bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative studies of the protein composition of red blood cell membranes from eight mammalian species
Authors: Matei H. , Frentescu L. , Benga Gh.
Published: May 2007

The polypeptide pattern of red blood cell (RBC) membranes from cow, sheep, horse, rabbit, guinea pig, rat, mouse, analyzed by polyacrylamide gel electrophoresis, was compared to human RBC counterpart. Some qualitative and quantitative differences were noted. Among the high molecular weight components the bands 2.1‐ 2.3 appeared slightly decreased in rabbit and rat and increased in sheep RBC membranes. Band 3 appeared to have a higher molecular weight in the cow, guinea pig and mouse RBCs, and a lower molecular weight in the sheep RBCs. Band 4.1 from the RBC membranes of cow, sheep, rabbit and guinea pig was splitted into two sub‐bands, while band 4.2 overlapped with band 4.1 in horse and guinea pig RBC membranes. There are marked differences in the number and position of bands in the 4.5 region, while band 4.9 is present in higher amounts in horse, rabbit and guinea pig RBC membranes. Band 6 (glyceraldehyde 3‐phosphate dehydrogenase) was undetectable in horse, rat and mouse RBC membranes and was decreased in sheep, rabbit and guinea pig. There are also major differences in the region of band 7 and below (“post‐7”). Band 8 was undetectable in horse, cow and guinea pig, and was in higher amounts in rat. A band corresponding to a molecular weight of about 22 kD in the “post‐8” region was present only in guinea pig RBC membranes.
Tri‐dimensional prostate cell cultures in simulated microgravity and induced changes in lipid second messengers and signal transduction
Authors: Clejan Sanda , O'Connor Kim , Rosensweig Nitsa
Published: May 2007

The high aspect rotating‐wall vessel (HARV) was designed to cultivate cells in an environment that simulate microgravity. We studied previously the effects of HARV cultivation on DU‐145 human prostate carcinoma cells. We determined that HARV cultivation produced a less aggressive, slower growing, less proliferative, more differentiated and less pliant cell than other cell cultivation methods. The result was a 3‐dimensional (3D) growth model of prostate cancer which mimics in vivo tissue growth. This work examines the signal transduction‐second messenger pathways existing temporarily in these HARV cells and correlates these features with the special properties in growth and 3D spheroid formation. We found an initial very active ceramide, a diacylglycerol increase together with increases in PI‐PLC and PLA2 a central defect in PLD (no phosphatic acid or phosphatidylethanol at any time during 15 days of HARV cultivation). There is a cross‐talk between ceramide and PI3K pathways with activation of PI3K, after 6 days of HARV growth concomitant with down‐regulation of ceramide. At this time, there is also an increase of cAMP (seen by increases in arachidonic acid). Taken together these results can explain the 3D organoidlike growth. We therefore developed a model for growth in HARV prostate cancer cells which involve temporal “switches” between second messengers, activation and cross‐talk between multiplicity of signaling pathways and a central defect in PLD pathways. Essential to the late slow growth, and 3D organotypic formation are the apoptotic, anti‐survival, anti‐proliferation and differentiation pathways in the first days of HARV, with growth of “new” different types of prostate cancer cells which set‐up for later “switch” in ceramide‐PI3K to survival and proliferation.
Oxidative damage following cerebral ischemia depends on reperfusion ‐ a biochemical study in rat
Authors: Nita D. Al. , Nita Viorica , Spulber St. , Moldovan M. , Popa Daniela Paula , Zagrean Ana‐Maria , Zagrean L.
Published: May 2007

The extent of brain injury during reperfusion appears to depend on the experimental pattern of ischemia/reperfusion. The goals of this study were: first, to identify the rate of free radicals generation and the antioxidant activity during ischemia and reperfusion by means of biochemical measurement of lipid peroxidation (LPO) and both enzymatic (superoxid dismutase ‐ SOD, catalase ‐ CAT, glutathion peroxidase ‐ GPx) and non‐enzymatic antioxidants activity (glutathione ‐ GSH); and second, to try to find out how the pattern of reperfusion may influence the balance between free radical production and clearance. Wistar male rats were subject of four‐vessel occlusion model (Pulsinelly & Brierley) cerebral blood flow being controlled by means of two atraumatic arterial microclamps placed on carotid arteries. The level of free radicals and the antioxidant activity were measured in ischemic rat brain tissue homogenate using spectrophotometrical techniques. All groups subjected to ischemia shown an increase of LPO and a reduction of the activity of enzymatic antioxidative systems (CAT, GPx, SOD) and non‐enzymatic systems (GSH). For both groups subjected to ischemia and reperfusion, results shown an important increase of LPO but less significant than the levels found in the group with ischemia only. Statistically relevant differences (p<0.01) between continuous reperfusion and fragmented reperfusion were observed concerning the LPO, CAT, SOD and GSH levels, oxidative aggresion during fragmented reperfusion being more important.
Renal cortical remodelling by NO‐synthesis blockers in rats is prevented by angiotensin‐converting enzyme inhibitor and calcium channel blocker
Authors: Mandarim‐de‐Lacerda C. A. , Pereira Leila M. M.
Published: May 2007

The cortical remodelling was studied when chronically nitric oxide synthesis (NOs) blockade (L‐NAME‐induced) hypertensive rats are simultaneously treated, or not, with angiotensin‐converting enzyme inhibitor or calcium channel blocker. Four groups of eight rats each were studied as follows: Control (C), L‐NAME (L), L‐NAME+Enalapril (L+E) and L‐NAME+Verapamil (L+V). The systolic blood pressure (SBP) was weekly recorded. The cortex of the left kidneys was analysed according to the vertical section design. The volume‐weighted mean glomerular volume (VWGV) was made through the “point‐sampled intercepts” method. Enalapril and verapamil were efficient in reducing the SBP in rats submitted to NOs blockade. Glomeruli had considerable alterations in L group rats (glomerular hypertrophy or sclerosis) and tubular atrophy. The VWGV was 100% greater in L group rats than in the C group rats, while it was 30% smaller in L+E and L+V groups than in L group. The tubular volume was 30–50% greater, while the tubular lenght was 20–30% smaller in L group than in the other groups. The renal cortical region showed glomerular sclerosis/hypertrophy and tubular remodelling in rats with NOs blockade that was efficiently prevented with the simultaneous treatment with enalapril or verapamil.
Gap junction remodeling and cardiac arrhythmogenesis: cause or coincidence?
Authors: Severs Nicholas J.
Published: May 2007

Gap junctions, clusters of transmembrane channels that link adjoining cells, mediate myocyte‐to‐myocyte electrical coupling and communication. The component proteins of gap junction channels are termed connexins and, in in vitro expression systems, gap‐junctional channels composed of different connexin types exhibit different biophysical properties. In common with other tissues, the heart expresses multiple connexin isoforms. Spatially defined patterns of expression of three connexin isoforms ‐ connexin43, connexin40 and connexin45 ‐ form the cell‐to‐cell conduction pathways responsible for the orderly spread of current flow that governs the normal cardiac rhythm. Remodeling of gap junction organization and connexin expression is a common feature of human heart disease conditions in which there is an arrhythmic tendency. This remodeling may take the form of disturbances in the distribution of gap junctions and/or quantitative alterations in connexin expression, notably reduced ventricular connexin43 levels. The idea that such changes may contribute to the development of a pro‐arrhythmic substrate in the diseased heart has gained ground over the last decade. Recent studies using transgenic mice models have raised new opportunities to explore the significance of gap junction remodeling in the diseased heart.
Akt and PTEN: New diagnostic markers of non‐small cell lung cancer?
Authors: David Odile
Published: May 2007

We are particularly interested in testing the principles of cell proliferation and apoptosis in the microenvironment of human lung cancers with respect to the cell survival protein Akt1 and PTEN2. Akt is a cytosolic protein which promotes cell survival by phosphorylative inactivation of targets in apoptotic pathways. Akt has been found to play a role in the survival of experimental cancer cell lines in breast, prostate, ovary, lung and brain tissue. PTEN is a tumor suppressor gene whose protein product is expressed in inverse proportion to phosphorylated Akt in endometrial and breast cancer cell lines. No studies of the diagnostic significance of Akt and PTEN in human lung cancers have been reported.
Chromosome‐mediated alterations of the MYC gene in human cancer
Authors: Popescu N. C. , Zimonjic D. B.
Published: May 2007

The step‐wise accumulation of genetic and epigenetic alterations in cancer development includes chromosome rearrangements and viral integration‐mediated genetic alterations that frequently involve proto‐oncogenes. Protooncogenes deregulation lead to unlimited, self‐sufficient cell growth and ultimately generates invasive and destructive tumors. C‐MYC gene, the cellular homologue of the avian myelocitic leukemia virus, is implicated in a large number of human solid tumors, leukemias and lymphomas as well as in a variety of animal neoplasias. Deregulated MYC expression is a common denominator in cancer. Chromosomal rearrangements and integration of oncogenic viruses frequently target MYC locus, causing structural or functional alterations of the gene. In this article, we illustrate how genomic rearrangements and viruses integration affect MYC locus in certain human lymphomas and solid tumors.
Essential arterial hypertension and polymorphism of angiotensiongen M235T gene
Authors: Procopciuc Lucia , Popescu T. , Jebeleanu Gh. , Pop D. , Zdrengehea D.
Published: May 2007

Several candidate genes, chosen from the renin‐ angiotensin system, were examined for their association with essential hypertension. The genes of the renin‐ angiotensin system (RAS) are good candidates for such an approach because this system is well known to be involved in the control of blood pressure. One of these candidate genes is the gene encoding for angiotensinogen (the most important gene of the RAS associated with essential hypertension in the most population, is the gene for angiotensin‐converting enzyme‐ ACE). One DNA polymorphism within exon 2‐ with threonine instead of methionine at position 235 (M235T) was found to be significantly associated with hypertension. The objective of this study is the analysis of M235T polymorphism in angiotensinogen gene in Romanian patients with essential hypertension as well as controls. We examined 38 patients with essential hypertension and 21 normotensive patients. In order to identify the M235T angioteninogen variant, we used the following methods: DNA extraction, PCR amplification and enzymatic digestion of the PCR product using Tth IIII restriction endonuclease enzyme. In the study groups, the M235T variant (Met?Thr in aminoacid position 235) was found more frequently in hypertensive patients (81,57%), than in control subjects (66,66%). We identified 52,63% M235T heterozygotes in the hypertensive group compared with 47,61% in the control group, and 28,94% T235T homozygotes in the hypertensive group compared with 19,04% in the control group. The results of our study suggest an association of the M235T polymorphism in the gene encoding angiotensinogen with essential hypertension
Chondromalacia induced by patellar subluxation: morphological and morphometrical aspects in rabbits
Authors: Sant'Anna M. M. S. , Apfel M. I. R.
Published: May 2007

The purpose of this study was to describe morphologically and quantify the changes of the articular cartilage in chondromalacia, concerning both the chondrocytes and extracellular matrix. Eight rabbits were submitted daily to patellar subluxation, causing chondromalacia after two weeks. The knee fragments obtained were processed by the standard methods. These experimental conditions caused degenerative alterations of the articular cartilage, varying from a slight decrease of proteoglycans, to fibrillations, clefts, and horizontal splitting. The results showed a significantly increase number of chondrocytes (p < 0,000139), although smaller in size (p < 0,000109). The immobilization for 2 weeks and the intermittent passive daily motion afterwards for a period of 2 weeks, was effective to cause patellar chrondomalacia in rabbits.
Neoductular progenitor cells regenerate hepatocytes in severely damaged liver: a comparative ultrastructural study
Authors: Mandache E. , Vidulescu Cristina , Gherghiceanu Mihaela , Dragomir P. , Popescu L. M.
Published: May 2007

In severely injured liver, stem cells give rise to progeny that tend to replace lost hepatocytes. Neoductular reaction appears as an inherent stage of liver reconstruction following severe damage caused by different pathological mechanisms. Few ultrastructural types of progenitor cells have been described, and some molecular phenotypes of progenitor stages have been characterized, but the details of the differentiation process are largely unknown. We prepared for light and electron microscopy examination human liver from biopsies of patients with chronic active hepatitis, and rat liver with allyl alcohol‐induced periportal necrosis. We found that progenitor neoductular cells acquire the hepatocytic polarity pattern during a multi‐step process apparently involving cell migration and dissolution of neoductular basement membrane. An intermediate stage with “mixed” ductular and hepatocytic polarity was described.
Real cells ‐ virtual computers
Authors: Popescu George Alex
Published: May 2007

Now it is quite usual to use real computers to simulte virtual cells. I suggest that real cells (e.g. cells cultured in vitro) might be considered and used as molecular automata. As an imaginary experience, a molecular automata can be built, using real cells and a chemical inert molecule. I suggest that one could be able to test statistical properties of a 2D gas trapped in a box using this sort of automata. Moreover, I would conjecture that any possible algorithm can be implemented in such molecular automata.
Co‐stimulatory and adhesion molecules of dendritic cells in rheumatoid arthritis
Authors: Balanescu Andra , Radu E. , Nat Roxana , Regalia T. , Bojinca Violeta , Predescu V. , Predeteanu Denisa
Published: May 2007

Dendritic cells (DCs) in the rheumatoid arthritis (RA) joint mediate the immunopathological process and act as a potent antigen presenting cell. We compared the expression of co‐stimulatory and adhesion molecules on DCs in RA patients versus controls with traumatic joint lesions and evalulated the correlation between the immunophenotypical presentation of DCs and the clinical status of the disease. Samples of peripheral venous blood, synovial fluid (SF) and synovial tissue (ST) were obtained from 10 patients with RA at the time of hip or knee replacement and from 9 control patients with knee arthroscopy for traumatic lesions. Clinical status was appreciated using the DAS28 score. Blood, SF and dissociated ST cell populations were separated by centrifugation and analyzed by flow cytometry. Cells phenotypes were identified using three‐color flow cytometry analysis for the following receptors HLA‐DR, CD80, CD83, CD86, CD11c, CD18, CD54, CD58, CD3, CD4, CD8, CD19, CD20, CD14, CD16, CD56. HLA‐DR molecules, co‐stimulatory receptors CD80, CD86, CD83 and adhesion molecules CD18, CD11c, CD54, CD58, were analyzed by two‐color immunofluorescence microscopy on ST serial sections. In patients with active RA (DAS28>5.1) we found a highly differentiated subpopulation of DCs in the ST and SF that expressed an activated phenotype (HLA‐DR, CD86+, CD80+, CD83+, CD11c+, CD54+, CD58+). No differences were found between circulating DCs from RA patients and control patients. Our data suggest an interrelationship between clinical outcome and the immunophenotypical presentation of DCs. Clinical active RA (DAS28>5.1) is associated with high incidence of activated DCs population in the ST and SF as demonstrated by expression of adhesion and co‐stimulatory molecules.
Synergistic effects of neurons and astrocytes on the differentiation of brain capillary endothelial cells in culture
Authors: Schiera Gabriella , Bono Epifania , Raffa Maria Pia , Gallo Alessia , Pitarresi Giovanna Laura , Di Liegro Italia , Savettieri G.
Published: May 2007

Brain capillary endothelial cells form a functional barrier between blood and brain, based on the existence of tight junctions that limit paracellular permeability. Occludin is one of the major transmembrane proteins of tight junctions and its peripheral localization gives indication of tight junction formation. We previously reported that RBE4.B cells (brain capillary endothelial cells), cultured on collagen IV, synthesize occludin and correctly localize it at the cell periphery only when cocultured with neurons. In the present study, we describe a three‐cell type‐culture system that allowed us to analyze the combined effects of neurons and astrocytes on differentiation of brain capillary endothelial cells in culture. In particular, we found that, in the presence of astrocytes, the neuron‐induced synthesis and localization of occludin is precocious as compared to cells cocultured with neurons only.
Adhesion inhibition “in vitro” by heparin derivatives correlates with their activity on angiogenesis in mice
Authors: Savu Simona Rizea , Silvestro L.
Published: May 2007

Heparin (HEP) play an important role in angiogenesis. Inhibition of matrix degrading enzymes and binding to adhesion molecules are some of the interaction mechanism. The bleeding risk and the need of parenteral administration, restrict the therapeutic use of HEP as angiogenesis modulator, presently derivatives, with different pharmacokinetic and anticoagulant properties, are available. In this study the “in vitro” anti‐adhesion activity, tested with PMNs and endothelial cells, was compared with the effect on angiogenesis, evaluated in Matrigel implanted mice. Some HEP derivatives, with low anticoagulant activity, showed a significant angiogenesis inhibition. A positive correlation between adhesion inhibition in vitro and anti‐angiogenesis effect in vivo was found suggesting that the interaction with adhesion molecules by HEP derivatives play a relevant role in the angiogenesis control.
Surface wound healing: a new, general function of eukaryotic cells
Authors: Meldolesi J.
Published: May 2007

The ability to repair surface wounds is a property, necessary for long‐term survival, expressed to various extents by all eukaryotic cell types except erythrocytes. The process is based on the rapid Ca2+‐induced exocytosis of various types of specific organelles, such as lysosomes and enlargeosomes, that decreases surface tension and makes possible the spontaneous fusion of lipid monolayers at the lesion edges. The recognized importance of the process in physiology and in several cases of pathology is discussed.
Involvement of protein kinase C‐δ in DNA damage‐induced apoptosis
Authors: Basu Alakananda
Published: May 2007

Apoptosis is a highly orchestrated cell suicidal program required to maintain a balance between cell proliferation and cell death. A defect in apoptotic machinery can cause cancer. Many anticancer drugs are known to kill tumor cells by inducing apoptosis, and a defect in apoptosis can lead to anticancer drug resistance. Apoptosis is regulated by a complex cellular signaling network. Several members of the protein kinase C (PKC) family serve as substrates for caspases and PKCδ isozyme has been intimately associated with DNA damage‐induced apoptosis. It can act both upstream and downstream of caspases. In response to apoptotic stimuli, the full‐length and the catalytic fragment of PKCδ may translocate to distinct cellular compartments, including mitochondria and the nucleus, to reach their targets. Both activation and intracellular distribution of PKCδ may have significant impact on apoptosis. This review intends to assimilate recent views regarding the involvement of PKCδ in DNA damage‐induced apoptosis.
Genetic clock of biologic rhythms
Authors: Badiu C.
Published: May 2007

Biologic rhythms are tighly regulated in all species, in order to addapt to circadian variations of light, temperature and other biological related living conditions. The intrinsic mechanisms of rhythm regulation from every cell to a whole organism is embedded into the genetic clockwork. The mammalian clock genes are reviewed with their interrelation. The per gene promoter is stimulated by clock/bmall heterodimer and trigger the per protoeins synthesis. Innitialy considered as a simple negative feed‐back, from to the phosphorylated per/cry heterodimer towards clock/bmall transcription stimulus, the clockweb of the cell became complex. General characteristics of cell clock genes are integrated in a model. In addition, the involvement of clock genes in peripheral tissues is discussed.
Differential gene expression in infarct scar and viable myocardium from rat heart following coronary ligation
Authors: Xu Y.‐J. , Chapman D. , Dixon I. M.C. , Sethi R. , Guo X. , Dhalla N. S.
Published: May 2007

Post‐myocardial infarction (MI) remodeling of cardiac myocytes and the myocardial interstitium results in alteration of gross ventricular geometry and ventricular dysfunction. To investigate the mechanisms of the remodeling process of the heart after large MI, the expression of various genes in viable left ventricle and infarct scar tissue were examined at 16 weeks post‐MI. Steady‐state expression of Na+‐K+ATPase α‐1 and −2, phospholamban (PLB), α‐myosin heavy chain (α‐MHC), ryanodine receptor (Rya) and Ca2+ ATPase (Serca2) mRNAs were decreased in the infarct scar vs noninfarcted sham‐operated controls (P < 0.05). On the other hand, Giα2 and β‐MHC mRNAs were upregulated (P < 0.05, respectively) in the infarct scar whereas Na+‐K+ ATPase‐β, Na+‐Ca2+ exchanger and Gs mRNAs were not altered vs control values. In viable left ventricle, the a‐1 subunit of Na+‐K+ATPase, α‐3, β‐isoforms, Rya, β‐MHC, Giα2, Gs and Na+‐Ca2+ exchanger were significantly elevated while expression of the a‐2 subunit of Na+‐K+ ATPase, PLB and Serca2 were significantly decreased compared to controls. Expression of CK2α mRNA was elevated in noninfarcted heart (145 ± 15%) and diminished in the infarct scar (66 ± 13%) vs controls. Expression of β‐MHC mRNA was elevated in both viable and infarct scar tissues of experimental hearts (140 ± 31% and 183 ± 30% vs. controls, respectively). These results suggest that cardiac genes in the infarcted tissue and viable left ventricle following MI are differentially regulated.
Electro‐cortical signs of early neuronal damage following transient global cerebral ischemia in rat
Authors: Moldovan M. , Zagrean Ana‐Maria , Avramescu S. , Savaran V. , Zagrean L.
Published: May 2007

During recovery after a transient global cerebral ischemia (TGCI), rat electrocorticogram (ECoG) shows epochs of synchronized activity (SA) alternating with epochs of low amplitude background activity (BA). The aim of this study was to compare the changes in these electrical activities during a 30‐min recovery period that followed either a noninjuring (3 minutes, N=10) or an injuring (10 minutes, N=10) TGCI. During TGCI there was a 3 fold reduction in amplitudes of both SA and BA but no changes in frequency. During reperfusion following a 3 minutes TGCI, the amplitudes of both SA and BA recovered to about 70%. During the reperfusion that followed a 10 minutes TGCI, BA showed no recovery, whereas SA recovered to about 40%. During the 30 min reperfusion, there was a timedependent decrease in the frequency of SA, but independent on the duration of TGCI. In contrast, the frequency of the BA did not change during reperfusion. Our data indicate that following cerebral ischemia the recovery of SA can take place independently of BA. The lack of recovery in BA may indicate early subcortical neuronal damage.
Intracellular calcium signals and control of cell proliferation: how many mechanisms?
Authors: Munaron L. , Antoniotti S. , Lovisolo D.
Published: May 2007

The progression through the cell cycle in non‐transformed cells is under the strict control of extracellular signals called mitogens, that act by eliciting complex cascades of intracellular messengers. Among them, increases in cytosolic free calcium concentration have been long realized to play a crucial role; however, the mechanisms coupling membrane receptor activation to calcium signals are still only partially understood, as are the pathways of calcium entry in the cytosol. This article centers on the role of calcium influx from the extracellular medium in the control of proliferative processes, and reviews the current understanding of the pathways responsible for this influx and of the second messengers involved in their activation.
Soluble, insoluble and geometric signals sculpt the architecture of mineralized tissues
Authors: Ripamonti U.
Published: May 2007

Bone morphogenetic and osteogenic proteins (BMPs/OPs), members of the transforming growth factor‐β (TGF‐β) superfamily, are soluble mediators of tissue morphogenesis and induce de novo endochondral bone formation in heterotopic extraskeletal sites as a recapitulation of embryonic development. In the primate Papio ursinus, the induction of bone formation has been extended to the TGF‐β isoforms per se. In the primate and in the primate only, the TGF‐β isoforms are initiators of endochondral bone formation by induction and act in a species‐, site‐ and tissue‐specific mode with robust endochondral bone induction in heterotopic sites but with limited new bone formation in orthotopic bone defects. The limited inductive capacity orthotopically of TGF‐β isoforms is associated with expression of the inhibitory Smads, Smad6 and Smad7. In primates, bone formation can also be induced using biomimetic crystalline hydroxyapatite matrices with a specific surface geometry and without the exogenous application of osteogenic proteins of the TGF‐β superfamily, even when the biomimetic matrices are implanted heterotopically in the rectus abdominis muscle. The sequence of events that directs new bone formation upon the implantation of highly crystalline biomimetic matrices initiates with vascular invasion, mesenchymal cell migration, attachment and differentiation of osteoblast‐like cells attached to the substratum, expression and synthesis of osteogenic proteins of the TGF‐β superfamily resulting in the induction of bone as a secondary response. The above findings in the primate indicate enormous potential for the bioengineering industry. Of particular interest is that biomimetic matrices with intrinsic osteoinductivity would be an affordable option in the local context.
Morphological and functional changes in rat hippocampal slice cultures after short‐term oxygen‐glucose deprivation
Authors: Lushnikova I. V. , Voronin K. Y. , Malyarevskyy P. Y. , Skibo G. G.
Published: May 2007

To study effects of short‐term cerebral ischemia, hippocampal slice cultures were subjected to oxygen and glucose deprivation (OGD) followed by a period of normoxic reoxygenation. Propidium iodide staining, and MTT/formazanassay were used to evaluate cell viability and metabolic activity. CA1 pyramidal cells were analyzed at the light‐and electron microscopic levels. Cell damage was found to be insignificant during the first hour after 10 min OGD but profound following 4 h, showing delayed neuronal cell damage caused by short‐term OGD. Our model can be used to characterize the mechanisms of cell damage caused by mild cerebral ischemia. These data might apply to further development of neuroprotective tools for the treatment of brain diseases.
The central role of Fas‐ligand cell signaling in inflammatory lung diseases
Authors: DosReis G. A. , Borges Valeria M. , Zin W. A.
Published: May 2007

Following inflammation and injury in the lung, loss of epithelial cell precursors could determine the balance between tissue regeneration and fibrosis. This review discusses evidence that proapoptotic Fas‐Fas ligand (FasL) signaling plays a central role in pulmonary inflammation, injury and fibrosis. FasL signaling induces inflammatory apoptosis in epithelial cells and alveolar macrophages, with concomitant IL‐1β and chemokine release, leading to neutrophil infiltration. FasL signaling plays a critical role in models of acute lung injury, idiopathic pulmonary fibrosis and silicosis; blockade of Fas‐FasL interactions either prevents or attenuates pulmonary inflammation and fibrosis. Serologic and immunohistochemical studies in patients support a major pathogenic role of Fas and FasL molecules in inflammatory lung diseases. Identification of the pathogenic role of FasL could facilitate the discovery of more effective treatments for currently untreatable inflammatory lung diseases.
Adult mesenchymal stem cells: characterization, differentiation, and application in cell and gene therapy
Authors: Baksh D. , Song L. , Tuan R. S.
Published: May 2007

A considerable amount of retrospective data is available that describes putative mesenchymal stem cells (MSCs). However, there is still very little knowledge available that documents the properties of a MSC in its native environment. Although the precise identity of MSCs remains a challenge, further understanding of their biological properties will be greatly advanced by analyzing the mechanisms that govern their self‐renewal and differentiation potential. This review begins with the current state of knowledge on the biology of MSCs, specifically with respect to their existence in the adult organism and postulation of their biological niche. While MSCs are considered suitable candidates for cell‐based strategies owing to their intrinsic capacity to self‐renew and differentiate, there is currently little information available regarding the molecular mechanisms that govern their stem cell potential. We propose here a model for the regulation of MSC differentiation, and recent findings regarding the regulation of MSC differentiation are discussed. Current research efforts focused on elucidating the mechanisms regulating MSC differentiation should facilitate the design of optimal in vitro culture conditions to enhance their clinical utility cell and gene therapy.
Immunomodulatory benefits of cyclosporine A in inflammatory bowel disease
Authors: Kountouras Jannis , Zavos Christos , Chatzopoulos Dimitrios
Published: May 2007

Etiopathogenesis of mucosal inflammation in inflammatory bowel disease remains a complex and enigmatic field; various factors (genetic, environmental and microbial) trigger an event that activates intestinal immune and nonimmune systems cluminating in inflammation and tissue injury. Specifically, both innate and adaptive immune systems seem to play important roles in the pathophysiology of this disease. Cyclosporine A represents a macrolide immune modulator with primary inhibitory effects on T helper lymphocyte production of interleukin‐2, and other cytokines leading to altered T‐lymphocyte and B‐lymphocyte function. The diversity of its therapeutic outcome reported in inflammatory bowel disease may be due to the intricate immuno‐pathogenic profile of the disease and the variety of the applied dose‐dependent courses of therapy. Cyclosporine A exerts additional actions on other components of the inflammatory infiltrate, including neutrophils and mast cells, thereby appearing to be a multi‐dynamic therapeutic approach, although with potential drawbacks, that may be applied alone or combined with other immunomodulatory agents in inflammatory bowel disease patients. Because cyclosporine A induces apoptosis of T‐lymphocytes responsible for perpetuation of the chronic inflammatory process in the disease with potential tumorigenic effect, it may exert a further inhibitory effects on cancer development in inflammatory bowel disease patients, and can be combined with other relative agents, such as rapamycin, which also promotes T‐lymphocyte apoptosis. Therefore, recently established multifactorial action of cyclosporine A in relation to the pathogenesis of the disease can open new horizons for prospective, controlled trials in large cohorts, aiming to emphasize cyclosporine A's potential.
Glutathione depletion‐induced chromosomal DNA fragmentation associated with apoptosis and necrosis
Authors: Higuchi Yoshihiro
Published: May 2007

Chromosomal DNA and mitochondrial dysfunctions play a role on mammalian cell death induced by oxidative stress. The major biochemical dysfunction of chromosome is the presence of an ordered cleavage of the DNA backborn, which is separated and visualized as an electrophoretic pattern of fragments. Oxidative stress provides chromatin giant DNA, 200‐800 kb or 50‐300 kb high molecular weight (HMW) DNA and internucleosomal DNA fragments are produced during apoptosis or necrosis induced by oxidative stress such as gluthione (GSH) depletion in several types of mammalian cells. Reactive oxygen species (ROS)‐mediated DNA fragmentation is Mitochondrial dysfunction on decrease of trans membrane potential, accumulation of ROS, membrane permeability transition transition and release of apoptotic factors during apoptosis or necrosis has been implicated. This review refers to the correlation of chromo‐somal DNA fragmentation and apoptosis or necrosis induced by GSH depletion, and the possible mechanisms of oxidative stress‐induced cell death.
Binding affinities for sulfonamide inhibitors with matrix metalloproteinase‐2 using a linear response method
Authors: Svab I. , Alexandru D. , Vitos Gabriella , Flonta Maria‐Luiza
Published: May 2007

Due to their involvement in many pathological conditions, matrix metalloproteinases (MMPs), are very attractive therapeutic targets. Our study focuses on one of them, MMP‐2, which is involved in tumor progression and metastasis. Recently, the solution structure of the catalytic domain of MMP‐2 complexed with a hydroxamic acid inhibitor (SC‐74020) was published by Feng et al. Using the Hanessian group published binding affinity data and the structure published by Feng as a basis, we have built a binding affinity model by targeting the S2’pocket of the enzyme with set of nine α‐N‐sulfonulamino hydroxamic acid derivatives. Two binding geometries of each ligand have been generated corresponding to two binding modes denoted A and B, respectively, of which the first one is targeting the S2’pocket and the second one the S1 pocket. For the binding affinity model developed for mode A the computed activities show a rmsd of 0.583 kcal/mol as compared with experimental data, and a correlation coefficient r2 of 0.779, while in the case of the binding mode B a rmsd of 0.834 kcal/mol and correlation coefficient r2 of 0.500, respectivley, were obtained. In conclusion, our data suggest a higher probability for the Phe76 gated S2’open form pocket to accommodate the substituent α versus the wide solvent exposed S1 subsite, probability which some research groups could have overlooked due to extensive use in their calculations of non revealing S2’pocket open state crystallographic structures instead of NMR ones.
Provocative use tests in CAPB‐allergic subjects with CAPB‐containing product
Authors: Fartasch M. , Diepgen T. L. , Kuhn M. , Basketter D. A.
Published: May 2007

Cocamidopropyl betaine (CAPB) has been identified as a cause of contact allergy in personal care products. Furthermore, it has been suggested that chemicals responsible are impurities, especially dimethylaminopropylamine (DMAPA). However, skin contact concentrations with these impurities, especially DMAPA. are very low. The aim of the study was to analyse whether subjects with previous positive patch tests to CAPB would react in provocative use tests of a product containing CAPB. 10 individuals with a clinical history of contact allergy to CAPB (by positive patch test and history) took part in a ROAT which used a CAPB‐based shower gel at 25% (DMAPA concentration < 1 ppm). None of the subjects showed positive allergic reactions. 1 of the test subjects did experience a flare of atopic dermatitis at the treatment site. Later, all 10 subjects were patch tested to 3 different concentrations of CAPB and DMAPA (0.1%, 0.3%, 1%) to verify the threshold that was capable of inducing a positive test reaction. 5/10 showed clear + reactions to 1% CAPB (typically at D3), whilst a further 3 gave marginal and/or irritant reactions. Only 1 of the subjects showed an allergic reaction to DMAPA. Finally, in uncontrolled use testing with the shower gel, none of the test subjects reported any adverse skin reactions. Thus, the study confirmed that CAPB‐sensitive individuals can use a CAPB‐based rinse‐off product without the risk of experiencing an allergic reaction to CAPB.
In vitro modulation of TLR‐2, CD1d and IL‐10 by adapalene on normal human skin and acne inflammatory lesions
Authors: Tenaud Isabelle , Khammari Amir , Dreno Brigitte
Published: April 2007

Abstract  The anti‐inflammatory mechanisms of adapalene, a synthetic retinoid used for the treatment of acne patients, are partially understood. They seem particularly related to the modulation of the non‐specific immunity. Recent studies have shown that Toll‐like receptor (TLR)‐2 expression, a receptor of the innate immune system, was increased in acne lesions and could play an essential role in acne‐linked inflammation. The aim of our study was to investigate the new mechanisms of the anti‐inflammatory activity of adapalene in vitro, and more specifically the modulatory effect of adapalene on the expression of TLR‐2, CD1d, a cell surface gycoprotein that plays a role as antigen‐presenting molecules and is responsible for the development of cutaneous inflammation, and also on the expression and the secretion of the anti‐inflammatory interleukin (IL)‐10 cytokine. Both explants of normal human skin and explants of acne patients were incubated with adapalene (10−7 or 10−6 m) or the control medium for 24 h. Evaluation of epidermal expression by immunohistochemistry showed a decreased expression of TLR‐2 and IL‐10 in explants of normal skin and explants of acne with adapalene. On the contrary, adapalene increased CD1d expression in explants of acne patients. Thus, adapalene can modulate the epidermal immune system by increasing the CD1d expression and by decreasing the IL‐10 expression by keratinocytes. Moreover, these modulations could increase the interactions between dendritic cells and T lymphocytes and could strengthen the antimicrobial activity against Propionibacterium acnes. The decreased expression of TLR‐2 by the keratinocytes can contribute to explain the anti‐inflammatory activity of adapalene observed in clinical practice.
Molecular diversity of HLA‐A, ‐B and ‐C alleles in a North Indian population as determined by PCR‐SSOP
Authors: Rani R. , Marcos C. , Lazaro A. M. , Zhang Y. , Stastny P.
Published: May 2007

We have used molecular methods to determine the frequencies of human leukocyte antigen (HLA)‐A, ‐B and ‐C alleles in normal, healthy, unrelated individuals from North India using polymerase chain reaction and hybridization with sequence‐specific oligonucleotide probes as there is no comprehensive report showing molecular diversity of all the class‐I alleles present in North Indians. A*0101, A*0206, A*0301, A*1101, A*6801, A*2401 and A*3101 were the most prevalent alleles of the A locus with 91.11% of the samples showing heterozygosity. At the HLA‐B locus a total of 47 B locus alleles were observed and the only allele found with an allele frequency of 15% was B*5801. Other frequent B‐locus alleles observed were B*5101, B*3503 and B*4006 with relatively less frequent alleles like B*5201, B*3501, B*0702, B*4403, B*5701, B*1801 and B*5501. Of the samples studied 92.31% were heterozygous for B‐locus alleles. Cw*0602 and Cw*0401 were the most frequent C‐locus alleles. Other frequent C‐locus alleles were Cw*0102, Cw*0302, Cw*0701, Cw*0702, Cw*1202, Cw*1203, Cw*1502 and Cw*1503. HLA alleles common in Africans like B*5801, A*68012, B*5301, B*44032, B*4006 and Cw*1701 were observed in the North Indians besides oriental alleles like B*1301, B*1502 and B*4001 confirming that the genetic make‐up of North Indians is Caucasoid with elements of Mongoloid and Negrito races. Some new/rare alleles like B*1802, described as a new allele from Thailand and B*8101, described earlier in a Bubi population were also observed although with low frequencies, showing the diversity of HLA class‐I alleles present in the North Indians.
Evaluation of a method for monoclonal antibody HLA‐B27 analysis with the CELL‐DYN Sapphire haematology analyser
Authors: AARSAND A. K. , JOHANNESSEN H. B. , SCOTT C. S.
Published: May 2007

Analysis of HLA‐B27 is usually performed by flow cytometry using commercial single or two colour fluorescence reagents. The CELL‐DYN Sapphire (CD‐Sapphire) is a high‐volume routine haematology analyser that allows cell population analysis by monoclonal antibody fluorochromes analogous to flow cytometry. In this study, in‐house flow cytometry analysis (n = 96, HLA‐B27, One Lambda) performed on routine patient samples was used as the comparison method for analysis of HLA‐B27, One Lambda (n = 40) and HLA‐B27/HLA‐B7, Immunotech (n = 96) reagents on the CD‐Sapphire. The One Lambda results agreed 100% with the comparison method and offered clear population discrimination. The Immunotech combination also had a high level of agreement, but interpretation was more complex because of the wider cross‐reactivity of the ABC‐m3 antibody with B7 and other HLA‐B alleles. When analysing HLA‐B27 with antibodies showing nonspecific reactivity, a cut‐off staining level yielding high specificity should be chosen, as the primary diagnostic value of HLA‐B27 is as a ‘rule‐out’ test for ankylosing spondylitis. The CD‐Sapphire incorporates automated sampling and lysis, and medical scientists familiar with the instrument would require little additional technical training to perform the analysis. The reduced preanalytical work and total turnaround time constitute an important step towards automation of HLA‐B27 and similar simple high‐volume flow cytometry analysis.
BREAKING DOWN THE BARRIERS TO CLINICAL SERVICE DELIVERY: WALK‐IN FAMILY THERAPY
Authors: Miller John K. , Slive Arnold
Published: May 2007

This article provides a description of a unique walk‐in family therapy service designed to overcome barriers to clinical delivery, as well as a survey of client experiences with the therapy. This therapy modality is aimed at providing an immediately accessible, affordable, nonstigmatizing, single‐session‐focused resource. The service operates from a systemic, collaborative, consumer oriented, pragmatic, non‐pathology perspective. Follow‐up telephone interviews were conducted with 43clients 3 to 6 months after they received treatment. Generally, former clients reported satisfaction with the service. The majority (67%) indicated some level of improvement, and 43% of participants found their single session sufficient to address their concerns. At the time of the session, the majority (86%) of clients were rated by their therapists as “customers” regarding their motivational readiness for change.
AN INTEGRATIVE INTERVENTION FOR PROMOTING RECOVERY FROM EXTRAMARITAL AFFAIRS
Authors: Gordon Kristina Coop , Baucom Donald H. , Snyder Douglas K.
Published: May 2007

The discovery or disclosure of an extramarital affair can have a devastating impact on partners, both individually and on the relationships. Research suggests that affairs occur relatively frequently in relationships and are a common presenting problem in couple therapy. However; despite their prevalence, there is little empirical treatment research in this area, and most therapists describe this problem as one of the more difficult to treat. In this study, we used a replicated case‐study design to explore the efficacy of an integrative treatment designed to help couples recover from an affair. Six couples entered and completed treatment. The majority of these couples were less emotionally or maritally distressed at the end of treatment, and the injured partners reported greater forgiveness regarding the affair. Details of the intervention, suggested adaptations of the treatment, and areas for future research are discussed.
TOWARD A MINI‐THEORY OF THE BLAMER SOFTENING EVENT: TRACKING THE MOMENT‐BY‐MOMENT PROCESS
Authors: Bradley Brent , Furrow James L.
Published: May 2007

In this article we preset the results of a discovery‐oriented task analysis research study identifying specific therapist behaviors that facilitate softening events in emotionally focused therapy (EFT) for couples. Therapy sessions conducted by an expert EFT therapist were examined. Six therapist content theme shifts were identified and specific interventions were delineated within each using an EFT coding scheme (EFT‐CS) created for this study. This study extends the theoretical understanding of the softening process‐a key change event in an empirically validated couples therapy approach‐and provides a detailed clinical map for the training of therapists.
TRAINING FAMILY THERAPISTS TO WORK WITH CHILDREN AND FAMILIES: A MODIFIED DELPHI STUDY
Authors: Sori Catherine Ford , Sprenkle Douglas H.
Published: May 2007

This study examined child inclusion issues and training marriage and family therapists (MFTs) to treat children. This modified Delphi study utilized a panel of experts, and gathered data through questionnaires and qualitative interviews. Panelists believe children should participate in family therapy sessions for both child and adult problems, except when parents are discussing sex or sensitive issues. Child‐focused courses should emphasize developmental issues, engaging techniques, theoretical issues, play therapy theory, MFT treatment for child disorders, and specific child/family problems. Panelists suggest numerous child‐focused references, but reached consensus for only one. Key therapist attributes and skills were identified. Deductive and inductive training methods and the role of supervision were highlighted. Although therapist playfulness and creativity were emphasized, few play techniques were included in the final profile.
REVIEWS
Authors: Harris Steven M.
Published: May 2007

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PARENTING SCHEMAS AND THE PROCESS OF CHANGE
Authors: Azar Sandra T. , Nix Robert L. , Makin‐Byrd Kerry N.
Published: May 2007

Parents' childrearing behaviors are guided by schemas of the caregiving role, their functioning in that role, what children need in general, and what their own children are like in particular. Sometimes, however, parenting schemas can be maladaptive because they are too rigid or simple, involve inappropriate content, or are dominated by negative affect. In this article, we describe parenting schemas and provide an overview of empirical work documenting the characteristics of maladaptive parenting schemas. We review how intervention practices common to multiple therapeutic approaches (cognitive–behavior therapy, family therapy, parent training, attachment‐based interventions, and psychoanalytic parent–infant psychotherapy) attempt to modify schemas to promote more optimal functioning among parents. We highlight how research in cognitive science may explain, in part, treatment effectiveness.
AESTHETIC FORMS OF DATA REPRESENTATION IN QUALITATIVE FAMILY THERAPY RESEARCH
Authors: Piercy Fred P. , Benson Kristen
Published: May 2007

In this article we provide a rationale for using alternative, aesthetic methods of qualitative representation (e.g., creative writing, art, music, performance, poetry) in qualitative family therapy research. We also provide illustrative examples of methods that bring findings to life, and involve the audience in reflecting on their meaning. One problem with such forms of data representation has been that, until recently, there have not been standards with which to evaluate them. We summarize evolving standards and explain when the forms are appropriate and when they are not. We also address issues of legitimacy and conflicting standards held by others.