Biological signals最新文献

Accumulated evidence has suggested that anion secretion in the epididymis may be subject to local paracrine/autocrine control in addition to neural and humoral regulation. The present paper reviews recent studies presenting evidence for the presence of major components of a tissue renin-angiotensin system in the rat epididymis and the regulatory effect of angiotensin II (Ang II) on epididymal anion secretion. The mechanisms for local generation of Ang II and its local action are discussed. The importance of paracrine/autocrine roles of Ang II in the maintenance of epididymal functions, as well as sperm functions is also addressed.

This work was undertaken to analyze the interrelationships between prolactin and cyclosporine in affecting immune responsiveness in submaxillary lymph nodes. Male rats received an anterior pituitary graft within breast muscles on day 5, or under the kidney capsule, on day 30 or 60 of life. On day 70 (rats operated on day 5 or 30) or on day 100 (rats operated on day 60) animals were injected with Freund's complete adjuvant and cyclosporine (5 mg/kg for 5 days), and were killed 2 days after immunization. Natural killer (NK) activity in submaxillary lymph node decreased in neonatally pituitary-grafted rats and increased in rats grafted on day 30 or 60, as did lymph node cellularity. Lipopolysaccharide (LPS)- and concanavalin A (ConA)-induced proliferation diminished in lymph nodes of rats grafted on day 30 or 60, respectively. Cyclosporine treatment diminished lymph node cell number and NK activity and increased the proliferative response to ConA. Cyclosporine depressive effect on lymph node cellularity was counteracted by the presence of a pituitary graft, as were the inhibition of NK activity and the stimulatory effect on ConA-induced cell proliferation. In pituitary-grafted rats, cyclosporine decreased submaxillary lymph node LPS-induced proliferation. Cyclosporine decreased the high circulating prolactin levels found in pituitary-grafted rats. The results are compatible with age-dependent, inhibitory and promoting activities of hyperprolactinemia on immune responses in lymph nodes, affected in a complex antagonistic and synergistic way by cyclosporine immunosuppression.

Many genes belonging to the cyclin-dependent kinase (cdk) family have been isolated from protozoans. While their role in cell cycle has yet to be proven unequivocally, at least one cdk can complement the cdc2ts/cdc28ts mutants in yeasts. Among the interesting questions relating to cdks in protozoa are: whether one cdk acts throughout the whole cell cycle and whether cyclin partnership is absolutely required. In protozoa, cell cycle control is closely associated with developmental control. Many life cycle differentiation phases can only occur during a specific window in the cell cycle. Because of different DNA biosynthetic pathways, some protozoa among the earliest eukaryotic lineages are unresponsive to common inhibitors of DNA synthesis like hydroxyurea. However, many protozoa do have different checkpoint controls in relation to their response to cell cycle inhibitors.

The present work seeks to verify if there is a difference in the number of somatostatin neurons in the cortex between normal aging versus Alzheimer patients and secondly if any of these neurons are dying via apoptosis. In our specimens, immuno-histochemistry revealed that there was no difference in the number of somatostatin neurons between the two study groups. Moreover, of the apoptotic cells that were found using the terminal dUTP nick end labeling (TUNEL) method, none contained somatostatin. It is concluded that while there is apoptotic cell death in normal aging and Alzheimer's disease, it does not seem to occur in neurons which contain somatostatin in any significant amount.

The carapace characteristics of horseshoe crabs (Limulus polyphemus) have been correlated by others with male mating performance and it has also been suggested that such mating differences might depend on visual differences. The effect of carapace character on horseshoe crab vision was therefore noninvasively investigated using the electroretinogram (ERG) of the lateral compound eye as a measure. Male Limulus were dichotomized on three carapace dimensions: clear versus dark eyes, light versus dark carapaces, and presence versus absence of barnacles. All dichotomizations gave similar results: No crab was ERG-blind. Analyses based on ERG magnitude yielded trivial sensitivity differences between these groups. However, analyses based on ERG latency indicated that response speeds exhibited reliably different trends between groups: Although responses to dim flashes were similar for all animals, increasing flash intensity produced significantly greater changes in the latencies of the ERGs in uniform males than in variegated males. This interactive dependence of ERG speed differences on flash energy cannot be the result of greater light absorption by the variegated specimens' darkened corneas. The visual capacities of variegated specimens are therefore somewhat altered, but certainly not absent. Equalizing animal size between groups did not measurably affect these results, implying that age was not a factor. The previously reported correlation of an individual male's appearance with its performance in mating competitions is extended by these data to include its sensory functioning as well.

The influence of melatonin on diurnal changes in the hematological profile was investigated in male albino rats. Following treatment with melatonin, under two different experimental protocols, blood samples were collected at 06.00, 12.00, 18.00 and 24.00 h from separate groups of animals for detailed hematological analysis. In experiment 1, melatonin (25 micrograms, s.c.) treatment, once daily at 17.00 h for 4 weeks, led to an alteration in the rhythm of RBC production with a decrease in its counts at 12.00 h. The total WBC counts were increased at 06.00 and 12.00 h and decreased at 18.00 and 24.00 h. In experiment 2, twice-daily administration of melatonin (once at 09.00 h and again at 17.00 h), for 2 weeks, resulted in a decrease in total RBC counts at 06.00 and 24.00 h, whereas at 18.00 h there was an increase, compared to the respective control values. The total WBC counts increased at 06.00, 12.00 and 18.00 h and decreased at 24.00 h. Erythrocyte indices like mean cell volume (MCV), mean cell hemoglobin (MCH) and mean cell hemoglobin concentration (MCHC), in both experiments, correlated with RBC, hemoglobin and hematocrit values. The WBC differential counts in experiment 1 revealed a decrease in total neutrophils at 24.00 h, whereas in experiment 2 there was a general decrease in their number. While in experiment 1 the total lymphocyte number was increased at 06.00 h and decreased at 18.00 and 24.00 h, in experiment 2 it was increased except at 24.00 h. It may be concluded that melatonin has a modulatory role in hemopoiesis and its rhythms. The stimulatory effect of melatonin on WBC supports its purported immunopotentiating action.

Fluorescence microscopic imaging (FMI) is one of the fastest growing and most powerful techniques to study cellular activities in a living single cell. FMI has been widely used to monitor the temporal and spatial changes of many important intracellular messengers such as Ca2+, H+ and cAMP. In the course of our study of cellular responses with confocal scanning fluorescence microscopy, we detected two sources of artifacts which may render experimental observations invalid. First, the water content of the DMSO used could affect the efficiency of loading of the fluorescence indicator into cells and also give rise to spurious fluorescence spots. Secondly, apparently spontaneous temperature-dependent oscillations of BCECF fluorescence and cellular pulsations were recorded in cells which might be misinterpreted as natural rhythmic behavior. These were later shown to be artifacts arising from changes in refractive indices of the immersion oil due to small fluctuations in temperature, which in turn leads to random shifts of the focal plane erroneously manifest as signal oscillations. Based on these observations, certain recommendations for the control and elimination of false images are presented.

Oxidatively modified low-density lipoprotein has been identified in early atherosclerotic lesions and may play an important role in atherogenesis. Minimally modified low-density lipoprotein (MM-LDL) derived by prolonged storage under sterile conditions results in mild oxidation and is recognised by the LDL receptor rather than the scavenger receptor. Therefore, it may be closer to the real pathophysiological circumstances in the initial state of atherosclerosis. Using a reverse transcription-polymerase chain reaction (RT-PCR) technique, the present study demonstrates that MM-LDL is capable of inducing gene expression of both interleukin-1 alpha (IL-1 alpha) and interleuking-1 beta (IL-1 beta) in human peripheral blood mononuclear cells in a dose-dependent manner. Concomitant treatment of the cells with the anti-oxidant probucol results in an inhibitory effect in steady-state levels of both IL-1 alpha and IL-1 beta mRNA and the effects were also shown in a dose-dependent fashion. We also found an inhibitory effect of MM-LDL on gene expression of platelet-derived growth factor B chain (PDGF-B) mRNA levels by mononuclear cells. Hence MM-LDL is biologically active and may contribute to the early stages of atherogenesis by stimulating the inflammatory cytokine IL-1 and the efficacy of probucol in inhibiting the progression of atherosclerosis may be due, both to its inhibition of IL-1 expression by intimal macrophages, and its prevention of LDL oxidation.

The conversion of adrenaline to aminochromes by the human erythrocyte plasma membranes at pH 9.5 was shown to be a complex reaction that proceeded at least by two distinct phases. The first one, corresponding to the formation of adrenochrome, is catalyzed in the presence of the membranes, suggesting the involvement of an enzyme-mediated process. Active oxygen species were identified as intermediates during this phase. Oxygen radical scavengers (catalase and superoxide dismutase) suggested H2O2 and O2- involvement. Adrenochrome formation was stimulated by NADH indicating the participation of another enzyme (NADH dehydrogenase) which is known to be present in the human erythrocyte plasma membrane. The second phase, corresponding to the disappearance of adrenochrome, is also stimulated by NADH and inhibited in the presence of the membranes. In this reaction, adrenochrome is converted to aminochromes via adrenochrome semiquinone. The formation of radical species is demonstrated by EPR spectroscopy. The results led to the proposal of a mechanism for the formation of adrenochrome and other oxidation products from adrenaline.

In the past several years, significant progress in many aspects of pulmonary fibrosis research has been made. Among them, the finding that a variety of cytokines play important roles in the complex process appears most intriguing. These cytokines include at least transforming growth factor-beta (TGF-beta), tumor necrosis factor-alpha (TNF-alpha), platelet-derived growth factor, fibroblast growth factors, (TGF-alpha), interleukin-1, monocyte chemoattractant protein-1 and macrophage inflammatory protein-1 alpha. These cytokines have been demonstrated to be produced at the sites of active fibrosis where they appear to be expressed by activated inflammatory cells, such as macrophages and eosinophils. More interestingly, other noninflammatory lung cells including mesenchymal cells, such as myofibroblasts, and epithelial cells, have been found to be significant sources as well, albeit in most instances at somewhat different time points than those by inflammatory cells. Study of the individual cytokines in vitro has revealed a variety of potential roles for these cytokines in the regulation of the fibrotic process in vivo, including chemoattractant, mitogenic activities for fibroblasts, stimulation of extracellular matrix and alpha-smooth muscle actin gene expression, alteration of the contractile phenotype of fibroblasts and regulation of diverse functions of lung inflammatory and epithelial cells which can further impact on the fibrotic process by autocrine and paracrine mechanisms. Of these cytokines, it appears that TGF-beta is probably the most important cytokine in terms of the direct stimulation of lung matrix expression which typifies fibrosis. Recently however, there is accumulating evidence to indicate that the situation is much more complex than any one single cytokine being solely responsible for the fibrotic response. The concept of complex lung cytokine networks, orchestrated by a few key cytokines, such as TNF-alpha, being responsible for this response has received strong support from recent studies. This means that it is the balance of positive (profibrogenic) and negative (antifibrogenic) forces generated from interaction among the various cytokines constituting these networks, which may finally determine the outcome of lung injury and inflammation. The importance of these cytokines also suggests new potential targets for designing new therapies for progressive pulmonary fibrosis, and perhaps their utility in prognostication as well.