Summary Glucose and insulin are generally considered to express opposite effects on insulin synthesis and secretion from pancreatic islets. For the most part this generalization has arisen from short-term experiments. Our studies focused on the chronic, long-term effects of variable insulin concentrations on insulin gene expression and secretion in cultures of HIT-T15 cells. From passage 70, HIT cells were split and passed weekly for 25 weeks in media containing either (A) 11.1 mmol/l glucose with no insulin added; (B) 11.1 mmol/l glucose with insulin added to maintain a level of approximately 4,000 U/ml; (C) 0.8 mmol/l glucose with no insulin added; (D) 0.8 mmol/l glucose with insulin added to maintain a level of approximately 4,000 U/ml; and (E) 0.8 mmol/l glucose with progressively less insulin added over time to mimic the gradual decrease in media insulin levels found in condition A. Our data indicate that during chronic passing of HIT cells, addition of exogenous insulin led to preserved levels of insulin mRNA, insulin content and insulin secretion in cells cultured in media containing 11.1 mmol/l glucose concentration. However, in media containing 0.8 mmol/l glucose concentration, addition of insulin diminished the levels of insulin mRNA, insulin content and insulin secretion. Nonetheless, in all cases exogenously added insulin sustained greater levels of insulin mRNA, insulin content and insulin secretion than the instance wherein media containing a high concentration of glucose only was used. These results indicate that short-term experiments assessing the effects of insulin on beta-cell function do not necessarily apply to chronic, more long-term experiments in which insulin can have variable time- and concentration-dependent effects on insulin gene expression and secretion.Abbreviations HIT
Hamster insulin-secreting tumour 相似文献
We previously described assay systems for generating antigen specific proliferating T cells to P. chabaudi antigens. In the present study we examine whether the various sensitization approaches confer immunity against a cloned virulent strain IP-PCI of P. chabaudi. We present data indicating that effective specific protective immunity can be induced through P. chabaudi antigen fed macrophages and antigen educated spleen cells (initiator lymphocytes). The expression of this protective immunity is proposed to depend on (a) antigen presentation and/or accessory function of macrophages and (b) the subsequent activation of T cell functions related to protection. Indeed analysis of different macrophage populations revealed a correlation between the expression of Ia molecules and IL-1 secretion with their capacity to induce antigen specific T cells in vivo and subsequent protective immune mechanisms. Thus these results emphasize the critical functions of accessory cells in determining the outcome of malaria infections. 相似文献
MicroRNAs (miRNAs) are postulated to be important regulators in cancers. Here, we report a genome-wide miRNA expression analysis in 52 acute myeloid leukemia (AML) samples with common translocations, including t(8;21)/AML1(RUNX1)-ETO(RUNX1T1), inv(16)/CBFB-MYH11, t(15;17)/PML-RARA, and MLL rearrangements. Distinct miRNA expression patterns were observed for t(15;17), MLL rearrangements, and core-binding factor (CBF) AMLs including both t(8;21) and inv(16) samples. Expression signatures of a minimum of two (i.e., miR-126/126*), three (i.e., miR-224, miR-368, and miR-382), and seven (miR-17-5p and miR-20a, plus the aforementioned five) miRNAs could accurately discriminate CBF, t(15;17), and MLL-rearrangement AMLs, respectively, from each other. We further showed that the elevated expression of miR-126/126* in CBF AMLs was associated with promoter demethylation but not with amplification or mutation of the genomic locus. Our gain- and loss-of-function experiments showed that miR-126/126* inhibited apoptosis and increased the viability of AML cells and enhanced the colony-forming ability of mouse normal bone marrow progenitor cells alone and particularly, in cooperation with AML1-ETO, likely through targeting Polo-like kinase 2 (PLK2), a tumor suppressor. Our results demonstrate that specific alterations in miRNA expression distinguish AMLs with common translocations and imply that the deregulation of specific miRNAs may play a role in the development of leukemia with these associated genetic rearrangements. 相似文献
Fibroblast growth factor (FGF), a key regulatory factor of cell growth and differentiation, is involved in embryonic development,
angiogenesis, and tumorigenesis. To date, four different FGF receptors (FGFRs) have been cloned and characterized. We examined
the expression of four FGFRs in human gastric cancer tissues and cell lines using Northern analysis, ribonuclease protection
assay, and immunohistochemistry. The mRNAs of FGFR-1 (10/14), FGFR-2 (9/14), and FGFR-4 (9/14) were up-regulated in cancer
compared with normal tissues. FGFR-3 mRNAs were barely detectable in both normal and cancer tissues. These FGFR mRNAs were
co-expressed in various combinations of two or three in the same tissue. Immunohistochemistry confirmed specific staining
of multiple FGFRs, except FGFR-3, in the cancer specimens. To investigate the functional significance of FGFR co-expression
we examined the invasive property of SNU-16 cells, which exhibited gene amplification of FGFR-2, -3, and -4 as well as over-expression
of keratinocyte growth factor receptor (KGFR), a splice variant of FGFR-2, and FGFR-4 mRNA. KGF plus acidic FGF (aFGF), KGF,
and aFGF treatment enhanced the invasive potential of SNU-16 cells over the control by 100%, 107%, and 47%, respectively,
indicating that neither additive nor synergistic effect was induced by stimulation with aFGF plus KGF. These results suggest
that co-expression of FGFRs in various combinations may cause subtle changes in the progression of gastric cancer.
Received: 16 February 1999 / Accepted: 6 March 2000 相似文献
The silent beta-thalassemia mutation, beta(+)-101C-->T, is the only mutation currently described in the distal beta-globin CACCC box. We present a novel mutation, a C-->G transversion, in the same position. Expression analysis in heterozygous subjects demonstrated that the mutation determines a 20% reduction in the output of the beta-globin gene. DNA-protein interaction and transactivation analysis correlated the decrease in the beta-globin synthesis with the reduced binding and transactivation of EKLF to the mutant promoter. These data predict that the beta-101C-->G mutation will display a silent thalassemia phenotype similar to that of the beta-101C-->T mutation. 相似文献
Introduction. Flat/constricted affect and anhedonia are symptoms found in several psychiatric disorders such as depression and schizophrenia. However, there are very few studies on the relationships between specific anhedonia subtypes and objectively assessed flat affect, and it appears that none of the existing studies examined potential moderation by sex.
Methods. Forty-seven undergraduate students (60% male) completed self-report questionnaires assessing three subtypes of anhedonia – non-social consummatory (CON) and anticipatory (ANT) anhedonia, and overall social anhedonia. Participants viewed 15 pictures (5 neutral and 10 negative) from the International Affective Picture System, whereas facial muscle reaction was recorded using electromyography (EMG).
Results. Male participants reporting a greater level of overall social or non-social CON anhedonia showed a greater EMG activity increase in the corrugator supercilii muscle to negative (vs. neutral) pictures. In females, the relationship was only found with social anhedonia and was opposite in direction, as increased social anhedonia related to less EMG activity change in the corrugator muscle.
Conclusions. The relationship between anhedonia and flat affect varied as a function of sex and anhedonia subtype. These findings may help explain discrepancies in the sparse existing literature examining this relationship in psychiatric populations and have implications for assessment and treatment of these symptoms across psychiatric disorders. 相似文献
Only one published study has investigated the effect of a threatening social context on the perception and expression of pain, showing that social threat leads to increased pain reports but reduced nonverbal pain expression. The current study aimed to replicate and extend these findings to further explore the effects of a threatening social context. Healthy, female participants (N?=?71) received 10 electrocutaneous stimuli delivered by a confederate. They were led to believe that the confederate was requested to administer 10 painful stimuli (control group) or that the confederate deliberately chose to deliver 10 painful stimuli when given the choice to deliver between 1 to 10 painful stimuli (social threat group). Self-reported pain intensity, unpleasantness, threat value of pain, and painful facial expression were assessed. Additionally, empathy and aggression toward the confederate were investigated. Social threat did not affect painful facial expression or self-reported pain intensity, but led to increased aggression toward the confederate. Moreover, perceived social threat predicted the threat value of pain and reduced empathy toward the confederate. We were not able to replicate the previously reported dissociation between pain reports and pain expression as a result of social threat. However, social threat was associated with an increased threat value of pain, increased aggression, and reduced empathy.
Perspective
A threatening social context affects how threatening pain is perceived and has interpersonal consequences such as increased aggression and reduced empathy, thereby creating a double burden on the individual suffering from pain. 相似文献
Hadrontherapy is an advanced form of radiotherapy that uses beams of charged particles (such as protons and carbon ions). Compared with conventional radiotherapy, the main advantages of carbon ion therapy are the precise absorbed dose localization, along with an increased relative biological effectiveness (RBE). This high ballistic accuracy of particle beams deposits the maximal dose to the tumor, while damage to the surrounding healthy tissue is limited. Currently, hadrontherapy is being used for the treatment of specific types of cancer. Previous in vitro studies have shown that, under certain circumstances, exposure to charged particles may inhibit cell motility and migration. In the present study, we investigated the expression of four motility-related genes in prostate (PC3) and colon (Caco-2) cancer cell lines after exposure to different radiation types. Cells were irradiated with various absorbed doses (0, 0.5 and 2 Gy) of accelerated 13C-ions at the GANIL facility (Caen, France) or with X-rays. Clonogenic assays were performed to determine the RBE. RT-qPCR analysis showed dose- and time-dependent changes in the expression of CCDC88A, FN1, MYH9 and ROCK1 in both cell lines. However, whereas in PC3 cells the response to carbon ion irradiation was enhanced compared with X-irradiation, the effect was the opposite in Caco-2 cells, indicating cell-type–specific responses to the different radiation types. 相似文献