bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cyclic AMP mediated GSTP1 gene activation in tumor cells involves the interaction of activated CREB‐1 with the GSTP1 CRE: A novel mechanism of cellular GSTP1 gene regulation
Authors: Lo Hui‐Wen , Ali‐Osman Francis 
Published: September 2002

AbstractThe human GSTP1 gene is frequently over‐expressed in many human cancers and the expression increases with tumor progression and is associated with a more aggressive biology, poor patient survival, and resistance to therapy. The molecular regulation of the human GSTP1 gene during malignancy is, however, still not well understood. Recently, we reported the presence of a cAMP response element (CRE) in the 5′‐region of the human GSTP1 gene, raising the possibility that the cAMP signaling pathway, frequently aberrant in human cancers, may play an important role in the transcriptional activation of the GSTP1 gene in human tumors. In this study, we report that the GSTP1 gene is an early cAMP response gene. Treatment of cells of the human lung carcinoma cell line, Calu‐6, with 25 μM forskolin to activate the cAMP pathway resulted in a rapid and significant (sevenfold after 30 min) increase in GSTP1 gene transcripts, which peaked at 12‐fold after 4 h. The forskolin‐activated GSTP1 transcription in Calu‐6 cells was suppressed dose‐dependently by a 2‐h pre‐treatment with 0.1, 1.0, and 10 μ of the adenylate cyclase inhibitor, 2′, 5′‐dideoxyadenosine. Western blot analysis showed a rapid, fivefold increase, in GSTP1 protein levels after treatment with 25 μM forskolin, with a peak at 2 h post‐treatment. The levels of phosphorylated CRE (Ser133) binding protein‐1 (CREB‐1) increased rapidly, sevenfold at 30 min, and reached 10‐fold at 4 h following forskolin treatment. Intracellular cAMP levels also increased rapidly reaching 12‐fold at 30 min. Gel mobility shift and supershift assays and DNase I footprinting analyses demonstrated that CREB‐1 bZIP and CREB‐containing nuclear extracts recognized the GSTP1 CRE with high affinity and specificity. Binding of CREB‐1 bZIP to the GSTP1 CRE was abolished when the GSTP1 CRE sequence, 5′‐CGTCA‐3′, was mutated at the core nucleotides. Finally, transfection studies using luciferase plasmid constructs showed the GSTP1 CRE to be required for the cAMP‐activated gene expression. Together, these findings describe a novel cAMP‐ and CREB‐1‐mediated mechanism of transcriptional regulation of the GSTP1 gene and suggest that this may be an important mechanism underlying the increased GSTP1 expression observed in tumors with an aberrant cAMP signaling pathway and in normal cells under conditions of stress, associated with increased intracellular cAMP. J. Cell. Biochem. 87: 103–116, 2002. © 2002 Wiley‐Liss, Inc.
Runx2, A multifunctional transcription factor in skeletal development
Authors: Komori Toshihisa 
Published: September 2002

AbstractThe identification of Runx2 (runt‐related protein 2) function has greatly advanced the understanding of skeletal development over the last 5 years. Runx2 is regulated transcriptionally and post‐translationally through the activity of many identified factors, although, the physiological significance of each remains to be demonstrated. The interaction of Runx2 with other transcription factors and cofactors has been shown to be important in Runx2‐dependent gene regulation. Runx2 plays important roles in multiple steps of skeletal development. Runx2 determines the lineage of osteoblasts from multipotent mesenchymal cells, enhances osteoblast differentiation at an early stage, and inhibits osteoblast differentiation at a late stage. Runx2 plays crucial roles in chondrocyte maturation and in the specification of cartilage phenotypes. Furthermore, Runx2 is involved in vascular invasion into cartilage and osteoclastogenesis. Therefore, the determination of Runx2 function and the investigation of the cascades of Runx2‐dependent gene regulation are important in the elucidation of skeletal biology. J. Cell. Biochem. 87: 1–8, 2002. © 2002 Wiley‐Liss, Inc.
Okadaic acid stimulates osteopontin expression through de novo induction of AP‐1
Authors: Kim Hyun‐Jung , Lee Mi‐Hye , Kim Hyun‐Jung , Shin Hong‐In , Choi Je‐Yong , Ryoo Hyun‐Mo 
Published: September 2002

AbstractOsteopontin, a major non‐collagenous bone matrix protein, is strikingly upregulated in various tissues under certain pathologic conditions, including cancer. However, the mechanism of upregulation of the osteopontin gene in tumor cells remains unclear. Okadaic acid, a strong non‐phorbol ester tumor promoter, is known to stimulate the expression of osteopontin. The aim of the present study was to understand the mechanism by which okadaic acid regulates osteopontin gene expression. Okadaic acid stimulated osteopontin mRNA expression in several cell lines within 3 h, and the increase in osteopontin mRNA was sustained for 24 h. New protein synthesis was required for the okadaic acid‐elicited increase in osteopontin mRNA expression. A serial promoter deletion study showed that the okadaic acid‐response element is located between positions −265 and −73, a sequence that includes the Runx2, Ets‐1, and AP‐1 binding sequences. Okadaic acid increased the mRNA expression of AP‐1 components but not of Runx2 or Ets‐1. Site‐directed mutagenesis and electrophoretic mobility shift assays confirmed that protein binding of the AP‐1 consensus sequence is necessary for the okadaic acid‐mediated osteopontin gene upregulation. These results indicate that de novo induction of the oncoprotein AP‐1 is required for okadaic acid‐stimulated osteopontin gene upregulation. J. Cell. Biochem. 87: 93–102, 2002. © 2002 Wiley‐Liss, Inc.
The development and validation of the Dormitory Observation Report: A behavioral rating instrument for juvenile delinquents in residential care
Authors: Veneziano Louis , Veneziano Carol 
Published: September 2002

AbstractIn order to provide an objective measure of problematic behavioral patterns among juvenile delinquents in residential facilities, the Dormitory Observation Report (DOR) was developed. The DOR assesses 11 dimensions of problematic behavioral patterns (e.g., physical assaultiveness, manipulativeness), as well as three dimensions of desirable behavioral patterns expected in an institutional setting (e.g., independent functioning, personal hygiene, care of surroundings). Empirical study regarding the reliability and validity of the DOR are reported, and the results are discussed in terms of the theoretical and practical implications of this instrument. © 2002 Wiley Periodicals, Inc. J Clin Psychol 58: 1103–1117, 2002.
The reliability of the Massachusetts Substance Abuse Management Information System
Authors: Soldz Stephen , Panas Lee , Rodriguez‐Howard Mayra 
Published: September 2002

AbstractState substance abuse management information systems increasingly are becoming important tools for research, program management, and policy formulation at federal and state levels. These systems are currently undergoing radical expansion, leading to the creation of statewide performance and outcome monitoring systems for publicly‐funded substance abuse treatment. This expansion makes imperative increased knowledge of the psychometric properties of the data in these systems. This study develops a method for examining the reliability of such data and applies it to the Massachusetts Substance Abuse Management Information System (SAMIS). Cohen's κ, intraclass correlations, and the techniques of Heise (1969) are used to assess the reliability of different types of variables. Results show that key variables on the SAMIS Admission Form exhibit moderate to high reliability, supporting the use of this data for aggregate analyses. At the same time, caution should be used in making judgments about individual patients. © 2002 Wiley Periodicals, Inc. J Clin Psychol 58: 1057–1069, 2002.
The psychological effects of a lifestyle management course on war veterans and their spouses
Authors: Devilly Grant J. 
Published: September 2002

AbstractThis research assessed the effect on a war‐veteran outpatient group in a week‐long residential lifestyle‐management course. This course also included the veterans' partners, and all participants were assessed at intake, post‐intervention, and at three‐ and six‐month follow‐ups. In summary, it was found that while there was a statistically significant drop in PTSD symptomatology for the veterans, the clinical utility of this improvement was minimal, with an estimated effect size of d = 0.19 by six‐month follow‐up. However, the veterans displayed a significant decrease in measures of depression, anxiety, and stress by six‐month follow‐up, all with small‐to‐moderate effect sizes. Likewise, ratings of anger showed statistically significant improvement with a moderate effect size. While dyadic adjustment displayed a significant improvement to six‐month follow‐up, the derived effect size was small for the veterans. The spouses (all females in this study) displayed larger effect sizes on all measures, with the exception of ratings of anger, where a small effect was noted. Subjective quality‐of‐life indices displayed a significant change in the desired direction, although with a minimal effect for the veterans and a small effect size for the females. It was not feasible to have a control group during this naturalistic investigation and, therefore, caution is advised in over‐generalizing from these data. However, these results warrant further ‘controlled’ investigation into the inclusion of spouses in the treatment of veterans and the utility of lifestyle‐management courses as a first step in the treatment of trauma related problems that have become chronic in nature within the veteran community. © 2002 Wiley Periodicals, Inc. J Clin Psychol 58: 1119–1134, 2002.
Do early responders to psychotherapy maintain treatment gains?
Authors: Haas Eric , Hill Robert D. , Lambert Michael J. , Morrell Barbara 
Published: September 2002

AbstractThis study examined early positive response to psychotherapy in a sample of 147 college student clients seeking therapy at a university counseling center. Early response was determined based on a score representing the difference between client‐obtained symptom distress session scores and expected scores derived from a large actuarial study of typical treatment response. In the present study, early positive response to therapy was associated with fewer psychological symptoms at therapy termination and follow‐up and maintenance of therapy gains. These results are discussed in relation to placebo effects and common factors and their primary importance in producing meaningful change. Future research directions are recommended that include the use of early response for exploring the contribution of client variables and theoretically derived interventions as they relate to the outcome of psychotherapy. © 2002 Wiley Periodicals, Inc. J Clin Psychol 58: 1157–1172, 2002.
Focusing on the positive, focusing on the negative: Implications for psychotherapy
Authors: Bohart Arthur C. 
Published: September 2002

AbstractEach of the contributions in this special section challenges some of our preciously held notions. We are challenged to be aware that an overfocus on positivity and optimism can be tyrannical, see the positivity in the negativity, realize that some pessimism can be adaptive, see that complaining has positive value, and be aware that false hope is not necessarily bad. Through an examination of these, I have suggested that (a) we have to be careful to deeply respect the individuality of our clients and to take seriously the possibility that there is some “ecological wisdom” in their apparently dysfunctional behavior, and (b) what is more important than optimism–pessimism, complaining versus not complaining, or false versus realistic hope is the degree to which the client adopts a task‐focused orientation towards problems. © 2002 Wiley Periodicals, Inc. J Clin Psychol 58: 1037–1043, 2002.
PTH‐dependent adenylyl cyclase activation in SaOS‐2 cells: Passage dependent effects on G protein interactions
Authors: Gao Hong , Bodine Peter V.N. , Murrills Richard , Bex Fred J. , Bilezikian John P. , Morris Stephen A 
Published: September 2002

AbstractParathyroid hormone (PTH) sensitive adenylyl cyclase activity (ACA) in SaOS‐2 cells varies as a function of cell passage. In early passage (EP) cells (< 6), ACA in response to PTH and forskolin (FOR) was relatively low and equivalent, whereas in late passage (LP) cells (> 22), PTH exceeded FOR dependent ACA. Potential biochemical mechanisms for this passage dependent change in ACA were considered. In EP, prolonged exposure to pertussis toxin (PT) markedly enhanced ACA activity in response to PTH, Isoproterenol and Gpp(NH)p, whereas ACA in response to FOR was decreased. In contrast, the identical treatment of LP with PT diminished all ACA in response to PTH, Gpp(NH)p, and FOR. The dose dependent effects of PT on subsequent [32P]ADP‐ribosylation of its substrates, GTPase activity, as well as FOR‐dependent ACA, were equivalent in EP and LP. The relative amounts of Gαi and Gαs proteins, as determined both by Western blot, PT and cholera toxin (CT) dependent [32P]ADP‐ribosylation, were quantitatively similar in EP and LP. Western blot levels of Gαs and Gαi proteins were not influenced by prior exposure to PT. Both PT and CT dependent [32P]ADP‐ribosylation were dose‐dependently decreased following exposure to PT. However, the PT‐dependent decline in CT‐dependent [32P]ADP‐ribosylation occurred with enhanced sensitivity in LP. The protein synthesis inhibitor cycloheximide partially reversed the PT associated decrease in FOR dependent ACA in EP. In contrast, cycloheximide completely reversed the PT associated decrease in FOR and as well as PTH dependent ACA in LP. Gαs activity, revealed by cyc− reconstitution, was not altered either by cell passage or exposure to PT. The results suggest that the coupling between the components of the complex may be pivotally important in the differential responsiveness of early and late passage SaOS‐2 cells to PTH. J. Cell. Physiol. 193: 10–18, 2002. © 2002 Wiley‐Liss, Inc.
Calcium channel blockers inhibit galvanotaxis in human keratinocytes
Authors: Trollinger Donna R. , Rivkah Isseroff R. , Nuccitelli Richard 
Published: September 2002

AbstractDirected migration of keratinocytes is essential for wound healing. The migration of human keratinocytes in vitro is strongly influenced by the presence of a physiological electric field and these cells migrate towards the negative pole of such a field (galvanotaxis). We have previously shown that the depletion of extracellular calcium blocks the directional migration of cultured human keratinocytes in an electric field (Fang et al., 1998; J Invest Dermatol 111:751–756). Here we further investigate the role of calcium influx on the directionality and migration speed of keratinocytes during electric field exposure with the use of Ca2+ channel blockers. A constant, physiological electric field strength of 100 mV/mm was imposed on the cultured cells for 1 h. To determine the role of calcium influx during galvanotaxis we tested the effects of the voltage‐dependent cation channel blockers, verapamil and amiloride, as well as the inorganic Ca2+ channel blockers, Ni2+ and Gd3+ and the Ca2+ substitute, Sr2+, on the speed and directionality of keratinocyte migration during galvanotaxis. Neither amiloride (10 μM) nor verapamil (10 μM) had any effect on the galvanotaxis response. Therefore, calcium influx through amiloride‐sensitive channels is not required for galvanotaxis, and membrane depolarization via K+ channel activity is also not required. In contrast, Sr2+ (5 mM), Ni2+ (1–5 mM), and Gd3+ (100 μM) all significantly inhibit the directional migratory response to some degree. While Sr2+ strongly inhibits directed migration, the cells exhibit nearly normal migration speeds. These findings suggest that calcium influx through Ca2+ channels is required for directed migration of keratinocytes during galvanotaxis and that directional migration and migration speed are probably controlled by separate mechanisms. J. Cell. Physiol. 193: 1–9, 2002. © 2002 Wiley‐Liss, Inc.
Calcium induces differentiation of primary human salivary acinar cells
Authors: Hiraki Akimitsu , Shirasuna Kanemitsu , Ikari Tatsuya , Shinohara Masanori , Garrod David R. 
Published: September 2002

AbstractCultivation of human parotid glands in serum‐free medium (Ca2+ concentration, 0.2 mM) with growth supplements resulted in isolation of a homogeneous population of epithelial cells without any mesenchymal cells. The isolated cells showed an undifferentiated phenotype with scant cytoplasmic organelles, and low levels of α‐amylase expression. The cells remained viable and undifferentiated for up to 24 passages when subcultured at 80% confluence in 0.2 mM Ca2+ medium with a 1:3 split ratios. There was little cell–cell contact. A Ca2+ switch from 0.2 to 1 mM induced cell–cell contact with translocation of desmosomal proteins from the cytoplasm to the cell membrane, and sequential differentiation of serous acinar cells with a glandular arrangement, well‐developed cytoplasmic organelles and an increased level of α‐amylase expression. These morphological changes and desmosome assembly were blocked by treatment with non‐specific PKC inhibitor. Moreover, the addition of PKC activator, tetradecanoylphorbol 13‐acetate (TPA), to 0.2 mM Ca2+ medium caused transient assembly of desmosome‐like structure, but did not induce cell–cell contact or morphological differentiation. Cultivation of the cells in 1.5 mM Ca2+ medium resulted in increased stratification of the cells and reduced α‐amylase expression. These findings provide the first demonstration that continuous cultivation in 1.0 mM Ca2+ medium is required for cellular differentiation of salivary gland acinar cells, and maintenance of the differentiated state. J. Cell. Physiol. 193: 55–63, 2002. © 2002 Wiley‐Liss, Inc.
Synergistic effect of the anti‐HER‐2/neu antibody and cisplatin in immortalized and primary mesothelioma cell lines
Authors: Toma Salvatore , Colucci Lucia , Scarabelli Linda , Scaramuccia Angelo , Emionite Laura , Betta Pier Giacomo , Mutti Luciano 
Published: September 2002

AbstractMalignant mesothelioma (MM) still remains a therapeutic and diagnostic problem to which new therapeutic perspectives are being continuously tried and tested. Three different primary cultures (MMGe‐1, MES MM 98, and MES 1) and one immortalized cell line (MSTO 211 H) of human MM were studied in order to evaluate the HER‐2/neu expression. Three out of four cell lines showed a different level of c‐erbB‐2 expression, the highest being detected on the MSTO 211 H cell line (fibroblastic phenotype), whereas MMGe‐1 resulted negative. The effect of the anti‐HER‐2/neu antibody (Trastuzumab) alone, and in combination with cisplatin (CDDP) at different doses (ranging from 0.1 to 100 μg/ml), was studied on all the c‐erB‐2 positive cell lines. Trastuzumab was able to inhibit cell proliferation in a time‐dependent manner, with growth inhibition also obtained at low concentrations (0.1–1 μg/ml). Combined treatment with Trastuzumab (10 μg/ml) and CDDP (1 μg/ml) showed synergism. Our results were encouraging, and suggest a rationale for further investigations in a clinical setting. J. Cell. Physiol. 193: 37–41, 2002. © 2002 Wiley‐Liss, Inc.
Sortilin is upregulated during osteoblastic differentiation of mesenchymal stem cells and promotes extracellular matrix mineralization
Authors: Maeda Shingo , Nobukuni Takahiro , Shimo‐Onoda Kazuki , Hayashi Kyoji , Yone Kazunori , Komiya Setsuro , Inoue Ituro 
Published: September 2002

AbstractOsteoblasts and adipocytes are derived from a common precursor in bone marrow, the mesenchymal stem cell (MSC). Factors driving human MSCs (hMSCs) to differentiate down the two lineages play important roles in determining bone density because it has been shown that bone volume loss associated with osteoporosis and aging is accompanied by reduced osteoblastic bone formation and increased marrow adipose tissue. The genes upregulated in hMSCs during osteogenic differentiation were screened using cDNA microarrays and were semi‐quantitated by real‐time RT‐PCR. One of the genes identified was sortilin, which was upregulated one day after osteogenic induction and remained upregulated for a week. The overexpression of sortilin in hMSCs using an adenovirus vector resulted in the acceleration of mineralization during osteogenic differentiation without affecting alkaline phosphatase activity. Lipoprotein lipase (LPL), produced by adipocytes, is bound by sortilin, which may mediate its endocytosis. By adding LPL to osteogenic induction medium, osteoblastic mineralization was inhibited in a dose‐dependent manner. Interestingly, sortilin overexpression abolished the LPL‐mediated suppression of osteogenic differentiation. hMSCs exist in marrow where LPL‐producing adipose cells are abundant and where osteogenesis is negatively regulated by LPL. Sortilin has a counter effect of promoting osteogenesis by acting as a scavenger of LPL. J. Cell. Physiol. 193: 73–79, 2002. © 2002 Wiley‐Liss, Inc.
Titin‐cap associates with, and regulates secretion of, Myostatin
Authors: Nicholas Gina , Thomas Mark , Langley Brett , Somers Wayne , Patel Ketan , Kemp C. Fred , Sharma Mridula , Kambadur Ravi 
Published: September 2002

AbstractMyostatin, a secreted growth factor, is a key negative regulator of skeletal muscle growth. To identify modifiers of Myostatin function, we screened for Myostatin interacting proteins. Using a yeast two‐hybrid screen, we identified Titin‐cap (T‐cap) protein as interacting with Myostatin. T‐cap is a sarcomeric protein that binds to the N‐terminal domain of Titin and is a substrate of the titin kinase. Mammalian two‐hybrid studies, in vitro binding assays and protein truncations in the yeast two‐hybrid system verified the specific interaction between processed mature Myostatin and full‐length T‐cap. Analysis of protein–protein interaction using surface plasmon resonance (Biacore, Uppsala, Sweden) kinetics revealed a high affinity between Myostatin and T‐cap with a KD of 40 nM. When T‐cap was stably overexpressed in C2C12 myoblasts, the rate of cell proliferation was significantly increased. Western analyses showed that production and processing of Myostatin were not altered in cells overexpressing T‐cap, but an increase in the retention of mature Myostatin indicated that T‐cap may block Myostatin secretion. Bioassay for Myostatin confirmed that conditioned media from myoblasts overexpressing T‐cap contained lower levels of Myostatin. Given that Myostatin negatively regulates myoblast proliferation, the increase in proliferation observed in myoblasts overexpressing T‐cap could thus be due to reduced Myostatin secretion. These results suggest that T‐cap, by interacting with Myostatin, controls Myostatin secretion in myogenic precursor cells without affecting the processing step of precursor Myostatin. J. Cell. Physiol. 193: 120–131, 2002. © 2002 Wiley‐Liss, Inc.