It is unclear why immunological control of HIV replication is incomplete in most infected individuals. We examined here the CD8+ T cell response to HIV-infected CD4+ T cells in rare patients with immunological control of HIV. Although high frequencies of HIV-specific CD8+ T cells were present in nonprogressors and progressors, only those of nonprogressors maintained a high proliferative capacity. This proliferation was coupled to increases in perforin expression. These results indicated that nonprogressors were differentiated by increased proliferative capacity of HIV-specific CD8+ T cells linked to enhanced effector function. In addition, the relative absence of these functions in progressors may represent a mechanism by which HIV avoids immunological control.
A unique cohort of HIV-1-infected long term nonprogressors (LTNP) with normal CD4 ؉ T cell counts and <50 copies͞ml of plasma were prospectively recruited for study. HLA typing revealed a dramatic association between the HLA B*5701 class I allele and nonprogressive infection [85% (11 of 13) vs. 9.5% (19 of 200) in progressors; P < 0.001]. Antigen-specific CD8 ؉ T cells were enumerated by flow cytometric detection of intracellular IFN-␥ in response to HIV antigens and HLA B*57-gag tetramer staining. No quantitative differences in the total HIV-specific CD8 ؉ T cell responses were observed between B*57 ؉ LTNP and five B*57 ؉ progressors (P ؍ 0.4). Although similar frequencies of peptide specific CD8 ؉ T cells were also found, the gag-specific CD8 ؉ T cell response in the LTNP group was highly focused on peptides previously shown to be B*57-restricted. These findings indicate that, within this phenotypically and genotypically distinct cohort, a host immune factor is highly associated with restriction of virus replication and nonprogressive disease. They also strongly suggest a mechanism of virus specific immunity that directly operates through the B*5701 molecule. Further characterization of qualitative differences in the virus-specific responses that distinguish HLA B*57 ؉ LTNP from progressors may ultimately define mechanisms of effective immune mediated restriction of virus replication.
The virus-specific CD8+ T cell responses of 21 HIV-infected patients were studied including a unique cohort of long-term nonprogressors with low levels of plasma viral RNA and strong proliferative responses to HIV Ags. HIV-specific CD8+ T cell responses were studied by a combination of standard cytotoxic T cell (CTL) assays, MHC tetramers, and TCR repertoire analysis. The frequencies of CD8+ T cells specific to the majority of HIV gene products were measured by flow cytometric detection of intracellular IFN-γ in response to HIV-vaccinia recombinant-infected autologous B cells. Very high frequencies (0.8–18.0%) of circulating CD8+ T cells were found to be HIV specific. High frequencies of HIV-specific CD8+ T cells were not limited to long-tern nonprogressors with restriction of plasma virus. No correlation was found between the frequency of HIV-specific CD8+ T cells and levels of plasma viremia. In each case, the vast majority of cells (up to 17.2%) responded to gag-pol. Repertoire analysis showed these large numbers of Ag-specific cells were scattered throughout the repertoire and in the majority of cases not contained within large monoclonal expansions. These data demonstrate that high numbers of HIV-specific CD8+ T cells exist even in patients with high-level viremia and progressive disease. Further, they suggest that other qualitative parameters of the CD8+ T cell response may differentiate some patients with very low levels of plasma virus and nonprogressive disease.
Background/AimsGastroesophageal reflux disease (GERD) is common in children. Recurrent exposure to gastric acid in GERD may contribute to tooth erosion.MethodsIn this prospective study, 54 GERD patients qualified according to endoscopy, pH-metry, and the GERD questionnaire and 58 healthy controls qualified by the GERD questionnaire were assessed. Two groups underwent dental evaluations for the presence, severity, and patterns of erosion and for the stage of dentition using a Tooth Wear Index. The health care providers who performed the dental exams did not know which children had been diagnosed with GERD.ResultsA total of 112 children, 3 to 12 years old were enrolled in the study, and 53 of 54 (98.1%) GERD patients and 11 of 58 (19.0%) controls had dental erosions (p<0.0001). In GERD patients, the posterior occlusal surfaces of milk teeth were more affected (p<0.0001). There was no correlation between GERD and the affected surfaces in permanent teeth, nor in the patterns or erosion grades (localized or general). In both groups, milk teeth had more erosions than permanent teeth, but the difference was not statistically significant.ConclusionsAccording to this study, there is a positive correlation between GERD and dental erosion. Posterior occlusal surface erosions in milk teeth could indicate GERD.
Johanson-Blizzard syndrome is a rare autosomal recessive disorder, characterized by exocrine pancreatic deficiency and a wide range of other abnormalities. We present here an infant with failure to thrive, exocrine pancreatic deficiency, short stature and developmental delay, cutis aplasia on the scalp, aplasia of alae nasi, hypospadias, hypothyroidism, myxomatous mitral valve, and patent ductus arteriosus. Molecular studies revealed a novel homozygous nonsense mutation in exon 38 of the UBR1 gene, which confirmed the diagnosis of Johanson-Blizzard syndrome. It should be acknowledged that the combination of exocrine pancreatic insufficiency and nasal wing hypo-aplasia is pathognomonic for this syndrome. Prompt diagnosis and exact monitoring of the patients with JBS are required to avoid further complications.
The results of this study suggest that biliary dyskinesia should be considered as part of the spectrum of symptomatic gallbladder disease that can be successfully treated with cholecystectomy and that biliary dyskinesia is associated with GERD and gastritis.
Calcified catheter "cast" found on radiologic studies after central venous catheter removal is a rare complication that has been reported twice. Both cases were associated with thrombus. In this case report, we present a 15-year-old boy with acute lymphoblastic leukemia who demonstrated on CT scan a radiopacity in his left brachiocephalic vein after removal of an implanted venous access device. This was initially thought to be a retained catheter fragment. Diagnostic studies, including venogram, excluded the presence of a retained catheter fragment. Additional procedures to retrieve a nonexistent catheter fragment were thus avoided. Therefore, a catheter "cast" should be considered as part of the differential diagnosis when calcification is found on an imaging study after removal of an implantable venous access device to prevent an unwarranted surgical exploration.
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