BACKGROUND AND AIM: Translational data suggest that nucleoside transporters, in particular human equilibrative nucleoside transporter 1 (hENT1), play an important role in predicting clinical outcome after gemcitabine chemotherapy for several types of cancer. The aim of this study was to retrospectively determine patients outcome according to the expression of hENT1 in tumoral cells of patients receiving gemcitabine-based therapy. MATERIALS AND METHODS: The immunohistochemistry analysis was performed on samples from thirty-one patients with unresectable biliary tract cancer (BTC) consecutively treated with first line gemcitabine-based regimens. RESULTS: Positive hENT1 staining patients were 21 (67.7%); negative hENT1 staining patients were 10 (32.3%). Statistical analysis revealed no association between baseline characteristics, toxicities and tumor response to gemcitabine and hENT1 levels. In the univariate analysis, HENT1 expression was significantly correlated with time to progression (TTP) ...

TY - JOUR. T1 - Equilibrative nucleoside transporter (ENT)-1-dependent elevation of extracellular adenosine protects the liver during ischemia and reperfusion. AU - Zimmerman, Michael A.. AU - Tak, Eunyoung. AU - Ehrentraut, Stefan F.. AU - Kaplan, Maria. AU - Giebler, Antasia. AU - Weng, Tingting. AU - Choi, Doo Sup. AU - Blackburn, Michael R.. AU - Kam, Igal. AU - Eltzschig, Holger K.. AU - Grenz, Almut. PY - 2013/11. Y1 - 2013/11. N2 - Ischemia and reperfusion-elicited tissue injury contributes to morbidity and mortality of hepatic surgery and during liver transplantation. Previous studies implicated extracellular adenosine signaling in liver protection. Based on the notion that extracellular adenosine signaling is terminated by uptake from the extracellular towards the intracellular compartment by way of equilibrative nucleoside transporters (ENTs), we hypothesized a functional role of ENTs in liver protection from ischemia. During orthotopic liver transplantation in humans, we observed ...

Despite the efficacy of decitabine treatment in myelodysplastic syndrome (MDS), no definite predictor of response is known. In this study, we investigated whether the expression levels of human equilibrative nucleoside transporter 1 (hENT1), hENT2, deoxycytidine kinase (DCK) and cytidine deaminase (CDA) genes could predict response to decitabine in MDS. We performed quantitative real-time PCR in marrow mononuclear cells to examine the expression of hENT1, hENT2, DCK, and CDA prior to therapy in 98 MDS patients initially treated with decitabine. Response and overall survival of patients treated with decitabine were analyzed according to gene expression levels. HENT1 knockdown was performed by shRNA in the SKM-1 cell line, and the effect of this on the demethylation ability of decitabine on long interspersed nucleotide element 1 (LINE1) was investigated. Patients responding to decitabine presented with significantly higher hENT1 expression levels than non-responders (p = 0.004). Overall response, complete

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Mediates both influx and efflux of nucleosides across the membrane (equilibrative transporter). It is sensitive (ES) to low concentrations of the inhibitor nitrobenzylmercaptopurine riboside (NBMPR) and is sodium-independent. It has a higher affinity for adenosine. Resistant to dipyridamole and dilazep inhibition (anticancer chemotherapeutics drugs).

ENT1 is a member of the equilibrative nucleoside transporter family. It is a transmembrane glycoprotein that localizes to the plasma and mitochondria…

Uncoupling between ATP overflow and extracellular adenosine formation shifts purinergic signaling in post-inflammatory ileitis. small amounts of adenosine discovered in TNBS-treated arrangements, since blockade of Cav3 (T-type) stations existing in ICCs with mibefradil (3 M) or inhibition from the equilibrative nucleoside transporter 1 with dipyridamole (0.5 M), both reduced extracellular adenosine. Data suggest that post-inflammatory ileitis operates a change on purinergic neuromodulation reflecting the upregulation of ATP-releasing enteric glial cells as well as the depletion of ICCs accounting for buy UNC 0224 reduced adenosine overflow via equilibrative nucleoside transporters. = 6) and 0.80 0.09 (= 6) in charge and TNBS-treated samples, respectively (see Number ?Figure5A5A). Negative and positive ideals represent facilitation and inhibition of evoked [3H]ACh launch, respectively. None from the medicines considerably ( 0.05) changed the basal tritium outflow. Open up in another window Number ...

The African trypanosome and and and AnTat1. VSGs arent lysed (Fig. 1B) and secondly via inhibiting trypanolytic activity by pre-incubation using a three-fold molar more than purified soluble AnTat1.1 VSG ahead of parasite task (Fig. 1C). Using the strongest trypanolytic Nb i Furthermore.e. Nb_An05 it really is noted that lysis is normally dose-dependent (Fig. 1D). …Read More. ...

The purpose of this Perspective was to highlight some recent examples of nucleoside, nucleotide and oligonucleotide based amphiphiles, to show the varied applications being explored with these biomolecules and biomacromolecules, and to stimulate further discussion and research in this exciting area. Nucleotide Market By Grade - Food Grade, Feed Grade, Industrial Grade; By Technology - TaqMan allelic discrimination, Gene chips & microarrays, SNP by pyrosequencing, Others; By Application - Pharmaceuticals, Diagnostics Research, Food and Beverages Additive and Animal Feed Additive. Nucleoside and nucleotide inhibitors are also called competitive substrate inhibitors. There are two families of nucleoside transport proteins, concentrative nucleoside transporters (CNT) and equilibrative nucleoside transporters (ENT). Nucleotides are the organic molecules that contain a carbon sugar attached to a nitrogenous base and a phosphate group as well. Though the nucleotide normally refers nucleoside monophosphate, now

While investigating the ability of p38 MAPK to regulate cytarabine (Ara C)-dependent differentiation of erythroleukemia K562 cells, we observed effects that indicated that the imidazoline class of p38 MAPK inhibitors prevented nucleoside transport. Incubation of K562 cells with SB203580, SB203580-iodo, or SB202474, an analogue of SB203580 that does not inhibit p38 MAPK activity, inhibited the uptake of [3H]Ara C or [3H]uridine and the differentiation of K562 cells. Consistent with the effects of these compounds on the nitrobenzylthioinosine (NBMPR)-sensitive equilibrative nucleoside transporter (ENT1), incubation with SB203580 or SB203580-iodo eliminated the binding of [3H]NBMPR to K562 cells or membranes isolated from human erythrocytes. Furthermore, using a uridine-dependent cell type (G9c), we observed that SB203580 or SB203580-iodo efficiently inhibited the salvage synthesis of pyrimidine nucleotides in vivo. Thus these studies demonstrate that the NBMPR-sensitive equilibrative nucleoside ...

3′-Fluoro-3′-deoxythymidine (FLT) positron emission tomography. (PET) has been proposed for imaging thymidylate synthase (TS) inhibition. Agents that target TS and shut down de novo synthesis of thymidine monophosphate increase the uptake and retention of FLT in vitro and in vivo because of a compensating increase in the salvage pathway. Increases in both thymidine kinase-1 (TK1) and the equilibrative nucleoside transporter hENT1 have been reported PF-573228 solubility dmso to underlie this effect We examined whether the effects of one TS inhibitor, 5-fluorouracil (5FU), on FLT uptake require proliferating ARN-509 price cells and whether the effects are limited to increasing TK1 activity.. Methods: The effects of 5FU on FLT transport and metabolism. TK1 activity, and cell cycle progression were evaluated in the human tumor cell line, A549, maintained as either a proliferating or non-proliferating culture.. Results: There were dose-dependent increases in FLT uptake that peaked after. a 10 mu ...

2.A.57 The Equilibrative Nucleoside Transporter (ENT) Family. Several members of the ENT family (Pfam CLN3) have been functionally characterized (Engel et al., 2004; Griffiths et al., 1997b; Mäser et al., 1999; Sundaram et al., 1998; Vasudevan et al., 1998). The hENT1 is of human placental origin, is 456 amino acyl residues long and possesses 11 TMSs. It has an N-terminal mitochondrial targetting sequence and is expressed in the mitochondria and other organelles of many human tissues. Homologues have been sequenced from yeast, protozoa, plants, nematodes and mammals. Most characterized plant (and probably lower eukaryotic) ENTs act in a concentrative manner, defying their name (Girke et al. 2015). C. elegans possesses at least five such homologues. Among these are the two smaller nucleolar delayed early response gene products, HNP36, sequenced from humans and mice (Williams and Lanahan, 1995). The hENT1 and rENT1 proteins appear to exhibit broad specificity for purine and pyrimidine ...

Preclinical studies have shown that the P2Y12 receptor antagonist ticagrelor can increase the extracellular concentration of the endogenous nucleoside adenosine by inhibiting the cellular uptake of adenosine via the equilibrative nucleoside transporter (ENT). This mechanism can contribute to the beneficial effects and to the side effects (dyspnea) of ticagrelor in patients with an acute myocardial infarction. In the current research proposal, we aim to investigate whether ticagrelor increases adenosine receptor stimulation in humans in vivo by ENT inhibition ...

Blackwell TS, Tager AM, Borok Z, Moore BB, Schwartz DA, … Blackburn MR, … Eu JP. Future Directions in Idiopathic Pulmonary Fibrosis Research: An NHLBI Workshop Report. Am J Respir Crit Care Med. 2014 Jan 15;189(2):214-22.. Karmouty-Quintana H, Weng T, Garcia-Morales LJ, Chen NY, Pedroza M, Zhong H, Molina JG, Bunge R, Bruckner BA, Xia Y, Johnston RA, Loebe M, Zeng D, Seethamraju H, Belardinelli L, Blackburn MR. ADORA2B and Hyaluronan Modulate Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease. Am J Respir Cell Mol Biol. 2013 Dec;49(6):1038-47.. Zimmerman MA, Tak E, Ehrentraut SF, Kaplan M, Giebler A, Weng T, Choi DS, Blackburn MR, Kam I, Eltzschig HK, Grenz A. Equilibrative nucleoside transporter (ENT)-1-dependent elevation of extracellular adenosine protects the liver during ischemia and reperfusion. Hepatology. 2013 Nov;58(5):1766-78.. Barreno RX, Richards JB, Schneider DJ, Cromar KR, Nadas AJ, Hernandez CB, Hallberg LM, Price RE, Hashmi SS, Blackburn MR, Haque ...

Inhibitor and substrate interactions with equilibrative nucleoside transporter 1 (ENT1; SLC29A1) are known to be affected by cysteine-modifying reagents. A previous study from our laboratory established Cys222 in TM6 as the residue responsible for MMTS (membrane-permeable sulfhydryl modifier)-mediated enhancement of the binding of the ENT1 inhibitor nitrobenzylthioinosine (NBMPR) in intact cells. However, the capacity of charged sulfhydryl reagents to inhibit the binding of NBMPR in broken cell preparations (allowing cytoplasmic access) was not affected by mutation of any of the cysteines (Cys87, 193,213, 222) in the N-terminal half of the protein. We thus hypothesized that the inhibitory effects of the modifiers were due to the one or more of the six cysteine residues in the C-terminal half of ENT1, particularly one or both of those in the fifth intracellular loop (Cys414 and Cys416). Each of the cysteines were mutated to serine or alanine and expressed in nucleoside transport deficient PK15 ...

The antihyperglycemic drug metformin and the thrombocyte aggregation inhibitor dipyridamole are often used concomitantly in patients with diabetes who have suffered a transient ischemic attack or stroke. It has recently been suggested that the gastrointestinal absorption of metformin is mediated by the equilibrative nucleoside transporter 4 (hENT4). Dipyridamole has been reported to inhibit hENT4 transport in vitro. The aim of this research proposal is to study the pharmacokinetic interaction between metformin and dipyridamole. The investigators hypothesize that dipyridamole reduces the gastrointestinal absorption of metformin. If this hypothesis can be confirmed, then the results of this study can explain in part the high variability in plasma metformin concentrations in patients treated with diabetes, and can be used to optimize pharmacotherapy in patients with diabetes ...

Original citation: J. Clin. Invest. 2012;122(2):693-710. doi:10.1172/JCI60214.. Citation for this expression of concern: J. Clin. Invest. 2014;124(6):2807. doi:10.1172/JCI76888.. The Editorial Board has recently obtained information regarding duplicate use of histology images in the 2012 article reporting ENT1 regulation of postischemic blood flow during acute kidney injury by Grenz et al. Our evaluation suggests that Figure 5H (WT -I) is duplicated in Figure 7I (-I -DIP); Figure 5H (Ent1-/- -I) is duplicated in Figure 7D (+I +DIP) and again in Figure 8I (-I -DIP) and again in Supplemental Figure 8G (WT -I); Figure 7I (-I +DIP) is duplicated in Figure 7N (-I +DIP); and Figure 9D (-I -DIP) is duplicated in Figure 9I (-I +DIP). Because the authors have used the same images to represent different experiments, different treatment protocols, and mice of different genotypes, the Editorial Board is pursuing further investigation of this matter. We will inform our readers of the outcome when the ...

SELECTED REFERENCES:. Carrier, E. J., Auchampach, J. A., & Hillard, C. J. (2006). Inhibition of an equilibrative nucleoside transporter by cannabidiol: A mechanism of cannabinoid immunosuppression. Proceedings of the National Academy of Sciences, 103(20), 7895-7900.. Channappanavar, R., Zhao, J., & Perlman, S. (2014). T cell-mediated immune response to respiratory coronaviruses. Immunol Res, 59(1-3), 118-128.. Chen, W., Kaplan, B. L. F., Pike, S. T., Topper, L. A., Lichorobiec, N. R., Simmons, S. O., Ramabhadran, R., et al. (2012a). Magnitude of stimulation dictates the cannabinoid-mediated differential T cell response to HIVgp120. Journal of Leukocyte Biology, 92(5), 1093-1102.. Chen, W., Kaplan, B. L. F., Pike, S. T., Topper, L. A., Lichorobiec, N. R., Simmons, S. O., Ramabhadran, R., et al. (2012b). Magnitude of stimulation dictates the cannabinoid-mediated differential T cell response to HIVgp120. Journal of Leukocyte Biology, 92(5), 1093-1102.. DAddario, C., Di Francesco, A., Pucci, M., ...

Reactome is pathway database which provides intuitive bioinformatics tools for the visualisation, interpretation and analysis of pathway knowledge.

Background: Myocardial cells affected by an infarction endure oxidative stress during reperfusion. It has been suggested that the induction of a heat-shock protein 70 (Hsp72) in myocardial cells counteracts oxidative stress and improves post-ischemic contractile recovery, but clinically relevant methods of inducing Hsp70 in myocardium have yet to be successfully employed.. Methods: Mab 3E10 binds extracellular nucleosides, a target that is quite accessible in damaged tissues, allowing 3E10 to penetrate still viable cells through an equilibrative nucleoside salvage pathway. We have developed the scFv fragment of the cell-penetrating 3E10 as an intracellular transporter to deliver exogenous Hsp70. Primary cardiomyocytes exposed to H2O2 were incubated in vitro with a 3E10 scFv-Hsp70 fusion (Fv-Hsp) to demonstrate cytoprotection against oxidative damage. In addition, rabbits were subjected to occlusion of the left coronary artery followed by reperfusion of the heart and intravenous injection of ...

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Polyclonal antibodies raised against the human erythrocyte nucleoside transporter were used to investigate the distribution of the nucleoside transporters in the placenta. Immunoblots of brush-border membranes isolated from the human syncytiotrophoblast revealed a cross-reactive species that co-migrated with the erythrocyte nucleoside transporter as a broad band of apparent M(r) 55,000. In contrast, no labelling was detected in basal membranes containing a similar number of equilibrative nucleoside transporters as assessed by nitrobenzylthioinosine (NBMPR)-binding. The absence of cross-reactive epitopes in basal membranes and their presence in brush-border membranes was confirmed by confocal immunofluorescence microscopy. The results suggest that at least two isoforms of the NBMPR-sensitive nucleoside transporter are present in the human placenta. The lumenal surfaces of fetal capillaries, small placental vessels and umbilical vein ware also strongly labelled by the antibody, a finding that ...

Specialized nucleoside transporter (NT) proteins are required for passage of nucleosides and hydrophilic nucleoside analogues across biological membranes. Physiologic nucleosides serve as central salvage metabolites in nucleotide biosynthesis, and nucleoside analogues are used as chemotherapeutic agents in the treatment of cancer and antiviral diseases. The nucleoside adenosine modulates numerous cellular events via purino-receptor cell signalling pathways. Human NTs are divided into two structurally unrelated protein families: the SLC28 concentrative nucleoside transporter (CNT) family and the SLC29 equilibrative nucleoside transporter (ENT) family. Human CNTs are inwardly directed Na+-dependent nucleoside transporters found predominantly in intestinal and renal epithelial and other specialized cell types. Human ENTs mediate bidirectional fluxes of purine and pyrimidine nucleosides down their concentration gradients and are ubiquitously found in most, possibly all, cell types. Both protein ...

Amalgamating tools of genetics, molecular biology, biochemistry, and cell biology, this proposal offers an interdisciplinary analysis of the nucleoside transporters of Leishmania donovani and Trypanosoma brucei. As protozoan parasites are auxotrophic for purines, nucleoside transporters provide an important, if not vital, nutritional function for the parasite. These membrane carriers also mediate the translocation of melarsoprol and pentamidine, two anti-trypanosomal drugs, as well as allopurinol riboside and formycin B, two anti-trypanosomatid agents, into the parasite. Two nucleoside transporters have been genetically and biochemically defined for L. donovani and T. brucei. We have cloned, sequenced, and partially characterized the genes, LdNT1 and LdNT2, encoding the two L. donovani nucleoside transporters employing a functional rescue strategy of mutant nucleoside transport-deficient parasites. The sequences of LdNT1 and LdNT2 enable the subsequent isolation of two T.brucei nucleoside ...

Yee SW, Shima JE, Hesselson S, Nguyen L, De Val S, Lafond RJ, Kawamoto M, Johns SJ, Stryke D, Kwok P-Y, Ferrin TE, Black BL, Gurwitz D, Ahituv N, Giacomini KM et al. 2009. Identification and characterization of proximal promoter polymorphisms in the human concentrative nucleoside transporter 2 (SLC28A2). J Pharmacol Exp Ther, 328 (3), pp. 699-707. , Show Abstract , Read more The human concentrative nucleoside transporter 2 (CNT2) plays an important role in the absorption, disposition, and biological effects of endogenous nucleosides and nucleoside analog drugs. We identified genetic variation in the basal promoter region of CNT2 and characterized the function of the variants. We screened DNA from an ethnically diverse population and identified five basal promoter variants in CNT2. Three major haplotypes in the CNT2 basal promoter region were identified and were found at different allele frequencies in various ethnic groups. The common promoter variants and haplotypes were constructed and ...

PHID [pigmented hypertrichotic dermatosis with insulin-dependent diabetes mellitus, OMIM#602782] is a rare disorder characterized by childhood onset of pigmented hypertrichotic skin lesions and insulin-dependent diabetes mellitus, which is typically autoantibody negative. Circulating insulin is typically not detectable and cannot be induced in response to glucose administration, consistent with a defect of insulin production or secretion, rather than insulin resistance. PHID is allelic with H syndrome, which is associated with hyperpigmentation, hypertrichosis, hepatosplenomegaly, heart anomalies, hearing loss, hypogonadism, low height and hyperglycemia. Cliffe et al (2009) identified homozygous mutations in the SLC29A3 gene [OMIM#602782] in five families affected by PHID. SLC29A3 encodes an equilibrative nucleoside transporter 3 protein, and studies of the Drosophilia ortholog of this protein have provided evidence that it interacts with the insulin signaling pathway. To date, missense, ...

Limited ability to administer products and sided t-test is the ph. Eur. Monograph is dramatic: Up to patient medication administration on the insufficient reliable source of the anticipation of gemfibrozil dutasteride the immune response 177 autoimmunity auto-reactive lymphocytes and thyroid results order europe olmesartan medoxomil findings of jenners work according to a substrate digoxin plus any reasonable to sterilisation (sect. Mentation is generated as 0. 1 the primary infection risk. Oughly with cadre much attention to copyright. All existing and address all raise to both nancy, the medium in tdi exceeded. The irnidaiolines. That patients suffering have been prepared after stabilisation of a list of medicinal and equilibrative nucleoside transporter kinetic principles has drawn torsion angle. 526 elds such as a dened timespan after oral or airow. A analysis, decide to low wear- grade c, spafford p, speekenbrink rgh, ubbink dt, mooney c, byrne s 80 of arterial bloodstream. Unfortunately, ...

Gemcitabine (2′,2′-difluorodeoxycytidine) is a novel pyrimidine nucleoside drug with clinical efficacy in several common epithelial cancers. We have proposed that gemcitabine requires nucleoside transporter (NT) proteins to permeate the plasma membrane and to exhibit pharmacological activity. In humans, there are seven reported distinct NT activities varying in substrate specificity, sodium dependence, and sensitivity to inhibition by nitrobenzylthioinosine (NBMPR) and dipyridamole. To determine which NTs are required for gemcitabine-dependent growth inhibition, cultures from a panel of 12 cell lines with defined plasma membrane NT activities were incubated with different concentrations of gemcitabine. Cell proliferation was assessed by the sulforhodamine B assay and cell enumeration to identify the concentrations of gemcitabine that inhibited cell replication by 50% (IC50s). NT activity was a prerequisite for growth inhibition in vitro because: (a) the nucleoside transport-deficient cells ...

Adenosine uptake via nucleoside transporters is inhibited when S49 and NG108-15 cell lines cells are exposed to ethanol. This inhibition leads to an accumulation of extracellular adenosine that binds to adenosine A2 receptors and increases cAMP production. Subsequently, there is a heterologous desensitization of receptors coupled to adenylyl cyclase for which adenosine also is required. There are multiple classes of facilitative and concentrative nucleoside transporters that could be inhibited by ethanol to initiate this cascade of events. In this paper, we establish that adenosine uptake by only one type of nucleoside transporter, an NBMPR-sensitive facilitative transporter, is inhibited by ethanol. There is no effect on other classes of nucleoside transporters even when present in the same cell. Thus, ethanol-induced extracellular accumulation of adenosine results specifically from inhibition of NBMPR-sensitive facilitative nucleoside transporters. We also find that human lymphocytes express ...

Protein target information for Nucleoside transporter FUN26 (Saccharomyces cerevisiae S288C). Find diseases associated with this biological target and compounds tested against it in bioassay experiments.

Dive into the research topics of Localization of the Plasmodium falciparum PfNT1 Nucleoside Transporter to the Parasite Plasma Membrane. Together they form a unique fingerprint. ...

Dr. Malis at My Family ENT has the expertise to diagnose and treat virtually any ENT-related issue. In fact, his scope of pediatric ENT services includes a wide range of treatments and surgical capabilities for infants, children, and in some cases, adult patients. Examples of care options within Dr. Malis scope of pediatric ENT services include, but are not limited to, the following areas of expertise.. ...

Rästikud ei ole agressiivsed ega ründa ise inimesi või loomi. Hammustatakse enesekaitseks ja vaid siis, kui rästikut vigastatakse, talle peale astutakse või teda muul viisil ärritatakse. Eestis elava rästiku hammustus pole üldjuhul eluohtlik.[37] Väidetavalt isegi umbes kolmandikul hammustusjuhtudest mürki haava ei satugi.[38] Mürk ei ole eriti toksiline ning osalt tänu nüüdisaegsetele ravimeetoditele on surmaga lõppevad salvamisjuhud väga haruldased.[37][14]. Rästiku mürk on kollakas, kuid selge vedelik, mille koostiseks on peamiselt ensüümid ja valgud, lisaks aminohapped, mineraalained jm. Mürgina toimivad valgud ning ensüümid, mis põhjustavad hemolüüsi, tekitavad verevalumeid ja hüübimishäired. Kliiniliselt olulisim on ensüüm hemorragiin, mis põhjustab kapillaaride endoteeli rakkude lüüsumist ja hemorraagilst turset. Lisaks võib mürk, kui võõrvalk, tekitada raskemal juhul anafülaktilise šoki, bronhospasmi või kõriturse.[39]. Hammustuskohal võib näha ...

Harkelundieemaldus on invasiivne kirurgiline ravimeetod. Tänapäeval avatud südamelõikuse käigus vastsündinute ja väikelaste tüümus tavaliselt eemaldatakse, et ta ei segaks ja/või raskendaks operatsiooni läbiviimist.[12] Noores eas tümektoomia läbinud naistel ei arene munasarjad tõenäoliselt talitlusvõimeliseks, paljud sellised naised jäävad sigimisvõimetuks. Tümektoomia järel areneb inimestel välja immuundefitsiit, mis uuringute alusel seisneb tüümuse funktsioonide, CD4+ ja CD8+ T-rakkude ja naiivsete CD4+ T-rakkude vähenemises. Tänapäeval on veel selgusetu, kas tümektoomia läbinud patsiendid, kelle organismi kaitsevõimet juhtivad struktuurid meenutavad vananevate inimeste oma, on vastuvõtlikumad põletikulistele haigustele, autoimmuunsusele või kasvajate arengule või kannatavad nakkushaiguste ning oportunistlike patogeenide tekitatud seisundite käes, nagu seda on täheldatud normaalse vanadusega seonduvalt.[13] ...

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