bluuebunny/crossref_metadata_2025_split huggingface dataset:
The San Salvador Earthquake of October 10, 1986—Processed Strong Motion Data
Authors: Shakal Anthony F. , Huang Moh-jiann , Linares Roberto 
Published: July 2003

Strong-motion records were recovered from nine accelerographs at seven stations of the El Salvador Geotechnical Investigation Center Strong Motion Network following the damaging 5.4 Ms San Salvador earthquake of October 10, 1986. The sites were all within 6 km of the epicenter; peak horizontal accelerations at ground level ranged from 0.32 to 0.72 g. The duration of strong shaking was about 3 seconds at most sites. One 10-story concrete building was instrumented with recorders at the basement, second floor, and roof level. The maximum accelerations recorded at this building were 0.47 g at the basement, 0.69 g at the second floor, and 0.91 g at the roof. Eight of the accelerograms were digitized and processed. A maximum horizontal velocity of 80 cm/s was obtained for a station 4 km from the epicenter. Peak velocity for the other stations ranged from 26 to 75 cm/s. The maximum horizontal displacements ranged from 5 to 18 cm. The San Salvador records and spectra are compared to other close-in observations such as the Station 2 record from the ML 5.6 Parkfield earthquake of 1966. The San Salvador records share many features with the Parkfield record. In general, the peak accelerations recorded at many of the stations are larger than previously recorded values at close-in distances from earthquakes of similar magnitude.
The Whittier Narrows, California Earthquake of October 1, 1987—CSMIP Strong Motion Data
Authors: Shakal A. , Huang M. J. , Cao T. Q. 
Published: July 2003

The Whittier Narrows earthquake of October 1, 1987 generated the largest set of strong-motion records ever obtained from a single earthquake. The California Strong Motion Instrumentation Program (CSMIP) recovered 128 strong-motion records from 101 stations. Of these 101 stations, 63 are ground-response stations and 38 are extensively-instrumented structures. The structures include 27 buildings, eight dams, a suspension bridge, an airport tower, and a power plant. This paper summarizes that data set and highlights records of particular interest. The duration of strong shaking was approximately 3 to 4 seconds at most stations. The maximum peak acceleration values in the CSMIP data set are 0.62 g on the ground and 0.54 g in a structure. The largest acceleration (0.62 g) was recorded at a station near Tarzana, approximately 45 km from the epicenter. Other records of particular interest discussed here include the record from a soft-story building on the Los Angeles State University campus and the records from the Vincent Thomas suspension bridge near Long Beach. Digitization and processing of the accelerograms are underway, and accelerograms from 12 ground-response stations have been digitized as of this writing. The spectra show that the motion at the Tarzana station was dominated by 3 Hz energy. Spectra from other sites are relatively flat and do not show this spectral peak. The attenuation of peak acceleration with distance for this earthquake is compared with the relationship of Joyner and Boore (1981) derived from past earthquakes. On average, the peak acceleration data from this earthquake are higher than would be predicted by the Joyner-Boore model.
Dynamic Expression Profile of p21WAF1/CIP1 and Ki-67 Predicts Survival in Rectal Carcinoma Treated With Preoperative Radiochemotherapy
Authors: Rau Beate , Sturm Isrid , Lage Hermann , Berger Stefan , Schneider Ulrike , Hauptmann Steffen , Wust Peter , Riess Hanno , Schlag Peter M. , Dörken Bernd , Daniel Peter T. 
Published: July 2003

Purpose: We investigated p53 and its downstream effectors p21WAF1/CIP1, BAX, and hMSH2 as well as the proliferation marker Ki-67 (mki-67/MIB-1) in patients undergoing preoperative radiochemotherapy for rectal carcinoma to identify prognostic and predictive factors. The focus of this study was on the dynamics of these genetic markers in a longitudinal study—that is, before and after radiochemotherapy. Patients and Methods: Expression of p53, BAX, p21WAF1/CIP1, Ki-67, and hMSH2 was investigated by immunohistochemistry in pre- and posttherapeutic tumor samples in 66 patients. Tumor DNA was screened for p53 mutations by single-strand conformation polymorphism–polymerase chain reaction (SSCP-PCR). Paired tumor samples (pretherapy and posttherapy) were collected prospectively. Results: Patients with a decrease in p21 expression following radiochemotherapy had better disease-free survival (P = .03). Similarly, patients with an increase in proliferative activity as measured by increased Ki-67 expression posttherapy had better disease-free survival (P < .005). In addition, we observed a significantly better prognosis for patients with high hMSH2 expression. In contrast, pretherapeutic levels of p53, BAX, or p21 expression and p53 mutation had no prognostic value, indicating that the combination of radiotherapy and chemotherapy might override defects in these genes. Conclusion: These findings are novel and support the clinical relevance of p21 in the suppression of both proliferation and apoptosis. Thus, the dynamic induction of p21WAF1/CIP1 was associated with a lower proliferative activity but an ultimately worse treatment outcome following neoadjuvant radiochemotherapy and tumor resection. Induction of p21, therefore, represents a novel resistance mechanism in rectal cancer undergoing preoperative radiochemotherapy.
Long-Term Cause-Specific Mortality of Patients Treated for Hodgkin’s Disease
Authors: Aleman Berthe M.P. , van den Belt-Dusebout Alexandra W. , Klokman Willem J. , van’t Veer Mars B. , Bartelink Harry , van Leeuwen Flora E. 
Published: July 2003

Purpose: To assess long-term cause-specific mortality of young Hodgkin’s disease (HD) patients. Patients and Methods: The study population consisted of 1,261 patients treated for HD before age 41 between 1965 and 1987. Follow-up was complete until October 2000. For 95% of deaths, the cause was known. Long-term cause-specific mortality was compared with general population rates to assess relative risk (RR) and absolute excess risk (AER) of death. Results: After a median follow-up of 17.8 years, 534 patients had died (55% of HD). The RR of death from all causes other than HD was 6.8 times that of the general population, and still amounted to 5.1 after more than 30 years. RRs of death resulting from solid tumors (STs) and cardiovascular disease (CVD) were increased overall (RR = 6.6 and 6.3, respectively), but especially in patients treated before age 21 (RR = 14.8 and 13.6, respectively). When these patients grew older, this elevated mortality decreased. The overall AER of death from causes other than HD increased throughout follow-up. Patients receiving salvage chemotherapy had a significantly increased RR of death from STs, compared to patients receiving initial therapy only. Conclusion: The main cause of death among HD patients was lymphoma, but after 20 years, HD mortality was negligible. The RRs and AERs of death from second primary cancers (SCs) and CVDs continued to increase after 10 years. Even more than 30 years after diagnosis, HD patients experienced elevated risk of death from all causes other than HD. Increased risk of death from SCs and CVDs was found especially in patients treated before age 21, but these risks seemed to abate with age.
Increased Age at Diagnosis Has a Significantly Negative Effect on Outcome in Children With Down Syndrome and Acute Myeloid Leukemia: A Report From the Children’s Cancer Group Study 2891
Authors: Gamis Alan S. , Woods William G. , Alonzo Todd A. , Buxton Allen , Lange Beverly , Barnard Dorothy R. , Gold Stuart , Smith Franklin O. 
Published: July 2003

Purpose: To determine the outcome of children with Down syndrome (DS) and acute myeloid leukemia (AML) receiving standard timing chemotherapy without bone marrow transplantation (BMT), with determination of prognostic factors. Patients and Methods: Children with DS and newly diagnosed AML or myelodysplasia were prospectively enrolled on Children’s Cancer Group study 2891 (N = 161) and treated uniformly with four standard timing induction courses of dexamethasone, cytarabine arabinoside, 6-thioguanine, etoposide, daunorubicin (DCTER) followed by intensively timed high-dose cytarabine. Results: Children with DS were significantly younger at diagnosis than those without (median age, 1.8 v 7.5 years, respectively; P < .001), with more megakaryocytic leukemia (70% v 6%; P < .001). Higher complete remission rates (91%) were achieved in children with DS than among those without DS (75%; P < .001). Equivalent grade 3 to 4 toxicity (29% v 30%; P = .84) was seen, though children with DS had greater pulmonary toxicity (P < .01) during induction and mucositis during intensification (P = .12). Children with DS had significantly better 8-year event-free survival (EFS; 77% v 21% standard and 40% intensive induction; P < .0001). Multivariate analysis in children with DS revealed that only age at diagnosis of 2 years or older was a risk factor for greater relapse risk (odds ratio, 4.9; P = .006) and worse survival. Children between ages 0 to 2 years (n = 94) had a 6-year EFS of 86%; those from 2 to 4 years (n = 58), 70%; and those older than 4 years (n = 9), 28%. Remission failures were the primary reason for worse 6-year EFSs (1% in those 0 to 2 years v 14% if >2 years; P = .002). Conclusion: Outcome for children with DS and AML is excellent with standard induction therapy, but declines with increasing age.
Randomized Phase II Comparison of Dose-Intense Gemcitabine: Thirty-Minute Infusion and Fixed Dose Rate Infusion in Patients With Pancreatic Adenocarcinoma
Authors: Tempero Margaret , Plunkett William , Ruiz van Haperen Veronique , Hainsworth John , Hochster Howard , Lenzi Renato , Abbruzzese James 
Published: July 2003

Purpose: To conduct a randomized phase II trial of dose-intense gemcitabine using a standard 30-minute infusion or the fixed dose rate (FDR) infusion (10 mg/m2/min) in patients with pancreatic adenocarcinoma. Patients and Methods: In this prospective trial, patients with locally advanced and metastatic pancreatic adenocarcinoma were treated with 2,200 mg/m2 gemcitabine over 30 minutes (standard arm) or 1,500 mg/m2 gemcitabine over 150 minutes (FDR arm) on days 1, 8, and 15 of every 4-week cycle. The primary end point of this trial was time to treatment failure. Secondary end points included time to progression, median survival, safety, and pharmacokinetic studies of gemcitabine. Results: Ninety-two patients were enrolled onto this study; 91% of the patients had metastatic disease. Time to treatment failure was comparable in both treatment groups; however, the median survival for all patients was 5.0 months in the standard arm and 8.0 months in the FDR arm (P = .013). For patients with metastases, the median survival was 4.9 months in the standard arm and 7.3 months in FDR arm (P = .094). The 1- and 2-year survival rates for all patients were 9% (standard arm) versus 28.8% (FDR; P = .014) and 2.2% (standard arm) versus 18.3% (FDR; P = .007), respectively. Patients in the FDR infusion arm experienced consistently more hematologic toxicity. Pharmacokinetic analyses demonstrated a two-fold increase in intracellular gemcitabine triphosphate concentration in the FDR arm (P = .046). Conclusion: Pharmacokinetic and clinical data in this trial supports the continued evaluation of the FDR infusion strategy with gemcitabine.
Neonatal Estrogen Down-Regulates Prostatic Androgen Receptor through a Proteosome-Mediated Protein Degradation Pathway
Authors: Woodham Carl , Birch Lynn , Prins Gail S. 
Published: July 2003

AbstractBrief exposure of male rats to estrogens during the neonatal period interrupts normal prostate development, alters epithelial cell differentiation, and predisposes this gland to hyperplasia and severe dysplasia analogous to prostatic intraepithelial neoplasia (PIN) with aging. Previous work demonstrated that the reduced growth, secretory activity, and androgen sensitivity that are observed in the adult ventral lobe are a function of reduced androgen receptor (AR) levels. Down-regulation of AR protein was found to occur immediately following neonatal exposure to estradiol benzoate (EB) and persist through adulthood and aging, indicating a permanent imprint on the ability of the prostate to express normal AR levels. To determine the intracellular mechanism of AR down-regulation by estrogens, the present study examined the effect of neonatal EB on AR gene transcription, mRNA levels, protein translation, and protein degradation in the d 10 ventral prostate glands. Nuclear run-on assays showed no alteration in AR gene transcription following exposure to EB on d 1–5 compared with controls. In situ hybridization and quantitative (q) RT-PCR revealed no difference in mRNA levels in the stromal or epithelial cells in response to estrogen exposure which, taken together, indicate that estrogen down-regulation of AR is mediated at the posttranscriptional level. AR translation was assessed with an in vitro transcription-translation assay in the presence of prostatic lysates from oil and estrogen-exposed animals, and no treatment effect was noted. AR degradation was examined in an in vitro assay validated with adult intact and castrate prostates. Prostatic lysates from intact rats initiated AR degradation with a t1/2 of 2.31 h, whereas proteins from castrate rats accelerated AR degradation to a t1/2 of 1.34 h (P &lt; 0.001). Prostatic lysates from control d 10 prostates induced AR degradation with a t1/2 of 1.49 h, whereas estrogenized prostates increased AR degradation to a t1/2 of 1.11 h (P &lt; 0.001). Proteosome inhibitors MG132 and ALLnL were able to reverse AR degradation induced by prostatic lysates from adult intact and castrate rats as well as from developing and estrogenized prostates, indicating that AR degradation was mediated through the proteosome pathway. Furthermore, the proteosome-mediated AR degradation in the estrogenized d 10 prostate was associated with a marked suppression of Akt phosphorylation that has been linked to AR degradation in other systems. Taken together, the present data show that exposure to neonatal estrogens down-regulates AR protein levels in the ventral prostate gland by accelerating AR degradation, which is mediated through the proteosome pathway.
Hypothalamic Melanin-Concentrating Hormone Is Induced by Cold Exposure and Participates in the Control of Energy Expenditure in Rats
Authors: Pereira-da-Silva Márcio , Torsoni Márcio A. , Nourani Hugo V. , Augusto Viviane D. , Souza Cláudio T. , Gasparetti Alessandra L. , Carvalheira José B. , Ventrucci Gislaine , Marcondes Maria Cristina C. G. , Cruz-Neto Ariovaldo P. , Saad Mário J. A. , Boschero Antonio C. , Carneiro Everardo M. , Velloso Lício A. 
Published: July 2003

Abstract
Short-term cold exposure of homeothermic animals leads to higher thermogenesis and food consumption accompanied by weight loss. An analysis of cDNA-macroarray was employed to identify candidate mRNA species that encode proteins involved in thermogenic adaptation to cold. A cDNA-macroarray analysis, confirmed by RT-PCR, immunoblot, and RIA, revealed that the hypothalamic expression of melanin-concentrating hormone (MCH) is enhanced by exposure of rats to cold environment. The blockade of hypothalamic MCH expression by antisense MCH oligonucleotide in cold-exposed rats promoted no changes in feeding behavior and body temperature. However, MCH blockade led to a significant drop in body weight, which was accompanied by decreased liver glycogen, increased relative body fat, increased absolute and relative interscapular brown adipose tissue mass, increased uncoupling protein 1 expression in brown adipose tissue, and increased consumption of lean body mass. Thus, increased hypothalamic MCH expression in rats exposed to cold may participate in the process that allows for efficient use of energy for heat production during thermogenic adaptation to cold.
Overexpressed Pituitary Tumor-Transforming Gene Causes Aneuploidy in Live Human Cells
Authors: Yu Run , Lu Wenge , Chen Jiandong , McCabe Chris J. , Melmed Shlomo 
Published: July 2003

Abstract
The mammalian securin, pituitary tumor-transforming gene (PTTG), is overexpressed in several tumors and transforms cells in vitro and in vivo. To test the hypothesis that PTTG overexpression causes aneuploidy, enhanced green fluorescent protein (EGFP)-tagged PTTG (PTTG-EGFP) was expressed in human H1299 cancer cells (with undetectable endogenous PTTG expression) and mitosis of individual live cells observed. Untransfected cells and cells expressing EGFP alone exhibited appropriate mitosis. PTTG-EGFP markedly prolonged prophase and metaphase, indicating that PTTG blocks progression of mitosis to anaphase. In cells that underwent apparently normal mitosis (35 of 65 cells), PTTG-EGFP was degraded about 1 min before anaphase onset. Cells that failed to degrade PTTG-EGFP exhibited asymmetrical cytokinesis without chromosome segregation (18 of 65 cells) or chromosome decondensation without cytokinesis (9 of 65 cells), resulting in appearance of a macronucleus. Fifty-one of 55 cells expressing a nondegradable mutant PTTG exhibited asymmetrical cytokinesis without chromosome segregation, and some (4 of 55) decondensed chromosomes, both resulting in macronuclear formation. During this abnormal cytokinesis, all chromosomes and spindles and both centrosomes moved to one daughter cell, suggesting potential chaos in the subsequent mitosis. In conclusion, failure of PTTG degradation or enhanced PTTG accumulation, as a consequence of overexpression, inhibits mitosis progression and chromosome segregation but does not directly affect cytokinesis, resulting in aneuploidy. These results demonstrate that PTTG induces aneuploidy in single, live, human cancer cells.
Parallel Phosphatidylinositol-3 Kinase and p42/44 Mitogen-Activated Protein Kinase Signaling Pathways Subserve the Mitogenic and Antiapoptotic Actions of Insulin-Like Growth Factor I in Osteoblastic Cells
Authors: Grey Andrew , Chen Qi , Xu Xin , Callon Karen , Cornish Jill 
Published: July 2003

AbstractIGF-I is an endocrine and paracrine regulator of skeletal homeostasis, principally by virtue of its anabolic effects on osteoblastic cells. In the current study, we examined the intracellular signaling pathways by which IGF-I promotes proliferation and survival in SaOS-2 human osteoblastic cells. Inhibition of each of the phosphatidylinositol-3 kinase (PI-3 kinase), p42/44 MAPK, and p70s6 kinase pathways partially inhibited the ability of IGF-I to stimulate osteoblast proliferation and survival. Because activation of p70s6 kinase is downstream of both PI-3 kinase and p42/44 MAPK activation in osteoblasts treated with IGF-I, this ribosomal kinase represents a convergence point for IGF-I-induced PI-3 kinase and p42/44 MAPK signaling in osteoblastic cells. In addition, abrogation of PI-3 kinase-dependent Akt signaling, which does not inhibit IGF-I-induced p70s6 kinase phosphorylation, also inhibited the antiapoptotic effects of IGF-I in osteoblasts. Finally, interruption of Gβγ signaling partially abrogated the ability of IGF-I to promote osteoblast survival, without inhibiting signaling through PI-3 kinase/Akt, p42/44 MAPKs, or p70s6 kinase. These data suggest that IGF-I signals osteoblast mitogenesis and survival through parallel, partly overlapping intracellular pathways involving PI-3 kinase, p42/44 MAPKs, and Gβγ subunits.
Na+/H+ Exchanger-Regulatory Factor 1 Mediates Inhibition of Phosphate Transport by Parathyroid Hormone and Second Messengers by Acting at Multiple Sites in Opossum Kidney Cells
Authors: Mahon Matthew J. , Cole Judith A. , Lederer Eleanor D. , Segre Gino V. 
Published: July 2003

Abstract
The opossum kidney (OK) line displays PTH-mediated activation of adenylyl cyclase and phospholipase C and inhibition of phosphate (Pi) uptake via regulation of the type IIa sodium-phosphate cotransporter, consistent with effects in vivo. OKH cells, a subclone of the OK cell line, robustly activates PTH-mediated activation of adenylyl cyclase, but is defective in PTH-mediated inhibition of sodium-phosphate cotransport and signaling via phospholipase C. Compared with wild-type OK cells, OKH cells express low levels of the Na+/H+ exchanger regulatory factor 1 (NHERF-1). Stable expression of NHERF-1 in OKH cells (OKH-N1) rescues the PTH-mediated inhibition of sodium-phosphate cotransport. NHERF-1 also restores the capacity of 8-bromo-cAMP and forskolin to inhibit Pi uptake, but the PTH dose-response for cAMP accumulation and inhibition of Pi uptake differ by 2 orders of magnitude. NHERF-1, in addition, modestly restores phorbol ester-mediated inhibition of Pi uptake, which is much weaker than that elicited by PTH. A poor correlation exists between the inhibition of Pi uptake mediated by PTH (∼60%) and the inhibition mediated by phorbol 12-myristate 13-acetate (∼30%) and the ability of these molecules to activate the protein kinase C-responsive reporter gene. Furthermore, we show that NHERF-1 directly interacts with type IIa cotransporter in OK cells. Although, PTH-mediated inhibition of Pi uptake in OK cells is largely NHERF-1 dependent, the signaling pathway(s) by which this occurs is still unclear. These pathways may involve cooperativity between cAMP- and protein kinase C-dependent pathways or activation/inhibition of an unrecognized NHERF-1-dependent pathway(s).
Sphingosine Kinase Transmits Estrogen Signaling in Human Breast Cancer Cells
Authors: Sukocheva Olga A. , Wang Lijun , Albanese Nathaniel , Pitson Stuart M. , Vadas Mathew A. , Xia Pu 
Published: July 2003

AbstractCurrent understanding of cytoplasmic signaling pathways that mediate estrogen action in human breast cancer is incomplete. Here we report that treatment with 17β-estradiol (E2) activates a novel signaling pathway via activation of sphingosine kinase (SphK) in MCF-7 breast cancer cells. We found that E2 has dual actions to stimulate SphK activity, i.e. a rapid and transient activation mediated by putative membrane G protein-coupled estrogen receptors (ER) and a delayed but prolonged activation relying on the transcriptional activity of ER. The E2-induced SphK activity consequently activates downstream signal cascades including intracellular Ca2+ mobilization and Erk1/2 activation. Enforced expression of human SphK type 1 gene in MCF-7 cells resulted in increases in SphK activity and cell growth. Moreover, the E2-dependent mitogenesis were highly promoted by SphK overexpression as determined by colony growth in soft agar and solid focus formation. In contrast, expression of SphKG82D, a dominant-negative mutant SphK, profoundly inhibited the E2-mediated Ca2+ mobilization, Erk1/2 activity and neoplastic cell growth. Thus, our data suggest that SphK activation is an important cytoplasmic signaling to transduce estrogen-dependent mitogenic and carcinogenic action in human breast cancer cells.