bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized Trial of the Combination of Lomeguatrib and Temozolomide Compared With Temozolomide Alone in Chemotherapy Naive Patients With Metastatic Cutaneous Melanoma
Authors: Ranson Malcolm , Hersey Peter , Thompson Damien , Beith Jane , McArthur Grant A. , Haydon Andrew , Davis Ian D. , Kefford Richard F. , Mortimer Peter , Harris Peter A. , Baka Sofia , Seebaran Augustus , Sabharwal Ami , Watson Amanda J. , Margison Geoffrey P. , Middleton Mark R. 
Published: June 2007

Purpose To evaluate tumor response, pharmacodynamic effects, and safety of a combination of lomeguatrib (LM), an O6-methylguanine DNA-methyltransferase (MGMT) inactivator, and temozolomide (TMZ), TMZ alone, and LM/TMZ after disease progression on TMZ alone in patients with advanced melanoma. Patients and Methods Patients with unresectable stage III or IV cutaneous melanoma who had no prior systemic chemotherapy were randomly assigned to receive either 40 to 80 mg LM and 125 mg/m2 TMZ or 200 mg/m2 TMZ on days 1 through 5 of each 28-day treatment cycle. Drugs were administered orally for up to six cycles of treatment. Patients on TMZ alone were offered LM/TMZ at progression, if fit enough to receive treatment. Results One hundred four patients were enrolled, with 52 in each trial arm. Twenty-seven TMZ-treated patients received LM/TMZ after progression on TMZ. Unexpectedly, analysis of tumor biopsies showed rapid recovery of MGMT after LM/TMZ with 40 mg/d LM. Therefore, doses of LM were escalated to 60 then 80 mg/d. Tumor response rates were 13.5% with LM/TMZ and 17.3% with TMZ alone. No patient responded to LM/TMZ having progressed through TMZ. Median time to disease progression was 65.5 days for LM/TMZ and 68 days for TMZ. All treatments were well tolerated, although hematologic and gastrointestinal adverse events were common. A higher incidence of hematological adverse events was observed in the LM/TMZ combination arm. Conclusion The efficacy of LM and TMZ in the current dosing schedule is similar to that of TMZ alone. To maintain MGMT depletion in tumor dosing of LM needs to be continued beyond that of TMZ.
Reversible Photon-mode Phosphorescence Switching of Heteroleptic Cyclometalated Iridium(III) Complexes via Photochromic Bisthienylethene Switch Linked to Ancillary Ligand
Authors: Lee Insuk , You Youngmin , Lim Seon-Jeong , Park Soo Young 
Published: June 2007

Abstract
A novel class of heteroleptic IrIII complexes covalently linked with photochromic bisthienylethene (BTE) switch showed optically addressed modulation in blue, green, and yellow phosphorescence. Additional enhancement of phosphorescence modulation was successfully achieved by the incorporation of multiple BTE switches or by the use of intermolecular energy transfer.
Molecular Monolayer Nanotubes Having 7–9 nm Inner Diameters Covered with Different Inner and Outer Surfaces
Authors: Kameta Naohiro , Mizuno Go , Masuda Mitsutoshi , Minamikawa Hiroyuki , Kogiso Masaki , Shimizu Toshimi 
Published: June 2007

Abstract
Novel unsymmetrical bolaamphiphile, bearing glucose- and triglycine-headgroups at both ends, exclusively self-assembled into nanotubes with 7–9-nm inner diameters, which consist of a single monolayer lined by polyglycine-II-type hydrogen-bond networks among the triglycine moieties.
Highly Catalytic Electrode for Glucose Electro-oxidation Based on Au Nanoparticles Electrodeposited onto HOPG Substrate
Authors: Aoun Sami Ben , Taniguchi Isao 
Published: June 2007

Abstract
The electrocatalytic oxidation of glucose at Au nanoparticles-modified highly oriented pyrolytic graphite (HOPG) electrode has been investigated, for the first time. Catalytic oxidation of glucose to gluconolactone was observed and an electro-oxidative pretreatment of the HOPG electrode showed a significant enhancement of the catalytic activity as a consequence of the significant change in the crystallographic orientations through enrichment in the Au(100) facets of the electrodeposited Au nanoparticles.
Platinum-catalyzed Aromatic C–H Silylation of Arenes with 1,1,1,3,5,5,5-Heptamethyltrisiloxane
Authors: Murata Miki , Fukuyama Naoaki , Wada Jun-ichi , Watanabe Shinji , Masuda Yuzuru 
Published: June 2007

Abstract
The intermolecular dehydrogenative coupling of 1,1,1,3,5,5,5-heptamethyltrisiloxane with arenes proceeded in the presence of a catalytic amount of platinum complexes prepared in situ from PtCl2 and hydrotris(pyrazolyl)borate derivatives.
Bright Green Upconversion Fluorescence of Yb3+, Er3+-codoped Fluoride Colloidal Nanocrystal and Submicrocrystal Solutions
Authors: Wang Yan , Qin Weiping , Zhang Jisen , Cao Chunyan , Zhang Jishuang , Jin Ye , Zhu Peifen , Wei Guodong , Wang Guofeng , Wang Lili 
Published: June 2007

Abstract
Hexagonal-phase LaF3: Yb3+, Er3+, hexagonal-phase NaGdF4: Yb3+, Er3+, cubic-phase NaYF4: Yb3+, Er3+ nanocrystals (NCs), and hexagonal-phase NaYF4: Yb3+, Er3+ submicrorods (MRs) were prepared with oleic acid as capping ligand. The NCs and MRs can be redispersed in nonpolar organic solvents, thus forming transparent and stable solutions. Under a 980-nm excitation from a diode laser, the Yb3+, Er3+-codoped NC and MR colloidal solutions present bright green upconversion fluorescence.
Halothane anaesthesia of normal and dystrophic hamsters
Authors: Carvell J. E. , Stoward P. J. 
Published: June 2007

Induction, carried out in a small clear-plastic box with 3·5% (v/v) halothane in 30:70 (v/v) oxygen: nitrous oxide, was quiet and rapid. Recovery was almost instantaneous. 2% halothane in the oxygen-nitrous oxide mixture was sufficient for maintenance anaesthesia. The anaesthetic mixture was given by face mask in an open circuit specially designed to function at low gas-flow rates. The halothane content of the muscle and blood after 25 min anaesthesia was estimated by gas chromatography of n-heptane extracts. The mean level(± s.e.m.) in blood was 22·8±2·7 mg/1OO ml (n=4), and in dystrophic muscle 226±36·8 mg/100 g wet weight of tissue (n=4): there was a positive correlation (r=0·94) between them ( p<:0·02).
A method for the collection of lymph from the prescapular lymph node of unanaethetized sheep
Authors: Glover D. J. , Hall J. G. 
Published: June 2007

A method for cannulating the efferent duct of the prescapular lymph node of sheep was developed and carried out on over 100 occasions so that lymph could be collected from unanaesthetized sheep under physiological conditions. On average the lymph flowed at 9 ml/h and contained 15 &times 106 lymphocytes/ml. The surgical procedure and relevant anatomical details are described.
Vaginal impedance measurement used for mating in the guinea-pig
Authors: Bartoš L. , Sedlàček J. 
Published: June 2007

A method for determining the phase of the oestrous cycle by measuring the electrical impedance of the vaginal mucous membrane was examined in the guinea-pig. The apparatus consisted of silver ring electrodes attached to a plastic rod and connected to a transistor indicator. A cyclic increase in impedance was found, and significantly higher values were recorded during the phase of increase (proestrus) than at other times of the cycle. By determining this peak the right time for pairing can be chosen. Conversely, the disappearance of this cyclic culmination in impedance pointed to early pregnancy with a high degree of reliability.
Studies on Tyzzer's disease in rats
Authors: Fries A. Schaich , Svendsen O. 
Published: June 2007

An outbreak of an epidemic disease occurred in a specified-pathogen-free (SPF) breeding colony of rats. The clinical signs and the post-mortem findings were characteristic for Tyzzer's disease. The causative agent, Bacillus piliformis, was demonstrated microscopically in ileum, liver and myocardium, and transmitted to mice where its pathogenicity appeared to be similar to that of another strain isolated from mice. B. piliformis from spontaneously-infected rats was demonstrated by indirect immunofluorescence technique. By means of the same technique it was found that the fluorescence antibody titre obtained of the individual sera from spontaneously-infected mice, rats and rabbits was the same, whether the antigen employed was organisms isolated from rats or mice. By testing sera from healthy rats in 3 different colonies by use of immunofluorescence technique, antibodies were found in several sera.
Genetic and physiological aspects of cholesterol accumulation in hyperresponding and hyporesponding rabbits
Authors: Zutphen L. F. M. Van , Bieman M. G. C. W. Den , HÜLsmann W. C. , Fox R. R. 
Published: June 2007

After a 5 week period of feeding a cholesterol-rich diet to rabbits, hyperresponders with high plasma cholesterol levels and hyporesponders with low plasma cholesterol levels could be distinguished from normal responders. The response was found to be correlated with the esterase genotype at the Est-2 locus. The increase in total body cholesterol was higher in hyper- than in hyporesponders. In both groups most of the accumulated dietary cholesterol was found in plasma and liver. Adrenal weight and plasma corticosterone levels were more increased in hyper- than in hyporesponders. The cholesterol-rich diet resulted in an augmentation of liver lipase and lipoprotein lipase activities. These lipolytic activities were more increased in hyper- than in the hyporesponders.
Husbandry and breeding of a newly-established colony of cotton-topped tamarins (Saguinus oedipus oedipus)
Authors: Brand H. M. 
Published: June 2007

From November 1976 to February 1979 a total of 8 litters were born to 6 females. Of the 14 infants, 10 were successfully reared by their parents. Housing, nutrition, a balance between environmental stability and stimulation, and female multiparity are seen as factors contributing to the breeding success of this colony. A controlled male and female pairing programme provided information on mating behaviour and gestation length. One gestation of at least 166 days was observed, longer than that of the common marmoset.
Procedures and equipment for the production and rearing of gnotobiotic lambs
Authors: Cushnie G. H. , Richardson A. J. , Sharman G. A. M. 
Published: June 2007

38 gnotobiotic lambs have been derived by hysterectomy and reared for up to 7 months as true ruminants. 10 cases of contamination have occurred, 4 of which were attributable to a breach in the protective barrier and 1 to a contaminated food pack. The technique permits the use of liquid and solid foods and the regular taking of rumen and other samples, and also regular removal of all excreta and the cleaning of lambs and cages.
Studies on the hygiene of drinking water for laboratory animals. 1. The effect of various treatments on bacterial contamination
Authors: Tober-Meyer B. K. , Bieniek H. J. 
Published: June 2007

Daily autoclaving of drinking-water bottles or daily replacement of their contents resulted in drinking water hygienically acceptable for laboratory rats. However, daily autoclaving of the bottles imposes an additional workload which many institutions cannot afford. The daily replacement of the drinking water is not desirable, since with the usual routines it is virtually impossible to guarantee a bottle is returned to the same cage. A reliable method of preventing bacterial growth for more then 1-2 days in the drinking water of conventional laboratory rats is its acidification with hydrochloric acid to pH 2·3-2·5.
Strain differences in kidney function of inbred rats: 1. Glomerular filtration rate and renal plasma flow
Authors: Hackbarth H. , Baunack E. , Winn M. 
Published: June 2007

Bodyweight, kidney weight and glomerular filtration rate showed significant differences between strains-70% of the total variance was ascribed to the between-strain variance component-while the renal plasma flow showed only a slight strain difference due to a high within-strain variance component (63%). Heritability in the broad sense was 0·78 for bodyweight, 0·85 for kidney weight, 0·66 for glomerular filtration rate and 0·35 for renal plasma flow. There were significant genetic correlations between bodyweight and kidney weight (0·90), bodyweight and glomerular filtration rate (0·73), and between glomerular filtration rate and renal plasma flow (0·71), but not between kidney weight and kidney functions. Significant environmental correlations could be calculated only between bodyweight and all other variables, so that for comparison between strains it seems better to correct renal functions for bodyweight than for kidney weight, which would increase the variation of glomerular filtration rate.
Mandible analysis of NOD and NON strains of mice
Authors: Komeda K. , Goto N. 
Published: June 2007

10 inbred strains of mice including NOD and NON were identified by discriminant and canonical discriminant analysis of the mandible measurements. The number of erroneous discriminations was 0·5% (1/199) for the females and 0% for males (0/232). In canonical discriminant analysis (discriminant analysis with reduction of dimensionality), NOD and NON inbred strains were separately located on 2-dimensional planes, Z1-Z2, Z1-Z3, and Z2-Z3. These results clearly indicate that the genetic constitution of NOD and NON differs, although they have been established from a common ancestor ICR mouse. Causes of divergence between NOD and NON mice arc discussed.
An investigation of genetic variation within a series of congenic strains of mice
Authors: Lovell D. P. , Totman P. , Bigelow S. W. , Nebert D. W. , Hoffman H. A. , Greig J. B. , Festing M. F. W. 
Published: June 2007

2 congenic strains of mice, B6N.AKN- Ahk and D2N.B6N- Ahb, imported from the USA, were found to be either segregating or fixed for an incorrect allele at a number of biochemical loci. B6N.AKN- Ahk, supposedly congenic with C57BL/6N, had the wrong genotype at 6 out of 12 biochemical loci; D2N.B6N- Ahb, supposedly congenic with DBA/2N, was segregating at 3 out of 9 loci. There was genetic variation in mandible shape within the 2 strains but no abnormal coat colours were found and no hybrid vigour in breeding performance was detected. Analyses in the USA confirmed these results and showed that 2 other congenic strains, C3N.D2N- Ahd and AKN.B6J- Ahb, were also segregating at a number of loci. Some of the alleles found in the C3N.D2N- Ahd mice must be the result of a genetic contamination. The simplest explanation for this breakdown in the backcrossing programme is genetic contamination with other congenic strains or recombinant inbred lines under development in the same laboratory. These findings emphasize the importance of continual genetic monitoring of all genetic stocks at regular intervals and in particular during the development of congenic and recombinant lines.
Effects of fibre on digestibility and passage time in Callithricidae
Authors: Krombach F. , Flurer C. , Zucker H. 
Published: June 2007

The effects of fibre in a pelleted diet on food intake, digestibility of crude fibre, dry matter and energy, on passage time and consistency of faeces were studied in 2 species of Callithricidae, Callithrix jacchus and Saguinus fuscicollis. Coarse cellulose, microcellulose, wheat bran and shrimp meal (chitin = crude fibre) were tested in diets containing 2, 4 and 6% total crude fibre, respectively. Digestibility and passage time were determined by inclusion of 0·5% Cr2O3 in the diet. Both celluloses had little influence on the digestibility of energy and dry matter. Digestibility of crude fibre was very low. Wheat bran led to evident depression of energy and dry matter digestibility. High digestibility of crude fibre occurred at the higher levels of inclusion in the diet. Shrimp meal was highly digested with little influence on digestibility of energy and dry matter, indicating considerable degradation of chitin. Wheat bran showed a marked effect, while microcellulose had no effect on passage time, consistency and volume of faeces.
RGS18 Acts as a Negative Regulator of Osteoclastogenesis by Modulating the Acid-Sensing OGR1/NFAT Signaling Pathway
Authors: Iwai Kaori , Koike Masato , Ohshima Shiro , Miyatake Kunio , Uchiyama Yasuo , Saeki Yukihiko , Ishii Masaru 
Published: June 2007

Abstract
We showed that RGS18, a myeloid lineage-specific RGS protein that is inhibited after activation of the RANK/RANKL system, is a negative regulator of osteoclastogenesis. RGS18 acts through an external acidosis-sensing osteoclastogenic mechanism through the OGR1/NFAT pathway.
Introduction: Osteoclasts are bone-resorbing multinuclear giant cells that are differentiated from mononuclear macrophage/monocyte lineage precursors stimulated by the RANK/RANKL system. The regulators of G-protein signaling (RGS) family is a diverse group of proteins that accelerate intrinsic GTP hydrolysis on heterotrimeric G-protein α subunits and play crucial roles in physiological regulation of G-protein –mediated cell signaling in various tissues and organs. We examined the expression and function of RGS18, a myeloid lineage-specific RGS protein, during osteoclastogenesis.
Materials and Methods: A macrophage/monocyte lineage cell line, RAW264.7, and primary osteoclast precursor monocytes derived from mouse bone marrow cultured with macrophage-colony stimulating factor (M-CSF ) (bone marrow–derived monocytes [BMMs]) were used in this study. Both cell types differentiate into osteoclast-like cells on activation by RANKL. Expression of different RGS proteins, including RGS18, was assessed by gene-specific RT-PCR. The subcellular distribution of RGS18 on native osteoclasts in bone tissues, as well as in RAW264.7 cells, was examined by immunohistochemistry using a specific polyclonal antibody. Short interfering RNA against RGS18 was used to inhibit the function endogenous RGS18 in these cell types. Activation of NFATc1, an osteoclastogenic transcription factor, on external acidosis was assessed by visualizing the nuclear localization of NFATc1 visualized with anti-NFATc 1 antibody.
Results: RAW264.7 and BMM cells both expressed mRNA for 10 different mammalian RGS proteins, including RGS18. Expression of RGS18 is significantly inhibited by RANKL both cell types, and inhibition of RGS18 function using RNA interference prominently enhanced osteoclastogenesis on stimulation with RANKL. The effect of RGS18 inhibition was reversed by blocking of proton-sensing OGR1 signaling, and overexpression of exogenous RGS18 inhibited extracellular acidosis-mediated NFATc1 activation. Immunohistochemical studies of mouse bone tissues revealed expression of RGS18 in osteoclasts in vivo.
Conclusions: RGS18 acts as a negative regulator of the acidosis-induced osteoclastogenic OGR1/NFAT signaling pathway, and RANKL stimulates osteoclastogenesis by inhibiting expression of RGS18. Therefore, the results suggest a novel control mechanism of osteoclastogenesis by RGS proteins.
Diphyllin, a Novel and Naturally Potent V-ATPase Inhibitor, Abrogates Acidification of the Osteoclastic Resorption Lacunae and Bone Resorption
Authors: Sørensen Mette G , Henriksen Kim , Neutzsky-Wulff Anita V , Dziegiel Morten H , Karsdal Morten A 
Published: June 2007

Abstract
Dissolution of the inorganic phase of bone by the osteoclasts mediated by V-ATPase and ClC-7 is a prerequisite for bone resorption. Inhibitors of osteoclastic V-ATPase or ClC-7 are novel approaches for inhibition of osteoclastic bone resorption. By testing natural compounds in acidification assays, diphyllin was identified. We characterized diphyllin with respect to the pharmacological effects on osteoclasts.
Introduction: Osteoclastic acidification of the resorption lacuna and bone resorption requires activity of both V-ATPase and the chloride channel ClC-7. Inhibition of these processes represents a novel approach for treatment of bone metabolic disorders. We identified diphyllin, a novel inhibitor of V-ATPase, and characterized this natural compound with respect to activity in human osteoclasts.
Materials and Methods: Diphyllin was tested in the acid influx assay and V-ATPase assay using bovine chromaffin granules. Human osteoclasts were generated from CD14+ monocytes cultured with macrophage-colony stimulating factor (M-CSF ) and RANKL. The effect of diphyllin on lysosomal acidification in human osteoclasts was studied using acridine orange. The effect of diphyllin on bone resorption by osteoclasts was measured as release of C-terminal cross-linked telopeptide of type I collagen (CTX-I ) and calcium into the supernatants and by scoring pit area. Osteoclast number, TRACP activity, and cell viability were measured. Furthermore, the effect of diphyllin on bone nodule formation was tested using the mouse osteoblast cell line MC3T3-E 1.
Results: In the acid influx assay, diphyllin potently inhibited the acid influx (IC50 = 0.6 nM). We found that diphyllin inhibited V-ATPase with an IC50 value of 17 nM, compared with 4 nM for bafilomycin A1. Moreover, diphyllin dose-dependently inhibited lysosomal acidification in human osteoclasts. Furthermore, we found that diphyllin inhibited human osteoclastic bone resorption measured by CTX-I (IC50 = 14 nM), calcium release, and pit area, despite increasing TRACP activity, numbers of osteoclasts, and cell viability. Finally, diphyllin showed no effect on bone formation in vitro, whereas bafilomycin A1 was toxic.
Conclusions: We identified a natural compound that potently inhibits V-ATPase and thereby lysosomal acidification in osteoclasts, which leads to abrogation of bone resorption. Because recent studies indicate that inhibition of the osteoclastic acidification leads to inhibition of resorption without inhibiting formation, we speculate that diphyllin is a potential novel treatment for bone disorders involving excessive resorption.
Environmental Toxicants May Modulate Osteoblast Differentiation by a Mechanism Involving the Aryl Hydrocarbon Receptor
Authors: Ryan Elizabeth P , Holz Jonathan D , Mulcahey Mary , Sheu Tzong-jen , Gasiewicz Thomas A , Puzas J Edward 
Published: June 2007

Abstract
The AHR mediates many of the toxicological effects of aromatic hydrocarbons. We show that AHR expression in osteoblasts parallels the induction of early bone-specific genes involved in maturation. The AHR may not only mediate the effects of toxicants, but with an as yet unidentified ligand, be involved in the differentiation pathways of osteoblasts.
Introduction: Metabolic bone diseases arise as a result of an imbalance in bone cell activities. Recent evidence suggests that environmental toxicants may be contributing factors altering these activities. One candidate molecule implicated in mediating the toxic effects of exogenous compounds is the aryl hydrocarbon receptor (AHR).
Materials and Methods: Osteoblasts isolated from neonatal rat calvaria were analyzed for AHR expression by quantitative PCR, Western blot, and immunohistochemistry. In addition, AHR activation was evaluated by electromobility gel shift assay and fluorescence microscopy.
Results: Our findings showed AHR expression in mature osteoblasts in vivo. The pattern of AHR expression peaks after alkaline phosphatase and before induction of osteocalcin. We first show that AHR functions as a transactivating receptor in osteoblasts, as evidenced by its ligand-dependent migration to the nucleus and its association with known dioxin response elements. AHR activation by 2,3,7,8-tetrachlorodibenzo -p -dioxin (TCDD) mediated the induction of cytochrome p450 1A1 and cycloxygenase-2 protein levels. This effect could be inhibited by the potent AHR antagonist, 3′4 methoxynitroflavone. Furthermore, lead treatment of osteoblasts upregulates the expression of AHR mRNA and protein levels, supporting a novel mechanism whereby lead in the skeleton may increase the sensitivity of bone cells to toxicant exposure.
Conclusions: These data imply that the AHR mediates the effects of aromatic toxicants on bone and that AHR expression is regulated during osteoblast differentiation.