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Results for “Functional perturbation”

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PubMed2003

The actin cytoskeleton as a therapeutic target: state of the art and future directions.

Dynamic processes such as cell migration and division depend on the actin cytoskeleton, a dense meshwork of protein polymers capable of undergoing rapid cycles of assembly and disassembly, under the control of a large number of actin-associated proteins. In cancer cells, structural and functional perturbations of the actin cytoskeleton correlate with higher proliferation rates and uncontrolled movement. Therefore, small molecules that act on the actin cytoskeleton of tumour cells and thus inhibit cell division and movement, may be of high therapeutic value. The dynamic properties of the actin cytoskeleton and the mechanism of action of actin-targeting drugs will be described.

Actin Cytoskeleton↗

PubMed1992

Identification and developmental expression of a novel low molecular weight neuronal intermediate filament protein expressed in Xenopus laevis.

Xenopus laevis is a valuable model system for the study of vertebrate neuroembryogenesis. However, very few well-characterized nervous system-specific molecular markers are available for studies in this organism. We screened a X. laevis adult brain cDNA library using a cDNA probe for mouse low molecular weight neurofilament protein (NF-L) in order to identify neuron-specific intermediate filament proteins. Clones for two distinct neuron-specific intermediate filament proteins were isolated and sequenced. One of these encoded for a Xenopus NF-L (XNF-L) and the other for a novel neuron-specific Xenopus intermediate filament protein (XNIF) that was present earlier and more abundantly than XNF-L during development. XNIF contained a central rod domain with multiple sequence features characteristic of IF proteins. The XNF-L was very similar to mouse NF-L, with a 77% sequence identity in the rod domain and the presence of a polyglutamic acid region in the tail domain, characteristic of type IV neurofilament proteins. In contrast, XNIF showed only 60% identity to mouse NF-L in the rod domain and lacked the glutamic acid-rich sequence in the tail domain. XNIF also had a very low (approximately 38%) sequence identity in the head and tail domains as compared to NF-L and other neurofilament proteins (45% identity to the head domain of alpha-internexin). In the adult frog, XNIF mRNA is detected by Northern blots only within the nervous system and by in situ hybridization histochemistry exclusively in neurons, particularly in the medullary reticular system and spinal cord. Antisera raised against the unique tail region of XNIF detected a single distinct 60 kDa band in Western blots of nervous system cytoskeletal preparations, and this XNIF immunoreactivity was concentrated in axons in the PNS and in small perikarya in the dorsal root ganglion. In contrast, NF-L immunoreactivity was principally in the large perikarya in the dorsal root ganglion. In development, XNIF mRNA appears more abundant than XNF-L mRNA in all premetamorphic stages examined. XNIF mRNA is first detectable at stage 24 (26 hr), whereas stable expression of XNF-L is at stage 35/36 (50 hr). XNIF immunoreactivity is detectable within the cement gland, within many neuronal cell bodies and axon tracts within the developing nervous system, and within all cellular layers of the developing retina. The availability of these two distinct neuron-specific intermediate filament proteins, with different temporal and spatial expression patterns, should provide new markers as well as targets for functional perturbation in the developing X. laevis nervous system.

Amino Acid Sequence↗

PubMed2005

Up-regulation of hnRNP A1 gene in sporadic human colorectal cancers.

We have previously reported that the heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1), a major hnRNP, binds to G-rich repetitive sequences and quadruplex (G4') structures in DNA, including the 5'-TTAGGG-3' telomere repeat and 5'-GGCAG-3' short-tandem-repeat. DNA synthesis arrest at the (GGG) sites within these repeats in vitro was retrieved by the addition of the hnRNP A1 protein or its N-terminal proteolytic product, UP1, in a dose-dependent manner. Therefore, functional perturbation of hnRNP A1 may abrogate the genomic stability of telomere repeats and other G-rich sequences, independent of its major role in transcriptional and translational regulation. In the present study, we conducted genetic and expression analysis of the hnRNP A1 gene in sporadic human colorectal cancers to clarify its possible involvement in human carcinogenesis. Of 30 lesions, one harbored a mutation at the -11 position from the translation initiation site, but none in the coding region. A single nucleotide polymorphism, an A or G-allele, was found in the 5' upstream promoter region of the gene. Quantitative gene expression analysis revealed that 60% (18/30) of cases showed over-expression of hnRNP A1 in cancer tissues by 2-fold or greater, compared to their normal colon tissues, with values of 78, 64 and 40% for clinicopathological stages II, III and IV, respectively. Although the biological consequences of hnRNP A1 overexpression in colorectal cancers remain to be clarified, it could contribute to maintenance of telomere repeats in cancer cells with enhanced cell proliferation. Alternatively, since the variations in the stoichiometry of hnRNP family proteins are considered to affect cell-specific gene expression, quantitative alteration of hnRNP A1 could result in facilitation of transformation of colon epithelial cells as a consequence of transcriptional and translational perturbation.

Adult↗

PubMedDate not supplied

[Cellular calcium ion signalling--from basic research to benefits for patients].

A large number of ion channels, enzymes, pumps and binding proteins participate in the generation of intracellular Ca2+ signals and their decoding. Ca2+ signalling takes place in the form of oscillations, waves and sparks. Such Ca2+ signals occur in almost all cells and regulate diverse cell functions. Perturbation of Ca2+ signalling leads to disease states. Drugs that act on Ca2+-signalling are commonly used in treatment of several diseases. Different molecules involved in Ca2+ signalling are potential targets for development of new therapies. Thus, basic research in Ca2+ signalling increases our understanding of the pathogenesis of diseases at a molecular level and the likelihood of development of new therapeutic modalities.

Calcium Channel Blockers↗

PubMed2005

A proteomic approach to assess intraneuronal inclusions associated with neurodegenerative disorders.

In neuroscience, proteomic technology is being used to discover the chemical features of neurodegenerative disorders, including Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis. Pathologically, one hallmark feature common to these diseases is the presence of proteinaceous inclusions within affected neurons. Proteomic assessment of diseased tissues and animal models reveals that the occurrence of these protein-rich aggregations may be due to perturbed functioning of a neuron-specific ubiquitin-recycling enzyme.

Animals↗

PubMed1991

Formation of cation channels in planar lipid bilayers by brefeldin A.

Brefeldin A (BFA) is a novel agent with the unique property of effecting a rapid increase of Golgi cisternae volume and subsequent loss of a recognizable Golgi apparatus in treated cells. Although a receptor-mediated mechanism has been proposed, the molecular basis of BFA action remains unknown (Lippincott-Schwartz, J., Glickman, J., Donaldson, J. G., Robbins, J., Kreis, T. E., Seamon, K. B., Sheetz, M. P., and Klausner, R. D. (1991) J. Cell Biol. 112, 567-577). Since a variety of ionophores distort Golgi architecture by initially causing osmotic swelling of the cisternae (Mollenhauer, H. H., Morre, D. J., and Rowe, L. D. (1990) Biochim. Biophys. Acta 1031, 225-246), Golgi membrane permeabilization by BFA seemed possible. We examined the effects of BFA on the conductance of planar lipid bilayers bathed in several aqueous salt solutions. Addition of BFA (1 microgram/ml) quickly augmented alkali cation conductance (K+ greater than Na+ much greater than Li+) but not anion conductance of the bilayer. Lower concentrations (1 ng/ml) indicated that BFA formed discrete, cation-selective channels in these bilayers. Given that Golgi cisternae volume increases immediately upon treatment with BFA, these findings suggest that alteration of ion gradients or Golgi membrane potential followed by an influx of water may be the mechanism by which BFA initiates disruption of Golgi structural integrity. Subsequent functional perturbations may then ensue either as a consequence of these initial structural changes or by a combination of several distinct mechanisms.

Brefeldin A↗

PubMed1991

Critical analysis of the histomorphometry of rat thyroid after treatment with thyroxin and propylthiouracil.

The morphological variations of rat thyroid follicles after treatment with either thyroxin or propylthiouracil were evaluated by histomorphometry. A silver impregnation technique allowed a precise visualization of thyroid follicles on histological sections. The histomorphometric values (cell height, follicular diameter, percentage of epithelial cells) were obtained using a semi-automatic image analyser. The statistical tests used were analysis of variance (Fisher's test) and the Newman-Keuls tests. The results obtained showed that thyroxin treatment did not lead to any modification in histomorphometric values. Propylthiouracil, on the contrary, caused profound alterations in the morphology of thyroid follicles and in particular an increase in the height of the follicular epithelium. These changes were induced by a deficiency in thyroid hormones leading to an increase in thyroid-stimulating hormone (TSH) release. This study shows that with rigorous methodology, histomorphometry is adaptable to the requirements of a simple and reproducible evaluation of substances capable of causing functional perturbations and their effects on the thyroid gland.

Animals↗

PubMed1991

[The biochemical bases of cardiovascular aging].

The majority of reports concerning the performance of senescent heart in both human and animal models states that, at rest, most hemodynamic parameters are substantially unchanged during aging, with the exception of a prolongation of left ventricular ejection time and a decrease in the early diastolic filling rate. A biochemical rationale for the increased early diastolic filling time with age seems to be the enhanced stiffness of left ventricular wall due to either myocardial hypertrophy or collagen tissue accumulation. The prolonged time of contraction and the inadequate response to stress of cardiac muscle in elderly subjects may be the consequence of changes in different steps of the excitation-contraction coupling, namely altered intracellular calcium homeostasis, reduced availability of highly energetic compounds, and impaired response to adrenergic stimulation. These defects can cause major hemodynamic changes when the heart is subjected to volume or pressure overload. In fact, during exercise, elderly subjects can reach a maximal heart rate slower than that of younger people. The possibility that the toxicity of oxygen reactive forms may provoke some age-related myocardial lesions such as structural alteration of membranes and enzyme inactivation is very attractive but the linkage between the most functional perturbations of aged hearts and peroxidative stress remains to be clarified.

Aging↗

PubMed1987

Type 1 reactions in leprosy--heterogeneity in T-cell functions related to the background leprosy type.

Nineteen each of paucibacillary borderline tuberculoid (BT) and multibacillary borderline borderline (BB)/borderline lepromatous (BL) leprosy patients undergoing type 1 reactions were compared with nonreactional stable patients of the appropriate leprosy type. In the BT reactional group, both phytohemagglutinin-induced and, more importantly, antigen-induced lymphoproliferation was reduced in 80%-90% of the patients. On the other hand, leukocyte migration inhibition was reduced in 40% and remained unchanged in the others. Suppressor-cell activity as evaluated by a costimulant assay was also reduced in a majority of the reactional BT individuals. In contrast, the bacilliferous BB and BL patients in reaction showed significant general improvement in leukocyte migration inhibition (p less than 0.001) and antigen-induced lymphoproliferation (p less than 0.05) as compared to the expected hyporesponsive/anergic uncomplicated BB-BL patients. Suppressor-cell activity also recovered during the reactional phase. However, no significant differences were observed in either of the reactional or stable leprosy types in the numbers of total T cells (OKT3+) and their subsets as defined by OKT4+ (helper/inducer) and OKT8+ (suppressor/cytotoxic) functional phenotypes. Moreover, during type 1 reactions the 48-hr delayed-type hypersensitivity (DTH) responses after intradermal injection of Mycobacterium leprae antigens continued to reflect the background leprosy type rather than the functional perturbations in the circulating T cells. Only a marginal increase in DTH was observed in some BT reactional individuals. No consistent pattern in the above in vitro T-cell-related responses was discernable in the same individuals 4-6 months after subsidence of reactions. The clinical entity of type 1 reactions encompassing paucibacillary and multibacillary leprosy shows a heterogeneity/dichotomy in T-cell responses which may reflect different immunological mechanisms underlying the reactional state.

Antigens, Bacterial↗

PubMed1985

Membrane lipid composition and cellular function.

Membrane fatty acid composition, phospholipid composition, and cholesterol content can be modified in many different kinds of intact mammalian cells. The modifications are extensive enough to alter membrane fluidity and affect a number of cellular functions, including carrier-mediated transport, the properties of certain membrane-bound enzymes, binding to the insulin and opiate receptors, phagocytosis, endocytosis, depolarization-dependent exocytosis, immunologic and chemotherapeutic cytotoxicity, prostaglandin production, and cell growth. The effects of lipid modification on cellular function are very complex. They often vary from one type of cell to another, and they do not exert a uniform effect on all processes in a single cell line. Therefore, it is not yet possible to make any generalizations or to predict how a given system will respond to a particular type of lipid modification. Many of the functional responses probably are caused directly by the membrane lipid structural changes, which affect either bulk lipid fluidity or specific lipid domains. The conformation or quaternary structures of certain transporters, receptors, and enzymes probably are sensitive to changes in the structure of their lipid microenvironment, leading to changes in activity. Prostaglandin production is modulated by the availability of substrate fatty acids stored in the membrane phospholipids, but the underlying chemical mechanism still involves a change in membrane lipid structure. While this is the most likely mechanism, the possibility that the membrane lipid compositional change is an independent event that occurs concurrently but is not causally related to the functional perturbations also must be considered.

Animals↗

PubMed1981

[Ultrastructural modifications in the hypophyseal-adrenocortical system in rabbits during experimentally induced parodontosis (author's transl)].

During parodontosis induced experimentally by irritation of dental pulp with carbolic acid in rabbits, the participation in the pathological process of adenohypophyseal ACTH-producing cells and of adrenocortical fasciculata cells was studied. Ultrastructural alterations suggesting stimulation of ACTH and glycocorticoid synthesis were observed. The data obtained prove that via afferent pathways to the central nervous system, irritation of the dental pulp induces morphofunctional alterations in the hypothalamo-adenohypophyseal neurosecretory system, by means of functional perturbation of the cerebral cortex leads to hypothalamus (CRF) leads to adenohypophysis (ACTH) leads to adrenal cortex (glucocorticoids)axis.

Adrenal Cortex↗

PubMed1994

A subgroup of murine monoclonal anti-deoxyribonucleic acid antibodies traverse the cytoplasm and enter the nucleus in a time-and temperature- dependent manner.

BACKGROUND: The capacity of lupus autoantibodies to enter living cells and bind to molecules for which they have intrinsic affinity is not well appreciated. In previous studies, we identified a subgroup of three murine monoclonal IgG anti-DNA antibodies, derived from lupus-prone MRL-lpr/lpr mice, that localized within nuclei of cells in multiple organs and induced functional perturbations, in vivo, after passive transfer to normal mice. To examine the mechanisms of this phenomenon, we now extend these observations, using the same monoclonal anti-DNA antibodies and cultured cell lines. EXPERIMENTAL DESIGN: Multiple experimental approaches were utilized to track nuclear localization of anti-DNA antibodies, including direct immunofluorescence, confocal microscopy and immunoelectron microscopy. The requirements for nuclear localization were further evaluated quantitatively, in nuclei isolated from co-cultures of cells and 125I-Ig, under varying experimental conditions. RESULTS: Nuclear localization was observed with the same subset of anti-DNA antibodies that localized within nuclei in vivo; it was dependent on the antigen-binding region of the molecule; and it was not found with other anti-DNA antibodies. At progressive intervals, the Ig were observed: at the cell surface, within the cytoplasm, clustered at the nuclear pore, and within the nucleus. Nuclear localization of Ig was found to be a time- and temperature- dependent process, specific for a subset of anti-DNA antibodies and dependent on the antigen binding region of the Ig. CONCLUSIONS: This is the first demonstration that monoclonal autoantibodies can traverse both the cell and nuclear membranes to localize within the nuclei of cultured cells. Furthermore, nuclear localization of Ig was regulated in a manner analogous to that of other large cytoplasmic proteins that enter the nucleus. This confirms and extends our results using the same antibodies in whole animals, and it provides the basis to further examine the underlying mechanisms and consequences of this phenomenon.

Animals↗

PubMed2004

5-Formyluracil-induced perturbations of DNA function.

Oxidation of the thymine methyl group can generate 5-formyluracil (FoU), which is known to be both mutagenic and chemically unstable in DNA. Synthetic oligonucleotides containing FoU at defined sites have been prepared to investigate potential mechanisms by which FoU might perturb DNA function. The half-life of the glycosidic bond of an FoU residue in single-stranded DNA under physiological conditions of temperature and pH is estimated to be approximately 148 days, orders of magnitude shorter than the parent pyrimidine, thymine. This reduced stability of FoU residues in DNA is attributed to the inductive properties of the 5-formyl substituent. Oxidative modification of the thymine methyl group could also inhibit association with sequence-specific DNA-binding proteins. Alternatively, the 5-formyl substituent of FoU could cross-link nonspecifically with protein amino groups. Transcription factor AP-1 is known to make specific contacts with thymine methyl groups of DNA in its recognition sequence. Substitution of T by FoU is shown to inhibit AP-1 (c-Jun homodimer) binding with a DeltaDeltaG of approximately 0.6 kcal/mol. No evidence of cross-link formation is observed with either AP-1 or polylysine. Molecular modeling studies on the FoU-containing oligonucleotide sequence corresponding to the duplex used in the experimental studies demonstrate that the 5-formyl substituent of an FoU residue paired with adenine lies in the plane of the pyrimidine base and is well protected from solvent on one face and only partially accessible on the other. The results of this study suggest that although FoU residues in DNA are considerably more labile than thymine, they are likely to be present long enough to miscode as well as interfere with DNA-protein interactions.

Binding, Competitive↗

PubMed2005

Global and critical test of the perturbation density-functional theory based on extensive simulation of Lennard-Jones fluid near an interface and in confined systems.

The structure of a Lennard-Jones (LJ) fluid subjected to diverse external fields maintaining the equilibrium with the bulk LJ fluid is studied on the basis of the third-order+second-order perturbation density-functional approximation (DFA). The chosen density and potential parameters for the bulk fluid correspond to the conditions situated at "dangerous" regions of the phase diagram, i.e., near the critical temperature or close to the gas-liquid coexistence curve. The accuracy of DFA predictions is tested against the results of a grand canonical ensemble Monte Carlo simulation. It is found that the DFA theory presented in this work performs successfully for the nonuniform LJ fluid only on the condition of high accuracy of the required bulk second-order direct correlation function. The present report further indicates that the proposed perturbation DFA is efficient and suitable for both supercritical and subcritical temperatures.

Chemistry, Physical↗

PubMed1992

Kinematic adaptations to perturbations as a function of practice in rhythmic drawing movements.

Kinematic adaptations in multijoint rhythmic drawing movements were investigated under unexpected perturbations in friction levels between stylus and writing surface. Changes in coupling and stability properties were assessed as a function of practice level by applying perturbations to subjects' dominant and nondominant limbs. Under nonperturbation and perturbation conditions, joint motions of right-handed subjects were highly coupled in the nondominant limb and uncoupled in the dominant limb. Stability analyses of the kinematic responses in the phase plane showed a relatively higher intrajoint resistance to perturbations in the nondominant limb as compared to the dominant limb for the elbow joint. indicating a decrease in global joint stiffness with practice. These changes in joint coupling and stiffness with practice were not observed for left-handed subjects. In addition, the stability to perturbations in the end-effector (stylus) kinematics was related to the amount of joint coupling in the nondominant limb, whereas in the dominant limb there existed no such coupling. It was concluded that (a) practice changes the responses to perturbations from anatomically specific early in practice to task-specific late in practice, and (b) this shift is related to the stability in the joint phase-plane dynamics, degree of coupling between joint angles, and the decoupling of the dynamics in the intrinsic and extrinsic control spaces.

Journal Article↗

PubMed2003

Perturbation of CD44 function affects chiasmatic routing of retinal axons in brain slice preparations of the mouse retinofugal pathway.

Neurons generated early in development of the ventral diencephalon have been shown to play a key role in defining the midline and the caudal boundary of the optic chiasm in the mouse retinofugal pathway. These functions have been attributed to a surface bound adhesion molecule, CD44 that is expressed in these chiasmatic neurons. In this study, we investigated the effects of perturbing normal CD44 functions on axon routing in brain slice preparations of the mouse retinofugal pathway. Two CD44 antibodies (Hermes-1 and IM7) were used that bind to distinct epitopes on the extracellular domain of the molecule. We found that both antibodies produced dramatic defects in routing of the retinal axons that arrive early in the chiasm. In preparations of embryonic day 13 (E13) and E14 pathways, the crossed component in the chiasm was significantly reduced after antibody treatment. However, such reduction in axon crossing was not observed in E15 chiasm, indicating that the lately generated crossed axons lost their responses to CD44. Furthermore, the anti-CD44 treatment produced a reduction in the uncrossed component in the E15 but not in younger pathways, suggesting a selective response of the lately generated axons, mostly from ventral temporal retina, but not those generated earlier, to the CD44 at the chiasmatic midline in order to make their turn for the uncrossed pathway. These findings provide evidence that a normal function of CD44 molecules in the chiasmatic neurons is essential for axon crossing and axon divergence at the mouse optic chiasm.

Animals↗

PubMed1998

Perturbed dentate gyrus function in serotonin 5-HT2C receptor mutant mice.

Serotonin systems have been implicated in the regulation of hippocampal function. Serotonin 5-HT2C receptors are widely expressed throughout the hippocampal formation, and these receptors have been proposed to modulate synaptic plasticity in the visual cortex. To assess the contribution of 5-HT2C receptors to the serotonergic regulation of hippocampal function, mice with a targeted 5-HT2C-receptor gene mutation were examined. An examination of long-term potentiation at each of four principal regions of the hippocampal formation revealed a selective impairment restricted to medial perforant path-dentate gyrus synapses of mutant mice. This deficit was accompanied by abnormal performance in behavioral assays associated with dentate gyrus function. 5-HT2C receptor mutants exhibited abnormal performance in the Morris water maze assay of spatial learning and reduced aversion to a novel environment. These deficits were selective and were not associated with a generalized learning deficit or with an impairment in the discrimination of spatial context. These results indicate that a genetic perturbation of serotonin receptor function can modulate dentate gyrus plasticity and that plasticity in this structure may contribute to neural mechanisms underlying hippocampus-dependent behaviors.

Animals↗

PubMed2000

Granulocyte colony-stimulating factor perturbs lymphocyte mitochondrial function and inhibits cell cycle progression.

Sera from healthy subjects receiving recombinant human granulocyte colony-stimulating factor (rHuG-CSF) to mobilize CD34(+) peripheral blood progenitors (PBPC) have been recently shown to induce unresponsiveness of allogeneic lymphocytes to mitogenic challenge. In the present investigation, the effects of rHuG-CSF on the early stages of lymphocyte activation-induced apoptosis and on lymphocyte cell cycle entry were evaluated. Sera were obtained from HLA-identical donors receiving rHuG-CSF to mobilize CD34(+) PBPC for allogeneic transplantation. Normal peripheral blood mononuclear cells (PBMC) were challenged with phytohemagglutinin (PHA) in the presence of serum collected before (preG) or after rHuG-CSF administration (postG). Mitochondrial function, that is, incorporation of 3,3'-dihexyloxacarbocyanine iodide [DiOC(6)(3)] and generation of reactive oxygen species (ROS) as well as expression of c-Myc and Bcl-2 family members (Bcl-2, Bcl-X(L), Bax) were evaluated by multiparameter flow cytometry. The activation-induced fragmentation of genomic DNA was detected by highly sensitive LM-PCR assay.CD4(+)DiOC(6)(3)(low) and CD8(+)DiOC(6)(3)(low) T lymphocytes increased and reached 32% (range 27%-38%) and 20% (range 15%-23%) of circulating T cells, respectively, on day 4 of rHuG-CSF administration. Hypergeneration of ROS could be demonstrated in 65% (range 58%-82%) of CD4(+) T lymphocytes and in 0.4% (range 0.2%-0. 8%) of circulating CD8(+) T cells. rHuG-CSF determined no alteration of mitochondrial function if added to allogeneic PBMC in vitro, thus suggesting indirect effects mediated by soluble factors; on the contrary, when PBMC were challenged with PHA in the presence of postG serum, both perturbation of mitochondrial transmembrane potential (Deltapsi(m)) and hypergeneration of ROS were induced, and lymphocytes were predominantly arrested in a G(0) -like phase of the cell cycle and displayed genomic DNA fragmentation. Interestingly, the preincubation of PBMC with a blocking antibody directed against CD95 abrogated the perturbation of lymphocyte Deltapsi(m), suggesting that the CD95 signaling pathway might play a role in the induction of apoptosis after PHA stimulation in the presence of postG serum. Moreover, Bax protein was overexpressed in postG (median fluorescence intensity = 180, range 168-186) compared with preG cultures (median fluorescence intensity = 75, range 68-80; p < 0.01), while no differences in Bcl-2, Bcl-X(L), and c-Myc staining intensity were observed. Our findings demonstrate a humoral-mediated rHuG-CSF-induced dissipation of lymphocyte mitochondrial Deltapsi(m); these effects might be mediated by Bax overexpression, with imbalance between apoptosis-promoting and apoptosis-inhibiting Bcl-2 family members and with subsequent induction of mitochondrial permeability transition. Whether immune dysfunction will favorably impact on incidence and severity of acute graft vs host disease after allogeneic PBPC transplantation remains to be determined.

Adult↗