bluuebunny/crossref_metadata_2025_split huggingface dataset:
Platelet-Derived Growth Factor–Induced p42/44 Mitogen-Activated Protein Kinase Activation and Cellular Growth Is Mediated by Reactive Oxygen Species in the Absence of TSC2/Tuberin
Authors: Finlay Geraldine A. , Thannickal Victor J. , Fanburg Barry L. , Kwiatkowski David J. 
Published: December 2005

Abstract
Tuberous sclerosis complex (TSC) is a genetic disorder caused by inactivating mutations in the TSC1 or TSC2 genes, which encode hamartin and tuberin, respectively. TSC is characterized by multiple tumors of the brain, kidney, heart, and skin. Tuberin and hamartin inhibit signaling by the mammalian target of rapamycin (mTOR) but there are limited studies of their involvement in other pathways controlling cell growth. Using ELT-3 cells, which are Eker rat–derived smooth muscle cells, we show that ELT-3 cells expressing tuberin (TSC2+/+) respond to platelet-derived growth factor (PDGF) stimulation by activating the classic mitogen-activated protein (MAP)/extracellular signal-regulated kinase kinase (MEK)-1–dependent phosphorylation of p42/44 MAP kinase (MAPK) with nuclear translocation of phosphorylated p42/44 MAPK. In contrast, in tuberin-deficient ELT-3 cells (TSC2−/−), PDGF stimulation results in MEK-1–independent p42/44 MAPK phosphorylation with reduced nuclear localization of phosphorylated p42/44 MAPK. Moreover, in TSC2−/− cells but not in TSC2+/+ cells, cellular growth and activation of p42/44 MAPK by PDGF requires the reactive oxygen species intermediate, superoxide anion (O2·−). Both baseline and PDGF-induced O2·− levels were significantly higher in TSC2−/− cells and were reduced by treatment with rapamycin and inhibitors of mitochondrial electron transport. Furthermore, the exogenous production of O2·− by the redox cycling compound menadione induced MEK-1–independent cellular growth and p42/44 MAPK phosphorylation in TSC2−/− cells but not in TSC2+/+ cells. Together, our data suggest that loss of tuberin, which causes mTOR activation, leads to a novel cellular growth-promoting pathway involving mitochondrial oxidant–dependent p42/44 MAPK activation and mitogenic growth responses to PDGF.
Identification and Characterization ofSurvival-Related Gene, a Novel Cell Survival Gene Controlling Apoptosis and Tumorigenesis
Authors: Yuan Zeng-Rong , Wang Ruoxiang , Solomon Jennifer , Luo Xunyi , Sun Hong , Zhang Liying , Shi Yufang 
Published: December 2005

AbstractApoptosis plays a critical role in cellular homeostasis during development, immune responses, and tumorigenesis. Recent studies have identified a number of genes that control this process. We report here our identification of a novel cell survival-related gene (SRG) from a human expression cDNA library by functional cloning. SRG shows no significant nucleotide sequence homology to any known genes in the Genbank. Our fluorescence in situ hybridization analysis has estimated that SRG is located at 1p36, agreeing with the location at 1p36.22 in the human genome sequence. SRG encodes a putative protein of 172 amino acids, which is mainly located in the perinuclear region. Northern blotting analysis indicates that SRG is highly expressed in many human cancer cell lines although it is low in most tissues except liver and placenta. To investigate the function of SRG in apoptosis, we transfected SRG cDNA into BAF/BO3 and B16/F0 cells and induced apoptosis by cytokine/serum deprivation. We found that SRG-transfected cells are resistant to apoptosis induced by cytokine/serum deprivation. In addition, mice bearing SRG-transfected melanoma had more tumor formation and larger tumor growth. Melanoma transfected with antisense SRG showed significantly less tumor formation and smaller tumor growth. Interestingly, mouse SRG gene was also identified on chromosome 4 and blocking SRG expression with small interfering RNA promoted serum deprivation–induced apoptosis of NIH3T3 cells. Our results show that SRG is a novel cell survival gene that critically controls apoptosis and tumor formation.
Lack of Poly(ADP-Ribose) Polymerase-1 Gene Product Enhances Cellular Sensitivity to Arsenite
Authors: Poonepalli Anuradha , Balakrishnan Lakshmidevi , Khaw Aik Kia , Low Grace Kah Mun , Jayapal Manikandan , Bhattacharjee Rabindra N. , Akira Shizuo , Balajee Adayabalam S. , Hande M. Prakash 
Published: December 2005

Abstract
Arsenite (As3+) has long been known to induce cancer and other degenerative diseases. Arsenite exerts its toxicity in part by generating reactive oxygen species. Identification of genetic factors that contribute to arsenic mutagenicity and carcinogenicity is critical for the treatment and prevention of arsenic exposure in human population. As poly(ADP-ribose) polymerase (PARP) is critical for genomic DNA stability, role of PARP-1 was evaluated in arsenic-induced cytotoxic and genotoxic effects. Our study revealed that telomere attrition, probably owing to arsenite-induced oxidative stress, was much more pronounced in PARP-1−/− mouse embryonic fibroblasts (MEF; 40%) compared with PARP-1+/+ MEFs (10-20%). Correlation observed between telomere reduction and apoptotic death in PARP-1 null cells strongly indicates that the telomere attrition might be a trigger for enhanced apoptotic death after arsenite treatment. Elevated DNA damage detected by alkaline comet assay points to an impaired repair ability of arsenite-induced DNA lesions in PARP-1−/− MEFs. Consistent with elevated DNA damage, increased micronuclei induction reflecting gross genomic instability was also observed in arsenite-treated PARP-1−/− MEFs. Microarray analysis has revealed that arsenite treatment altered the expression of about 311 genes majority of which have known functions in cellular responses to stress/external stimulus and cell growth and/or maintenance. Our results suggest an important role for PARP-1 gene product in the maintenance of chromosome-genome stability in response to arsenite-induced DNA damage.
Triple Gene-Deleted Oncolytic Herpes Simplex Virus Vector Double-Armed with Interleukin 18 and Soluble B7-1 Constructed by Bacterial Artificial Chromosome–Mediated System
Authors: Fukuhara Hiroshi , Ino Yasushi , Kuroda Toshihiko , Martuza Robert L. , Todo Tomoki 
Published: December 2005

Abstract
Conditionally replicating herpes simplex virus type 1 (HSV-1) vectors are promising therapeutic agents for cancer. Certain antitumor functions may be added to oncolytic activities of recombinant HSV-1 vectors by inserting transgenes into the viral genome. Because conventional homologous recombination techniques had required time-consuming processes to create “armed” oncolytic HSV-1 vectors, we established an innovative construction system using bacterial artificial chromosome and two recombinase systems (Cre/loxP and FLPe/FRT). Using G47Δ, a safe and efficacious oncolytic HSV-1 with triple gene mutations, as the backbone, this system allowed a rapid generation of multiple vectors with desired transgenes inserted in the deleted ICP6 locus. Four oncolytic HSV-1 vectors, expressing murine interleukin 18 (mIL-18), soluble murine B7-1 [B7-1-immunoglobulin (B7-1-Ig)], both, or none, were created simultaneously within 3 months. In vitro, all newly created recombinant vectors exhibited virus yields and cytopathic effects similar to the parental G47Δ. In two immunocompetent mouse tumor models, TRAMP-C2 prostate cancer and Neuro2a neuroblastoma, the vector expressing both mIL-18 and B7-1-Ig showed a significant enhancement of antitumor efficacy via T-cell–mediated immune responses. The results show that “arming” with multiple transgenes can improve the efficacy of oncolytic HSV-1 vectors. The use of our system may facilitate the development and testing of various armed oncolytic HSV-1 vectors.
Activated B-RAF Is an Hsp90 Client Protein That Is Targeted by the Anticancer Drug 17-Allylamino-17-Demethoxygeldanamycin
Authors: da Rocha Dias Silvy , Friedlos Frank , Light Yvonne , Springer Caroline , Workman Paul , Marais Richard 
Published: December 2005

Abstract
Hsp90 is a ubiquitously expressed molecular chaperone that folds, stabilizes, and functionally regulates many cellular proteins. The benzoquinone ansamysin 17-allylamino-17-demethoxygeldanamycin (17-AAG) is an anticancer drug that disrupts Hsp90 binding to its clients, causing their degradation through the ubiquitin-dependent proteasomal pathway. The protein kinase B-RAF is mutated in ∼7% of human cancers. The most common mutation (∼90%) is V600EB-RAF, which has constitutively elevated kinase activity, stimulates cancer cell proliferation, and promotes survival. Here, we show that V600EB-RAF is an Hsp90 client protein that requires Hsp90 for its folding and stability. V600EBRAF is more sensitive to degradation by 17-AAG treatment than WTB-RAF and we show that the majority of the other mutant forms of B-RAF are also sensitive to 17-AAG–mediated proteasomal degradation. Our data show that B-RAF is an important target for 17-AAG in human cancer.
β4 Integrin Is a Transforming Molecule that Unleashes Met Tyrosine Kinase Tumorigenesis
Authors: Bertotti Andrea , Comoglio Paolo M. , Trusolino Livio 
Published: December 2005

Abstract
Cell multiplication in the absence of integrin-derived adhesive signals (anchorage-independent growth) is the phenotypic hallmark of neoplastic transformation. Therefore, the frequently observed up-regulation of some integrins in tumors has been interpreted as an epiphenomenon and not as a causative factor of oncogenic conversion. β4 integrin stimulates proliferation and survival of epithelial cells and is overexpressed in human carcinomas, often in concomitance with up-regulation of the Met tyrosine kinase receptor for hepatocyte growth factor. Met is not endowed with transforming ability but can exploit the β4 cytoplasmic tail as a substrate/adaptor for amplification of mitogenic and antiapoptotic responses, independently of cell adhesion. Here, we show that overexpression of β4 is sufficient to transform rodent fibroblasts, enhances anchorage-independent growth of breast carcinoma cells, and induces tumorigenesis in nude mice; conversely, RNA interference–mediated depletion abrogates the transformed phenotype of neoplastic cells. These autonomous oncogenic properties are dramatically exacerbated upon Met coexpression, suggesting that the integrin can instigate the latent tumorigenic potential of the kinase. A β4 nonadhesive variant still cooperates with Met for cellular transformation, confirming the adhesion-independent function of β4 in magnification of Met biological effects. Conversely, a β4 signaling-incompetent mutant that cannot be efficiently tyrosine phosphorylated by Met and displays reduced ability to activate phosphatidylinositol 3-kinase–dependent and Ras-dependent pathways aborts transformation. Our findings define β4 as a signaling accomplice (a “servo-oncogene”) of tyrosine kinase proto-oncogenes in primary carcinogenesis, evoke an unorthodox function for a prototypic adhesion molecule in the positive regulation of anchorage-independent growth, and suggest the use of β4 as a target for anticancer therapy.
Psychosocial Dynamics of the US Catholic Church Sexual Abuse Crisis
Authors: Barber William H. 
Published: December 2005

Background: This paper presents open systems analysis of the organizational dynamics of the US Catholic Church sexual abuse crisis. Most of the current literature on the crisis assigns culpability to various parties involved – in most cases to bishops and Church officials in Rome. This analysis offers a way of understanding events that goes beyond assigning culpability on the part of Church leaders. Material and Discussion: As an open system, a church is a system of interdependent, purposive activities, one that survives and develops through interchanges with its environment including the society of which it is a part. Key elements in this discussion include the dynamics that result from the idiosyncratic church structures and processes, and the apparent preoccupation with sexual matters, all of which are imbedded in a religious belief system and a high dependency culture. Conclusions: The picture is of a church experiencing the catastrophe of thousands of cases accusing priests of sexual abuse of young people, of an institution that has lost its capacity for openness as it is overwhelmed by the heapedon needs of members from a flood of constituencies. Key elements in this discussion include the description of the Church as an open system, the notions of primary task, sentient group life, a high dependency culture and the unconscious motivation operating in individuals, groups and the total Church enterprise.
Outcome following emergency surgery for refractory severe ulcerative colitis in a tertiary care centre in India
Authors: Pal Sujoy , Sahni Peush , Pande Girish K , Acharya Subrat K , Chattopadhyay Tushar K 
Published: December 2005

Abstract

Background
Steroid-based intensive medical therapy for severe ulcerative colitis is successful in 60–70% of such patients. Patients with complications or those refractory to medical therapy require emergency colectomy for salvage. Little is known about the impact of timing of surgical intervention and surgical outcomes of such patients undergoing emergency surgery in India where the diagnosis is often delayed or missed in patients who are poor, malnourished and non-compliant to medical treatment.

Methods
The clinical records of all patients undergoing emergency surgery for severe ulcerative colitis or its complication in the Department of GI surgery AIIMS, New Delhi, India, between January 1985 and December 2003 were retrieved and data pertaining to demographic features, duration of intensive medical therapy, presence of complications, time from admission to emergency surgery, surgical procedure, in-hospital morbidity and mortality and follow up status extracted.

Results
A total of 72 patients underwent emergency surgery (Subtotal colectomy: 60; ileostomy alone under local anaesthesia: 12). Poor nutritional status was seen in 61% of the patients.
Twenty-one patients (29%) underwent emergency surgery for complications of severe ulcerative colitis such as colonic perforation (spontaneous 6, iatrogenic 4), massive lower gastrointestinal haemorrhage (5), toxic megacolon (4) and large bowel obstruction (2). The remaining patients (n = 51) underwent emergency surgery following failed intensive therapy; 17 underwent surgery ≤5 days (Group I) and 34 were operated >5 days (Group II) after initiation of intensive therapy. In this group all the post-operative deaths (n = 8) occurred in those who were operated after 5 days. The difference in mortality in these two groups (i.e. surgical intervention ≤ or >5 days) was statistically significant {0/17 (Group I) vs 8/34 (Group II); p = 0.03}.
Overall, 12 patients died (in-hospital mortality: 16.7%). The mortality was higher (10/43; 23.3%) in our early experience (i.e. 1985–1995) when compared to our subsequent experience (2/29; 6.9%) (1996–2003).
A total of 48 patients (including 3 awaiting a restorative procedure) are alive on follow up (66.7%; 3 patients lost to follow up). A restorative procedure could be successfully completed in 81% of the survivors of the emergency procedure.

Conclusion
To optimize the outcome, a combined team of physicians and surgeons should be involved in the management of patients with severe ulcerative colitis with focus on nutritional support, correction of metabolic derangements, close clinical monitoring and timely assessment for the need for emergency surgery. This retrospective analysis shows that improved results can be achieved with experience and by following a policy of early surgical intervention within 5 days, especially in patients who have failed intensive medical therapy.
On the genetic involvement of apoptosis-related genes in Crohn's disease as revealed by an extended association screen using 245 markers: no evidence for new predisposing factors
Authors: Wagenleiter Sonja EN , Jagiello Peter , Akkad Denis A , Arning Larissa , Griga Thomas , Klein Wolfram , Epplen Jörg T 
Published: December 2005

AbstractCrohn's disease (CD) presents as an inflammatory barrier disease with characteristic destructive processes in the intestinal wall. Although the pathomechanisms of CD are still not exactly understood, there is evidence that, in addition toe.g. bacterial colonisation, genetic predisposition contributes to the development of CD. In order to search for predisposing genetic factors we scrutinised 245 microsatellite markers in a population-based linkage mapping study. These microsatellites cover gene loci the encoded protein of which take part in the regulation of apoptosis and (innate) immune processes. Respective loci contribute to the activation/suppression of apoptosis, are involved in signal transduction and cell cycle regulators or they belong to the tumor necrosis factor superfamily, caspase related genes or the BCL2 family. Furthermore, several cytokines as well as chemokines were included. The approach is based on three steps: analyzing pooled DNAs of patients and controls, verification of significantly differing microsatellite markers by genotyping individual DNA samples and, finally, additional reinvestigation of the respective gene in the region covered by the associated microsatellite by analysing single-nucleotide polymorphisms (SNPs). Using this step-wise process we were unable to demonstrate evidence for genetic predisposition of the chosen apoptosis- and immunity-related genes with respect to susceptibility for CD.
Hypoxia silences the neural activities in the early phase of the phrenic neurogram of eupnea in the piglet
Authors: Akay Metin 
Published: December 2005

AbstractObjectiveWe investigated phrenic neurogram patterns during eupnea (normal breathing) and severe hypoxia (gasping) during early maturation in the piglet.MethodsWe used continuous wavelet transform and short time Fourier transform methods to examine the similarity of breathing patterns in both time and frequency domains during early maturation. The phrenic neurogram was recorded during eupnea, severe hypoxia, and recovery from severe hypoxia in piglets in three different age groups: 3–6 days, 10–15 days and 29–35 days.ResultsDuring the first week of postnatal age, respiratory patterns of phrenic activity were marked by frequency components between 30 and 300 Hz during both the early (first half) and late (second half) phases of the neurogram signals during eupnea. The results suggest that there is little difference between the respiratory patterns in both time and frequency domains during eupnea compared to gasping for the first week of postnatal age in piglets. After the first week of postnatal age, the duration of the phrenic neurogram burst significantly increases and the patterns during the early phase of the phrenic neurogram are different from those observed for gasping. However, the patterns that mark the late phase of the phrenic neurograms are still the same as those of gasping.ConclusionOur most significant finding is that hypoxia silences the neural activity in the early phase of phrenic neurogram regardless of maturation.
Adolescent idiopathic scoliosis screening for school, community, and clinical health promotion practice utilizing the PRECEDE-PROCEED model
Authors: Mirtz Timothy A , Thompson Mark A , Greene Leon , Wyatt Lawrence A , Akagi Cynthia G 
Published: December 2005

AbstractBackgroundScreening for adolescent idiopathic scoliosis (AIS) is a commonly performed procedure for school children during the high risk years. The PRECEDE-PROCEDE (PP) model is a health promotion planning model that has not been utilized for the clinical diagnosis of AIS. The purpose of this research is to study AIS in the school age population using the PP model and its relevance for community, school, and clinical health promotion.MethodsMEDLINE was utilized to locate AIS data. Studies were screened for relevance and applicability under the auspices of the PP model. Where data was unavailable, expert opinion was utilized based on consensus.ResultsThe social assessment of quality of life is limited with few studies approaching the long-term effects of AIS. Epidemiologically, AIS is the most common form of scoliosis and leading orthopedic problem in children. Behavioral/environmental studies focus on discovering etiologic relationships yet this data is confounded because AIS is not a behavioral. Illness and parenting health behaviors can be appreciated. The educational diagnosis is confounded because AIS is an orthopedic disorder and not behavioral. The administration/policy diagnosis is hindered in that scoliosis screening programs are not considered cost-effective. Policies are determined in some schools because 26 states mandate school scoliosis screening. There exists potential error with the Adam's test. The most widely used measure in the PP model, the Health Belief Model, has not been utilized in any AIS research.ConclusionThe PP model is a useful tool for a comprehensive study of a particular health concern. This research showed where gaps in AIS research exist suggesting that there may be problems to the implementation of school screening. Until research disparities are filled, implementation of AIS screening by school, community, and clinical health promotion will be compromised. Lack of data and perceived importance by school/community health planners may influence clinical health promotion practices.
A retrospective study of mushroom poisoning in Iran
Authors: Pajoumand A , Shadnia S , Efricheh H , Mandegary A , Hassanian-Moghadam H , Abdollahi M 
Published: November 2005

The objective of this study was to describe the pattern of mushroom poisoning in adults admitted to the Loghman Hakim Hospital Poison Center from 1992 to 2002. All patients ≥ 12 years of age were included in the study. The frequency of mushroom poisoning with respect to age, sex, season, reason, place of residence, latent phase, clinical and laboratory findings, treatment, and outcome of patients was investigated. Of the 72 421 poisoning cases admitted to Loghman-Hakim Hospital Poison Center from 1992 to 2002, only 37 were poisoned by consumption of toxic mushrooms. As some of the patients' files were incomplete, only 25 files were included in the study. Of this number, 68% were male. The patients' age ranged between 12 and 65 years, with a mean of 31 years of age. All cases were accidental and mostly from Tehran (36%) and the northern provinces (rainy woodlands) of Iran (32%). Autumn was the most common season for poisoning with a frequency of 80%. The latent phase of poisonings was between 0.5 and 12 hours. The most frequently reported symptoms were vomiting (84%), nausea (60%), abdominal pain (60%) and diarrhea (40%). Jaundice was observed in 44% of cases, with a 50% rate of hepatic encephalopathy. A total of 66% of patients were discharged and the duration range of hospitalization was 1-12 days. In conclusion, people should be more informed of the dangers posed by wild mushrooms. Training of physicians and nurses in the accurate diagnosis and management of patients poisoned with poisonous mushrooms would improve the rate of survival.
Processes of Similarity Judgment
Authors: Larkey Levi B. , Markman Arthur B. 
Published: December 2005

AbstractSimilarity underlies fundamental cognitive capabilities such as memory, categorization, decision making, problem solving, and reasoning. Although recent approaches to similarity appreciate the structure of mental representations, they differ in the processes posited to operate over these representations. We present an experiment that differentiates among extant structural accounts of similarity in their ability to account for patterns of similarity ratings. These data pose a challenge for transformation‐based models and all but one mapping‐based model, the Similarity as Interactive Activation and Mapping (SIAM) model of similarity.