bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blockage of 2-Deoxy-d-Ribose-Induced Angiogenesis with Rapamycin Counteracts a Thymidine Phosphorylase-Based Escape Mechanism Available for Colon Cancer under 5-Fluorouracil Therapy
Authors: Seeliger Hendrik , Guba Markus , Koehl Gudrun E. , Doenecke Axel , Steinbauer Markus , Bruns Christiane J. , Wagner Christine , Frank Erika , Jauch Karl-Walter , Geissler Edward K. 
Published: September 2005

Abstract
Purpose: Colorectal neoplasms remain a leading cause of cancer-related deaths. A recognized weakness of conventional 5-fluorouracil (5-FU) therapy relates to expression of the intracellular enzyme, thymidine phosphorylase (TP). Although TP promotes 5-FU cytotoxicity, TP-derived 2-deoxy-d-ribose (dRib) counterproductively stimulates tumor angiogenesis. Here, the newly discovered antiangiogenic drug rapamycin was combined with 5-FU to counteract the potential escape mechanism of dRib-induced angiogenesis.
Experimental Design: Orthotopic tumor growth was assessed in rapamycin and 5-FU-treated BALB/c mice with TP-expressing CT-26 colon adenocarcinoma cells. To examine liver metastasis, green-fluorescent protein-transfected CT-26 cells were visualized by fluorescence microscopy after intraportal injection. Cell counting and Ki67 staining were used to determine in vitro and in vivo cell expansion, respectively. In vitro angiogenic effects of dRib were assessed with endothelial cell migration and aortic ring assays. Western blotting detected dRib effects on p70/S6 kinase activation.
Results: Rapamycin treatment of mice bearing orthotopic tumors inhibited tumor growth more than did 5-FU, and mice treated with both drugs typically developed no tumors. In the liver metastasis assay, combination therapy blocked metastatic expansion of solitary tumor cells. Interestingly, complex drug activities were suggested by tumor-cell proliferation being more sensitive to 5-FU than to rapamycin in vitro, but more sensitive to rapamycin in vivo. With regard to angiogenesis, dRib-induced endothelial cell migration and aortic ring formation were completely abrogated by rapamycin, correlating with blockage of dRib-induced p70/S6 kinase activation in endothelial cells.
Conclusions: Inhibition of dRib-induced angiogenesis with rapamycin counteracts a potential TP-based escape mechanism for colorectal cancer under 5-FU therapy, introducing a novel, clinically feasible, combination treatment option for this common neoplasm.
Inhibition of Src Tyrosine Kinase Impairs Inherent and Acquired Gemcitabine Resistance in Human Pancreatic Adenocarcinoma Cells
Authors: Duxbury Mark S. , Ito Hiromichi , Zinner Michael J. , Ashley Stanley W. , Whang Edward E. 
Published: September 2005

Abstract
Purpose: We tested the hypotheses that Src tyrosine kinase overactivity represents a chemoresistance mechanism and that Src inhibition may enhance gemcitabine cytotoxicity in pancreatic adenocarcinoma cells.
Experimental Design: Pancreatic adenocarcinoma cells PANC1, MiaPaCa2, Capan2, BxPC3, and PANC1GemRes, a stably gemcitabine-resistant subline of PANC1, were exposed to combinations of gemcitabine and Src tyrosine kinase inhibitor 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2). Src expression, phosphorylation (Tyr-416), and activity were analyzed by immunoblotting and in vitro kinase assay. Expression of the M2 subunit of ribonucleotide reductase (RRM2), a putative chemoresistance enzyme, was quantified by Northern and Western blot. Cellular proliferation was quantified by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptosis was characterized by YO-PRO-1/propidium iodide staining, fluorometric caspase profiling, and caspase inhibition (Z-Val-Ala-Asp-fluoromethyl ketone). The effects of constitutively active and dominant negative Src were determined. The therapeutic efficacy of PP2 in combination with gemcitabine was tested in nude mice orthotopically xenografted with PANC1GemRes.
Results: Greater gemcitabine resistance was associated with higher Src phosphorylation and activity, both of which were higher in PANC1GemRes, relative to PANC1; total Src levels were alike. PANC1GemRes overexpressed RRM2. PP2 enhanced inherent gemcitabine chemosensitivity and attenuated gemcitabine resistance in PANC1GemRes. Constitutively active Src increased gemcitabine chemoresistance; dominant negative Src impaired gemcitabine chemoresistance. PP2 augmented gemcitabine-induced caspase-mediated apoptosis, suppressed RRM2 expression, and decreased activity of the RRM2-regulating transcription factor E2F1 in PANC1GemRes. PP2 and gemcitabine in combination substantially decreased tumor growth and inhibited metastasis in vivo.
Conclusions: Increased Src tyrosine kinase activity represents a potential chemoresistance mechanism and a promising therapeutic target warranting further investigation in gemcitabine-resistant pancreatic adenocarcinoma.
Regional Energy Security Cooperation and Geo-Politics with Specific References to India
Authors: Prabhakar Akhilesh Chandra 
Published: September 2005

AbstractThe path from Africa to Indonesia – via West Asia, Central Asia, South Asia, and Southeast Asia – has been of vital interest to North America. Situated at a junction of three continents – namely Asia, Africa, and Europe – linkage over land and across sea between Europe and the Indian Sub-continent on the one side and Africa and India on the other side, it offers the shortest and cheapest trade and transit routes between the West and the East. It commands a vast reservoir of oil – about 60 percent of the world's proven reserves of oil – which enormously contributes to the affluence of the United States.
Rain/No-Rain Classification Methods for Microwave Radiometer Observations over Land Using Statistical Information for Brightness Temperatures under No-Rain Conditions
Authors: Seto Shinta , Takahashi Nobuhiro , Iguchi Toshio 
Published: September 2005

Abstract
One of the goals of the Global Precipitation Measurement project, the successor to the Tropical Rainfall Measuring Mission (TRMM), is to produce a 3-hourly global rainfall map using several spaceborne microwave radiometers. It is important, although often difficult, to classify radiometer observations over land as either “rain” or “no rain” because background land surface conditions change significantly with time and location. In this study, a no-rain brightness temperature database was created to infer land surface conditions using simultaneous observations by TRMM Microwave Imager (TMI) and precipitation radar (PR) with a resolution of 1 month and 1° latitude × 1° longitude. This paper proposes new rain/no-rain classification (RNC) methods that use the database to determine the background brightness temperature. The proposed RNC methods and the RNC method developed for the Goddard profiling algorithm (GPROF; the standard rain-rate retrieval algorithm for TMI) are applied to all TMI observations for the entire year of 2000, and the results are evaluated against the RNC made by PR as the “truth.” The first method (M1) simply uses the average brightness temperature at 85-GHz vertical polarization [denoted as TB (85 V)] under no-rain conditions as the background brightness temperature at 85-GHz vertical polarization [denoted as TBe (85 V)]. The second method (M2) uses a regression equation between TB (85 V) and TB (22 V) under no-rain conditions from the database. Here, TBe (85 V) is calculated by substituting the observed TB (22 V) into the regression equation. The ratio of accurate rain detection by GPROF to all rain occurrences detected by PR was 59%. This ratio was 57% for M1 and 63% for M2. The ratio with the weight of the rain rate was 81% for M1 and 86% for M2; it was 80% for GPROF. These comparisons were made by setting a threshold using a constant coefficient k0 to make the ratio of false rain detection to all no-rain occurrences detected by PR almost the same (approximately 0.85%) for all three methods. Further comparisons among the methods are made, and the reasons for the differences are investigated herein.
Apocalyptic Suicide: From a Pathological to an Eschatological Interpretation
Authors: Dein Simon , Littlewood Roland 
Published: September 2005

Background: The authors examine the possible interpretations of apocalyptic suicide – a form of suicide amongst a group which believes that the world will end imminently. Material: Through a literature search the authors identify a number of paradigmatic cases exemplifying this phenomenon including Jonestown, Waco, The Order of the Solar Temple and Heaven's Gate. Discussion: Interpretations of apocalyptic suicide might consider individual factors – the most common approach – but also the social and eschatological themes which are found in the group's ideological work. Religious violence (including suicide) may be precipitated in a dialectical interaction between group members and the perceived outside world. We consider here the ideological aspects that commonly lead to a dualist epistemology for the group. Conclusion: Apocalyptic suicide involves a shift of personal self and agency to the social self of the charismatic group.
Subjective Experience of Recovery from Schizophrenia-Related Disorders and Atypical Antipsychotics
Authors: Jenkins Janis H. , Strauss Milton E. , Carpenter Elizabeth A. , Miller Dawn , Floersch Jerry , Sajatovic Martha 
Published: September 2005

Aims: This article investigates the subjective experience of the process of improvement and recovery from the point of view of persons diagnosed (according to research diagnostic criteria) with schizophrenia and schizo-affective disorders. Methods: A community study of persons using psychiatric services was conducted for a sample of ninety subjects taking atypical antipsychotic medications. Sociodemographic data and clinical ratings were collected to complement the qualitatively developed Subjective Experience of Medication Interview (SEMI), which elicits narrative data on everyday activities, medication and treatment, management of symptoms, expectations concerning recovery, stigma, and quality of life. Results: Recovery was observed through: (1) relatively low ratings of psychiatrically observed symptomatology through BPRS scores; (2) the subjective sense among the majority (77.4%) of participants that taking medication plays a critical role in managing symptoms and avoiding hospitalization; and (3) the subjective sense articulated by the vast majority (80%) that they would recover from their illness and that the quality of their lives would improve (70.6%). Conclusion: The overall quality of improvement and recovery is best characterized as an incremental, yet definitively discernable, subjective process.
The Social Functioning Questionnaire: A Rapid and Robust Measure of Perceived Functioning
Authors: Tyrer Peter , Nur Ula , Crawford Mike , Karlsen Saffron , MacLean Claire , Rao Bharti , Johnson Tony 
Published: September 2005

Background: The Social Functioning Questionnaire (SFQ), an eight-item selfreport scale (score range 0–24), was developed from the Social Functioning Schedule (SFS), a semi-structured interview which has been used primarily with non-psychotic patients and has good test-retest and inter-rater reliability as well as construct validity. The SFQ was developed following the need for a quick assessment of perceived social function. Aims: To give further details of old and new data sets from studies involving over 4000 subjects assessed with the SFQ illustrating its epidemiological and clinical associations. Method: New data were analysed from a national epidemiological study, a comparison of key-worker and subject versions of the SFQ, and reanalysis of data from three earlier clinical studies, of psychiatric emergencies, general practice psychiatric patients and those with recurrent psychotic illnesses. These data were examined further to determine their range, their relationship to other clinical measures, and change over time in clinical trials. Results: The population mean score in 4164 subjects was 4.6 and the data from all studies suggested that a score of 10 or more indicated poor social functioning. Those presenting as psychiatric emergencies had the poorest social function (mean 11.4) and psychiatric patients from general practice the best function (mean 7.7) of the clinical populations. The eight item scores had a normal distribution in psychiatric populations and a skewed one in a normal population; scores were relatively stable over the short (weeks) and long-term (months), and were high in the presence of acute mental health disturbance and personality disorder, giving support to the validity of the scale. The results from a UK sample of a randomly selected population specifically weighted for ethnic minorities showed similar social function across groups.
Differential effects of GATA-1 on proliferation and differentiation of erythroid lineage cells
Authors: Zheng Jie , Kitajima Kenji , Sakai Eiko , Kimura Tohru , Minegishi Naoko , Yamamoto Masayuki , Nakano Toru 
Published: September 2005

AbstractThe zinc finger transcription factor GATA-1 is essential for both primitive (embryonic) and definitive (adult) erythropoiesis. To define the roles of GATA-1 in the production and differentiation of primitive and definitive erythrocytes, we established GATA-1-null embryonic stem cell lines in which GATA-1 was able to be conditionally expressed by using the tetracycline conditional gene expression system. The cells were subjected to hematopoietic differentiation by coculturing on OP9 stroma cells. We expressed GATA-1 in the course of primitive and definitive erythropoiesis and analyzed the ability of GATA-1 to rescue the defective erythropoiesis caused by the GATA-1 null mutation. Our results show that GATA-1 functions in the proliferation and maturation of erythrocytes in a distinctive manner. The early-stage expression of GATA-1 during both primitive and definitive erythropoiesis was sufficient to promote the proliferation of red blood cells. In contrast, the late-stage expression of GATA-1 was indispensable to the terminal differentiation of primitive and definitive erythrocytes. Thus, GATA-1 affects the proliferation and differentiation of erythrocytes by different mechanisms.
Proangiogenic role of neutrophil-like inflammatory heterophils during neovascularization induced by growth factors and human tumor cells
Authors: Zijlstra Andries , Seandel Marco , Kupriyanova Tatyana A. , Partridge Juneth J. , Madsen Mark A. , Hahn-Dantona Elizabeth A. , Quigley James P. , Deryugina Elena I. 
Published: September 2005

AbstractA quantitative in vivo angiogenesis model employing collagen onplants placed on the chick embryo chorioallantoic membrane (CAM) has been used in this study to assess the spatial and temporal associations between neutrophil-like inflammatory cells, namely chicken heterophils, and the development of new blood vessels. Previously we have demonstrated that monocytes/macrophages infiltrating the onplants were associated with extracellular matrix remodeling and angiogenesis, in particular by delivering MMP-13 collagenase. By introducing chicken gelatinase B (chMMP-9) as a specific marker for heterophils, we now show that the onset and extent of angiogenesis induced by purified growth factors or by human HT-1080 fibrosarcoma cells correlated with the initial influx of chMMP-9–positive heterophils. This early heterophil arrival was followed by the infiltration of monocytes/macrophages and appeared to sustain further blood vessel formation. The disruption of inflammatory cell influx by 2 mechanistically distinct anti-inflammatory drugs, cortisone and ibuprofen, significantly inhibited angiogenesis, indicating a functional involvement of these inflammatory cells in new blood vessel development. A direct addition of isolated heterophils or purified chMMP-9 into the HT-1080 onplants engrafted into cortisone- or ibuprofen-treated embryos reversed the antiangiogenic effects of the drugs. The exogenously added heterophils induced in vivo a further infiltration of endogenous heterophils and monocytes and dramatically rescued the impaired angiogenesis, highlighting the importance of early inflammatory leukocytes in tumor-induced angiogenesis. Moreover, purified heterophils incorporated into onplants lacking growth factors or tumor cells induced angiogenesis in nontreated embryos, further indicating a direct proangiogenic role for neutrophil-like leukocytes.
NF-κB as a target for the prevention of graft-versus-host disease: comparative efficacy of bortezomib and PS-1145
Authors: Vodanovic-Jankovic Sanja , Hari Parameswaran , Jacobs Paulette , Komorowski Richard , Drobyski William R. 
Published: September 2005

AbstractNF-κB is a transcription factor that controls the expression of a number of genes important for mediating immune and inflammatory responses. In this study, we examined whether bortezomib and PS-1145, each of which inhibits NF-κB, could protect mice from lethal graft-versus-host disease (GVHD), which is characterized by immune activation and proinflammatory cytokine production. When administered within the first 2 days after transplantation, bortezomib and PS-1145 both protected mice from fatal GVHD, did not compromise donor engraftment, and effected marked reduction in the levels of serum cytokines that are normally increased during GVHD. Extending the course of bortezomib administration or delaying the initiation of this agent for as few as 3 days after bone marrow transplantation (BMT), however, significantly exacerbated GVHD-dependent mortality because of severe pathological damage in the colon. In contrast, prolonged administration of PS-1145, which, unlike bortezomib, is a selective inhibitor of NF-κB, caused no early toxicity and resulted in more complete protection than that observed with an abbreviated PS-1145 treatment schedule. These results confirm a critical role for NF-κB in the pathophysiology of GVHD and indicate that targeted inhibition of NF-κB may have a superior therapeutic index and may constitute a viable therapeutic approach to reduce GVHD severity. (Blood. 2006;107:827-834)
Runx1 function in hematopoiesis is required in cells that express Tek
Authors: Li Zhe , Chen Michael J. , Stacy Terryl , Speck Nancy A. 
Published: September 2005

AbstractRunx1 expression marks the putative hemogenic endothelium between embryonic days (E) 8.5 to 11.5 of mouse gestation and is required for the formation of intra-aortic hematopoietic clusters, leading to the hypothesis that Runx1 is required for the transition from endothelial to hematopoietic cell. To address this hypothesis, we ablated the Runx1 gene by Cre-recombinase-mediated excision, with Cre expression under the control of the Tek promoter and enhancer. Most embryos died between E12.5 and E13.5 with a phenotype almost identical to Runx1 deficiency. We conclude that Runx1 function in establishing definitive hematopoiesis is required in a Tek+ cell.
FcϵR1 and toll-like receptors mediate synergistic signals to markedly augment production of inflammatory cytokines in murine mast cells
Authors: Qiao Huihong , Andrade Marcus V. , Lisboa Felipe A. , Morgan Katrina , Beaven Michael A. 
Published: September 2005

AbstractMast cells mediate both IgE-dependent allergic reactions and protective responses against acute infections, possibly through the activation of Toll-like receptors (TLRs). We find that antigen interacts synergistically with TLR2 and TLR4 ligands to markedly enhance production of cytokines in murine mast cell lines. However, the TLR ligands neither stimulated degranulation and release of arachidonic acid nor influenced such responses to antigen, probably because these ligands failed to generate a necessary calcium signal. The enhanced cytokine production could be attributed to synergistic activation of mitogen-activated protein kinases in addition to the engagement of a more effective repertoire of transcription factors for cytokine gene transcription. The synergistic interactions of TLR ligands and antigen might have relevance to the exacerbation of IgE-mediated allergic diseases by infectious agents.
T cell avidity and tumor recognition: implications and therapeutic strategies
Authors: McKee Mark D , Roszkowski Jeffrey J , Nishimura Michael I 
Published: September 2005

AbstractIn the last two decades, great advances have been made studying the immune response to human tumors. The identification of protein antigens from cancer cells and better techniques for eliciting antigen specific T cell responsesin vitroandin vivohave led to improved understanding of tumor recognition by T cells. Yet, much remains to be learned about the intricate details of T cell – tumor cell interactions. Though the strength of interaction between T cell and target is thought to be a key factor influencing the T cell response, investigations of T cell avidity, T cell receptor (TCR) affinity for peptide-MHC complex, and the recognition of peptide on antigen presenting targets or tumor cells reveal complex relationships. Coincident with these investigations, therapeutic strategies have been developed to enhance tumor recognition using antigens with altered peptide structures and T cells modified by the introduction of new antigen binding receptor molecules. The profound effects of these strategies on T cell – tumor interactions and the clinical implications of these effects are of interest to both scientists and clinicians. In recent years, the focus of much of our work has been the avidity and effector characteristics of tumor reactive T cells. Here we review concepts and current results in the field, and the implications of therapeutic strategies using altered antigens and altered effector T cells.
Recurrent Heat-Related Illnesses During Antipsychotic Treatment
Authors: Kwok Jeffrey SS , Chan Thomas YK 
Published: September 2005

OBJECTIVE To report a case of recurrent heat-related illnesses associated with the use of benzhexol, chlorpromazine, and zuclopenthixol decanoate. CASE SUMMARY During the summer of 2004, a 48-year-old man with a history of diabetes mellitus and schizophrenia was twice admitted to the hospital because of heat-related illnesses. On both occasions, he had been working under the sun in an open car park. His medications included benzhexol 2 mg twice daily, chlorpromazine 650 mg at bedtime, and zuclopenthixol decanoate intramuscular injection 600 mg every 4 weeks. In the first admission, the clinical diagnosis was heat stroke. He was discharged home on day 14, with precautionary advice against heat stroke. In the second admission, the clinical diagnosis was heat exhaustion. He was discharged home on day 4 and reminded of the precautions against heat stroke. An objective causality assessment revealed that the adverse event was possibly drug related in the first admission and probably drug related in the second admission. DISCUSSION Several drugs can impair thermoregulation during exercise or under conditions of environmental heat stress. Anticholinergic drugs or drugs with anticholinergic effects can inhibit sweating and reduce heat elimination. Neuroleptics (antipsychotics), such as phenothiazines, have combined anticholinergic and central thermoregulatory effects. The set point of the temperature regulation center can be elevated by the antidopaminergic effect of antipsychotics, such as phenothiazines and thioxanthenes. CONCLUSIONS Certain drugs may induce or worsen heat-related illnesses. During a heat wave, special attention should be given to those most at risk, and the importance of preventive measures should be emphasized.