Pre-B cells and other possible precursor lymphoid cell lines derived from patients with X-linked agammaglobulinemia

A group of unique Epstein-Barr virus-containing cell lines was derived from the bone marrow of three patients with X-linked agammaglobulinemia. Efforts to obtain cell lines from the peripheral blood of these patients were uniformly unsuccessful. Immunofluorescence analyses as well as biosynthetic studies with [(35)S]methionine indicated unusual patterns of Ig synthesis in many of these bone marrow derived lines. Seven of the lines were of particular interest in that two produced no Ig of any type; two others showed no Ig by fluorescence but small amounts by [(35)S]methionine labeling; one expressed only cytoplasmic μ chains without any evidence of light chain synthesis, and two produced primarily μ chains with only slight amounts of light chains. One of the lines without membrane or cytoplasmic Ig studied in detail grew like a typical lymphoid line and was carried in intermittent culture over a period of 2 yr without Ig expression. One line grew quite differently and resembled the round cell type described previously, which has been obtained from a variety of sources. The cell line with cytoplasmic μ chains and no light-chain expression had the characteristic properties of pre-B cells. Three normal type Ig-producing cell lines also were obtained from the patients. The accumulated evidence obtained in the present study indicates that these unusual cell lines represent normal precursor cells of the B-cell lineage; these grew out in these cases because of the virtual absence of mature B cells that ordinarily overgrow the culture system. However, the possibility that in certain instances they reflect abnormal Ig synthesis characteristic of the disease has not been ruled out.     

Effect of influenza virus vaccine on the expression of human immunodeficiency virus co-receptor CCR5.

BACKGROUND: Administration of influenza vaccine to human immunodeficiency virus (HIV)-infected children can lead to increased viral load. CCR5 and CXCR4 are known to play an important role in HIV cell entry and viral replication. OBJECTIVE: To determine the effects of influenza vaccine on chemokine receptors and on viral load in HIV-infected children. METHODS: Eight HIV-infected children receiving stable therapy and 11 healthy adults were enrolled. Chemokine expression and immune activation were determined before and 48 hours after influenza vaccination. CCR5 and beta-chemokine gene expression were analyzed using real-time polymerase chain reaction. Viral load was measured at baseline, 48 hours, and 6 to 12 weeks. RESULTS: Forty-eight hours after influenza vaccination, mean CCR5 expression was significantly decreased on the CD3 (21.1% vs 11.3% in HIV-infected children; P = .02; and 18.3% vs 10.7% in controls; P = .008) and CD4 (13.0% vs 3.6% in the HIV group; P = .04; and 13.6% vs 6.5% in controls; P = .02) lymphocytes. This was observed in conjunction with an increase in HLA-DR expression on T lymphocytes in HIV-infected children (P = .046). No significant changes were observed in HIV viral load, CD3 and CD8 lymphocyte counts, expression of interleukin 2 receptor and CXCR4, or gene expression of CCR5 and beta-chemokines 48 hours after vaccination. CONCLUSIONS: Influenza virus vaccine markedly decreased chemokine receptor CCR5 expression on CD4 T lymphocytes. However, this immunomodulatory effect does not seem to affect overall viral replication in HIV-infected children who received highly active antiretroviral therapy.     

The relationship between performance monitoring, satisfaction with life, and positive personality traits

Neural reflections of performance monitoring, including the error-related negativity (ERN) component of the event-related potential (ERP), are modulated by personality and affective constructs. Little is known, however, about the relationship between positive personality traits and neural indices of performance monitoring. We investigated the relationship between measures of positive personality traits, including satisfaction with life, dispositional optimism, and positive affect, and indices of performance monitoring in a sample of 45 neurologically-healthy individuals. Increased satisfaction with life was associated with decreased (i.e., less negative) ERN amplitude. Dispositional optimism and positive affect were not related to ERN amplitude. Results remained consistent when negative affect and measures of positive personality were accounted for using multiple regression. There were no relationships between measures of positive personality and the post-error positivity (Pe) or behavioral indices. Findings are consistent with an affective salience interpretation of the ERN, with errors potentially being less meaningful for individuals with higher satisfaction with life.     

Characterization of the antibody response against Plasmodium falciparum erythrocyte membrane protein 1 in human volunteers

The immune response against the Plasmodium falciparum variant surface antigen P. falciparum erythrocyte membrane protein 1 (PfEMP1) is a key component of clinical immunity against falciparum malaria. In this study, we used sera from human volunteers who had been infected with the P. falciparum 3D7 strain to investigate the development, specificity, and dynamics of anti-PfEMP1 antibodies measured against six different strain 3D7 Duffy binding-like domain 1α (DBL1α) fusion proteins. We observed that a parasitemia of 20 to 200 infected erythrocytes per μl was required to trigger an antibody response to DBL1α and that antibodies against one DBL1α variant cross-react with other DBL1α variants. Both serum and purified immunoglobulin Gs (IgGs) were able to agglutinate infected erythrocytes, and purified anti-DBL1α IgGs bound to the live infected red blood cell surface in a punctate surface pattern, confirming that the IgGs recognize native PfEMP1. Analysis of sera from tourists naturally infected with P. falciparum suggests that the anti-PfEMP1 antibodies often persisted for more than 100 days after a single infection. These results help to further our understanding of the development of acquired immunity to P. falciparum infections.     

Context- but not familiarity-dependent forms of object recognition are impaired following excitotoxic hippocampal lesions in rats

Dual-process models of recognition memory in animals propose that recognition memory is supported by two independent processes that reflect the operation of distinct brain structures: a familiarity process that operates independently of the hippocampus and a context-dependent (episodic) memory process that is dependent on the hippocampus. A novel variant of an object recognition procedure was used to examine this proposal. Healthy rats showed a preference for exploring a novel object rather than a familiar object: a familiarity-dependent recognition effect. They also showed a preference for exploring a familiar object that was presented in a different spatiotemporal context rather than a familiar object that was presented either in a different spatial or temporal context: a context-dependent form of recognition that is sensitive to "what" object has been presented "where" and "when." Rats with excitotoxic hippocampal lesions showed the familiarity-dependent but not the context-dependent form of recognition. The results provide support for dual-process theories of recognition memory.     

Double dissociation of function within the hippocampus: a comparison of dorsal, ventral, and complete hippocampal cytotoxic lesions

Rats with complete cytotoxic hippocampal lesions exhibited spatial memory impairments in both the water maze and elevated T maze. They were hyperactive in photocell cages; swam faster in the water maze; and were less efficient on a nonspatial, differential reinforcement of low rates (DRL) task. Performance on both spatial tasks was also impaired by selective dorsal but not ventral lesions; swim speed was increased by ventral but not dorsal lesions. Both partial lesions caused a comparable reduction in DRL efficiency, although these effects were smaller than those of complete lesions. Neither partial lesion induced hyperactivity when rats were tested in photocell cages, although both complete and ventral lesion groups showed increased activity after footshock in other studies (Richmond et al., 1999). These results demonstrate possible functional dissociations along the septotemporal axis of the hippocampus.     

Targeted alpha-radionuclide therapy of functionally critically located gliomas with 213Bi-DOTA-[Thi8,Met(O2)11]-substance P: a pilot trial

Purpose  

Functionally critically located gliomas represent a challenging subgroup of intrinsic brain neoplasms. Standard therapeutic recommendations often cannot be applied, because radical treatment and preservation of neurological function are contrary goals. The successful targeting of gliomas with locally injected beta radiation-emitting ⁹⁰Y-DOTAGA-substance P has been shown previously. However, in critically located tumours, the mean tissue range of 5 mm of ⁹⁰Y may seriously damage adjacent brain areas. In contrast, the alpha radiation-emitting radionuclide ²¹³Bi with a mean tissue range of 81 μm may have a more favourable toxicity profile. Therefore, we evaluated locally injected ²¹³Bi-DOTA-substance P in patients with critically located gliomas as the primary therapeutic modality.     

Innate immunity and its role against infections.

LEARNING OBJECTIVES: This article reviews current concepts of the innate immune system that offers protection against infections. It offers an overview for the readers to understand how innate immunity, consisting of different receptors, cells, and mediators recognizes pathogens and exerts protective function against pathogens. DATA SOURCES AND STUDY SELECTION: MEDLINE-search articles including original research papers, review articles, textbooks, and references identified from bibliographies of relevant articles. RESULTS AND CONCLUSIONS: The innate immune system is nonspecific immunity present since birth not requiring repeated exposure to pathogens. It is capable of differentiation between self and nonself. Because of its nonspecificity, it has a broad spectrum of resistance to infection. Further, it is thought to play an important role in the control of adaptive immunity by regulating co-stimulatory molecules and effector cytokines. Innate immunity includes pattern recognition molecules/receptors, antimicrobial peptides, the complement system, inflammatory mediators, and cytokines produced by immune cells. Pattern recognition molecules/receptors recognize pathogen-associated molecular patterns that are essential for microorganisms' survival and pathogenicity. Although innate immunity has recently gained increasing importance, further studies are necessary for a better understanding of its role.