bluuebunny/crossref_metadata_2025 huggingface dataset:
The Reaction of Diazocyclopentadienyl Compounds with Cyclomanganated Arenes as a Route to Ligand‐Appended Cymantrenes
Authors: Djukic Jean‐Pierre , Michon Christophe , Heiser Dirk , Kyritsakas‐Gruber Nathalie , de Cian André , Dötz Karl Heinz , Pfeffer Michel
Published: April 2004

The thermolysis of various cyclomanganated arenes in the presence of 5‐diazocyclopentadiene, 7‐diazoindene or 9‐diazofluorene afforded the corresponding arenes tethered with cymantrenyl, benzocymantrenyl or dibenzocymantrenyl groups in fair to good yields. This reaction implies a multi‐facetted mechanism that consists of three steps: the insertion of an alkylidene moiety into a C−Mn bond, a CAr−C bond formation and several haptotropic ring‐slippages. The coupling reaction has proven to be particularly efficient with Mn(CO)4 chelates derived from acetylarenes and nitrogen‐containing heterocycles. In one case of a 2‐phenyl‐2‐oxazoline complex, the coupling with 9‐diazofluorene yields a new η1‐dibenzocymantrene complex in which the Mn(CO)4 moiety is chelated and is part of a six‐membered metallacycle. The results of this study are mainly supported by the molecular structures of nine new complexes obtained by X‐ray diffraction analyses. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Cobalt(II), Nickel(II), Copper(II), and Zinc(II) Complexes with a p‐tert‐Butylcalix[4]arene Fitted with Phosphinoyl Pendant Arms
Authors: Videva Vladimira , Chauvin Anne‐Sophie , Varbanov Sabi , Baux Christophe , Scopelliti Rosario , Mitewa Mariana , Bünzli Jean‐Claude G.
Published: April 2004

A series of complexes of MIIX2 transition metal salts (X = ClO4, M = Co, Ni, Cu, Zn; X = Cl, M = Cu, Zn) with a calix[4]arene substituted at the lower rim {L = 5,11,17,23‐tetra‐tert‐butyl‐25,26,27,28‐tetrakis[(dimethylphosphinoyl)methoxy]calix[4]arene} are isolated and characterized. Two different stoichiometries are evidenced, 1:1 for the CoII, NiII, and CuII complexes, independently of the anion (Cl− or ClO4−), as well as for the Zn(ClO4)2 complex, while a 2:1 metal/ligand ratio is found for the complex with ZnCl2. The coordination mode and structure of the complexes are investigated by several spectroscopic and magnetochemical methods, both in the solid state and in solution. Coordination through the phosphoryl groups of the ligand is ascertained by X‐ray diffraction and IR and NMR spectroscopic data. The crystal structure of the 2:1 Zn compound (triclinic, P$\bar 1$
, Z = 2) shows the presence of the tetrametallic species Zn4L2 with three different tetrahedral Zn environments, ZnCl2O2, ZnCl3O, and ZnClO3, the latter bridging two ligand molecules. Magnetic susceptibility, EPR data, and electronic spectra are indicative of a tetrahedral arrangement of the ligands in the CoII (high‐spin d7) 1:1 complex, which is also most probably the ligand geometry in the NiII and CuII 1:1 complexes. In solution, the extent of the interaction between L and the MII ions has been determined by UV/Vis spectrophotometric titrations. The resulting stability constants for 1:1 complexes are in the range log K1 = 4.8−5.4. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
New Types of Homochiral Helical Coordination Polymers Constructed by exo‐Bidentate Binaphthol Derivatives
Authors: Wang Ruihu , Xu Lijin , Li Xingshu , Li Yueming , Shi Qian , Zhou Zhongyuan , Hong Maochun , Chan Albert S. C.
Published: April 2004

Assembly of axially chiral (S)‐2,2′‐bis(3‐pyridylmethyleneoxy)‐1,1′‐binaphthalene [(S)‐L1] and (S)‐2,2′‐bis(4‐pyridylmethyleneoxy)‐1,1′‐binaphthalene [(S)‐L2] with AgNO3 resulted in a double‐stranded helical coordination polymer encapsulating guest water molecules and a helix‐like complex with inter‐immersion clefts, respectively, in which helical chirality is due to axial chirality of the 1,1′‐bi‐2‐naphthol scaffold. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Analysis of the impact of prawn trawling on benthic species in the Great Barrier Reef Marine Park
Authors: Toscas P. J. , Faddy M. J. , Burridge C. Y.
Published: April 2004

Prawn trawling is a major fishing activity in the Great Barrier Reef Marine Park, generating millions of dollars for the Australian economy. It is important that appropriate management decisions are made to ensure the sustainability of the industry. An experimental study was conducted to quantify the recovery of seabed fauna after repeated trawling. Data from the study were composed of counts of observed benthic organisms on the seabed. The data were analysed using models based on a generalization of the simple Poisson process, which allows for over‐dispersion and under‐dispersion relative to the Poisson distribution. It was found that these models more faithfully described the data than more standard models such as the Poisson or negative binomial. It is argued that the use of inappropriate models can result in unreliable inferences, which in turn could lead to poor management decisions. Copyright © 2004 John Wiley & Sons, Ltd.
Isolation and synthesis of a new natural lactone in apple juice (Malus × domestica var. Orin)
Authors: Kitaura Taro , Endo Hirokatsu , Nakamoto Hideki , Ishihara Masakazu , Kawai Tetsuo , Nokami Junzo
Published: April 2004

A new lactone having a characteristic sweet and fruity aroma was isolated as a trace component from the juice of Malus × domestica var. Orin. The structure of the lactone was elucidated as 4,8‐dimethylnon‐7‐en‐4‐olide (1) by the spectroscopic evidences and synthesis. The chiral GC analyses of the natural and the synthesized lactones revealed that the R/S ratio of the lactone in the apple juice is 23/77. The odoriferous properties of the both enantiomers are also described. Copyright © 2004 John Wiley & Sons, Ltd.
Chemical composition of the essential oil of Cuminum cyminum L. from China
Authors: Li Rong , Jiang Zi‐Tao
Published: April 2004

The essential oil of the seeds of Cuminum cyminum L. from China was isolated by hydrodistillation in a yield of 3.8%. The chemical composition of the essential oil was examined by GC and GC–MS; 37 components, representing 97.97% of the oil, were identiﬁed. Cuminal (36.31%), cuminic alcohol (16.92%), γ‐terpinene (11.14%), safranal (10.87%), p‐cymene (9.85%) and β‐pinene (7.75%) were the major components. Copyright © 2004 John Wiley & Sons, Ltd.
Essential oils of Galeopsis pubescens and G. tetrahit from Tuscany (Italy)
Authors: Flamini Guido , Cioni Pier Luigi , Morelli Ivano
Published: April 2004

The essential oils obtained from the ﬂowering aerial parts of Galeopsis pubescens and G. tetrahit growing on Monte Amiata (Italy) have been studied. Sesquiterpenes were the main constituents of both essential oils (88.9% and 90.4%, respectively); the major compounds were germacrene D and bicyclogermacrene (about 60% and 6%, respectively). The differences between the two essential oils were mostly quantitative and were referred mainly to β‐caryophyllene (5.7% and 2.1%, respectively) and (E)‐β‐farnesene (1.1% and 5.6%). This is the ﬁrst report about the composition of essential oils from this genus. Copyright © 2004 John Wiley & Sons, Ltd.
Essential oil composition of Stachys sylvatica L. from Italy
Authors: Tirillini Bruno , Pellegrino Roberto , Bini Laura Maleci
Published: April 2004

The oil composition of inﬂorescences and leaves of Stachys sylvatica L. from Italy was analysed by GC–MS. The most abundant compounds in the oil from the inﬂorescences were germacrene D (55.2%), (E)‐β‐farnesene (9.1%) and n‐tetracosane (6.9%), whilst germacrene D (31.7%), n‐tetracosane (7.8%) and mint sulphide (6.4%) were the main compounds in the oil from the leaves. Copyright © 2004 John Wiley & Sons, Ltd.
Micromorphology of trichomes and composition of essential oil of Teucrium capitatum
Authors: Antunes Teresa , Sevinate‐Pinto Isabel , Barroso José G. , Cavaleiro Carlos , Salgueiro Lígia R.
Published: April 2004

The morphology and distribution of the glandular trichomes of Teucrium capitatum L., as well as the chemical composition of the essential oils, were studied. Important differences were found with regard to the major constituents of the essential oils of ﬁve populations of T. capitatum grown in Portugal. The oil isolated from one population was characterized by a high content of oxygenated monoterpenes (33.0%), isomenthone (7.7%) being the major constituent. Another oil from a population collected from the same region was dominated by monoterpene and sesquiterpene hydrocarbons (43.9% and 23.2%, respectively), α‐pinene (7.7%), sabinene (11.2%) and β‐pinene (10.3%) being the main compounds. The oils from the other three populations were characterized by a high content of both sesquiterpene hydrocarbons (23.0%, 32.2% and 33.2%) and oxygenated sesquiterpenes (39.7%, 23.4% and 20.4%). T‐cadinol (24.1%) and α‐cadinol (9.8%) were the major compounds in the oil from one population, whereas δ‐cadinene (7.5% and 9.8%) and E‐caryophyllene (5.4%) or α‐muurolol (6.0%) were the major constituents in the other samples. The indumentum of the vegetative and reproductive ograns from the ﬁve populations of T. capitatum, observed under scanning electron microscopy, showed the same type and distribution of glandular and non‐glandular trichomes. Since the ecological and edaphic features of the collecting sites were quite similar, the chemical polymorphism observed seems to be due to genetic factors. Copyright © 2004 John Wiley & Sons, Ltd.
Essential oil composition of ‘kewda’ (Pandanus odoratissimus) from India
Authors: Raina V. K. , Kumar Ajai , Srivastava S. K. , Syamsundar K. V. , Kahol A. P.
Published: April 2004

The chemical composition of the essential oil obtained by hydrodistillation of staminate inﬂorescences of kewda (Pandanus odoratissimus L.) has been compared with the kewda oil from the local market. Both the oils were subjected to high‐resolution GC and GC–MS, which resulted in the identiﬁcation and quantiﬁcation of 85 and 59 components, amounting to 98.7% and 98.6% of the total oils, respectively. The major components of the hydrodistilled kewda oil were 2‐phenyl ethyl methyl ether (37.7%), terpinen‐4‐ol (18.6%), α‐terpineol (8.3%) and 2‐phenyl ethyl alcohol (7.5%), whereas the major constituents of kewda oil from the local market were 2‐phenyl ethyl alcohol (33.2%), 2‐phenyl ethyl methyl ether (16.1%), benzyl benzoate (11.0%), viridine (8.8%) and germacrene B (8.3%). Copyright © 2004 John Wiley & Sons, Ltd.
Chemical composition of the volatile oil from the pericarp (husk) of large cardamom (Amomum subulatum Roxb.)
Authors: Pura Naik J. , Jagan Mohan Rao L. , Mohan Kumar T. M. , Sampathu S. R.
Published: April 2004

The large cardamom pericarp (husk) yielded 0.18% volatile oil by Clevenger hydrodistillation method. This oil was analysed for physical parameters viz. speciﬁc gravity (0.9148), refractive index (1.4733) and optical rotation (−7.700). The volatile oil was subjected to GC–MS analysis and 37 compounds were identiﬁed, constituting > 98% of the total oil. The major compounds characterized were 1,8‐cineole (38.7%), β‐pinene (13.6%), α‐terpineol (12.6%), spathulenol (8.3%), 4‐terpineol (4.5%), germacrene‐D (3.0%), α‐pinene (2.8%) and β‐selinene (2.7%). GC and GC–MS data revealed that the 1,8‐cineol content was less than 50% when compared with the seed oil. Copyright © 2004 John Wiley & Sons, Ltd.
Convenient syntheses of iso‐methyl‐branched long‐chain aliphatic aldehydes, known to contribute signiﬁcantly to meat ﬂavour
Authors: Yuasa Yoshifumi , Tsuruta Haruki
Published: April 2004

Convenient syntheses of iso‐methyl‐branched long‐chain aliphatic aldehydes, which are common meat ﬂavour compounds, are described. The Grignard reaction of isoamyl or isobutylmagnesium bromide and ω‐bromo‐α‐alkanols in the presence of a catalytic amount of dilithium tetrachlorocuprate gave iso‐methylalkanols. The oxidation of the alkanols using sodium hypochlorite in the presence of a catalytic amount of 4‐benzoyloxy‐2,2,6,6‐tetramethylpiperidine‐N‐oxide (BzOTEMPO) gave the corresponding iso‐methylalkanals in high yield. Copyright © 2004 John Wiley & Sons, Ltd.
Anatomy of option features in convertible bonds
Authors: Lau Ka Wo , Kwok Yue Kuen
Published: April 2004

Several earlier theoretical studies on the optimal issuer's calling policy of a convertible bond suggest that the issuer should call the bond as soon as the conversion value exceeds the call price. However, empirical studies on actual cases of calling by convertible bond issuers reveal that firms “delayed” calling their convertible bonds until the conversion value well exceeded the call price. In this paper, we construct valuation algorithms that price risky convertible bonds with embedded option features. In particular, we examine the impact of the soft call and hard call constraints, notice period requirement and other factors on the optimal issuer's calling policy. Our results show that the critical stock price at which the issuer should optimally call the convertible bond depends quite sensibly on these constraints and requirements. The so‐called “delayed call phenomena” may be largely attributed to the underestimation of the critical call price due to inaccurate modeling of the contractual provisions. © 2004 Wiley Periodicals, Inc. Jrl Fut Mark 24:513–532, 2004
Contract modifications and the basis behavior of live cattle futures
Authors: Newsome James E. , Wang George H. K. , Boyd M. E. , Fuller Marty J.
Published: April 2004

The purpose of this study was to assess the basis behavior of the Live Cattle Futures contract at the Chicago Mercantile Exchange (CME) before and after the 1995 contract changes. Additionally, an alternative method of basis calculation utilizing weighted mean futures prices versus settlement futures prices was compared to determine which method provides a better representation of the basis level.

Within a regression model with heteroskedascity error framework, we found that the level of nearby basis in the period after June 1995 has shifted lower and the average monthly open interest of net commercial long positions has substantially increased after the contract modifications. These empirical results are consistent with the notion that more long activity entered the market in response to the contract modifications. Additionally, an alternative (new) measure of basis calculation (cash price minus weighted mean futures price) produced similar results to two other commonly used measures. In conclusion, the 1995 contract changes have neither increased nor decreased the volatility of live cattle basis. © 2004 Wiley Periodicals, Inc. Jrl Fut Mark 24:557–590, 2004
The antiapoptotic effect of guanosine is mediated by the activation of the PI 3‐kinase/AKT/PKB pathway in cultured rat astrocytes
Authors: Di Iorio Patrizia , Ballerini Patrizia , Traversa Ugo , Nicoletti Ferdinando , D'Alimonte Iolanda , Kleywegt Sonya , Werstiuk Eva S. , Rathbone Michel P. , Caciagli Francesco , Ciccarelli Renata
Published: April 2004

Guanosine has many trophic effects in the CNS, including the stimulation of neurotrophic factor synthesis and release by astrocytes, which protect neurons against excitotoxic death. Therefore, we questioned whether guanosine protected astrocytes against apoptosis induced by staurosporine. We evaluated apoptosis in cultured rat brain astrocytes, following exposure (3 h) to 100 nM staurosporine by acridine orange staining or by oligonucleosome, or caspase‐3 ELISA assays. Staurosporine promoted apoptosis rapidly, reaching its maximal effect (∼ 10‐fold over basal apoptotic values) in 18–24 h after its administration to astrocytes. Guanosine, added to the culture medium for 4 h, starting from 1 h prior to staurosporine, reduced the proportion of apoptotic cells in a concentration‐dependent manner. The IC50 value for the inhibitory effect of guanosine is 7.5 × 10−5 M. The protective effect of guanosine was not affected by inhibiting the nucleoside transporters by propentophylline, or by the selective antagonists of the adenosine A1 or A2 receptors (DPCPX or DMPX), or by an antagonist of the P2X and P2Y purine receptors (suramin). In contrast, pretreatment of astrocytes with pertussis toxin, which uncouples Gi‐proteins from their receptors, abolished the antiapoptotic effect of guanosine. The protective effect of guanosine was also reduced by pretreatment of astrocytes with inhibitors of the phosphoinositide 3‐kinase (PI3K; LY294002, 30 μM) or the MAPK pathway (PD98059, 10 μM). Addition of guanosine caused a rapid phosphorylation of Akt/PKB, and glycogen synthase kinase‐3β (GSK‐3β) and induced an upregulation of Bcl‐2 mRNA and protein expression. These data demonstrate that guanosine protects astrocytes against staurosporine‐induced apoptosis by activating multiple pathways, and these are mediated by a Gi‐protein‐coupled putative guanosine receptor. © 2004 Wiley‐Liss, Inc.
New oligodendrocytes are generated after neonatal hypoxic‐ischemic brain injury in rodents
Authors: Zaidi Aliya U. , Bessert Denise A. , Ong Jennifer E. , Xu Haiyan , Barks John D.E. , Silverstein Faye S. , Skoff Robert P.
Published: April 2004

Neonatal hypoxic‐ischemic (HI) white matter injury is a major contributor to chronic neurological dysfunction. Immature oligodendrocytes (OLGs) are highly vulnerable to HI injury. As little is known about in vivo OLG repair mechanisms in neonates, we studied whether new OLGs are generated after HI injury in P7 rats. Rats received daily BrdU injections at P12–14 or P21–22 and sacrificed at P14 to study the level of cell proliferation or at P35 to permit dividing OLG precursors to differentiate. In P14 HI‐injured animals, the number of BrdU+ cells in the injured hemisphere is consistently greater than controls. At P35, sections were double‐labeled for BrdU and markers for OLGs, astrocytes, and microglia. Double‐labeled BrdU+/myelin basic protein+ and BrdU+/carbonic anhydrase+ OLGs are abundant in the injured striatum, corpus callosum, and the infarct core. Quantitative studies show four times as many OLGs are generated from P21–35 in HI corpora callosa than controls. Surprisingly, the infarct core contains many newly generated OLGs in addition to hypertrophied astrocytes and activated microglia. These glia and non‐CNS cells may stimulate OLG progenitor proliferation or induce their migration. At P35, astrogliosis and microgliosis are dramatic ipsilaterally but only a few microglia and some astrocytes are BrdU+. This finding indicates microglial and astrocytic hyperplasia occurs shortly after HI but before the P21 BrdU injections. Although the neonatal brain undergoes massive cell death and atrophy the first week after injury, it retains the potential to generate new OLGs up to 4 weeks after injury within and surrounding the infarct. © 2004 Wiley‐Liss, Inc.
Volume‐regulated anion conductance in cultured rat cerebral astrocytes requires calmodulin activity
Authors: Olson James E. , Li Guang‐Ze , Wang Ling , Lu Luo
Published: April 2004

We examined the calmodulin dependence of anion channel activation during hypo‐osmotic swelling in rat cerebral astrocytes. Control cells bathed in iso‐osmotic (290 mOsm) phosphate‐buffered saline (PBS) and recorded using a patch electrode containing 140 mM KCl increased membrane conductance threefold over basal levels after 12 min in hypo‐osmotic (200 mOsm) PBS. Cells injected with monoclonal anticalmodulin antibody demonstrated no increase in membrane conductance during a subsequent exposure to hypo‐osmotic PBS. In contrast, cells iontophoretically injected with monoclonal antiglial fibrillary acidic protein antibody or with anticalmodulin antibody absorbed with an excess of free calmodulin demonstrated an increase in conductance during hypo‐osmotic exposure similar to that of control cells. Conductance in iso‐osmotic conditions was unchanged by antibody injection. Similar results were obtained when using patch electrode and bath solutions containing chloride as the only cell permeant ion, indicating a calmodulin‐dependent anion current is activated with this degree of hypo‐osmotic treatment. Western blots confirmed the specificity of the anticalmodulin and antiglial fibrillary acidic protein antibodies used in this study for proteins of 17 and 51 kD, respectively. In addition, in vitro studies demonstrated inhibition of the calmodulin‐dependent activation of phosphodiesterase by the anticalmodulin antibody. Thus, binding of this antibody to calmodulin causes functional inhibition of calmodulin activity. No change in the intensity or cellular distribution of calmodulin immunostaining was observed during 30 min of hypo‐osmotic exposure. However, increased immunostaining for activated calmodulin kinase IIα was observed after 10 min of hypo‐osmotic exposure, suggesting initiation of calmodulin‐dependent processes by cell swelling. The data indicate calmodulin activity is critical for activation of volume‐regulated anion channels in rat cerebral astrocytes. © 2004 Wiley‐Liss, Inc.
Adenosine A3 receptor‐induced CCL2 synthesis in cultured mouse astrocytes
Authors: Wittendorp Maria C. , Boddeke Hendrikus W.G.M. , Biber Knut
Published: April 2004

During neuropathological conditions, high concentrations of adenosine are released, stimulating adenosine receptors in neurons and glial cells. It has recently been shown that stimulation of adenosine receptors in glial cells induces the release of neuroprotective substances such as NGF, S‐100β, and interleukin‐6 (IL‐6). It has therefore been suggested that glial adenosine receptors are involved in neuroprotection. Since recently neuroprotective effects of the chemokine CCL2 (formerly known as MCP‐1) have been reported, we investigated the possible effect of adenosine receptor stimulation on glial CCL2 synthesis. Here we show that stimulation of cultured murine astrocytes with the selective adenosine A3 receptor agonist 2‐chloro‐N6‐(3‐iodobenzyl)‐N‐methyl‐5′‐carbamoyladenosine (CL‐IB‐MECA) induced the release of CCL2. Specific ligands for adenosine A1 or A2 receptors did not affect CCL2 release. Furthermore, CL‐IB‐MECA‐induced CCL2 synthesis was inhibited by adenosine A3 receptor antagonists. These results show that stimulation of adenosine A3 receptors in astrocytes induced the release of CCL2, thus supporting the assumption that adenosine receptors in glial cells regulate the synthesis of neuroprotective substances. © 2004 Wiley‐Liss, Inc.
Neck dissection in the combined‐modality therapy of patients with locoregionally advanced head and neck cancer
Authors: Argiris Athanassios , Stenson Kerstin M. , Brockstein Bruce E. , Mittal Bharat B. , Pelzer Harold , Kies Merrill S. , Jayaram Prathima , Portugal Louis , Wenig Barry L. , Rosen Fred R. , Haraf Daniel J. , Vokes Everett E.
Published: April 2004

Purpose.

The purpose of this study was to evaluate the role of neck lymph node (ND) in the combined dissection modality therapy for locoregionally advanced head and neck.

Methods.

We identified patients with N2–N3 head and neck cancers who were enrolled in three consecutive multicenter phase II studies of concurrent chemoradiotherapy utilizing 5‐fluorouracil and hydroxyurea on an alternate‐week schedule with radiotherapy twice daily plus either cisplatin (C‐FHX) or paclitaxel (T‐FHX). Patients with unknown primary tumors, nasopharyngeal or paranasal sinus primaries, nonsquamous histology, progression or death during therapy, or incomplete therapy were excluded.

Results.

A total of 131 patients were analyzed. Seventy‐nine percent had N2 stage. ND was performed in 92 patients (70%), either prior to enrollment (n = 31) or after chemoradiotherapy (n = 61). With a median follow‐up of 4.6 years, the 5‐year locoregional and neck progression‐free survival (PFS) rates were higher in patients with ND versus patients without ND: 88% versus 74% (p = .02) and 99% versus 82% (p = .0007). respectively; there was also a trend toward improved overall survival (OS) with ND, but PFS and distant PFS were comparable. In the subset of patients with N3 disease, ND was associated not only with better locoregional control but also with improved distant PFS. However, in patients with clinical complete response (n = 92), no significant differences in PFS (68% vs 75% at 5 years, p = .53) or any other survival parameters with or without ND were observed.

Conclusions.

ND improves neck control and is required for patients with clinically residual disease or N3 neck cancer but has no significant impact on the outcome of patients with N2 stage disease who are rendered clinically disease‐free with intensive concurrent chemoradiotherapy.© 2003 Wiley Periodicals, Inc. Head Neck 26: 447–455, 2004
Overexpression of p27BBP in head and neck carcinomas and their lymph node metastases
Authors: Rosso Paola , Cortesina Giorgio , Sanvito Francesca , Donadini Alessandra , Di Benedetto Barbara , Biffo Stefano , Marchisio Pier Carlo
Published: April 2004

Background.

p27BBP is a regulator of ribosome assembly and an essential nuclear and cytoplasmic component of eukaryotes.

Methods.

We investigated the immunochemical distribution of p27BBP in head and neck carcinomas, in the associated normal mucosa, and in regional lymph nodes.

Results.

p27BBP is detectable in mucosal cells but is overexpressed in carcinomas, highly concentrated in large polymorphous nucleoli, and even larger and more evident in lymph node metastatic foci. Western blotting confirms increased p27BBP in carcinomas versus normal mucosa and also in metastatic versus normal lymph nodes. The overexpression of p27BBP corresponds to mRNA upregulation in carcinomas. Unexpectedly, a 52‐kDa band specifically reacting with antibodies to p27BBP was observed in several carcinomas.

Conclusions.

p27BBP alterations are common events in the transition to malignancy and are probably involved in squamous carcinoma progression. Immune reagents raised to p27BBP may provide additional diagnostic tools for surgical pathology of tumor boundaries and lymph nodes. The 52‐kDa band may represent an abnormal form of p27BBP expressed by transformed airway epithelia. © 2004 Wiley Periodicals, Inc. Head Neck 26: 408–417, 2004
Differential contributions of dorsal hippocampal subregions to memory acquisition and retrieval in contextual fear‐conditioning
Authors: Lee Inah , Kesner Raymond P.
Published: April 2004

The hippocampus is an essential neural structure in developing contextual memory in a situation in which rapid development of associative learning should occur. We tested a subregion‐specific contribution in the hippocampus to memory acquisition and retrieval, using the contextual fear‐conditioning paradigm. The current results suggest that all three subregions (i.e., CA3, CA1, and dentate gyrus) of the hippocampus contribute to rapid acquisition of contextual memory in the initial phase of acquisition. The involvement of CA3 seems to be important at the earliest stage of acquisition, presumably for developing instant representation of a context. The role of CA3, however, was minimal in retrieving contextual memory after a long time period (i.e., 24 h), whereas the other subregions (i.e., CA1 and dentate gyrus) were critically involved. The results indicate time‐dependent differential contributions of the hippocampal subregions to memory acquisition and retrieval in contextual fear‐conditioning. © 2004 Wiley‐Liss, Inc.
Amygdala‐kindling induces alterations in neuronal density and in density of degenerated fibers
Authors: von Bohlen und Halbach Oliver , Schulze Katrin , Albrecht Doris
Published: April 2004

Kindling is characterized by a progressive intensification of seizure activity culminating in generalized seizures following repeated administration of an initially subconvulsive electrical or chemical stimulus. Since it is known that epilepsy induces morphological alterations in the limbic system, we examined the neuropathological consequences of kindling with a sensitive silver‐staining method for the visualization of damaged neurons and Nissl staining for the estimation of the neuronal densities in different limbic areas. Wistar rats implanted with electrodes in the left basolateral nucleus were stimulated until 15 consecutive stage V seizures (scale of Racine). Amygdala‐kindled animals had reduced cell density in the amygdala and increased density of fragments of degenerated axons. Reduced neuronal density and the occurrence of degenerated axons in kindled animals were more prominent in the ipsilateral than in the contralateral hemisphere. In addition, more degenerated axons were found in cortical structures of kindled than sham‐operated animals. These results indicate that kindling induced morphological alterations that were not restricted to either the ipsilateral hemisphere or the stimulated region. These morphological changes might be responsible for the emotional and behavioral disturbances that can accompany epilepsy. © 2004 Wiley‐Liss, Inc.
Expression, interaction, and proteolysis of death‐associated protein kinase and p53 within vulnerable and resistant hippocampal subfields following seizures
Authors: Araki Tomohiro , Shinoda Sachiko , Schindler Clara K. , Quan‐Lan Jing , Meller Robert , Taki Waro , Simon Roger P. , Henshall David C.
Published: April 2004

Death‐associated protein (DAP) kinase is a novel regulator of cell death whose in vivo target(s) and role in neuronal cell death remain uncertain. Since DAP kinase has been implicated in p53‐mediated apoptosis, a pathway activated following epileptic brain injury, we examined the relationship between DAP kinase and p53 following seizures. Rats underwent brief (40‐min) seizures evoked by intraamygdala kainic acid, which caused the death of ipsilateral CA3 neurons while preserving the contralateral CA3 subfield. Seizures caused a small decline in levels of the ∼160‐kD DAP kinase within injured ipsilateral hippocampus, commensurate with the appearance of an ∼60‐kD fragment, and proteolysis of the p53 inhibitor, murine double minute gene 2 (MDM2). Expression of p53 increased within the ipsilateral hippocampus, and DAP kinase was detected within p53 immunoprecipitates. In contrast, DAP kinase and MDM2 were not proteolyzed within the seizure damage‐resistant contralateral hippocampus. Furthermore, DAP kinase and p53 did not interact within the contralateral hippocampus, and p53 cellular localization redistributed from the nucleus to cytoplasm commensurate with p53 proteolysis. These data suggest that DAP kinase may be involved in the p53 pathway during seizure‐induced neuronal death. © 2004 Wiley‐Liss, Inc.
Neuregulin1 downregulates postsynaptic GABAa receptors at the hippocampal inhibitory synapse
Authors: Okada Masayoshi , Corfas Gabriel
Published: April 2004

The growth factor neuregulin 1 (NRG1) has been proposed to contribute to the formation and maturation of neuromuscular and interneuronal synapses by upregulating the expression of specific neurotransmitter receptor subunits. In the present report, we show that, in the hippocampus, NRG1 is expressed in a pattern suggesting that it regulates synapse development in the CA1 region. However, in contrast to what has been shown in other synapses, NRG1 reduces the expression of γ‐aminobutyric acid (GABA)A receptors α subunits in hippocampal slices, and the mean amplitude of GABAergic miniature inhibitory postsynaptic currents (IPSCs) in hippocampal CA1 pyramidal neurons, without affecting IPSC kinetics or frequency. These effects of NRG1 occur without concomitant changes in glutamate receptors and other synaptic proteins. We propose that the role of NRG1 in the formation and maturation in the hippocampal inhibitory synapse is downregulation, rather than upregulation, of receptor subunit expression. These results suggest that NRG1 may contribute to the reduction in GABAergic synaptic activity in hippocampal CA1 pyramidal neurons that normally occurs during early postnatal development, and that alterations in NRG1 signaling in the hippocampus may contribute to schizophrenia and epilepsy. © 2004 Wiley‐Liss, Inc.
Stress generates emotional memories and retrograde amnesia by inducing an endogenous form of hippocampal LTP
Authors: Diamond David M. , Park Collin R. , Woodson James C.
Published: April 2004

Models of the neurobiology of memory have been based on the idea that information is stored as distributed patterns of altered synaptic weights in neuronal networks. Accordingly, studies have shown that post‐training treatments that alter synaptic weights, such as the induction of long‐term potentiation (LTP), can interfere with retrieval. In these studies, LTP induction has been relegated to the status of a methodological procedure that serves the sole purpose of disturbing synaptic activity in order to impair memory. This perspective has been expressed, for example, by Martin and Morris (2002: Hippocampus 12:609–636), who noted that post‐training LTP impairs memory by adding “behaviorally meaningless” noise to hippocampal neural networks. However, if LTP truly is a memory storage mechanism, its induction should represent more than just a means with which to disrupt memory. Since LTP induction produces retrograde amnesia, the formation of a new memory should also produce retrograde amnesia. In the present report, we suggest that one type of learning experience, the storage of fear‐related (i.e., stressful) memories, is consistent with this prediction. Studies have shown that stress produces potent effects on hippocampal physiology, generates long‐lasting memories, and induces retrograde amnesia, all through mechanisms in common with LTP. Based on these findings, we have developed the hypothesis that a stressful experience generates an endogenous form of hippocampal LTP that substitutes a new memory representation for preexisting representations. In summary, our hypothesis implicates the induction of endogenous synaptic plasticity by stress in the formation of emotional memories and in retrograde amnesia. © 2004 Wiley‐Liss, Inc.
Ontogeny of seizure‐induced increases in BDNF immunoreactivity and TrkB receptor activation in rat hippocampus
Authors: Danzer Steve C. , He Xiaoping , McNamara James O.
Published: April 2004

The present work tested the hypothesis that the anatomic and developmental patterns of status epilepticus‐induced increases of brain‐derived neurotrophic factor (BDNF) protein coincided with status epilepticus‐induced increases of phospho‐Trk immunoreactivity, a measure of TrkB receptor activation, in rat hippocampus. In P22 rats, robust increases of phospho‐Trk immunoreactivity were detected in the mossy fiber pathway of the hippocampus one day following kainate‐induced status epilepticus. Conversely, no change in phospho‐Trk immunoreactivity was detected in P8 or P14 rats. In P17 rats, intermediate levels of increased phospho‐Trk immunoreactivity were detected, again in the mossy fiber pathway. Like phospho‐Trk immunoreactivity, marked increases of BDNF immunoreactivity were detected in the mossy fiber pathway of P22 but not P14 rats. Dissociations were found in P17 rats following status epilepticus in that striking increases of BDNF, but not phospho‐Trk immunoreactivity were detected. Immunoprecipitation and Western blot analyses of hippocampal extracts after status epilepticus showed increased phospho‐TrkB, but not TrkB immunoreactivity in P22 rats, thereby confirming and extending the immunohistochemical findings. While most of the findings support the hypothesis, important dissociations among individual animals at P17 were identified. Together the findings are consistent with the proposal that status epilepticus‐induced increase of BDNF content in the mossy fibers is necessary, but not sufficient, to effect activation of TrkB, as revealed by phospho‐Trk immunoreactivity. Furthermore, these results provide the first characterization of seizure‐induced increases in BDNF protein and TrkB receptor activation in developing animals. © 2004 Wiley‐Liss, Inc.
Intraseptal infusion of the cholinergic agonist carbachol impairs delayed‐non‐match‐to‐sample radial arm maze performance in the rat
Authors: Bunce Jamie G. , Sabolek Helen R. , Chrobak James J.
Published: April 2004

The medial septal nucleus regulates the physiology and emergent functions (e.g., memory formation) of the hippocampal formation. This nucleus is particularly rich in cholinergic receptors and is a putative target for the development of cholinomimetic cognitive enhancing drugs. A large number of studies have demonstrated that direct intraseptal drug infusions can produce amnestic or promnestic effects. While a few studies have examined the effects of direct intraseptal infusion of cholinomimetics on spatial memory performance (with drug “on‐board” at the time of testing), the effects of post‐acquisition infusions have not been assessed. We hypothesized that post‐acquisition intraseptal infusion of cholinomimetics, by promoting hippocampal theta and suppressing the occurrence of hippocampal sharp waves, may disrupt the long‐term retention and consolidation of memory. The present study examined the effects of intraseptal infusion of the cholinergic agonist carbachol in a delayed‐non‐match‐to‐sample radial maze task. Treatments were administered immediately following (within 1 min) the sample session with a retention session 2 h later. Carbachol infusions (12.5–125 ng in 0.5 μl) produced a linear dose‐dependent decrease in correct entries and increase in retroactive errors, without any change in proactive errors or latency‐per‐choice. These findings suggest that post‐acquisition intraseptal cholinergic treatments can produce amnesia. These findings are discussed with regard to multi‐stage models of hippocampal‐dependent memory formation and the further development of therapeutic strategies in the treatment of mild cognitive impairment as well as age‐related cognitive decline and Alzheimer's dementia. © 2004 Wiley‐Liss, Inc.
Effect of early isolation on the synaptic function in the dentate gyrus and field CA1 of the guinea pig
Authors: Bartesaghi Renata
Published: April 2004

We previously reported that neonatal isolation shapes neuron morphology remarkably in the dentate gyrus and hippocampus of the guinea pig, a precocial rodent whose brain is at an advanced stage of maturation at birth. The aim of the present work was to investigate the effects of early isolation on the physiology of the hippocampal trisynaptic circuit. Male and female guinea pigs were assigned at 6–7 days of age to either a social or an isolated environment. After 90–100 days, the animals were anesthetized and electrophysiological experiments were carried out. The monosynaptic response evoked by medial perforant path stimulation in the dentate gyrus (DG) and the following response trisynaptically evoked in field CA1 by the DG‐CA3 system were evaluated with several stimulus protocols: (1) current source‐density (CSD) analysis; (2) input/output function; (3) paired‐pulse potentiation (PPP); and (4) long‐term potentiation (LTP). Isolated animals exhibited a reduction in the magnitude of the current sinks in the middle molecular layer and granule cell layer of the DG and in the input/output function of the granule cell population excitatory postsynaptic potential (EPSP) and population spike (PS) over a wide range of stimuli. The latter effect was larger in males. The ratio between the PS and EPSP of the granule cells was reduced in isolated compared to control males, but the opposite occurred in females. Isolation affected PPP of the granule cell response in males only, causing a larger facilitation of the PS. No isolation‐related effects were found in the magnitude of the LTP of the DG response in either sex. Isolated animals exhibited a reduction in the current sinks in stratum radiatum and stratum pyramidale of field CA1 and in the input/output function of the EPSP and PS of field CA1. These effects were larger in males. The results show that early isolation causes a reduction in the synaptic function of the DG‐CA3‐CA1 system, driven by perforant path volleys. The isolation‐induced impairment in signal processing along the hippocampal network suggests that the outcome of early isolation may be an impairment in the memory functions in which the entorhinal‐hippocampal system plays a key role. © 2004 Wiley‐Liss, Inc.
Pharmacological dissection of calcium channel subtype‐related components of strontium inflow in large mossy fiber boutons of mouse hippocampus
Authors: Tokunaga Takashi , Miyazaki Kenichi , Koseki Makoto , Mobarakeh Jalal Izadi , Ishizuka Toru , Yawo Hiromu
Published: April 2004

Several subtypes of voltage‐dependent calcium channels (VDCCs) are present in the presynaptic terminals. In the mammalian hippocampus, P/Q‐, N‐, and R‐ but not L‐type VDCCs are involved in the fast transmitter release from large mossy fiber (MF) boutons, which are associated with CA3 pyramidal cell dendrites. We investigated whether L‐type VDCCs are indeed absent in these large MF boutons. With the use of Sr2+ as the Ca2+ substitute, the stimulus‐evoked Sr2+ increment (Δ[Sr2+]pre) was evaluated fluorometrically. Δ[Sr2+]pre appeared to be proportional to Sr2+ inflow through VDCCs and was specifically attenuated by conventional VDCC subtype‐selective antagonists. The P/Q‐type selective ω‐agatoxin IVA (AgTxIVA) blocked Δ[Sr2+]pre with an IC50 of 28 nM and by 30–35% at its maximum effective concentration of 0.5 μM. The N‐type selective ω‐conotoxin GVIA (CgTxGVIA) blocked Δ[Sr2+]pre with an IC50 of 15 nM and by 20–25% at its maximum effective concentration of 1 μM. The R‐type selective SNX‐482 blocked Δ[Sr2+]pre with an IC50 of 79 nM and by 20–25% at its maximum effective concentration of 1 μM. The effects of these toxins did not overlap at their maximum effective concentrations and about 70–80% of Δ[Sr2+]pre was blocked by the simultaneous exposure to these toxins. Δ[Sr2+]pre component that is resistant to AgTxIVA, CgTxGVIA, and SNX‐482 was significantly potentiated by an L‐type agonist, (S)‐(−)‐Bay K8644, and attenuated by an L‐type antagonist, nimodipine, suggesting that L‐type VDCCs are present in large MF terminals. The L‐type agonist, (±)‐Bay K8644, also potentiated Sr2+ inflow into individual boutons identified as large MF boutons under confocal microscopy. Almost similar results were observed for Ca2+ inflow‐dependent fluorescence increments. L‐type VDCCs appear to be present in large MF boutons and mediate a substantial Ca2+ inflow into presynaptic terminals during action potentials. © 2004 Wiley‐Liss, Inc.
Co‐expression of calretinin and γ‐aminobutyric acid in neurons of the entorhinal cortex of the common marmoset monkey
Authors: Pothuizen Helen H.J. , Feldon Joram , Jongen‐Rêlo Ana L.
Published: April 2004

The γ‐aminobutyric acid (GABA)‐containing interneuron population in the entorhinal cortex has been shown to consist of several subpopulations. In addition to GABA, these neurons contain another neurochemical substance, such as a neuropeptide or a calcium binding protein. In the present study, we examined the co‐localization of calretinin and GABA in the entorhinal cortex of the common marmoset Callithrix jacchus, a New World monkey. Although the function of calretinin remains unclear, there are indications that it might have a protective role against cell death in a number of neuropathological diseases. Furthermore, it might have a regulatory role in the neurotransmission of GABAergic neurons. In contrast to the rat brain, sparse data exist regarding the degree of co‐expression of these two markers in the monkey brain. Using immunofluorescence and confocal laser scanning microscopy, we found that an average of 56% of the calretinin‐positive neurons in the monkey entorhinal cortex contained GABA, whereas about 27% of the GABA‐positive neurons co‐expressed calretinin. Interestingly, these numbers were higher in the superficial layers of the entorhinal cortex in comparison with the deep layers. However, no differences were found in co‐localization percentages between the different entorhinal subfields. In general, the degree of co‐localization was higher in comparison to findings in the rat entorhinal cortex. The higher amount of co‐localization observed in the present study might reflect species differences between the primate and the non‐primate brain. © 2004 Wiley‐Liss, Inc.
Progenitor cells from the CA3 region of the embryonic day 19 rat hippocampus generate region‐specific neuronal phenotypes in vitro
Authors: Shetty Ashok K.
Published: April 2004

Progenitor cells that endure in different regions of the CNS after the initial neurogenesis can be expanded in culture and used as a source of donor tissue for grafting in neurodegenerative diseases. However, the proliferation and differentiation characteristics of residual neural progenitor cells from distinct regions of the CNS are mostly unknown. This study elucidated the characteristics of progenitor cells that endure in the CA3 region of the hippocampus after neurogenesis, by in vitro analyses of cells that are responsive to epidermal growth factor (EGF) or fibroblast growth factor‐2 (FGF‐2) in the embryonic day 19 (E19) rat hippocampus. Isolated cells from the E19 CA3 region formed neurospheres in the presence of either EGF or FGF‐2, but the yield of neurospheres was greater with FGF‐2 exposure. Differentiation cultures revealed a greater yield of neurons from FGF‐2 neurospheres (60%) than from EGF neurospheres (35%). Exposure to brain‐derived neurotrophic factor (BDNF) enhanced the yield of neurons from EGF neurospheres but had no consequence on FGF‐2 neurospheres. A large number of neurons from EGF/FGF‐2 neurospheres demonstrated clearly palpable morphological features of CA3 pyramidal neurons and lacked γ‐aminobutyric acid (GABA) expression. However, a fraction of neurons (17–20%) from EGF/FGF‐2 neurospheres expressed GABA, and exposure to BDNF increased the number of GABAergic neurons (30%) from EGF neurospheres. Neurons from EGF/FGF‐2 neurospheres also contained smaller populations of calbindin‐ and calretinin‐positive interneuron‐like cells. Thus, progenitor cells responsive to FGF‐2 are prevalent in the CA3 region of the E19 rat hippocampus and give rise to a greater number of neurons than progenitor cells responsive to EGF. However, both FGF‐2‐ and EGF‐responsive progenitor cells from E19 CA3 region are capable of giving rise to CA3 field‐specific phenotypic neurons. These results imply that progenitor cells that persist in the hippocampus after neurogenesis remain regionally restricted and hence retain their ability to give rise to region‐specific phenotypic neurons even after isolation and expansion in vitro. © 2004 Wiley‐Liss, Inc.