bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design of Chebyshev‐type IIR filters with approximately linear phase characteristics
Authors: Takeuchi Ryousuke , Zhang Xi , Yoshikawa Toshinori , Takei Yoshinori 
Published: October 2003

AbstractDigital filters with a linear phase characteristic are needed in many applications for signal processing. In this paper, design of a Chebyshev‐type IIR filter with approximate linear phase characteristics in the passband is described. First, it is shown that a flat stopband can easily be realized by placing multiple zeros at the specified frequency points in the stopband. Next, the complex Remez exchange algorithm is applied to the passband so that the filter design problem is formulated as an eigenvalue problem. Hence, by solving the eigenvalue problem, the filter coefficients can be derived easily. Further, by means of iterative calculations, an equiripple characteristic of the error function in the passband is obtained. Finally, it is shown that a reverse Chebyshev‐type IIR filter with an approximate linear phase characteristic can also be obtained by parallel connection of the proposed Chebyshev‐type filter and a delay line. © 2003 Wiley Periodicals, Inc. Electron Comm Jpn Pt 3, 87(2): 1–9, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjc.10133
Poly(ADP‐ribose) and carcinogenesis
Authors: Masutani Mitsuko , Nakagama Hitoshi , Sugimura Takashi 
Published: October 2003

AbstractPoly(ADP‐ribose) and poly(ADP‐ribose) polymerase (PARP) were discovered about 40 years ago, but their significance was not well elucidated until recently. In the early stage of the history of PARP, the presence of antibodies in the sera of human patients with lupus erythematosus indicated its natural occurrence. PARP, as well as the degrading enzyme, poly(ADP‐ribose) glycohydrolase (PARG), are present in most eukaryotes except for yeasts. Studies that used inhibitors of PARP indicated the involvement of PARP and poly(ADP‐ribose) in DNA damage repair, and eventually PARP was purified and the gene was cloned. Molecular analysis then revealed various functional domains, such as the one for binding to strand breaks of DNA. Parp‐1–deficient and Parg‐deficient cells showed, in general, enhanced sensitivity to the lethal effects of ionizing radiation and alkylating agents. Parp‐1 knockout mouse embryonic stem cells developed into teratocarcinoma‐like tumors when injected subcutaneously into nude mice, these tumors featuring giant cells similar to syncytiotrophoblastic giant cells with hyperploidy. Parp‐1 was also found in centrosomes, suggesting that poly(ADP‐ribose) and PARP‐1 are functionally involved in the maintenance of chromatin structure and the equal distribution of chromosomes into daughter cells. Intriguing findings on the real biological significance continue to be generated, with new light shed on mechanisms of carcinogenesis and pointing to novel cancer treatments. Highlights during the last four decades of studies by laboratories focusing on poly(ADP‐ribose)/PARP, including our own, are condensed and summarized in this review. © 2003 Wiley‐Liss, Inc.
Multiple roles of the tuberous sclerosis complex genes
Authors: Yeung Raymond S. 
Published: October 2003

AbstractSoon after proposing the “two‐hit” hypothesis for tumorigenesis, Knudson pursued further experimental validation of the concept by using a rat model of dominantly inherited renal tumor. Today, the Eker rat is one of the best characterized models of tuberous sclerosis complex (TSC) and has been used extensively for study of the function of the TSC2 tumor suppressor gene. Along with TSC1, these two genes behave as expected for tumor suppressor genes with evidence for loss of heterozygosity in tumors and suppression of growth when expressed in proliferating cells. Despite much experimental work, the mechanisms of these genes have remained elusive until recently. This review summarizes some of the current concepts in our understanding of the biological and biochemical function of the TSC genes. © 2003 Wiley‐Liss, Inc.
Sustained calpain activation associated with lysosomal rupture executes necrosis of the postischemic CA1 neurons in primates
Authors: Yamashima Tetsumori , Tonchev Anton B. , Tsukada Toshiyuki , Saido Takaomi C. , Imajoh‐Ohmi Shinobu , Momoi Takashi , Kominami Eiki 
Published: October 2003

AbstractBecause of the paucity of primate experimental models, the precise molecular mechanism of ischemic neuronal death remains unknown in humans. This study focused on nonhuman primates to determine which cascade necrosis or apoptosis is predominantly involved in the development of delayed (day 5) neuronal death in the hippocampal CA1 sector undergoing 20 min ischemia. We investigated expression, activation, and/or translocation of μ‐calpain, lysosome‐associated membrane protein‐1 (LAMP‐1), caspase‐3, and caspase‐activated DNase (CAD), as well as morphology of the postischemic CA1 neurons and DNA electrophoresis pattern. Immunoblotting showed sustained (immediately after ischemia until day 5) and maximal (day 3) activation of μ‐calpain. The immunoreactivity of activated μ‐calpain became remarkable as coarse granules at lysosomes on day 2, while it translocated throughout the perikarya on day 3. The immunoreactivity of LAMP‐1 also showed a dynamic and concomitant translocation that was maximal on days 2–3, indicating calpain‐mediated disruption of the lysosomal membrane after ischemia. In contrast, immunoblotting demonstrated essentially no increase in the activated caspase‐3 at any time points after ischemia, despite upregulation of pro‐caspase‐3. Although expression of CAD was slightly upregulated on day 1 or 2, or both, it was much less compared with lymph node or intestine tissues. Furthermore, light and electron microscopy showed eosinophilic coagulation necrosis and membrane disruption without apoptotic body formation, while DNA electrophoresis did not show a ladder pattern, but rather a smear pattern. Sustained calpain activation and the resultant lysosomal rupture, rather than CAD‐mediated apoptosis, may cause ischemic neuronal necrosis in primates. © 2003 Wiley‐Liss, Inc.
Intracellular correlate of EPSP‐spike potentiation in CA1 pyramidal neurons is controlled by GABAergic modulation
Authors: Staff Nathan P. , Spruston Nelson 
Published: October 2003

AbstractThe hippocampus has been used extensively as a model to study plastic changes in the brain's neural circuitry. Immediately after high‐frequency stimulation to hippocampal Schaffer collateral axons, a dramatic change occurs in the relationship between the presynaptic CA3 and the postsynaptic CA1 pyramidal neurons. For a fixed excitatory postsynaptic potential (EPSP), there arises an increased likelihood of action potential generation in the CA1 pyramidal neuron. This phenomenon is called EPSP‐spike (E‐S) potentiation. We explored E‐S potentiation, using patch‐clamp techniques in the hippocampal slice preparation. A specific protocol was developed to measure the action potential probability for a given synaptic strength, which allowed us to quantify the amount of E‐S potentiation for a single neuron. E‐S potentiation was greatest when γ‐aminobutyric acid (GABA)ergic inhibition was intact, suggesting that modulation of inhibition is a major aspect of E‐S potentiation. Expression of E‐S potentiation also correlated with a reduced action‐potential threshold, which was greatest when GABAergic inhibition was intact. Conditioning stimuli produced a smaller threshold reduction when inhibition was blocked, but some reduction also occurred in the absence of a conditioning stimulus. Together, these results suggest that E‐S potentiation is caused primarily through a reduction of GABAergic inhibition, leading to larger EPSPs and reduced action potential threshold. Our findings do not rule out, however, the possibility that modulation of voltage‐gated conductances also contributes to E‐S potentiation. © 2003 Wiley‐Liss, Inc.
Expression of plasma membrane GABA transporters but not of the vesicular GABA transporter in dentate granule cells after kainic acid seizures
Authors: Sperk Günther , Schwarzer Christoph , Heilman Jutta , Furtinger Sabine , Reimer Richard J. , Edwards Robert H. , Nelson Nathan 
Published: October 2003

AbstractKainic acid‐induced seizures cause a marked increase in the expression of glutamate decarboxylase 67 (GAD67) in granule cells of the dentate gyrus. To determine the possible modes of sequestration of newly formed γ‐aminobutyric acid (GABA), we used in situ hybridization and immunocytochemistry to investigate the expression of several proteins related to GABA in dentate granule cells of rats 4 h to 60 days after kainic acid‐induced status epilepticus and in controls. GAD67 and GAD65 mRNA levels were increased by up to 300% and 800%, respectively, in the granule cell layer 6–24 h after kainate injection. Subsequently, increased GAD and GABA immunoreactivity was observed in the terminal field of mossy fibers and in presumed dendrites of granule cells. mRNA of both known plasma membrane GABA transporters (GAT‐1 and GAT‐3) was expressed in granule cells of control rats. GAT‐1 mRNA levels increased (by 30%) 9 h after kainate injection but were reduced by about 25% at later intervals. GAT‐3 mRNA was reduced (by 35–75%) in granule cells 4 h to 30 days after kainic acid injection. In contrast, no expression of the mRNA or immunoreactivity of the vesicular GABA transporter was detected in granule cells or in mossy fibers, respectively. GABA transaminase mRNA was only faintly expressed in granule cells, and its levels were reduced (by 60–65%) 12 h to 30 days after kainate treatment. The results indicate that GABA can be taken up and synthesized in granule cells. No evidence for the expression of the vesicular GABA transporter (VGAT) in granule cells was obtained. After sustained epileptic seizures, the markedly increased expression of glutamate decarboxylase and the reduced expression of GABA transaminase may result in increased cytoplasmic GABA concentrations in granule cells. It is suggested that, during epileptic seizures, elevated intracellular GABA and sodium concentration could then result in nonvesicular release of GABA from granule cell dendrites. GABA could then act on GABA‐A receptors, protecting granule cells from overexcitation. © 2003 Wiley‐Liss, Inc.
Increased levels of acidic calponin during dendritic spine plasticity after pilocarpine‐induced seizures
Authors: Ferhat Lotfi , Esclapez Monique , Represa Alfonso , Fattoum Abdellatif , Shirao Tomoaki , Ben‐Ari Yezekiel 
Published: October 2003

AbstractWe have previously shown that, in HEK 293 cells, overexpression of acidic calponin, an actin‐binding protein, induces remodeling of actin filaments, leading to a change in cell morphology. In addition, this protein is found in dendritic spines of adult hippocampal neurons. We hypothesized that this protein plays a role in regulating actin‐based filaments during dendritic spine plasticity. To assess this hypothesis, the pilocarpine model of temporal lobe epilepsy was selected because an important reorganization of the glutamatergic network, which includes an aberrant sprouting of granule cell axons, neo‐synaptogenesis, and dendritic spine remodeling, is well established in the dentate gyrus. This reorganization begins after the initial period of status epilepticus after pilocarpine injection, during the silent period when animals display a normal behavior, and reaches a plateau at the chronic stage when the animals have developed spontaneous recurrent seizures. Our data show that the intensity of immunolabeling for acidic calponin was clearly increased in the inner one‐third of the molecular layer of the dentate gyrus, the site of mossy fiber sprouting, and neo‐synaptogenesis, at 1 and 2 weeks after pilocarpine injection (silent period) when the reorganization was taking place. In contrast, in chronic pilocarpine‐treated animals, when the reorganization was established, the levels of labeling for acidic calponin in the inner molecular layer were similar to those observed in control rats. In addition, double immunostaining studies suggested that the increase in acidic calponin levels occurred within the dendritic spines. Altogether, these results are consistent with an involvement of acidic calponin in dendritic spine plasticity. © 2003 Wiley‐Liss, Inc.
Nitric oxide synthase and arginase in the rat hippocampus and the entorhinal, perirhinal, postrhinal, and temporal cortices: Regional variations and age‐related changes
Authors: Liu Ping , Smith Paul F. , Appleton Ian , Darlington Cynthia L. , Bilkey David K. 
Published: October 2003

AbstractIncreasing evidence suggests that nitric oxide synthase (NOS)/nitric oxide (NO) contributes to the aging process. By contrast, the role of arginase, which shares a common substrate with NOS, has not been determined. In the present study, regional variations and age‐related changes in NOS and arginase in the hippocampus and its neighboring structures were investigated for the first time. In young adult rats, high levels of NOS activity were found in the entorhinal, perirhinal, and postrhinal cortices, whereas low values were located in the hippocampus and the temporal cortex. Interestingly, arginase activity showed an overall inverse pattern with the lowest levels in the entorhinal and perirhinal cortices. When a comparison was carried out between young (4‐month‐old) and aged (24‐month‐old) rats, significant increases in total NOS activity were found in the aged entorhinal and temporal cortices, and a significant decrease in arginase activity was observed in the aged postrhinal cortex. Western blotting demonstrated significant decreases in both neuronal and endothelial NOS expression in the aged hippocampus and postrhinal cortex, whereas arginase I and II expression did not show age‐related changes in any region examined. Activity and protein expression of inducible NOS were not detected in any tissue from either group. The present findings of region‐specific changes in NOS and arginase appear to support the potential involvement of NOS/NO in the aging process and raise the issue of a possible contribution of arginase to aging. © 2003 Wiley‐Liss, Inc.
Reversal of breast cancer resistance protein–mediated drug resistance by tryprostatin A
Authors: Woehlecke Holger , Osada Hiroyuki , Herrmann Andreas , Lage Hermann 
Published: October 2003

AbstractMDR in human cancers is one of the major causes of failure of chemotherapy. A member of the superfamily of ABC transporters, BCRP, was demonstrated to confer an atypical MDR phenotype to tumor cells. To overcome the BCRP‐mediated drug resistance, the fungal secondary metabolite TPS‐A, a diketopiperazine, was analyzed with regard to its potency to reverse the BCRP‐mediated drug‐resistant phenotype. At concentrations of 10–50 μM, TPS‐A reversed a mitoxantrone‐resistant phenotype and inhibited the cellular BCRP‐dependent mitoxantrone accumulation in the human gastric carcinoma cell line EPG85‐257RNOV, the human breast cancer cell line MCF7/AdrVp (both exhibiting acquired BCRP‐mediated MDR) and the BCRP cDNA‐transfected breast cancer cell line MCF‐7/BCRP clone 8. No cytotoxicity was seen at effective concentrations. These data indicate that TPS‐A is a novel BCRP inhibitor. © 2003 Wiley‐Liss, Inc.
15‐hydroxy‐eicosatetraenoic acid arrests growth of colorectal cancer cells via a peroxisome proliferator‐activated receptor gamma‐dependent pathway
Authors: Chen George G. , Xu Hu , Lee Janet F.Y. , Subramaniam Malayannan , Leung Ka L. , Wang Su H. , Chan Ursula P.F. , Spelsberg Thomas C. 
Published: October 2003

AbstractPeroxisome proliferator‐activated receptor gamma (PPARγ) inhibits cell growth via promoting apoptosis. Human colorectal cancer tissues had abundant PPARγ but the incidence of apoptosis was very low, suggesting a defect in the PPARγ pathway. Here, we found that 15‐hydroxy‐eicosatetraenoic acid (15S‐HETE), an endogenous ligand for PPARγ, was significantly decreased in the serum of patients with colorectal cancer. Treatment of colon cancer cells with 15S‐HETE inhibited cell proliferation and induced apoptosis, which was preceded by an increase in TGF‐β‐inducible early gene (TIEG) and a decrease in Bcl‐2. The action of 15S‐HETE could be blocked when PPARγ was suppressed. Overexpression of Bcl‐2 prevented the apoptosis. The levels of TIEG and 15‐lipoxygenase (15‐LOX), the enzyme responsible for 15S‐HETE production, was decreased in colorectal cancer. Therefore, colorectal cancer is associated with decreased 15S‐HETE. Treatment of colon cancer cells with 15S‐HETE inhibits cell proliferation and induces apoptosis in a PPARγ‐dependent pathway involving augmentation of TIEG and reduction of Bcl‐2 expression. © 2003 Wiley‐Liss, Inc.
Autocrine motility factor signaling induces tumor apoptotic resistance by regulations Apaf‐1 and Caspase‐9 apoptosome expression
Authors: Haga Arayo , Funasaka Tatsuyoshi , Niinaka Yasufumi , Raz Avraham , Nagase Hisamitsu 
Published: October 2003

AbstractAutocrine motility factor (AMF) is a cytokine that regulates locomotion and metastasis of tumor cells. It is well known that expression levels of AMF secretion and its receptor (AMF R) are closely related to tumor malignancy and rheumatoid arthritis. We have established that AMF signaling induced anti‐apoptotic activity and that human fibrosarcoma HT‐1080 line that secreted high levels of AMF were resistant to drug‐induced apoptosis. These cells did not express the apoptotic protease activating factor‐1 (Apaf‐1) and Caspase‐9 genes that encode for the proteins that form the “apoptosome” complex. The disappearance of the Apaf‐1 and Caspase‐9 gene was recovered by a cellular signaling inhibitor of protein kinase C, phosphatidylinositol 3‐phosphate kinase and mitogen‐activated protein kinase of the in vitro cultured human fibrosarcoma HT‐1080 line. Treatment with these inhibitors favored apoptotic cell death induced by anti‐cancer drugs of the murine ascites Ehrlich line. Apoptotic resistance of tumor cells allows them to escape death from cancer chemotherapy, so an understanding of malignant anti‐apoptotic activities is important. Antibodies against AMF induced Ehrlich ascites apoptosis in vitro, and effectively aided in vivo apoptosis induced by anti‐cancer drugs. The results might indicate a novel route by which tumor cells protect themselves with products, such as AMF, and proliferate despite various stresses and chemical insults; AMF regulates expression of Apaf‐1 and caspase‐9 genes via a complex signaling pathway and indirectly regulates formation of the apoptosome. © 2003 Wiley‐Liss, Inc.
Cyclic AMP inhibits TGFβ1‐induced cell‐scattering and invasiveness in murine‐transformed keratinocytes
Authors: Santibáñez Juan F. , Olivares Daniela , Guerrero Javier , Martínez Jorge 
Published: October 2003

AbstractMouse‐transformed keratinocytes cultured in the presence of transforming growth factor β1 (TGF‐β1) acquire an array of morphologic and functional properties that give rise to a migratory phenotype that expresses mesenchymal molecular markers. This cellular conversion involves activation of the Ras‐ERK pathway, enhancement of urokinase (uPA) and matrix metalloproteinase‐9 (MMP‐9) expression and induction of invasiveness. In our present work, we demonstrate that cAMP and forskolin are able to prevent the expression of these mesenchymal properties, probably due to blockade of the Ras‐ERK pathway. Our results also show that cAMP and forskolin are able to abolish the TGF‐β1‐induced reorganization of the actin cytoskeleton that is characteristic of the mesenchymal phenotype and also inhibits the disruption of the E‐cadherin cell to cell interactions. The latter responses seem to depend on the activity of protein kinase A, as demonstrated by the activation of the Ras‐ERK pathway by specific protein kinase A inhibitors. © 2003 Wiley‐Liss, Inc.
Freshly isolated bone marrow cells induce death of various carcinoma cell lines
Authors: Larmonier Nicolas , Ghiringhelli François , Larmonier Claire B. , Moutet Monique , Fromentin Annie , Baulot Emmanuel , Solary Eric , Bonnotte Bernard , Martin François 
Published: October 2003

AbstractIn some carcinomas such as digestive tract carcinomas, bone marrow infiltration by tumor cells is a frequent event but usually remains a micrometastatic disease and rarely induces overt bone lesions. The mechanisms responsible for the control of these metastases in the bone marrow remain poorly known. We show that freshly isolated bone marrow cells from human, murine and rat origin rapidly kill a wide range of syngeneic or xenogeneic carcinoma cell lines in culture. Further analysis of this cytotoxic process in the rat indicated that neither resident bone marrow macrophages nor NK cells were responsible for this cytotoxic effect that was restricted to a subpopulation of bone marrow cells expressing CD90 (Thy‐1), a marker of hemopoietic precursors. The tumoricidal activity of these cells did not require long‐term culture nor addition of exogenous cytokines or growth factors. A subset of CD90+ cells that rapidly differentiates into CD163(ED2)‐expressing macrophages was observed to be responsible for tumor cell killing. These macrophages induced a non‐apoptotic death of tumor cells, a process that required both a direct interaction with the tumor cell and nitric oxide (NO) production through the activation of inducible nitric oxide‐synthase (iNOS). This ability of pluripotent hemopoietic stem cells to rapidly differentiate into macrophages capable of killing invasive tumor cells may account for the limited expansion of micrometastases of some carcinomas in the bone marrow. © 2003 Wiley‐Liss, Inc.
Clinical value of p53, c‐erbB‐2, CEA and CA125 regarding relapse, metastasis and death in resectable non‐small cell lung cancer
Authors: Pollán Marina , Varela Gonzalo , Torres Antonio , de la Torre Mercedes , Ludeña M Dolores , Ortega M Dolores , Pac Joaquín , Freixenet Jorge , Gómez Guillermo , Sebastián Fernando , Díez Manuel , Arrabal Ricardo , Canalís Emili , García‐Tirado Javier , Arnedillo Aurelio , Rivas Juan José , Minguella Joan , Gómez Ana , García Mauricio , Aragonés Nuria , Pérez‐Gómez Beatriz , López‐Abente Gonzalo , González‐Sarmiento Rogelio , Rojas Jose María 
Published: October 2003

AbstractThe prognostic value of p53 and c‐erbB‐2 immunostaining and preoperative serum levels of CEA and CA125 was investigated in a prospective multicentric study including 465 consecutive non‐small cell lung cancer (NSCLC) patients with resectable tumors. Four end‐points were used: lung cancer death, first relapse (either locoregional or metastasis), loco‐regional recurrence and metastasis development. Standard statistical survival methods (Kaplan‐Meier and Cox regression) were used. The specificity of the prognostic effect across different types of tumors was also explored, as had been planned in advance. Our results showed, once again, that pathological T and N classifications continue to be the strongest predictors regarding either relapse or mortality. Three of the studied markers seemed to add further useful information, however, but in a more specific context. For example, increased CEA concentration defined a higher risk population among adenocarcinomas but not among people with squamous tumors; and p53 overexpression implied a worse prognosis mainly in patients with well differentiated tumors. The analysis of type of relapse proved to be very informative. Thus, CA125 level was associated with a worse prognosis mainly related with metastasis development. Another interesting result was the influence of smoking, which showed a clear dose‐response relationship with the probability of metastasis. For future studies, we recommend the inclusion of different endpoints, namely considering the relationship of markers with the type of relapse involved in lung‐cancer recurrence. They can add useful information regarding the complex nature of prognosis. © 2003 Wiley‐Liss, Inc.