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PubMed1984

Paraneoplastic syndromes and constitutional symptoms in prediction of metastatic behavior of small cell carcinoma of the lung.

Small cell carcinoma of the lung is frequently associated with a paraneoplastic syndrome or constitutional symptoms. To examine correlations between paraneoplastic syndromes or constitutional symptoms and tumor behavior, the clinical and pathologic features were reviewed in 85 patients with small cell carcinoma of the lung who underwent complete autopsy at The Johns Hopkins Hospital between 1962 and 1983. The 28 (33 percent) subjects with a paraneoplastic syndrome survived significantly longer (10.5 +/- 1.5 months) than those without a paraneoplastic syndrome (7.4 +/- 0.7 months) (p less than 0.05), and they had significantly higher frequencies of tumor invasion into major bronchi (p less than 0.01) and more extensive metastases to bone marrow (p less than 0.05), but significantly lower frequencies of and less extensive metastases to the central nervous system (p less than 0.005). The 35 (41 percent) subjects with constitutional symptoms had markedly increased tumor burdens (p less than 0.005) with significantly more extensive metastases to bone marrow, liver, and lungs (all p less than 0.05). The findings suggest that subjects with small cell carcinoma of the lung associated with a paraneoplastic syndrome tend to have a more benign clinical course with prolonged survival; in addition, the significantly lower frequency of central nervous system metastases in these patients may be due to a paucity of the subpopulations of tumor cells that have the propensity to metastasize to the brain. In contrast, it appears that constitutional symptoms develop in patients with small cell carcinoma of the lung because of rapid tumor growth, coupled with impairment of synthetic activity in the liver due to extensive infiltration of tumor into hepatic parenchyma.

Adult↗
PubMed1991

Constitutive antigen presentation by mouse splenic macrophages is restricted to the progeny of a distinct progenitor population.

Mouse splenic macrophage progenitors differ in their ability to give rise to cloned progeny that constitutively present complex protein antigens to T-cell hybridomas. To determine if the constitutive presentation of diverse antigens is restricted to cells derived from the same subpopulation of progenitors, we expanded macrophage clones into multiple subcultures and compared them for the ability to present different antigens to their respective antigen-specific T-cell hybridomas. Only subcultures derived from the same minority fraction of splenic macrophage progenitors were capable of constitutively presenting the antigens, and the activity of these subcultures was unaffected by the addition of recombinant murine IFN-gamma. This suggests that a specialized sub-population of constitutive antigen-presenting macrophages exists in the spleens of mice.

Animals↗
PubMed1985

Genetic factors and fetal growth sex constitution and birthweight in twins.

Fetal growth is considered a multifactorially-influenced characteristic. Genetic factors were found to play the main role in fetal growth determination, and it is the polygenic inheritance. The paper reviews the birthweights of 360 unlike-sexed two-egg twins, born at the Clinic of Gynecology and Obstetrics, Faculty of Medicine in Beograd, from January 1, 1970 through June 30, 1984. The mean birthweight differences between the male (2954.94 +/- 704.28 g) and female (2313.19 +/- 651.32 g) fetuses, amounted to 141.75 g. The difference is highly significant (P less than 0.01); variation coefficient shows that the examined groups were homogenous (VC was below 30%). The results were discussed from the genetic point of view, and particularly from the point of view of sex constitution, with special respect to the effect of Y chromosome on fetal growth. It has been known that human somatic development, body weight, bone maturation and teeth development are influenced by variety of factors. In addition to nutritional and other factors of the external environment, genetic and humoral factors are leading. The fact that fetuses with XY male constitution are heavier at birth than female fetuses with XX constitution, made us consider the correlation between genotype-phenotype, and the mentioned characteristics. This study was aimed at finding out the role of genetic factors in fetal growth, with respect to sex constitution, particularly to chromosome effect on fetal growth in unlike-sexed two-egg twins.

Birth Weight↗
PubMed1995

Testosterone treatment in adolescent boys with constitutional delay of growth and development.

Administration of androgens to adolescent boys with constitutional delay in growth has been highly controversial. One hundred forty-eight adolescent boys with constitutional delay of growth and puberty with a mean age of 14.3 +/- 0.7 years were treated with testosterone enanthate 100 mg intramuscularly each month for 6 months. Growth parameters, sexual maturation, and circulating concentrations of testosterone and insulin-like growth factor-I (IGF-I) were compared with those for 50 age-matched adolescent boys with constitutional delay of growth and puberty with a mean age of 14.1 +/- 0.9 years who did not receive any treatment. The mean height growth velocity, height standard deviation score, weight gain, and IGF-I concentration were significantly greater in the treatment group after 1 year of follow-up evaluation. The advancement in bone age equaled that in chronologic age in the treatment group, with no significant change in the bone age to chronologic age ratio (BA/CA) before versus after therapy. All subjects in the treatment group had clearly entered puberty by the end of 1 year. Testicular size increased significantly in the treatment group and they had significantly higher serum testosterone concentrations 6 months after the end of testosterone therapy as compared with the control group, denoting activation of the hypothalamic-pituitary testicular axis. All subjects in the treatment group were psychologically satisfied with the enhanced growth and increased muscle mass, versus only 40% of those in the control group. In conclusion, our regimen appears to be efficacious and safe for treatment of boys with constitutional delay of growth and puberty and has no deleterious effect on skeletal age.

Adolescent↗
PubMed1981

Transposable elements associated with constitutive expression of yeast alcohol dehydrogenase II.

The yeast structural gene ADR2, coding for the glucose-repressible alcohol dehydrogenase (ADHII), has been isolated by complementation of function in transformed yeast. The chromosomal DNA from nine yeast strains with cis-dominant constitutive mutations (ADR3c) has been investigated by restriction enzyme analysis, using the cloned ADR2 DNA as a hybridization probe. Seven mutants appear to have insertions of approximately 5.6 kg near the 5' end of the ADR2-coding region. Four of these insertions have the same restriction pattern as the yeast transposable element Ty1. Two differ from Ty1 by the presence of an additional Hind III site, and a seventh insertion differs from Ty1 at a number of restriction sites. All are inserted in the same orientation with respect to the structural gene. A DNA fragment containing the ADR2 gene and adjacent sequences from a constitutive mutant has been cloned and shown by heteroduplex analysis to contain an insertion near the 5' end of the structural gene. The cloned insertion sequence hybridizes to multiple genomic DNA fragments, indicating that it contains a moderately repetitive sequence. Thus it appears that insertion of a transposable element near the 5' terminus of the structural gene can produce constitutive expression of a normally glucose-repressed enzyme. Such insertions seem to be the most common way of generating cis-dominant constitutive mutations of ADHII.

Alcohol Oxidoreductases↗
PubMed1995

Constitutional and acquired trisomy 8.

Trisomy 8 is seen in a range of disorders both constitutional and acquired. The full constitutional condition presents with physical stigmata, skeletal abnormalities and a mild to moderately retarded IQ. Trisomy 8 is frequently seen as a mosaic in the blood or in the skin or both. Trisomy 8 as an acquired condition is found in haematological disorders, notably in myelodysplasia (MDS) and acute myeloid leukaemia (AML), and is restricted to the malignant cells. These arise in the bone marrow and may also be found in the peripheral blood. Reported in the issue (Zollino et al. (1995) Leukemia Res. 19(10), 733) is a case of a patient with constitutional trisomy 8 mosaicism who developed myelodysplasia with trisomy 8 in 95-100% of bone marrow cells. Here we consider the implications of this case to the diagnosis of both malignant and constitutional conditions.

Chromosomes, Human, Pair 8↗
PubMed1995

Myelodysplastic syndrome in a child with constitutional trisomy 8 mosaicism and normal phenotype.

Trisomy 8 is a frequently acquired cytogenetic abnormality in myeloid malignancies, but may also represent a constitutional chromosome abnormality with a wide phenotypic variation. We report a case of myelodysplastic syndrome (MDS) that developed in a child with trisomy 8 mosaicism and normal phenotype. Bone marrow (BM) cells all showed trisomy 8 with additional clonal abnormalities in most cells. Based on the present case and a review of previously published cases of myeloid malignancies in patients with trisomy 8 mosaicism, it appears likely that the malignant cells developed from the trisomic cell population, suggesting that constitutional trisomy 8 may be a predisposing condition to myeloid malignancies. Trisomy 8 in malignant cells is usually considered an acquired abnormality, but this implies a risk of ignoring a constitutional trisomy 8 mosaicism. Examination for constitutional trisomy 8, despite a normal phenotype, may therefore be warranted in hematologic malignancies with trisomy 8 of BM cells to evaluate further the possible association and to preclude erroneous use of trisomy 8 as a tumor marker.

Child↗
PubMed1992

Expression of major histocompatibility complex (MHC) class I genes in astrocytes correlates with the presence of nuclear factors that bind to constitutive and inducible enhancers.

The molecular basis of constitutive and inducible major histocompatibility complex (MHC) class I gene expression was studied in murine astrocytes in primary culture. Astrocytes constitutively expressed MHC class I molecules and treatment of these cells with interferon-gamma (IFN-gamma) further induced expression. The conserved region containing the upstream MHC class I regulatory element (MHC-CRE) and juxtaposed interferon consensus sequence (ICS) enhanced constitutive MHC class I promoter activity. As seen with cell surface expression of MHC molecules, treatment of astrocytes with IFN-gamma increased MHC class I promoter activity. Inducible expression required the presence of the MHC-CRE/ICS enhancer region. Nuclear factors that bind to the MHC-CRE and ICS were constitutively expressed in cultured astrocytes and IFN-gamma treatment further induced binding activity both to the MHC-CRE and ICS and correlated with induction of MHC class I gene expression. This study identifies the MHC-CRE and ICS as the major cis elements in controlling MHC class I promoter activity and suggests that the expression of nuclear factor binding activities to these enhancer elements is a basic transactivating mechanism for the expression of MHC class I genes in astrocytes.

Animals↗
PubMed1990

T-cell restricted and unrestricted expression of transfected human interleukin-2 gene: phorbol ester- and calcium-inducible versus constitutive expression.

Interleukin-2 (IL-2) gene expression is tightly controlled and generally limited to antigenic stimulation of T cells. To study the cell-specific expression of the IL-2 gene, we transfected the intact human IL-2 gene, including 2.0 kb of 5' and 0.3 kb of 3' flanking sequences, into mouse NIH-3T3 fibroblasts and BFS lymphoma T cells and into human epithelial HeLa cells. Stable transformants (NIH-3T3,HeLa and BFS cells) carried an intact transfected IL-2 gene and constitutively expressed cytoplasmic human IL-2 mRNA which was not detected in vector-transfected cells. Constitutive expression of IL-2 mRNA in human IL-2 gene-transfected NIH-3T3 and HeLa cells was associated to the secretion of bioactive IL-2 protein, while no IL-2 production was observed in untransfected or vector-transfected cells. Cytoplasmic IL-2 mRNA observed in transfectants was larger (1.4 kb) than endogenous IL-2 mRNA of human T cells, although smaller than RNA containing unspliced intact introns. No alternative promoters or polyadenylation signals were used by these cells, but some intronic sequences were present in the 1.4 kb mRNA. Phorbol ester and calcium ionophore did not modulate the expression of the transfected IL-2 gene in NIH-3T3 and HeLa cells, while these agents increased its expression in transfected BFS lymphoma T cells. We conclude that when transfected into lymphoid and non-lymphoid cells the intact human IL-2 gene is constitutively expressed, while its phorbol ester/calcium-mediated inducible expression is restricted to T cells. This suggests that the constitutive and inducible expression of the IL-2 gene can be dissociated and are presumably subjected to separate regulatory pathways.

Animals↗
PubMed2005

Curcumin induces growth-arrest and apoptosis in association with the inhibition of constitutively active JAK-STAT pathway in T cell leukemia.

Adult T cell leukemia is an aggressive and frequently fatal malignancy that expressess constitutively activated growth-signaling pathways in association with deregulated growth and resistance to apoptosis. Curcumin (diferuloylmethane) is a naturally occurring yellow pigment, isolated from the rhizomes of the plant Curcuma longa that has traditionally been used in the treatment of injury and inflammation. But the effect and mechanism of action of curcumin on T cell leukemia is not known. To investigate the antitumor activity of curcumin in T cell leukemia, we examined its effect on constitutive phosphorylation of JAK and STAT proteins, proliferation, and apoptosis in HTLV-I-transformed T cell lines. HTLV-I-transformed T cell leukemia lines, MT-2, HuT-102, and SLB-1, express constitutively phosphorylated JAK3, TYK2, STAT3, and STAT5 signaling proteins. In vitro treatment with curcumin induced a dose-dependent decrease in JAK and STAT phosphorylation resulting in the induction of growth-arrest and apoptosis in T cell leukemia. The induction of growth-arrest and apoptosis in association with the blockade of constitutively active JAK-STAT pathway suggests this be a mechanism by which curcumin induces antitumor activity in T cell leukemia.

Antineoplastic Agents, Phytogenic↗
PubMed2006

Two distinct chloride ion requirements in the constitutive protein secretory pathway.

The role of chloride ions in regulated secretion is well described but remains poorly characterised in the constitutive system. In the liver, newly synthesised proalbumin is transported to the trans Golgi network where it is converted to albumin by a furin protease and then immediately secreted. We used this acid-dependent hydrolysis and the measurement of specific protein secretion rates to examine the H+ and Cl- ion dependence of albumin synthesis and secretion, a major constitutive protein secretory event in all mammals. Using permeabilised primary rat hepatocytes we show that ordinarily chloride ions are essential for the processing of proalbumin to albumin. However Cl- is not required for transport which continues but releases solely proalbumin. Prior treatment of the cells with Tris (used as a membrane-permeable weak base to neutralise Golgi luminal pH) both eliminated the formation of albumin and very greatly reduced secretion. After washing out Tris, both authentic secretion and processing could be restarted if Cl-, ATP, GTP, cAMP, Ca2+ and cytosolic proteins were added. Hence a requirement for chloride in transport, in addition to processing, can be uncovered by first neutralising pH gradients. Furthermore, the chloride channel blocker DIDS (4,4-diisothiocyanostilbene 2,2-disulphonic acid) reversibly inhibited the constitutive secretory pathway. However, the total mass of proalbumin detectable in DIDS-treated cells fell to 36% of control while the fraction processed to albumin remained almost constant. This clearly dissociates a large part of the Cl- requirement of the constitutive protein secretory pathway from the function of known liver Golgi Cl- channels.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMedDate not supplied

Evaluation of biobank constitution and use: multicentre analysis in France and propositions for formalising the activities of research ethics committees.

Biobanks are collections of biological material and related files gathered and stored for clinical or research purposes. Here, we investigated the questions raised during the evaluation of biobanks by biomedical Research Ethics Committees (RECs), particularly in the context of genetic research. We sent a questionnaire to all RECs in France to survey their concerns and the ethical criteria used when evaluating research involving the storage of biological samples. Most of the RECs think that they should be consulted to evaluate the constitution of biobanks. The proportion of RECs of this opinion depended on whether the biobank is being constituted in the absence of an associated research project (initially created for clinical purposes or for undefined research) (14/28), whether the biobank is being constituted for research use (21/28) or whether an existing research biobank is being re-used (19/28). Views diverged concerning the way ethics principles are applied, showing that REC evaluations of biobanks might be formalised at each of the following steps: constitution, use and re-use. In this paper, we suggest concrete elements that could be integrated into the application of the new French law concerning the protection of the human beings participating in research as well as into international recommendations.

Biomedical Research↗
PubMed2006

Constitutive activation of zebrafish Stat5 expands hematopoietic cell populations in vivo.

OBJECTIVE: Constitutive activation of Stat5 has been observed in a variety of malignancies, particularly myeloid leukemias. To directly investigate the in vivo consequences of Stat5 perturbation, we expressed constitutively active forms in zebrafish. METHODS: We generated mutants of the zebrafish stat5.1 protein (N646H, H298R/N714F, and N714F) based on previously identified constitutively active mutants of murine Stat5a. The in vitro properties of these mutants were determined using phosphorylation-specific antibodies and luciferase reporter assays, and their in vivo effects were analyzed through microinjection of zebrafish embryos. RESULTS: Two of these stat5.1 mutants (N646H and H298R/N714F) showed increased tyrosine phosphorylation and transactivation activity compared to the wild-type protein. Expression of either mutant led to a range of hematological perturbations, which were more pronounced for the H298R/N714F mutant. Interestingly, expression of wild-type also produced generally similar phenotypes. Further analysis showed that expression of the H298R/N714F mutant led to increased numbers of early and late myeloid cells, erythrocytes, and B cells. Some nonhematopoietic developmental perturbations were also observed, but these were equally prominent with wild-type or mutant forms. CONCLUSION: These data implicate Stat5 activity as a direct critical regulator of hematological cell proliferation, suggesting a causal role for constitutively-active Stat5 in the etiology of hematological malignancies.

Amino Acid Substitution↗
PubMed2006

Identification of a constitutively active variant of LuxO that affects production of HA/protease and biofilm development in a non-O1, non-O139 Vibrio cholerae O110.

Pathogenesis of Vibrio cholerae depends on the concerted action of numerous virulence factors that includes a secreted hemagglutinin (HA) protease. Recent studies have evidenced that the expression of these virulence factors as well as the genes responsible for biofilm development is subject to control by quorum sensing in this organism. At low cell density, LuxO, the pivotal regulator of quorum-sensing circuit, has been shown to be phosphorylated at aspartate-47. Working in concert with sigma-54, LuxO-P activates the downstream repressor, which turned out to be four sRNAs [Lenz, D.H., Mok, K.C., Lilley, B.N., Kulkarni, R.V., Wingreen, N.S., Bassler, B.L., 2004. The small RNA chaperone Hfq and multiple small RNAs control quorum sensing in Vibrio harveyi and Vibrio cholerae. Cell 118, 69-82]. Subsequently, these sRNAs form complex with sRNA chaperone, Hfq. The Hfq-sRNA complex causes the destabilization of hapR mRNA transcript. HapR is a positive regulator of hapA that encodes HA/protease. At high cell density, dephosphorylation of LuxO impairs its function to activate the expression of sRNA, which in turn promotes HapR expression and causes protease production. It has been demonstrated that conversion of aspartate to glutamate (D47E) renders the LuxO molecule active without being phosphorylated. This variant of LuxO is referred as constitutively active LuxO or con-LuxO [Freeman, J.A., Bassler, B.L., 1999. A genetic analysis of the function of LuxO, a two-component response regulator involved in quorum sensing in Vibrio harveyi. Mol Microbiol 31, 665-677]. Other than D47E, mutation at L104Q also develops con-LuxO [Vance, R.E., Zhu, J., Mekalanos, J.J., 2003. A constitutively active variant of the quorum-sensing regulator LuxO affects protease production and biofilm formation in Vibrio cholerae. Infect. Immun. 71, 2571-2576]. The purpose of this study was to investigate the cause of protease negative phenotype of a non-O1, non-O139 strain of V. cholerae O110. In the process of exploring the nature of the phenotype, a constitutively active variant of LuxO molecule was characterized which represses protease production and enhances biofilm formation by this strain. Unlike luxU, disruption of luxO restored the protease production, which showed the constitutively active nature of LuxO protein in this strain.

Amino Acid Sequence↗
PubMed2006

A planar biaxial constitutive relation for the luminal layer of intra-luminal thrombus in abdominal aortic aneurysms.

The rupture risk of abdominal aortic aneurysms (AAAs) is thought to be associated with increased levels of wall stress. Finite element analysis (FEA) allows the prediction of wall stresses in a patient-specific, non-invasive manner. We have recently shown that it is important to include the intra-luminal thrombus (ILT), present in approximately 70% of AAA, into FEA simulations of AAA. All FEA simulations to date assume an isotropic, homogeneous material behavior for this material. The purpose of this work was to investigate the multi-axial biomechanical behavior of ILT and to derive an appropriate constitutive relation. We performed planar biaxial testing on the luminal layer of nine ILT specimens obtained fresh in the operating room (9 patients, mean age 71+/-4.5 years, mean diameter 5.9+/-0.4 cm), and a constitutive relation was derived from this data. Peak stretch and maximum tangential modulus (MTM) values were recorded for the equibiaxial protocol in both the circumferential (theta) and longitudinal (L) directions. Stress contour plots were used to investigate the presence of mechanical anisotropy, after which an appropriate strain energy function was fit to each of the specimen datasets. The peak stretch values for the luminal layer of the ILT were (mean+/-SEM) 1.18+/-0.02 and 1.13+/-0.02 in the theta and L directions, respectively (p=0.14). The MTM values were 20+/-2 and 23+/-3N/cm(2) in the theta and L directions, respectively (p=0.37). From these results and our observation of the symmetry of the stress contour plots for each specimen, we concluded that the use of an isotropic strain energy function for ILT is appropriate. Each specimen data set was then fit to a second-order polynomial strain energy function of the first invariant of the left Cauchy-Green strain tensor, resulting in an accurate fit (average R(2)=0.92+/-0.02; range 0.80-0.99). Comparison of our previously reported, uniaxially derived constitutive relation with the biaxially derived relation derived here shows large differences in the predicted mechanical response, underscoring the importance of the appropriate experimental methods used to derive constitutive relations. Further work is merited in an effort to produce more accurate predictions of wall stresses in patient-specific AAA, and viscoelastic behaviors of the ILT.

Aged↗
PubMed2006

Constitutively-active human LH receptors are self-associated and located in rafts.

Several naturally occurring mutations in human luteinizing hormone receptors (LHR) at position 578 are associated with constitutive activation of the receptor. To determine whether human LHRs that signal in the absence of ligand are self-associated, fluorescence resonance energy transfer (FRET) between receptors was evaluated. Values for FRET between wild type LHR in the absence of ligand were less than 1% and increased significantly to over 11% after exposure to hCG. Constitutively active receptors exhibited 11-15% FRET efficiency in the absence of hormone and these values did not change with hCG treatment. A large fraction of constitutively active LHR-D578H receptors were also associated with so-called plasma membrane rafts. Disruption of these membrane microdomains reduced FRET efficiency but did not affect signalling through cAMP. Thus, in the absence of ligand, constitutively active receptors are self-associated and located in high buoyancy membrane fractions, both characteristics of the hormone-treated wild type receptor.

Animals↗
PubMed2006

A constitutive model of the posterior cruciate ligament.

Further to our previous work on the development of a general constitutive framework for transversely isotropic viscohyperelasticity (Limbert, G, Middleton, J. A transversely isotropic viscohyperelastic material. Application to the modelling of biological soft connective tissues. Int J Solids Struct 2004;41(15):4237-60.), we propose a phenomenological constitutive law to describe the anisotropic viscohyperelastic behaviour of the human posterior cruciate ligament (PCL) at high strain rates. The mechanical formulation is based on the definition of a Helmholtz free energy function containing a hyperelastic and a viscous potential. The equations are valid for arbitrary kinematics and satisfy elemental thermodynamic principles. Identification of the constitutive model with experimental data obtained from human PCL specimens was performed and showed the ability of the model to capture accurately the mechanical characteristics of the PCL at various strain rates. Influence of the isotropic and directional viscous stress responses on the global mechanical response are discussed in connection with the modelling hypotheses. This work was motivated by the need to provide an accurate constitutive model of the PCL to be used in finite element analyses of human occupants in car crash simulations. Besides uniaxial tests along the natural fibre orientation of the PCL, additional tests such as equibiaxial, strip biaxial compression-tension and shear tests were also performed in order to assess the physical response of the model in different loading situations. It was found that the model performed as well in these conditions.

Anisotropy↗
PubMed2006

c-Jun N-terminal kinase mediates constitutive human eosinophil apoptosis.

Eosinophils are considered to play an important role in the pathogenesis of asthma. Glucocorticoids are potent anti-inflammatory agents for the treatment of chronic inflammatory diseases and they have been shown to increase the rate of eosinophil apoptosis. c-Jun N-terminal kinase (JNK) has been suggested to participate in the signaling pathways of apoptosis. The aims of the present study were to examine whether JNK is involved in the regulation of constitutive eosinophil apoptosis and whether it mediates dexamethasone-induced apoptosis of human eosinophils. Isolated human eosinophils were cultured with and without dexamethasone and the JNK inhibitor L-JNKI-1. Apoptosis was assessed by measuring the relative DNA content of propidium iodide-stained cells and confirmed by Annexin V-binding and morphological analysis with bright field microscopy. The phosphorylation of both JNK and c-Jun were measured by Western blotting. During a 40h culture, dexamethasone (1muM) enhanced human eosinophil apoptosis by 10-30%. Culture with L-JNKI1 (10muM) inhibited apoptosis in dexamethasone-treated cells by 53%. Furthermore, L-JNKI1 decreased the rate of constitutive eosinophil apoptosis by 64%. However, the enhancement of eosinophil apoptosis by dexamethasone was not reversed by L-JNKI1. Slow activation of JNK in constitutive apoptosis as well as a similar tendency in dexamethasone-induced eosinophil apoptosis could be observed by Western blot analyses. c-Jun was found to be active both in the presence and absence of dexamethasone. However, no further phosphorylation of the serine residue 63 of c-Jun could be seen. Taken together, our present results suggest that JNK is active during apoptosis of human eosinophils both in the presence and absence of glucocorticoids. JNK seems to mediate constitutive human eosinophil apoptosis. However, the activity of JNK is not enhanced by glucocorticoids and the effects of glucocorticoids cannot be reversed by JNK inhibition. JNK therefore seems not to mediate glucocorticoid-induced human eosinophil apoptosis.

Annexin A5↗