SEARCH · PubMed Health

Results for “Functional perturbation”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 145 records · Page 8Linked to original sources

PubMed1990

Differential roles of multiple adhesion molecules in cell migration: granule cell migration in cerebellum.

The migration of cerebellar granule cells from the external granular layer to the internal granular layer is mediated by the radical Bergmann glial fiber. Recent works have shown that cell adhesion molecules, extra-cellular matrix proteins and proteolytic enzymes or their activators are involved in this process. Immuno-localization studies showed differential temporal and spatial expression patterns of different adhesion molecules, their isoforms, and post-translational modification during different stages of granule cell migration. Functional perturbation experiments using cerebellar explant cultures demonstrated that several adhesion molecules as well as plasminogen activator are involved in granule cell migration and are required in different stages. Other systems used to study granule cell migration including dissociated microwell cultures and granule cell deficient mouse mutants are discussed in the context of adhesion molecules. The results accumulated so far suggest that the migration of granule cells is a complex process in which the cooperation of a group of molecules with different functions, some for adhesion some for de-adhesion, are required to fulfill the different needs during the migratory course.

Animals↗

PubMed2001

Phagocytosis mediated by Yersinia invasin induces collagenase-1 expression in rabbit synovial fibroblasts through a proinflammatory cascade.

We show that the interaction of the Yersinia surface protein, invasin, with rabbit synovial fibroblasts mediates bead phagocytosis and induces expression of interleukin 1alpha (IL-1alpha), tumor necrosis factor-alpha (TNF-alpha) and MMP-1/collagenase-1 (CL-1). Presentation of invasin as a ligand on the surface of 4.5 microm beads induced phagocytosis and increased CL-1 expression 20-fold after 24 hours. By contrast, presentation of invasin as a spreading substrate did not induce CL-1 expression. CL-1 induction following phagocytosis of invasin-coated beads was mediated by a mechanism dependent on high-affinity binding to beta1 integrins and the function of the small GTPase RhoA. Expression of a function-perturbing mutant, RhoAN19, abrogated bead-induced CL-1 expression. RhoA activation coupled bead phagocytosis with signal transduction because expression of constitutively active mutant RhoV14 was sufficient to trigger CL-1 expression. The signal-transduction cascade elicited by bead phagocytosis triggered NFkappaB activation, stimulating a proinflammatory cellular response with transient increases in TNF-alpha production that peaked at 2 hours and induction of IL-1alpha that was sustained for at least 10 hours. Inhibition of IL-1alpha function by blocking antibodies or IL-1 receptor antagonist showed that IL-1alpha is the autocrine intermediary for subsequent CL-1 induction.

Adhesins, Bacterial↗

PubMed2005

Single nucleotide polymorphisms in the human norepinephrine transporter gene affect expression, trafficking, antidepressant interaction, and protein kinase C regulation.

The role of norepinephrine (NE) in attention, memory, affect, stress, heart rate, and blood pressure implicates NE in psychiatric and cardiovascular disease. The norepinephrine transporter (NET) mediates reuptake of released catecholamines, thus playing a role in the limitation of signaling strength in the central and peripheral nervous systems. Nonsynonymous single nucleotide polymorphisms (SNPs) in the human NET (hNET) gene that influence transporter function can contribute to disease, such as the nonfunctional transporter, A457P, identified in orthostatic intolerance. Here, we examine additional amino acid variants that have been identified but not characterized in populations that include cardiovascular phenotypes. Variant hNETs were expressed in COS-7 cells and were assayed for protein expression and trafficking using cell-surface biotinylation and Western blot analysis, transport of radiolabeled substrate, antagonist interaction, and regulation through protein kinase C (PKC)-linked pathways by the phorbol ester beta-phorbol-12-myristate-13-acetate. We observed functional perturbations in 6 of the 10 mutants studied. Several variants were defective in trafficking and transport, with the most dramatic effect observed for A369P, which was completely devoid of the fully glycosylated form of transporter protein, was retained intracellularly, and lacked any transport activity. Furthermore, A369P and another trafficking variant, N292T, impeded surface expression of hNET when coexpressed. F528C demonstrated increased transport and, remarkably, exhibited both insensitivity to down-regulation by PKC and a decrease in potency for the tricyclic antidepressant desipramine. These findings reveal functional deficits that are likely to compromise NE signaling in SNP carriers in the population and identify key regions of NET contributing to transporter biosynthesis, activity, and regulation.

Animals↗

PubMedDate not supplied

Structural effects of the local anesthetic bupivacaine hydrochloride on the human erythrocyte membrane and molecular models.

The interaction of the local anesthetic bupivacaine with the human erythrocyte membrane and molecular models is described. The latter consisted of isolated unsealed human erythrocyte membranes (IUM), large unilamellar vesicles (LUV) of dimyristoylphosphatidylcholine (DMPC), and phospholipid multilayers built-up of DMPC and dimyristoylphosphatidylethanolamine (DMPE), representatives of phospholipid classes located in the outer and inner monolayers of the human erythrocyte membrane, respectively. Optical and scanning electron microscopy revealed that bupivacaine induced erythrocyte spheroechinocytosis. According to the bilayer couple hypothesis, this result implied that bupivacaine inserted in the outer monolayer of the erythrocyte membrane. Experiments performed on IUM and DMPC LUV by fluorescence spectroscopy and X-ray diffraction on DMPC and DMPE multilayers confirmed this result. Changes in the molecular organization of membranes alter lipid-protein interactions and induce functional perturbation of membrane proteins such as Na(+) channels. Since local anesthetics may control the influx of Na(+) into the human erythrocyte, in order to relate the structural perturbations induced by bupivacaine in these systems to Na(+) transport, the interaction of this anesthetic with isolated toad skin was also studied. Electrophysiological measurements indicated a significant decrease in the potential difference and in the short-circuit current of the skin after the application of the anesthetic, reflecting inhibition of the active transport of ions. These results suggest that bupivacaine-induced conformational changes of the lipid molecules alter the lipid-protein boundaries of the outer moiety of the erythrocyte membrane, thus interfering with the function of neighboring sodium channels.

Anesthetics, Local↗

PubMed2007

Distinct neuronal circuits mediate experience-dependent, non-associative osmotactic responses in Drosophila.

Osmotactic responses can be modified in an experience-dependent manner and have been used to condition animals in negative or positive associative paradigms. Experience-dependent non-associative defects in avoidance of aversive odors were reported in Drosophila learning mutants. This prompted an examination of the contribution of the mushroom bodies and inner antenoglomerular tract, the two neuronal populations implicated in processing olfactory information to experience-dependent non-associative osmotactic responses. Silencing inner antenoglomerular tract synapses results in defective osmotaxis after experiencing a different odor, but not electric shock. Conversely, structural or functional perturbation of the mushroom bodies precipitates osmotactic deficits after prior experience of electric shock but not odors. These effects on osmotaxis are specific, long lasting and independent of the aversive or attractive properties of the odors. Deficient osmotactic responses only after electric shock stimulation were exhibited by mutants with altered cAMP levels, but all other mutants in genes preferentially expressed in the mushroom bodies responded normally. Our results suggest that the mushroom bodies and inner antenoglomerular tract are essential for normal osmotactic responses after prior stimulation with electric shock or another odor respectively. Finally, these experience-dependent non-associative paradigms are excellent methods of functionally ascertaining normal activity of the mushroom bodies and inner antenoglomerular tract in putative leaning and memory mutants.

Analysis of Variance↗

PubMed2000

Inhibition of pig granulosa cell adhesion and growth in vitro by immunoneutralization of epithelial cadherin.

Epithelial cadherin (E-cadherin) is a member of the cadherin family of calcium-dependent cell adhesion molecules and is present in the ovary. Although expression of E-cadherin is high in healthy pig granulosa cells and low in granulosa cells of atretic follicles, the importance of E-cadherin-mediated adhesion in granulosa cell function is unclear. The aim of the present study was to determine the impact of immunoneutralization of E-cadherin on granulosa cell adhesion, DNA synthesis and cell proliferation in vitro. Before attachment, pig granulosa cells were exposed to a monoclonal E-cadherin antibody (DECMA-1) which blocks E-cadherin function. Controls included substitution of the antibody with either mouse ascites fluid or another E-cadherin antibody directed against the cytoplasmic domain and which was therefore inaccessible in intact cells. Both granulosa cell proliferation and insulin-like growth factor I-induced DNA synthesis were inhibited significantly in the presence of DECMA-1 compared with controls (P < 0.05). Control granulosa cells in culture formed large clusters with many cells packed tightly together. However, after 48 h exposure to the function-perturbing E-cadherin antibody, there was a significant decrease in the size of the granulosa cell clusters (P < 0.05) and the degree of cell-cell contact was reduced compared with control cultures. No effects on DNA synthesis, cell proliferation or cell adhesion were observed when DECMA-1 was substituted with either mouse ascites fluid or the antibody specific for the cytoplasmic domain of E-cadherin. In conclusion, these data provide evidence to support the hypothesis that E-cadherin is important for maintaining granulosa cell contact, DNA synthesis and cell proliferation in vitro. These results indicate that E-cadherin plays a fundamental role in maintaining both the structure and function of ovarian follicles.

Analysis of Variance↗

PubMed1999

HGF induces FAK activation and integrin-mediated adhesion in MTLn3 breast carcinoma cells.

Expression of hepatocyte growth factor (HGF) and its tyrosine kinase receptor, c-Met, is positively correlated with breast carcinoma progression. We found that in invasive and metastatic MTLn3 breast carcinoma cells, HGF stimulated both initial adhesion to and motility on the extracellular matrix (ECM) ligands laminin 1, type I collagen, and fibronectin. Next, analysis with function-perturbing antibodies showed that adhesion to the different ECM proteins was mediated through specific beta1 integrins. In MTLn3 cells, HGF induced rapid tyrosine phosphorylation and activation of both c-Met and focal adhesion kinase (FAK). Cell anchorage and adhesion to the ECM substrates was required for HGF-induced FAK activation, since HGF failed to trigger tyrosine phosphorylation of FAK in suspended cells. Our results provide evidence that the 2 signaling pathways, integrin/ECM and c-Met/HGF, cooperate synergistically to induce FAK activation in an adhesion-dependent manner, leading to enhanced cell adhesion and motility. Moreover, we found that a FRNK (the FAK-related non-kinase)-like molecule is expressed in MTLn3 cells. Since FRNK acts as a competitive inhibitor of FAK function, our results suggest that a FRNK-like protein could facilitate disassembly of focal adhesions and likely be responsible for the HGF-induced scattering and motility of MTLn3 cells.

Animals↗

PubMed1999

Laminin and beta1 integrins are crucial for normal mammary gland development in the mouse.

We have examined the role of integrin-extracellular matrix interactions in the morphogenesis of ductal structures in vivo using the developing mouse mammary gland as a model. At puberty, ductal growth from terminal end buds results in an arborescent network that eventually fills the gland, whereupon the buds shrink in size and become mitotically inactive. End buds are surrounded by a basement membrane, which we show contains laminin-1 and collagen IV. To address the role of cell-matrix interactions in gland development, pellets containing function-perturbing anti-beta1 integrin, anti-alpha6 integrin, and anti-laminin antibodies respectively were implanted into mammary glands at puberty. Blocking beta1 integrins dramatically reduced both the number of end buds per gland and the extent of the mammary ductal network, compared with controls. These effects were specific to the end buds since the rest of the gland architecture remained intact. Reduced development was still apparent after 6 days, but end buds subsequently reappeared, indicating that the inhibition of beta1 integrins was reversible. Similar results were obtained with anti-laminin antibodies. In contrast, no effect on morphogenesis in vivo was seen with anti-alpha6 integrin antibody, suggesting that alpha6 is not the important partner for beta1 in this system. The studies with beta1 integrin were confirmed in a culture model of ductal morphogenesis, where we show that hepatocyte growth factor (HGF)-induced tubulogenesis is dependent on functional beta1 integrins. Thus integrins and HGF cooperate to regulate ductal morphogenesis. We propose that both laminin and beta1 integrins are required to permit cellular traction through the stromal matrix and are therefore essential for maintaining end bud structure and function in normal pubertal mammary gland development.

Animals↗

PubMed1996

Adhesion of human trabecular meshwork cells to extracellular matrix proteins. Roles and distribution of integrin receptors.

PURPOSE: To examine the adhesion of human trabecular meshwork cells with various extracellular matrix (ECM) proteins and to evaluate the roles and distribution of integrin receptors. METHODS: Cultured human trabecular meshwork cells were added to 96-well plates either uncoated or coated with proteins including fibronectin, laminin, and vitronectin, as well as collagen types I, III, IV, V, and VI. After incubation for 1 hour, the adhesion of cells was measured. Expression of cell surface integrins was determined by cell enzyme-linked immunoadsorbent assay (ELISA) and immunoprecipitation. Distribution was visualized by immunofluorescence staining using integrin-specific antibodies. For function perturbation and peptide inhibition studies, cells were preincubated with either integrin antibodies or synthetic peptides before the adhesion assays. RESULTS: Human trabecular meshwork cells attached to plates coated with ECM proteins in a dose-dependent manner. Fibronectin, vitronectin, and collagen types I and IV were the preferred ECM substrates. Cell ELISA revealed the presence of integrins alpha 1, alpha 2, alpha 3, alpha 4, alpha 5, alpha 6, alpha v, beta 1, beta 3, beta 5, alpha 5 beta 1, and alpha v beta 3 and the absence of beta 2 and beta 4 on human trabecular meshwork cells. Results from immunostaining experiments were consistent with those from cell ELISA studies. Attachment of cells to ECM proteins was blocked by specific integrin antibodies. Cell adhesion to fibronectin and vitronectin was inhibited by peptides containing the Arg-Gly-Asp sequence. CONCLUSIONS: Extracellular matrix proteins mediate the adhesion of human trabecular meshwork cells in culture. Integrin receptors appear to have functional roles in the cell-matrix interactions.

Adolescent↗

PubMed2026

Spatial scaling of metagenomic diversity reveals ecological disruption in the gut microbiome of gout patients.

Gout, a painful inflammatory arthritis, is characterized by hyperuricemia and monosodium urate crystal deposition, with growing evidence linking its pathogenesis to gut microbiome dysbiosis. However, traditional diversity metrics fail to capture the complex spatial organization of microbial communities. This study addresses this gap by applying the novel metagenomic Diversity-Area Relationship (m-DAR) model to investigate scaling laws in the gout microbiome-quantifying how metagenomic diversity changes with the number of individuals sampled. Our analysis of gut microbiomes from gout patients and healthy controls revealed fundamental ecological disruptions. We found that gout microbiomes exhibited significantly altered scaling patterns: they showed greater inter-individual dissimilarity (higher z-values) at the level of rare genes (q = 0), but weaker scaling of dominant genes (q = 1-3) compared to healthy controls. Crucially, the maximal accrual diversity (MAD) was substantially lower in gout patients, indicating a severely constrained potential for total microbial gene diversity. Furthermore, profiling of metagenomic functional gene clusters (MFGCs) uncovered widespread functional perturbations, including increased diversity scaling for carbohydrate-active enzymes (CAZy) but decreased scaling in essential metabolic pathways (KEGG, KO). These results demonstrate that the gout gut microbiome is defined by a loss of ecological structure, featuring reduced homogeneity in dominant taxa, expanded rare biosphere variation, and an overall collapsed diversity capacity. This work introduces an ecological framework for characterizing dysbiosis in gout that complements traditional diversity metrics and may inform the development of microbiome-based therapeutic strategies. Further research is needed to translate these ecological patterns into clinical applications.

Humans↗

PubMed2005

Morphological and biochemical perturbations in rat erythrocytes following in vitro exposure to Fenvalerate and its metabolite.

Erythrocytes are a convenient model to understand the membrane oxidative damage induced by various xenobiotic-prooxidants. In this investigation, we have examined the potency of Fenvalerate (FEN) and its metabolite, p-chlorophenyl isovaleric acid (p-CPIA) to induce oxidative stress response in rat erythrocytes in vitro in terms of lipid peroxidation and effects on selected antioxidant enzymes. Susceptibility of erythrocytes to FEN exposure was further investigated in terms of morphological alterations by scanning electron microscopy and protein damage by gel electrophoresis of erythrocyte ghosts. Following in vitro exposure, FEN caused a significant induction of oxidative damage in erythrocytes at concentrations beyond 0.1 mM as evidenced by increased thiobarbituric acid reactive substances (TBARS) levels. The response was both concentration and time dependent. At higher concentrations, significant decreases in the activities of vital antioxidant enzymes viz., catalase, superoxide dismutase, glutathione transferase and glutathione reductase were also discernible clearly suggesting the potency of both, parent compound and its metabolite to induce oxidative stress in erythrocytes. Scanning electron micrographs of erythrocytes following FEN exposure at higher concentrations revealed various degrees of distortion in shape and ruptured membranes. Furthermore, gel electrophoresis studies revealed consistent and significant aggregation of only band 3 protein in erythrocyte membranes exposed to either FEN or p-CPIA at higher concentrations. These in vitro findings show that FEN and its metabolite have the propensity to cause significant oxidative damage in rat erythrocytes, which is associated with marked damage to membrane proteins. These data suggest that both structural and functional perturbations may ensue in erythrocytes following exposure to FEN at higher concentrations under in vivo situations.

Animals↗

PubMed2003

The future of regulatory toxicology: impact of the biotechnology revolution.

The molecular biology revolution and the advent of genomic and proteomic technologies are facilitating rapid advances in our understanding of the molecular details of cell and tissue function. These advances have the potential to transform toxicological and clinical practice, and are likely to lead to the supplementation or replacement of traditional biomarkers of cellular integrity, cell and tissue homeostasis, and morphological alterations that result from cell damage or death. New technologies that permit simultaneous monitoring of many hundreds, or thousands, of macro- and small molecules ("-omics" technologies) promise to allow functional monitoring of multiple (or perhaps all) key cellular pathways simultaneously. Elucidation of cellular responses to molecular damage, including evolutionarily conserved inducible molecular defense systems, suggests the possibility of new biomarkers based on molecular responses to functional perturbations and cellular damage. Our improved understanding of the molecular basis of various pathologies suggests that monitoring specific molecular responses may provide improved prediction of human outcomes. Responses that can be monitored directly in the human should provide "bridging biomarkers" that may eliminate much of the current uncertainty in extrapolating from laboratory models to human outcome. Another aspect of genomics is our enhanced ability to associate DNA sequence variations with biological outcomes and individual sensitivity. The human genome sequence has revealed that sequence variations are very common, and may be an important determinant of variation in biological outcomes. The impending availability of a complete human haplotype map linked to standard genetic markers greatly facilitates identification of genetic variations that convey sensitivity or resistance to chemical exposures. Genetic approaches have already linked a large number of genetic variants (polymorphisms) with human diseases and adverse reactions from exposure to drugs or toxicants, suggesting an important role in sensitivity to drugs and environmental agents, disease susceptibilities, and therapeutic responses. As these opportunities are transformed into reality, regulatory toxicological practice is likely to be shaped in the future by the combination of conventional pathology, toxicology, molecular genetics, biochemistry, cell biology, and computational bio-informatics-resulting in the broad application of molecular approaches to monitoring functional disturbances.

Animals↗

PubMed1997

Characterization of monoclonal antibodies against tenascin-C: no apparent effect on kidney development in vitro.

Tenascin-C is an extracellular matrix glycoprotein found in embryonic mesenchyme. The precise biological function of tenascin-C is unknown, but different parts of the molecule have effects on cell adhesion and other cellular activities. We studied the expression and role of tenascin-C in the embryonic mouse kidney. By Northern blots, no tenascin-C was detectable in uninduced mesenchyme from day 11 embryonic kidneys, but after 24 hours of in vitro culture both major splice variants of tenascin-C were detected. The larger variant was the predominant form. By in situ hybridization tenascin-C mRNA in 13-day old embryonic kidneys was detected in the mesenchyme surrounding newly formed epithelial structures. In 17-day old embryonic kidneys, tenascin-C mRNA was detected in mesenchyme around the forming epithelial structures in the cortex, and expression was also seen in mesenchyme surrounding the capsular epithelium of glomeruli. In newborn kidneys, expression had shifted to the medulla but was still confined to mesenchymal areas. We have characterized 6 new monoclonal antibodies against mouse tenascin-C, which all stain embryonic kidneys from different stages in a pattern consistent with earlier reports and with the mRNA data. The binding sites of the monoclonal antibodies on the tenascin-C molecule were mapped to discrete regions of tenascin-C. These six and five previously described antibodies against tenascin-C were tested in antibody perturbation experiments. Three of these have been shown by in vitro assays to perturb function of other cell types. Despite this, none of them inhibited development of mouse kidneys in organ culture, although they were tested at 1 mg/ml. It raises the possibility that tenascin-C is not crucial for kidney development. Alternatively, tenascin-C has more subtle functions which could not be identified with the assays used here.

Animals↗

PubMed1998

Design of protein function by physical perturbation method.

Based on three-dimensional structure of proteins, a rational strategy to design the protein function by physical perturbation method was proposed and tested on one of the well-examined enzymes, thermolysin for higher catalytic activity. An attempt was made to change the electrostatic potential and the dynamic property of three-dimensional structure around the active sites by single-amino-acid mutations, and the physical property of the mutants was then evaluated. Several mutants were found to have remarkably higher enzymatic activity than wild type. The multiple mutation was introduced and the logarithm of the activity was found to be almost additive. A ten times higher active mutant was realized by simultaneously introducing three single-mutations. This strategy can be easily extended to not only other enzymes but also other kinds of proteins than enzymes to modify or control the protein function based on their three-dimensional structures.

Amino Acid Substitution↗

PubMed1998

Protein tyrosine kinases: structure, substrate specificity, and drug discovery.

Protein tyrosine kinases (PTKs) play a crucial role in many cell regulatory processes. It is therefore not surprising to see that functional perturbation of PTKs results in many diseases. Despite the diverse primary structure organization of various PTKs, the catalytic or kinase domains of various PTKs as well as that of Ser/Thr kinases are generally conserved. The high resolution crystal structure of a few PTKs has been solved in the last few years. In contrast to the well-defined linear peptide substrate motifs recognized by specific Ser/Thr kinases, the identification of specific substrate motifs for PTK has been slow. It is not until recently that through the use of combinatorial peptide library methods that specific recognition motifs for specific PTKs have begun to emerge. Efficient and specific peptide substrates for some PTKs with Km at the mid microM range have been identified. Based on these peptide substrates, relatively potent (IC50 at the low microM range) and highly selective pseudosubstrate-based peptide inhibitors have been developed. There has been enormous effort in the development of PTK inhibitors for diseases such as cancer, psoriasis, and osteoporosis. Several new high-throughput PTK assay technologies have recently been described. Small molecules against specific PTK have been developed. Most of them are competitive inhibitors at the ATP binding site. Some of these inhibitors have already been in clinical trial.

Amino Acid Sequence↗

PubMed2002

Ab-initio study of NMR chemical shifts of water under normal and supercritical conditions.

We present a theoretical investigation of the hydrogen nuclear magnetic resonance (NMR) chemical shift and the magnetic susceptibility of normal and supercritical water using a recently developed ab initio approach in the framework of density functional perturbation theory. The results are in very good agreement with experiment. The shifts can be used to determine whether the atomic configurations, taken from a first principles simulation, give a good description of the system on a microscopic scale. In particular, the hydrogen chemical shifts are very sensitive to the character of the hydrogen bond network, which plays a crucial role in the macroscopic properties of liquid water under normal and supercritical conditions.

Journal Article↗

PubMed2004

The calculation of the vibrational frequencies of crystalline compounds and its implementation in the CRYSTAL code.

The problem of numerical accuracy in the calculation of vibrational frequencies of crystalline compounds from the hessian matrix is discussed with reference to alpha-quartz (SiO(2)) as a case study and to the specific implementation in the CRYSTAL code. The Hessian matrix is obtained by numerical differentiation of the analytical gradient of the energy with respect to the atomic positions. The process of calculating vibrational frequencies involves two steps: the determination of the equilibrium geometry, and the calculation of the frequencies themselves. The parameters controlling the truncation of the Coulomb and exchange series in Hartree-Fock, the quality of the grid used for the numerical integration of the Exchange-correlation potential in Density Functional Theory, the SCF convergence criteria, the parameters controlling the convergence of the optimization process as well as those controlling the accuracy of the numerical calculation of the Hessian matrix can influence the obtained vibrational frequencies to some extent. The effect of all these parameters is discussed and documented. It is concluded that with relatively economical computational conditions the uncertainty related to these parameters is smaller than 2-4 cm(-1). In the case of the Local Density Approximation scheme, comparison is possible with recent calculations performed with a Density Functional Perturbation Theory method and a plane-wave basis set.

Journal Article↗

PubMed1995

Initiation of non-neoplastic late effects: the role of endothelium and connective tissue.

While early radiation lesions might be a direct consequence of parenchymal cell loss, late-radiation injury most probably develops as a consequence of functional perturbations that may involve both parenchymal and nonparenchymal elements. Damage to blood vessels and consequent perturbations in blood flow and endothelial physiology play an important role in the development of late effects. The development of late-radiation damage has been studied in three different tissue systems: the skin, kidney and central nervous system. The results suggested that damage to vascular tissue played a major role in the development of radiation-induced late effects.

Animals↗