Prevention of travelers' diarrhea by the tablet formulation of bismuth subsalicylate

Within 48 hours of arrival in Mexico, 182 US students participated in a study to compare the efficacy of two dosages of bismuth subsalicylate (262 mg per tablet) as a prophylactic agent against diarrhea. The students were randomly assigned to receive two tablets (high dose) or one tablet (low dose) of bismuth subsalicylate four times daily or a placebo four times daily during a three-week period. Among these completing the trial, diarrhea (four or more unformed stools in 24 hours or three in eight hours, plus one other symptom) occurred in seven (14%) of 51 receiving the high-dose regimen compared with 15 (24%) of 63 receiving the low-dose regimen and 23 (40%) of 58 in the placebo group. Protection rates were 65% for high-dose and 40% for low-dose bismuth subsalicylate. Diarrhea caused by enterotoxigenic Escherichia coli was found in one student receiving the high-dose regimen, in no students receiving the low-dose regimen, and in seven placebo-treated subjects. Bismuth subsalicylate was well tolerated; the most common side effects were blackening of tongues and stools. Bismuth subsalicylate use in both dosages was associated with tinnitus at a low, clinically insignificant frequency of 1.2 days per 100 days of treatment. The dosage of two tablets of bismuth subsalicylate four times daily (2.1 g/d) appears to be a safe and effective means of reducing the occurrence of travelers' diarrhea among persons at risk for periods up to three weeks.     

基于反向滤波器的倒谱法估计平均骨小梁间距

目的 探讨用改进的倒谱方法估计平均骨小梁间距(mean trabecular bone spacing,MTBS)的可行性.方法 提出了一种基于反向滤波器的改进的倒谱分析方法用于估计MTBS,并将该方法应用于仿真及离体牛胫骨松质骨中的实验信号.结果 改进的倒谱方法能有效减少超声换能器脉冲响应和组织散射特性对倒谱的干扰,而且实现简单,计算量小.结论 相比于传统的倒谱方法,改进的倒谱方法在估计MTBS时, 对弥散散射和噪声有更强的鲁棒性,因此估计MTBS的精度更高.     

Production of multiple cytokines by cultured human melanomas*

Abstract We screened a panel of 8 primary and 21 metastatic melanoma cell lines for constitutive secretion of cytokines. Melanomas expressed bioactivity for TGF-β (8/25 lines) and IFN (7/12), but not IL-2. Immu-noassays detected IL-1α (4/25), IL-1β (12/25), 1L-6 (13/29), IL-8 (29/ 29), TGF-β₂, (5/12) and GM-CSF (11 /29). but not IL-3, IL-4, TNF-α, or IFN-γ. There was no preferential association of cytokine production with cells cultured from primary versus metastatic disease, and only IL-8 was produced by all lines tested. These data demonstrate that cultured melanomas produce a variety of cytokines which are potentially capable of influencing tumor growth in vivo.     

CTLA-4 is required for the induction of high dose oral tolerance

Mucosal and systemic administrations of high dose antigens induce long- lasting peripheral T cell tolerance. We and others have shown that high dose peripheral T cell tolerance is mediated by anergy or deletion and is preceded by T cell activation. Co-stimulatory molecules B7-1 (CD80)/B7-2 (CD86) and their counter-receptors CD28/CTLA-4 play pivotal roles in T cell activation and immune regulation. In the present study, we examined the roles of the B7 co-stimulation pathway in the generation of high dose peripheral T cell tolerance. We found that blocking B7:CD28/CTLA-4 interaction at the time of tolerance induction partially prevented T cell tolerance, whereas selective blockade of B7:CTLA-4 interaction completely abrogated peripheral T cell tolerance induced by either oral or i.p. antigens. These results suggest that CTLA-4-mediated feedback regulation plays a crucial role in the induction of high dose peripheral T cell tolerance.      

Molecular genetic characterization of XRCC4 function

XRCC4 is a generally expressed protein of 334 amino acids that is involved in the repair of DNA double-strand breaks and in V(D)J recombination, but its function is unknown. In this study, we have used a mutational approach and the yeast two-hybrid method to perform an initial characterization of this protein. We show that the XRCC4 protein is located in the nucleus. We also demonstrate that several potential phosphorylation sites are not required for XRCC4 function in a transient V(D)J recombination assay. In addition, we show that XRCC4 forms a homodimer in vivo with the homodimerization domain being located within amino acids 115-204. Finally, we define a core domain of XRCC4 that functions in V(D)J recombination and comprises amino acids 18-204. Potential functions of XRCC4 are discussed.      

CD8<Superscript>+</Superscript>, HLA-unrestricted,cytotoxic T-lymphocyte line against malignant melanoma

A CD8⁺ cytotoxic T lymphocyte (CTL) line was derived from the peripheral blood mononuclear cells of a patient with primary melanoma. The CD8⁺ CTL line specifically lysed the autologous primary melanoma cells and not the natural killer cell-sensitive K562 cells or lymphokine activated killer cell-sensitive DAUDI cells. When a large panel of human leukocyte antigen (HLA)-matched and -unmatched allogeneic melanoma, glioma, breast and colorectal carcinoma cells was tested as targets in cytolysis assays, 4 HLA-matched and two HLA-unmatched allogeneic metastatic melanoma lines were lysed by the CD8⁺ CTL. Lysis of autologous and allogeneic melanoma cells was dependent on the effector-to-target cell ratio. Lysis of autologous melanoma cells was not blocked by anti-HLA class I or class II antibodies, confirming that the cytolytic activity of the CD8⁺ CTL was HLA-unrestricted. CTL lysis of autologous melanoma cells was CD3 (T cell receptor) dependent and FAS-FAS-L, and CD1 independent. Identification of the melanoma-associated antigen recognized by the HLA-unrestricted CTL may provide a vaccine for a broad population of melanoma patients.