bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of PLA2isoforms by cell swelling and ischaemia/hypoxia
Authors: Lambert I. H. , Pedersen S. F. , Poulsen K. A. 
Published: May 2006

AbstractPhospholipase A2(PLA2) activity is increased in mammalian cells in response to numerous stimuli such as osmotic challenge, oxidative stress and exposure to allergens. The increased PLA2activity is seen as an increased release of free, polyunsaturated fatty acids, e.g. arachidonic acid and membrane‐bound lysophospholipids. Even though arachidonic acid acts as a second messenger in its own most mammalian cells seem to rely on oxidation of the fatty acid into highly potent second messengers via, e.g. cytochrome P450, the cyclo‐oxygenase, or the lipoxygenase systems for downstream signalling. Here, we review data that illustrates that stress‐induced PLA2activity involves various PLA2subtypes and that the PLA2in question is determined by the cell type and the physiological stress condition.
Signal transduction mechanisms of K+‐Cl− cotransport regulation and relationship to disease
Authors: Adragna N. C. , Ferrell C. M. , Zhang J. , Di Fulvio M. , Temprana C. F. , Sharma A. , Fyffe R. E. W. , Cool D. R. , Lauf P. K. 
Published: May 2006

AbstractThe K+‐Cl− cotransport (COT) regulatory pathways recently uncovered in our laboratory and their implication in disease state are reviewed. Three mechanisms of K+‐Cl− COT regulation can be identified in vascular cells: (1) the Li+‐sensitive pathway, (2) the platelet‐derived growth factor (PDGF)‐sensitive pathway and (3) the nitric oxide (NO)‐dependent pathway. Ion fluxes, Western blotting, semi‐quantitative RT‐PCR, immunofluorescence and confocal microscopy were used. Li+, used in the treatment of manic depression, stimulates volume‐sensitive K+‐Cl− COT of low K+ sheep red blood cells at cellular concentrations <1 mm and inhibits at >3 mm, causes cell swelling, and appears to regulate K+‐Cl− COT through a protein kinase C‐dependent pathway. PDGF, a potent serum mitogen for vascular smooth muscle cells (VSMCs), regulates membrane transport and is involved in atherosclerosis. PDGF stimulates VSM K+‐Cl− COT in a time‐ and concentration‐dependent manner, both acutely and chronically, through the PDGF receptor. The acute effect occurs at the post‐translational level whereas the chronic effect may involve regulation through gene expression. Regulation by PDGF involves the signalling molecules phosphoinositides 3‐kinase and protein phosphatase‐1. Finally, the NO/cGMP/protein kinase G pathway, involved in vasodilation and hence cardiovascular disease, regulates K+‐Cl− COT in VSMCs at the mRNA expression and transport levels. A complex and diverse array of mechanisms and effectors regulate K+‐Cl− COT and thus cell volume homeostasis, setting the stage for abnormalities at the genetic and/or regulatory level thus effecting or being affected by various pathological conditions.
Hypertonicity‐induced cation channels
Authors: Wehner F. , Bondarava M. , Ter Veld F. , Endl E. , Nürnberger H. R. , Li T. 
Published: May 2006

AbstractWhenever studied in a quantitative fashion, hypertonicity‐induced cation channels (HICCs) are found to be the main mediators of regulatory volume increase. In most instances, these channels are either inhibited by amiloride (but insensitive to Gd3+ and flufenamate) or they are efficiently blocked by Gd3+ and flufenamate (but insensitive to amiloride). Of note, however, from two preparations so far a mixed type of pharmacology has also been reported. Whereas the ion selectivity of amiloride‐sensitive HICCs has not been studied in much detail yet, amiloride‐insensitive channels are either equally permeable to Na+, K+, Cs+ and Li+ but impermeable to N‐methyl‐d‐glucamine (NMDG+) or they exhibit a permeability to Li+ and NMDG+ that amounts to some 50% when compared with that of Na+. Also in this respect, however, some peculiarities do exist. Concerning the actual molecular correlate, evidence was reported that HICCs may be related to the (amiloride‐sensitive) epithelial Na+ channel and/or to transient receptor potential channels. Recent findings suggest that HICCs may contribute to cell proliferation, just as the K+ channels that are employed in regulatory volume decrease are mediators of the opposing process, i.e. apoptosis.
Osmotic shock‐induced suicidal death of erythrocytes
Authors: Lang F. , Lang K. S. , Lang P. A. , Huber S. M. , Wieder T. 
Published: May 2006

AbstractOsmotic shock triggers eryptosis, a suicidal death of erythrocytes characterized by cell shrinkage, cell membrane blebbing and phosphatidylserine exposure at the cell surface. Phosphatidylserine‐exposing erythrocytes are recognized by macrophages, engulfed, degraded and thus cleared from circulating blood. Eryptosis following osmotic shock is mediated by two distinct signalling pathways. On the one hand, osmotic shock stimulates a cyclooxygenase leading to formation of prostaglandin E2 and subsequent activation of Ca2+‐permeable cation channels. On the other hand, osmotic shock activates a phospholipase A2 leading to release of platelet activating factor, which in turn activates a sphingomyelinase and thus stimulates the formation of ceramide. The increased cytosolic Ca2+ concentrations on the one hand and ceramide on the other trigger phospholipid scrambling of the cell membrane with the subsequent shift of phosphatidylserine from the inner to the outer cell membrane leaflet. Ca2+ further activates Ca2+‐sensitive K+ channels leading to cellular KCl loss and further cell shrinkage. The cation channels are inhibited by Cl− anions, erythropoietin and dopamine. The sphingomyelinase is inhibited by high concentrations of urea. Thus, the high Cl− and urea concentrations in renal medulla presumably prevent the triggering of eryptosis despite hyperosmolarity. The mechanisms involved in eryptosis may not only affect the survival of erythrocytes but may be similarly operative in nucleated cells exposed to osmotic shock.
Could chronic pain and spread of pain sensation be induced and maintained by glial activation?
Authors: Hansson E. 
Published: May 2006

AbstractAn injury often starts with acute physiological pain, which becomes inflammatory or neuropathic, and may sometimes become chronic. It has been proposed recently that activated glial cells, astrocytes and microglia within the central nervous system could maintain the pain sensation even after the original injury or inflammation has healed, and convert it into chronic by altering neuronal excitability. Glial cell activation has also been proposed to be involved in the phenomenon of spread of pain sensation ipsilaterally or to the contralateral side (i.e. mirror image pain). Substance P and calcitonin gene‐related peptide, released due to an inflammatory process, interact with the endothelial cells of the blood–spinal cord and blood–brain barriers. The barriers open partially and substances may influence adjacent glial cells. Such substances are also released from neurones carrying the ‘pain message’ all the way from the injury to the cerebral cortex. Pro‐inflammatory cytokines may be released from the microglial cells, and astroglial Ca2+‐transients or oscillations may spread within the astroglial networks. One theory is that Ca2+‐oscillations could facilitate the formation of new synapses. These new synapses could establish neuronal contacts for maintaining and spreading the pain sensation. If this theory holds true, it is possible that Ca2+ waves, production of cytokines and growth factors could be modified by selective anti‐inflammatory drugs to achieve a balance in the activities of the different intercellular and intracellular processes. This paper reviews current knowledge about glial mechanisms underlying the phenomena of chronic pain and spread of the pain sensation.
The taurine transporter: mechanisms of regulation
Authors: Han X. , Patters A. B. , Jones D. P. , Zelikovic I. , Chesney R. W. 
Published: May 2006

AbstractTaurine transport undergoes an adaptive response to changes in taurine availability. Unlike most amino acids, taurine is not metabolized or incorporated into protein but remains free in the intracellular water. Most amino acids are reabsorbed at rates of 98–99%, but reabsorption of taurine may range from 40% to 99.5%. Factors that influence taurine accumulation include ionic environment, electrochemical charge, and post‐translational and transcriptional factors. Among these are protein kinase C (PKC) activation and transactivation or repression by proto‐oncogenes such asWT1, c‐Jun, c‐Myb and p53. Renal adaptive regulation of the taurine transporter (TauT) was studiedin vivoandin vitro. Site‐directed mutagenesis and the oocyte expression system were used to study post‐translational regulation of the TauT by PKC. Reporter genes and Northern and Western blots were used to study transcriptional regulation of the taurine transporter gene (TauT). We demonstrated that (i) the body pool of taurine is controlled through renal adaptive regulation ofTauTin response to taurine availability; (ii) ionic environment, electrochemical charge, pH, and developmental ontogeny influence renal taurine accumulation; (iii) the fourth segment of TauT is involved in the gating of taurine across the cell membrane, which is controlled by PKC phosphorylation of serine 322 at the post‐translational level; (iv) expression ofTauTis repressed by the p53 tumour suppressor gene and is transactivated by proto‐oncogenes such asWT1, c‐Jun, and c‐Myb; and (v) over‐expression ofTauTprotects renal cells from cisplatin‐induced nephrotoxicity.
Aldosterone remodels human endothelium
Authors: Oberleithner H. , Riethmüller C. , Ludwig T. , Hausberg M. , Schillers H. 
Published: May 2006

AbstractAim:  In response to aldosterone endothelial cells swell and stiffen. Although amiloride‐sensitive sodium and water uptake is known to be involved, the underlying mechanisms are yet unclear. We tested the hypothesis whether the intracellular accumulation of water or organic matter is responsible for the structural and functional alterations.Methods:  Atomic force microscopy was used as an imaging tool and a mechanical nanosensor. Cell water, organic cell matter and cell pressure was measured at single cell level in human umbilical vein endothelial cells (HUVEC). Furthermore, we tested by means of a miniature perfusion chamber in vitro the physical robustness to blood flow of the aldosterone‐treated endothelium.Results:  In response to a three‐day treatment with 1 nm aldosterone HUVEC swell. To our surprise, cell water decreased from 82 ± 6% to 71 ± 5% while intracellular organic matter increased from 18 ± 1.8% to 29 ± 3.0%. These changes were paralleled by a rise in cell pressure of 114%, measured in living HUVEC in vitro. Blood flow across the endothelium was found significantly altered after aldosterone treatment. Imaging the endothelial monolayer after blood perfusion disclosed large gaps between cells treated with aldosterone. The mineralocorticoid receptor blockers, spironolactone and eplerenone could prevent the aldosterone actions.Conclusion:  Mild aldosteronism causes intracellular accumulation of organic matter at the cost of cell water. This makes endothelium stiff and vulnerable to shear stress. The measurements could explain clinical observations that high blood pressure combined with high plasma aldosterone concentration may damage the endothelium of blood vessels.
Expression of iNOS mRNA associated with suppression of colonic contraction in rat colitis
Authors: Lundberg S. , Holst M. , Hellström P. M. 
Published: May 2006

AbstractAim:  Nitric oxide (NO) synthesis and inducible NO synthase (NOS) expression are increased in colon of patients with inflammatory bowel disease (IBD) and associated with decreased contractility. The aim was to investigate which subtype of NOS that is activated in experimental colitis.Methods:  Experimental colitis was induced in Sprague–Dawley rats by Escherichia coli endotoxin. Expression of different subtypes of NOS was compared in normal and inflamed colon using reverse transcriptase‐polymerase chain reaction. In organ baths, isometric contractile responses to acetylcholine (ACh) were studied in the colon, before and after incubation with the NOS inhibitor; Nω‐nitro‐L‐arginine methyl ester (L‐NAME) and NO donor glyceryl trinitrate.Results:  Inflammation decreased colonic contraction to ACh from a pD2 value of 7.09 ± 0.16 to 5.30 ± 0.17 (P < 0.001), and reduced maximal response to ACh. Pre‐treatment with L‐NAME reversed contractility and shifted the pD2 for ACh from 5.30 ± 0.17 to 6.60 ± 0.19 (P < 0.001) along with a normalized contraction efficacy. RT‐PCR product of iNOS was obtained only in rats treated with endotoxin.Conclusion:  Expression of iNOS is increased in inflamed colonic tissue. The induced overproduction of NO is likely to be responsible for the decreased motility in colitis where NO is suggested to exert a suppressive tone on colonic contractility, which is reversed by blockade of the enzyme.
Volume transmission and wiring transmission from cellular to molecular networks: history and perspectives
Authors: Agnati L. F. , Leo G. , Zanardi A. , Genedani S. , Rivera A. , Fuxe K. , Guidolin D. 
Published: May 2006

AbstractThe present paper deals with a fundamental issue in neuroscience: the inter‐neuronal communication. The paper gives a brief account of our previous and more recent theoretical contributions to the subject and also reports new recent data that support some aspects of our proposal on two major modes of communication in the central nervous system: the wiring and the volume transmission. There exist two competing theories on inter‐neuronal communication: the neuron doctrine and the theory of the diffuse nerve network, supported by Cajal and Golgi, respectively (see their respective Nobel Lectures). The present paper gives a brief account of a view on inter‐neuronal communication in the brain, the volume and wiring transmission concept that to a great extent reconcile these two theories. Thus, the theory of volume and wiring transmission are summarized and its recent developments that allow to extend these two modes of communication from the cellular network to the molecular network level is also briefly illustrated. The explanatory value of this broadened view is further enhanced by our recent proposal on the existence of a Global Molecular Network enmeshing the entire central nervous system. It may be interesting to note that also the Global Molecular Network theory is reminiscent of the old reticular theory of Apathy. Finally, the so‐called ‘tide hypothesis’ for diffusion of signals in the brain is briefly discussed and its possible extension to the molecular level is for the first time introduced. Early indirect evidence supporting volume transmission in the brain was the discovery of transmitter‐receptor mismatches. Thus, as an experimental part of the present paper a new approach to evaluate transmitter‐receptor mismatches is given and evidence for inter‐relationships between temperature micro‐gradients and mismatches is provided.
In the absence of (early) invasive carcinoma, vulvar intraepithelial neoplasia associated with lichen sclerosus is mainly of undifferentiated type: new insights in histology and aetiology
Authors: van Seters M , ten Kate F J W , van Beurden M , Verheijen R H M , Meijer C J L M , Burger M P M , Helmerhorst T J M 
Published: May 2006

Background:Differentiated vulvar intraepithelial neoplasia (VIN) is presumed to be the precursor of invasive squamous cell carcinoma (SCC) of the vulva. It is commonly assumed that differentiated VIN is related to lichen sclerosus (LS). However, evidence for this is limited to a small number of studies describing epithelial alterations adjacent to vulvar SCC.Aim:To study the histology and human papillomavirus (HPV) status in patients with a history of both LS and VIN without coexistent SCC.Methods:Original biopsy specimens and surgical specimens of patients retrieved from the pathology files were revised for the presence of LS, VIN and (early) invasive SCC, specifically focused on the two different types of VIN: differentiated and undifferentiated. Thereafter, VIN lesions were tested for the presence of HPV DNA.Results:Twenty-seven patients fulfilled the criteria for LS and VIN without SCC. In all 27 patients, LS was found to be related to undifferentiated VIN. Grading yielded the following results: VIN 1 (n = 10), VIN 2 (n = 11) and VIN 3 (n = 6). Additionally, VIN lesions from 26 patients could be tested for the presence of HPV DNA. HPV DNA, predominantly type 16, was present in 8 (31%) of them. Seven of these eight patients had VIN 2 or 3. During follow-up, three patients progressed to (early) invasive carcinoma. In two of these patients, differentiated VIN was observed overlying early invasive SCC.Conclusions:VIN related to LS without coexisting SCC is likely to be undifferentiated, in contrast to what was previously thought. HPV DNA was demonstrated in 31% of the lesions, and was strongly related to high-grade VIN.
Survivin promoter polymorphism and cervical carcinogenesis
Authors: Borbély A A , Murvai M , Szarka K , Kónya J , Gergely L , Hernádi Z , Veress G 
Published: May 2006

Background:Survivin, a novel member of the inhibitor of apoptosis family, plays an important role in cell cycle regulation. A common polymorphism at the survivin gene promoter (G/C at position 31) was shown to be correlated with survivin gene expression in cancer cell lines.Aim:To investigate whether this polymorphism could be involved in the development of human papillomavirus (HPV)-associated cervical carcinoma.Methods:Survivin promoter polymorphism was detected in patients with cervical cancer, in patients with equivocal cytological atypia and in a control population using polymerase chain reaction (PCR-restriction fragment length polymorphism (RFLP) and PCR-single strand conformation polymorphism analysis. HPV was typed in patients with cervical cancer and cytological atypia using PCR-RFLP.Results:No statistically significant differences were found in the genotype distributions of the survivin promoter variants among our study groups.Conclusions:The survivin promoter polymorphism at position 31 may not represent an increased risk for the development of cervical cancer, at least in the population studied here.
Pathobiological characteristics of intestinal and diffuse-type gastric carcinoma in Japan: an immunostaining study on the tissue microarray
Authors: Zheng Huachuan , Takahashi Hiroyuki , Murai Yoshihiro , Cui Zhengguo , Nomoto Kazuhiro , Miwa Shigeharu , Tsuneyama Koichi , Takano Yasuo 
Published: May 2006

Aim:To investigate the pathobiological features of intestinal and diffuse-type gastric carcinomas in the Japanese population.Methods:The expression of fragile histine triad (FHIT), phosphatase and tensin homology deleted from human chromosome 10 (PTEN), caspase-3, Ki-67, mutant p53, matrix metalloproteinase (MMP)-2, MMP-9, and extracellular matrix metalloproteinase inducer (EMMPRIN) on tissue microarrays of gastric carcinomas by immunostaining was examined in comparison with the clinicopathological characteristics between intestinal and diffuse-type cases.Results:Intestinal-type carcinoma frequently occurred in old men, whereas the diffuse type comparatively occurred more in young women (p<0.05). The diffuse-type carcinoma was more inclined to invasion into muscularis propria, lymphatic invasion and lymph node metastasis, and belonged to higher International Union against Cancer (UICC) staging (p<0.05) compared with intestinal-type counterparts. Expression of FHIT, PTEN, Ki-67, caspase-3, mutant p53 and EMPPRIN was higher in intestinal-type carcinomas than in diffuse-type carcinomas (p<0.05). Kaplan–Meier analysis indicated that patients with intestinal-type carcinomas had a higher cumulative survival rate (p<0.05).Conclusion:Intestinal-type gastric carcinomas with a more favourable prognosis frequently show high levels of proliferation and apoptosis, and always accompany strong expression of FHIT, PTEN and mutant p53 and EMMPRIN. EMMPRIN expression might underlie the molecular basis of liver metastasis and higher proliferation of intestinal-type gastric carcinomas in Japan. Lauren’s classification thus proved pathologically relevant for the clinical treatment of gastric carcinomas.
Angiotensin II-mediated oxidative stress and procollagen-1 expression in cardiac fibroblasts: blockade by pravastatin and pioglitazone
Authors: Chen Jiawei , Mehta Jawahar L. 
Published: May 2006

Angiotensin II (ANG II), a product of renin-angiotensin system activation, enhances collagen synthesis, which is a key event in cardiac remodeling after myocardial infarction. Inhibition of cardiac remodeling is now a target of multiple therapies, including 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, commonly known as statins, and peroxisome proliferator-activated receptor-γ (PPAR-γ) ligands. We examined the potential antifibrotic effect of the combination of a statin (pravastatin) and a PPAR-γ ligand (pioglitazone) in ANG II-treated mouse cardiac fibroblasts. ANG II treatment induced procollagen-1 expression, which was inhibited by pravastatin and pioglitazone in a dose-dependent fashion. Pretreatment of fibroblasts with low therapeutic concentrations of either pravastatin (0.1 μM) or pioglitazone (5 μM) only slightly decreased ANG II-induced NADPH oxidase expression, superoxide anion production, and procollagen-1 expression; however, the combination of pravastatin and pioglitazone markedly modulated these effects of ANG II. The combination also blocked ANG II-mediated p38 MAPK and p44/42 MAPK activation. Electrophoretic mobility shift assay showed that ANG II activated transcription factors NF-κB and activator protein-1 (AP-1). Although pravastatin and pioglitazone alone had a variable effect on NF-κB and AP-1 activation, their combination exerted a potent inhibitory effect on the activation of both NF-κB and AP-1. The effects of pravastatin and pioglitazone in combination on superoxide generation and procollagen-1 expression mimicked those of α-tocopherol and γ-tocopherol, two potent antioxidants. Thus it appears that there is a positive interaction between pravastatin and pioglitazone in modulating ANG II-mediated oxidative stress, inhibiting MAPK activation, and procollagen-1 expression.
Octopamine-like immunoreactivity in the brain and suboesophageal ganglion of two parasitic wasps, Cotesia glomerata and Cotesia rubecula
Authors: Bleeker Maartje , van der Zee Brenda , Smid Hans 
Published: May 2006

Abstract
Two closely related parasitoid wasp species, Cotesia glomerata L. and C. rubecula Marshall (Hymenoptera: Braconidae), differ in their display of associative learning and memory during host searching. As octopamine is involved in learning and memory in insects we investigated octopaminergic pathways in the brain and suboesophageal ganglion (SOG) of the two wasps. We used an anti-octopamine antibody and subsequent whole mount analysis using a confocal laserscanning microscope and pertinent software. Three groups of octopaminergic cells were located in the brain and suboesophageal ganglion. One group was located near the antennal lobes and consisted of six to eight cell bodies. A second group was located ventrally in the SOG and was most likely formed by ventral unpaired median (VUM) and VCBN (ventral cell body neurite) neurons. A third group was located in the pars intercerebralis and consisted of four to six cells. Octopamine-like immunoreactivity was furthermore present in the central body, protocerebral bridge, the SOG, antennal lobe, near the alpha and beta lobes of the mushroom bodies and in the mushroom body calyces. Due to the used methods and a high variability in staining intensity it was not possible to detect if there were any differences in the number of neurons, in arborisation patterns or in labelling intensity between the two wasp species.