Genetic diversity and antigenic polymorphism in Plasmodium falciparum: extensive serological cross-reactivity between allelic variants of merozoite surface protein 2

Diversity in the surface antigens of malaria parasites is generally assumed to be a mechanism for immune evasion, but there is little direct evidence that this leads to evasion of protective immunity. Here we show that alleles of the highly polymorphic merozoite surface protein 2 (MSP-2) can be grouped (within the known dimorphic families) into distinct serogroups; variants within a serogroup show extensive serological cross-reactivity. Cross-reactive epitopes are immunodominant, and responses to them may be boosted at the expense of responses to novel epitopes (original antigenic sin). The data imply that immune selection explains only some of the diversity in the msp-2 gene and that MSP-2 vaccines may need to include only a subset of the known variants in order to induce pan-reactive antibodies.     

Care-Seeking Behavior for Newborns in Rural Zambia

Maternal and Child Health Journal - Mothers in resource-limited areas face barriers in initiating care for ill newborns, leading to delays that may contribute to newborn mortality. This qualitative...     

Docosahexaenoic acid and vitamin E can reduce human monocytic U937 cell apoptosis induced by tumor necrosis factor

The effects of polyunsaturated fatty acids and vitamin E on tumor necrosis factor (TNF)-induced apoptosis of human monocytic U937 cells was explored to assess to what extent these nutrients could attenuate apoptosis. Preincubation of U937 cells with arachidonic acid for 24 h did not affect TNF-induced apoptosis. Eicosapentaenoic acid slightly but significantly reduced the proportion of apoptotic cells only when apoptosis was induced by TNF without cycloheximide (CHI). In contrast, preincubation with docosahexaenoic acid (DHA) greatly (40 approximately 70%) attenuated apoptosis induced by stimulation with either TNF or TNF + CHI for 3 h. The inhibition of apoptosis was accompanied by enrichment of DHA in membrane phospholipids, indicating that DHA probably exerted its inhibitory activity after being incorporated into the phospholipids. Vitamin E also played a role as a partial inhibitor of apoptosis 3 h after TNF addition. This vitamin could further reduce the apoptosis of DHA-treated cells, and such an additive effect was obvious when apoptosis was induced at a low frequency. Longer-range stimulation of U937 cells with TNF showed that inhibition of apoptosis by preincubating cells with either DHA or vitamin E was not significant 9 h after TNF addition, but that preincubation with both DHA and vitamin E could reduce the proportion of apoptotic cells even at this time point. Our findings suggested that ingestion of nutrients such as DHA and vitamin E might exert beneficial effects on organ dysfunction associated with various TNF-related diseases.     

Normal motor learning during pharmacological prevention of Purkinje cell long-term depression

Systemic delivery of (1R-1-benzo thiophen-5-yl-2[2-diethylamino)-ethoxy] ethanol hydrochloride (T-588) prevented long-term depression (LTD) of the parallel fiber (PF)-Purkinje cell (PC) synapse induced by conjunctive climbing fiber and PF stimulation in vivo. However, similar concentrations of T-588 in the brains of behaving mice and rats affected neither motor learning in the rotorod test nor the learning of motor timing during classical conditioning of the eyeblink reflex. Rats given doses of T-588 that prevented PF-PC LTD were as proficient as controls in learning to adapt the timing of their conditioned eyeblink response to a 150- or 350-ms change in the timing of the paradigm. The experiment indicates that PF-PC LTD under control of the climbing fibers is not required for general motor adaptation or the learning of response timing in two common models of motor learning for which the cerebellum has been implicated. Alternative mechanisms for motor timing and possible functions for LTD in protection from excitotoxicity are discussed.     

Analysis of T cell receptor V(beta) gene expression and clonality in bronchoalveolar fluid lymphocytes from a patient with chronic eosinophilic pneumonitis

Chronic eosinophilic pneumonitis (CEP) is characterized by longstanding respiratory symptoms accompanied by a massive pulmonary eosinophil infiltration. T lymphocytes in bronchoalveolar lavage (BAL) from patients with chronic eosinophilic pneumonitis are considered to recognize unknown antigens. To analyze the pathogenesis of CEP, we examined the T cell receptor (TCR) repertoire and T cell clonotype of BAL lymphocytes and peripheral blood lymphocytes (PBLs) in a 66-year-old woman patient with CEP. The expression of TCR BV gene was analyzed by the family PCR method using specific primers for 20 TCR BV genes and BC gene. The clonotype of BAL and peripheral T cells was examined by the PCR-single-strand conformation polymorphism (SSCP) method. Functional sequences of some T cell clones were also carried out. A TCR repertoire of BAL T cells was heterogeneous as well as PBLs. However, SSCP analysis showed that distinct T cell clonotypes were detected in BAL T cells, TCR BV3, BV4, BV6, BV8, BV9, BV14, and BV18-positive T cell clones especially, expanded clonally in BAL from the patient. Sequencing analysis showed that GVD, LGG, RDXS, and SSG amino acid sequence motif were found in the CDR3 in lung-specific T cells. BAL-specific T cell clones accumulated in the patient with CEP. Thus, we can conclude that BAL T cells are induced by the antigen-driven stimulation and these cells might play a crucial role in the generation of CEP. Accepted for publication: 27 February 2001     

Conventional endometrioid adenocarcinomas of the endometrium recurring as clear cell tumors: comparative immunohistochemical analyses

Endometrial carcinomas are known to have the potential for recurrences that are distinctly discordant at the morphologic and immunophenotypic levels from their antecedent primary tumors. This report describes 3 patients with stage I, low or intermediate grade, conventional endometrioid carcinomas that recurred at the vaginal apex as notably clear cell-rich, higher grade, histotypically ambiguous neoplasms. Comparative immunohistochemical analyses were performed on all cases on both the original and the recurrent tumors using a panel of 8 biomarkers, including estrogen receptor, progesterone receptor, vimentin, p53, p16, hepatocyte nuclear factor 1β, BAF250a (ARID1A), and stathmin or oncoprotein-18 (STMN1). Notable immunophenotypic differences (relative to the original tumor) in case 1 included the relative loss of vimentin and estrogen receptor and the acquisition of p53, p16, and STMN1 expression in the recurrence. In case 2, significant p16 and STMN1 expression were identified only in the recurrence. In case 3, there were no significant immunophenotypic differences between the original tumor and the recurrence. In all 3 cases, the recurrent and original tumors showed no significant differences in BAF250a, hepatocyte nuclear factor 1β, and progesterone receptor expression. In summary, our cases confirm that endometrioid carcinomas can recur as clear cell-rich tumors. The relative acquisition of STMN1 expression in 2 of the 3 recurrences and p53 overexpression in 1 of 3 recurrences suggests that this phenomenon represents a form of tumor evolution, and this may be a potential contributor to tumor progression in these patients.