Human platelets exert cytotoxic effects on tumor cells

Monocytes are thought to play a role in host resistance to tumor cell growth in animals and humans. In addition, platelets are known to be involved in tumor metastases. To investigate the interaction of these two cell types and their effect on tumor cells, human monocytes and platelets were examined using an in vitro monocyte-tumor cell cytotoxicity assay. Monocytes alone resulted in 32% +/- 1.5 (mean +/- SEM) tumor cell kill. When platelets were added to monocytes in a 1:1 ratio, an increase in cytotoxicity to 61% +/- 3.2 was observed. The cytotoxicity noted when platelets were added to a fixed number of monocytes and tumor cells was dependent on the number of platelets added. A decrease in cytotoxicity from 32% +/- 1.5 to 12% +/- 2.3 was observed when contaminating platelets were removed from monocyte preparations. Platelets added to tumor cells in the absence of any monocytes were also toxic, resulting in a maximum kill of 95% at a 4:1 platelet/tumor cell ratio. Secreted products of freshly isolated platelets may be responsible for much of the observed cytotoxicity, since supernatants from the platelets were toxic for tumor cells. Platelets pretreated with a cyclooxygenase inhibitor (ASA) or a lipoxygenase inhibitor had decreased cytotoxicity compared with untreated platelets. Our results indicate that products of platelet arachidonate metabolism are toxic for tumor cell lines. They also suggest that the role of the platelet must be considered when studying monocyte-tumor cell cytotoxicity.     

Mouse strain variability in the expression of the hematopoietic stem cell antigen Ly-6A/E by bone marrow cells

The cell surface molecule Ly-6A/E provides a convenient marker for primitive stem cells in the hematopoietic tissues of both fetal and adult mice. However, previous studies have shown that Ly-6A/E expression by lymphocytes is variable depending on the haplotype of the Ly-6 locus. Therefore, strain-specific variation in Ly-6A/E expression by bone marrow (BM) cells was investigated. The results show that Ly-6a mice have, on average, 50% of the number of BM cells expressing Ly-6A/E relative to that for Ly-6b mice. Furthermore, among the 5% of BM cells that do not express antigens characteristic of mature T, B, myeloid, or erythroid lineages, which include the primitive hematopoietic stem cell compartment, Ly-6a mice have, on average, more than fivefold fewer Ly- 6A/E+ cells relative to that for Ly-6b mice. Isolation of Ly-6A/E- and Ly-6A/E+ cells from mice of both haplotypes showed that, whereas 99% of the marrow repopulating activity (MRA) of C57BL/Ka (Ly-6b) mice could be recovered in the Ly-6A/E+ fraction, only about 25% of the MRA of BALB/c (Ly-6a) was recoverable in the same population. On a per-cell basis, the Ly-6A/E+ cells that were isolated from BALB/c mice were essentially equivalent in MRA to those isolated from C57BL/Ka mice. Thus, whereas a large percentage of the hematopoietic stem cells of Ly- 6a mice do not express the Ly-6A/E molecule, the antigen may be used to isolate a subset of stem cells from these mice. These results show that hematopoietic stem cell phenotype can vary between mouse strains and imply that caution should be exercised in the identification of human stem cell antigens such as CD34, because a similar variability may occur between individual humans. To further explore the influence of Ly- 6 haplotype on Ly-6A/E expression by specific cell subsets, lymph-node lymphocytes from a panel of mouse strains were analyzed by multiparameter flow cytometry for correlated expression of Ly-6A/E, CD4, and CD8. All Ly-6a strains examined had less than 20% Ly-6A/E+ cells, and those cells were predominantly CD8+ T lymphocytes. In contrast, the Ly-6b strains had greater than 30% Ly-6A/E+ cells, and those cells included CD4+, CD8+, and B lymphocytes.     

Transient leukemoid proliferation of the cytogenetically unbalanced +21 cell line of a constitutional mosaic boy

A newborn without any signs of Down's syndrome was found to have an acute proliferation that remitted without drug therapy. Chromosomal analysis of blood, bone marrow, and skin cells revealed that the child was a constitutional mosaic with normal cells and a low number of cells in which one no. 21 chromosome was replaced by a probably isochromosome for the no. 21 long arm: 46,XY/46,XY,i(21q). The abnormal cell line of the mosaic appeared to be selectively involved in this proliferation.     

Extracellular truncations of h beta c, the common signaling subunit for interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-5, lead to ligand-independent activation

The hypothesis that extracellular truncation of the common receptor subunit for interleukin-3 (IL-3), granulocyte-macrophage colony- stimulating factor, and IL-5 (h beta c) can lead to ligand-independent activation was tested by infecting factor-dependent hematopoietic cell lines with retroviruses encoding truncated forms of h beta c. A truncation, resembling that in v-Mpl, and retaining 45 h beta c-derived extracellular residues, led to constitutive activation in the murine myeloid cell line, FDC-P1. However, infection of cells with retrovirus encoding a more severely truncated receptor, retaining only 7 h beta c- derived extracellular residues, did not confer factor independence on these cells. These experiments show that truncation activates the receptor and define a 37-amino acid segment of h beta c (H395-A431) which contains two motifs conserved throughout the cytokine receptor superfamily (consensus Y/H XX R/Q VR and WSXWS), as essential for factor-independent signaling. The mechanism of activation was also investigated in less severe truncations. A receptor that retains the entire membrane-proximal domain (domain 4) also conferred factor independent growth on FDC-P1 cells; however, a retrovirus encoding a truncated form of h beta c having two intact membrane proximal domains did not have this ability, suggesting that domain 3 may have an inhibitory role in h beta c. The ability of these receptors to confer factor independence was cell specific as demonstrated by their inability to confer factor-independent growth when introduced into the murine IL-3-dependent pro-B cell line BaF-B03. These results are consistent with a model in which activation requires unmasking of an interactive receptor surface in domain 4 and association with a myeloid- specific receptor or accessory component. We suggest that in the absence of ligand intramolecular interactions prevent inappropriate signaling.     

注射用双黄连与几种抗生素联合体外抑菌活性的研究

目的：探讨注射用双黄连与抗生素联合使用的临床意义。方法：参考中国药典抗生素微生物检定法，测定注射用双黄连与头孢拉定等６种抗生素配伍使用后对金葡菌及克雷白氏肺炎杆菌的抑菌圈直径的变化。结果：注射用双黄连与氨苄青霉素、普鲁卡因青霉素、头孢唑啉钠及红霉素配伍后对金葡萄的体外抑菌效果明显增强；与头孢拉定、头孢唑啉钠及普鲁卡因青霉素配伍后对克氏肺炎杆菌的体外抑菌效果有不同程度的增强。结论：对于不同的细菌感染     

Mortality and failure among tuberculosis patients who did not complete treatment in Vietnam: a cohort study

Background  

Tuberculosis treatment failure and death rates are low in the Western Pacific Region, including Vietnam. However, failure or death may also occur among patients who did not complete treatment, i.e. reported as default or transfer-out. We aimed to assess the proportion failures and deaths among new smear-positive pulmonary tuberculosis patients with reported default or transfer-out.     

鼓槌石斛中一新的联苄类化合物——鼓槌石斛素

从兰科鼓槌石斛(Dendrobium chrysotoxum)中分得一新的联苄类化合物,经光谱分析(UV,IR,MS,¹HNMR,¹³CNMR和DIFNOE),其结构确定为4-羟基-3,5,3',4'-四甲氧基联苄,命名为鼓槌石斛素。关键词鼓槌石斛;鼓槌石斛素;联苄类化合物。     

Modulation of noradrenaline release from the sympathetic nerves of human right atrial appendages by presynaptic EP3- and DP-receptors

Strips of human right atrial appendages were preincubated with [³H]noradrenaline and then superfused with physiological salt solution containing inhibitors of uptake₁ and uptake₂. Tritium overflow was evoked by transmural electrical stimulation (standard frequency: 2 Hz). Prostaglandin E₂ (PGE₂) inhibited the electrically evoked tritium overflow; at the highest concentration investigated, tritium overflow was reduced by about 80% and the pIC_50% value was 7.14. The effect of PGE₂ was not affected by rauwolscine, which, by itself, increased the evoked overflow. Naproxen failed to affect the evoked tritium overflow and its inhibition by PGE₂. The inhibitory effect of PGE₂ on the electrically evoked tritium overflow was mimicked by prostaglandin E₁, the EP₁/EP₃-receptor agonist sulprostone and the EP₂/EP₃-receptor agonist misoprostol with the rank order of potency (pEC_50%): sulprostone (7.68) > misoprostol (7.10) > PGE₁ (6.39). In contrast, PGF_2α, the IP/EP₁-receptor agonist iloprost and the stable thromboxane A₂ analogue U46619 (9,11-dideoxy-11α,9α-epoxy-methanoprostaglandin F_2α) did not change evoked tritium overflow. PGD₂ caused facilitation. These results suggest that the sympathetic nerve fibres innervating human atrial appendages are endowed with presynaptic inhibitory EP₃ and facilitatory DP-receptors. The EP₃-receptors appear not to be tonically activated and do not interact with the α₂-autoreceptors. Received: 11 May 1998 / Accepted: 29 July 1998