bluuebunny/crossref_metadata_2025_split huggingface dataset:
TNFerade Biologic, an Adenovector With a Radiation-Inducible Promoter, Carrying the Human Tumor Necrosis Factor Alpha Gene: A Phase I Study in Patients With Solid Tumors
Authors: Senzer Neil , Mani Sridhar , Rosemurgy Alexander , Nemunaitis John , Cunningham Casey , Guha Chandan , Bayol Natalia , Gillen Michelle , Chu Karen , Rasmussen Camilla , Rasmussen Henrik , Kufe Donald , Weichselbaum Ralph , Hanna Nader 
Published: January 2004

PurposeTNFerade is a replication deficient adenovector that expresses human tumor necrosis factor alpha under control of the radiation-inducible Egr-1 promoter. The goals of this study were to determine the safety and toxicity of TNFerade in combination with radiation therapy.Patients and MethodsTNFerade was administered by intratumoral administration, weekly for 6 weeks with concomitant radiation (30 to 70 Gy). Seven dose levels were studied (4 × 107particle units [pu] to 4 × 1011pu) in patients with solid tumors being treated with radiation.ResultsThirty-six patients were assessable for toxicity and 30 for tumor response. Most frequent TNFerade-related toxicities were fever (22%), injection site pain (19%), and chills (19%). No dose-limiting toxicities were observed. Overall, 21 of 30 patients (70%) demonstrated objective tumor response (five complete responses, nine partial responses, and seven minimal responses). In four of five patients with synchronous lesions, a differential response between lesions treated with TNFerade + radiation compared with radiation only was observed.ConclusionThis is the first human study with TNFerade and radiation. The integrated treatment was well tolerated in patients with predominantly prior treatment-refractory solid tumors. Controlled prospective clinical trials have been initiated to more fully define the therapeutic contribution of TNFerade.
Selective CD4+ Lymphopenia in Melanoma Patients Treated With Temozolomide: A Toxicity With Therapeutic Implications
Authors: Su Y.B. , Sohn Sejean , Krown Susan E. , Livingston Philip O. , Wolchok Jedd D. , Quinn Carolyn , Williams Linda , Foster Theresa , Sepkowitz Kent A. , Chapman Paul B. 
Published: January 2004

Purpose Standard schedule temozolomide (TMZ; daily for 5 days every 4 weeks) is often used in melanoma patients, but phase III data show that it is no more effective than standard dacarbazine. Extended TMZ dosing regimens may be superior by delivering the drug continuously at a higher dose over time. Using an extended dosing schedule, we noted a high incidence of lymphopenia and occasional opportunistic infections (OIs). Here we report our retrospective experience in the first 97 patients. Materials and Methods TMZ was administered at 75 mg/m2/d orally for 6 weeks every 8 weeks, although nine patients were treated continuously without a break. Seventeen patients were treated with TMZ alone; 73 patients received TMZ with thalidomide; seven patients received TMZ with low-dose interferon alfa. Results Median duration of TMZ treatment was 113 days; 29% received ≥ 24 weeks of therapy. Lymphopenia was seen in 60% of patients (absolute lymphocyte count < 800/μL) with a median of 101 days to lymphopenia. TMZ did not cause significant neutropenia or thrombocytopenia. Lymphopenia was not more common in patients treated concomitantly with thalidomide. In all patients analyzed for lymphocyte subsets, lymphopenia induced by TMZ affected the CD4+ compartment preferentially. There were two documented OIs (Pneumocystis and Aspergillus pneumonia) as well as other infections indicative of T-cell dysfunction in another 21 patients. Conclusion TMZ at this dose and schedule results in CD4+ lymphopenia in a majority of patients that can result in OIs. Pneumocystis pneumonia prophylaxis should be considered for patients who develop sustained lymphopenia on TMZ.
Reproductive Abnormalities in Human Insulin-Like Growth Factor-Binding Protein-1 Transgenic Male Mice
Authors: Froment Pascal , Staub Christophe , Hembert Stéphanie , Pisselet Claudine , Magistrini Michèle , Delaleu Bernadette , Seurin Danielle , Levine Jon E. , Johnson Larry , Binoux Michel , Monget Philippe 
Published: January 2004

AbstractAdult transgenic mice overexpressing human insulin-like growth factor-binding protein-1 in the liver present reproductive abnormalities in both sexes. In the present work, we have investigated the mechanisms responsible for limiting breeding capacity in these transgenic male mice. Homozygous adult transgenic male mice (3–6 months old) exhibited irregular copulatory behavior and a reduction of the number of pregnancies per female as well as of litter size per pregnancy. Genital tract weight, more specifically epididymal and seminal vesicle weights, were reduced by 45% in homozygous transgenic vs. nontransgenic mice. Homozygous transgenic mice exhibited a 30% reduction of the length of seminiferous tubules (P = 0.007), a 30% decrease in daily sperm production per testis (P = 0.019), and a 50% decrease in the number of spermatozoa in testis (P = 0.037), associated with morphological abnormalities of the sperm heads leading to an approximately 50% reduction of fertilized two-cell eggs (P = 0.002) and of implanted embryos on d 5.5 after mating (P = 0.004). The round spermatids also appeared altered in their morphology. In addition, Leydig cells in homozygous transgenic mice exhibited an altered appearance, with a 1.8-fold increase in lipid droplets in their cytoplasm (P &lt; 0.001). Moreover, the concentration of 3β-hydroxysteroid dehydrogenase was 66% lower in testis from transgenics compared with those from normal mice (P = 0.01), leading to a tendency toward lower plasma testosterone levels (P = 0.1). Interestingly, LH concentrations were increased by 40% in transgenic pituitary extracts (P = 0.02), and basal LH secretion by pituitary explants in vitro was increased by 60% in homozygous transgenic vs. normal mice (P = 0.04), suggesting an alteration of LH pulsatile secretion in vivo. In conclusion, these data suggest that the breeding impairment of human insulin-like growth factor-binding protein-1 transgenic males is due at least in part to an alteration of the process of spermatogenesis, leading to a diminution of sperm production and of its quality. Minor impairment of steroidogenesis may also contribute to the reduced reproductive capacity of these animals. Our observations are consistent with the idea that normal spermatogenesis and perhaps also steroidogenesis are dependent on the actions of sufficient concentrations of unbound IGF-I.
A Novel Missense Mutation in the Mouse Growth Hormone Gene Causes Semidominant Dwarfism, Hyperghrelinemia, and Obesity
Authors: Meyer Carola W. E. , Korthaus Dirk , Jagla Wolfgang , Cornali Emmanuelle , Grosse Johannes , Fuchs Helmut , Klingenspor Martin , Roemheld Stephanie , Tschöp Matthias , Heldmaier Gerhard , de Angelis Martin Hrabé , Nehls Michael 
Published: January 2004

AbstractThe SMA1-mouse is a novel ethyl-nitroso-urea (ENU)-induced mouse mutant that carries an a→g missense mutation in exon 5 of the GH gene, which translates to a D167G amino acid exchange in the mature protein. Mice carrying the mutation are characterized by dwarfism, predominantly due to the reduction (sma1/+) or absence (sma1/sma1) of the GH-mediated peripubertal growth spurt, with sma1/+ mice displaying a less pronounced phenotype. All genotypes are viable and fertile, and the mode of inheritance is in accordance with a semidominant Mendelian trait. Adult SMA1 mice accumulate excessive amounts of sc and visceral fat in the presence of elevated plasma ghrelin levels, possibly reflecting altered energy partitioning. Our results suggest impaired storage and/or secretion of pituitary GH in mutants, resulting in reduced pituitary GH and reduced GH-stimulated IGF-1 expression. Generation and identification of the SMA1 mouse exemplifies the power of the combination of random mouse mutagenesis with a highly detailed phenotype-analysis as a successful strategy for the detection and analysis of novel gene-function relationships.
Human Chorionic Gonadotropin-Dependent Regulation of 17β-Hydroxysteroid Dehydrogenase Type 4 in Preovulatory Follicles and Its Potential Role in Follicular Luteinization
Authors: Brown Kristy A. , Boerboom Derek , Bouchard Nadine , Doré Monique , Lussier Jacques G. , Sirois Jean 
Published: January 2004

Abstract17β-Hydroxysteroid dehydrogenase type 4 (17βHSD4) has a unique multidomain structure, with one domain involved in 17β-estradiol inactivation. The objective of the study was to investigate the regulation of 17βHSD4 during human chorionic gonadotropin (hCG)-induced ovulation/luteinization. The equine 17βHSD4 cDNA was cloned and was shown to encode a 735-amino acid protein that is highly conserved (81–87% identity) compared with other mammalian orthologs. RT-PCR/Southern blot analyses were performed to study the regulation of 17βHSD4 transcripts in equine preovulatory follicles isolated between 0–39 h after hCG treatment. Results showed the presence of basal 17βHSD4 mRNA expression before hCG treatment, but an increase was observed in follicles obtained 24 h after hCG (P &lt; 0.05). Analyses of isolated preparations of granulosa and theca interna cells identified basal mRNA expression in both layers, but granulosa cells appeared as the predominant site of follicular 17βHSD4 mRNA induction. A specific polyclonal antibody was raised against a fragment of the equine protein and used to study regulation of the 17βHSD4 protein. Immunoblots showed an increase in full-length 17βHSD4 protein in follicles 24 h after hCG (P &lt; 0.05), in keeping with mRNA results. Immunohistochemical data confirmed the induction of the enzyme in follicular cells after hCG treatment. Collectively, these results demonstrate that the gonadotropin-dependent induction of follicular luteinization is accompanied by an increase in 17βHSD4 expression. Considering the estrogen-inactivating function of 17βHSD4, its regulated expression in luteinizing preovulatory follicles appears as a potential complementary mechanism to reduce circulating levels of 17β-estradiol after the LH surge.
Distinct Components of Janus Kinase/Signal Transducer and Activator of Transcription Signaling Pathway Mediate the Regulation of Systemic and Tissue Localized Renin-Angiotensin System
Authors: Guo Yueling , Mascareno Eduardo , Siddiqui M. A. Q. 
Published: January 2004

AbstractIn an attempt to demonstrate the linkage between the Janus kinase (Jak)/signal transducer and activator of transcription (STAT) signaling and the activity of the systemic or local renin-angiotensin system in vivo, we produced transgenic mice harboring angiotensinogen (ANG) promoter containing the wild-type or mutant STAT target site (St-domain) fused to the luciferase reporter. The ANG-promoter-driven luciferase expression was dependent upon phosphorylation of Jak2, as administration of tyrphostin AG490, a potent inhibitor of Jak2, down-regulated the ANG promoter activity and abolished the stimulated endogenous ANG mRNA level in the liver. Administration of angiotensin II peptide to the mice resulted in prominent expression of luciferase in the liver and heart of animals containing wild type St-domain, but not in transgenes with mutant St-domain. Angiotensin II-induced signaling caused activation of STAT proteins in the liver (systemic), the pattern of which was distinct from that in the heart (local). The inducible expression of ANG promoter appears to be mediated by physical association of p300 with STAT 5B in liver and STAT 3 and STAT 5A in heart. Taken together, these results point to the differences in signaling mechanisms in the circulating and localized renin-angiotensin system and identify at least two molecular steps, the tyrosyl phosphorylation of Jak2 and the STAT/St-domain interaction, as pivotal in the regulation of ANG gene transcription.
Hydroformylation of Mixed Octenes Using Rhodium–Bulky Phosphonite Complexes with Excellent Catalytic Activity and Stability
Authors: Jeon Jong-Ki , Park Young-Kwon , Kim Ji Man 
Published: January 2004

Abstract
Rhodium catalyst liganded with tetrakis-(2,4-di-t-butylphenyl)-4,4′-biphenylphosphonite exhibited an excellent catalytic activity as well as stability for the hydroformylation of mixed olefins, especially butene dimer.
Formation of Micro and Nanoscale Patterns of Monolayer Templates for Position Selective Immobilization of Oligonucleotide Using Ultraviolet and Electron Beam Lithography
Authors: Niwa Daisuke , Omichi Kaoru , Motohashi Norikazu , Homma Takayuki , Osaka Tetsuya 
Published: January 2004

Abstract
Formation of organosilane monolayer templates using ultraviolet and electron-beam (EB) lithography was investigated. The oligonucleotides were covalently immobilized with high selectivity only to the amino-monolayer modified regions locally formed on the template surfaces at micro and nanometer scale. By using EB lithography, patterned immobilization in nanometer scale, as small as 20 nm, was achieved.
Intramolecular Proton Transfer Inducing a Biszwitterion Structure in a N4 Schiff Base
Authors: Karamé Iyad , Tommasino M Lorraine , Faure René , Fenet Bernard , Lemaire Marc 
Published: January 2004

Abstract
X-ray and NMR evidences of a sulfonated and tetradentate N4 Schiff base pointed out unusual iminium groups. This produces amide groups and the protons transfer leads to an overall biszwitterion structure.
A Novel 1-D Ladder-like Coordination Polymer [Eu(dipic)1.5(H2O)4·3H2O]∞
Authors: Liu Zhiliang , Zhang Deqing , Liu Caiming , Zhu Daoben 
Published: January 2004

Abstract
A novel one-dimensional infinite ladder-like lanthanide (EuIII) coordination polymer was obtained by hydrothermal method and its structure and magnetic and photoemission properties were investigated.
Resolution of the Acid-base Fraction Curves of the Calixarene Derivatives with Chemometric Methods
Authors: Wang Li , Zhu Zhong-Liang , Shi Xian-Fa 
Published: January 2004

Abstract
The acid-base properties of several new calix[4]arene derivatives were studied with chemometric methods by measurement of their UV absorbances under different pH. Resolving the acid-base fraction curves with chemometric methods, the pKa of these derivatives were determined and the fraction curves and pure absorbing spectra of each absorbing component in the calixarene system were obtained. The proton dissociation behavior of these derivatives was also discussed in this paper.
Interconversion between syn and anti Conformations of 1,3-Bis(O-cyanomethyl)-p-tert-butylthiacalix[4]arene
Authors: Bhalla Vandana , Kumar Manoj , Kabuto Chizuko , Hattori Tetsutaro , Miyano Sotaro 
Published: January 2004

Abstract
1,3-Bis(O-cyanomethyl)-p-tert-butylthiacalix[4]arene (5) has been found to interconvert between syn and anti conformations in solution. The equilibrium shifts toward the anti form with increasing solvent polarity. In the solid state, it adopts a pinched cone conformation with the syn arrangement of the cyanomethyl groups. Reduction of the equilibrium mixture of 5 with LiAlH4 gives only anti stereoisomer of 1,3-bis(O-aminoethyl)-p-tert-butylthiacalix[4]arene.
An Unbridged Platinum(III) Dimer with Added Chloro Ligands in Equatorial Sites, [Pt2Cl2(phpy)4] (Hphpy = phenylpyridine), Synthesized by an Oxidation with Aurous Complex
Authors: Yamaguchi Tadashi , Kubota Osamu , Ito Tasuku 
Published: January 2004

Abstract
An unsupported platinum(III) dimer having added chloro ligands at equatorial sites and novel axial-equatorial chelate ligands, [Pt2Cl2(phpy)4] (Hphpy = phenylpyridine) was obtained from an oxidative addition reaction of [Pt(phpy)2] with [AuCl(SMe2)].
Original Paper: Informed consent for breast screening: what should we tell women?
Authors: Marshall T , Adab P 
Published: January 2004

Objective: To illustrate visually the lifetime probabilities of the principal outcomes of the UK breast screening programme in a readily understandable format. Methods: We derived prognostic data from a modelling exercise using published effectiveness data and routine data sources. We calculated the probability that a woman will survive to the age of 75 if she chooses to participate fully in breast screening from age 50 to 64 and if she chooses not to participate. We also calculated her probability of being referred for assessment, undergoing fine-needle biopsy and undergoing open biopsy. We present these data in two alternative decision aid formats. These alternative formats illustrate visually the outcomes for 1000 women and 100 women choosing each alternative: breast screening or no breast screening. Results: A woman participating in breast screening from age 50 to 64 increases her chances of surviving to age 75 by 0.6%. She has a 21.8% probability of surviving to age 75 and being referred for assessment but no further investigation. She has a 5.7% probability of undergoing core biopsy and a 0.9% probability of undergoing open biopsy. This information can easily be presented visually. Conclusions: We can provide realistic estimates of the effects of the breast screening programme on mortality in a readily understandable format. If we wish women to make an informed choice about breast screening they must be given this information.
Original Paper: Does evidence-based information about screening for prostate cancer enhance consumer decision-making? A randomised controlled trial
Authors: Gattellari M , Ward J E 
Published: January 2004

Objectives: Efforts to educate men about the controversy surrounding prostate cancer screening are well intended but rarely evaluated rigorously. We evaluated an evidence-based (EB) booklet for men designed to promote informed decision-making. We also determined whether men's preference for involvement in decision-making ("passive", "collaborative" or "active") modified its impact. Setting and methods: Men aged 40-70 years were recruited from the practices of 13 local general practitioners (GPs) in Sydney, Australia. They completed a self-administered questionnaire before seeing their GP, who, according to pre-randomised codes, distributed either our EB booklet or conventional information. Post-test questionnaires were mailed to men three days later. Of the 248 eligible men recruited, 214 (86% response rate) returned post-test questionnaires. Knowledge of evidence and of risk of developing and dying from prostate cancer, attitudes, interest in screening for prostate-specific antigen (PSA), worry and decisional conflict were the main outcome measures. Results: Compared with those receiving conventional information, men receiving the EB booklet had significantly improved knowledge (50% of items correct, 95% CI 46-53%; vs 45% correct, 95% CI 42-48%) (p=0.048) and lower levels of decisional conflict (mean 21.6, 95% CI 20.7-22.5; vs mean 24.3, 95% CI 23.4-25.2) (p<0.001). Interest in PSA screening was significantly reduced in both groups at post-test (p<0.001). Men preferring a "passive" approach to decision-making gained as much from our EB booklet as those with "active" or "collaborative" preferences. Conclusions: Our findings show the benefits of providing evidence-based information to men about PSA screening. Our EB booklet facilitated informed choice, even among "passive" decision-makers.
Review: Screening for vulnerability to psychological disorders in the military: an historical survey
Authors: Jones E , Hyams K C , Wessely S 
Published: January 2004

Objectives: To evaluate attempts in the military to screen for vulnerability to psychological disorders from World War I to the present. Methods: An extensive literature review was conducted by hand-searching leading medical and psychological journals relating to World Wars I and II. Recent publications were surveyed electronically and UK archives investigated for British applications. Results: Despite the optimism shown in World War I and the concerted efforts of World War II, followup studies showed that screening programmes did not succeed in reducing the incidence of psychological casualties. Furthermore, they had a counter-productive effect on manpower, often rejecting men who would have made good soldiers. Continued experimentation with screening methods for psychiatric vulnerability failed to yield convincing results during the post-war period. Conclusions: Although well-measured variables, such as intelligence, have been shown to predict success in training and aptitude, no instrument has yet been identified which can accurately assess psychological vulnerability. Previous attempts have failed because of false-positives, false-negatives and reluctance in the target population because of stigma. Early findings suggest that psychological surveillance, if not screening, may yield valuable results when applied to military populations exposed to stress.
The quality of routine examinations of the newborn performed by midwives and SHOs; an evaluation using video recordings
Authors: Bloomfield L , Rogers C , Townsend J , Wolke D , Quist-Therson E 
Published: January 2004

Objective: To evaluate the quality of the routine examination of the newborn as carried out by senior house officers (SHOs) and midwives. Design: Randomised controlled trial set in a district general hospital in Southeast England. Eligible babies were randomised to a midwife (11) or an SHO (8) who were then video recorded undertaking the routine newborn examination. Main outcome measures: Quality of 62 observed technical and communication components of the newborn examination, as agreed between independent consultant paediatrician and senior midwife raters. Results: Major differences were found in the rated quality of examinations between midwives and SHOs for the examinations of the heart and lungs, for the overall quality of the examination, and in areas of communication skills. Quality of examination of the hips was assessed as poor for both professional groups. Where there were significant differences between examiners, the quality of the midwives' examinations was higher. Inter-rater agreement between the consultant paediatricians and senior midwives ranged from excellent to poor for different items of the examination with a mean kappa value of 0.42 across all items indicating moderate agreement. Conclusions: The quality of midwife examinations exceeded that of SHOs. All midwives who examine receive formalised training in the examination of the newborn; SHOs may benefit from similar specific training. Training for both professional groups may need to be reviewed, particularly in relation to agreement on 'gold standards' for the screening of developmental dysplasia of the hip.