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Biomedical subjects

F Wang

Publications and source records attributed to F Wang.

At least 397 records · Page 22Linked to original sources
PubMed1997

An animal model for acute and persistent Epstein-Barr virus infection.

Epstein-Barr virus (EBV) is a human lymphocryptovirus that causes infectious mononucleosis, persists asymptomatically for life in nearly all adults, and is associated with the development of B cell lymphomas and nasopharyngeal carcinomas. A highly similar rhesus lymphocryptovirus naturally endemic in rhesus monkeys was used to orally infect naïve animals from a pathogen-free colony. This animal model reproduced key aspects of human EBV infection, including oral transmission, atypical lymphocytosis, lymphadenopathy, activation of CD23(+) peripheral blood B cells, sustained serologic responses to lytic and latent EBV antigens, latent infection in the peripheral blood, and virus persistence in oropharyngeal secretions. This system may be useful for studying the pathogenesis, prevention, and treatment of EBV infection and associated oncogenesis.

Animals↗
PubMed1997

Identification of a functional imperfect estrogen-responsive element in the 5'-promoter region of the human cathepsin D gene.

17beta-Estradiol (E2) induces cathepsin D gene expression in MCF-7 human breast cancer cells. Previous studies have identified an Sp1-imperfect estrogen-responsive element (ERE) half-site [GGGCGG(N)23ACGGG] (-199 to -165) in the promoter region which forms an Sp1-estrogen receptor (ER) complex and confers E2 responsiveness on the corresponding Sp1-ERE-chloramphenicol acetyl transferase (CAT) construct. Further analysis of downstream regions of the promoter identified a CGCCC(N)3TGACC sequence (-119 to -107) which is homologous to the adenovirus major late promoter element (MLPE) and binds the ER to form a retarded band in a gel electrophoretic mobility shift assay. The corresponding promoter-CAT construct is also E2-inducible. The MLPE resembles an imperfect palindromic ERE containing imperfect (5') and perfect (3') ERE half-sites; analysis of oligonucleotides with mutations in these half-sites shows that only the perfect ERE half-site is required for binding the ER, whereas both sites are required for transactivation. In vivo exonuclease III footprinting showed that treatment with E2 also enhanced binding at the MLPE site. Identification of this second functional enhancer sequence in the 5'-promoter region of cathepsin D is consistent with the increasingly complex cell-specific regulation of hormone-responsive genes.

Base Sequence↗
PubMed1997

Sphingosine 1-phosphate stimulates rho-mediated tyrosine phosphorylation of focal adhesion kinase and paxillin in Swiss 3T3 fibroblasts.

Sphingosine 1-phosphate (SPP), a sphingolipid second messenger implicated in the mitogenic action of platelet-derived growth factor [Olivera, A. and Spiegel, S. (1993) Nature (London) 365, 557-560], induced rapid reorganization of the actin cytoskeleton resulting in stress-fibre formation. SPP also induced transient tyrosine phosphorylation of focal adhesion kinase (p125(FAK)), a cytosolic tyrosine kinase that localizes in focal adhesions, and of the cytoskeleton-associated protein paxillin. Exoenzyme C3 transferase, which ADP-ribosylates Rho (a Ras-related small GTP binding protein) on asparagine-41 and renders it biologically inactive, inhibited both stress-fibre formation and protein tyrosine phosphorylation induced by SPP. Thus Rho may be an upstream regulator of both stress-fibre formation and tyrosine phosphorylation of p125(FAK) and paxillin. Pretreatment with PMA, an activator of protein kinase C (PKC), inhibited the stimulation of stress-fibre formation induced by 1-oleoyl-lysophosphatidic acid (LPA) but not that by SPP. Similarly, PMA also decreased LPA-induced tyrosine phosphorylation of p125(FAK) and paxillin without abrogating the response to SPP. Thus PKC is involved in LPA- but not SPP-dependent signalling. The polyanionic drug suramin, a broad-specificity inhibitor of ligand-receptor interactions, did not inhibit either the mitogenic effect of SPP or its stimulation of tyrosine phosphorylation of p125(FAK). However, suramin markedly inhibited these responses induced by LPA. These results suggest that in contrast with LPA, SPP may be acting intracellularly in Swiss 3T3 fibroblasts to stimulate tyrosine phosphorylation of p125(FAK) and paxillin and cell growth.

3T3 Cells↗
PubMed1997

Divergence in signal transduction pathways of platelet-derived growth factor (PDGF) and epidermal growth factor (EGF) receptors. Involvement of sphingosine 1-phosphate in PDGF but not EGF signaling.

Platelet-derived growth factor (PDGF) and serum, but not epidermal growth factor (EGF), stimulated sphingosine kinase activity in Swiss 3T3 fibroblasts and increased intracellular concentrations of sphingosine 1-phosphate (SPP), a sphingolipid second messenger (Olivera, A., and Spiegel, S. (1993) Nature 365, 557-560). We report herein that DL-threo-dihydrosphingosine (DHS), a competitive inhibitor of sphingosine kinase that prevents PDGF-induced SPP formation, specifically inhibited the activation of two cyclin-dependent kinases (p34(cdc2) kinase and Cdk2 kinase) induced by PDGF, but not by EGF. SPP reversed the inhibitory effects of DHS on PDGF-stimulated cyclin-dependent kinases and DNA synthesis, demonstrating that the DHS effects were mediated via inhibition of sphingosine kinase. DHS also markedly reduced PDGF-stimulated but not EGF-stimulated mitogen-activated protein kinase activity and DNA binding activity of activator protein-1. Examination of the early signaling events of PDGF action revealed that DHS did not affect PDGF-induced autophosphorylation of the growth factor receptor or phosphorylation of the SH2/SH3 adaptor protein Shc and its association with Grb2. This sphingosine kinase inhibitor did not abrogate activation of phosphatidylinositol 3-kinase by PDGF. In agreement, treatment with SPP had no effect on these responses but did, however, potently stimulate phosphorylation of Crk, another SH2/SH3 adaptor protein. Moreover, DHS inhibited PDGF-stimulated, but not EGF-stimulated, Crk phosphorylation. Thus, regulation of sphingosine kinase activity defines divergence in signal transduction pathways of PDGF and EGF receptors leading to mitogen-activated protein kinase activation.

3T3 Cells↗
PubMed1997

Reversion of the malignant phenotype of human breast cells in three-dimensional culture and in vivo by integrin blocking antibodies.

In a recently developed human breast cancer model, treatment of tumor cells in a 3-dimensional culture with inhibitory beta1-integrin antibody or its Fab fragments led to a striking morphological and functional reversion to a normal phenotype. A stimulatory beta1-integrin antibody proved to be ineffective. The newly formed reverted acini re-assembled a basement membrane and re-established E-cadherin-catenin complexes, and re-organized their cytoskeletons. At the same time they downregulated cyclin D1, upregulated p21(cip,wat-1), and stopped growing. Tumor cells treated with the same antibody and injected into nude mice had significantly reduced number and size of tumors in nude mice. The tissue distribution of other integrins was also normalized, suggesting the existence of intimate interactions between the different integrin pathways as well as adherens junctions. On the other hand, nonmalignant cells when treated with either alpha6 or beta4 function altering antibodies continued to grow, and had disorganized colony morphologies resembling the untreated tumor colonies. This shows a significant role of the alpha6/beta4 heterodimer in directing polarity and tissue structure. The observed phenotypes were reversible when the cells were disassociated and the antibodies removed. Our results illustrate that the extracellular matrix and its receptors dictate the phenotype of mammary epithelial cells, and thus in this model system the tissue phenotype is dominant over the cellular genotype.

Animals↗
PubMed1997

Hydrogen exchange/electrospray ionization mass spectrometry studies of substrate and inhibitor binding and conformational changes of Escherichia coli dihydrodipicolinate reductase.

Escherichia coli dihydrodipicolinate reductase is one of seven enzymes in the succinylase pathway of bacterial L-lysine biosynthesis. The binding of NADH, a substrate, and 2,6-pyridinedicarboxylate, an inhibitor, to the recombinant, overexpressed enzyme has been analyzed using hydrogen/deuterium exchange and electrospray ionization/mass spectrometry. NADH binding reduces the extent of deuterium exchange, as does the subsequent binding of 2,6-pyridinedicarboxylate. Pepsin digestion of the deuterated enzyme and enzyme-inhibitor complex coupled with liquid chromatography/mass spectrometry has allowed the identification of four peptides whose deuterium exchange slows considerably upon the binding of the substrate or inhibitor. Two of these peptides represent regions known or thought to bind NADH and 2,6-pyridinedicarboxylate. Two additional peptides are located at the interdomain hinge region and are proposed to be exchangeable in the "open", catalytically inactive, conformation but are nonexchangeable in the "closed", catalytically active conformation formed after NADH and 2,6-pyridinedicarboxylate binding and domain closure. These studies provide a clear example of a catalytically essential domain movement in this enzyme.

Amino Acid Sequence↗
PubMed1997

Alpha 2A-adrenergic receptors are expressed by diverse cell types in the fetal primate cerebral wall.

The cellular elements of the fetal monkey cerebral wall expressing alpha 2A, the most common subtype of the alpha 2 receptor class, were examined by using nonisotopic in situ hybridization and immunohistochemistry with double-labeling for cell type-specific markers. At the three embryonic ages examined, E70, E90, and E120, alpha 2A receptors were expressed throughout the embryonic cerebral wall. In the E70 and E90 fetuses, alpha 2A receptors were observed in most cells of the proliferative zones. Some alpha 2A-positive cells also expressed a proliferation-associated antigen, Ki-67, suggesting that the receptors are present in dividing cells. Furthermore, at E90, alpha 2A receptors were detected on fibers passing between the ventricular and subventricular proliferative zones. At all ages studied, alpha 2A receptors were expressed by migrating neurons in the intermediate zone, characterized by a spindle-like shape, radial alignment, and close association with radial glia. alpha 2A receptors were also expressed by postmigrational microtubule-associated protein-2-positive neurons of the intermediate and subplate zones and the cortical plate. In the marginal zone, alpha 2A receptors were present in the Cajal-Retzius neurons. Finally, alpha 2A receptors were seen in the glial fibrillary acidic protein-positive cells at all ages studied. In addition, dopamine-beta-hydroxylase immunohistochemistry, employed to determine the potential source of noradrenaline in the embryonic cerebral wall, revealed noradrenergic innervation in the marginal, subplate, and intermediate zones of the monkey occipital lobe as early as E70. Based on our observations and available data on alpha 2A signal transduction pathways, we propose that these receptors are involved in regulating the generation, migration, and maturation of cerebral cortical cells.

Animals↗
PubMed1997

The significance of allelic deletions and aneuploidy in colorectal carcinoma. Results of a 5-year follow-up study.

BACKGROUND: A prospective study was initiated to analyze the prognostic value of both the deletion of candidate tumor suppressor genes and the DNA content in colorectal carcinoma specimens. METHODS: A prospective study was initiated in 1988, into which 104 patients from the Brooklyn VA Medical Center were accrued through March 1992. DNA restriction endonuclease digests, obtained by the Southern blot technique, were examined for allelic deletions by cDNA probes pnm23-H1 (17q21) YNZ 22.1 (17p13), and p15-65 (18q21). DNA content was measured by image analysis cytometry of Feulgen-stained tumor imprints. Median follow-up was 5.5 years (range, 4-8.5 years). RESULTS: Patients with nm23-H1 allelic deletions were 3 times as likely to develop distant metastases as patients without nm23-H1 deletions (relative risk [RR], 3.89; 95% confidence interval [CI], 1.39, 10.89). This connection was even stronger after adjustment for TNM stage and site of primary tumor (RR, 5.27; 95% CI, 1.67, 16.68). No significant association of 17p or 18q deletions or ploidy with either distant metastases or overall survival was noted. In multivariate analysis, clinicopathologic variables associated with decreased survival included intracellular mucin production, nuclear grade, TNM stage, and nerve invasion. CONCLUSIONS: A combination of clinicopathologic and molecular biologic variables may identify patients at high risk for death from disseminated colorectal carcinoma.

Aged↗
PubMed1997

Additive estrogenic activities of a binary mixture of 2',4',6'-trichloro- and 2',3',4',5'-tetrachloro-4-biphenylol.

The estrogenic activity of 2',4',6'-trichloro-4-biphenylol (HO-PCB3), 2',3',4',5'-tetrachloro-4-biphenylol (HO-PCB4), and an equimolar mixture of both compounds (HO-PCB3/HO-PCB4) was investigated in the 21-day-old B6C3F1 mouse uterus, MCF-7 and MDA-MB-231 human breast cancer cells, HepG2 cells, and in a yeast-based reporter gene assay. Treatment of the animals with 17beta-estradiol (E2) (0.02 microg/kg/day x3) resulted in increased uterine wet weight, peroxidase activity and progesterone receptor binding. Treatment with 18, 73, 183 or 366 micromol/kg (x3) doses of HO-PCB3, HO-PCB4, or HO-PCB3/HO-PCB4 (equimolar) caused a dose-dependent increase in estrogenic activity; a maximal-induced response was not observed at any dose and the activity of the mixture was additive. Binding of E2, HO-PCB3, HO-PCB4, and HO-PCB3/HO-PCB4 to the mouse uterine estrogen receptor (ER) was determined in a competitive binding assay using [3H]E2 as the radioligand. The IC50 values were 1.1 x 10(-8), 3.4 x 10(-6), 9.9 x 10(-7), and 4.25 x 10(-6) m, respectively. HO-PCB3 and HO-PCB4 maximally induced MCF-7 cell proliferation, rat creatine kinase, and human complement C3 (C3-LUC) reporter gene activity at concentrations of 10(-5) to 10(-6) m, and these compounds were 10(3) to 10(4) less potent than E2. The HO-PCB3/HO-PCB4 mixture was active at the high concentration (10(-5) m) and was additive for these responses. HO-PCB3 and HO-PCB4 also exhibited estrogenic activity in human HepG2 cells cotransfected with C3-LUC and an ER expression plasmid, and the estrogenic activity of the HO-PCB mixture was additive. Similar results were obtained in yeast transformed with the human ER and a double estrogen responsive element upstream of the beta-gal reporter gene. The effects of variable ER expression on the potential synergistic interactions of HO-PCB3/HO-PCB4 were investigated in HepG2 cells cotransfected with C3-LUC (405 ng/well) and variable amounts of ER expression plasmid (270, 27, 2.7, or 0.27 ng/well). The results show that as ER levels decreased, the magnitude of the induction response by E2, HO-PCB3, HO-PCB4, and HO-PCB3/HO-PCB4 also decreased. However, the activities of the HO-PCB mixture were additive at high and low levels of ER. Similar results were obtained in MDA-MB-231 cells cotransfected with C3-LUC and variable amounts of ER expression plasmid. The results of this study demonstrate that for several estrogen-responsive assays in the mouse uterus; MCF-7, HepG2, and MDA-MBA-231 human cancer cells; and a yeast based-reporter gene assay, both HO-PCB3 and HO-PCB4 exhibited estrogenic activity. The estrogenic activity of an equimolar mixture of these compounds was additive at high and low levels of ER expression.

Animals↗
PubMed1997

Dissociated secretion of islet amyloid polypeptide and insulin in serum-free culture media conditioned by human pancreatic adenocarcinoma cell lines.

CONCLUSION: The cosecretion of insulin and islet amyloid polypeptide (IAPP) is altered when isolated rat pancreatic islets are incubated in culture media conditioned by human pancreatic cancer cells. BACKGROUND: Pancreatic cancer is usually associated with impaired glucose tolerance. This study investigates the tumor-derived influence on beta-cell secretion of pancreatic islets. METHODS: Four conditioned media were prepared from two human pancreatic cancer cell lines (Panc-1 and HPAF), a hamster pancreatic cancer cell line (PC-1), and a fibroblast cell line (Ag1523). Isolated rat pancreatic islets were incubated first in the conditioned media or nonconditioned control medium for 24 h, then in the same kind of media containing 100 microM carbamylcholine for 90 min. Insulin and IAPP secretion were measured by radioimmunoassay. RESULTS: Islets in media conditioned by Panc-1 and HPAF cells demonstrated dissociation of insulin and IAPP secretion. During 24-h incubation, the dissociation was expressed as selectively decreased insulin secretion. With addition of 100 microM carbamylcholine, the dissociation was expressed as normal secretion of insulin and hypersecretion of IAPP. As a result, the IAPP/insulin molar ratios were increased in both groups during both time periods. The islets in PC-1 and Ag1523 media did not show any significant changes in insulin and IAPP secretion.

Adenocarcinoma↗
PubMed1997

Antineoplastic drugs that interfere with iron metabolism in cancer cells.

Normal iron metabolism can be perturbed with iron chelators, toxic metals that bind to transferrin, toxic metals bound to transferrin or antineoplastic agents covalently linked to transferrin. These agents cause significant inhibition of tumor cell growth in cell culture and have been shown to have significant in vivo antineoplastic activity. Cell culture studies showed that deferoxamine mesylate inhibits cell growth and division in both the MCF-7 human breast and HeLa human cervical carcinoma cell lines. Animal studies demonstrated that when deferoxamine mesylate is injected intravenously into rats that are on a low iron diet, there is a significant reduction in the growth of 13762NF mammary adenocarcinomas. Gallium, indium and the antineoplastic agent cisplatin were bound to the iron binding site of transferrin and inhibit the growth of malignant carcinoma cell lines. Gallium-transferrin and indium-transferrin were at least 10 times more inhibitory to both MCF-7 and HeLa cell lines than their free salts. Further cell culture studies demonstrated that cisplatin-transferrin complexes act synergistically with doxorubicin to inhibit the growth of cultured MCF-7 cells. In a Phase I clinical trial of cisplatin-transferrin complex there was a 36% (four of 11 patients) response rate in breast cancer patients with advanced disease. In a second clinical study the sequential administration of deferoxamine mesylate (2 days at 6 g/day in 8 hrs), cisplatin-transferrin complex (7 days at 500 mg/day) and FAC (5-fluorouracil, doxorubicin and cyclophosphamide at 450, 45 and 450 mg/m2, respectively) to advanced breast cancer patients resulted in partial responses in seven of eight patients treated. Future work will concentrate on substituting transferrin based agents with daunorubicin or doxorubicin attached to the surface of the transferrin, and gallium or indium bound to the iron binding site, to increase efficacy of the second component of the sequential combination chemotherapy.

Animals↗
PubMed1997

Outcomes of cataract extraction with multifocal intraocular lens implantation: functional status and quality of life.

OBJECTIVE: The authors measured functional status after bilateral implantation of a multifocal versus a monofocal intraocular lens (IOL). METHODS: A retrospective, case-control study was done on 100 subjects implanted bilaterally with a silicone-optic foldable zonal progressive IOL under United States Food and Drug Administration Investigational Device Exemption protocol and 103 control subjects implanted bilaterally with a monofocal IOL of similar design who were matched on age and postoperative corrected distance acuity. The Cataract TyPE specification, a 17-item functional status instrument, was modified, validated, and administered via telephone interview. The measures of vision, functional status, and quality of life were compared between patients and controls. RESULTS: The instrument was valid (Cronbach's alpha = 0.94) and correlated moderately (Pearson's r= 0.34) with Snellen acuity. Multifocal subjects were more likely than monofocal controls to never wear spectacles (41% vs. 11.7%; P < 0.001). Multifocal subjects rated their vision without spectacles significantly better than those with monofocal IOLs (9.0 vs. 7.9; P < 0.001). The difference was most significant in rating of near vision without spectacles (7.8 vs. 5.0; P < 0.001). Multifocal subjects reported less limitation in specific visual tasks without spectacles (0.3 vs. 0.8; P < 0.001, where 1.0 represents "slightly" limited). This difference was consistently observed in subscales related to distance vision activities (0.1 vs. 0.4; P < 0.001), near vision activities (0.6 vs. 1.4; P < 0.001), and social activities (0.1 vs. 0.6; P < 0.001). CONCLUSIONS: In this study, subjects with bilateral multifocal IOLs reported better overall vision, less limitation in visual function, and less spectacle usage than monofocal controls.

Aged↗
PubMed1997

Infant mortality among various nationalities in the middle part of Guizhou, China.

This paper describes infant mortality, leading causes of death, and some associated factors among the Han, the Miao, the Bouyei and other minority nationalities in three counties of the middle part of Guizhou Province, China. The results showed that the overall infant mortality rate (IMR) in these areas was 125.7 per 1000 live births during 1985-1987. There existed a great disparity in IMR among different nationalities. The rate was 103.1 (Han), 148.8 (Miao), 161.2 (Bouyei) and 145.0 (other ethnic groups) per 1000 live births, respectively. The five leading causes of death in infants were respiratory diseases, neonatal tetanus, birth asphyxia, infectious diseases and diarrhoea. These causes of death combined resulted in an IMR of 104.1 per 1000 live births. However, these diseases varied in importance for infants of different nationalities. We considered the relationship between infant death and maternal and child health care. The location of birth, the kinds of birth attendants and utilization of health facilities might be associated with differentials of infant mortality among these nationalities. Maternal education was associated with infant survival, but it might not be the only factor in decreasing or eliminating the differential of IMR among various nationalities. Based upon the findings, it is urgent to improve maternal and child health care and investigate further cultural and sociological factors among various nationalities.

Anthropology, Cultural↗
PubMed1997

A spatial equilibrium model for region size, urbanization ratio, and rural structure.

"Earlier economic models of city size have either focused on urban agglomeration effects while ignoring the spatial structure of the rural hinterland, or made unrealistic assumptions (for example, uniform rural population distribution) so as to simplify the problem. Following the classic von Thunen framework, we present a two-sector spatial equilibrium model of a city located at the center of an agricultural hinterland. The city produces industrial goods, and the rural area produces agricultural goods. Both goods are consumed both by urban and by rural residents. Market equilibrium for these goods determines: (1) the spatial size of the region, (2) the urbanization ratio (urban to total population) and the population size of the city, and (3) the rural spatial structure (wage, population distribution, land rent, and agricultural yield). Given various sets of exogenous parameters pertaining to the industrial, agricultural, and transportation production functions and to population preferences, the model is solved numerically, and response functions are estimated and analyzed."

Agriculture↗
PubMed1997

Differential expression of D1 and D5 dopamine receptors in the fetal primate cerebral wall.

Previous film autoradiographic studies demonstrated that, during corticogenesis, dopamine receptors of the D1 class are abundant in the embryonic primate cerebral wall. In the present study, we expand these findings by identifying the cellular elements of the fetal occipital cerebral wall expressing D1 and D5 subtypes of the D1 dopamine receptor class. We have examined tissue from monkey fetuses collected at 70, 90 and 120 days of gestation using antibodies directed against C-termini of the D1 and D5 dopamine receptors. At all three embryonic ages studied, we found D1 and D5 receptors expressed by multiple cell types of the embryonic cerebral wall. Both D1 and D5 receptor proteins are produced by pyramidal neurons of the cortical plate and by a variety of interstitial neurons of the subplate and intermediate zones. D1 and D5 receptors are also present in cells of the proliferative ventricular and subventricular zones, some of which were identified as dividing cells. In addition, D1 and D5 receptors are detectable in the protoplasmic astroglial and ependymal cells distinguishable in monkey fetuses collected at 120 days of gestation. Some cellular elements of the embryonic monkey cerebral wall express only one subtype of the D1 dopamine receptor class. For example, embryonic Cajal-Retzius neurons in the marginal zone and migrating neurons in the intermediate zone are immunoreactive only to D5 antisera. In contrast, radial glia can be labeled only with D1 receptor-specific antisera. Finally, only D1 receptors are detectable in the blood vessels penetrating the embryonic monkey cerebral wall. Based on these observations, we propose that dopamine receptors of the D1 class play an important role in regulating cerebral cortical formation and that D1 and D5 receptor subtypes may participate in regulation of different aspects of this process.

Animals↗
PubMed1997

Reports on surveillance of antimicrobial resistance in individual countries.

In preparation for the meeting of the World Health Organization Working Group on Monitoring and Management of Bacterial Resistance to Antimicrobial Agents, representatives of 10 countries were asked to provide brief reports on the status of surveillance in their countries. Some gave extensive information on the methods used to test susceptibility of nosocomial pathogens to a variety of antibiotics; some described in detail the network of reference laboratories available to hospitals and individual clinicians for monitoring, identifying, and testing infectious agents; others chose to describe how their countries deal with the resistance of the most frequently isolated pathogen to a commonly used drug. The following summary of these reports shows the broad range of problems encountered and solutions undertaken by these 10 countries in dealing with the increasingly alarming problem of bacterial resistance to antimicrobial agents.

Algeria↗
PubMed1997

The role of cytokines in disease progression in heart failure.

Recent studies have identified the importance of biologically active molecules such as neurohormones as mediators of disease progression in heart failure. More recently it has become apparent that in addition to neurohormones, another portfolio of biologically active molecules, termed cytokines, are also expressed in the setting of heart failure. This article reviews recent clinical and experimental material that suggests that the cytokines, much like the neurohormones, may represent another class of biologically active molecules that are responsible for the development and progression of heart failure.

Animals↗