bluuebunny/crossref_metadata_2025_split huggingface dataset:
Azirine/Oxindole Ring Enlargement via Amidinium Intermediates
Authors: Mekhael Maged K. G. , Bienz Stefan , Linden Anthony , Heimgartner Heinz 
Published: September 2004

AbstractA novel general method for the synthesis of oxindoles, namely the ‘azirine/oxindole ring enlargement via amidinium‐intermediates’ has been established: the reaction of 2H‐azirin‐3‐amines 1 with BF3⋅OEt2 in THF solution at −78° leads to 1,3,3‐trialkyl‐2‐amino‐3H‐indolium tetrafluoroborates 14 in good yields (Scheme 5). Treatment of aqueous solutions of 14 at 0° with aqueous NaOH (30%) and extraction with CH2Cl2 gives oily substances that are either hydrates of 1,3,3‐trialkyl‐2‐dihydroindol‐2‐imines 15 or the corresponding indolium hydroxides. These products are transformed to the corresponding 1,3,3‐trialkyl‐2,3‐dihydroindol‐2‐ones 17 in modest yields upon refluxing in H2O/THF. Reaction of 14 with Ac2O in pyridine at ca. 23° for 16 h followed by aqueous workup and chromatographic separation leads to mixtures of N‐(1,3,3‐trialkyl‐2,3‐dihydro‐indol‐2‐yliden)acetamides 16 and oxindoles 17 (Scheme 6). Hydrolysis of 16 with aqueous HCl under reflux for 1–2 h gives oxindoles 17 in a good yield. Several oxindoles, spiro‐oxindoles, and 5‐substituted oxindoles were synthesized by means of the reactions mentioned above.
Synthesis and Oxidation of N‐Aminoglyconolactams: A Synthesis of Mannostatin A
Authors: Hu Guixian , Vasella Andrea 
Published: September 2004

AbstractThe N‐amino‐ribono‐1,5‐lactam 4 was prepared in two high‐yielding steps from the known methanesulfonate 2. Oxidation of 4 with t‐BuOCl in the presence of 2,6‐lutidine afforded the tetrazene 6 (63%). Oxidation with MnO2 gave the deaminated lactam 7 (40%), which was also obtained, together with the lactone 8, upon oxidation of 4 with PhSeO2H. Oxidation with Mn(OAc)3/Cu(OAc)2 provided the lactam 7 as the major and the dimer 9 as the minor product. Oxidation of 4 with 3 equiv. of Pb(OAc)4 in toluene at room temperature gave two cyclopentanes, viz. the acetoxy epoxide 10 and the diazo ketone 11 in a combined yield of 78%. Oxidation with Pb(OBz)4 provided 11 and the crystalline benzoyloxy epoxide 12. The crystal structure of 12 was established by X‐ray analysis. The N‐amino‐glyconolactams 41, 46, and 51 were prepared similarly to 4. Their oxidation with Pb(OAc)4 provided the diazo ketones 56, 57, and 58 as the only isolable products. Oxidation of the N‐amino‐mannono‐1,5‐lactam 55 with Pb(OAc)4 in the presence of DMSO gave the sulfoximine 59. Mannostatin A, a strong α‐mannosidase inhibitor, was synthesized from the acetoxy epoxide 10 (obtained in 48% from 4) in seven steps and in an overall yield of 45%.
Cyclopentanes from N‐Aminoglyconolactams: Reaction Mechanism and Improved Access to Diazocyclopentanones
Authors: Hu Guixian , Vasella Andrea 
Published: September 2004

AbstractOne of the two mechanisms to rationalize the Pb(OAc)4 oxidation of 1 to 2 and 3 postulates the intermediate generation of a carbene 25 via the acetoxy‐diazepinone 22 and the oxadiazoline 23 (Scheme 2). This mechanism was excluded on the basis of the oxidation of the diazepinone 32 that was synthesized in six steps from the ribonolactone 26. Oxidation of 32 with Pb(OAc)4 provided the unstable acetoxy‐diazepinone intermediate 22, its C(5) epimer, and the stable 5‐O‐acetyl‐1,5‐ribonolactone 33; the 1H‐NMR spectra of the products of the oxidation of 32 and the decomposition of 22 showed no evidence for the formation of the acetoxy epoxide 2 and the diazo ketone 3, excluding 22 as intermediate in the oxidation of 1. To increase the yield of the diazo‐cyclopentanones, we oxidized the acetohydrazide 34, the 4‐toluenesulfonohydrazide 44, and the N,O‐diacetate 46 with Pb(OAc)4. Oxidation of the acetohydrazide 34 with Pb(OAc)4 led to a higher yield of the diazo ketone 3 (40%) than oxidation of the N‐amino‐ribonolactam 1 without affecting the yield of 2. Oxidation of the 4‐toluenesulfonohydrazide 44 gave mostly the product 45 of C‐acetoxylation, while the analogous oxidation of 46 gave the acetoxy lactone 33; neither 2 nor 3 could be detected among the products, excluding 46 as intermediate of the oxidation of 34. Oxidation of the N‐acetamido‐lyxonolactam 47 with Pb(OAc)4 provided the diazo ketone 8 (77 vs. 37% from 5); higher yields of diazo ketones resulted also from the oxidation of the acetohydrazides 48 and 49.
Design of an Intercalating Linker Leading to the First Efficiently 5′,5′‐Linked Alternate‐Strand Hoogsteen Triplex with High Stability and Specificity
Authors: Jessen Carsten H. , Pedersen Erik B. 
Published: September 2004

AbstractThis is the first report describing the design, synthesis, and incorporation of an intercalating linker leading to an efficiently 5′,5′‐linked alternate strand Hoogsteen triplex. Using molecular modeling, the 5′,5′ problem was solved in a rather simple way. The two relatively distant 5′‐ends have been connected with a molecule that provides rigidity to the structure, while being flexible enough to allow stacking upon all four strands. The synthesis of the core of the designed molecule was conducted by Sonogashira coupling of an appropriately substituted iodobenzene with 1,3‐diethynylbenzene to give a conjugated system with three benzene rings interconnected with triple bonds. For the alternate‐strand triplex obtained with the intercalating linker, the stability obtained is higher than that of the corresponding homotriplex of equivalent total length and with the same nucleotides. This is deduced from a 5° higher melting temperature of the alternating triplex. The sensitivity towards mismatches in the alternate‐strand triplex is in the same range (ΔTm=−13° to −19°) as those observed for homotriplexes.
Epstein‐Barr virus latent membrane 2A (LMP2A) down‐regulates telomerase reverse transcriptase (hTERT) in epithelial cell lines
Authors: Chen Fu , Liu Cheng , Lindvall Charlotta , Xu Dawei , Ernberg Ingemar 
Published: September 2004

AbstractThe latent membrane protein (LMP) 2A, one of the membrane‐spanning polypeptides encoded by the Epstein‐Barr virus (EBV), has been implicated in the maintenance of viral latency and appears to function in part by inhibiting B‐cell receptor (BCR) signaling through its ITAM motifs. It has also been suggested that LMP2A is involved in tumorigenesis mediated by EBV. In our study, we determined regulatory effects of LMP2A on the telomerase reverse transcriptase (hTERT) expression. We observed a significant and constant reduction of hTERT mRNA accompanied by decreased telomerase activity in epithelial cells expressing LMP2A. It was further shown that LMP2A inhibited the hTERT promoter activity in transient transfections of both B cells and epithelial cells, and that the ITAM motif was required for this inhibition. Thus LMP2A expression leads to the transcriptional repression of the hTERT gene through specific pathways, which may thereby contribute to the control of EBV‐latency.
Regulation of the multidrug resistance transporter P‐glycoprotein in multicellular prostate tumor spheroids by hyperthermia and reactive oxygen species
Authors: Wartenberg Maria , Gronczynska Sabina , Bekhite Mohamed M. , Saric Tomo , Niedermeier Wilhelm , Hescheler Jürgen , Sauer Heinrich 
Published: September 2004

AbstractHyperthermia is an important component of many cancer treatment protocols. In our study the regulation of the multidrug resistance (MDR) transporter P‐glycoprotein by hyperthermia was studied in multicellular prostate tumor spheroids. Hyperthermia treatment of small (50–100 μm) tumor spheroids significantly increased P‐glycoprotein and mdr‐1 mRNA expression with a maximum effect at 42°C, whereas only moderate elevation of P‐glycoprotein was found in large (350–450 μm) tumor spheroids. Hyperthermia caused an elevation of intracellular reactive oxygen species (ROS). Inhibition of ROS generation with NADPH‐oxidase inhibitors diphenylen iodonium (DPI) and 4‐(2‐aminoethyl)benzenesulfonyl fluoride (AEBSF) abolished P‐glycoprotein expression but did not affect its transcript levels following heat treatment. This indicates that P‐glycoprotein levels are controlled by regulating its translation rate or stability. Hyperthermia incubation resulted in a differential activation of p38 mitogen‐activated protein kinase (MAPK), extracellular regulated kinase 1,2 (ERK1,2), and c‐jun N‐terminal kinase (JNK) immediately, 4 hr and 24 hr after treatment. Furthermore, upregulation of hypoxia‐inducible factor 1α (HIF‐1α) was observed. Elevation of HIF‐1α and P‐glycoprotein expression following hyperthermia treatment were abolished upon coadministration of the p38 inhibitor SB203580. In contrast the JNK inhibitor SP600125 and the ERK1,2 inhibitor UO126 resulted in increase of HIF‐1α and P‐glycoprotein in the control as well as the hyperthermia‐treated samples, indicating negative regulation of intrinsic HIF‐1α and P‐glycoprotein expression by ERK1,2 and JNK signaling cascades. In summary our data demonstrate that hyperthermia‐induced upregulation of P‐glycoprotein and HIF‐1α is mediated by activation of p38, whereas ERK1,2 and JNK are involved in repression of P‐glycoprotein and HIF‐1α under control conditions.
Preoperative genetic diagnosis of gastric carcinoma based on chromosomal loss and microsatellite instability
Authors: Hong Seung‐Jin , Choi Sang‐Wook , Lee Kang‐Hoon , Lee Sung , Min Ki‐Ouk , Rhyu Mun‐Gan 
Published: September 2004

AbstractThe degree of chromosomal losses and the presence of microsatellite instability (MSI) in gastric carcinomas have been categorized into low‐risk (low‐level loss and MSI) and high‐risk (baseline‐ and high‐level losses) genotypes. With the aim of making a preoperative diagnosis, this study confirmed the stem line genotype that is common over an entire tumor as well as in a single biopsy specimen. Biopsy specimens were obtained from 91 gastric carcinoma patients and examined for their microsatellite genotypes using a panel of 41 microsatellite markers on 8 cancer‐associated chromosomes. The genotype of the biopsy specimens was compared with that of a surgical specimen, which had been multifocally examined for its intratumoral heterogeneity. Of the 91 pairs of biopsy and surgical specimens, 87 (96%) containing either the same (60 cases) or a similar (17 cases) number of chromosomal losses were categorized into the same microsatellite genotype, and the remaining 4 pairs (4%) were classified into a different genotype. The surgical specimens showed that an extraserosal invasion and lymph node metastasis are frequently associated with either a high‐level (4 or more) of chromosomal losses irrespective of the tumor size (73% and 85%) or the large carcinomas > 5 cm in diameter irrespective of the tumor genotype (76% and 83%). The status of the extraserosal invasion and lymph node metastasis (0.691 and 0.802 receiver operating characteristic areas, respectively) predicted by the biopsy genotype and the tumor size corresponded closely to the surgical pathology results. Therefore, the extent of chromosomal losses and the presence of an MSI determined on a biopsy specimen will provide valuable information for making a preoperative genetic diagnosis of a gastric carcinoma.
Expression of prostate‐specific antigen (PSA) and human glandular kallikrein 2 (hK2) in ileum and other extraprostatic tissues
Authors: Olsson A. Yvonne , Bjartell Anders , Lilja Hans , Lundwall Åke 
Published: September 2004

AbstractProstate‐specific antigen (PSA) is a widely used marker for prostate cancer. In the literature, there are reports of nonprostatic expression of PSA that potentially can affect early diagnosis. However, the results are scattered and inconclusive, which motivated us to conduct a more comprehensive study of the tissue distribution of PSA and the closely related protein human glandular kallikrein 2 (hK2). RT‐PCR, in situ hybridization and immunohistochemistry were used to detect expression of both PSA and hK2 in secretory epithelial cells of trachea, thyroid gland, mammary gland, salivary gland, jejunum, ileum, epididymis, seminal vesicle and urethra, as well as in Leydig cells, pancreatic exocrine glands and epidermis. Immunometric measurements revealed that the concentration of PSA in nonprostatic tissues represents less than 1% of the amount in normal prostate. Pronounced expression of PSA was detected in the Paneth cells in ileum, which prompted us to compare functional parameters of PSA in ileum and prostate. We found that in homogenates from these 2 tissues, PSA manifested equivalent amidolytic activity and capacity to form complexes with protease inhibitors in blood in vitro. Thus, PSA released from sources other than the prostate may add to the plasma pool of this protein, but given the lower levels detected from those sites, it is unlikely that nonprostatic PSA normally can interfere with the diagnosis of prostate cancer. Nevertheless, this risk should not be neglected as it may be of clinical significance under certain circumstances. Supplementary material for this article can be found on the International Journal of Cancer website at http://www.interscience.wiley.com/jpages/0020‐7136/suppmat/index.html.
Electrospinning of gelatin fibers and gelatin/PCL composite fibrous scaffolds
Authors: Zhang Yanzhong , Ouyang Hongwei , Lim Chwee Teck , Ramakrishna Seeram , Huang Zheng‐Ming 
Published: September 2004

AbstractIn this article, ultrafine gelatin (Gt) fibers were successfully produced with the use of the electrical spinning or electrospinning technique. A fluorinated alcohol of 2,2,2‐trifluoroethanol (TFE) was used as the dissolving solvent. The morphology of the electrospun gelatin fibers was found to be dependent on the alteration of gelatin concentration ranging from 2.5% w/v to 12.5% w/v at 2.5% increment intervals. Based on the electrospun gelatin fibers obtained, 10% w/v gelatin/TFE solution was selected and mixed with 10% w/v poly(ϵ‐caprolactone) (PCL) in TFE at a ratio of 50:50 and co‐electrospun to produce gelatin/PCL composite membranes. Contact‐angle measurement and tensile tests indicated that the gelatin/PCL complex fibrous membrane exhibited improved mechanical properties as well as more favorable wettability than that obtained from either gelatin or PCL alone. The gelatin/PCL fibrous membranes were further investigated as a promising scaffold for bone‐marrow stromal cell (BMSC) culture. Scanning electron microscopy (SEM) and laser confocal microscopy observations showed that the cells could not only favorably attach and grow well on the surface of these scaffolds, but were also able to migrate inside the scaffold up to 114 μm within 1 week of culture. These results suggest the potential of using composite gelatin/PCL fibrous scaffolds for engineering three‐dimensional tissues. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 72B: 156–165, 2005
Calcium sulfate: Analysis of MG63 osteoblast‐like cell response by means of a microarray technology
Authors: Carinci Francesco , Piattelli Adriano , Stabellini Giordano , Palmieri Annalisa , Scapoli Luca , Laino Gregorio , Caputi Sergio , Pezzetti Furio 
Published: September 2004

AbstractCalcium sulfate (CaS) is an highly biocompatible material that has the characteristic of being one of the simplest as well as one of the synthetic bone‐like graft with the longest clinical history, spanning more than 100 years. Solidified or crystallized CaS is very osteogenic in vivo. As the surface CaS dissolves in body fluid, the calcium ions form calcium phosphate that reprecipitates on the surface forming an osteoblast “friendly” environment. How this “friendly” environment alters osteoblast activity to promote bone formation is poorly understood. We therefore attempted to address this question by using microarray techniques to identified genes that are differently regulated in osteoblasts exposed to CaS. By using DNA microarrays containing 19,200 genes, we identified in osteoblast‐like cells line (MG‐63) cultured with CaS (Surgiplaster, Classimplant, Roma, Italy) several genes that expression was significantly upregulated. The differentially expressed genes cover a broad range of functional activities: (a) immunity, (b) lysosomal enzymes production, (c) cell cycle regulation, (d) and signaling transduction. It was also possible to detect some genes whose function is unknown. The data reported are, to our knowledge, the first genetic portrait of CaS effects. They can be relevant to better understand the molecular mechanism of bone regeneration and as a model for comparing other materials with similar clinical effects. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 71B: 260–267, 2004
Fast topological analysis of 2D and 3D grids of data: Application to the atoms in molecule (AIM) and the electron localization function (ELF)
Authors: Soler Philippe , Fuster Franck , Chevreau Hilaire 
Published: September 2004

AbstractThe topological analysis of grids of data is used for determination of surfaces or volumes around maxima. The volumes are then related to chemical information such as atoms or bonds, and can be used for integration of local properties such as electronic population. The problem of global connectivity is reversed into the question of local connectivity yielding a linear scaling partition algorithm. Two packages are developed for a very fast analysis and partition of 2D or 3D grids of data, applications being made to C2H2, C2H4, C6H6, H2CO, and H2CS molecules using the Atoms in Molecule (AIM) or Electron Localization Function (ELF). © 2004 Wiley Periodicals, Inc. J Comput Chem 25: 1920–1925, 2004
A polynomial version of the generator coordinate Dirac–Fock method
Authors: Haiduke Roberto L. A. , De Macedo Luiz G. M. , Barbosa Rugles C. , Da Silva Albérico B. F. 
Published: September 2004

AbstractA polynomial version of the Generator Coordinate Dirac–Fock (p‐GCDF) method is introduced and applied to develop Adapted Gaussian Basis Sets (AGBS) for helium‐ and beryllium‐like atomic species (He, Ne+8, Ar+16, Sn+48, Be, Ne+6, Ar+14, and Sn+46) and for Kr and Xe atoms. The Dirac–Fock–Coulomb and Dirac–Fock–Breit energies obtained with these basis sets are in excellent agreement with numerical finite‐difference calculations. Moreover, the sizes of the AGBS generated here with the p‐GCDF method are significantly smaller than the size of previous relativistic Gaussian basis sets. © 2004 Wiley Periodicals, Inc. J Comput Chem 25: 1904–1909, 2004
Interconversion behavior of the CH bond in the CH radical cation: Ab initio molecular dynamics study
Authors: Ohta Yasuhito , Ohta Koji 
Published: September 2004

AbstractThermal motion of CH is investigated by performing an ab initio molecular dynamics method with the second‐order Møller‐Plesset (MP2)/6‐311G** force field. In the trajectories obtained at 400 K, we have observed rapid interconversion behavior of the geometrical parameters of CH with the frequency of 0.6/ps, where the CH pair forming the small angle around 55° is switched to another pair on subpicosecond time scale. The switching patterns are found to be classified into the following two types. Type 1: one CH of the small angled CH pair is switched to one CH of the other CH pair. Type 2: the small angled CH pair is switched to the other CH pair, which has been newly observed in the present ab initio MD calculation. The four CH bonds of CH are characterized by the long and short CH bonds in a time region of the trajectories, and also for the time‐evolution of CH bonds such interconversion behavior is observed. The switching patterns of the geometrical parameters are compared with those in the interconversion scheme between six equivalent C2v symmetry structures of CH [Paddon‐Row, M. N. et al., J Am Chem Soc 1985, 107, 7696]. We have also investigated the electronic energy fluctuation due to thermal motion of CH. The standard deviation of total electronic energy at 400 K is evaluated to be 1.2 kcal/mol. © 2004 Wiley Periodicals, Inc. J Comput Chem 15: 1910–1919, 2004
OCTN3: A Na+‐independent L‐carnitine transporter in enterocytes basolateral membrane
Authors: Durán J.M. , Peral M.J. , Calonge M.L. , Ilundáin A.A. 
Published: September 2004

AbstractL‐carnitine transport has been measured in enterocytes and basolateral membrane vesicles (BLMV) isolated from chicken intestinal epithelia. In the nominally Na+‐free conditions chicken enterocytes take up L‐carnitine until the cell to medium L‐carnitine ratio is 1. This uptake was inhibited by L‐carnitine, D‐carnitine, γ‐butyrobetaine, acetylcarnitine, tetraethylammonium (TEA), and betaine. L‐3H‐carnitine uptake into BLMV showed no overshoot, and it was (i) Na+‐independent, (ii) trans‐stimulated by intravesicular L‐carnitine, and (iii) cis‐inhibited by TEA and cold L‐carnitine. L‐3H‐carnitine efflux from L‐3H‐carnitine preloaded enterocytes was also Na+‐independent, and trans‐stimulated by L‐carnitine, D‐carnitine, γ‐butyrobetaine, acetylcarnitine, TEA, and betaine. Both, uptake and efflux of L‐carnitine were inhibited by verapamil and unaffected by either extracellular pH or palmitoyl‐L‐carnitine. RT‐PCR with specific primers for the mouse OCTN3 transporter revealed the existence of OCTN3 mRNA in mouse intestine, which was confirmed by in situ hybridization studies. Immunohystochemical analysis showed that OCTN3 protein was mainly associated with the basolateral membrane of rat and chicken enterocytes, whereas OCTN2 was detected at the apical membrane. In conclusion, the results demonstrate for the first time that (i) mammalian small intestine expresses OCTN3 mRNA along the villus and (ii) that OCTN3 protein is located in the basolateral membrane. They also suggest that OCTN3 could mediate the passive, Na+ and pH‐independent L‐carnitine transport activity measured in the three experimental conditions. © 2004 Wiley‐Liss, Inc.
Regulation of Indian hedgehog mRNA levels in chondrocytic cells by ERK1/2 and p38 mitogen‐activated protein kinases
Authors: Lai Lick Pui , DaSilva Kevin A. , Mitchell Jane 
Published: September 2004

AbstractIndian hedgehog (Ihh) is produced by growth plate pre‐hypertrophic chondrocytes, and is an important regulator of endochondral ossification. However, little is known about the regulation of Ihh in chondrocytes. We have examined the role of integrins and mitogen‐activated protein (MAP) kinases in Ihh mRNA regulation in CFK‐2 chondrocytic cells. Cells incubated with the β1‐integrin blocking antibody had decreased Ihh mRNA levels, which was accompanied by decreases of activated extracellular signal‐regulated kinases (ERK1/2) and activated p38 MAPK. Ihh mRNA levels were also inhibited by U0126, a specific MEK1/2 inhibitor, or SB203580, a specific p38 MAPK inhibitor. Cells transfected with constitutively active MEK1 or MKK3 had increased Ihh mRNA levels, which were diminished by dominant‐negative MEK1, p38α or p38β. Stimulation of the PTH1R with 10−8 M rPTH (1–34) resulted in dephosphorylation of ERK1/2 that was evident within 15 min and sustained for 1 h, as well as transient dephosphorylation of p38 MAPK that was maximal after 25 min. PTH stimulation decreased Ihh mRNA levels, and this effect was blocked by transfecting the cells with constitutively active MEK1 but not by MKK3. These studies demonstrated that activation of ERK1/2 or p38 MAPK increased Ihh mRNA levels. Stimulation of the PTH1R or blocking of β1‐integrin resulted in inhibition of ERK1/2 and p38 MAPK and decreased levels of Ihh mRNA. Our data demonstrate the central role of MAPK in the regulation of Ihh in CFK‐2 cells. © 2004 Wiley‐Liss, Inc.