bluuebunny/crossref_metadata_2025 huggingface dataset:
Hyperosmotic activation of the CD95 death receptor system
Authors: Reinehr R. , Häussinger D.
Published: May 2006

Apoptosis is characterized by cell shrinkage, nuclear condensation, DNA fragmentation and apoptotic body formation. These features distinguish apoptosis from other types of cell death, such as necrosis. Whereas some signs of apoptosis, such as externalization of phosphatidylserine, altered mitochondrial function or activation of caspases are cell type‐ and death signal‐dependent, apoptotic cell volume decrease (AVD) is an early and ubiquitous event and little is known about the signalling events, which are localized upstream of the plasma membrane transport steps leading to AVD and the proapoptotic events, which are induced by osmolyte loss and cell shrinkage. In hepatocytes hyperosmotic shrinkage sensitizes the cells towards CD95 ligand‐induced apoptosis by activating the CD95 system. This complex process with a NADPH oxidase‐derived reactive oxygen species signal as an important upstream event, allows via Yes, JNK and epidermal growth factor‐receptor activation for CD95 tyrosine phosphorylation as a prerequisite for CD95 targeting to the plasma membrane and formation of the death inducing signalling complex. Other covalent modifications such as CD95‐tyrosine‐nitration or CD95‐serine/threonine‐phosphorylation can interfere with the CD95 activation process. The findings not only provide a mechanistic explanation for the high susceptibility of dehydrated cells for apoptosis, but also give insight into the role of AVD.
The hepatocyte integrin system and cell volume sensing
Authors: Häussinger D. , Reinehr R. , Schliess F.
Published: May 2006

Alterations of cell volume induced by either aniso‐osmotic environments or under the influence of hormones, concentrative amino acid uptake and oxidative stress were recognized as an independent signal contributing to the regulation of metabolism and gene expression. The regulation of cell function by hydration changes requires structures, which register fluctuations of cell hydration (osmosensing) and thereby activate intracellular signalling pathways towards effector sites (osmosignalling). Meanwhile, it is well established that osmosensing and signalling integrate into the overall context of hormone‐ and nutrient‐induced signal transduction. Recent evidence suggests integrins to play a major role in osmosensing and signalling due to hepatocyte swelling. This review focuses on the role of integrins in sensing of hepatocyte swelling as triggered by hypo‐osmolarity, glutamine and insulin and the relevance of integrin‐dependent osmosignalling for inhibition of autophagic proteolysis, stimulation of canalicular bile acid excretion and regulatory volume decrease.
Swelling‐activated chloride channels in aqueous humour formation: on the one side and the other
Authors: Do C. W. , Civan M. M.
Published: May 2006

Aqueous humour is secreted by the ciliary epithelium comprising pigmented and non‐pigmented cell layers facing the stroma and aqueous humour respectively. Net chloride secretion likely limits the rate of aqueous humour formation and proceeds in three steps: stromal chloride entry into pigmented cells, diffusion through gap junctions and final non‐pigmented cell secretion. Swelling‐activated chloride channels function on both epithelial surfaces. At the stromal surface, swelling‐ and cyclic adenosine monophosphate‐activated maxi‐chloride channels can recycle chloride, reducing net chloride secretion. At the aqueous‐humour surface, swelling‐ and A3 adenosine receptor‐activated chloride channels subserve chloride release into the aqueous humour. The similar macroscopic properties of the two non‐pigmented cell chloride currents suggest that both flow through a common conduit. In addition, measurements of intraocular pressure (IOP) in living wild‐type and mutant mice have confirmed that A3 adenosine receptor‐activated agonists and antagonists increase and lower IOP respectively. Isolated ciliary epithelial cells are commonly perfused with hypotonic solution to probe and characterize chloride channels, but the physiological role of swelling‐activated channels has been unclear without knowing their epithelial distribution. Recently, hypotonic challenge has been found to stimulate the chloride‐sensitive short‐circuit current across the intact bovine ciliary epithelium, suggesting that the net effect of the swelling‐activated chloride currents is oriented to enhance aqueous humour formation. Taken together, the results suggest that swelling‐activated chloride channels are predominantly oriented to enhance aqueous humour secretion, and these chloride channels at the aqueous surface may be identical with adenosine receptor‐activated chloride channels which likely modulate aqueous inflow and IOP in the living mouse.
How tonicity regulates genes: story of TonEBP transcriptional activator
Authors: Jeon U. S. , Kim J.‐A. , Sheen M. R. , Kwon H. M.
Published: May 2006

TonEBP stimulates genes whose products drive cellular accumulation of organic osmolytes and HSP70, which protect cells from the deleterious effects of hypertonicity and urea, respectively. Mice deficient in the TonEBP gene display severe atrophy of the renal medulla because cells failed to adapt to the hyperosmolality. Emerging data suggest that TonEBP plays a key role in the urinary concentrating mechanism by stimulating the UT‐A urea transporters and possibly AQP2 water channel. Thus, TonEBP is an essential regulator in the urinary concentrating mechanism. Studies on structural basis of TonEBP function have revealed the structure of the DNA binding domain, and defined the transactivation domains. Molecular mechanisms underlying the nucleocytoplasmic trafficking, transactivation, and phosphorylation in response to changes in tonicity need to be understood in molecular detail. Such knowledge is needed for the identification of the sensor that detects changes in ambient tonicity and signals to TonEBP.
The role of the neutral amino acid transporter SNAT2 in cell volume regulation
Authors: Franchi‐Gazzola R. , Dall'Asta V. , Sala R. , Visigalli R. , Bevilacqua E. , Gaccioli F. , Gazzola G. C. , Bussolati O.
Published: May 2006

Sodium‐dependent neutral amino acid transporter‐2 (SNAT2), the ubiquitous member of SLC38 family, accounts for the activity of transport system A for neutral amino acids in most mammalian tissues. As the transport process performed by SNAT2 is highly energized, system A substrates, such as glutamine, glycine, proline and alanine, reach high transmembrane gradients and constitute major components of the intracellular amino acid pool. Moreover, through a complex array of exchange fluxes, involving other amino acid transporters, and of metabolic reactions, such as the synthesis of glutamate from glutamine, SNAT2 activity influences the cell content of most amino acids, thus determining the overall size and the composition of the intracellular amino acid pool. As amino acids represent a large fraction of cell organic osmolytes, changes of SNAT2 activity are followed by modifications in both cell amino acids and cell volume. This mechanism is utilized by many cell types to perform an effective regulatory volume increase (RVI) upon hypertonic exposure. Under these conditions, the expression of SNAT2 gene is induced and newly synthesized SNAT2 proteins are preferentially targeted to the cell membrane, leading to a significant increase of system A transport Vmax. In cultured human fibroblasts incubated under hypertonic conditions, the specific silencing of SNAT2 expression, obtained with anti‐SNAT2 siRNAs, prevents the increase in system A transport activity, hinders the expansion of intracellular amino acid pool, and significantly delays cell volume recovery. These results demonstrate the pivotal role played by SNAT2 induction in the short‐term hypertonic RVI and suggest that neutral amino acids behave as compatible osmolytes in hypertonically stressed cells.
Tyrosine kinases and osmolyte fluxes during hyposmotic swelling
Authors: Pasantes‐Morales H. , Lezama R. A. , Ramos‐Mandujano G.
Published: May 2006

Recent evidence documents the involvement of protein tyrosine kinases (TK) in the signalling network activated by hyposmotic swelling and regulatory volume decrease. Both receptor type and cytosolic TK participate as signalling elements in the variety of cell adaptive responses to volume changes, which include adhesion reactions, reorganization of the cytoskeleton, temporal deformation/remodelling of the membrane and stress‐detecting mechanisms. The present review refers to the influence of TK on the activation/operation of the osmolyte efflux pathways, ultimately leading to cell volume recovery, i.e. the osmosensitive Cl− channel (Cl), the K+ channels activated by swelling in the different cell types and the taurine efflux pathway as representative of the organic osmolyte pathway.
Activation of PLA2isoforms by cell swelling and ischaemia/hypoxia
Authors: Lambert I. H. , Pedersen S. F. , Poulsen K. A.
Published: May 2006

Phospholipase 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

The 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

Whenever 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

Osmotic 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

An 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

Taurine 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

Aim:  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

Aim:  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

The 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.
Preparation of 1-Adamantyl Ketones: Structure, Mechanism of Formation and Biological Activity of Potential By-Products
Authors: Vícha Robert , Nečas Marek , Potáček Milan
Published: May 2006

Reactions between adamantane-1-carbonyl chloride and several Grignard reagents as well as interactions with solvents have been examined. Some new and unexpected adamantane derivatives were isolated, fully characterized and their biological activity determined. In particular, an unexpected isochromanone 16 was formed in an SEAr process, in which a stable hydrocarbon was the leaving group.
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.
Best practice in primary care pathology: review 4: Figure 1
Authors: Smellie W S A , Forth J , Sundar S , Kalu E , McNulty C A M , Sherriff E , Watson I D , Croucher C , Reynolds T M , Carey P J
Published: May 2006

This fourth best practice review examines four series of common primary care questions in laboratory medicine are examined in this review: (1) safety monitoring for three common drugs; (2) use of prostate-specific antigen; (3) investigation of vaginal discharge; and (4) investigation of subfertility. The review is presented in question–answer format, referenced for each question series. The recommendations represent a precis of the guidance found using a standardised literature search of national and international guidance notes, consensus statements, health policy documents and evidence-based medicine reviews, supplemented by Medline Embase searches to identify relevant primary research documents. They are not standards but form a guide to be set in the clinical context. Most of them are consensus based rather than evidence based. They will be updated periodically to take account of new information.
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.
INFRARED FACE RECOGNITION BASED ON LOG-GABOR WAVELETS
Authors: CHEN XUERONG , JING ZHONGLIANG
Published: May 2006

Despite the variety of approaches and tools studied, face recognition is not accurate or robust enough to be used in uncontrolled environments. Recently, infrared (IR) imagery of human faces is considered as a promising alternative to visible imagery. IR face recognition is a biometric which offers the security of fingerprints with the convenience of face recognition. However, IR has its own limitations. The presence of eyeglasses has more influence on IR than visible imagery. In this paper, a method based on Log-Gabor wavelets for IR face recognition is proposed. The method first derives a Log-Gabor feature vector from IR face image, then obtains the independent Log-Gabor features by using independent component analysis (ICA). Experimental results show that the proposed method works well, even in challenging situations.
AN INTERACTIVE 3D VISUALIZATION SYSTEM BASED ON PC USING INTEL SIMD, 3D TEXTURING AND THINNING TECHNIQUES
Authors: YUAN FEINIU , LIAO GUANGXUAN , FAN WEICHENG , LANG WENHUI , LIU ZHENGMIN
Published: May 2006

An efficient 3D visualization system has not only fast volume rendering algorithms but also effective navigation methods. Rendering speed is one of key technologies in most 3D visualization applications. We exploit software, Pentium 4 and graphics hardware technologies, such as threshold segmentation, Intel SIMD and 3D texturing, to obtain interactive volume rendering on a standard PC without specialized expensive hardware. Path planning is essential in many 3D visualization applications, such as virtual endocopy, in order to accelerate exploring. There are three major types of methods to extract the navigation path from a 3D data set, including manual, 3D distance transform and thinning based techniques. 3D thinning is a desirable method to extract skeletons of objects, but it has some severe problems to be solved. It is time consuming with discontinuity and small branches. An effective encoding and coordinates transform based scheme is presented to generate a look up table of 3D thinning templates to speed up path extracting, and a two-pass tracking technique is followed to trim the small branches of skeletons. Tri-pass cubic Bezier technique is proposed to decrease large curvatures caused by discrete representation of path. A smooth and C 1 continuity navigation path is thus produced by our algorithms. Following this path, the camera moves and rotates smoothly without any dithering. Our system is very useful and can be widely applied due to full utilization of the existing inexpensive capabilities of PCs.
SELECTIVE VOTING — GETTING MORE FOR LESS IN SENSOR FUSION
Authors: ROKACH LIOR , MAIMON ODED , ARBEL REUVEN
Published: May 2006

Many real life problems are characterized by the structure of data derived from multiple sensors. The sensors may be independent, yet their information considers the same entities. Thus, there is a need to efficiently use the information rendered by numerous datasets emanating from different sensors. A novel methodology to deal with such problems is suggested in this work. Measures for evaluating probabilistic classification are used in a new efficient voting approach called "selective voting", which is designed to combine the classification of the models (sensor fusion). Using "selective voting", the number of sensors is decreased significantly while the performance of the integrated model's classification is increased. This method is compared to other methods designed for combining multiple models as well as demonstrated on a real-life problem from the field of human resources.
LEARNING SPARSE MIXTURE MODELS FOR DISCRIMINATIVE CLASSIFICATION
Authors: LIU WEIXIANG , ZHENG NANNING , ZHENG SONGFENG
Published: May 2006

Recently Saul and Lee proposed a mixture model for discriminative classification of non-negative data via non-negative matrix factorization for feature extraction. In order to improve the generalization, this paper considers a sparse version of the model. The basic idea is to minimize the sum of the weights of un-normalized mixture models for posterior distributions according to regularization method. Experiments on CBCL face database and USPS digit data set assess the validity of the proposed approach.
Wave reflection effects in the central circulation of American alligators (Alligator mississippiensis): what the heart sees
Authors: Syme Douglas A. , Gamperl A. Kurt , Braun Marvin H. , Jones David R.
Published: May 2006

A large central compliance is thought to dominate the hemodynamics of all vertebrates except birds and mammals. Yet large crocodilians may adumbrate the avian and mammalian condition and set the stage for significant wave transmission (reflection) effects, with potentially detrimental impacts on cardiac performance. To investigate whether crocodilians exhibit wave reflection effects, pressures and flows were recorded from the right aorta, carotid artery, and femoral artery of six adult, anesthetized American alligators ( Alligator mississippiensis) during control conditions and after experimentally induced vasodilation and constriction. Hallmarks of wave reflection phenomena were observed, including marked differences between the measured profiles for flow and pressure, peaking of the femoral pressure pulse, and a diastolic wave in the right aortic pressure profile. Pulse wave velocity and peripheral input impedance increased with progressive constriction, and thus changes in both the timing and magnitude of reflections accounted for the altered reflection effects. Resolution of pressure and flow waves into incident and reflected components showed substantial reflection effects within the right aorta, with reflection coefficients at the first harmonic approaching 0.3 when constricted. Material properties measured from isolated segments of blood vessels revealed a major reflection site at the periphery and, surprisingly, at the junction of the truncus and right aorta. Thus, while our results clearly show that significant wave reflection phenomena are not restricted to birds and mammals, they also suggest that rather than cope with potential negative impacts of reflections, the crocodilian heart simply avoids them because of a large impedance mismatch at the truncus.
Calculation of threshold and saturation points of sigmoidal baroreflex function curves
Authors: McDowall Lachlan M. , Dampney Roger A. L.
Published: May 2006

The logistic sigmoid function curve provides an accurate description of the baroreflex input-output relationship and is the most commonly used equation for this purpose. The threshold (Thr) and saturation (Sat) values for the baroreflex are commonly defined as the values of mean arterial pressure (MAP) at which the reflexly controlled variable (e.g., heart rate or sympathetic nerve activity) is within 5% of the upper or lower plateau, respectively, of the sigmoid function. These values are referred to here as Thr5% and Sat5%. In many studies, Thr and Sat are calculated with the equations Thr = A3 − 2.0/ A2 and Sat = A3 + 2.0/ A2, where A3 is the value of MAP at the point where the reflexly controlled variable is at the midpoint of its range and A2 is the gain coefficient. Although it is commonly stated that the values of Thr and Sat calculated with these equations represent Thr5% and Sat5%, we show here that instead they are significantly greater and less than Thr5% and Sat5%, respectively. Furthermore, the operating range (difference between Thr and Sat) calculated with these equations is 32% less than the difference between Thr5% and Sat5%. We further show that the equations that provide correct values of Thr5% and Sat5% are Thr5% = A3 − 2.944/ A2 and Sat5% = A3 + 2.944/ A2. We propose that these be used as the standard equations for calculating threshold and saturation values when a logistic sigmoid function is used to model the open-loop baroreflex function curve.
Allometric scaling of wall shear stress from mice to humans: quantification using cine phase-contrast MRI and computational fluid dynamics
Authors: Greve Joan M. , Les Andrea S. , Tang Beverly T. , Draney Blomme Mary T. , Wilson Nathan M. , Dalman Ronald L. , Pelc Norbert J. , Taylor Charles A.
Published: May 2006

Allometric scaling laws relate structure or function between species of vastly different sizes. They have rarely been derived for hemodynamic parameters known to affect the cardiovascular system, e.g., wall shear stress (WSS). This work describes noninvasive methods to quantify and determine a scaling law for WSS. Geometry and blood flow velocities in the infrarenal aorta of mice and rats under isoflurane anesthesia were quantified using two-dimensional magnetic resonance angiography and phase-contrast magnetic resonance imaging at 4.7 tesla. Three-dimensional models constructed from anatomic data were discretized and used for computational fluid dynamic simulations using phase-contrast velocity imaging data as inlet boundary conditions. WSS was calculated along the infrarenal aorta and compared between species to formulate an allometric equation for WSS. Mean WSS along the infrarenal aorta was significantly greater in mice and rats compared with humans (87.6, 70.5, and 4.8 dyn/cm2, P < 0.01), and a scaling exponent of −0.38 ( R2 = 0.92) was determined. Manipulation of the murine genome has made small animal models standard surrogates for better understanding the healthy and diseased human cardiovascular system. It has therefore become increasingly important to understand how results scale from mouse to human. This noninvasive methodology provides the opportunity to serially quantify changes in WSS during disease progression and/or therapeutic intervention.
Leg crossing improves orthostatic tolerance in healthy subjects: a placebo-controlled crossover study
Authors: Krediet C. T. Paul , van Lieshout Johannes J. , Bogert Lysander W. J. , Immink Rogier V. , Kim Yu-Sok , Wieling Wouter
Published: May 2006

Vasovagal syncope is the most common cause of transient loss of consciousness, and recurrent vasovagal fainting has a profound impact on quality of life. Physical countermaneuvers are applied as a means of tertiary prevention but have so far only proven useful at the onset of a faint. This placebo-controlled crossover study tested the hypothesis that leg crossing increases orthostatic tolerance. Nine naïve healthy subjects [6 females, median age 25 yr (range 20–41 yr), mean body mass index 23 (SD 2)] were subjected to passive head-up tilt combined with a graded lower body negative pressure challenge (20, 40, and 60 mmHg) determining orthostatic tolerance thrice, in randomized order: 1) control, 2) with leg crossing, and 3) with oral placebo. Blood pressure (Finometer), heart rate, and changes in thoracic blood volume (impedance), stroke volume, and cardiac output (Modelflow) were followed during orthostatic stress. Primary outcome was time to presyncope (systolic blood pressure ≤85 mmHg, heart rate ≥140 beats/min). With leg crossing, orthostatic tolerance increased from 26 ± 2 to 34 ± 2 min (placebo 23 ± 3 min, P < 0.001). During leg crossing, mean arterial pressure (81 vs. 81 mmHg) and cardiac output (95 vs. 94% supine) remained unchanged; heart rate increase was lower (13 vs. 18 beats/min, P < 0.05); stroke volume was higher (79 vs. 74% supine, P < 0.05); and there was a trend toward lower thoracic impedance. Leg crossing increases orthostatic tolerance in healthy human subjects. As a measure of prevention, it is a worthwhile addition to the management of vasovagal syncope.
Compensatory growth of coronary arterioles in postinfarcted heart: regional differences in DNA synthesis and growth factor/receptor expression patterns
Authors: Dedkov Eduard I. , Zheng Wei , Tomanek Robert J.
Published: May 2006

Previous studies have not addressed regional differences in adaptive arteriolar growth in the surviving left ventricular (LV) myocardium after infarction in appropriately aged animals, namely middle-aged or older. Accordingly, we examined the adaptive postinfarction growth of arterioles in two distinct regions, i.e., the LV free wall (LVFW) and septum, of middle-aged rats. We induced a myocardial infarction (MI) in 12-mo-old rats to analyze 1) protein expression in VEGF/Flt-1/Flk-1 and angiopoietin (Ang)-1/Ang-2/Tie-2 systems, 2) the arteriolar DNA synthesis, 3) the extent of the arteriolar bed, and 4) the alteration in minimal coronary vascular resistance. In both regions, arteriolar DNA synthesis was activated between days 4 and 7 after MI. Whereas in the LVFW the degree of DNA synthesis declined between days 11 and 14 post-MI, it continued to rise in the septum, and at day 14, the percentage of the arterioles undergoing DNA synthesis was comparable in the LVFW and the septum (9.7 ± 1.6 and 7 ± 2.1%, respectively). Arteriolar DNA synthesis was mainly associated with upregulation of Ang-2 and Tie-2 in both LV regions. Although 4 wk after MI the arteriolar beds in the LVFW and the septum expanded to the size of sham-operated rats, this growth did not compensate for the greater minimal coronary vascular resistance in the former. Thus our findings suggest that 1) the dynamics in adaptive arteriolar growth were similar between the two regions, despite a delay in the septum; and 2) the perfusion deficit in post-MI rats cannot be accounted for by inadequate adaptive growth of arterioles.
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.
Signaling and regulation of endothelial cell survival by angiopoietin-2
Authors: Harfouche Rania , Hussain Sabah N. A.
Published: May 2006

Angiopoietins are ligands for endothelial cell-specific Tie-2 receptors. Whereas angiopoietin-1 (Ang-1) activates these receptors and promotes cell survival, migration, and sprouting, little information is available regarding how Ang-2 influences these cells. In this study, we evaluated signaling pathways and biological effects of physiological concentrations of Ang-2 in cultured human umbilical vein endothelial cells. Ang-2 at 150 and 300 ng/ml elicited a transient (reaching peak values within 15 min of exposure) increase in the phosphorylation of Tie-2 receptors, protein kinase B (Akt), ERK1/2, and p38 members of the mitogen-activated protein kinases. However, unlike Ang-1, Ang-2 significantly inhibited JNK/SAPK phosphorylation. When vascular endothelial growth factor (VEGF) was present along with Ang-2, ERK1/2 phosphorylation was inhibited, whereas augmentation of Ang-1-induced ERK1/2 phosphorylation was triggered by VEGF. Ang-2 treatment had no effect on cell migration and in vitro wound healing but significantly attenuated serum deprivation-induced apoptosis and promoted survival. These effects were completely reversed by phosphatidylinositol 3 (PI3)-kinase and ERK1/2 inhibitors but were augmented by an inhibitor of the p38 pathway. These results suggest that Ang-2 promotes endothelial cell survival through the ERK1/2 and PI3-kinase pathways and that this angiopoietin is not a strong promoter of endothelial cell migration. We also conclude that the nature of interactions in terms of ERK1/2 activation between Ang-2 and VEGF is different from that of Ang-1 and VEGF.