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PubMed1992

Biochemical basis of the constitutive repressor cleavage activity of recA730 protein. A comparison to recA441 and recA803 proteins.

The recA730 mutation results in constitutive SOS and prophage induction. We examined biochemical properties of recA730 protein in an effort to explain the constitutive activity observed in recA730 strains. We find that recA730 protein is more proficient than the wild-type recA protein in the competition with single-stranded DNA binding protein (SSB protein) for single-stranded DNA (ssDNA) binding sites. Because an increased aptitude in the competition with SSB protein has been previously reported for recA441 protein and recA803 protein, we directly compared their in vitro activities with those of recA730 protein. At low magnesium ion concentration, both ATP hydrolysis and lexA protein cleavage experiments demonstrate that these recA proteins displace SSB protein from ssDNA in a manner consistent with their in vivo repressor cleavage activity, i.e. recA730 protein > recA441 protein > recA803 protein > recAwt protein. Additionally, a correlation exists between the proficiency of the recA proteins in SSB protein displacement and their rate of association with ssDNA. We propose that an increased rate of association with ssDNA allows recA730 protein to displace SSB protein from the ssDNA that occurs naturally in Escherichia coli and thereby to become activated for the repressor cleavage that leads to SOS induction. RecA441 protein is similarly activated for repressor cleavage; however, in this case, significant SSB protein displacement occurs only at elevated temperature. At physiological magnesium ion concentration, we argue that recA803 protein and wild-type recA protein do not displace sufficient SSB protein from ssDNA to constitutively induce the SOS response.

Adenosine Triphosphatases↗

PubMed1992

Regulated, but not constitutive, secretory proteins bind porcine chymotrypsinogen.

Endocrine and exocrine cells exhibit both a constitutive and a regulated secretory pathway. In the latter pathway, secretory proteins are stored at a high concentration in secretory granules and are released by exocytosis in response to appropriate external stimuli. Sorting between the two secretory pathways is believed to take place in the trans-Golgi tubular network. To account for experimental data, it has been proposed that sorting receptors exist which bind a variety of regulated secretory proteins, including foreign secretory proteins introduced into the cells by transfection. In support of the sorting receptor hypothesis Chung et al. (Chung, K.-N., Walter, P., Aponte, G. W., and Moore, H.-P.H. (1989) Science 243, 192-197) isolated a group of 25-kDa canine pancreatic "hormone-binding proteins" that bound regulated but not constitutive secretory proteins. To determine if similar proteins are present in other species and tissues, we have screened porcine pancreas, parathyroid, adrenal medulla, and pituitary glands. A 31-kDa protein, similar to that identified by Chung et al. (1989), which binds to regulated but not to constitutive secretory proteins was identified in porcine pancreas. This protein was not detected in the parathyroid, adrenal medulla, or pituitary glands, however, which argues against it serving as a general sorting receptor. NH2-terminal sequencing, immunoreactivity, and proteolytic activity data indicate that the porcine 31-kDa protein is similar if not identical to porcine chymotrypsinogen A or B.

Adrenal Medulla↗

PubMed2003

Resistance to gefitinib in PTEN-null HER-overexpressing tumor cells can be overcome through restoration of PTEN function or pharmacologic modulation of constitutive phosphatidylinositol 3'-kinase/Akt pathway signaling.

PURPOSE: Tyrosine kinase (TK) inhibitors are emerging as a promising new approach to the treatment of HER overexpressing tumors, however optimal use of these agents awaits further definition of the downstream signaling pathways that mediate their effects. We reported previously that both EGFR- and Her2-overexpressing tumors are sensitive to the new EGFR-selective TK inhibitor gefitinib (ZD1839, "Iressa"), and sensitivity to this agent correlated with its ability to down-regulate Akt. However, EGFR-overexpressing MDA-468 cells, which lack PTEN function, are resistant to ZD1839, and ZD1839 is unable to down-regulate Akt activity in these cells. EXPERIMENTAL DESIGN: To study the role of PTEN function, we generated MDA468 cells with tet-inducible PTEN expression. RESULTS: We show here that the resistance of MDA-468 cells to ZD1839 is attributable to EGFR-independent constitutive Akt activation caused by loss of PTEN function in these cells. Reconstitution of PTEN function through tet-inducible expression restores ZD1839 sensitivity to these cells and reestablishes EGFR-stimulated Akt signaling. Although restoration of PTEN function to tumors is difficult to implement clinically, much of the effects of PTEN loss are attributable to overactive PI3K/Akt pathway signaling, and this overactivity can be modulated by pharmacologic approaches. We show here that pharmacologic down-regulation of constitutive PI3K/Akt pathway signaling using the PI3K inhibitor LY294002 similarly restores EGFR-stimulated Akt signaling and sensitizes MDA-468 cells to ZD1839. CONCLUSIONS: Sensitivity to ZD1839 requires intact growth factor receptor-stimulated Akt signaling activity. PTEN loss leads to uncoupling of this signaling pathway and results in ZD1839 resistance, which can be reversed with reintroduction of PTEN or pharmacologic down-regulation of constitutive PI3K/Akt pathway activity. These data have important predictive and therapeutic clinical implications.

Breast Neoplasms↗

PubMed2003

Role of p53 in regulating constitutive and X-radiation-inducible CD95 expression and function in carcinoma cells.

The p53 tumor suppressor protein is known to regulate the expression of the CD95 (Fas/APO-1) death receptor in a small subset of normal cell types as well as in many cancer cell types. However, whether p53-dependent regulation of CD95 expression is consistently associated with increased susceptibility to CD95-mediated cell death is poorly understood. To address this issue, we examined constitutive and induced CD95 surface expression and function in wild-type p53-expressing carcinoma cells relative to their isogenic p53-inactivated counterparts. We compared HCT116 colorectal carcinoma cells with their p53 biallelic knock-outs and control-transfected MCF-7 breast carcinoma cells with MCF-7 cells expressing a miniprotein inhibitor of p53 (p53DD). In both cell lines, the constitutive expression of surface CD95 was significantly reduced in p53-inactivated cells, as was the apoptotic response to agonistic anti-CD95 antibody. In both cell lines, only cells with wild-type p53 activity exhibited up-regulation of surface CD95 after ionizing irradiation. Interestingly, induction of CD95 expression substantially enhanced the apoptotic response to CD95 ligation only in MCF-7 cells but not in HCT116 cells. These findings provide direct evidence for a major role for wild-type p53 activity in regulating constitutive expression and function of CD95 in carcinoma cells; however, they also demonstrate that the functional effect of DNA damage-induced up-regulation of CD95 may be cell type specific.

Apoptosis↗

PubMedDate not supplied

Constitutive expression of Rb associated protein 46 (RbAp46) reverts transformed phenotypes of breast cancer cells.

The retinoblastoma (Rb) suppressor associated protein 46 (RbAp46) is a subunit of chromatin modifying and remodeling complexes. Previously, we found that RbAp46 functions as a potent growth inhibitor. It is also a downstream effector of the Wilms' tumor suppressor, WT1. The findings that expression levels of WT1 were down-regulated in breast cancer cell lines and in subsets of primary breast tumors led us to investigate the possible role of RbAp46 in breast cancer tumorigenesis. Here, we found that RbAp46 expression levels were decreased in five established breast cancer cell lines compared to a normal mammary gland epithelial cell line. To investigate the effect of constitutive expression of RbAp46 on the transformed phenotypes of breast cancer cells, we established stable cell lines that constitutively express exogenous RbAp46 using three breast cancer cell lines, MCF-7, MDA-MB-231 and MDA-MB-436. We have found that RbAp46 expression suppressed colony formation of these breast cancer cells in soft-agar, and inhibited tumor formation of these cells in nude mice. Our data demonstrated that constitutive RbAp46 expression suppresses the transformed phenotypes of breast cancer cells, and suggested that dysregulation of RbAp46 expression may contribute to breast cancer tumorigenesis.

Animals↗

PubMedDate not supplied

Inositol hexaphosphate inhibits constitutive activation of NF- kappa B in androgen-independent human prostate carcinoma DU145 cells.

BACKGROUND: One practical and translational approach to control prostate cancer (PCA) and associated death could be its preventive intervention by dietary agents. Several studies in recent years have shown both preventive and interventive efficacy of inositol hexaphosphate (IP6) in different animal tumor models, however, its effects in PCA and associated mechanisms have not been assessed in detail. Since transcription factor NF-kappa B is constitutively active in advanced and androgen-independent human PCA DU145 cells, here we assessed whether IP6 inhibits this constitutively active NF-kappa B and associated upstream effectors and whether such an affect of IP6 has biological relevance in causing inhibition of proliferation and induction of apoptosis in DU145 cells. MATERIALS AND METHODS: We used DU145 cells and assessed NF-kappa B activation by gel shift assay. Western immunoblot and in-beads kinase assay were used for protein levels and enzyme activity. Proliferation was measured by BrdU labeling and apoptosis by annexin V/PI staining followed by FACS analysis. RESULTS: Treatment of cells with 1 and 2 mM doses of IP6 resulted in a strong inhibition of NF-kappa B activation, which was consistent with a decrease in nuclear levels of NF-kappa B sub-unit proteins p65 and p50. IP6-treated cells also showed a strong inhibition in phospho-I kappa B alpha protein levels concomitant with a significant increase in total I kappa B alpha levels. This effect of IP6 also corroborated with a significant inhibition in IKK alpha kinase activity. In other studies, IP6-treated cells showed strong inhibition in cell proliferation and induction of apoptosis. CONCLUSION: Our results suggest that IP6 could be a potent dietary agent in controlling the growth of advanced PCA cells and inducing their apoptotic death, in part, by its inhibitory effect on constitutively active NF-kappa B signaling pathway.

Apoptosis↗

PubMed2004

The suppressor of cytokine signaling-1 is constitutively expressed in chronic myeloid leukemia and correlates with poor cytogenetic response to interferon-alpha.

BACKGROUND AND OBJECTIVES: Interferon-alpha (IFN-alpha) has proven useful for treating chronic myeloid leukemia (CML). However, only 7% of patients achieve a complete cytogenetic response. Although efforts to understand the molecular basis of this resistance to IFN-alpha have been made, the mechanism is still unknown. Because suppressor of cytokine signaling (SOCS) proteins are negative regulators of cytokine-induced signaling, it has been hypothesized that aberrant SOCS expression could confer resistance against cytokine therapy. DESIGN AND METHODS: In order to analyze the role of SOCS-1 in the acquisition of IFN-alpha resistance in this setting, we examined SOCS-1 mRNA expression using reverse transcription polymerase chain reaction (RT-PCR) in 75 newly diagnosed chronic phase-CML patients who received IFN-alpha therapy. RESULTS: SOCS-1 was constitutively expressed in 49 (65%) of 75 CML patients at diagnosis. Constitutive SOCS-1 expression was more frequently observed among Hasford high-risk patients (p = 0.05) and was also independently associated with a shorter median progression-free survival time (p = 0.001) and poor cytogenetic response to IFN-alpha treatment (p 0.0001). INTERPRETATION AND CONCLUSIONS: Our data indicate that constitutive expression of SOCS-1 occurs at an early stage in CML pathogenesis and probably influences the clinical behavior of the disease.

Adult↗

PubMed1992

Constitutive expression of a megakaryocytic functional property by murine erythroleukemia (Friend) cells: the incorporation of serotonin.

Murine Friend-derived erythroleukemia cells (MEL) are generally believed to be unipotential progenitors inducible to terminal erythroid differentiation. However, we found that MEL can constitutively incorporate significant amounts of radiolabeled serotonin ([3H]5-HT). Because this process is typical of cells belonging to the megakaryocytic lineage, we investigated the significance and mechanisms of 5-HT incorporation in the MEL system. We observed that: 1) normal murine erythroid cells and erythroid progenitors do not incorporate [3H]5-HT, as well as normal murine myeloid cells and the human myeloid cell line HL-60; on the other hand, the human erythroleukemia cell lines K562 and HEL, which have been shown to constitutively express megakaryocytic features, were able to incorporate [3H]5-HT; 2) MEL incorporated 5-HT by an active and saturable mechanism, dependent on temperature and sodium concentration in the medium; and 3) 5-HT uptake was very rapid. Moreover, because about 65% of cell-associated radioactivity was no longer displaced by the cold substrate, we assumed it to represent "true" cytoplasmic internalization. Finally, 5-HT incorporation by MEL was inhibited by clomipramine, ouabain, and reserpine, which are known inhibitors of 5-HT uptake in platelets. The commitment of MEL to terminal erythroid differentiation by hexamethylene bisacetamide or dimethyl sulfoxide greatly reduced the capacity to incorporate [3H]5-HT. These results seem to suggest that the MEL system, although mainly erythroid as regards its differentiation capability, constitutively expresses features of the megakaryocytic lineage, possibly disclosed by the ability to incorporate 5-HT. This hypothesis was further supported by the findings that 30%-40% of uninduced MEL were labeled by a polyclonal antibody raised against murine platelets that selectively recognized megakaryocytes in murine bone marrow smears.

Acetamides↗

PubMed1992

Constitutive expression of exogenous myc in myelomonocytic cells: acquisition of a more transformed phenotype and inhibition of differentiation induction.

The effects of deregulated expression of the human c-myc and MC29 v-myc oncogenes have been examined in a murine myelomonocytic cell line J774 (c-myc) and in a variety of myelomonocytic cell lines of different degrees of maturity generated from primary hematopoietic tissue (v-myc). Introduction of a Moloney murine leukemia virus long terminal repeat (LTR) c-myc construct into J774 cells resulted in constitutive expression of the exogenous myc gene and a concomitant increase in the degree of transformation and tumorigenicity of the cells. In addition, constitutive expression of exogenous myc inhibited induced differentiation of these cells by a variety of treatments including addition to the medium of lipopolysaccharide (LPS) or the phorbol ester 12-O-tetradecanoyl phorbol 13-acetate (TPA) as well as complete withdrawal of serum from the medium. The degree of increased transformation, tumorigenicity and inhibition of terminal differentiation was dependent upon the level of exogenous myc expression. For the v-myc-generated myelomonocytic cell lines, introduction of v-myc resulted in a high degree of transformation and, irrespective of the differentiation status of the cells, a block of induced differentiation. These results indicate that the level of constitutive myc expression can affect the transformed phenotype, tumorigenicity and differentiation inducibility of myelomonocytic cells.

Animals↗

PubMedDate not supplied

Scleroderma fibroblasts constitutively express the long pentraxin PTX3.

OBJECTIVE: PTX3 is a secreted molecule which consists of a C-terminal domain similar to classical pentraxins (e.g. C-reactive protein) and of an unrelated N-terminal domain. Unlike the classical pentraxins, PTX3 is expressed in response to IL-1beta and TNF-alpha but not to IL-6. The present study was designed to investigate the expression of PTX3 in normal and scleroderma fibroblasts. METHODS: Normal and SSc fibroblasts were cultured in the presence and absence of inflammatory cytokines. PTX3 mRNA expression in fibroblasts was evaluated by Northern analysis. PTX3 protein levels in fibroblast culture medium were estimated by ELISA. RESULTS: Normal fibroblasts were induced to express high levels of P7X3 mRNA by IL-1beta and TNF-alpha but not by other cytokines or growth factors. Scleroderma fibroblasts, unlike normal fibroblasts, constitutively expressed high levels of PTX3 in the absence of deliberate stimulation. The constitutive expression of PTX3 in SSc fibroblasts was not modified by anti-TNF-alpha antibodies or IL-1 receptor antagonist. In contrast, IFN-gamma and TGF-beta inhibited the constitutive but not the stimulated expression of PTX3 in SSc fibroblasts. CONCLUSIONS: PTX3 is a main feature of activated scleroderma fibroblasts.

C-Reactive Protein↗

PubMed2004

[Arterial hypertension in adolescents with different physical constitution including those with signs of metabolic syndrome].

AIM: Detection of clinico-paraclinical features of arterial hypertension (AH) in adolescents with different physical constitution including signs of metabolic syndrome (MS). MATERIAL AND METHODS: Blood levels of uric acid, cholesterol, triglycerides (TG), high and low density lipoproteins were examined and glucose tolerance test was made in 108 adolescents with arterial hypertension (AH) and different physical constitution (normal, with overweight and obese). Waist and hip distribution of fat was assessed. The control group consisted of 108 healthy adolescents. RESULTS: Most of the hypertensive children had hyperuricemia (HU), some of the patients combined HU with changes in glycemic profile of blood. The above abnormalities were especially evident in patients with MS who were characterized by abdominal obesity, higher blood pressure, subnormal high density lipoproteins, higher triglycerides and total cholesterol in blood, more severe HU and defects in glycemic profile of blood. CONCLUSION: MS in adolescents may be of genetic origin as well as constitutional HU and insulin resistance may be mutually dependent signs combination of which with other factors presents the whole spectrum of clinical and paraclinical manifestations of MS. Detection of HU and insulin resistance with their correction in a preclinical disease stage (in children and adolescents) may represent a new line in prevention of AH and MS in adults.

Adolescent↗

PubMed1992

Sequence requirements for precursor cleavage within the constitutive secretory pathway.

We have recently demonstrated that the Arg-X-Lys/Arg-Arg sequence is a signal for precursor cleavage catalyzed by furin, a mammalian homologue of the yeast precursor-processing endoprotease Kex2, within the constitutive secretory pathway. In this study, we further examined sequence requirements for the constitutive precursor cleavage by expression of various prorenin mutants with amino acid substitutions around the native Lys-Arg cleavage site in Chinese hamster ovary cells. The results delineate the following sequence rules that govern the constitutive precursor cleavage. (a) A basic residue (Lys or Arg) at the 4th (position -4) or 6th (position -6) residue upstream of the cleavage site besides basic residues at positions -1 and -2 is necessary. (b) At position -2, a Lys residue is more preferable than Arg. (c) At position -4, an Arg residue is more preferable than Lys. (d) At position 1, a hydrophobic aliphatic amino acid is not suitable.

Amino Acid Sequence↗

PubMed2005

Constitutional mosaic trisomy 21 and azoospermia: a case report.

Constitutional full trisomy 21 is a common disorder in which abnormal spermatogenesis has been previously described. However, constitutional mosaic trisomy 21 in an otherwise normal but infertile male has not been explored. We report a case with low level mosaic trisomy 21 in a non-syndrome but azoospermic patient. We also propose that the patient's azoospermia may be related to the constitutional mosaic trisomy 21 and thus resulting in a late onset of testicular failure.

Adult↗

PubMedDate not supplied

Aspects of constitutive and acquired antibioresistance in Aeromonas hydrophila strains isolated from water sources.

Over the last three decades, the literature pointed out the implications of Aeromonas species in human pathology. These species were described as being involved in intestinal (several outbreaks of acute gastroenteritis of choleric/dysenteric form or chronic diarrhoea, ulcerative colitis, etc.) in normal adults or children, as well as in extraintestinal infections in immunocompromised hosts. This last aspect included a large range of cutaneous injuries (micronecrosis, abscesses, bums, cellulites, furunculosis), joint, bones, respiratory, urinary tract, ocular infections up to meningitis, endocarditis, peritonitis, hepatobilliary disease, endotoxic shock and septicemia (as consequence of leech microvascular surgery). During the last decade, the literature reported a high mortality in Aeromonas infections determined by certain phenospecies (A. hydrophila and A. veronii) especially in extraintestinal infections in immunocompromised patients. In microbiologists' opinion this high rate of mortality was probably due to poor knowledge concerning the aspects of antibioresistance in Aeromonas strains, to empiric treatments with antibiotics to which these bacteria exhibiting constitutive resistance lead to insuccessful results, and at last to the increasing trend of aeromonads resistance to certain antibiotics after 1996. The literature mentioned also that for a great number of Beta-lactamase producing Aeromonas strains, the use of microdilution method (by comparison to disk diffusion in agar medium) giving false results made more difficult the true knowledge of Aeromonas antibioresistance patterns. At the same time, in 2002, the literature mentioned 4 ecological compartments considered as "reservoirs for dissemination and transfer of microbial antibioresistance i.e. humans, animals, plants and natural soil and water. In the last time, more and more data of the literature revealed that some bacteria with role of reservoir of antibioresistance in the natural environment, even without a direct medical impact, however they could play an indirect one remaining permanent sources of R genes for bacterial strains with pathogenic abilities implicated in human pathology (i.e. Aeromonas infections in man related to different professional activities such as fishing, surfing, swimming, diving, etc.). The purpose of this work was to determine the aspects related to constitutive and acquired antibioresistance in 35 A. hydrophila strains isolated in aquatic environment of Danube Delta (10 salmaster waters, 5 aquatic plants, 5 fish intestinal content, 5 fish sapling, 5 snake and oyster shells). The strains were biochemically identified by using API20E and API20NE kits. The antibioresistance spectrum was determined by disk diffusion method following NCCLS 2000 recommendations. The choice and disposal of antibiotics on the Mueller Hinton plate was done to allow the interpretive reading and the phenotypic detection of different antibioresistance mechanisms, as follows: beta-lactamases (PEN, ME, AMX, AMC, CAZ) and carbapenemase (IMP) production; porin deficiency (FOX); efflux mechanism (C, TE, NOR). All tested strains exhibited high resistance to penicillin, aspect pleading for constitutive penicillinase production in Aeromonas strains. With reference to other penicillins (ME, AMX, AMC) and cephalosporins (CAZ, FOX) the tested strains exhibited 2 different antibioresistance patterns: AMX-R, AMC-S, CAZ-S (65%) indicating the presence of beta-lactamase sensitive to inhibitors and AMX-R, AMC-R, CAZ-S (22%) indicating the presence of beta-lactamase resistant to inhibitors. Resistance to FOX in 8% of strains signifies a phenotypical marker for the presence of porin deficiency. Only one Aeromonas strain (2.8%) was resistant to IMP. Three strains (8%) were simultaneous resistant to TE and TMP/SMX, NOR and CHL probably due to the presence of a resistance plasmid (codifying an efflux/ enzymatic mechanism). These aspects are pleading for the necessity to investigate the bacterial antibioresistance patterns of bacterial strains isolated from the environment, in the purpose to identify the factors responsible for the spreading of certain antibioresistance mechanisms in the external medium as risk factors for the colonization process with possible impact upon the human pathology.

Aeromonas hydrophila↗

PubMedDate not supplied

Constitutive activation of transcription factor NFkappaB as a possible marker of sensitivity of neoplastic cells to anthracyclines.

NFkappaB, a member of the Rel family of transcription factors has been found to be critically important for control of cell proliferation and apoptosis. Although rare, there are systems in which NFkappaB has occurred as pro-apoptotic factor. The potent activators of NFkappaB are anthracycline anticancer drugs which induce the events of apoptosis. These results could point to the pro-apoptotic role of NFkappaB. Recent studies have shown that activation of that transcription factor well correlated with cytotoxic activity of anthracyclines. Potential mechanism through which NFkappaB could play a role in tumorigenesis involves its constitutive activation which was shown in a wide variety of tumour types. The aim of this study was to define the level of activity of NFkappaB in the native human tumour cells differing in sensitivity to anthracycline analogs to study the mechanism responsible for cytotoxic action of these drugs. Constitutive activation of NFkappaB was determined with use of ELISA test and confocal microscopy. As was shown, both methods have occurred as quite comparable. Constitutive activation of NFkappaB was observed in all neoplastic cells tested independently on sensitivity to anthracyclines. However, these results do not exclude the supportive role of NFkappaB in apoptotic activity of these drugs. It is necessary to study the influence of the compounds tested here on NFkappaB activation and on the induction and intensity of apoptotic processes.

Anthracyclines↗

PubMed2006

Generation of a constitutively active mutant of human GPR48/LGR4, a G-protein-coupled receptor.

GPR48, also known as leucine-rich repeat (LRR)-containing G-protein-coupled receptor 4 (LGR4), is a member of the G-protein-coupled receptor (GPCR) family of proteins. However, its biological functions remain unclear, since neither its ligand nor signal transduction pathway have been identified, and it is usually difficult to solve the function of such orphan receptors. The aim of this study was to generate a constitutively active form of human GPR48, that would form a ligand-independent active conformation and may function in a similar manner to activated GPR48 following ligand binding. We introduced four independent mutations into transmembrane domains V and VI of a human GPR48 cDNA. The wild-type and mutant GPR48s were expressed in HEK293 cells by transient transfection of appropriate expression plasmids. Since ligand-activated receptors for gonadotropins, which are structurally similar to GPR48, stimulate adenylate cyclase and increase cellular cyclic AMP, we investigated, whether the GPR48-transfected cells showed altered cyclic AMP levels. The cellular cyclic AMP level in HEK293 cells was increased following transfection of wild-type GPR48 in a dose-dependent manner. Moreover, transfection of a GPR48-T7551 mutant, in which threonine-755 was replaced with isoleucine, dramatically increased the cyclic AMP level. Stable transformants derived from HCT116 cells that constitutively expressed the GPR48-T7551 mutant also showed high cyclic AMP levels. These results indicate that the GPR48-T7551 mutant is a constitutively active mutant. This mutant may be useful for studying the biological functions of GPR48 and GPR48-mediated signal transduction, even if the specific ligand remains unknown in the future.

Amino Acid Sequence↗

PubMed1991

[Interrelations between the main forms of the course of schizophrenia and the morphological phenotype of patients' constitution (clinico- anthropometric data)].

In order to study interrelations between schizophrenia forms and the constitutional morphological type of the patients, as many as 840 schizophrenic patients and 282 normal subjects of the control group underwent ++clinico-anthropometric examinations. Comparison of the distribution of the pyknic, normosthenic and asthenic types of build-up in patients with schizophrenia and in the control group of healthy subjects did not reveal material differences and tropism of this endogenous psychosis to the constitution. It has been shown at the same time that at the probability level, the asthenic somatotype is the basis for continuous-progressive forms of the disease; the pyknic type of the build-up is based on the recurrent and shift-like forms with circular features, whereas the normosthenic somatic type forms the basis for the attack-like progressive form. The data obtained permit a conclusion that formation of schizophrenia forms is determined not only by the general pathological regularities common to the given disease but also by the individual typological peculiarities characteristic of different ++morpho-phenotypes of constitution.

Adolescent↗

PubMed2006

[Constitutive activation of signal transducers and activators of transcription 3 and expression of its target gene products in human ESCC cell line].

OBJECTIVE: To investigate the expression of signal transducers and activators of transcription 3 (STAT3) and its target gene products including vascular endothelial growth factor (VEGF) and Bcl-2 in two human esophageal squamous cell carcinoma (ESCC) cell lines for understanding whether STAT3 signaling transduction pathway was constitutively activated in ESCC cell lines. METHODS: Western blotting was used to determine the protein levels of STAT3, p-STAT3 (activated STAT3), VEGF and Bcl-2 in two ESCC cell lines (EC9706 and Eca109). Nuclear proteins from the ESCC cell lines were extracted to evaluate the DNA-binding activity by electrophoretic mobility gel shift assay (EMSA). RT-PCR was used to detect the mRNA of STAT3, VEGF and Bcl-2. RESULTS: Western blotting and RT-PCR revealed that STAT3, VEGF and Bcl-2 protein and mRNA were overexpressed in the two ESCC cell lines, which contained constitutively activated STAT3 signaling transduction pathway. The results of EMSA of the nuclear protein showed high DNA-binding activity of STAT3. CONCLUSION: STAT3 signaling transduction pathway is constitutively activated in human ESCC cell lines, suggesting that STAT3 may play a critical role in the carcinogenesis of the esophagus.

Carcinoma, Squamous Cell↗