bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis and Immunological Activity of a Branched Peptide Carrying the T‐cell Epitope of gp43, the Major Exocellular Antigen of Paracoccidioides brasiliensis
Authors: Taborda C. P. , Nakaie C. R. , Cilli E. M. , Rodrigues E. G. , Silva L. S. , Franco M. F. , Travassos L. R. 
Published: January 2004

AbstractThe 43 kDa glycoprotein (gp43) of Paracoccidioides brasiliensis is the major diagnostic antigen of paracoccidioidomycosis (PCM), a prevalent fungal infection in South America. A 15‐mer sequence from gp43, denominated P10, induced T‐CD4+ T helper 1 cellular immune responses in mice of three different haplotypes and protected against intratracheal challenge by a virulent isolate of P. brasiliensis. In an attempt to improve delivery of P10, a promiscuous antigen also presented by human leucocyte antigen‐DR alleles, aiming at immunotherapy, we synthesized a multiple antigen peptide with the protective T‐cell epitope expressed in a tetravalent 13‐mer analog of P10 (M10). M10 induced specific lymph node cell proliferation in mice preimmunized with peptides in complete Freund's adjuvant (CFA). In addition, M10 immunization without CFA significantly protected intratracheally infected mice. We conclude that M10 is a candidate for an anti‐PCM vaccine. In this report we describe: (1) the synthesis of M10; (2) the induction of M10‐elicited T‐cell response and (3) in vivo protection of mice immunized with M10 and challenged by a virulent strain of P. brasiliensis.
The Effects of Interferon‐α2a on Concentrations of Immunoglobulins, Complement and Lymphocytes in Patients with Multiple Sclerosis
Authors: Ulvestad E. , Aarseth J. H. , Vedeler C. , Nyland H. , Myhr K.‐M. 
Published: January 2004

AbstractMultiple sclerosis (MS) patients treated with type I interferon experience reduced disease activity. Because immunoglobulins (Igs), complement and lymphocytes have been given a role in the pathogenesis of MS, we investigated the longitudinal effect of interferon‐α2a (IFNA) on the variability of these parameters. Patients were treated for 6 months with 4.5 million international units (MIU) IFNA (24 patients), 9.0 MIU IFNA (21 patients) or placebo (23 patients). IFNA induced a significant increase in concentrations of total IgG and IgG subclasses 1, 3 and 4. At 6 months, the mean concentration of IgG had increased by 1.51 g/l (CI: 0.82, 2.21) in the 9.0 MIU IFNA group. There was no significant effect of IFNA treatment on concentrations of IgG2 and IgA, while the effect on IgM was borderline significant. After 6 months, IgM had increased by 0.29 g/l (CI: −0.01, 0.65) in the 9.0 MIU IFNA group. IFNA induced a significant increase in the concentration of C1 inhibitor (INH). At 3 months, the mean concentration of C1 INH had increased by 0.033 g/l (CI: 0.01, 0.05). At 3 months, C4 had increased by 0.05 g/l (CI: 0.01, 0.09) in the 9.0 MIU IFNA group. The effect of IFNA on C4 was inconclusive but indicates an effect during the initial phase of the treatment. C3 showed no significant treatment‐mediated change. IFNA induced a significant decrease in lymphocyte concentrations by 0.56 × 106 lymphocytes/ml (CI: −0.81, −0.31) at 3 months. There were no significant associations between changes in immune parameters and changes in clinical and magnetic resonance imaging scores. The results verify that IFNA modulates and activates both the innate and the adaptive arms of the immune system. The observations should be of relevance when evaluating mechanisms of action of IFN treatment in MS.
The four mouse IgG isotypes differ extensively in bactericidal and opsonophagocytic activity when reacting with the P1.16 epitope on the outer membrane PorA protein of Neisseria meningitidis
Authors: Michaelsen T. E. , Kolberg J. , Aase A. , Herstad T. K. , Høiby E. A. 
Published: January 2004

AbstractMouse monoclonal antibodies (MoAbs) of the four IgG isotypes, all specific for the P1.16 epitope on the meningcoccal PorA protein, were tested for functional activities. The avidities of the antibodies, measured by NH4SCN elution in enzyme‐linked immunosorbent assay, showed similar values for all the MoAbs. The serum bactericidal activity (SBA) defined as the lowest concentration of antibodies giving 50% reduction in the number of meningococcal colony‐forming units using human serum as complement, showed a hierarchy of IgG3 >> IgG2b > IgG2a >> IgG1. For the opsonophagocytosis (OP), the hierarchy was IgG3 > IgG2b = IgG2a >> IgG1. OP was measured in flow cytometry using log‐phase live meningococci as target cells, normal human peripheral blood polymorphonuclear cells (PMNs) as effector cells and human serum as a complement source. The mouse MoAbs were negative in OP when using human PMNs in the absence of complement. The results demonstrate the importance of choosing the right isotype of mouse MoAbs when using them to judge the potential vaccine importance of their corresponding antigen. If such MoAbs should be used for passive vaccination against infectious diseases, the isotype would presumably play an important role for their anticipated clinical effects.
Low Number of H‐2Dd‐Negative Haematopoietic Cells in Mixed Bone Marrow Chimeras Convey In Vivo Tolerance to H‐2Dd‐Negative Cells But Fail to Prevent Resistance to H‐2Dd‐Negative Leukaemia
Authors: Johansson M. H. , Höglund P. 
Published: January 2004

AbstractNatural killer (NK) cells kill cells lacking self major histocompatibility complex (MHC) class I. This missing self reactivity is beneficial in haploidentical bone marrow transplantations to cure leukaemia, in which donor‐derived NK cells reject MHC disparate leukaemia cells and prevent relapse. To understand the role of NK cells in transplantation, we have studied NK cell tolerance in mice receiving mixed bone marrow transplants with limiting number of the MHC disparate component. Using an MHC class I (Dd) transgenic mouse model, we generated bone marrow chimeras carrying mixtures of Dd‐positive and ‐negative cells. NK reactivity against Dd‐negative cells (missing self) was assayed by outgrowth of lymphoma cells, stability of the chimerism in vivo and killing of Concanavalin A blasts in vitro. Up to 20% Dd‐negative haematopoietic cells reduced, but did not abrogate, rejection of Dd‐negative tumours and killing of Dd‐negative T‐cell blasts. In contrast, the ratios between Dd‐positive and ‐negative cells were stable in vivo, suggesting tolerance to normal cells. Our data suggest that NK cell tolerance to normal cells and tumours in mixed MHC environments is differentially regulated, tolerance to normal cells being more easily induced. These results are important in relation to the role of NK cells in antileukaemic reactions after bone marrow transplantation.
Limited Magnitude and Breadth in the HLA‐A2‐Restricted CD8 T‐Cell Response to Nef in Children with Vertically Acquired HIV‐1 Infection
Authors: Chandwani R. , Jordan K. A. , Shacklett B. L. , Papasavvas E. , Montaner L. J. , Rosenberg M. G. , Nixon D. F. , Sandberg J. K. 
Published: January 2004

AbstractCD8 T cells are believed to play a key role in the immune control of human immunodeficiency virus‐1 (HIV‐1) infection in children as well as in adults. We have used an enhanced EliSpot (AmpliSpot) assay to quantitate CD8 T‐cell responses directed to five human leucocyte antigen (HLA)‐A2‐presented HIV‐1 epitopes derived from the key viral antigen Nef. Responses were assayed in one group of 21 children with vertically acquired HIV infection and one group of 19 adult subjects with chronic infection. The paediatric group displayed significantly weaker and more narrowly focused CD8 T‐cell responses as compared with the adult subjects. Two epitopes stood out as the most frequently and strongly recognized, suggesting that they should be considered immunodominant in the CD8 T‐cell response to HIV‐1 Nef. Interestingly, the most frequently and strongly recognized epitope in both adults and children was previously identified in HLA‐A2‐transgenic mice, demonstrating the usefulness of such mice in finding natural viral epitopes. These findings indicate significant weakness in strength and breadth of the CD8 T‐cell response to the target protein Nef in infected children and prompt renewed efforts into the immunology of vertically acquired HIV‐1 infection.
Uninvestigated dyspepsia and non‐ulcer dyspepsia—the use of endoscopy and the roles of Helicobacter pylori eradication and antisecretory therapy
Authors: Chey W. D. , Moayyedi P. 
Published: January 2004

SummaryDue to its prevalence, impact on quality‐of‐life and the associated significant health resource utilization, dyspepsia is a major healthcare concern. The available management strategies for uninvestigated dyspepsia include prompt endoscopy, the ‘test‐and‐treat’ strategy for Helicobacter pylori, and empiric antisecretory therapy. There is consensus that endoscopy should be reserved for patients with alarm features (e.g. symptom onset after 45 years of age, recurrent vomiting, weight loss, dysphagia, evidence of bleeding, anaemia), H. pylori‐positive individuals who fail test‐and‐treat, and those with an inadequate response to empiric antisecretory therapy. Factors influencing the decision between test‐and‐treat and empiric antisecretory therapy in uninvestigated dyspepsia include the local prevalence of H. pylori and peptic ulcer disease and the proportion of ulcers attributable to H. pylori. For uninvestigated dyspepsia in patients without alarm features, test‐and‐treat is the preferred initial management method in Europe based on the relatively high prevalence of H. pylori/peptic ulcer disease whereas empiric antisecretory therapy is preferred in many parts of the United States, where the prevalence of H. pylori/peptic ulcer disease is relatively low. In patients with non‐ulcer dyspepsia, H. pylori eradication and empiric antisecretory therapy result in comparable and small, but statistically significant, improvements in dyspepsia. Empiric antisecretory therapy is the preferred initial method of managing non‐ulcer dyspepsia in Europe and the US. The test‐and‐treat approach would receive increased enthusiasm if H. pylori cure is shown to prevent development of gastric cancer in non‐ulcer dyspepsia patients in a large Western trial.
Should NSAID/low‐dose aspirin takers be tested routinely for H. pylori infection and treated if positive? Implications for primary risk of ulcer and ulcer relapse after initial healing
Authors: Hunt R. H. , Bazzoli F. 
Published: January 2004

Summary Helicobacter pylori infection and the use of nonsteroidal anti‐inflammatory drugs (NSAIDs) can each result in gastric or duodenal ulcer(s) and ulcer complications. Together, H. pylori infection and NSAIDs account for approximately 90% of peptic ulcer disease. In 2003, the results of studies suggest, and guidelines recommend, the careful selection of anti‐inflammatory drugs – NSAIDs or selective COX‐2 inhibitors (coxibs) based upon patients gastrointestinal history and use of aspirin therapy. Testing for, and cure of, H. pylori infection is recommended in patients prior to the initiation of NSAID therapy and in those who are currently receiving NSAIDs and have a history of dyspepsia, peptic ulcer or ulcer complications. For patients who present with peptic ulcer bleeding but require NSAIDs long‐term, H. pylori eradication therapy should be considered, followed by continuous proton pump inhibitor prophylaxis to prevent re‐bleeding, regardless of which kind of NSAID (nonselective NSAID /coxib) is being prescribed. Routine testing for, and eradication of, H. pylori infection has not been recommended for current takers of NSAIDs with no or low risk of complications. The management of patients taking low‐dose aspirin is complex, but eradication of H. pylori infection alone in those with a past history of bleeding does not guarantee complete protection and therefore a proton pump inhibitor should also be given. The success of eradication therapy should always be confirmed, because of the risk of ulcer recurrence and bleeding in H. pylori‐infected patients who require anti‐inflammatory treatments.
Impact of Helicobacter pylori on society—role for a strategy of ‘search and eradicate’
Authors: Forman D. , Graham D. Y. 
Published: January 2004

Summary Helicobacter pylori infection is causally related to gastric cancer, a malignancy associated with high morbidity and poor prognosis, and to peptic ulcer disease, a disease with high morbidity and modest mortality. Theoretically, H. pylori eradication is the most practical means of preventing gastric cancer and peptic ulcer disease. From a public policy perspective, the current evidence is insufficient to assess accurately the magnitude of the benefits of a universal ‘search and treat’ approach. Nonetheless, it is possible to identify high‐risk patients for whom testing for the presence of H. pylori infection, with the intention‐to‐treat infected individuals is currently indicated. This list includes patients with ulcers or dyspepsia, first‐degree relatives of patients with peptic ulcer or gastric cancer, gastric cancer patients after potentially curative resection of their gastric cancer, patients in whom long‐term acid antisecretory therapy or long‐term nonsteroidal anti‐inflammatory drug therapy (including low‐dose aspirin) is planned, and finally those who desire testing. Population screening among asymptomatic individuals with a high risk of gastric cancer, such as Korean‐ and Japanese‐Americans, appears logical, but from a public health perspective should be done as a component of controlled intervention studies. There are no known H. pylori infections without risk of a symptomatic outcome, therefore screening represents a rational strategy for cancer prevention. Adoption of such a policy will require carefully balancing the costs of the programme with its benefits.
Epidemiology and management of gastro‐oesophageal reflux in children
Authors: Gold B. D. 
Published: January 2004

SummaryThe management of gastro‐oesophageal reflux disease (GERD) continues to garner vast amounts of attention among physicians who care for adults. However, there is an increasing awareness of the fact that this disease, as well as several other lifelong digestive diseases (i.e. Crohn's disease) may actually have their origins in childhood. Paediatric gastro‐oesophageal reflux (GER) is likely to share a similar pathophysiology to adult GER, and mounting evidence from published preliminary data suggests a genetic susceptibility to GERD. However, further studies will be necessary to confirm this hypothesis. In children, GER has a distinct presentation from that in adults, with the diagnostic work‐up based upon the patient's age as well as their presenting signs and symptoms. Like their adult counterparts, the early detection and treatment of GER in children may result in a better long‐term outcome, improved quality‐of‐life, and a reduction in overall healthcare burden. While the treatment of GER in infants tends to be conservative (i.e. positioning during feeding, smaller feedings), its management in older children parallels that of adults and includes lifestyle changes and pharmacological therapy. However, with persistent symptoms, acid suppression is the mainstay of GERD management in both children and adults. Several studies in children have verified that acid suppression with a proton pump inhibitor is superior to histamine‐2 receptor antagonists. Among the proton pump inhibitors, both lansoprazole and omeprazole have been the subject of published adult and paediatric studies demonstrating their short and long‐term safety, in addition to their efficacy in a variety of oesophageal and supra‐oesophageal GERD related conditions. These two proton pump inhibitors are manufactured as capsules containing enteric‐coated granules that can be emptied into soft foods or liquids without compromising their pharmacological effects or pharmacokinetic properties. Lansoprazole is also available as a strawberry‐flavoured suspension that is acceptable to children and as an oral disintegrating tablet.
Approaches to endoscopic‐negative reflux disease: part of the GERD spectrum or a unique acid‐related disorder?
Authors: Tack J. , Fass R. 
Published: January 2004

SummaryEndoscopic‐negative reflux disease (ENRD) is the most common presentation of gastro‐oesophageal reflux disease (GERD)—affecting up to 70% of these individuals. In the last three decades therapeutic studies have focused solely on the treatment of patients with erosive oesophagitis. However, more recent studies have shifted our attention to defining, understanding and treating those with ENRD. GERD has traditionally been approached as a spectrum with ENRD at the mild end and complicated GERD (i.e. patients with erosive oesophagitis, stricture and Barrett's oesophagus) being at the other end, suggesting that patients' disease may progress over time along the spectrum. Current data indicate that ENRD should be approached as a unique entity rather than a part of the GERD spectrum and that over time only a few patients with ENRD will develop GERD‐related complications. Patients with ENRD are a heterogenous group of patients with different aetiologies for their heartburn symptoms, including motor events, reflux of acidic or nonacidic gastric contents, minute changes in intraesophageal pH (pH < 4), mucosal hypersensitivity, and emotional or psychological abnormalities. By dropping the spectrum concept, which emphasizes oesophageal mucosal injury, we can focus our attention on the specific mechanisms that lead to symptom generation in each of the three unique groups of GERD (ENRD, erosive oesophagitis and Barrett's oesophagus) and on the specific therapeutic modalities that benefit each of these individual groups. Acid suppressive therapy with proton pump inhibitors is highly effective in healing erosions and controlling symptoms in those with erosive oesophagitis. In those with ENRD the resolution or control of heartburn with proton pump inhibitor therapy is greater than that with placebo or H2 receptor antagonist, but not as consistent nor as impressive as the results observed in studies of patients with erosive oesophagitis. By considering the mechanisms involved in ENRD symptom generation, future studies that include high‐dose proton pump inhibitors, promotility agents (alone or in combination with proton pump inhibitors), transient lower oesophageal sphincter reducers, or pain modulators (e.g. tricyclic antidepressant agents) may prove beneficial.
Supra‐oesophageal manifestations of gastro‐oesophageal reflux disease
Authors: Malagelada J. R. 
Published: January 2004

SummarySupra‐oesophageal manifestations of gastro‐oesophageal reflux disease (GERD) are common and often under‐appreciated, in part due to the absence of classic symptoms of heartburn and regurgitation. Patients with supra‐oesophageal manifestations of GERD may report symptoms involving the pulmonary, otolaryngologic or pharyngeal systems. Endoscopy is often negative and therefore of limited diagnostic value in these patients, and while laryngoscopy and 24 h dual‐channel intra‐oesophageal pH‐metry may have greater yields they are costly, invasive and time‐consuming. Therefore, a trial of proton pump inhibitor therapy is now widely considered a first‐line diagnostic test in those with suspected GERD‐induced supra‐oesophageal symptoms. The dose as well as duration of the proton pump inhibitor trial is dependent upon a patient's presenting symptoms. For example, GERD‐related non‐cardiac chest pain may be relieved with a short‐term (e.g. 1 week) treatment with standard doses of a proton pump inhibitor. The use of high‐dose twice daily proton pump inhibitor therapy for an extended period (e.g. 2–3 months) may be required before any discernible improvement in pulmonary symptoms or pharyngo‐laryngitis is noted. Patients who do not experience symptom improvement following a proton pump inhibitor trial may require further diagnostic evaluations including 24 h oesophageal pH studies, while on acid anti‐secretory therapy, to establish the absence of persistent acid reflux. The role of anti‐reflux surgical or endoscopic interventions in those with supra‐oesophageal manifestations of GERD remains to be established.
Approaches to the long‐term management of adults with GERD—proton pump inhibitor therapy, laparoscopic fundoplication or endoscopic therapy?
Authors: Freston J. W. , Triadafilopoulos G. 
Published: January 2004

SummaryThe goals of gastro‐oesophageal reflux disease (GERD) treatment are to control symptoms, heal the injured oesophageal mucosa, and prevent complications. Pharmacological therapy is effective in producing acute symptom relief and mucosal healing, as well as the long‐term maintenance of remission. Proton pump inhibitors are the mainstay of GERD therapy. However, the need for daily administration, failure to provide complete symptom relief and costs of these agents may limit their use in some patients, prompting a consideration of alternative treatment strategies. Laparoscopic fundoplication may achieve symptom relief and healing of the oesophagitis in these individuals, but its invasiveness, cost and inherent surgical risks have created an interest in endoscopic therapies for GERD, with several emerging during the past few years. These interventions may either be viewed as an alternative therapy or as ‘bridge’ therapy, with patients still choosing to be treated with acid anti‐secretory drugs or fundoplication if the endoscopic procedure fails to provide adequate symptom relief or if symptoms recur. Patient selection is critical for the success of fundoplication as well as endoscopic procedures, with ideal candidates being those with well‐established endoscopically documented GERD, abnormal pH monitoring, normal oesophageal motility studies, and who have experienced at least partial symptom relief with proton pump inhibitor therapy. Hiatal hernia is not a contra‐indication to fundoplication, while endoscopic intervention is best suited for those with a hiatal hernia of less than 3 cm in length. The long‐term efficacy, cost‐effectiveness, and impact of endoscopic procedures on extra‐oesophageal manifestations of GERD and risk for GERD‐related complications has not been determined.
Screening and surveillance of Barrett's oesophagus: what is a cost‐effective framework?
Authors: Spechler S. J. , Barr H. 
Published: January 2004

SummaryThere is a strong association between symptomatic gastro‐oesophageal reflux and oesophageal adenocarcinoma. With this in mind, the American College of Gastroenterology has recently revised its practice guidelines for the screening of patients with chronic gastro‐oesophageal reflux disease (GERD) to identify those at risk of oesophageal adenocarcinoma, and recommends surveillance to identify curable oesophageal neoplasms in patients with established Barrett's oesophagus. Patients  with chronic GERD symptoms, particularly those aged over 50 years, should undergo upper endoscopy. Patients  found to have Barrett's oesophagus should be treated with acid suppression for GERD symptoms and then undergo regular surveillance endoscopy. Surveillance endoscopy every 3 years is recommended for those without dysplasia. For patients with verified low‐grade dysplasia, yearly surveillance endoscopy is recommended. For those with focal high‐grade dysplasia (defined as high‐grade dysplastic changes involving fewer than five crypts), the condition may be followed with endoscopic surveillance performed at 3‐month intervals. If there is verified, multifocal high‐grade dysplasia, intervention (e.g. oesophagectomy) may be considered. Both observational and computer models suggest a benefit associated with screening and surveillance. Endoscopic screening and surveillance for Barrett's oesophagus compares favourably with mammography for the detection of breast cancer and other accepted medical practices.