Immunomodulatory Activity of A Novel Nucleoside, 7-thia-8-oxoguanosine: I. Activation of Natural Killer Cells in Mice

We reported recently that a novel immunomodulator, 7-thia-8-oxoguanosine (7T80G)² inhibited formation of pulmonary melanoma metastases (1), prevented against viral infection in mice (2) and potentiated the efficacy of a weakly immunogenic leukemia vaccine (3). Since certain tumor metastases and virus infected cells are targets to natural killer cells (NK cells), we now investigated whether 7T80G is capable of activating NK cells in mice using NK cell sensitive YAC-1 and B16 and NK cell insensitive P815 targets. CBA/CaJ spleen cells incubated in vitro with 7T80G at concentrations ranging from 0.005 to 0.5 mM responded with increased NK cell activity (32-62 %) compared to controls (4-8%) to YAC-1 targets. Similar levels of augmentation in NK cell activity were observed when 40-168 mg/kg of 7T80G was administered in vivo. In addition to the spleen, 7T80G activated NK cells in the bone marrow (BM), the lungs, the liver, and in peritoneal exudate cells (PE). Although 7T80G elicited activation of NK cells was observed as early as three hours after treatment, the maximal activity was observed after 24 h in the spleen; 12 h in the BM; 48 h in the lungs, and 72 h in PE. Administration of the drug by s.c, i.v., and i.p. routes all induced activition of NK cells in spleen, BM and PE. 7T80G was found to activate NK cells in seven inbred and an outbred mouse strain, suggesting that the induced cytotoxicity against allogeneic and syngeneic tumor cells is not strain specific as well as independent of MHC restriction. C3H/He, CBA/CaJ and BDF/1 displayed higher levels of increased NK cell activity, whereas AKR mice were low responders. Low concentrations of IL-2 (0.25-5 U/ml) that induce little or no NK cell activity, when used in combination with 7T80G, elicited significant enhancement of NK cell cytotoxicity. In contrast, IFN and 7T80G showed no such synergism.     

Review of determinants of patients' preferences for adjuvant therapy in cancer.

PURPOSE: Many studies have determined cancer patients' preferences for adjuvant therapy, for example, by asking patients the extent of benefit they would need in order to accept the therapy. However, little is known about the determinants that influence these preferences. Our research goal was to explore which determinants underlie patients' preferences by means of a literature review. METHODS: PubMed searches were conducted to identify studies in which cancer patients' preferences for adjuvant therapy had been elicited by means of a treatment preference instrument. Twenty-three papers were evaluated with regard to reported relationships between preferences and potential determinants. A total of 40 determinants were recorded and classified into one of seven categories: (1) treatment-related determinants, (2) sociodemographic characteristics and current quality of life, (3) clinical characteristics, (4) measurement instrument-related determinants, (5) time-related determinants, (6) cognitive/affective determinants, and (7) specialist-related determinants. Results: The benefit and toxicity of treatment, experience of the treatment, and having dependents (eg, children) living at home were important determinants of patients' preferences. Furthermore, qualitative data suggested that cognitive/affective and specialist-related determinants might have a large impact on patients' treatment preferences. CONCLUSION: Our results show that patients' preferences cannot fully be explained on the basis of treatment-related determinants and patient and clinical characteristics. More research is needed in the area of cognitive/affective and specialist-related determinants because of the lack of quantitative results. Furthermore, we recommend carrying out larger studies in which the (internal) relationships between determinants and preferences are assessed in the context of a cognitive cost-benefit model.     

Pretreatment of bone with osteoclasts affects phenotypic expression of osteoblast-like cells.

Implant surface morphology regulates osteoblast phenotypic expression. Osteoblast sensitivity to non-biologic surfaces suggests that native bone surface features may also affect osteoblast response. To test this, MG63 osteoblast-like cells were grown for 7 days on bovine cortical bone wafers pretreated with rat bone marrow osteoclasts for 0, 10 or 20 days. Response to osteoclast-treated surfaces was compared to the response of MG63 cells to titanium surfaces with smooth and rough microtopographies. Cell number, differentiation (alkaline phosphatase activity and osteocalcin levels), and local factors (PGE(2) and TGF-beta1) were measured in confluent cultures. Compared to culture on plastic, cell number was reduced on all three types of bone wafers; this effect was dose-dependent with increasing resorption of the surface. Alkaline phosphatase specific activity was increased (P相似文献   

Coma arousal procedure: A therapeutic intervention in the treatment of head injury

This study reports on the efficacy of a 'coma arousal procedure'. This procedure involved a programme of vigorous sensory stimulation administered to comatose patients by relatives using Comakits. An experimental group of 12 severely head-injured patients received the coma arousal procedure while a matched control group did not. Total duration of coma and weekly Glasgow Coma Scale Scores were recorded for the two groups. Results indicate that the total duration of coma was significantly shorter and that coma lightened more rapidly for the experimental group.     

Drawing the Boundaries: Exploring gender issues in young children's classifications of work using visual representations

This study examines young children's perceptions of work through a specific example. Reception class children at an inner city school were shown pictures of the same figure washing in four different contexts, ranging from housework to paid employment, in order to examine early classifications and conceptual systems relating to the concept of work and to ascertain whether these were gender related. Individual children varied in the complexity of their ideas, but the majority had not yet began to form hierarchical classifications of work which favour paid employment. There was evidence however that some children were beginning to devalue traditional women's work, suggesting that gender stereotypes are still prevalent amongst this age group, despite efforts by the educational system to counter this.     

Growth modulation of hepatocytes and rat liver epithelial cells (WB-F344) by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)

Modulation of DNA synthesis by 2,3,7,8-tetrachlorodi-benzo-p-dioxin(TCDD) was studied in primary cultures of hepatocytes and inrat liver epithelial cells (WB-F344) to develop models for studieson the interactions between the activated Ah receptor and cellulargrowth control. In hepatocytes TCDD either positively or negativelymodulated EGF-stimulated DNA synthesis. In the presence of ethlnylestradiol10^–12 M TCDD moderately increased EGF-stimulated DNA synthyesis(