bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cannabis-induced cytotoxicity in leukemic cell lines: the role of the cannabinoid receptors and the MAPK pathway
Authors: Powles Thomas , Poele Robert te , Shamash Jonathan , Chaplin Tracy , Propper David , Joel Simon , Oliver Tim , Liu Wai Man 
Published: September 2004

Abstract
Δ9-Tetrahydrocannabinol (THC) is the active metabolite of cannabis. THC causes cell death in vitro through the activation of complex signal transduction pathways. However, the role that the cannabinoid 1 and 2 receptors (CB1-R and CB2-R) play in this process is less clear. We therefore investigated the role of the CB-Rs in mediating apoptosis in 3 leukemic cell lines and performed microarray and immunoblot analyses to establish further the mechanism of cell death. We developed a novel flow cytometric technique of measuring the expression of functional receptors and used combinations of selective CB1-R and CB2-R antagonists and agonists to determine their individual roles in this process. We have shown that THC is a potent inducer of apoptosis, even at 1 × IC50 (inhibitory concentration 50%) concentrations and as early as 6 hours after exposure to the drug. These effects were seen in leukemic cell lines (CEM, HEL-92, and HL60) as well as in peripheral blood mononuclear cells. Additionally, THC did not appear to act synergistically with cytotoxic agents such as cisplatin. One of the most intriguing findings was that THC-induced cell death was preceded by significant changes in the expression of genes involved in the mitogen-activated protein kinase (MAPK) signal transduction pathways. Both apoptosis and gene expression changes were altered independent of p53 and the CB-Rs.
Final adult height of patients who received hematopoietic cell transplantation in childhood
Authors: Sanders Jean E. , Guthrie Katherine A. , Hoffmeister Paul A. , Woolfrey Ann E. , Carpenter Paul A. , Appelbaum Frederick R. 
Published: September 2004

AbstractGrowth impairment and growth hormone (GH) deficiency are complications after total body irradiation (TBI) and hematopoietic cell transplantation (HCT). To determine the impact of GH therapy on growth, the final heights of 90 GH-deficient children who underwent fractionated TBI and HCT for malignancy were evaluated. Changes in height standard deviation (SD) from the diagnosis of GH deficiency to the achievement of final height were compared among 42 who did and 48 who did not receive GH therapy. At HCT, GH-treated patients were younger (P = .001), more likely to have undergone central nervous system irradiation (P = .007), and shorter (P = .005) than patients who did not receive GH therapy. After HCT, GH deficiency was diagnosed at 1.5 years (range, 0.8-9.5 years) for GH-treated and 1.2 years (range, 0.9-8.8 years) for nontreated patients. GH therapy was associated with significantly improved final height in children younger than 10 years at HCT (P = .0001), but GH therapy did not impact the growth of older children. Girls (P = .0001) and children diagnosed with acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), or myelodysplastic syndromes (MDS) (compared with acute lymphoblastic leukemia [ALL] or non-Hodgkin lymphoma [NHL]; P = .02) also showed more rapid growth than their counterparts. These data demonstrate that GH therapy improves the final height of young children after fractionated TBI.
The pattern of methacholine responsiveness in mice is dependent on antigen challenge dose
Authors: Zosky Graeme R , von Garnier Christophe , Stumbles Philip A , Holt Patrick G , Sly Peter D , Turner Debra J 
Published: September 2004

Abstract
Background
Considerable variation exists in the protocols used to induce hyperresponsiveness in murine models of allergic sensitisation. We examined the effect of varying the number of antigen exposures at challenge on the development of methacholine responsiveness in systemically sensitised mice.

Methods
BALB/c mice were sensitised with ovalbumin (OVA), challenged with 1, 3 or 6 OVA aerosols. Lung function was measured using low frequency forced oscillations and partitioned into components representing the airways (Raw) and lung parenchyma (tissue damping (G) and tissue elastance (H)). Responsiveness to inhaled methacholine (MCh), inflammatory cell profile and circulating IgE were assessed 24 and 48 hours after challenge. The threshold dose of MCh required to elicit a detectable response (sensitivity) and response to 30 mg.mL-1 (maximal response) were determined for each compartment.

Results
Sensitivity; All three OVA protocols resulted in an increased sensitivity to MCh in Raw but not in G or H. These responses where present at 24 and 48 hrs, except 1 OVA aerosol in which changes had resolved by 48 hrs. Maximal response; 1 OVA aerosol increased maximal responses in Raw, G and H at 24 hrs, which was gone by 48 hrs. Three OVA aerosols increased responses in H at 48 hrs only. Six OVA challenges caused increases in Raw, G and H at both 24 and 48 hrs. Eosinophils increased with increasing antigen challenges. IgE was elevated by OVA sensitisation but not boosted by OVA aerosol challenge.

Conclusions
The pattern of eosinophilia, IgE and MCh responsiveness in mice was determined by antigen dose at challenge. In this study, increased sensitivity to MCh was confined to the airways whereas increases in maximal responses occurred in both the airway and parenchymal compartments. The presence of eosinophilia and IgE did not always coincide with increased responsiveness to inhaled MCh. These findings require further systematic study to determine whether different mechanisms underlie airway and parenchymal hyperresponsiveness post antigen challenge.
Depressed and Well Mothers' Emotion Interpretation Accuracy and the Quality of Mother—Infant Interaction
Authors: Broth Michelle Robbins , Goodman Sherryl H. , Hall Christine , Raynor Lynne Catherine 
Published: September 2004

AbstractThe inadequate parenting associated with mothers' depression may be related to mothers' problems in interpreting infants' emotional expressions. The relations between depressed and well mothers' accuracy at interpreting babies' facial expressions and the quality of the mothers' interactions with their infants were examined. In partial support of our hypotheses, depressed mothers' level of depressive symptoms was associated with less accuracy, especially regarding positive emotions. Contrary to expectations, depressed mothers did not differ from well mothers in terms of their emotion accuracy. Furthermore, depressed mothers' accuracy at interpreting infants' emotions was not significantly related to the quality of their interaction with their infants; in contrast, well mothers' accuracy for infants' negative emotions was associated with better interaction quality. These findings provide new information about depressed mothers' emotional interpretations and their parenting. The different pattern of findings for depressed and well mothers suggests that other mediating factors are important, which are discussed.
When Infants Lose Exclusive Maternal Attention: Is It Jealousy?
Authors: Hart Sybil L. , Carrington Heather A. , Tronick E. Z. , Carroll Sebrina R. 
Published: September 2004

AbstractTo characterize infant reactions to jealousy evocation, 94 6‐month‐olds and their mothers were videotaped in an episode where the mothers directed positive attention toward a lifelike doll, and in 2 contrasting interactions: face‐to‐face play and a still‐face perturbation. Cross‐context comparisons of affects and behaviors revealed that jealousy evocation responses were distinguished by diminished joy and heightened anger and intensity of negative emotionality, comparable to levels displayed during the still‐face episode; heightened sadness, with durations exceeding those displayed during still‐face exposure; and an approach response consisting of interest, looks at mother, and diminished distancing, which was more pronounced than that demonstrated during play. Infants' heightened anger and sadness during jealousy evocation correlated with heightened maternal sensitivity and dyadic vocal turn‐taking, respectively, during play; and infants' diminished joy and interest during jealousy evocation were associated with heightened maternal withdrawal and intrusiveness, respectively, during play. Both fear and mother‐directed gaze were greater in girls. The discussion argues for interpreting the infant's mixed and agitated reaction to jealousy evocation as evidence of jealousy.
Young Infants' Behavioral Reactivity to Mild Perturbation: Developmental Continuity, Stability, and Organization
Authors: Hsu Hui‐Chin , Porter Christin L. 
Published: September 2004

AbstractThis study investigated the developmental continuity, stability, and organization of infants' behavioral response to mild stress from 1 to 3 months of age. Changes in infant stress reactivity were expected to coincide with a suspected neurobiological shift around the 2nd month. A total of 53 infants and their mothers participated in this study. At 1 and 3 months, infants' stress reactivity to mild perturbation was assessed by withdrawing a pacifier during nonnutritive sucking. Infant baseline heart rate activity and maternal reports of infant temperament were also obtained. Focusing on facial and vocal negativity, behavioral measures of infant reactivity to pacifier withdrawal were coded from videos. Results showed that developmental continuity and individual instability characterized changes in infant stress reactivity over the 2nd‐month transition. Developmental reorganization was also evidenced by changes in the direction and magnitude of infant stress reactivity in relation to baseline heart period and maternal temperament ratings, respectively. These findings provide direct supporting evidence for the contention that changes in infant stress reactivity to mild perturbation may be a function of developmental shifts in underlying neurobiological mechanisms in early infancy.
The Onset of Working Memory in Infants
Authors: Reznick J. Steven , Morrow Judy D. , Goldman Barbara Davis , Snyder Jessica 
Published: September 2004

AbstractWe used an optimized configuration of the delayed‐response task to explore the ability of young infants to remember which of 2 locations was correct across 12 trials after a 1‐ to 2‐sec delay. Performance improved with age, particularly after 5.5 months. These findings suggest an onset of appreciable working memory for many infants in the middle of their 6th month.
Multiplex Sum-frequency Spectroscopy with Electronic Resonance Enhancement
Authors: Ishibashi Taka-aki , Onishi Hiroshi 
Published: September 2004

Abstract
Multiplex detection of broad bandwidth light brings remarkable improvements in the experimental design of sum-frequency spectroscopy. Highly sensitive, interface-specific observations of molecular vibrations are demonstrated with examples of n-alkyl chains covalently anchored on Si(111) and an organic compound chemisorbed on TiO2(110).
Lithium Alkoxide-promoted Michael Reaction between Silyl Enolates and α,β-Unsaturated Carbonyl Compounds
Authors: Mukaiyama Teruaki , Tozawa Takashi , Fujisawa Hidehiko 
Published: September 2004

Abstract
Michael reaction between silyl enolates and α,β-unsaturated carbonyl compounds by using a catalytic amount of Lewis base such as lithium alkoxide in DMF proceeds smoothly to afford the corresponding Michael-adducts in good yields with moderate to high diastereoselectivities. This reaction can be reasonably explained by considering an alkoxide anion-initiated autocatalytic process.
A Community-Based Educational Intervention to Improve Antithrombotic Drug Use in Atrial Fibrillation
Authors: Jackson Shane L , Peterson Gregory M , Vial Janet H 
Published: September 2004

BACKGROUND Despite evidence that antithrombotics are effective in reducing the risk of stroke in atrial fibrillation (AF), they remain underused. OBJECTIVE To perform a controlled trial of a comprehensive educational program promoting the rational prescribing of antithrombotics for stroke prevention in AF. METHODS The intervention was conducted in Southern Tasmania, Australia, using Northern Tasmania as a control area. General practitioners were sent locally produced guidelines on stroke risk stratification and antithrombotic drug use in AF, which were followed by academic detailing visits. Outcomes were measured using evaluation feedback from the general practitioners, and drug utilization data were provided by a series of patients presenting to the hospital with an admission diagnosis of AF and dispensing of antithrombotic therapy under the Australian Pharmaceutical Benefits Scheme. RESULTS During the educational intervention, 272 guidelines were mailed and, subsequently, 162 general practitioners were visited and the guidelines discussed. Hospital admission data before and after the intervention revealed a significant increase in the use of warfarin in patients at high risk of stroke (33% vs 46% of eligible patients; p < 0.05). Analysis of prescription data for warfarin also indicated that the increase in use of warfarin within the intervention region was significantly greater than for the control region (p < 0.001). CONCLUSIONS The educational program described here led to a significant increase in the prescribing of warfarin for stroke prevention in patients with AF.
The Human H2A and H2B Histone Gene Complement
Authors: Albig W. , Trappe R. , Kardalinou E. , Eick S. , Doenecke D. 
Published: September 2004

AbstractSequences and expression patterns of newly isolated human histone H2A and H2B genes and the respective proteins were compared with previously isolated human H2A and H2B genes and proteins. Altogether, 15 human H2A genes and 17 human H2B genes have been identified. 14 of these are organized as H2A/H2B gene pairs, while one H2A gene and three H2B genes are solitary genes. Two H2A genes and two H2B genes turned out to be pseudogenes. The 13 H2A genes code for at least 6 different amino acid sequences, and the 15 H2B genes encode 11 different H2B isoforms. Each H2A/H2B gene pair is controlled by a divergent promoter spanning 300 to 330 nucleotides between the coding regions of the two genes. The highly conserved divergent H2A/H2B promoters can be classified in two groups based on the patterns of consensus sequence elements. Group I promoters contain a TATA box for each gene, two Oct-1 factor binding sites, and three CCAAT boxes. Group II promoters contain the same elements as group I promoters and an additional CCAAT box, a binding motif for E2F and adjacent a highly conserved octanucleotide (CACAGCTT) that has not been described so far. Five of the 6 gene pairs and 4 solitary genes with group I promoters are localized in the large histone gene cluster at 6p21.3–6p22, and one gene pair is located at 1q21. All group II promoter associated genes are contained within the histone gene subcluster at D6S105, which is located at a distance of about 2 Mb from the major subcluster at 6p21.3–6p22 containing histone genes with group I promoters. Almost all group II H2A genes encode identical amino acid sequences, whereas group I H2A gene products vary at several positions. Using human cell lines, we have analyzed the expression patterns of functional human H2A/H2B gene pairs organized within the two histone gene clusters on the short arm of chromosome 6. The genes show varying expression patterns in different tumor cell lines.
Studies with Lysine N6-Hydroxylase. Effect of a Mutation in the Assumed FAD Binding Site on Coenzyme Affinities and on Lysine Hydroxylating Activity
Authors: Stehr M. , Smau L. , Singh M. , Seth O. , Macheroux P. , Ghisla S. , Diekmann H. 
Published: September 2004

AbstractThe proposed FAD binding site of L-lysine N
The Recombinant Thermosome from the Hyperthermophilic Archaeon Methanopyrus kandleri: In Vitro Analysis of Its Chaperone Activity
Authors: Minuth T. , Henn M. , Rutkat K. , Andrä S. , Frey G. , Rachel R. , Stetter K.O. , Jaenicke R. 
Published: September 2004

AbstractThe archaeonIn order to obtain the chaperonin in amounts sufficient for functional investigations, the gene encoding the 60 kDa subunit was expressed inThe results demonstrate that the recombinant
Not More than Three Tissue Kallikreins Identified from Organs of the Guinea Pig
Authors: Fiedler F. , Betz G. , Hinz H. , Lottspeich F. , Raidoo D.M. , Bhoola K.D. 
Published: September 2004

AbstractThe large and varied multigene families of tissue kallikreins of rat and mouse are considered to selectively release as many bioactive peptides. In order to determine whether a similar family of enzymes is expressed in the organs of the guinea pig purification studies were performed. Tissue kallikreins from the submandibular gland, coagulating gland/prostate complex and the pancreas were separated by affinity chromatography on benzamidine-Sepharose. Amino-terminal sequences, the patterns of hydrolysis rates of a number of peptideGuinea pig tissue kallikreins 1 and 2 have been reported previously. In the present study we have identified a third type, designated tissue kallikrein 1a because of its sequence similarity to kallikrein 1, which differs from the latter in the catalytic properties. The inferred occurrence of not more than two or three independent tissue kallikrein genes in the guinea pig contrasts with the varied family of enzymes expressed by the large number of such genes present in rats and mice. Expression in the guinea pig (and also in humans) of only a small number of tissue kallikreins makes specific processing of a multitude of biologically active peptides by such enzymes unlikely.
Homo-Dimeric Spherulin 3a: A Single-Domain Member of the bg-Crystallin Superfamily
Authors: Kretschmar M. , Mayr E.-M. , Jaenicke R. 
Published: September 2004

Abstract
The βγ-crystallin superfamily of eye lens proteins comprises a class of structurally related members with a wide variety of different functions. Common features of these proteins are 1. the Greek-key motif of antiparallel β-sheets, called the crystallin fold, and 2. the high intrinsic long-term stability. Spherulin 3a (S3a), a dormant protein from the spherules of Physarum polycephalum, is the only known single-domain protein within the βγ-crystallin family. Based on sequence homology and ‘domain swapping’, it has been proposed to represent an evolutionary ancestor of present-day eye lens crystallins. Since S3a is highly expressed in spherulating plasmodia of P. polycephalum under a variety of stress conditions, it can be assumed that the protein may serve as a compatible solute in the cytosol of the slime mold. In order to investigate the stability and other physicochemical properties of a single-domain all-β protein, we isolated natural S3a. For the large-scale purification, the recombinant protein was cloned and expressed in Escherichia coli. The detailed spectral and biochemical analysis proved the recombinant protein to be authentic. In its native form, S3a is dimeric. Due to its exposed cysteine residues (Cys4), in the absence of reducing agents intermolecular disulfide cross-linking leads to the formation of higher oligomers. In order to preserve the native quaternary structure without aggregation artifacts in denaturation/renaturation experiments, the Cys4→Ser mutant (S3a C4S) was produced. Both the wild-type protein and its mutant are indistinguishable in their physicochemical properties. At pH 3–4, both proteins form a stable compact intermediate (A-state). Concentration-dependent thermal and chemical denaturation showed that the equilibrium unfolding of S3a obeys the simple two-state model with no significant occurrence of folding intermediates.
Plectin: A Cytolinker by Design
Authors: Steinböck F.A. , Wiche G. 
Published: September 2004

AbstractPlectin is a cytoskeletal protein of > 500 kDa that forms dumbbell-shaped homodimers comprising a central parallel α-helical coiled coil rod domain flanked by globular domains, thus providing a molecular backbone ideally suited to mediate the protein's interactions with an array of other cytoskeletal elements. Plectin self-associates and interacts with actin and intermediate filament cytoskeleton networks at opposite ends, and it binds at both ends to the hemidesmosomal transmembrane protein integrin beta-4, and likely to other junctional proteins. The central coiled coil rod domain can form bridges over long stretches and serves as a flexible linker between the structurally diverse N-terminal domain and the highly conserved C-terminal domain. Plectin is also a target of p34cdc2kinase that regulates its dissociation from intermediate filaments during mitosis.
Regulation of the Sea Urchin Early H2A Histone Gene Expression Depends on the Modulator Element and on Sequences Located near the 3′ End
Authors: Palla F. , Melfi R. , Gaetano L. Di , Bonura C. , Anello L. , Alessandro C. , Spinelli G. 
Published: September 2004

Abstract
Transcription of the sea urchin early histone genes occurs transiently during early cleavage, reaching the maximum at the morula stage and declining to an undetectable level at the gastrula stage. To identify the regulatory elements responsible for the timing and the levels of transcription of the H2A gene, we used promoter binding studies in nuclear extracts and microinjection of a CAT transgene driven by the early H2A promoter. We found that morula and gastrula nuclear proteins produced indistinguishable DNase I footprint patterns on the H2A promoter. Two sites of interactions, centred on the modulator/enhancer and on the CCAAT box respectively, were detected. Deletion of the modulator or coinjection of an excess of modulator sequences severely affected the expression of two transgenes driven by the enhancer-less and modulator-containing H2A promoter. Finally, a DNA fragment containing 3′ coding and post-H2A spacer sequences, where upon silencing three micrococcal nuclease hypersensitive sites were previously mapped, specifically repressed at the gastrula stage the expression of the transgene driven by the H2A promoter. These results indicate that the modulator is essential for the expression of early H2A gene and that sequences for down-regulation are localized near the 3′ end of the H2A gene.
A Novel Way to Induce Erythroid Progenitor Self Renewal: Cooperation of c-Kit with the Erythropoietin Receptor
Authors: Wessely O. , Bauer A. , Quang C. Tran , Deiner E.-M. , Lindern M. von , Mellitzer G. , Steinlein P. , Ghysdael J. , Beug H. 
Published: September 2004

AbstractRed blood cells are of vital importance for oxygen transport in vertebrates. Thus, their formation during development and homeostasis requires tight control of both progenitor proliferation and terminal red cell differentiation. Self renewal (i.e. long-term proliferation without differentiation) of committed erythroid progenitors has recently been shown to contribute to this regulation. Avian erythroid progenitors expressing the EGF receptor/c-ErbB (SCF/TGFα progenitors) can be induced to long-term proliferation by the c-ErbB ligand transforming growth factor α and the steroids estradiol and dexamethasone. These progenitors have not yet been described in mammals and their factor requirements are untypical for adult erythroid progenitors. Here we describe a second, distinct type of erythroid progenitor (EpoR progenitors) which can be established from freshly isolated bone marrow and is induced to self renew by ligands relevant for erythropoiesis, i.e. erythropoietin, stem cell factor, the ligand for c-Kit and the glucocorticoid receptor ligand dexamethasone. Limiting dilution cloning indicates that these EpoR progenitors are derived from normal BFU-E/CFU-E. For a detailed study, mEpoR progenitors were generated by retroviral expression of the murine Epo receptor in bone marrow erythroblasts. These progenitors carry out the normal erythroid differentiation program in recombinant differentiation factors only. We show that mEpoR progenitors are more mature than SCF/TGFα progenitors and also do no longer respond to transforming growth factor α and estradiol. In contrast they are now highly sensitive to low levels of thyroid hormone, facilitating their terminal maturation into erythrocytes.