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Homeostatic Control (homeostatic + control)
Selected AbstractsA role for innate immunity in type 1 diabetes?DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 2 2003H. Beyan Abstract Two arms of the immune system, innate and adaptive immunity, differ in their mode of immune recognition. The innate immune system recognizes a few highly conserved structures on a broad range of microorganisms. On the other hand, recognition of self or autoreactivity is generally confined to the adaptive immune response. Whilst autoimmune features are relatively common, they should be distinguished from autoimmune disease that is infrequent. Type 1 diabetes is an immune-mediated disease due to the destruction of insulin secreting cells mediated by aggressive immune responses, including activation of the adaptive immune system following genetic and environmental interaction. Hypotheses for the cause of the immune dysfunction leading to type 1 diabetes include self-reactive T-cell clones that (1) escape deletion in the thymus, (2) escape from peripheral tolerance or (3) escape from homeostatic control with an alteration in the immune balance leading to autoimmunity. Evidence, outlined in this review, raises the possibility that changes in the innate immune system could lead to autoimmunity, by either priming or promoting aggressive adaptive immune responses. Hostile microorganisms are identified by genetically determined surface receptors on innate effector cells, thereby promoting clearance of these invaders. These innate effectors include a few relatively inflexible cell populations such as monocytes/macrophages, dendritic cells (DC), natural killer (NK) cells, natural killer T (NKT) cells and ,, T cells. Recent studies have identified abnormalities in some of these cells both in patients with type 1 diabetes and in those at risk of the disease. However, it remains unclear whether these abnormalities in innate effector cells predispose to autoimmune disease. If they were to do so, then modulation of the innate immune system could be of therapeutic value in preventing immune-mediated diseases such as type 1 diabetes. Copyright © 2002 John Wiley & Sons, Ltd. [source] Maintenance of the relative proportion of oligodendrocytes to axons even in the absence of BAX and BAKEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2009Kumi Kawai Abstract Highly purified oligodendroglial lineage cells from mice lacking functional bax and bak genes were resistant to apoptosis after in-vitro differentiation, indicating an essential role of the intrinsic apoptotic pathway in apoptosis of oligodendrocytes in the absence of neurons (axons) and other glial cells. These mice therefore provide a valuable tool with which to evaluate the significance of the intrinsic apoptotic pathway in regulating the population sizes of oligodendrocytes and oligodendroglial progenitor cells. Quantitative analysis of the optic nerves and the dorsal columns of the spinal cord revealed that the absolute numbers of mature oligodendrocytes immunolabeled for aspartoacylase and adult glial progenitor cells expressing NG2 chondroitin sulfate proteoglycan were increased in both white matter tracts of adult bax/bak -deficient mice and, to a lesser extent, bax -deficient mice, except that there was no increase in NG2-positive progenitor cells in the dorsal columns of these strains of mutant mice. These increases in mature oligodendrocytes and progenitor cells in bax/bak -deficient mice were unexpectedly proportional to increases in numbers of axons in these white matter tracts, thus retaining the oligodendroglial lineage to axon ratios of at most 1.3-fold of the physiological numbers. This is in contrast to the prominent expansion in numbers of neural precursor cells in the subventricular zones of these adult mutant mice. Our study indicates that homeostatic control of cell number is different for progenitors of the oligodendroglial and neuronal lineages. Furthermore, regulatory mechanism(s) operating in addition to apoptotic elimination through the intrinsic pathway, appear to prevent the overproduction of highly mitotic oligodendroglial progenitor cells. [source] DNA supercoiling in Escherichia coli is under tight and subtle homeostatic control, involving gene-expression and metabolic regulation of both topoisomerase I and DNA gyraseFEBS JOURNAL, Issue 6 2002Jacky L. Snoep DNA of prokaryotes is in a nonequilibrium structural state, characterized as ,active' DNA supercoiling. Alterations in this state affect many life processes and a homeostatic control of DNA supercoiling has been suggested [Menzel, R. & Gellert, M. (1983) Cell34, 105,113]. We here report on a new method for quantifying homeostatic control of the high-energy state of in vivo DNA. The method involves making small perturbation in the expression of topoisomerase I, and measuring the effect on DNA supercoiling of a reporter plasmid and on the expression of DNA gyrase. In a separate set of experiments the expression of DNA gyrase was manipulated and the control on DNA supercoiling and topoisomerase I expression was measured [part of these latter experiments has been published in Jensen, P.R., van der Weijden, C.C., Jensen, L.B., Westerhoff, H.V. & Snoep, J.L. (1999) Eur. J. Biochem.266, 865,877]. Of the two regulatory mechanisms via which homeostasis is,conferred, regulation of enzyme activity or regulation of enzyme expression, we quantified the first to be responsible for 72% and the latter for 28%. The gene expression regulation could be dissected to DNA gyrase (21%) and to topoisomerase I (7%). On a scale from 0 (no homeostatic control) to 1 (full homeostatic control) we quantified the homeostatic control of DNA supercoiling at 0.87. A 10% manipulation of either topoisomerase I or DNA gyrase activity results in a 1.3% change of DNA supercoiling only. We conclude that the homeostatic regulation of the nonequilibrium DNA structure in wild-type Escherichia coli is almost complete and subtle (i.e. involving at least three regulatory mechanisms). [source] Prolonged exposure of naïve CD8+ T cells to interleukin-7 or interleukin-15 stimulates proliferation without differentiation or loss of telomere lengthIMMUNOLOGY, Issue 2 2006Diana L. Wallace Summary Interleukin (IL)-7 and IL-15 are cytokines implicated in homeostatic control of the peripheral CD8 T-cell pool. We compared the effects of IL-7 and IL-15 on survival and proliferation of purified human CD8+ T-cell subsets. Low concentrations of either cytokine reduced the spontaneous apoptosis of all subsets, and enhancement of survival corresponded to the extent of Bcl-2 up-regulation. Surprisingly, although minimal proliferation of naïve CD8+ T cells was observed during the first week of culture with cytokines, a marked expansion of these cells occurred at later time points, particularly in response to IL-15. This occurred largely without phenotypic change or acquisition of effector function, indicating a dissociation of differentiation from proliferation. Notably, progression of naïve CD8+ T cells through several cell divisions resulted in up-regulation of telomerase and the maintenance of telomere length. These data show that IL-7 and IL-15 induce cell proliferation and rescue from apoptosis in a concentration, time and subset-dependent manner, and have implications for the homeostatic expansion of the naïve CD8+ T-cell pool. [source] New insights into the role of extracellular matrix during tumor onset and progressionJOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2002Serenella M. Pupa Recently, a view of the tumor as a functional tissue interconnected with the microenvironment has recently been described. For many years, the stroma has been studied in the context of the malignant lesion, and only rarely has its role been considered before carcinogenic lesions appear. Recent studies have provided evidence that stromal cells and their products can cause the transformation of adjacent cells through transient signaling that leads to the disruption of homeostatic regulation, including control of tissue architecture, adhesion, cell death, and proliferation. It is now well established that tumor progression requires a continually evolving network of interactions between neoplastic cells and extracellular matrix. A relevant step of this process is the remodeling of microenvironment which surrounds tumors leading to the release of ECM-associated growth factors which can then stimulate tumor and/or endothelial cells. Finally, tumor cells reorganizing the extracellular matrix to facilitate communications and escape the homeostatic control exerted by the microenvironment modify response to cytotoxic treatments. © 2002 Wiley-Liss, Inc. [source] Short-Days Induce Weight Loss in Siberian Hamsters Despite Overexpression of the Agouti-Related Peptide GeneJOURNAL OF NEUROENDOCRINOLOGY, Issue 6 2010P. H. Jethwa Many vertebrates express profound annual cycles of body fattening, although it is not clear whether these represent differential activity of the central pathways known to mediate homeostatic control of food intake and energy expenditure, or whether the recent discovery of a major role for pars tuberalis-ependymal signalling points towards novel mechanisms. We examined this in the Siberian hamster (Phodopus sungorus) by using gene transfection to up-regulate a major orexigenic peptide, agouti-related peptide (AgRP), and then determined whether this increased anabolic drive could prevent the short-day induced winter catabolic state. Infusions of a recombinant adeno-associated virus encoding an AgRP construct into the hypothalamus of hamsters in the long-day obese phase of their seasonal cycle produced a 20% gain in body weight over 6 weeks compared to hamsters receiving a control reporter construct, reflecting a significant increase in food intake and a significant decrease in energy expenditure. However, all hamsters showed a significant, prolonged decrease in body weight when exposed to short photoperiods, despite the hamsters expressing the AgRP construct maintaining a higher food intake and lower energy expenditure relative to the control hamsters. Visualisation of the green fluorescent protein reporter and analysis of AgRP-immunoreactivity confirmed widespread expression of the construct in the hypothalamus, which was maintained for the 21-week duration of the study. In conclusion, the over-expression of AgRP in the hypothalamus produced a profoundly obese state but did not block the seasonal catabolic response, suggesting a separation of rheostatic mechanisms in seasonality from those maintaining homeostasis of energy metabolism. [source] Pinealectomy reduces hepatic and muscular glycogen content and attenuates aerobic power adaptability in trained ratsJOURNAL OF PINEAL RESEARCH, Issue 1 2007Cristina das Neves Borges-Silva Abstract:, The current study emphasizes the crucial role of the pineal gland on the effects of chronic training in different tissues focusing on carbohydrate metabolism. We investigated the maximal oxygen uptake (aerobic power), muscle and liver glycogen content, and also the enzymes involved in the carbohydrate metabolism of rat adipose tissue. Pinealectomized and sham-operated adult male Wistar rats were distributed into four groups: pinealectomized (PINX) untrained, pinealectomized trained, control untrained and control trained. The maximal oxygen uptake capability was assayed before and after the training protocol by indirect open circuit calorimetry. The rats were killed after 8 wk of training. Blood samples were collected for glucose and insulin determinations. The glycogen content was assayed in the liver and muscle. Maximal activities of epididymal adipose tissue enzymes (hexokinase, pyruvate kinase, lactate dehydrogenase, citrate synthase and malic enzyme) as well as adipocyte size were determined. The exercise training in control animals promoted an increase in the aerobic power and in liver glycogen content but caused a reduction in the malic enzyme activity in adipose tissue. However, PINX trained animals, in contrast to trained controls, showed a decrease in the aerobic power and in liver and muscle glycogen content, as well as an increase in the activity of the adipocyte enzymes involved in carbohydrate metabolism. In conclusion, these data show that the pineal gland integrity is necessary for the homeostatic control of energy metabolism among adipose, muscle and hepatic tissues. The pinealectomized animals showed alterations in adaptive responses of the maximal oxygen uptake to training. Therefore, the pineal gland must be considered an influential participant in the complex adaptation to exercise and is involved in the improvement of endurance capacity. [source] Vitamin A: Is It a Risk Factor for Osteoporosis and Bone Fracture?NUTRITION REVIEWS, Issue 10 2007Judy D. Ribaya-Mercado ScD Results from observational studies of the association between vitamin A intake or serum concentration and bone mineral density or fracture are mixed. The inconsistencies may be due, in part, to difficulties in obtaining an accurate assessment of vitamin A intake or status. Serum retinol is a poor measure of vitamin A status because it is subject to homeostatic control. Stable-isotope-dilution methodology gives a validated assessment of the total-body and liver vitamin A stores and is recommended in future studies on vitamin A status and osteoporosis. The potential for exacerbating an already serious public health problem with intakes of vitamin A currently considered safe indicates further research into this matter is warranted. [source] Interaction of hydrogen sulfide with ion channelsCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 7 2010Guanghua Tang Summary 1. Hydrogen sulfide (H2S) is a signalling gasotransmitter. It targets different ion channels and receptors, and fulfils its various roles in modulating the functions of different systems. However, the interaction of H2S with different types of ion channels and underlying molecular mechanisms has not been reviewed systematically. 2. H2S is the first identified endogenous gaseous opener of ATP-sensitive K+ channels in vascular smooth muscle cells. Through the activation of ATP-sensitive K+ channels, H2S lowers blood pressure, protects the heart from ischemia and reperfusion injury, inhibits insulin secretion in pancreatic , cells, and exerts anti-inflammatory, anti-nociceptive and anti-apoptotic effects. 3. H2S inhibited L-type Ca2+ channels in cardiomyocytes but stimulated the same channels in neurons, thus regulating intracellular Ca2+ levels. H2S activated small and medium conductance KCa channels but its effect on BKCa channels has not been consistent. 4. H2S-induced hyperalgesia and pro-nociception seems to be related to the sensitization of both T-type Ca2+ channels and TRPV1 channels. The activation of TRPV1 and TRPA1 by H2S is believed to result in contraction of nonvascular smooth muscles and increased colonic mucosal Cl, secretion. 5. The activation of Cl, channel by H2S has been shown as a protective mechanism for neurons from oxytosis. H2S also potentiates N -methyl- d -aspartic acid receptor-mediated currents that are involved in regulating synaptic plasticity for learning and memory. 6. Given the important modulatory effects of H2S on different ion channels, many cellular functions and disease conditions related to homeostatic control of ion fluxes across cell membrane should be re-evaluated. [source] Local dynamic changes in confined extracellular environments within organsCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 10 2009Natasha Behrendorff Summary 1Herein we review past work that has studied the composition of luminal fluid in organs, with a focus on measures of calcium and pH in the exocrine glands. This luminal environment is ,external' to the mammalian body and is not subject to the usual mechanisms of homeostatic control. Instead, it is controlled by the behaviour of the cells that line the lumen. 2We discuss the likely possibility that rapid and local changes in calcium and pH occur within microdomains in the lumen. Further, we present preliminary evidence, using live cell imaging of intact pancreatic fragments, that supports the idea that pH changes do occur. Our evidence indicates that exocytosis of secretory granules in pancreatic acinar cells leads to a loss of protons from the granule and a subsequent local acidification of the lumen. 3These changes in luminal composition are placed in the context of diseases of the pancreas, such as cystic fibrosis and pancreatitis, both of which are known to result in perturbations of luminal fluid composition. [source] Gene deletion of either interleukin-1,, interleukin-1,,converting enzyme, inducible nitric oxide synthase, or stromelysin 1 accelerates the development of knee osteoarthritis in mice after surgical transection of the medial collateral ligament and partial medial meniscectomyARTHRITIS & RHEUMATISM, Issue 12 2003Kristen M. Clements Objective To investigate the development of osteoarthritis (OA) after transection of the medial collateral ligament and partial medial meniscectomy in mice in which genes encoding either interleukin-1, (IL-1,), IL-1,,converting enzyme (ICE), stromelysin 1, or inducible nitric oxide synthase (iNOS) were deleted. Methods Sectioning of the medial collateral ligament and partial medial meniscectomy were performed on right knee joints of wild-type and knockout mice. Left joints served as unoperated controls. Serial histologic sections were obtained from throughout the whole joint of both knees 4 days or 1, 2, 3, or 4 weeks after surgery. Sections were graded for OA lesions on a scale of 0,6 and were assessed for breakdown of tibial cartilage matrix proteoglycan (aggrecan) and type II collagen by matrix metalloproteinases (MMPs) and aggrecanases with immunohistochemistry studies using anti-VDIPEN, anti-NITEGE, and Col2-3/4Cshort neoepitope antibodies. Proteoglycan depletion was assessed by Alcian blue staining and chondrocyte cell death, with the TUNEL technique. Results All knockout mice showed accelerated development of OA lesions in the medial tibial cartilage after surgery, compared with wild-type mice. ICE-, iNOS-, and particularly IL-1,,knockout mice developed OA lesions in the lateral cartilage of unoperated limbs. Development of focal histopathologic lesions was accompanied by increased levels of MMP-, aggrecanase-, and collagenase-generated cleavage neoepitopes in areas around lesions, while nonlesional areas showed no change in immunostaining. Extensive cell death was also detected by TUNEL staining in focal areas around lesions. Conclusion We postulate that deletion of each of these genes, which encode molecules capable of producing degenerative changes in cartilage, leads to changes in the homeostatic controls regulating the balance between anabolism and catabolism, favoring accelerated cartilage degeneration. These observations suggest that these genes may play important regulatory roles in maintaining normal homeostasis in articular cartilage matrix turnover. [source] | |||||||||||||