C , MATSUDA T , SAKANAKA M , OKAMOTO S , NOSE M , OHASHI Y
Published: April 2004

MRL/Mp mice bearing the Fas deletion mutant gene, lpr (MRL/lpr), spontaneously develop polyarthritis, sialoadenitis and dacryoadenitis, resembling rheumatoid arthritis (RA), and also corneal involvement such as keratopathy and scleritis, which is a major complication in RA patients. In this study, we found that the expression levels of IL-1β and MMP-1 mRNAs in cornea were high in both MRL/lpr and MRL/Mp-+/+ strains of mice at an age younger than when they develop any inflammatory lesions. This was not true of other inbred strains, even those bearing the lpr gene, and also not of (NZB × NZW) F1 lupus mice. There was no significant difference in the expression of IL-1α and TGFβ in cornea in these strains. Using crosses between MRL/lpr and C3H/HeJ-lpr/lpr (C3H/lpr) mice, at least the expression of IL-1β was found to be under the control of the MRL genetic background, likely with a recessive mode of inheritance. Considering that IL-1β in cornea was detected particularly in the epithelial layer, the high expression of IL-1β in cornea is most likely involved in the genetic predisposition for corneal involvement and possibly also for arthritis in an MRL strain of mice.
Human intestinal epithelial cell-derived interleukin (IL)-18, along with IL-2, IL-7 and IL-15, is a potent synergistic factor for the proliferation of intraepithelial lymphocytes
Authors: OKAZAWA A , KANAI T , NAKAMARU K , SATO T , INOUE N , OGATA H , IWAO Y , IKEDA M , KAWAMURA T , MAKITA S , URAUSHIHARA K , OKAMOTO R , YAMAZAKI M , KURIMOTO M , ISHII H , WATANABE M , HIBI T
Published: April 2004

Intestinal epithelial cell (IEC)-derived cytokines, such as stem cell factor (SCF), interleukin (IL)-7 and IL-15 are known to be required for the development of intestinal intraepithelial lymphocytes (IELs). A newly described cytokine, IL-18, has also been shown to be produced by intestinal epithelial cells. To demonstrate the functional effects of IL-18 on human IELs, we assessed IL-18/IL-18 receptor expression in IEC/IEL and proliferation following stimulation of intestinal IELs by IL-18. IL-18 transcripts were detected both in freshly isolated human colonic epithelial cells and in various colonic epithelial cell lines. IL-18 protein was also detected by ELISA and flow cytometric analysis using antihuman IL-18-specific monoclonal antibody (MoAb). Furthermore, IELs constitutively expressed the IL-18 receptor in addition to the IL-2 and IL-7 receptors. More importantly, IL-18 augmented significant proliferative responses of IEL in combination with IL-2, IL-7 and IL-15 both in the presence and in absence of anti-CD3 MoAb. These results suggest that IL-18 might play a crucial role in the proliferation and maintenance of intestinal IELs.
Characterization of M cell formation and associated mononuclear cells during indomethacin-induced intestinal inflammation
Authors: LÜGERING A , FLOER M , LÜGERING N , CICHON C , SCHMIDT M A , DOMSCHKE W , KUCHARZIK T
Published: April 2004

M cells represent an important gateway for the intestinal immune system by delivering luminal antigens through the follicle-associated epithelium to the underlying immune cells. The goal of this study was to characterize this route of antigen uptake during intestinal inflammation by characterizing M cell formation and M cell-associated lymphocytes after indomethacin challenge in rats. We demonstrated increased M cell formation as early as 12 h after a single injection of indomethacin. The elevated M cell counts were determined until day 3 and returned to basal levels after 7 days. Electron microscopic studies revealed an expansion of mononuclear cells inside the M cell pocket that were characterized predominantly as B cells, T cell receptor (TCR)αβ- and CD4-positve T cells, whereas other markers such as CD11b, CD8 and CD25 remained unchanged. In situ hybridization studies showed increased expression of interleukin (IL)-4 by lymphocytes during intestinal inflammation in the Peyer's patch follicle. These studies illuminate the relevance of M cells during intestinal inflammation and suggest that M cells derive from epithelial cells in a certain microenvironment.
Molecular analysis of B-cell differentiation in selective or partial IgA deficiency
Authors: ASANO T , KANEKO H , TERADA T , KASAHARA Y , FUKAO T , KASAHARA K , KONDO N
Published: April 2004

Selective IgA deficiency is the most common form of primary immunodeficiency, the molecular basis of which is unknown. To investigate the cause of selective IgA deficiency, we examined what stage of B-cell differentiation was blocked. DNA and RNA were extracted from three Japanese patients with selective IgA deficiency and three with a partial IgA deficiency. In selective IgA deficiency patients, Iα germline transcript expression levels decreased and α circle transcripts were not detected. Stimulation with PMA and TGF-β1 up-regulated Iα germline and α circle transcripts. In some patients, IgA secretion was induced by stimulation with anti-CD40, IL-4 and IL-10. In partial IgA deficiency patients, Iα germline, α circle transcripts and Cα mature transcripts were detected in the absence of stimulation. Our findings suggest that the decreased expression level of Iα germline transcripts before a class switch might be critical for the pathogenesis of some patients with selective IgA deficiency. However, in patients with a partial IgA deficiency, B-cell differentiation might be disturbed after a class switch.
Itraconazole antagonizes store-operated influx of calcium into chemoattractant-activated human neutrophils
Authors: STEEL H C , ANDERSON R
Published: April 2004

We have investigated the effects of itraconazole (0·1–10 µm), an antimycotic which is often used prophylactically in primary and secondary immunodeficiency disorders, including chronic granulomatous disease, on mobilization of Ca2+ and restoration of Ca2+ homeostasis following activation of neutrophils with FMLP or PAF. Transmembrane fluxes of Ca2+, as well as cytosolic concentrations of the cation were measured using a combination of spectrofluorimetric and radiometric procedures. The abruptly occurring increases in cytosolic Ca2+ following activation of the cells with either FMLP (1 µm) or PAF (200 nm) were unaffected by itraconazole. However, the subsequent store-operated influx of the cation was attenuated by itraconazole at concentrations of 0·25 µm and higher. The itraconazole-mediated inhibition of uptake of Ca2+ was not associated with detectable alterations in the intracellular concentrations of cyclic AMP, ATP or inositol triphosphate, and appeared to be compatible with antagonism of store-operated Ca2+ channels. Although a secondary property, this anti-inflammatory activity of itraconazole, if operative in vivo, may be beneficial in conditions associated with dysregulation of neutrophil Ca2+ handling such as CGD.
Genetic variants in the CCR gene cluster and spontaneous viral elimination in hepatitis C-infected patients
Authors: MASCHERETTI S , HINRICHSEN H , ROSS S , BUGGISCH P , HAMPE J , FOELSCH U R , SCHREIBER S
Published: April 2004

Hepatitis C virus (HCV) infection results in chronic hepatitis in more than 80% of infected patients while 10–20% of patients recover spontaneously. Host genetic factors may influence the ability to clear the virus after infection. Six single nucleotide polymorphisms and a 32 bp deletion in the genes coding for CCR3, CCR2 and CCR5 (which are all located in a cluster on chromosome 3) were investigated in 465 consecutively recruited patients infected with HCV and 370 matched controls. Genetic variants were tested for association with spontaneous viral elimination and, in the chronically infected patients, stage of fibrosis and response to antiviral therapy. The G190A polymorphism (variant allele Ile64) in the first transmembrane domain of CCR2 was under-represented in the 29 patients who had cleared the hepatitis C virus spontaneously (P = 0·018). None of the other variants in the CCR gene cluster showed association with the natural course of the infection, stage of fibrosis or response to therapy.
An imbalance of naive and memory/effector subsets and altered expression of CD38 on T lymphocytes in two girls with hyper-IgM syndrome
Authors: COSTA-CARVALHO B T , VIANA M A , BRUNIALTI M K C , KALLAS E G , SALOMAO R
Published: April 2004

In this report we evaluated CD4+ T, CD8+ T and natural killer (NK) cell counts, the levels of naive/memory subsets within the CD4+ T lymphocyte population, expression of CD38 on T lymphocytes, and CD4+ and CD8+ T cell cytokine production in two girls with hyper-IgM (HIM) syndrome. Both girls developed recurrent infections early in infancy, presenting a wide spectrum of clinical manifestations, with a strikingly different disease severity between them. CD4+ T cell counts were low in both children (patient 1: 214 cells/mm3 and patient 2: 392 cells/mm3), and the CD4/CD8 T cell ratio was 0·4 for patient 1, the patient with the more severe disease, and 1·4 for patient 2. NK cell numbers were low in patient 1 (60 cells/mm3) and borderline (286 cells/mm3) with regard to normal levels in patient 2. An imbalance of naive and memory/effector cell subsets was found in both girls, with the percentage of CD45RA+ 27+ (naive) CD4+ T lymphocytes being 5·8 and 12·4 for patients 1 and 2, respectively. Expression of CD38 on the surface of T lymphocytes was low in patient 1. Detection of intracellular interferon (IFN)-γ and tumour necrosis factor (TNF)-α in CD4+ and CD8+ T lymphocytes upon PMA-Io stimulus was preserved in both children. In conclusion, we found low numbers of CD4+ T lymphocytes and a dramatic redistribution of naive and memory/effector CD4+ T lymphocytes in two girls with non-X-linked HIM syndrome. Furthermore, we found low expression of CD38 on T lymphocytes and low numbers of NK cells in the patient with the more severe disease, indicating a possible role for these cells in the pathogenesis of this immunodeficiency.
Primary immune response to keyhole limpet haemocyanin following trauma in relation to low plasma glutamine
Authors: BOELENS P G , FONK J C M , HOUDIJK A P J , SCHEPER R J , HAARMAN H J T H M , MEIJER S , VAN LEEUWEN P A M , VON BLOMBERG-VAN DER FLIER B M E
Published: April 2004

Severe trauma can lead to a compromised immune response, thereby increasing susceptibility to infections. Here we will study to what extent these early changes in the immune status upon trauma affect a primary immune response to keyhole limpet haemocyanin (KLH). Because glutamine is the preferred respiratory substrate for immune competent cells and known to be depleted after trauma, we studied the immune status and the primary sensitization in relation to the glutamine plasma concentration in a group of severe trauma patients [injury severity score (ISS) >17]. Trauma patients (n = 31) were sensitized with KLH within 12 h after trauma; plasma glutamine concentrations and immune parameters were determined, after which KLH-specific immune responsiveness was evaluated on days 9 and 14. Low plasma glutamine concentrations were found after trauma. Significantly elevated numbers of granulocytes and CD14-positive leucocytes were found, whereas the HLA-DR expression on CD14-positive cells was significantly lower in trauma patients than in healthy controls. Trauma did not change the in vitro proliferative capacity of lymphocytes when cultured with glutamine; however, when lymphocytes were cultured without glutamine, trauma resulted in lower proliferation than healthy controls. Phytohaemagglutinin-(PHA)-induced interferon (IFN)-γ and interleukin (IL)-10 production was significantly lower after trauma, whereas IL-4 production was not affected. KLH sensitization following trauma resulted in poor skin test reactivity and low in vitro KLH-induced lymphocyte proliferation compared to controls. In contrast, the development of anti-KLH IgM, IgG, IgA, IgG1, IgG2, IgG3 and IgG4 production on days 9 and 14 following trauma was not different from that in healthy controls. Major trauma was associated with a reduced cell-mediated immune response, correlating with low plasma glutamine concentrations, while no effects of trauma were found on the development of a primary humoral immune response.
Cellular responses and cytokine production in post-treatment hookworm patients from an endemic area in Brazil
Authors: GEIGER S M , MASSARA C L , BETHONY J , SOBOSLAY P T , CORRÊA-OLIVEIRA R
Published: April 2004

Human hookworm infections are distributed widely in tropical areas and have a significant impact on host morbidity and human health. In the present study, we investigated the cellular responsiveness and cytokine production in peripheral blood mononuclear cells (PBMC) from Necator americanus-infected schoolchildren who had recently received chemotherapy, and compared them with non-infected endemic controls. Hookworm patients and treated, egg-negative individuals showed a lower cellular reactivity against phytohaemagglutinin (PHA) and hookworm antigen when compared with egg-negative endemic controls. The baseline production of proinflammatory tumour necrosis factor-α (TNF-α) in PBMC from infected patients and treated, egg-negative individuals was elevated. On the other hand, PHA- or hookworm antigen-induced interleukin (IL)-12 and interferon (IFN)-γ secretion was higher in endemic controls than in hookworm patients, who either continued egg-positive or were egg-negative after treatment. Also, PBMC from endemic controls secreted more IL-5 and IL-13 than the other patient groups. Opposite to that, the spontaneous as well as the antigen-driven IL-10 secretion was lower in endemic controls when compared with the other groups. In summary, patently hookworm-infected as well as egg-negative treated patients disclosed an elevated spontaneous cellular secretion of proinflammatory TNF-α, a prominent secretion of regulatory Th2-type IL-10 and an impaired production of IL-12, IFN-γ, IL-5 and IL-13.
Increased serum C3 levels in Crry transgenic mice partially abrogates its complement inhibitory effects
Authors: KANG H J , BAO L , XU Y , QUIGG R J , GICLAS P C , HOLERS V M
Published: April 2004

Complement receptor 1-related gene/protein y (Crry) is a potent murine complement regulator that inhibits C3 convertases. Transgenic mice that overexpress soluble Crry (sCrry), directed systemically by the metallothionein-I promoter, have been used as an animal model for chronic blockade of complement activation. Recently we have found that alternative pathway (AP) activity in Crry transgenic mice was not inhibited as much as expected. To elucidate the mechanism of this effect, we evaluated the AP activities and levels of sCrry and AP complement components in transgenic and non-transgenic mice. In transgenic mice, expression of sCrry was induced by feeding zinc sulphate solution to 70·1 ± 42·7 µg/ml mean serum level. Its corresponding level of purified sCrry inhibited 49% of AP activity of normal mice serum; however, the actual AP activities in transgenic mice were not decreased when compared to non-transgenic mice (130·2 ± 9·0%versus 113·0 ± 35·4%). Expressed sCrry was functional, as immunoprecipitation and removal of sCrry from transgenic sera with rabbit anti-Crry polyclonal antibody resulted in enhanced AP activity, consistent with initial levels of sCrry. We then compared the changes to C3, factor B, factor H and factor D serum levels in transgenic and non-transgenic mice after induction of sCrry expression. Of these only C3 was increased after zinc feeding in transgenic mice compared to non-transgenic mice (142·8 ± 14·1%versus 121·4 ± 15·1%, P = 0·023). These results suggest that the inhibitory effect of chronic exposure to sCrry is compensated by concomitant alteration in C3 levels. This result also suggests the presence of a complement regulatory protein controls the level of serum C3, which has potential importance in the design and interpretation of studies involving chronic use of complement inhibitors.
Transfer factors as immunotherapy and supplement of chemotherapy in experimental pulmonary tuberculosis
Authors: FABRE R A , PÉREZ T M , AGUILAR L D , RANGEL M J , ESTRADA-GARCÌA I , HERNÁNDEZ-PANDO R , ESTRADA PARRA S
Published: April 2004

Problems of logistics, compliance and drug resistance point to an urgent need for immunotherapeutic strategies capable of shortening the current six month antibiotic regimens used to treat tuberculosis. One potential immunotherapeutic agent is transfer factors. Transfer factors (TF) are low molecular weight dialysable products from immune cells which transmit the ability to express delayed-type hypersensitivity (DTH) and cell mediated immunity from sensitized donors to nonimmune recipients. In this study we determined the efficiency of TF as immunotherapy to treat experimental tuberculosis. When BALB/c mice are infected via the trachea with Mycobacterium tuberculosis H37Rv there is an initial phase of partial resistance dominated by Th-1 type cytokines plus tumour necrosis factor-alpha (TNFα) and the inducible isoform of nitric oxide synthase (iNOS), followed by a phase of progressive disease characterized by increasing expression of IL-4, diminished expression of TNFα and iNOS, and low DTH. Animals in this late progressive phase of the disease (day 60) were treated with different doses of TF (one injection per week) obtained from spleen cells when the peak of immune protection in this animal model is reached (day 21), or with different doses of TF from peripheral leucocytes of PPD + healthy subjects. We show here that the treatment with murine or human TF restored the expression of Th-1 cytokines, TNFα and iNOS provoking inhibition of bacterial proliferation and significant increase of DTH and survival. This beneficial effect was dose dependent. Interestingly, murine TF in combination with conventional chemotherapy had a synergistic effect producing significant faster elimination of lung bacteria loads than chemotherapy alone.
IgG1 antimycobacterial antibodies can reverse the inhibitory effect of pentoxifylline on tumour necrosis factor alpha (TNF-α) secreted by mycobacterial antigen-stimulated adherent cells
Authors: THAKURDAS S M , HASAN Z , HUSSAIN R
Published: April 2004

Chronic inflammation associated with cachexia, weight loss, fever and arthralgia is the hallmark of advanced mycobacterial diseases. These symptoms are attributed to the chronic stimulation of tumour necrosis factor (TNF)-α. Mycobacterial components directly stimulate adherent cells to secrete TNF-α. We have shown recently that IgG1 antimycobacterial antibodies play a role in augmenting TNF-α in purified protein derivative (PPD)-stimulated adherent cells from non-BCG-vaccinated donors. We now show that IgG1 antibodies can also augment TNF-α expression in stimulated adherent cells obtained from BCG-vaccinated donors and this augmentation is not linked to interleukin (IL)-10 secretion. In addition IgG1 antimycobacterial antibodies can reverse the effect of TNF-α blockers such as pentoxifylline and thalidomide. These studies therefore have clinical implications for anti-inflammatory drug treatments which are used increasingly to alleviate symptoms associated with chronic inflammation.
Reproducibility of a novel model of murine asthma-like pulmonary inflammation
Authors: MCKINLEY L , KIM J , BOLGOS G L , SIDDIQUI J , REMICK D G
Published: April 2004

Sensitization to cockroach allergens (CRA) has been implicated as a major cause of asthma, especially among inner-city populations. Endotoxin from Gram-negative bacteria has also been investigated for its role in attenuating or exacerbating the asthmatic response. We have created a novel model utilizing house dust extract (HDE) containing high levels of both CRA and endotoxin to induce pulmonary inflammation (PI) and airway hyperresponsiveness (AHR). A potential drawback of this model is that the HDE is in limited supply and preparation of new HDE will not contain the exact components of the HDE used to define our model system. The present study involved testing HDEs collected from various homes for their ability to cause PI and AHR. Dust collected from five homes was extracted in phosphate buffered saline overnight. The levels of CRA and endotoxin in the supernatants varied from 7·1 to 49·5 mg/ml of CRA and 1·7–6 µg/ml of endotoxin in the HDEs. Following immunization and two pulmonary exposures to HDE all five HDEs induced AHR, PI and plasma IgE levels substantially higher than normal mice. This study shows that HDE containing high levels of cockroach allergens and endotoxin collected from different sources can induce an asthma-like response in our murine model.
Survival of Erwinia amylovora on pears and on fruit containers in cold storage and outdoors
Authors: Ceroni P. , Minardi P. , Babini V. , Traversa F. , Mazzucchi U.
Published: April 2004

The survival of Erwinia amylovora during cold storage or outdoors may be a relevant factor in the spread of fireblight. The survival of E. amylovora was studied in cold storage on pear fruits, on container materials and on packaging paper, and outdoors on wood (oak and poplar) and on polyethylene. The samples were contaminated with a bacterial suspension of a mutant strain, washed, concentrated by centrifugation, and the final concentrates were used for plate counting. In cold storage, reisolation from the calyx was successful even after 101 days, whereas on pear surfaces, it was unsuccessful after just 1 day. On oak and poplar wood, reisolation was obtained up to 77 days in cold storage for both types of wood, but only up to 27 and 55 days, respectively, outdoors. Reisolation from packaging paper in cold storage was successful up to 14 days. Reisolation from polyethylene outdoors was unsuccessful after 24 h. Survival curves were calculated for each material. On the basis of a model of inoculum transmission, and using the survival curves, a phytosanitary risk period for the different types of materials was estimated.
L’hybridation moléculaire: une technique de détection du Potato spindle tuber viroid adaptée aux plans de surveillance
Authors: Ollivier F.
Published: April 2004

La maladie des tubercules fusiformes de la pomme de terre est due au Potato spindle tuber viroid (PSTVd), microorganisme qui ne peut être détecté par des méthodes sérologiques classiques. En France, le Laboratoire National de la Protection des Végétaux (Station de Quarantaine Pomme de Terre) a débuté les tests de détection du viroïde avec une méthode «reverse‐PAGE», ne nécessitant pas de réactif spécifique mais peu adaptée aux grandes séries d’analyses. Il a ensuite maîtrisé une technique d’hybridation moléculaire qui, associée à une technique d’extraction permettant de travailler de grandes séries d’échantillons frais ou lyophilisés en flux continu, supporte la comparaison avec une technique RT‐PCR encore en phase de validation. Malgré la relative lourdeur de la technique d’hybridation moléculaire (comparée aux techniques sérologiques classiques), la méthode a pu être transférée dans deux laboratoires partenaires qui réalisent une partie des tests des programmes officiels français de surveillance, confirmant la fiabilité et la robustesse de la méthode mise au point.
Results of the systematic survey and control of Plum pox potyvirus in Slovenia
Authors: Viršček Marn M. , Mavrič I. , Benko‐Beloglavec A. , Knapič V. , Weilguny H.
Published: April 2004

Sharka, caused by Plum pox potyvirus (PPV), was first observed in Slovenia in 1987. In the following years, the presence of PPV was confirmed by DAS‐ELISA in samples originating from orchards, individual trees and propagation material of stone fruits. In 1998, a systematic survey was initiated to prevent and control the spread of sharka and to establish pest‐free production sites. In the first 3 years of the systematic survey, the presence of PPV was also monitored outside production sites for propagating material and their buffer zones, in order to establish the current incidence of sharka in Slovenia. The results showed an overall presence of PPV infection in Slovenia. Since 2000, the survey has focused mainly on nurseries, mother trees and stool‐beds. In spite of strict official supervision and eradication measures, the incidence of sharka in propagating material production sites increased until 2002. A significant decrease in the number of PPV‐infected mother trees, stool‐beds, nurseries and buffer zones was finally obtained in 2002, as a consequence of the vast effort dedicated to containment of sharka in Slovenia.
Traitement phytosanitaire du bois par chauffage à cœur
Authors: Aléon D.
Published: April 2004

Suite à l’adoption de la NIMP no. 15 et en particulier l’exigence relative au traitement à la chaleur des emballages en bois, une étude a été menée par le Centre Technique du Bois et de l’Ameublement. Cette étude vise à disposer d’abaques de montée en température du bois permettant de garantir un traitement à cœur pendant 30 min à 56 °C en mesurant la température de l’ambiance et non celle à cœur du bois. Un tel système de mesure de température, outre sa facilité de mise en oeuvre, présente de meillures garanties que l’ensemble du bois dans la chambre a subi un traitement adéquat.
A conceptual framework for agent‐based agile manufacturing cells
Authors: Yu Jianming , Krishnan Krishna K.
Published: April 2004

Abstract.  Agile manufacturing techniques are perceived as the manufacturing systems of the future. Agile manufacturing cells are dynamic and reconfigurable and the modelling of the manufacturing cells and its interaction mechanism is critical to its successful use. This paper deals with the architecture and cooperation mechanism of web‐based agile manufacturing cells. Based on an analysis of structure and organization requirements of agile manufacturing cells and a comparison of three basic architectures of manufacturing systems, the quasi‐heterarchical architecture is used for the agile manufacturing cell. Functional layers are defined in this architecture to make the cell's control system reconfigurable and reusable. Agent technology is adopted for implementation of each layer's functions to establish an agent‐based model of agile manufacturing cells. Four types of agents including cooperation agent, job management agent, resource broker agent, and resource control agent are defined, and their functions discussed. Finally, a real time interaction mechanism of the agents is presented by considering the activities during the agents’ cooperation in an agile manufacturing cell.
An application of the Delta Model and BPR in transforming electronic business – the case of a food ingredients company in UK
Authors: Tang Nelson K. H. , Yasa Prabhaker R. , Forrester Paul L.
Published: April 2004

Abstract.  Companies are leveraging existing resources and the internet to come up with new or modified business models to respond to the demands of e‐business. Companies in the food processing industry are also waking to the reality that e‐business technology can make a big difference to the bottom line. This paper presents the result of an action research project which applied a new approach labelled as the Delta Model developed by Hax and Wilde (2001) of Sloan School of Management to strategy development for brick‐n‐mortar companies launching e‐business initiatives. The case company is called Whetstone Food Ingredients (WFI), located in UK. The company is firmly embedded in the agri‐product industry and operates in the ‘egg by‐product’ subsector. This paper is based upon action research supplemented by a programme of in‐depth interviews with managers at WFI for various aspects of their supply chain and e‐business initiatives. On the basis of these interviews and the companies also made a range of documents available throughout. These included internal memos, strategy plans, operational control documents and minutes of meetings. The Delta Model and Davenport's methodology of business process reengineering were adopted to structure this analysis. Used in conjunction, they helped to develop a vision, analyse the business processes, identify critical business processes, benchmark the critical processes, and then develop the information technology infrastructure. The infrastructure thus supported the critical business processes and leveraged the e‐business supply chain to enable the company to gain competitive edge.
The ERP challenge in China: a resource‐based perspective
Authors: He Xin (James)
Published: April 2004

Abstract.  This paper introduces a resource‐based perspective (RBP) model on enterprise recourse planning (ERP) challenges to help make ERP decisions in China.  While  ERP  aims  at  integrating  functional‐area  information  systems  within  a company into a coherent, enterprise‐wide, and web‐enabled network, its implementation is especially challenging to enterprises in China because of high implementation costs, technical complexity, lack of information technology infrastructure, lack of well‐trained employees, lack of incentives to state‐owned enterprises, and a corporate culture different from that in the West. A RBP of a firm, however, posits that firms should compete on the basis of unique corporate resources that are valuable, rare, difficult to imitate, and unsubstitutable. Thus, this research assesses major ERP challenges in China based upon a three‐tier decision process in pursuit of a sustainable competitive advantage. This RBP model is then embedded with data from a survey research to illustrate potential applications and managerial implications.
Analysis, design, and development model: a case study of an internet‐based system for insert and parameter selection
Authors: Ghahramani Bahador
Published: April 2004

Abstract.  The analysis, design, and development model (ADDM) is based on the systems lifecycle process (SLCP) in which analysts begin to understand external client requirements and internal client specifications as they are designing and developing a complex system. In the ADDM, clients and system analysts (SA) continuously interact as the system is being designed, developed, tested and maintained. In the design phase, system development can be altered when it is most cost‐effective. Depending on the type of environment and SA preference and expertise, various interfaces and software and hardware configurations are created during the SLCP. The SLCP ensures effective standardization and continuous quality improvements throughout development. The model follows modern information technology principles to integrate and monitor SLCP phases. A case is presented that describes an application of the ADDM. This case outlines the architecture of an e‐commerce production system (ECPS). The system has a three‐tier structure consisting of the client interface, Java server page (JSP) and database module. The model assists in designing economic production operations in an industrial setting by allowing a client to retrieve current production data needed for operations through the internet.
Sphingolipid‐free Leishmania are defective in membrane trafficking, differentiation and infectivity
Authors: Denny Paul W. , Goulding David , Ferguson Michael A. J. , Smith Deborah F.
Published: April 2004

Sphingolipids are structural components of the eukaryotic plasma membrane that are involved, together with cholesterol, in the formation of lipid microdomains (rafts). Additionally, sphingolipid metabolites have been shown to modulate a wide variety of cellular events, including differentiation and apoptosis. To investigate the role of de novo sphingolipid biosynthesis in Leishmania, we have focused on serine palmitoyltransferase (SPT), which catalyses the first, rate‐limiting step in the synthetic pathway. Genetic ablation of one SPT subunit, LmLCB2, yields viable null parasites that can no longer synthesize ceramide and sphingolipids de novo. Unexpectedly, LmLCB2 expression (and sphingolipid biosynthesis) is stage regulated in Leishmania, being undetectable in intramacrophage parasites. As expected from this observation, the LmLCB2 null mutants maintain infectivity in vivo. However, they are compromised in their ability to form infective extracellular parasites, correlating with a defect in association of the virulence factor, leishmanolysin or GP63, with lipid rafts during exocytosis and an observed relocalization of a second virulence factor, lipophosphogycan, during differentiation. Thus, de novo sphingolipid biosynthesis is critical for membrane trafficking events in extracellular Leishmania but has at best a minor role in intracellular pathogenesis.