bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis, Biological Evaluation and in silico Metabolic and Toxicity Prediction of Some Flavanone Derivatives.
Authors: Moorthy Narayana Subbiah Hari Narayana , Singh Rahul Jitendra , Singh Hemendra Pratap , Gupta Sayan Dutta
Published: March 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Synthesis of Indolizines and Benzoindolizines by Annulation of Donor—Acceptor Cyclopropanes with Electron‐Deficient Pyridines and Quinolines.
Authors: Morra Nicholas A. , Morales Christian L. , Bajtos Barbora , Wang Xin , Jang Hyosook , Wang Jian , Yu Ming , Pagenkopf Brian L.
Published: March 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Simple Synthesis of Some Pentafluoropropenyl Derivatives of Pyrimidine and Purine Based on Addition—Elimination Reaction.
Authors: Wojtowicz‐Rajchel Hanna , Migas Michal , Koroniak Henryk
Published: March 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Rapid Approach to 3,5‐Disubstituted 1,4‐Benzodiazepines via the Photo‐Fries Rearrangement of Anilides.
Authors: Ferrini Serena , Ponticelli Fabio , Taddei Maurizio
Published: March 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Nine New ent‐Labdane Diterpenoids from the Aerial Parts of Andrographis paniculata.
Authors: Chen Li‐Xia , Qiu Feng , Wei Hong , Qu Ge‐Xia , Yao Xin‐Sheng
Published: March 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Synthesis of Urea‐Tethered Disaccharides in Water.
Authors: Ichikawa Yoshiyasu , Matsukawa Yohei , Tamura Mari , Ohara Fumiyo , Isobe Minoru , Kotsuki Hiyoshizo
Published: March 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Alkaloids from Aristolochia manshuriensis (Aristolochiaceae).
Authors: Zhang Yun‐Tian , Jiang Jian‐Qin
Published: March 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
A Short Synthesis of the Carbazole Alkaloid Clausine E (V).
Authors: Bergman Jan , Johnson Ann‐Louise
Published: March 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
A Concise, Convergent Total Synthesis of Monocerin.
Authors: Cassidy John H. , Farthing Christopher N. , Marsden Stephen P. , Pedersen Anders , Slater Mark , Stemp Geoffrey
Published: March 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
A New Antifungal Macrolide, Eushearilide (I), Isolated from Eupenicillium shearii.
Authors: Hosoe Tomoo , Fukushima Kazutaka , Takizawa Kayoko , Itabashi Takeshi , Kawahara Nobuo , Vidotto Valerio , Kawai Ken‐ichi
Published: March 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Inorganic Fullerene‐like Structures ‐ IFs
Authors: Tenne Reshef
Published: March 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Support Materials and Characterization Tools for Nanostructured Catalysts
Authors: de Jong K. P.
Published: March 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Electron Transfer Reactions Between Chloroaurate(III) Complexes and Various Inorganic and Organic Reducing Agents in Acid Medium — A Brief Review
Authors: Pal Biswajit , Sen Pratik K. , Gupta Kalyan K. Sen
Published: March 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Gold Catalysis
Authors: Hashmi A. Stephen K. , Hutchings Graham J.
Published: March 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Identification of Oxidation Products and Oxidation Pathways of High Molecular Weight Dicarboxylic Acids under Hydrothermal Condition
Authors: Jin Fangming , Cao Jianxun , Enomoto Heiji , Moriya Takehiko
Published: March 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Asymmetric Synthesis of Cyanohydrins
Authors: Chen Fu‐Xue , Feng Xiaoming
Published: March 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Carbanion Generation Through Tin‐Lithium Exchange of Vinyl‐, Aryl‐, and Hetarylstannanes
Authors: Rim Chinwon , Son David Y.
Published: March 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Carbonylation of Epoxides
Authors: Nakano Koji , Nozaki Kyoko
Published: March 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Oxidative Carbonylations
Authors: Gabriele Bartolo , Salerno Giuseppe , Costa Mirco
Published: March 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Carbonylations of Aldehydes
Authors: von Wangelin Axel Jacobi , Neumann Helfried , Beller Matthias
Published: March 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Hypervalent Iodine(V) Reagents in Organic Synthesis
Authors: Ladziata Uladzimir , Zhdankin Viktor V.
Published: March 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Chiral N‐Oxides in Asymmetric Catalysis
Authors: Malkov Andrei V. , Kocovsky Pavel
Published: March 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Sodium—Nitrogen Compounds
Authors: Jonczyk A. , Kowalkowska A.
Published: March 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Organometallic Compounds of Potassium
Authors: Mordini Alessandro , Valacchi M.
Published: March 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Mechanistic Aspects of the Ketene—Imine Cycloaddition Reactions
Authors: Venturini Alessandro , Gonzalez Javier
Published: March 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
A phase II and pharmacodynamic study of gefitinib in patients with refractory or recurrent epithelial ovarian cancer
Authors: Posadas Edwin M. , Liel Meghan S. , Kwitkowski Virginia , Minasian Lori , Godwin Andrew K. , Hussain Mahrukh M. , Espina Virginia , Wood Bradford J. , Steinberg Seth M. , Kohn Elise C.
Published: March 2007

BACKGROUND

The primary objective of this study was to evaluate the biochemical effects of gefitinib on its target signal‐transduction pathways in patients with recurrent epithelial ovarian cancer (EOC). The secondary objectives included assessing clinical activity and toxicity and determining the association between biochemical and clinical outcomes.

METHODS

Twenty‐four heavily pretreated patients with EOC who had good end‐organ function and performance status and who had measurable disease received gefitinib 500 mg daily. Prospectively planned core‐needle tumor biopsies were obtained before treatment and after 4 weeks. Protein expression of total and phosphorylated (p) epidermal growth factor receptor (EGFR), protein kinase B (AKT), and extracellular regulated kinase (ERK) was quantified in microdissected tumor cells using tissue lysate array proteomics.

RESULTS

All tumor samples had detectable levels of EGFR and p‐EGFR. A decrease in the quantity of both EGFR and p‐EGFR was observed with gefitinib therapy in >50% of patients. This was not associated with clinical benefit, nor were responses observed. However, trends for increased gastrointestinal and skin toxicity were observed with greater phosphorylation or quantities of EGFR, ERK, and AKT in tumor samples (P ≤ .05). Gefitinib had limited clinical activity as monotherapy despite documented target inhibition.

CONCLUSIONS

The results from this study demonstrated that gefitinib inhibited the phosphorylation of EGFR in EOC tumor cells, providing proof of target in a clinical setting. Combinatorial therapy with molecular therapeutics against complementary targets may prove successful. Cancer 2007. Published 2007 by the American Cancer Society.
A review of hypofractionated palliative radiotherapy
Authors: Lutz Stephen T. , Chow Edward L. , Hartsell William F. , Konski Andre A.
Published: March 2007

Radiotherapy commonly is employed to address symptoms in patients with symptoms caused by cancer. For this article, the authors reviewed data supporting the use of hypofractionated palliative radiotherapy. In addition to single‐fraction treatment for painful bony metastasis, the available literature suggested that courses of 2 to 14 external‐beam fractions may provide equivalent relief to longer course treatment in patients with a poor prognosis who have primary cancers of the lung, rectum, bladder, prostate, head and neck, spleen, and gynecologic system. Hypofractionated treatment delivers palliation that is time efficient, cost effective, and minimally toxic. Evidence suggests that the reluctance of radiation oncologists to provide single‐fraction treatment acts as a barrier to referrals from palliative care professionals. Collaboration in education, research, and patient advocacy will advance the common objectives of the 2 specialties and lead to an appropriate increase in the use of palliative hypofractionated radiotherapy. Cancer 2007. © 2007 American Cancer Society.
Prostate‐specific antigen velocity and prostate cancer gleason grade and stage
Authors: Pinsky Paul F. , Andriole Gerald , Crawford E. David , Chia David , Kramer Barnett S. , Grubb Robert , Greenlee Robert , Gohagan John K.
Published: March 2007

BACKGROUND.

Increased preoperative prostate‐specific antigen (PSA) velocity (PSAV) has been associated with increased prostate cancer mortality and higher Gleason scores. The authors evaluated the relation between PSAV, biopsy Gleason score, and pathologic stage in men who were enrolled in a prostate cancer screening trial.

METHODS.

Data were analyzed from 1441 men who were enrolled in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial who received ≥2 PSA screens and were diagnosed with prostate cancer within 1 year of the last screen. PSAV was estimated by using all screening PSA values within 6 years prediagnosis.

RESULTS.

Both PSA and PSAV were related to biopsy Gleason score. The multivariable odds ratios (OR), controlling for PSA and demographics, for having a Gleason score of 7 to 10 were 1.3 (95% confidence interval [95% CI], 0.9–1.9), 2.2 (95% CI, 1.5–3.3), and 2.3 (95% CI, 1.4–3.9) for men with PSAV values from 0.5 to 1 ng/mL per year, from 1 to 2 ng/mL per year, and >2 ng/mL per year, respectively, compared with men who had PSAV values <0.5 ng/mL per year. The median PSAV was 0.60 ng/mL per year for men with Gleason scores from 2 to 6 versus 0.84 ng/mL per year for men with Gleason scores from 7 to 10 (P < .0001). Among 658 men who underwent prostatectomy, both PSA and PSAV were associated with advanced pathologic stage in univariate analyses; however, when the analysis controlled for clinical stage and biopsy Gleason score, the associations of PSA and PSAV were no longer statistically significant.

CONCLUSIONS.

PSAV and PSA levels were associated independently with biopsy Gleason score. Among men who underwent prostatectomy, PSAV and PSA were not predictive of advanced pathologic stage when the analysis was controlled for biopsy Gleason score and clinical stage. It cannot be determined yet whether PSAV is predictive of long‐term prostate cancer outcome in this cohort. Cancer 2007. Published 2007 by the American Cancer Society.
Successfully improving access and accrual to oncology clinical trials
Authors: Nott Louise , Yeend Susan , Pirc Louise , Pittman Ken , Patterson Kevin , Price Timothy J.
Published: March 2007

Clinical trials recruitment rates remain low despite the acceptance of recognized barriers. Development of a satellite center as a method of improving recruitment can improve access to clinical trials.
The benefit of using whole‐body, low‐dose, nonenhanced, multidetector computed tomography for follow‐up and therapy response monitoring in patients with multiple myeloma
Authors: Horger Marius , Kanz Lothar , Denecke Barbara , Vonthein Reinhard , Pereira Philippe , Claussen Claus D. , Driessen Christoph
Published: March 2007

BACKGROUND.

The objectives of this study were to assess the status and clinical course of patients with multiple myeloma based on the direct visualization of changes in medullary, extramedullary, and focal osteolytic myeloma involvement by using whole‐body, low‐dose, multidetector computed tomography (WBLD‐MDCT) and to compare those results with an assessment based on conventional hematologic parameters.

METHODS.

Between June 2002 and December 2005, WBLD‐MDCT scans were obtained from 131 consecutive multiple myeloma patients with or without therapy, resulting in a total of 439 examinations. The number and size of osteolytic lesions and the number, size, and density of focal or diffuse medullary and extramedullary lesions were analyzed. Those results and the results at follow‐up were related to current laboratory tests for myeloma. Validation was achieved by the combined reading of both hematologic and radiologic parameters at follow‐up.

RESULTS.

Association between both diagnostic modalities was assessed by using European Group for Blood and Marrow Transplantation response criteria, resulting in an agreement of κ = 0.70. Hematologic parameters proved correct in 84% of all examinations, whereas WBLD‐MDCT resulted in correct assessment in 94% of all examinations. Among 91 of 439 examinations that produced discrepant findings (21%), WBLD‐MDCT proved correct in 68 of 91 examinations (75%), as determined at further follow‐up (95% confidence interval, 66–83%; P = .000003; sign test). The combination of WBLD‐MDCT with conventional, laboratory‐based follow‐up resulted in significantly greater diagnostic accuracy compared with laboratory testing alone.

CONCLUSIONS.

The results from this study indicated that WBLD‐MDCT represents a reliable, imaging‐based method for the direct monitoring of the course of patients with myeloma under specific therapy, and it showed good concordance with established hematologic parameters. It is noteworthy that, in the current investigation, WBLD‐MDCT proved to be even more reliable than conventional, laboratory‐based follow‐up. Cancer 2007. © 2007 American Cancer Society.
Quality of life among long‐term non‐Hodgkin lymphoma survivors
Authors: Mols Floortje , Aaronson Neil K. , Vingerhoets Ad J. J. M. , Coebergh Jan‐Willem W. , Vreugdenhil Gerard , Lybeert Marnix L. M. , van de Poll‐Franse Lonneke V.
Published: March 2007

BACKGROUND.

The objective of this population‐based study was to document the long‐term effects (5–15 years postdiagnosis) of non‐Hodgkin lymphoma and its treatment on health‐related quality of life (HRQL) and social problems.

METHODS.

The population‐based Eindhoven Cancer Registry was used to select all patients who were diagnosed with non‐Hodgkin lymphoma from 1989 to 1998. Three hundred sixty patients were invited to complete the 36‐item Short Form Health Survey (SF‐36) and the Quality of Life‐Cancer Survivors questionnaire, and 294 patients (82%) responded.

RESULTS.

Patients who had received chemotherapy reported significantly worse psychological and social well‐being and health‐related quality of life (HRQL) than patients who had not received chemotherapy. Radiotherapy and watchful waiting were not associated significantly with HRQL outcomes. Patients who were diagnosed from 10 to 15 years earlier reported better social well‐being than patients who were diagnosed from 5 to 9 years earlier. Compared with an age‐matched, normative sample from the general population, patients reported significantly worse general health and less vitality, but they reported less bodily pain. Practical problems were reported with work (41%), obtaining health care insurance (6%) and life insurance (15%), and obtaining a home mortgage (22%).

CONCLUSIONS.

From 5 to 15 years after diagnosis, the general health perceptions and vitality levels of non‐Hodgkin lymphoma survivors remained significantly lower than those of their peers in the of general population. In addition, survivors faced practical problems with work and finances that deserve additional attention during the period of rehabilitation. Cancer 2007. © 2007 American Cancer Society.
Histone deacetylase inhibitor trichostatin a potentiates doxorubicin‐induced apoptosis by up‐regulating PTEN expression
Authors: Pan Lina , Lu Jun , Wang Xiuli , Han Liping , Zhang Yu , Han Songyan , Huang Baiqu
Published: March 2007

BACKGROUND.

The tumor suppressor gene PTEN is a major negative regulator of the PI3K/Akt cellular survival pathway. Overexpression of PTEN by adenoviral transfection increases doxorubicin‐induced apoptosis. Whereas doxorubicin‐induced apoptosis can be potentiated by the histone deacetylase (HDAC) inhibitor Trichostatin A (TSA), the mechanisms underlying this process remain unclear. The aim of this work was to investigate whether changes in PTEN expression are involved in TSA/doxorubicin‐induced apoptosis.

METHODS.

We treated 293 T cells with TSA and doxorubicin, detected apoptosis by using Hoechst 33342 staining, and examined changes of PTEN and Egr‐1 expression by quantitative real‐time polymerase chain reaction (PCR). Luciferase reporter assay was used to evaluate the promoter activity of PTEN and Western blot and enzyme‐linked immunosorbent assay (ELISA) were used to confirm changes in the expression of PTEN. The chromatin immunoprecipitation (ChIP) assay was performed to estimate the acetylation level of PTEN promoter.

RESULTS.

Doxorubicin‐induced apoptosis was enhanced by TSA, whereas small interfering RNA (siRNA) targeting PTEN inhibited TSA/doxorubicin‐induced apoptosis. Also, TSA promoted Egr‐1 expression, which is the main transcription factor of PTEN, and this resulted in up‐regulation of PTEN expression, which consequently potentiated apoptosis. Moreover, histone acetyltransferase p300 was able to synergistically activate PTEN transcription with Egr‐1, implicating the role of histone acetylation in the regulation of PTEN expression.

CONCLUSIONS.

TSA promoted doxorubicin‐induced apoptosis through a mechanism that involved the stimulation of Egr‐1 expression, acetylation of core histones at the PTEN promoter, and consequently induction of PTEN transcription. These findings provide a theoretical basis for the therapeutic application of combined treatment of TSA/doxorubicin for cancer. Cancer 2007. © 2007 American Cancer Society.
Ferric and Ferrous Iron in Nitroso‐Myoglobin: Computer Simulations of Stable and Metastable States and Their Infrared Spectra
Authors: Nutt David R. , Meuwly Markus
Published: March 2007

The binding of NO to iron is involved in the biological function of many heme proteins. Contrary to ligands like CO and O2, which only bind to ferrous (FeII) iron, NO binds to both ferrous and ferric (FeIII) iron. In a particular protein, the natural oxidation state can therefore be expected to be tailored to the required function. Herein, we present an ab initio potential‐energy surface for ferric iron interacting with NO. This potential‐energy surface exhibits three minima corresponding to η1‐NO coordination (the global minimum), η1‐ON coordination and η2 coordination. This contrasts with the potential‐energy surface for FeII–NO, which exhibits only two minima (the η2 coordination mode for FeII is a transition state, not a minimum). In addition, the binding energies of NO are substantially larger for FeIII than for FeII. We have performed molecular dynamics simulations for NO bound to ferric myoglobin (MbIII) and compare these with results obtained for MbII. Over the duration of our simulations (1.5 ns), all three binding modes are found to be stable at 200 K and transiently stable at 300 K, with eventual transformation to the η1‐NO global‐minimum conformation. We discuss the implication of these results related to studies of rebinding processes in myoglobin.
Neurotrophic rationale in glaucoma: A TrkA agonist, but not NGF or a p75 antagonist, protects retinal ganglion cellsin vivo
Authors: Shi ZhiHua , Birman Elena , Saragovi H. Uri
Published: March 2007

Glaucoma is a major cause of vision impairment, which arises from the sustained and progressive apoptosis of retinal ganglion cells (RGC), with ocular hypertension being a major risk or co‐morbidity factor. Because RGC death often continues after normalization of ocular hypertension, growth factor‐mediated protection of compromised neurons may be useful. However, the therapeutic use of nerve growth factor (NGF) has not proven effective at delaying RGC death in glaucoma. We postulated that one cause for the failure of NGF may be related to its binding to two receptors, TrkA and p75. These receptors have distinct cellular distribution in the retina and in neurons they induce complex and sometimes opposing activities. Here, we show in anin vivotherapeutic model of glaucoma that a selective agonist of the pro‐survival TrkA receptor was effective at preventing RGC death. RGC loss was fully prevented by combining the selective agonist of TrkA with intraocular pressure‐lowering drugs. In contrast, neither NGF nor an antagonist of the pro‐apoptotic p75 receptor protected RGCs. These results further a neurotrophic rationale for glaucoma. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007.
Expression of FOS, EGR‐1, and ARC in the amygdala and hippocampus of female rats during formation of the intromission mnemonic of pseudopregnancy
Authors: Yang Jasmine J. , Oberlander Joseph G. , Erskine Mary S.
Published: March 2007

Pseudopregnancy (PSP) in the female rat is a neuroendocrine condition that is induced by repeated and intermittent vaginocervical stimulation received during mating and involves the expression of bicircadian prolactin surges and cessation of normal estrous cyclicity for 10–12 days postmating. The temporal patterning and number of intromissions received by the female are critical for PSP initiation, and thus, short‐term encoding of VCS occurs during transduction of intromissions into PSP. In this experiment, we characterized and compared the mating‐induced neural activation patterns within amygdalar and hippocampal regions using expression of the immediate early genes FOS, EGR‐1, and ARC. Cycling female rats mated on proestrus received 15 or 5 intromissions under paced or nonpaced mating conditions. High numbers of intromissions during nonpaced mating or low numbers received during paced mating are sufficient to induce PSP, while five nonpaced intromissions and mounts without intromission are insufficient. Here we demonstrate that the CA1 region of the hippocampus was selectively sensitive to PSP‐sufficient but not PSP‐insufficient mating stimulation by showing significant effects of paced mating for all three IEGs. Paced mating also stimulated the expression of ARC within the basolateral, cortical, and central nuclei of the amygdala. The posterodorsal medial amygdala also showed selective EGR‐1 responses to PSP‐sufficient mating stimulation. There was no effect of hemisphere on IEG expression. The postmating expression profiles of these IEGs provide evidence that limbic areas involved in encoding and consolidation of memory are involved in initiating the neuroendocrine memory of PSP. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007.
Interaction between hindbrain and spinal networks during the development of locomotion in zebrafish
Authors: Chong Mabel , Drapeau Pierre
Published: March 2007

Little is known about the role of the hindbrain during development of spinal network activity. We set out to identify the activity patterns of reticulospinal (RS) neurons of the hindbrain in fictively swimming (paralyzed) zebrafish larvae. Simultaneous recordings of RS neurons and spinal motoneurons revealed that these were coactive during spontaneous fictive swim episodes. We characterized four types of RS activity patterns during fictive swimming: (i) a spontaneous pattern of discharges resembling evoked high‐frequency spiking during startle responses to touch stimuli, (ii) a rhythmic pattern of excitatory postsynaptic potentials (EPSPs) whose frequency was similar to the motoneuron EPSP frequency during swim episodes, (iii) an arrhythmic pattern consisting of tonic firing throughout swim episodes, and (iv) RS cell activity uncorrelated with motoneuron activity. Despite lesions to the rostral spinal cord that prevented ascending spinal axons from entering the hindbrain (normally starting at ∼20 h), RS neurons continued to display the aforementioned activity patterns at day 3. However, removal of the caudal portion of the hindbrain prior to the descent of RS axons left the spinal cord network unable to generate the rhythmic oscillations normally elicited by application of N‐methyl‐D‐aspartate (NMDA), but in ∼40% of cases chronic incubation in NMDA maintained rhythmic activity. We conclude that there is an autonomous embryonic hindbrain network that is necessary for proper development of the spinal central pattern generator, and that the hindbrain network can partially develop independently of ascending input. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007.
BDNF‐mediated modulation of GABA and glycine release in dorsal horn lamina II from postnatal rats
Authors: Bardoni Rita , Ghirri Alessia , Salio Chiara , Prandini Massimiliano , Merighi Adalberto
Published: March 2007

Recent studies show that excitatory glutamatergic transmission is potentiated by BDNF in superficial dorsal horn, both at the pre‐ and the postsynaptic site. The role of BDNF in modulating GABA and glycine‐mediated inhibitory transmission has not been fully investigated. To determine whether the neurotrophin is effective in regulating the spontaneous release of the two neurotransmitters, we have recorded miniature inhibitory postsynaptic currents (mIPSCs) in lamina II of post‐natal rats. We show that application of BDNF enhanced the spontaneous release of GABA and glycine, in presence of tetrodotoxin. The effect was blocked by the trk‐receptor inhibitor k‐252a. Amplitude and kinetics of mIPSCs were not altered. Evoked GABA and glycine IPSCs (eIPSCs) were depressed by BDNF and the coefficient of variation of eIPSC amplitude was significantly increased. By recording glycine eIPSCs with the paired‐pulse protocol, an increase of paired‐pulse ratio during BDNF application was observed. We performed parallel ultrastructural studies to unveil the circuitry involved in the effects of BDNF. These studies show that synaptic interactions between full length functional trkB receptors and GABA‐containing profiles only occur at non peptidergic synaptic glomeruli of types I and II. Expression of trkB in presynaptic vesicle‐containing dendrites originating from GABAergic islet cells, indicates these profiles as key structures in the modulation of inhibitory neurotransmission by the neurotrophin. Our results thus describe a yet uncharacterized effect of BDNF in lamina II, giving further strength to the notion that the neurotrophin plays an important role in pain neurotransmission. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007.
Extracellular ATP in activity‐dependent remodeling of the neuromuscular junction
Authors: Jia Min , Li Min‐Xu , Fields R. Douglas , Nelson Phillip G.
Published: March 2007

Electrical activity during early development affects the development and maintenance of synapses (Spitzer [2006]: Nature 4447:707–712), but the intercellular signals regulating maintenance of synapses are not well identified. At the neuromuscular junction, adenosine 5‐triphosphate (ATP) is coreleased with acetylcholine at activated nerve terminals to modulate synaptic function. Here we use cocultured mouse motor neurons and muscle cells in a three‐compartment cell culture chamber to test whether endogenously released ATP plays a role in activity‐dependent maintenance of neuromuscular synapses. The results suggest that ATP release at the synapse counters the negative effect of electrical activity, thus stabilizing activated synapses. Confirming our previous work (Li et al. [2001]: Nat Neurosci 4:871–872), we found that in doubly innervated muscles, electrical stimulation induced heterosynaptic downregulation of the nonstimulated convergent input to the muscle fiber with no or little change of the stimulated inputs. However, in preparations that were stimulated in the presence of apyrase, an enzyme that degrades extracellular ATP, synapse downregulation of stimulated inputs was substantial and significant, and end plate potentials were reduced. Apyrase treatment for 20 h in the absence of stimulation did result in moderate diminution, but this was prevented by blocking spontaneous neural activity with tetrodotoxin. The P2 receptor blocker, suramin, also induced activity‐dependent synapse diminution. The decrease in synaptic efficacy produced by prolonged stimulation in the presence of apyrase persisted for greater than 20 h, consistent with a developmental time‐course and distinct from the rapid neuromodulatory actions of ATP that have been demonstrated by others. We conclude that extracellular ATP promotes stabilization of the neuromuscular junction and may play a role in activity‐dependent synaptic modification during development. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007.
The G‐protein coupling properties of the human sweet and amino acid taste receptors
Authors: Sainz Eduardo , Cavenagh Margaret M. , LopezJimenez Nelson D. , Gutierrez Joanne C. , Battey James F. , Northup John K. , Sullivan Susan L.
Published: March 2007

The human T1R taste receptors are family C G‐protein‐coupled receptors (GPCRs) that act as heterodimers to mediate sweet (hT1R2 + hT1R3) and umami (hT1R1 + hT1R3) taste modalities. Each T1R has a large extracellular ligand‐binding domain linked to a seven transmembrane‐spanning core domain (7TMD). We demonstrate that the 7TMDs of hT1R1 and hT1R2 display robust ligand‐independent constitutive activity, efficiently catalyzing the exchange of GDP for GTP on Gα subunits. In contrast, relative to the 7TMDs of hT1R1 and hT1R2, the 7TMD of hT1R3 couples poorly to G‐proteins, suggesting that in vivo signaling may proceed primarily through hT1R1 and hT1R2. In addition, we provide direct evidence that the hT1Rs selectively signal through Gαi/o pathways, coupling to multiple Gαi/o subunits as well as the taste cell specific Gβ1γ13 dimer. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007.
Effect of lipopolysaccharide on intracellular killing of Leishmania enriettii and correlation with macrophage oxidative metabolism
Authors: Mauël Jacques , Buchmüller‐Rouiller Yolande
Published: March 2007

The effect of lipopolysaccharide (LPS) on the lymphokine (LK)‐dependent activation of murine peritoneal macrophages for intracellular killing of Leishmania enriettii parasites was investigated. Exposure to LPS alone did not induce macrophages to kill the parasite. In the presence of LK or recombinant interferon‐γ, however, which by themselves rendered the macrophages only weakly cytotoxic, considerable stimulation of intracellular parasite killing was achieved already at a LPS concentration of 1 ng/ml. The response to LPS was of the same magnitude in macrophages tested for intracellular killing as in parallel assays of extracellular cytolysis of target cells. Acquisition of leishmanicidal activity by macrophages exposed to LK and LPS correlated with stimulation of the respiratory burst, as shown by increased hexose monophosphate shunt levels, and priming for elevated chemiluminescence and O2− and H2O2 production. Polymyxin B blocked both this LPS‐dependent metabolic activity and intracellular parasite destruction. Intracellular killing was, however, not solely dependent on oxidative metabolism of macrophages since (a) in the absence of LK, LPS stimulated respiratory burst activity, yet no intracellular killing was observed, and (b) triggering of the respiratory burst by phorbol myristate acetate or zymosan did not affect intracellular parasite survival. These results suggest that, in this experimental model, efficient intracellular parasite killing depends both on increased production of oxygen metabolites and on the availability of so far unidentified factor(s), the synthesis of which requires exposure of macrophages to both LK and LPS.
Specific lysis of Listeria monocytogenes‐infected macrophages by class II‐restricted L3T4+ T cells
Authors: Kaufmann Stefan H. E. , Hug Erika , Väth Ulla , De Libero Gennaro
Published: March 2007

Mice were infected with the intracellular bacterium, Listeria monocytogenes, and T cell clones from spleens, lymph nodes and peritoneal exudates were established. The capacity of L3T4+, Lyt2− T‐cell clones to specifically lyse L. monocytogenes‐infected macrophages was analyzed. As a source of target cells, bone marrow macrophages (BMMΦ) after 9 days of culture in hydrophobic teflon bags were used. These BMMΦ were totally Ia−; however, significant Ia‐expression could be induced by interferon‐γ (IFN‐γ). IFN‐γ‐stimulated BMMΦ, after priming with live or killed L. monocytogenes organisms were effectively lysed by the vast majority of L3T4+ T cell clones. In the absence of either IFN‐γ stimulation or antigen priming, no lysis occurred. Cytolysis was demonstrable in a conventional 4‐h 51Cr‐release assay and in an 18‐h neutral red uptake assay and was antigen specific and class II restricted. Native T cells from L. monocytogenes‐infected mice failed to lyse stimulated, L. monocytogenes‐primed BMMΦ and gained their cytolytic activity after antigenic restimulation in vitro. These data demonstrate that L. monocytogenes‐specific L3T4+ T cells could lyse MΦ presenting listerial antigens provided that Ia antigen expression had been induced. L3T4+ T cell clones produced IFN‐γ after restimulation with antigen plus accessory cells in vitro and IFN‐γ secretion could be increased by costimulation with recombinant IL 2. These T cell clones conferred significant protection upon recipient mice which was more pronounced in the liver. The possible relevance of lysis by L3T4+ T cells of infected MΦ to protection against and pathogenesis of intracellular bacterial infections is discussed.
Sequence analysis of a cDNA clone of a gene encoding a component of a putative phosphorylcholine‐specific T suppressor factor and functional property of its gene product
Authors: Yamasaki Noriyuki , Sugimura Kazuhisa , Hiida Megumi , Naito Tsutomu , Watanabe Takeshi
Published: March 2007

We have isolated a putative phosphorylcholine (PC)‐T cell suppressor factor (TsF) cDNA clone, p6‐5, from a cDNA library of a T hybridoma which constitutively secretes a PC‐TsF in vitro [8]. In the present study, we determined the nucleotide sequence of the p6‐5 gene and found that the p6‐5 sequence is 86% homologous to rat preproelastase 1 gene, one of the serine protease genes. An oligopeptide (14 mer, TsF14) deduced from the p6‐5 sequence was synthesized and antisera against TsF14 were prepared in rabbits. Anti‐TsF14‐conjugated Sepharose 4B specifically absorbed the PC‐TsF activity from the culture supernatant of PC‐TsF‐secreting T hybridomas. In contrast, the binding molecule eluted from the anti‐TsF14‐conjugated Sepharose suppressed the antibody response PC specifically. These results indicated that the p6‐5 polypeptide is a component of the PC‐TsF molecule.
Isogeneic monoclonal antibodies against anti‐α(1 → 3)dextran idiotypes I. Isotypes, idiotope specificity and representation of idiotopes in antisera from mice of various genetic constitutions
Authors: Wilke Joachim , Weiler Eberhardt
Published: March 2007

Eight isogeneic anti‐idiotypic hybridomas were raised against BALB/c myeloma protein MOPC104E and one against J558. Both myelomas react specifically with the α(1 → 3) glucosidic linkage of dextran B1355 fraction S (Dex). Six anti‐MOPC 104E proteins were IgG1, one was IgG2b and one IgM. The anti‐J558 protein was IgG1. Competitive interactions of the anti‐idiotopes and antigen with anti‐Dex proteins were measured. Dex itself was effective, but also an α(1→3) glucosidic heptasaccharide (N7‐CHO).

In order to assess the anti‐idiotope specificity of hybridoma proteins, three anti‐Dex molecules were used: MOPC 104E, J558 and hybridoma protein Hdex14. These differed from each other in VH amino acid positions 54–55, or 100–101, respectively. By their serological reaction pattern our anti‐idiotope proteins could be divided into 3 groups: cross‐reactive, partially cross‐reactive and strictly specific for the immunogen. The latter ones were in the majority, and were called “private”, in contrast to the cross‐reactive “public” anti‐idiotopes. The serological pattern was followed, in general, by the mouse‐to‐mouse distribution of idiotopes in physiological anti‐Dex sera. Public idiotopes were closely correlated in their expression with anti‐Dex activity. “Private” idiotopes showed no correlation, and displayed a characteristically high degree of fluctuation from mouse to mouse.

Among the different mouse strains that were compared with respect to idiotope expression in anti‐Dex sera, two stand out: C57BL‐Igha, which carries chromosome 12 of BALB/c, (as selected through allotype) on the C57BL/6 genome, and BALB‐Ighb, dex+, a recombinant in chromosome 12 linking the dex+ trait from BALB/c to the CH allotype from C57BL/6. The latter strain expressed significantly more of the private idiotopes than the former. This observation is discussed in terms of the position effect of classical genetics and network concepts.
Cyclosporin A does not affect the in vitro induction of antigen‐specific delayed‐type hypersensitivity‐mediating T cells
Authors: Shidani Babak , Motta Iris , Truffa‐Bachi Paolo
Published: March 2007

The effect of cyclosporin A (CsA) on the in vitro induction of sheep red blood cell (SRBC)‐specific T cells mediating the delayed‐type hypersensitivity (DTH) reaction was studied. CsA (1 μg/ml) addition to the culture medium totally inhibits the in vitro anti‐SRBC humoral response but does not interfere with the generation of anti‐SRBC DTH‐mediating T (TDTH) cells. The induction of TDTH requires the presence of antigen and their expression is mediated selectively by the antigen used in the culture. The TDTH cells generated are Lyt‐1+, 2− and their induction occurs with a similar efficiency in CsA‐treated and untreated cultures: the frequency of the TDTH cells increases by a factor of 10 to 20 during the 6‐day incubation period. Lyt‐2+ suppressor cells are also generated in CsA‐treated or untreated cultures. Our results suggest that a small fraction of T cells can be driven into the proliferative pathway by antigen even in presence of CsA.
Long‐lived B cells: mitogen reactivity as a tool for studying their life‐spans
Authors: Lévy Martine , Coutinho António
Published: March 2007

A population of noncycling small lymphocytes has been selectively enriched in mice by treatment with hydroxyurea (HU) over 4 consecutive days. This cell population, present in the spleen of HU‐treated mice, contained a high frequency of lipopolysac‐charide (LPS)‐reactive cells and this could be used as a functional marker to follow their persistence after transfer to LPS‐nonresponder recipient mice. The results reported here show that cells selected after a long‐term HU treatment have considerably less decay, after transfer in recipient mice, than normal spleen cells. Furthermore, they demonstrate that HU‐selected B cells survive in the recipient mice for periods up to 3 months, and are, consequently, true long‐lived lymphocytes.
Epstein‐Barr virus mediates a switch in responsiveness to transforming growth factor, type beta, in cells of the B cell lineage
Authors: Blomhoff Heidi Kiil , Smeland Erlend , Mustafa Abu Salim , Godal Tore , Ohlsson Rolf
Published: March 2007

The functional performance of the transforming growth factor beta (TGFβ), appears to depend on the target cell phenotype as well as in vitro culture conditions. We show here that Epstein‐Barr virus (EBV) infection may induce a change in responsiveness to TGFβ, since TGFβ inhibits traverse of the cell cycle of activated normal human B cells, but promotes cell proliferation of EBV‐positive Burkitt's lymphoma cell lines as well as EBV‐infected B cells. We present evidence that the switch in the responsiveness to TGFβ is mediated by EBV infection, irrespective of the proliferative status of target cells, and thus may contribute to the initiation as well as the maintenance of certain B cell neoplasias.
C3 convertase of the human alternative pathway of complement: modulation of enzyme activity and stability by mouse monoclonal antibodies to Bb
Authors: Fishelson Zvi , Müller‐Eberhard Hans J.
Published: March 2007

To further characterize functional sites on C3b, Bb, the C3 convertase of the alternative pathway of complement, we examined the effect of four monoclonal antibodies on its activity and stability. These antibodies recognized antigenic epitopes on human Bb which were not fully exposed in intact factor B. Three of the monoclonal antibodies inhibited lysis of rabbit erythrocytes by normal human serum in the presence of Mg2+ and EGTA. Two of these antibodies markedly inhibited the activity of purified C3b, Bb deposited on rabbit erythrocytes. However, all four monoclonal antibodies increased the half‐life of the C3 convertase. Thus, these results demonstrate that binding of antibodies to Bb may concomitantly stabilize C3b, Bb and abate its activity. It is likely that such antibodies induce in Bb conformational changes which increase the C3b, Bb complex stability but may also hinder its catalytic site.
Deficient tumor‐specific immunity in old mice: in vivo mediation by suppressor cells, and correction of the defect by interleukin 2 supplementation in vitro but not in vivo
Authors: Bruley‐Rosset Martine , Payelle Béatrice
Published: March 2007

The capacity of old (18–24 months) C57BL/6 mice to develop an immune reaction against MC‐B6‐1 fibrosarcoma cells was studied using in vivo adoptive transfer experiments (Winn assay) and in vitro T cell‐mediated cytotoxicity test. Anti‐tumor immunity was found to decline with age, as indicated by a decreased anti‐tumor growth T cell activity. A suppressive activity was also found present in the splenic T cell population of old mice which can inhibit the in vivo generation of immune T cells in young mice.

These suppressors, or their precursors, were resistant to cyclophosphamide treatment and were effective only when administered 3 days before the immunization of young mice. These mice developed immune T cells perfectly when the suppressors were administered 3 days after immunization, indicating that suppressors may act at an early phase of T cell activation. The protective activity of T cells in vivo correlated well with the in vitro T cell cytotoxicity for MC‐B6‐1 tumor cells, as both were depressed in old mice. Exogenous interleukin 2 (IL 2) addition during the 4‐day culture period partially restored the low cytotoxic activity of old immunized lymphocytes, suggesting that specific clones were present but that a lack of IL 2 limited their expansion. However, in vivo supplementation with IL 2 administered after immunization did not increase the protection mediated by old immunized T cells but, rather, increased the suppression. This work demonstrates the presence of a T cell suppressive activity in the spleen of old mice but also indicates that precursors of cytotoxic cells are generated by the immunization. It seems that in vitro IL 2 addition increases cytotoxic cells while in vivo IL 2 administration amplifies the development of suppressor cells generated during immunization of aged mice.