bluuebunny/crossref_metadata_2025_split huggingface dataset:
Forskolin increases neuregulin receptors in human Schwann cells without increasing receptor mRNA
Authors: Fregien Nevis L. , White Linda A. , Bunge Mary Bartlett , Wood Patrick M. 
Published: July 2004

AbstractForskolin and heregulin synergistically drive human Schwann cell (HSC) proliferation in vitro, but the role of forskolin is not completely understood. To learn how forskolin might affect receptor levels in HSC cultured from adult nerve roots, we first studied expression and localization of HER2 and HER3 in intact roots, using Western blotting and light and electron microscopic immunocytochemistry. We then determined the effect of forskolin and heregulin on receptor expression in HSC cultured from nerve roots using Western blotting and RNase protection assays. HER2 and HER3 were expressed in nonmyelinating Schwann cells in roots and in cultured HSCs before exposure to forskolin. HER2, but not HER3, was also expressed in endoneurial fibroblasts and in cultured nerve root‐derived fibroblasts. Treatment with forskolin for 24 h consistently increased HER2 and HER3 protein levels in HSCs but did not alter HER2 and HER3 mRNA levels. In addition, 24‐h treatment with heregulin alone decreased HER2 and HER3 protein levels, an effect not previously described. When both heregulin and forskolin were present, HER2 and HER3 protein levels were similar to initial control values. The effect of forskolin on receptor levels was mimicked by dibutyryl‐cAMP and receptor levels in both untreated and forskolin treated HSCs were decreased by treatment with the protein kinase A inhibitor H‐89. Following pretreatment of HSCs with forskolin, increased receptor levels were correlated with increased rates of thymidine incorporation into HSCs. These results suggest that forskolin/heregulin synergy might derive, at least in part, from post‐transcriptional effects leading to increased steady‐state receptor levels. © 2004 Wiley‐Liss, Inc.
A novel mechanism of FK506‐mediated neuroprotection: Downregulation of cytokine expression in glial cells
Authors: Zawadzka Malgorzata , Kaminska Bozena 
Published: July 2004

AbstractImmunosuppressant FK506 is neuroprotective in experimental models of cerebral ischemia, but the molecular mechanisms underlying this neuroprotection remain unknown. We have demonstrated that FK506 inhibits the signaling pathways that regulate hypertrophic/proliferative responses in cultured astrocytes. Ischemia/reperfusion injury is associated with the proliferation and hypertrophy of astrocytes and with inflammatory responses. In the present work, we sought to determine whether FK506 neuroprotection after middle cerebral artery occlusion (MCAo) in rat is mediated via suppression of glia activation and changes in cytokine expression. Neurological deficits, infarct size, and astrocyte/microglial response were quantified in rats subjected to 90 min of MCAo. Changes in the mRNA expression of interleukin‐1β (IL‐1β), IL‐6, and tumor necrosis factor‐α (TNF‐α) in ipsilateral and contralateral cortices were determined by reverse transcription‐polymerase chain reaction (RT‐PCR). FK506 administered at 1 mg/kg, 60 min after MCAo, produced a significant improvement in neurological function and reduction of infarct volume. In FK506‐treated rats, a significant reduction of IL‐1β, IL‐6, and TNF‐α expression was observed 12 h after reperfusion. FK506 neuroprotection was associated with a significant downregulation of IL‐1β expression in astrocytes and microglia in the injured side. FK506 selectively decreased the levels of TNF‐α, and IL‐1β mRNAs in astrocytes in vitro, with no effect on transforming growth factor‐β 1 (TGF‐β1) and IL‐6 expression. Moreover, FK506 inhibits lipopolysaccharide (LPS)‐induced activation and cytokine expression in microglia in vitro. Our findings suggest that astrocytes and microglia are targets for FK506, and that modulation of glial response and inflammation may be a mechanism of FK506‐mediated neuroprotection in ischemia. © 2004 Wiley‐Liss, Inc.
Absence of the cell cycle inhibitor p21Cip1 reduces LPS‐induced NO release and activation of the transcription factor NF‐κB in mixed glial cultures
Authors: Tusell Josep Maria , Saura Josep , Serratosa Joan 
Published: July 2004

AbstractWe have studied possible differences in glial activation between cells from wild‐type and p21Cip1−/− mice. We compared the effect of serum mitogenic stimulation on proliferation rate and on the total number of glial cells after 7 days of culture. No differences between wild‐type and p21Cip1−/− glial cells were observed. We also compared the effect of lipopolysaccharide (LPS) from Escherichia coli, an agent widely used to induce glial activation. Nitric oxide (NO) and tumor necrosis factor‐α (TNF‐α) release, and nuclear factor kappa‐B (NF‐κB) activation were evaluated as indicators of glial activation. We observed an attenuation of NO release and NF‐κB activation in p21Cip1−/− glial cells when compared with glial cells from wild‐type mice. In contrast, TNF‐α release was enhanced in p21Cip1−/− glia. These results suggest that the cell cycle inhibitor p21Cip1 plays a role in the inflammatory response induced by LPS. © 2004 Wiley‐Liss, Inc.
Glial and neuronal expression of polyglutamine proteins induce behavioral changes and aggregate formation in Drosophila
Authors: Kretzschmar Doris , Tschäpe Jakob , Bettencourt Da Cruz Alexandre , Asan Esther , Poeck Burkhard , Strauss Roland , Pflugfelder Gert O. 
Published: July 2004

AbstractPatients with polyglutamine expansion diseases, like Huntington's disease or several spinocerebellar ataxias, first present with neurological symptoms that can occur in the absence of neurodegeneration. Behavioral symptoms thus appear to be caused by neuronal dysfunction, rather than cell death. Pathogenesis in polyglutamine expansion diseases is largely viewed as a cell‐autonomous process in neurons. It is likely, however, that this process is influenced by changes in glial physiology and, at least in the case of DRPLA glial inclusions and glial cell death, seems to be an important part in the pathogenesis. To investigate these aspects in a Drosophila model system, we expressed polyglutamine proteins in the adult nervous system. Glial‐specific expression of a polyglutamine (Q)‐expanded (n = 78) and also a nonexpanded (n = 27) truncated version of human ataxin‐3 led to the formation of protein aggregates and glial cell death. Behavioral changes were observed prior to cell death. This reveals that glia is susceptible to the toxic action of polyglutamine proteins. Neuronal expression of the same constructs resulted in behavioral changes similar to those resulting from glial expression but did not cause neurodegeneration. Behavioral deficits were selective and affected two analyzed fly behaviors differently. Both glial and neuronal aggregates of Q78 and Q27 appeared early in pathogenesis and, at the electron microscopic resolution, had a fibrillary substructure. This shows that a nonexpanded stretch can cause similar histological and behavioral symptoms as the expanded stretch, however, with a significant delay. © 2004 Wiley‐Liss, Inc.
Interaction with antigen‐specific T cells regulates expression of the lactate transporter MCT1 in primary rat astrocytes: Specific link between immunity and homeostasis
Authors: Korn Thomas , Magnus Tim , Jung Stefan 
Published: July 2004

AbstractMonocarboxylates like lactate are provided by astrocytes and can be used as fuel by neurons and oligodendrocytes. In an autoimmune inflammatory environment, homeostatic functions of astrocytes are incompletely understood. In primary Lewis rat astrocytes, co‐culture with MHC class II‐restricted myelin basic protein (MBP)‐specific T cells in the presence of MBP resulted in a marked upregulation of the astrocytic lactate transporter MCT1 that is to export lactate into the extracellular space. It was evident that the increase in MCT1 was triggered by T cells in an antigen‐dependent manner. The glial isoform of the glucose transporter GLUT1 was not regulated under these conditions. T‐cell blasts that had been pre‐activated by antigen and splenic antigen‐presenting cells (APCs) beforehand also led to an increase in the expression of astrocytic MCT1 after co‐culture. Resting T cells did not induce a relevant upregulation of MCT1 in astrocytes. However, resting T cells stimulated the expression of MCT1 when anti‐MHC class II antibodies, but not when anti‐MHC class I antibodies, were added to the co‐culture. Therefore, even in the presence of inactive T cells, complexation of MHC class II molecules on astrocytes might lead to the regulation of certain astrocytic transport proteins. Consistent with the in vitro experiments, an upregulation of MCT1 was observed in the spinal cord of autoimmune encephalitic rats while GLUT1 expression appeared to be unchanged. This T‐cell‐mediated regulation of MCT1 might contribute to a compensatory or protective mechanism in order to guarantee substrate pools for neurons and oligodendrocytes under inflammatory conditions. © 2004 Wiley‐Liss, Inc.
Glycogen phosphorylase isozyme pattern in mammalian retinal Müller (glial) cells and in astrocytes of retina and optic nerve
Authors: Pfeiffer‐Guglielmi Brigitte , Francke Mike , Reichenbach Andreas , Fleckenstein Burkhard , Jung Günther , Hamprecht Bernd 
Published: July 2004

AbstractMüller cells, the radially oriented dominant macroglial cells of the retina, are known to contain abundant glycogen as well as the key enzyme for its degradation, glycogen phosphorylase (GP), but the expressed isozyme pattern is unknown. To elucidate the isoform expression pattern, specific antisera directed against the brain (BB) and muscle (MM) isoforms of GP were applied to retinal sections, isolated Müller cells, and sections of the optic nerve. We show that Müller cells of rat, rabbit, guinea pig, and mouse retina exclusively express the BB isoform. Astrocytes of rat and rabbit optic nerve, as well as retina express only the BB isoform. In contrast, astrocytes in the brain and spinal cord as well as the epithelial cells of the pars caeca and of the ciliary body express both the BB and MM isoform. This result may indicate some differences in the role of glycogen in retinal macroglia and brain astrocytes, reflecting a local specialization of macroglia in the retina proper. © 2004 Wiley‐Liss, Inc.
Methods for detecting functional classifications in neuroimaging data
Authors: Bowman F. DuBois , Patel Rajan , Lu Chengxing 
Published: July 2004

AbstractData‐driven statistical methods are useful for examining the spatial organization of human brain function. Cluster analysis is one approach that aims to identify spatial classifications of temporal brain activity profiles. Numerous clustering algorithms are available, and no one method is optimal for all areas of application because an algorithm's performance depends on specific characteristics of the data.K‐means and fuzzy clustering are popular for neuroimaging analyses, and select hierarchical procedures also appear in the literature. It is unclear which clustering methods perform best for neuroimaging data. We conduct a simulation study, based on PET neuroimaging data, to evaluate the performances of several clustering algorithms, including a new procedure that builds on thekth nearest neighbor method. We also examine three stopping rules that assist in determining the optimal number of clusters. Five hierarchical clustering algorithms perform best in our study, some of which are new to neuroimaging analyses, with Ward's and the beta‐flexible methods exhibiting the strongest performances. Furthermore, Ward's and the beta‐flexible methods yield the best performances for noisy data, and the popularK‐means and fuzzy clustering procedures also perform reasonably well. The stopping rules also exhibit good performances for the top five clustering algorithms, and the pseudo‐T2and pseudo‐F stopping rules are superior for noisy data. Based on our simulations for both noisy and unscaled PET neuroimaging data, we recommend the combined use of the pseudo‐F or pseudo‐T2stopping rule along with either Ward's or the beta‐flexible clustering algorithm. Hum Brain Mapp 23:109–119, 2004. © 2004 Wiley‐Liss, Inc.
The national cancer data base report on squamous cell carcinoma of the base of tongue
Authors: Zhen Weining , Karnell Lucy H. , Hoffman Henry T. , Funk Gerry F. , Buatti John M. , Menck Herman R. 
Published: July 2004

AbstractBackground.This study provides the largest contemporary overview of presentation, care, and outcome for base of tongue squamous cell carcinoma (SCC).Methods.We extracted 16,188 cases from the National Cancer Data Base (NCDB). Chi‐square analyses were performed on selected cross‐tabulations. Observed and disease‐specific survival were used to analyze outcome.Results.Three‐quarters had advanced‐stage (III–IV) disease. Radiation therapy alone (24.5%) and combined with surgery (26.9%) were the most common treatments. Five‐year observed and disease‐specific survival rates were 27.8% and 40.3%, respectively. Poorer survival was significantly associated with older age, low income, and advanced‐stage disease. For early‐stage disease, surgery with or without irradiation had higher survival than irradiation alone. For advanced‐stage disease, surgery with irradiation had the highest survival.Conclusions.Survival rates were low for base of tongue SCC, with most deaths occurring within the first 2 years. Income, stage, and age were significant prognostic factors. In this nonrandomized series, surgery with radiation therapy offered patients with advanced‐stage disease the best survival. © 2004 Wiley Periodicals, Inc. Head Neck 26: 660–674, 2004
Methyl Homologues of Methyl Jasmonate and Methyl Dihydrojasmonate (Hedione®) from Sorbyl Alcohol
Authors: Giersch Wolfgang , Farris Iris 
Published: July 2004

AbstractTreatment of cycloalkanone dimethyl acetals 3–6 with sorbyl alcohol (=(2E,4E)‐hexa‐2,4‐dien‐1‐ol; 1) in the presence of acids afforded the novel cycloalkenones 8, 9, 11, and 13 via a domino reaction (Claisen rearrangement with intramolecular ene reaction and retro‐ene reaction). Cyclopentenone 8 was readily transformed into 14 and 15, methyl homologues of racemic methyl jasmonate (16) and methyl dihydrojasmonate (=Hedione®; 17), respectively. The organoleptic properties of 14 and 15 are also discussed.
Spirocyclic Ethers Related to Ambrox®: Synthesis and Structure‐Odor Relationships
Authors: Winter Beat 
Published: July 2004

AbstractThe seven spirocyclic ethers 4–10, related to the tricyclic odorant Ambrox ® (1) and its diastereoisomers 2 and 3, were synthesized. Their odoriferous activity/inactivity was correlated with the steric accessibility of the ether O‐atom, calculated by computer‐aided molecular modeling. The olfactory properties of the active compounds are discussed.
Diradical‐Promoted Two‐Carbon Ring‐Expansion Reactions by Thermal Isomerization: Synthesis of Functionalized Macrocyclic Ketones
Authors: Rüedi Georg , Hansen Hans‐Jürgen 
Published: July 2004

AbstractA new method for the smooth and highly efficient preparation of functionalized macrocyclic ketones has been developed. Pyrolysis of medium‐ and large‐ring 3‐vinylcycloalkanones by dynamic gas‐phase thermo‐isomerization (DGPTI) at 600–630° yielded, under insertion of a previously attached vinyl side chain by means of a 1,3‐C shift, the corresponding γ,δ‐unsaturated cycloalkanones. The yield of the two‐carbon ring‐expanded ketones greatly depended on the relative ring strains of substrate and product (5–87%, cf. Table 5). The formation of minor amounts of one‐carbon ring‐expanded cycloalkenes (<10%) can be ascribed to a subsequent decarbonylation step. A reaction mechanism involving initial cleavage of the weakest single bond in the molecule has been established (cf. Scheme 6). Recombination within the generated diradical intermediate in terminal vinylogous position led to the observed products, while reclosure gave recovered starting material. Substituents on the vinyl moiety were transferred locospecifically into the ring‐expanded products. An isopropenyl group did not significantly affect the isomerization process, whereas substrates bearing a prop‐1‐enyl group in β‐position enabled competing intramolecular H‐abstraction reactions, leading to acyclic dienones (cf. Schemes 9–11). DGPTI of the 13‐membered analogue directly yielded 4‐muscenone, which, upon hydrogenation, led to the valuable musk odorant (±)‐muscone. Increasing the steric hindrance on the vinyl moiety gave rise to diminishing amounts of the desired γ,δ‐unsaturated cycloalkanones. This novel two‐carbon ring‐expansion protocol was also successfully applied to 3‐ethynylcycloalkanones, giving rise to the corresponding ring‐expanded cyclic allenes (cf. Scheme 13).
Enantioselectivity in Odor Perception
Authors: Hölscher Bernd , Braun Norbert A. , Weber Berthold , Kappey Claus‐Hermann , Meier Manfred , Pickenhagen Wilhelm 
Published: July 2004

AbstractThe 3‐methyl‐4‐(tricyclo[5.2.1.02,6]dec‐4‐en‐8‐ylidene)butan‐2‐ols (=Fleursandol®; rac‐10), a new class of sandalwood odorants, were synthesized in their enantiomerically pure forms by use of tricyclo[5.2.1.02,6]dec‐4‐en‐8‐ones 17 and ent‐17 and (tetrahydro‐2H‐pyran‐2‐yl)‐protected 4‐bromo‐3‐methylbutan‐2‐ols 22 and ent‐22 as starting materials (Schemes 2–4). Only four of 16 possible stereoisomers of rac‐10 possess the typical, very pleasant, long‐lasting sandalwood odor (Table 1). The (2S,3R,4E,1′R,2′R,6′R,7′R)‐isomer ent‐10a is by far the most important representative, with an odor threshold of 5 μg/l in H2O.
Towards Functionalized Silicon‐Containing α‐Amino Acids: Asymmetric Syntheses of Sila Analogs of Homoserine and Homomethionine
Authors: Smith Richard J. , Bienz Stefan 
Published: July 2004

AbstractThe homoserine and homomethionine sila analogs, (R)‐HOSi(Me2)CH2CH(NH2)CO2H ((R)‐21) and (R)‐MeSCH2Si(Me2)CH2CH(NH2)CO2H ((R)‐24), respectively, were each synthesized in nine steps and in 30 and 23% overall yield, respectively, from commercially available ClSiMe2CH2Cl. The key step of both syntheses was the asymmetric α‐bromination of an Evans amide to introduce the stereogenic center of the amino acids with defined absolute configuration. While the preparation of the homomethionine analog (R)‐24 followed the expected pathway, the sila analog of homoserine, (R)‐21, was unexpectedly formed during the catalytic hydrogenation of an N3CH2‐substituted silane derivative.
γ,δ‐ and δ,ε‐Unsaturated Aldehydes from γ‐ and δ‐Lactones in One Step. Preliminary Communication
Authors: Giersch Wolfgang , Naef Ferdinand 
Published: July 2004

AbstractA one‐step transformation of γ‐ and δ‐(spiro)lactones into γ,δ‐ and δ,ε‐unsaturated aldehydes with an excess of formic acid in the vapor phase over a supported manganese catalyst is described for the first time. The scope and limitations of this new reaction are shown with different lactones as substrate, and a mechanistic rationale is proposed.
Efficient Synthesis of (−)‐(R)‐Muscone by Enantioselective Protonation
Authors: Fehr Charles , Galindo José , Farris Iris , Cuenca Ana 
Published: July 2004

AbstractA new synthesis of (−)‐(R)‐muscone ((R)‐1) by means of enantioselective protonation of a bicyclic ketone enolate as the key step (see 6→(S)‐4 in Scheme 2) is presented. The C15 macrocyclic system is obtained by ozonolysis (Scheme 7).
Comparative Infrared, Raman, and Natural‐Bond‐Orbital Analyses of King's Sultam
Authors: Hagemann Hans , Dulak Marcin , Wesolowski Tomasz A. , Chapuis Christian , Jurczak Janusz 
Published: July 2004

AbstractBy means of 1H‐NOESY‐ and Raman‐spectroscopic analyses, we experimentally demonstrated the presence of the equatorial NMe conformer of King's sultam 4b in solution, resulting from a rapid equilibrium. As a consequence, the value of the N lone‐pair anomeric stabilization should be revised to 1.5–1.6 kcal/mol. Independently from the N tilting, natural bond orbital (NBO)‐comparative analyses suggest that the S d* orbitals do not appear as primordial and stereospecific acceptors for the N lone pair. Second, the five‐membered‐ring sultams do not seem to be particularly well‐stabilized by the SC σ* orbital in the N‐substituted pseudo‐axial conformation, as opposed to an idealized anti‐periplanar situation for the six‐membered‐ring analogues. In this latter case, the other anti‐periplanar CC σ* and C(1′)H/C(2′) σ*orbitals are as important, if not more, when compared to the SC σ* participation. In the pseudo‐equatorial conformation, γ‐sultams particularly benefit from the N lone‐pair hyperconjugation with the anti‐periplanar SO1 σ* and C(2)H/C or C(1′)H/C σ* orbitals. This is also the case for δ‐sultams when the steric requirement of the N‐substituent exceeds 1.6 kcal/mol. When both axial and equatorial conformations are sterically too exacting, the N‐atom is prone to sp2 hybridization or/and conformational changes (i.e., 12c). In that case also, the mode of stereoelectronic stabilization differs from γ‐ to δ‐sultams.
Studies on the Synthesis of Trisaccharide Analogues of the Antibiotic Moenomycin A
Authors: Yang Guangbin , Hennig Lothar , Findeisen Matthias , Oehme Ramona , Giesa Sabine , Welzel Peter 
Published: July 2004

AbstractA new approach for the synthesis of moenomycin trisaccharide analogues is reported in which three monosaccharide building blocks are used and allows the introduction of different substituents at the 6‐position of unit E (Scheme 2). Furthermore, a new procedure for the introduction and manipulation of unit F is described (Scheme 3).
Synthesis of 2‐Aryl‐ and 2‐Heteroaryl‐3,5‐dimethoxy‐1,4‐benzoquinones Involving Pd‐Catalyzed Cross‐Coupling of (2,3,4,6‐Tetramethoxyphenyl)boronic Acid
Authors: Leão Lana Enio José , Carazza Fernando , Aparacida de Oliveira Rosilene 
Published: July 2004

AbstractA series of 2‐aryl‐ and 2‐heteroaryl‐substituted 3,5‐dimethoxy‐1,4‐benzoquinones (compounds 27–36) have been synthesized by cross‐coupling of (2,3,4,6‐tetramethoxyphenyl)boronic acid (2) with aromatic bromides or iodides in the presence of [Pd0(Ph3)4] and Na2CO3, followed by AgO‐promoted oxidation of the resulting biaryl compounds 17–26.
Synthesis of A/B Ring Analogs of Territrem B and Evaluation of Their Biological Activities
Authors: Zhao Jinhao , Zhao Feng , Wang Yanguang , Li Haibo , Zhang Qijun , Guénard Daniel , Ge Qiufu , Wei Erqing , Jiang Hao , Wu Yihang , Wang Lin , Jiang Hualiang , Guéritte Françoise , Wu Xiumei , Cheng Christopher H. K. , Lee Shoei‐Sheng , Zhao Yu 
Published: July 2004

AbstractTwo series of territrem B analogs, i.e., 5–10, containing both the 2‐en‐1‐one‐A‐ring and the aromatic‐E‐ring pharmacophores were designed and synthesized from jujubogenin (4a). The anti‐acetylcholinesterase (anti‐AChE), anti‐caspase‐3, and other biological activities of these territrem‐B analogs and their intermediates were assessed. Compound 9b, 22a, and 24f were shown to be weak inhibitors of AChE. None of the synthesized compounds exhibited significant inhibitory activity on caspase‐3. On the other hand, compounds 22e, 24a, 7b, and 8a showed mild cytotoxicity on cultured KB cells, with IC50 values of 2.0, 3.5, 6.5, and 14 μM, respectively. In addition, compounds 23b and 5f were active against injury arising from oxygen‐glucose deprivation.