Predominance of HLA-restricted cytotoxic T-lymphocyte responses to serotype-cross-reactive epitopes on nonstructural proteins following natural secondary dengue virus infection

We examined the memory cytotoxic T-lymphocytic (CTL) responses of peripheral blood mononuclear cells (PBMC) obtained from patients in Thailand 12 months after natural symptomatic secondary dengue virus infection. In all four patients analyzed, CTLs were detected in bulk culture PBMC against nonstructural dengue virus proteins. Numerous CD4+ and CD8+ CTL lines were generated from the bulk cultures of two patients, KPP94-037 and KPP94-024, which were specific for NS1.2a (NS1 and NS2a collectively) and NS3 proteins, respectively. All CTL lines derived from both patients were cross-reactive with other serotypes of dengue virus. The CD8+ NS1.2a-specific lines from patient KPP94-037 were HLA B57 restricted, and the CD8+ NS3-specific lines from patient KPP94-024 were HLA B7 restricted. The CD4+ CTL lines from patient KPP94-037 were HLA DR7 restricted. A majority of the CD8+ CTLs isolated from patient KPP94-024 were found to recognize amino acids 221 to 232 on NS3. These results demonstrate that in Thai patients after symptomatic secondary natural dengue infections, CTLs are mainly directed against nonstructural proteins and are broadly cross-reactive.     

Development of the multidimensional index of life quality. A quality of life measure for cardiovascular disease

OBJECTIVES: The purpose of this study was to design a multidimensional measure of health-related quality of life appropriate for patients with cardiovascular disease that was psychometrically sound, brief, and easy to administer. METHODS: Qualitative interviews conducted with healthy subjects and patients with cardiovascular diseases identified nine major quality of life domains. Based on the responses of 129 cardiovascular disease patients recruited from hospitals and clinics, a criterion-based approach was used to select 35 questionnaire items that best tapped these domains. Psychometric properties of the Multidimensional Index of Life Quality (MILQ) were tested with a sample of 348 patients with various cardiovascular diseases. RESULTS: Cronbach's alpha was 0.76 or higher for eight of the nine MILQ domains. Test-retest reliability coefficients were 0.73 or greater in all but two domains. Individual domain scores as well as a weighted overall quality of life index were correlated highly with self-assessed health and the number of heart-related symptoms. CONCLUSIONS: The Multidimensional Index of Life Quality is a psychometrically reliable and valid instrument for measuring quality of life in patients with cardiovascular diseases. The MILQ also may be a suitable measure for other types of chronic diseases.     

Auditory hallucinations in nonpsychotic children with affective syndromes and migraines: report of 13 cases

This report describes the discovery of a possible association between auditory hallucinations, migraine, and affective/anxiety disorders in nonpsychotic children. The cases were culled by a review of all consultations in an outpatient practice in an 8-month period. Thirteen cases of nonpsychotic children who experienced hallucinations (auditory in 12) were found. All but one suffered from a variety of major affective or anxiety/panic disorders and migraine headaches. The family histories were strongly positive for affective/anxiety disorders and migraine, and four of the parents also had a history of hearing voices. The age of onset of the auditory hallucinations, where known (8 cases), was between 4 and 8 years. In only two cases did the voices accompany the migraine attacks, and these two children also heard voices at other times. Although a strong association between migraine and anxiety, panic, and affective syndromes in adults has been repeatedly found in epidemiologic study, no such association has been studied in children, and this is the first known report of a possible association between migraine, affective/anxiety disorders, and auditory hallucinations in nonpsychotic children. It suggests the need for epidemiologic study.     

Fc epsilon receptor I on dendritic cells delivers IgE-bound multivalent antigens into a cathepsin S-dependent pathway of MHC class II presentation

In this study, we elucidate the Fc epsilon RI-mediated Ag uptake and presentation mechanisms of dendritic cells (DC). We found that Fc epsilon RI-bound IgE, after polyvalent but not after monovalent ligation, is efficiently internalized into acidic, proteolytic compartments, degraded, and delivered into organelles containing MHC class II, HLA-DM, and lysosomal proteins. To follow the fate of the fragmented ligand, we sought to interfere with invariant chain (Ii) degradation, a process critical for peptide loading of nascent MHC class II molecules. We found DC to express cathepsin (Cat) S, a cysteine protease involved in Ii processing by B cells. Exposure of DC to a specific, active-site inhibitor of Cat S resulted in the loss of anti-Cat S immunoreactivity, led to the appearance of an N-terminal Ii remnant, and decreased the export of newly synthesized MHC class II to the DC surface. Furthermore, inactivation of Cat S as well as blockade of protein neosynthesis by cycloheximide strongly reduced IgE/Fc epsilon RI-mediated Ag presentation by DC. Thus, multimeric ligands of Fc epsilon RI, instead of being delivered into a recycling MHC class H pathway, are channeled efficiently into MIIC (MHC class II compartment)-like organelles of DC, in which Cat S-dependent Ii processing and peptide loading of newly synthesized MHC class II molecules occur. This IgE/Fc epsilon RI-dependent signaling pathway in DC may be a particularly effective route for immunization and a promising target for interfering with the early steps of allergen presentation.     

Somatostatin receptor imaging of olfactory neuroblastoma

BACKGROUND: Cure of H. pylori infection in peptic ulcer patients significantly reduces the risk of ulcer recurrence. Since data on the rate of H. pylori reinfection in patients undergoing successful anti-H. pylori therapy are sparse, this study was conducted with the aim of determining the H. pylori reinfection rate in peptic ulcer patients receiving antibacterial treatment to heal their ulcer and cure H. pylori infection. METHODS: A total of 217 patients with H. pylori-associated duodenal or gastric ulcer were followed up after treatment with various antibacterial regimens resulting in histologically documented cure of H. pylori infection. Endoscopic and histological examinations were performed 4 weeks after completion of treatment and after 1, 2 and 5 years, or whenever dyspeptic symptoms occurred. To assess the H. pylori status two antral and two corpus biopsies were obtained for histological examination. RESULTS: Out of 217 patients with initially cured H. pylori infection 175 were available for endoscopic follow-up. At the time of analysis, 44 patients were re-examined after 1 year, 113 patients after 2 years and 18 patients after 5 years, giving a total of 360 patient years of follow-up. The mean duration of follow-up was 24.7 months. H. pylori reinfection was confirmed histologically in eight patients, three of whom becoming H. pylori-positive again within the first year of follow-up. Six of the eight patients with H. pylori reinfection also suffered an ulcer relapse. Eight cases of reinfection in 360 patient years represents an overall reinfection rate of 2.2%. Within the first 2 years of follow-up the reinfection rate was 0.8% per year. CONCLUSION: Our data suggest that H. pylori reinfection is rare in peptic ulcer patients receiving successful anti-H. pylori therapy. H. pylori reinfection frequently coincides with ulcer recurrence. Cure of H. pylori infection results in cure of peptic ulcer disease, provided H. pylori reinfection does not occur.     

Computational study of packing a collagen-like molecule: quasi-hexagonal vs "Smith" collagen microfibril model

The lateral packing of a collagen-like molecule, CH3CO-(Gly-L-Pro-L-Pro)4-NHCH3, has been examined by energy minimization with the ECEPP/3 force field. Two current packing models, the Smith collagen microfibril twisted equilateral pentagonal model and the quasi-hexagonal packing model, have been extensively investigated. In treating the Smith microfibril model, energy minimization was carried out on various conformations including those with the symmetry of equivalent packing, i.e., in which the triple helices were arranged equivalently with respect to each other. Both models are based on the experimental observation of the characteristic axial periodicity, D = 67 nm, of light and dark bands, indicating that, if any superstructure exists, it should consist of five triple helices. The quasi-hexagonal packing structure is found to be energetically more favorable than the Smith microfibril model by as much as 31.2 kcal/mol of five triple helices. This is because the quasi-hexagonal packing geometry provides more nonbonded interaction possibilities between triple helices than does the Smith microfibril geometry. Our results are consistent with recent x-ray studies with synthetic collagen-like molecules and rat tail tendon, in which the data were interpreted as being consistent with either a quasi-hexagonal or a square-triangular structure.