bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the gender dimensions of reconstruction processes post‐hurricane Mitch
Authors: Bradshaw Sarah
Published: September 2002

The paper will consider the reconstruction process in Nicaragua post hurricane Mitch. First, the success of civil society co‐ordinations at promoting common people‐centred agendas will be highlighted and contrasted with the difficulties they have faced in becoming gender inclusive spaces. Second, the extent to which the official rhetoric they helped to promote has been translated into reality is examined, suggesting that on the ground projects remain at best ‘women‐centred’. Copyright © 2002 John Wiley & Sons, Ltd.
Poverty and lone parenthood: the case of Iran
Authors: Doostgharin Taghi
Published: September 2002

This study examined the poverty and the new family forms in Iran. Data collected from different resources in Iran are used to examine the determinants of welfare participation among female single parents. Results indicate that in Iran only families on very low incomes receive any welfare assistance, and there is neither universal family allowance, nor any housing benefit or maternity benefit. In other words, life on welfare in Iran is an acceptable option only to the extremely poor lone mother and offers a life only at the margin of society. In fact for the majority of these lone mothers there are very few areas of employment open to them and those that are tend to have very low wages. Copyright © 2002 John Wiley & Sons, Ltd.
The new EU ACP partnership agreement
Authors: Dearden Stephen , Mira Salama Clara
Published: September 2002

This article reviews and assesses the recent Cotonou Partnership Agreement between the ACP group of developing countries and the EU. It places the Agreement in the context of the EU's commitment to refocusing its development policy and reforming its aid administration. It emphasises the innovative elements of the Agreement that set it apart from its Lome predecessors—the intention to move to reciprocal regional free trade agreements; the emphasis upon good governance; the rule of law and human rights; the enhanced role for non‐State actors and the private sector and the adoption of a rolling programme of aid provision. Copyright © 2002 John Wiley & Sons, Ltd.
Evaluating European Union promotion of human rights, democracy and good governance: towards a participatory approach
Authors: Crawford Gordon
Published: September 2002

Following an examination of European Union (EU) rhetoric on promoting human rights and democracy in third countries, this article focuses on how its practice can best be evaluated. It analyses recent evaluation studies of European Community (EC) democracy programmes in different regions, but finds that methodological shortcomings restrict their value. Thus, an alternative evaluation methodology is proposed. This is based on a participatory approach in which informed local actors would play a key role in assessing EC efforts. Advantages include a more rigorous critique, with lessons learnt integrated into revised programmes characterised by greater domestic control and authorship, as befits the nature of democratization. Copyright © 2002 John Wiley & Sons, Ltd.
Double arterial phase dynamic MRI with sensitivity encoding (SENSE) for hypervascular hepatocellular carcinomas
Authors: Yoshioka Hiroshi , Takahashi Nobuyuki , Yamaguchi Masayuki , Lou Douqiang , Saida Yukihisa , Itai Yuji
Published: September 2002

Purpose

To investigate the efficacy of SENSE MRI, including the double arterial phase dynamic study, to detect hypervascular hepatocellular carcinomas (HCCs).

Materials and Methods

MRI of the liver was performed in 40 consecutive patients (20 by conventional MRI and 20 by SENSE MRI). The SENSE technique was used to obtain breath‐hold T1‐weighted FSE images (TR/TE = 556/12 msec), respiratory‐triggered T2‐weighted FSE images (TR/TE = 1800/90 msec) with and without fat suppression, and dynamic MR images (TR/TE/FA = 160–168/4.6 msec/70°). In each arterial dominant phase and portal dominant phase, two scans were consecutively performed with one breath‐hold, leading to the double arterial phase and double portal phase images with SENSE.

Results

The sensitivity of SENSE MRI for HCCs diagnosed from all MR images, including dynamic study, T1‐weighted images, and T2‐weighted images, was 91.7%, while that of conventional MRI was 76.3%. The positive predictive value of SENSE MRI for HCCs was 91.7%, while that of conventional MRI was 87.9%. In terms of HCCs ≤ 10 mm, the sensitivity and positive predictive values of SENSE MRI were 78.6% and 78.6%, respectively, while those of conventional MRI were 27.3% and 60.0%, respectively. The number of detected HCCs ≤ 10 mm was significantly larger in SENSE MRI than in conventional MRI (P < 0.05). The cause of false‐positive lesions on SENSE MR images was an arterioportal shunt.

Conclusion

SENSE MRI with double arterial phase dynamic study showed higher sensitivity compared to the conventional technique. Therefore, SENSE MRI is a promising method for the detection of HCC. J. Magn. Reson. Imaging 2002;16:259–266. © 2002 Wiley‐Liss, Inc.
Analysis of the spatial characteristics of metabolic abnormalities in newly diagnosed glioma patients
Authors: Li Xiaojuan , Lu Ying , Pirzkall Andrea , McKnight Tracy , Nelson Sarah J.
Published: September 2002

Purpose

To evaluate the role of 3D MR spectroscopic imaging (MRSI) as a tool for characterizing heterogeneity within a lesion in glioma patients.

Materials and Methods

Forty‐nine patients with newly diagnosed glioma were studied with 3D water‐suppressed proton (1‐H) MRSI. Signal intensities from choline (Cho), creatine (Cr), N‐acytel aspartate (NAA), and lactate/lipid (LL) were estimated from the spectra. Regions of interest (ROIs) corresponding to the metabolic abnormalities were defined and compared with the anatomic lesions.

Results

This study showed that the tumor burden measured with either the volumes of the metabolic abnormalities or the metabolic levels in the most abnormal voxels was correlated with the degree of malignancy of the tumor. The volumes of elevated Cho and decreased NAA were useful for distinguishing low‐grade from high‐grade lesions. The volume of abnormal LL was correlated with the existence of necrosis and with the volume of contrast‐enhancing lesions in high‐grade lesions. The differences in the volume of abnormal LL were also statistically significant between patients in each grade.

Conclusion

These 3D‐MRSI data provide important additional information to conventional MRI for evaluating and characterizing gliomas. J. Magn. Reson. Imaging 2002;16:229–237. © 2002 Wiley‐Liss, Inc.
Parametric imaging of tumor perfusion using flow‐ and permeability‐limited tracers
Authors: Bogin Liora , Margalit Raanan , Mispelter Joel , Degani Hadassa
Published: September 2002

Purpose

To quantitatively evaluate the spatial distribution of flow‐ and permeability‐limited perfusion in MCF7 human breast cancer tumors orthotopically implanted in CD1‐NU mice.

Materials and Methods

Flow‐limited perfusion was derived from 2H‐MRI recorded before and after infusion of deuterated water. Permeability‐limited perfusion was evaluated from GdDTPA‐enhanced 1H‐MRI.

Results

The dominant processes in tumor perfusion, namely blood flow and capillary permeability, were mapped in orthotopically implanted MCF7 human breast cancer tumors. The dynamic data were processed according to physiological models, yielding parametric maps of intravascular volume fraction, water perfusion rate, GdDTPA permeability rate constant, and extracellular volume fraction accessible to GdDTPA. The maps exhibited the heterogeneous distribution of each perfusion parameter. Most of the tumor tissue (≥95%) was perfused with HDO, while GdDTPA was perfused in only about 50% of it. In most loci the perfusion rate was limited by capillary permeability to GdDTPA.

Conclusion

The results demonstrated the instructive value of tracers with different properties used in conjunction to achieve a deeper understanding of tumor perfusion capacity. This study offers tools for the accurate, noninvasive evaluation of drug delivery efficacy. J. Magn. Reson. Imaging 2002;16:289–299. © 2002 Wiley‐Liss, Inc.
Dynamic coronary MR angiography and first‐pass perfusion with intracoronary administration of contrast agent
Authors: Tsekos Nikolaos V. , Woodard Pamela K. , Foster Glenn J. , Moustakidis Pavlos , Sharp Terry L. , Herrero Pilar , Gropler Robert J.
Published: September 2002

Purpose

To evaluate whether dynamic imaging of the coronary arteries can be performed with intracoronary infusion of low‐dose gadolinium (Gd)‐based contrast agent and assess the effect of long duration and multiple infusions on the image signal‐to‐noise ratio (SNR) and contrast‐to‐noise ratio (CNR).

Materials and Methods

Dynamic coronary magnetic resonance (MR) imaging (130 msec/image) and contrast agent first pass myocardial perfusion studies were performed with intracoronary infusions of low‐dose Gd‐based MR contrast agent on dogs (N = 4) using a fast multislice gradient recalled echo (GRE) sequence.

Results

Contrast‐enhanced coronary arteries were clearly imaged during infusion periods as long as 2.3 minutes. The SNR and CNR of the contrast‐enhanced coronary arteries remained essentially unchanged over multiple consecutive angiographic sessions. In addition, we demonstrated that first pass studies performed with intracoronary injection of MR contrast agent can be used as a means of assessing regional myocardial perfusion.

Conclusion

These studies demonstrated that, using intracoronary infusion of Gd, coronary magnetic resonance angiography (MRA) can be performed with high temporal resolution, and multiple low‐dose slow infusions of Gd‐based MR contrast agent can be performed without compromise of the vessel SNR and CNR. J. Magn. Reson. Imaging 2002;16:311–319. © 2002 Wiley‐Liss, Inc.
Hybrid phased array for improved internal auditory canal imaging at 3.0‐T MR
Authors: Kocharian Armen , Lane John I. , Bernstein Matt A. , Lin Chen , Witte Robert J. , Huston John , Felmlee Joel P.
Published: September 2002

Purpose

To develop and evaluate a hybrid phased array for internal auditory canal (IAC) imaging at 3.0 T.

Materials and Methods

A hybrid phased array was designed and built as two circular surface receive‐only coils combined with a volume transmit‐receive birdcage head coil for simultaneous image acquisition. Phantom and volunteer images were obtained to assess the coil performance.

Results

The phantom data show that significant signal‐to‐noise ratio (SNR) improvement was achieved in the region corresponding to the inner ear, i.e., by a factor of 2.5 compared to the standard head coil data. Volunteer IAC image quality was deemed superior as compared to images acquired at 3.0 T using a standard head coil.

Conclusion

This hybrid array combined with three‐dimensional fast spin‐echo (FSE) acquisition resulted in improved high spatial resolution IAC imaging. J. Magn. Reson. Imaging 2002;16:300–304. © 2002 Wiley‐Liss, Inc.
Evaluation of tissue perfusion in a rat model of hind‐limb muscle ischemia using dynamic contrast‐enhanced magnetic resonance imaging
Authors: Luo Yanping , Mohning Kurt M. , Hradil Vincent P. , Wessale Jerry L. , Segreti Jason A. , Nuss Merrill E. , Wegner Craig D. , Burke Sandra E. , Cox Bryan F.
Published: September 2002

Purpose

To evaluate the feasibility of using dynamic contrast‐enhanced magnetic resonance imaging (MRI) for assessment of muscle perfusion in a rat model of hind‐limb ischemia.

Materials and Methods

The acute alteration and chronic recovery in muscle perfusion and perfusion reserve after femoral artery ligation were quantified using the maximum Gd‐DTPA uptake rate obtained by a T1‐weighted gradient‐recalled echo sequence. Radionuclide‐labeled microsphere blood flow measurements were performed for comparison with the MR perfusion measurement on a separate set of animals.

Results

After femoral artery ligation, a significant reduction in resting muscle perfusion was only observed at 1 hour post‐ligation during the 28‐day follow‐up period. Muscle perfusion reserve was severely diminished following the ligation. Despite significant recovery over time, perfusion reserve to the ligated limb reached only 63% of the perfusion capacity in the unaffected limb by 42 days post ligation. A strong correlation (r = 0.86) between MR perfusion and microsphere blood flow measurements was observed for evaluation of relative changes in muscle perfusion.

Conclusion

Dynamic contrast‐enhanced MRI with Gd‐DTPA is useful to assess time‐dependent changes in muscle perfusion and perfusion reserve in this hind‐limb ischemia model. J. Magn. Reson. Imaging 2002;16:277–283. © 2002 Wiley‐Liss, Inc.
Isomer separation of hyperbranched polyesteramides with gas‐phase H/D exchange and a novel MSn approach: DoDIP
Authors: Koster Sander , Duursma Marc C. , Guo Xinghua , van Benthem Rolf. A. T. M. , de Koster Chris G. , Boon Jaap J. , Heeren Ron M. A.
Published: September 2002

Two approaches are introduced that provide information about the isomeric composition of hyperbranched polyesteramides. The first approach is based on a novel tandem mass spectrometric (MSn) approach that allows the study of different types of isomeric structures by a separation based on their difference in appearance energy. The method is called DoDIP: dissociation of depleted ion populations. A first MS/MS step is used to fragment isomers with relatively low appearance energy. The isomers with higher appearance energy are fragmented in a second MS/MS step of higher energy. The second approach is based on gas‐phase H/D exchange experiments that result in a bimodal isotopic distribution for oligomers XnDn+1 of which one distribution corresponds to a type of isomeric structure that exhibits H/D exchange behaviour and the other to an isomeric structure that does not exhibit H/D exchange behaviour. X is a difunctional anhydride of phthalic acid (P), 1,2‐cyclohexanedicarboxylic acid (C), succinic acid (S) or glutaric acid (G). D in XnDn+1 is a trifunctional diisopropanolamine and n the degree of polymerization. The type of isomeric structure that does not exhibit H/D exchange behaviour has a non‐alternating monomer sequence that contains an amine bond with a relatively high proton affinity. The other isomeric structure that does exhibit H/D exchange behaviour has an alternating monomer sequence containing only amide and ester bonds with relatively low proton affinity. Oligomer structures were confirmed with additional MS2 experiments after H/D exchange. H/D exchange experiments on the fragments obtained after MS2 of the parent ion show that next to previously postulated mechanisms for the cleavage of the ester and amide bond another reaction pathway must be operational. A new mechanism is introduced to explain the H/D exchange behaviour of the fragments that requires a cleavage of the amide bonds only. Two types of fragments are formed by this mechanism. One type is protonated due to the cleavage of the amide bond whereas the other type has an oxazolonium ion structure due to the loss of an additional H2O. Copyright © 2002 John Wiley & Sons, Ltd.
Tracing glycoprotein structures: electrospray ionization tandem mass spectrometric analysis of sugar–peptide adducts
Authors: Jerić Ivanka , Versluis Cornelis , Horvat Štefica , Heck Albert J. R.
Published: September 2002

Owing to the diversity of carbohydrate structures and their significance for the function of many biopolymers, structural analysis of various carbohydrate‐related compounds is of great importance. Electrospray ionization tandem mass spectrometry (ESI‐MS/MS) was used to establish the fragmentation behaviour of a range of sugar–peptide adducts as model compounds of widespread glycoprotein structures. The compounds used in this study were chosen to provide correlation of distinct fragment ions with specific structural differences, namely position and type of carbohydrate–peptide bond and structure of the sugar moiety. All compounds show N‐ and C‐terminal sequence ions along with losses of up to three water molecules. Fructose‐related Amadori compounds exhibit M + 78 modified N‐terminal peptide fragment ions. Fragmentation of glucose–peptide esters is characterized by the sugar ring fragmentation. Additionally, under the ESI‐MS conditions applied, the esters studied undergo intramolecular reaction giving cyclic sugar–peptide structures that can be traced by the presence of N‐terminal peptide M + 42 adducts. Detailed analysis of cyclic fructose‐related compound comprising structural features of both studied groups revealed a rich fragmentation pattern derived from amino acid residues and water molecules losses from [M − 2H2O + H]+ ion. Also, some interesting differences were found with respect to the nature of carbohydrate moieties. Copyright © 2002 John Wiley & Sons, Ltd.
Determination of clindamycin in animal plasma by high‐performance liquid chromatography combined with electrospray ionization mass spectrometry
Authors: Cherlet Marc , Croubels Siska , De Backer Patrick
Published: September 2002

A method for the quantification of clindamycin in animal plasma using high‐performance liquid chromatography combined with electrospray ionization mass spectrometry (LC/ESI‐MS/MS) is presented. Lincomycin is used as the internal standard. The sample preparation includes a simple deproteinization step with trichloroacetic acid. Chromatographic separation is achieved on an RP‐18 Hypersil column using gradient elution with 0.01 M ammonium acetate and acetonitrile as mobile phase. Good linearity was observed in the range 0–10 µg ml−1. The limit of quantification of the method is 50 ng ml−1 and the limit of detection is 1.3 ng ml−1. The method was shown out to be of use for pharmacokinetic studies of clindamycin formulations in dogs. Copyright © 2002 John Wiley & Sons, Ltd.
Mass spectrometric identification of in vivo carbamylation of the amino terminus of Ectothiorhodospira mobilis high‐potential iron–sulfur protein, isozyme 1
Authors: Van Driessche G. , Vandenberghe I. , Jacquemotte F. , Devreese B. , Van Beeumen J. J.
Published: September 2002

The complete amino acid sequence of a novel high‐potential iron–sulfur protein (HiPIP) isozyme 1 from the moderately halophilic phototrophic bacterium Ectothiorhodospira mobilis was determined by a combined approach of chemical and mass spectrometric sequencing techniques. By mass analysis of the apo‐ and holo‐protein in the positive electrospray ionization mode using different electrospray solvents, the protein was found to be post‐translationally modified by a moiety of 43 Da. Further analysis showed the nature and location of this modification to be a carbamyl group at the N‐terminus of the HiPIP. This rare type of modification has previously been reported to occur in the water‐soluble human lens αB‐crystallin, class D β‐lactamases and some prokaryotic ureases, albeit at an internal lysine residue. In this paper, we discuss the mass spectrometric features of a carbamylated residue at the N‐terminus of a peptide or a lysine side‐chain during sequence analysis by collision‐induced dissociation tandem mass spectrometry. Our data provide evidence for the first case of a prokaryotic carbamylated electron transport protein occurring in vivo. Copyright © 2002 John Wiley & Sons, Ltd.
Operation of an academic open access mass spectrometry facility with particular reference to the analysis of synthetic compounds
Authors: Greaves John
Published: September 2002

Open access mass spectrometry now provides the opportunity to move this spectroscopic method to the beginning of the analytical chain, a place formerly the exclusive province of NMR and TLC. To date this transition has been occurring in industrial settings but there has been less change in the academic environment. This paper provides one blueprint for setting up such a facility, primarily in support of organic synthesis but also for the use of biological scientists. The open access format used at UCI utilizes four instruments: an ESI‐TOFMS system used in the flow injection mode, two GC/MS systems (one in EI and one in CI) and a MALDI‐TOFMS system. The first three instruments have autosamplers and open access software whereas the MALDI system has a fully automated plate handling interface. This level of automation allows access to the instruments by a user community of more than 100 users, day or night. The decisions made in setting up these instruments were based on a ‘keep it simple’ philosophy, given the fact that the primary type of data of interest is the molecular mass of the analyte and that data are required for a very wide range of structures. Copyright © 2002 John Wiley & Sons, Ltd.
Hepatocyte growth factor stimulates the proliferation and migration of oligodendrocyte precursor cells
Authors: Yan Henglin , Rivkees Scott A.
Published: September 2002

Hepatocyte growth factor (HGF) was initially identified as a potent mitogen for mature hepatocytes and has since been found to affect a variety of cells. Evidence suggests that HGF may also influence the nervous system, in that HGF stimulates the proliferation of myelin‐forming Schwann cells and olfactory ensheathing cells. However, it is not known whether HGF influences oligodendrocytes. To address this issue, oligodendrocyte precursors were obtained from neonatal rat cerebra and cultured. Immunostaining and Western blotting revealed expression of both HGF and the HGF receptor (c‐Met) by cultured oligodendrocytes. When the ability of HGF to stimulate oligodendrocyte division and migration was examined, we observed that treatment with HGF (10–50 ng/ml) elicited twofold increases in oligodendrocyte precursor proliferation. HGF also enhanced oligodendrocyte precursor migration, with 2.5‐fold increases in rates of migration seen after treatment for 8 hr. HGF also influenced inducing the oligodendrocyte cytoskeleton by altering patterns of F‐actin and β‐tubulin distribution and enhanced the expression of actin and β‐tubulin. These observations show that a functional HGF/c‐Met system is present in oligodendrocytes, which can influence the growth, development, and cytoskeletal organization of oligodendrocytes. © 2002 Wiley‐Liss, Inc.
Alterations in matrix metalloproteinase‐9 levels and tissue inhibitor of matrix metalloproteinases‐1 expression in a transforming growth factor‐β transgenic model of hydrocephalus
Authors: Zechel Jennifer , Gohil Harsh , Lust W. David , Cohen Alan
Published: September 2002

The development of spontaneous hydrocephalus in mouse models resulting from the overexpression of transforming growth factor‐β (TGFβ‐1) has been previously described, although the mechanism by which this occurs remains obscure. It has been previously demonstrated that increased expression of TGFβ has consequences for the levels of matrix metalloproteinases (MMPs) and their specific inhibitors (tissue inhibitors of MMPs, or TIMPs). These remodeling proteins play an important role in extracellular matrix (ECM) maintenance through degradation and deposition of ECM components. The present study investigated the relationship between elevated levels of TGFβ‐1, the ECM modulators TIMP‐1 and MMP‐9, and development of hydrocephalus in the neonatal mouse. In newborn pups, TIMP‐1 mRNA levels were equal between animals expressing the TGFβ‐1 transgene and littermates without the transgene. However, immunohistochemistry of littermate pups shows that the distribution of TIMP‐1 was changed from homogeneous with large punctate concentrations of signal to uniform, dense staining in hydrocephalic animals carrying the TGFβ‐1 transgene. The mRNA levels of MMP‐9 were decreased in the transgenic animals, as were the activity levels MMP‐9. These results suggest that the remodeling protein MMP‐9 and its specific inhibitor, TIMP‐1, may contribute to the spontaneous development of hydrocephalus in this transgenic model by altering the ECM environment. © 2002 Wiley‐Liss, Inc.
Analysis of neuronal gene expression with laser capture microdissection
Authors: Vincent Valerie A.M. , DeVoss Jason J. , Ryan Heather S. , Murphy Greer M.
Published: September 2002

The brain is a heterogeneous tissue in which the numbers of neurons, glia, and other cell types vary among anatomic regions. Gene expression studies performed on brain homogenates yield results reflecting mRNA abundance in a mixture of cell types. Therefore, a method for quantifying gene expression in individual cell populations would be useful. Laser capture microdissection (LCM) is a new technique for obtaining pure populations of cells from heterogeneous tissues. Most studies thus far have used LCM to detect DNA sequences. We developed a method to quantify gene expression in hippocampal neurons from mouse brain using LCM and real‐time reverse transcriptase‐polymerase chain reaction (RT‐PCR). This method was optimized to permit histochemical or immunocytochemical visualization of nerve cells during LCM while minimizing RNA degradation. As an example, gene expression was quantified in hippocampal neurons from the Tg2576 mouse model for Alzheimer's disease. © 2002 Wiley‐Liss, Inc.
Malignant rhabdoid tumor shows incomplete neural characteristics as revealed by expression of SNARE complex
Authors: Yoshida Shinobu , Narita Tsutomu , Taga Takashi , Ohta Shigeru , Takeuchi Yoshihiro
Published: September 2002

To elucidate the biological differences in neural phenotype between malignant rhabdoid tumor (MRT) and neuroblastoma cell lines, we examined the expression of solube N‐ethylmaleimide‐sensitive fusion protein attachment protein receptor (SNARE) complex proteins in MRT cell lines under differentiation induction with 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA). Six MRT cell lines (TM87‐16, STM91‐01, TTC642, TTC549, YAM‐RTK1, and TTC1240) and six neuroblastoma cell lines (IMR‐32, NH12, SCCH26, TGW, NB‐1, and NB‐NR) were used in this study. Expression of SNAREs: the vesicle SNARE (synaptotagmin, synaptophysin, and synaptobrevin‐2) and the target SNARE (syntaxin 1A, SNAP‐25A/B) was examined. Our results showed that in MRT cells, only two cell lines (TM87‐16, TTC642) expressed the vesicle SNARE and the target SNARE with the exception of SNAP‐25B, while all neuroblastoma cells expressed the entire SNARE complex. During differentiation, synaptotagmin was upregulated in these two MRT cell lines. Interestingly, synaptophysin was downregulated in these MRT cell lines in contrast with the neuroblastoma cell lines. SNAP‐25B was not expressed in MRT cells after differentiation with TPA. MRT cells having a neural phenotype morphologically looked like neuroblastoma cells after treatment with TPA. However, the expression of SNARE complex was incomplete in MRT cells. Our results suggest that the biological characteristics of MRT cells with neural phenotype are distinct from those of neuroblastoma cells. © 2002 Wiley‐Liss, Inc.
Characterization of cholera toxin B subunit‐induced Ca2+ influx in neuroblastoma cells: Evidence for a voltage‐independent GM1 ganglioside‐associated Ca2+ channel
Authors: Fang Yu , Xie Xin , Ledeen Robert W. , Wu Gusheng
Published: September 2002

The role of endogenous GM1 ganglioside in neurite outgrowth has been studied in N18 and NG108‐15 neuroblastoma cells with the GM1‐specific ligand cholera toxin B subunit (Ctx B), which stimulates Ca2+ influx together with neuritogenesis. Our primary goal has been to identify the nature of the calcium channel that is modulated by GM1. An L‐type voltage‐operated Ca2+ channel (VOCC) was previously proposed as the mediator of this phenomenon. This investigation, employing fura‐2 fluorescent measurements and specific channel blockers and other agents, revealed that GM1 modulates a hitherto unidentified Ca2+ channel not of the L type. It was opened by Ctx B; was permeable to Ca2+ and Ba2+ but not Mn2+; and was blocked by Ni2+, Cd2+, and La3+. Although most dihydropyridines inhibited Ctx B‐induced Ca2+ influx as well as neurite outgrowth at higher concentrations, they and other VOCC blockers at normally employed concentrations failed to do so, suggesting uninvolvement of VOCC. In addition, Ca2+ influx induced by Ctx B was not mediated by cGMP‐dependent or G‐protein‐coupled nonselective cation channels, as demonstrated by the cGMP antagonist Rp‐cGMPS or the G‐protein/receptor uncoupling agent suramin, respectively. Finally, Ca2+ influx was unlikely to be due to inhibition or reversal of Na+‐Ca2+ exchanger via Ctx B induction of Na+ uptake, insofar as no effect was seen on blocking Na+ channels, inhibiting Na+‐K+‐ATPase, or eliminating extracellular Na+. The results suggest that this novel channel is gated by interaction with GM1, which, when associated with the channel and bound by appropriate ligand, promotes Ca2+ influx. This in turn induces signaling for the onset of neuritogenesis. © 2002 Wiley‐Liss, Inc.
Human bone marrow stromal cell cultures conditioned by traumatic brain tissue extracts: Growth factor production
Authors: Chen Xiaoguang , Katakowski Mark , Li Yi , Lu Dunyue , Wang Lei , Zhang Lijie , Chen Jieli , Xu Yongxian , Gautam Subhash , Mahmood Asim , Chopp Michael
Published: September 2002

Treatment of traumatic brain injury (TBI) with bone marrow stromal cells (MSCs) improves functional outcome in the rat. However, the specific mechanisms by which introduced MSCs provide benefit remain to be elucidated. Currently, the ability of therapeutically transplanted MSCs to replace injured parenchymal CNS tissue appears limited at best. Tissue replacement, however, is not the only possible compensatory avenue in cell transplantation therapy. Various growth factors have been shown to mediate the repair and replacement of damaged tissue, so trophic support provided by transplanted MSCs may play a role in the treatment of damaged tissue. We therefore investigated the temporal profile of various growth factors, brain‐derived neurotrophic factor (BDNF), nerve growth factor (NGF), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and hepatocyte growth factor (HGF), within cultures of human MSCs (hMSCs) conditioned with cerebral tissue extract from TBI. hMSCs were cultured with TBI extracts of rat brain in vitro and quantitative sandwich enzyme‐linked immunosorbent assays (ELISAs) were performed. TBI‐conditioned hMSCs cultures demonstrated a time‐dependent increase of BDNF, NGF, VEGF, and HGF, indicating a responsive production of these growth factors by the hMSCs. The ELISA data suggest that transplanted hMSCs may provide therapeutic benefit via a responsive secretion of an array of growth factors that can foster neuroprotection and angiogenesis. © 2002 Wiley‐Liss, Inc.
Characterization of neuronal death induced by focally evoked limbic seizures in the C57BL/6 mouse
Authors: Araki Tomohiro , Simon Roger P. , Taki Waro , Lan Jing‐Quan , Henshall David C.
Published: September 2002

Research into the molecular mechanisms of epileptic brain injury is hampered by the resistance of key mouse strains to seizure‐induced neuronal death evoked by systemically administered excitotoxins such as kainic acid. Because C57BL/6 mice are extensively employed as the genetic background for transgenic/knockout modeling in cell death research but are seizure resistant, we sought to develop a seizure model in this strain characterized by injury to the hippocampal CA subfields. Adult male C57BL/6 mice underwent focally evoked seizures induced by intraamygdala microinjection of kainic acid. Kainic acid (KA) effectively elicited ipsilateral CA3 pyramidal neuronal death within a narrow dose range of 0.1–0.3 μg, with mortality <10%. With employment of the most consistent (0.3 μg) dose, seizures were terminated 15, 30, 60, or 90 min after KA by diazepam. Damage was largely restricted to the ipsilateral CA3 subfield of the hippocampus, but injury was also consistent within CA1, suggesting that this mouse model better reflects the hippocampal neuropathology of human temporal lobe epilepsy than does the rat, in which CA1 is typically spared. Confirming this CA1 injury as seizure specific and not a consequence of ischemia, we used laser‐Doppler flowmetry to determine that cerebral perfusion did not significantly change (97% to 118%) over control. Degenerating cells were >95% neuronal as determined by neuron‐specific nuclear protein (NeuN) counterstaining of terminal deoxynucleotidyl transferase‐mediated dUTP nick end‐labeled (TUNEL) brain sections. Furthermore, TUNEL‐positive cells often exhibited the morphological features of apoptosis, and small numbers were positive for cleaved caspase‐3. These data establish a mouse model of focally evoked seizures in the C57BL/6 strain associated with a restricted pattern of apoptotic neurodegeneration within the hippocampal subfields that may be applied to research into the molecular basis of neuronal death after seizures. © 2002 Wiley‐Liss, Inc.
Role of low‐affinity p75 receptor in nerve growth factor‐inducible growth arrest of PC12 cells
Authors: Ito Hisanori , Nomoto Hiroshi , Furukawa Shoei
Published: September 2002

Mutant PC12 cell clones (PC84 cells) were obtained by transfection with nerve growth factor (NGF) cDNA. These cells secreted active NGF, extended short processes, and proliferated faster than the parental PC12 cells. These features are of great interest because the parental PC12 cells cease proliferation and extend long processes when transfected with NGF cDNA. PC84 cells expressed a high level of acetylcholinesterase activity and neurofilament M, which indicates that PC84 cells were differentiated. The inhibition of TrkA by K252a diminished the short processes of PC84 cells but had no effect on their fast proliferation. The expression level of TrkA in PC84 cells was comparable to that in PC12 cells; whereas that of another NGF receptor, p75, was significantly lower. These data suggest that the decrease of p75 contributed to the continuous growth of PC84 cells, which was confirmed by suppressing p75 activity of PC12 cells with the antisense oligonucleotide of p75 or with anti‐p75 neutralizing antibody. The treated cells did not cease proliferation in the presence of NGF and extended short processes. Our results suggest that NGF signaling via TrkA affects the differentiation characteristics of PC12 cells but that an additional signaling via p75 is necessary for the growth arrest of the cells. © 2002 Wiley‐Liss, Inc.
Rationale and definition of the lateral extension of the inguinal lymphadenectomy for vulvar cancer derived from an embryological and anatomical study
Authors: Micheletti Leonardo , Levi Alessandro Cesare , Bogliatto Fabrizio , Preti Mario , Massobrio Marco
Published: September 2002

Background and Objectives

The objective of the present study was to define the location of the most lateral superficial inguinal node lying along the inguinal ligament, through an embryological and anatomotopographical study, in order to rationalize the lateral extension of the groin lymphadenectomy in vulvar cancer.

Methods

Sections of the upper portion of the femoral triangle belonging to three human fetuses, whose crown‐rump (CR) length ranged from 70 to 310 mm, corresponding to a developmental age of 11 and 35 weeks, were studied. In addition, for an objective topographical evaluation of the disposition of the superficial inguinal lymph nodes, adult cadavers photographs of dissected Scarpa's triangle, reported in anatomical atlases, were analyzed.

Results

Both the embryological investigation and the anatomotopographical evaluation on cadavers photographs demonstrate that the most lateral superficial inguinal lymph node does not rise above the medial margin of the sartorius muscle, nor far lateral to the point where the superficial circumflex iliac vessels cross the inguinal ligament.

Conclusions

On the basis of the present study, the authors believe that the superficial circumflex iliac vessels could represent the lateral surgical landmark, easily detectable, at which the inguinal lymphadenectomy should cease. Therefore, there is no need to extend the lateral excision to the anterior superior iliac spine. Finally, leaving the fatty tissue laterally to these vessels, some lymphatic channels could be preserved, decreasing the incidence and the entity of wound seroma and lymphedema. J. Surg. Oncol. 2002;81:19–24. © 2002 Wiley‐Liss, Inc.
Desmopressin inhibits lung and lymph node metastasis in a mouse mammary carcinoma model of surgical manipulation
Authors: Giron Santiago , Tejera Agueda M. , Ripoll Giselle V. , Gomez Daniel E. , Alonso Daniel F.
Published: September 2002

Background and Objectives

Desmopressin (DDAVP) is a synthetic derivative of vasopressin with hemostatic and fibrinolytic properties that has been used during surgery in patients with bleeding disorders. Our aim was to investigate the effect of DDAVP on lung and lymph node metastatic cell colonization using a preclinical mouse mammary carcinoma model of subcutaneous tumor manipulation and surgical excision.

Methods

Female BALB/c mice bearing the highly aggressive F3II mammary carcinoma were subjected to repeated manipulations of primary tumors (0.5 kg/cm2 during 2 min), followed (or not) by surgical excision. DDAVP was administered intravenously 30 min before and 24 h after each manipulation or surgery, at a dose of 2 μg/kg. At the end of the experiment, mice were sacrificed and necropsied.

Results

Tumor manipulation induced dissemination to the axillary nodes and increased up to 6‐fold the number of metastatic lung nodules. Perioperative treatment with DDAVP dramatically reduced regional metastasis. The incidence of lymph node involvement in manipulated animals was 12% with DDAVP and 87% without treatment (P < 0.02). Histopathological analysis of axillary nodes from DDAVP‐treated animals showed sinusal histiocytosis and no evidence of cancer cells. Metastatic lung nodules were also reduced about 65% in animals treated with DDAVP (P = 0.026).

Conclusions

Our results suggest a potential clinical application of DDAVP in the management of breast cancer, as well as other aggressive solid tumors. DDAVP may be useful to reduce the risk of metastatic cell colonization both during and after surgical manipulation. J. Surg. Oncol. 2002;81:38–44. © 2002 Wiley‐Liss, Inc.
Review of the clinical, histological, and molecular aspects of pancreatic endocrine neoplasms
Authors: Gumbs A.A. , Moore P.S. , Falconi M. , Bassi C. , Beghelli S. , Modlin I. , Scarpa A.
Published: September 2002

Pancreatic endocrine neoplasms (PENs) are rare tumors, and little is known about their genetic and chromosomal alterations. Elucidation of the molecular events involved in PEN carcinogenesis has been hindered by the fact that PENs have been considered a single disease entity. The emergence of novel molecular characterization strategies has, however, made it apparent that these lesions exhibit diverse molecular fingerprints, which will facilitate the precise delineation of PEN prognosis, histopathology, and carcinogenesis. J. Surg. Oncol. 2002;81:45–53. © 2002 Wiley‐Liss, Inc.
Biliary carcinoembryonic antigen in the diagnosis of occult hepatic metastases from colorectal cancer
Authors: Li Destri Giovanni , Curreri Roberto , Lanteri Raffaele , Gagliano Giuseppe , Rodolico Margherita , Di Cataldo Antonio , Puleo Stefano
Published: September 2002

Background and Objectives

Twenty five percent of patients who undergo radical surgical treatment for colorectal cancer have occult hepatic metastases that become evident during the follow‐up period. We evaluated whether biliary carcinoembryonic antigen (CEA) measurements could be used in these patients to diagnose occult hepatic metastases.

Methods

Three groups of patients were enrolled in the study. The first group consisted of patients treated for lithiasis of the common bile duct, the second group was affected by colorectal cancer and evident hepatic metastases, and the third group of patients underwent radical surgical treatment for colorectal cancer but had no evident hepatic metastases.

Results

In the first study group, mean biliary CEA level was 0.52 ng/mL (normal value: 0–5 ng/mL) (diagnostic accuracy: 100%), 83.3 ng/mL in the second group (diagnostic accuracy: 91%) and 3.9 ng/mL in the third group. We registered only one false‐positive result in the third group, whereas biliary CEA level was above normal values in the three patients in whom hepatic metastases developed (diagnostic accuracy: 89.5%).

Conclusions

This study suggests that biliary CEA determination could represent an important method to select patients affected by occult hepatic metastases for inclusion in appropriate treatment protocols. J. Surg. Oncol. 2002;81:8–11. © 2002 Wiley‐Liss, Inc.
Are the axillary lymph nodes treated by standard tangent breast fields?
Authors: McCormick Beryl , Botnick Marc , Hunt Margie , Petrek Jeanne
Published: September 2002

Background and Objectives

With the increasing use of sentinel lymph node biopsy, a growing proportion of women with early‐stage invasive breast cancer are undergoing breast conserving surgery without a formal axillary lymph node dissection. A frequent question raised is whether the level I‐II axillary lymph nodes are treated with standard breast tangent fields. In an attempt to answer this question, surgical clips placed at the time of the level I‐II axillary lymph node dissection were used as a surrogate for the location of the nodes and the simulator films for tangent fields of 45 patients were analyzed.

Methods

Study criteria were as follows: five or more clips placed in the axilla, and all clips and the humeral head visualized on the medial tangent film. Clips were scored as “in” or “out” of the tangent field, as defined by the delineator wires. All technical parameters were analyzed to determine whether any reproducible techniques would consistently include all of the clips and, hypothetically, the axillary nodes at levels I and II.

Results

All clips were included in the medial tangent breast radiation field in only 38% (17 of 45) of cases.

Conclusions

The standard, two‐field tangent breast fields do not reliably encompass the all level I‐II axillary lymph nodes as defined by this study, but some of the nodes were treated in all 45 cases. J. Surg. Oncol. 2002;81:12–16. © 2002 Wiley‐Liss, Inc.
Synthesis of 1‐amino‐2‐methylindoline by Raschig process: Parallel reactions, modeling, and optimization
Authors: Elkhatib M. , Peyrot L. , Metz R. , Tenu R. , Elomar F. , Delalu H.
Published: September 2002

The reaction between chloramine and 2‐methylindoline was studied at pH 12.89, T = 40°C, and for different initial concentrations of reactants. The interaction includes two concurrent bimolecular mechanisms leading to 1‐amino‐2‐methylindoline and 2‐methylindole. The rate laws were determined at the first moments of the reaction by using a differential method. By considering the totality of the reactions that occur in the medium, an appropriate mathematical model was developed. It permits to follow the evolution of the system over time and to calculate the final yields of reaction products. An optimization in terms of the initial contents of 2‐methylindoline and chloramine was performed. It indicated that the maximum yield of 1‐amino‐2‐methylindoline does not exceed 56%. The results show the limit of the Raschig process for the synthesis of indolic hydrazines in aqueous medium. © 2002 Wiley Periodicals, Inc. Int J Chem Kinet 34: 575–584, 2002
Palladium(II) complexes of aliphatic amines and their oxidation by chloramine‐T in perchloric acid medium
Authors: Grover Neeti , Kambo Neelu , Upadhyay Santosh K.
Published: September 2002

The formation of palladium(II) complexes with aliphatic amines and their oxidation by chloramine‐T in perchloric acid medium has been studied. The spectrophotometric studies showed the formation of 1:1 and 1:2 complexes between palladium(II) and amine in absence of HClO4. An increase in [HClO4] in reaction mixture suppresses the complex formation and in presence of [HClO4] ∼10−3 mol dm−3 only a 1:1 complex between palladium(II) and amine has been observed. The effect of Cl− on the complex formation has also been studied.

Palladium(II)‐catalyzed oxidation of these amines by chloramine‐T showed a first‐order dependence of rate with respect to each—oxidant, substrate, catalyst, and H+. The mechanism consistent with kinetic data for the oxidation process has been proposed in absence as well as in presence of initial [Cl−]. © 2002 Wiley Periodicals, Inc. Int J Chem Kinet 34: 603–612, 2002
Kinetics and mechanism of oxidation of aurate(I) by peroxydisulphate in aqueous hydrochloric acid
Authors: Babshet R. M. , Gokavi G. S.
Published: September 2002

The reaction between Au(I), generated by reaction of thallium(I) with Au(III), and peroxydisulphate was studied in 5 mol dm−3 hydrochloric acid. The reaction proceeds with the formation of an ion‐pair between peroxydisulphate and chloride ion as the Michealis–Menten plot was linear with intercept. The ion‐pair thus formed oxidizes AuCl2− in a slow two‐electron transfer step without any formation of free radicals. The ion‐pair formation constant and the rate constant for the slow step were determined as 113 ± 20 dm−3 mol−1 and 5.0 ± 1.0 × 10−2 dm3 mol−1 s−1, respectively. The reaction was retarded by hydrogen ion, and formation of unreactive protonated form of the reductant, HAuCl2, causes the rate inhibition. From the hydrogen ion dependence of the reaction rate, the protonation constant was calculated to be as 0.6 ± 0.1 dm3 mol−1. The activation parameters were determined and the values support the proposed mechanism. © 2002 Wiley Periodicals, Inc. Int J Chem Kinet 34: 589–594, 2002
Genetic analyses of mouse skin tumor progression susceptibility using SENCAR inbred derived strains
Authors: Stern Mariana C. , Benavides Fernando , LaCava Margaret , Conti Claudio J.
Published: September 2002

Susceptibility to tumor development varies among individuals in the human population. This variability can also be found among different strains of mice, particularly in the mouse skin chemical carcinogenesis model. The genetic mechanisms underlying mouse skin tumor susceptibility are not fully understood. The SENCAR stock has been found to be the most sensitive mice for skin carcinogenesis studies; however, little is known about the genes underlying tumor susceptibility, particularly, those involved in tumor progression. Experiments with the SSIN/Sprd mice, an inbred strain derived from the outbred SENCAR stock, suggested that papilloma development, tumor promotion, and their conversion into squamous cell carcinomas (SCCs), progression, are regulated by different genes. In the highly sensitive SSIN/Sprd mice, papillomas rarely progress to SCC. Using crosses between the outbred SENCAR and the SSIN/Sprd mice, we previously determined that papilloma progression in the SENCAR stock could be controlled by at least one autosomal dominant gene. However, the outbred nature of the SENCAR stock precluded us from extending those findings. More recently, another inbred strain was developed from the outbred SENCAR stock, the SENCARB/Pt. These mice have similar tumor promotion sensitivity to the SSIN/Sprd but in contrast, have high papilloma progression susceptibility, similar to the outbred original stock. In the present study, we generated F1, F2, and backcross hybrids between the SSIN/Sprd and SENCARB/Pt mice to determine a possible model for tumor progression susceptibility and to map the putative tumor susceptibility genes. Our tumor data suggests that papilloma progression susceptibility in the SENCAR mouse skin model could be genetically determined by one susceptibility gene. Our preliminary linkage analysis failed to identify one strong susceptibility locus to confirm this but provided some evidence for at least one possible susceptibility locus in mouse chromosome 14. © 2002 Wiley‐Liss, Inc.