bluuebunny/crossref_metadata_2025 huggingface dataset:
Distribution of somatic H1 subtypes is non‐random on active vs. inactive chromatin II: Distribution in human adult fibroblasts
Authors: Parseghian Missag H. , Newcomb Robert L. , Hamkalo Barbara A.
Published: August 2002

For nearly twenty years researchers have observed changes in the histone H1 subtype content of tissues as an organism develops into an adult. To better understand the consequences of such changes, immunofractionation of chromatin using previously characterized antibodies specific for human H1 subtypes was employed in the analysis of a fibroblast cell strain derived from a 37‐year‐old individual. DNAs isolated from immunoprecipitates were probed for the existence of a variety of DNA sequences. The results presented lend further support to a previously‐proposed model (Parseghian et al. [2000] Chromosome Res 8:405‐424) in which transcription of a sequence is accompanied by the selective depletion of subtypes. The data also suggest that there is more total H1 on actively transcribed sequences in these cells as compared to fetal fibroblasts and that there is less difference in the subtype compositions of active genes vs. inactive sequences in this strain. Specifically, the consequences of these changes appear to correlate with the attenuation of the heat shock response in aging fibroblasts. In a broader context, these results could explain why there are reductions in transcription in cells from mature tissue that approach senescence. J. Cell. Biochem. 83: 643–659, 2001. © 2001 Wiley‐Liss, Inc.
Expression of AP‐2 transcription factor and of its downstream target genes c‐kit, E‐cadherin and p21 in human cutaneous melanoma
Authors: Baldi Alfonso , Santini Daniele , Battista Tullio , Dragonetti Emanuele , Ferranti Giulio , Petitti Tommasangelo , Groeger Angela M. , Angelini Anna , Rossiello Raffaele , Baldi Feliciano , Natali Pier Giorgio , Paggi Marco G.
Published: August 2002

The AP‐2 transcription factor plays a pivotal role in regulating the expression of several genes involved in tumor growth and progression of melanoma. We determined, by Western blot, variation in the level of expression of AP‐2 and three of its downstream targets, c‐kit, E‐cadherin, and p21 in several human melanoma cell lines and, by immunohistochemistry, in a group of 99 histological samples including benign and malignat melanocytic lesions. A significant negative correlation between AP‐2 expression level and tumor thickness was found. Moreover, AP‐2 expression was positively associated with E‐cadherin and c‐kit expression. In contrast, there was a significant negative association between AP‐2 and p21 expression levels. These findings suggest that p21 is independent of AP‐2 transactivator function during the latest phases of melanoma progression. Finally, AP‐2, c‐kit, E‐cadherin, and p21 expression levels did not show to be able to distinguish between dysplastic nevi and nevi without dysplasia. We conclude that changes in the expression of these proteins are involved in the later phases of melanoma progression, and may be responsible for the transition from local invasive melanoma to metastasis. J. Cell. Biochem. 83: 364–372, 2001. © 2001 Wiley‐Liss, Inc.
Polypeptide growth factors and phorbol ester induce progressive ankylosis (Ank) gene expression in murine and human fibroblasts*
Authors: Guo Yan , Hsu Debbie K.W. , Feng Sheau‐Line Y. , Richards Christine M. , Winkles Jeffrey A.
Published: August 2002

Polypeptide growth factors promote cellular proliferation by binding to specific plasma membrane‐anchored receptors. This interaction triggers the phosphorylation of signal transducing molecules and the transcriptional activation of numerous genes. We have used a differential display approach to identify fibroblast growth factor (FGF)‐1‐inducible genes in murine NIH 3T3 fibroblasts. Here we report that one of these genes encodes ank, a type IIIa transmembrane protein reported to function in cells as an inorganic pyrophosphate transporter. FGF‐1 induction of ank mRNA expression is first detectable at 2 h after growth factor addition and is dependent on de novo RNA and protein synthesis. Ank gene expression is also upregulated after treating quiescent fibroblasts with several other mitogenic agents (e.g., calf serum or platelet‐derived growth factor‐BB) or the tumor promoter phorbol 12‐myristate 13‐acetate. Furthermore, in comparison to parental NIH 3T3 cells, oncogene‐transformed NIH 3T3 cells constitutively express elevated levels of ank mRNA. FGF‐1 also increases ank gene expression in non‐immortalized human embryonic lung fibroblasts. Finally, the murine and human ank genes are expressed in vivo in a tissue‐specific manner, with highest levels of mRNA expression found in brain, heart, and skeletal muscle. These results indicate that ank is a growth factor‐regulated delayed‐early response gene in mammalian cells, and we propose that increased ank expression during cell cycle progression may be necessary to maintain proper intracellular pyrophosphate levels during conditions of high cellular metabolic activity. J. Cell. Biochem. 84: 27–38, 2002. © 2001 Wiley‐Liss, Inc.
Atomic charges, dipole moments, and Fukui functions using the Hirshfeld partitioning of the electron density
Authors: De Proft F. , Van Alsenoy C. , Peeters A. , Langenaeker W. , Geerlings P.
Published: August 2002

In the Hirshfeld partitioning of the electron density, the molecular electron density is decomposed in atomic contributions, proportional to the weight of the isolated atom density in the promolecule density, constructed by superimposing the isolated atom electron densities placed on the positions the atoms have in the molecule. A maximal conservation of the information of the isolated atoms in the atoms‐in‐molecules is thereby secured. Atomic charges, atomic dipole moments, and Fukui functions resulting from the Hirshfeld partitioning of the electron density are computed for a large series of molecules. In a representative set of organic and hypervalent molecules, they are compared with other commonly used population analysis methods. The expected bond polarities are recovered, but the charges are much smaller compared to other methods. Condensed Fukui functions for a large number of molecules, undergoing an electrophilic or a nucleophilic attack, are computed and compared with the HOMO and LUMO densities, integrated over the Hirshfeld atoms in molecules. © 2002 Wiley Periodicals, Inc. J Comput Chem 12: 1198–1209, 2002
Cyclic bi‐embeddings of Steiner triple systems on 12s + 7 points
Authors: Bennett G. K. , Grannell M. J. , Griggs T. S.
Published: August 2002

A cyclic face 2‐colourable triangulation of the complete graphKnin an orientable surface exists forn ≡ 7 (mod 12). Such a triangulation corresponds to a cyclic bi‐embedding of a pair of Steiner triple systems of ordern, the triples being defined by the faces in each of the two colour classes. We investigate in the general case the production of such bi‐embeddings from solutions to Heffter's first difference problem and appropriately labelled current graphs. Forn = 19 andn = 31 we give a complete explanation for those pairs of Steiner triple systems which do not admit a cyclic bi‐embedding and we show how all non‐isomorphic solutions may be identified. Forn = 43 we describe the structures of all possible current graphs and give a more detailed analysis in the case of the Heawood graph. © 2002 Wiley Periodicals, Inc. J Combin Designs 10: 92–110, 2002; DOI 10.1002/jcd.10001
1‐rotationally resolvable 4‐cycle systems of 2Kv
Authors: Fu Hung‐Lin , Mishima Miwako
Published: August 2002

In this article, it is shown that there exists a 1‐rotationally resolvable 4‐cycle system of 2Kυif and only if υ ≡ 0 (mod 4). To prove that, some special sequences of integers are utilized. © 2002 Wiley Periodicals, Inc. J Combin Designs 10: 116–125, 2002; DOI 10.1002/jcd.10006
Differential localization of ErbB2 in different tissues of the rat female reproductive tract: Implications for the use of specific antibodies for ErbB2 analysis
Authors: Idris Nebila , Carraway Coralie A. Carothers , Carraway Kermit L.
Published: August 2002

ErbB2 has been implicated in numerous functions, including normal and aberrant development of a variety of tissues. Although no soluble ligand has been identified for ErbB2, we have recently shown that ASGP‐2, the transmembrane subunit of the cell surface glycoprotein Muc4 (also called sialomucin complex, SMC), can act as an intramembrane ligand for ErbB2 and modulate its activity. Muc4/SMC is abundantly expressed at the apical surface of most epithelia of the rat female reproductive tract. Since Muc4/SMC can interact with ErbB2 when they are expressed in the same cell and membrane, we investigated whether these two proteins are co‐expressed and co‐localized in tissues of the female reproductive tract. Using an anti‐ErbB2 antibody from Dako, we found moderate staining at the basolateral surface of the oviduct and also around the cell membrane of the most superficial and medial layers of the stratified epithelia of the vagina. In contrast, Neomarkers neu Ab1 antibody intensely stained the apical surface of the epithelium of the oviduct and the medial and basal layers of the stratified epithelia of the vagina, substantially overlapping the distribution of Muc4/SMC. Furthermore, Muc4/SMC and ErbB2 association in different tissues of the female reproductive tract was demonstrated by co‐immunoprecipitation analysis. Interestingly, phosphorylated ErbB2 detected by anti‐phospho‐ErbB2 is primarily present at the apical surface of the oviduct. Thus, our results show that differentially localized forms of ErbB2 are recognized by different antibodies and raise interesting questions about the nature of the different forms of ErbB2, the mechanism for differential localization, and possible functions of ErbB2 in the female reproductive tract. They also raise a cautionary note about the use of different ErbB2 antibodies for expression and localization studies. © 2001 Wiley‐Liss, Inc.
Induction of neutrophil apoptosis and secondary necrosis during endotoxin‐induced pulmonary inflammation in mice
Authors: Medan Djordje , Wang Liying , Yang Xiaodong , Dokka Sujatha , Castranova Vincent , Rojanasakul Yon
Published: August 2002

The present study investigated the relationship between apoptotic and necrotic cell death and their role in pulmonary inflammatory response to endotoxin. Pulmonary administration of lipopolysaccharide (LPS) caused a rapid increase in the levels of pro‐inflammatory cytokine TNF‐α and inflammatory cell influx in the bronchoalveolar lavage (BAL) fluids. Control mice showed only resident alveolar macrophages with no apoptosis, whereas LPS‐treated mice showed clear apoptosis of BAL cells. Microscopic studies confirmed the presence of apoptotic neutrophils and macrophages ingesting apoptotic bodies. The number of apoptotic neutrophils increased concomitantly with the increase in neutrophil influx which peaked 1 day after the treatment. However, necrosis was not detected at this early time, but increased subsequently and peaked at day 3. The levels of necrosis and apoptosis were both elevated and prolonged at high LPS doses. Treatment of mice with phosphatidylserine (PS)‐containing liposome, known to inhibit macrophage phagocytosis of apoptotic cells, increased the level of apoptosis and necrosis caused by LPS, whereas control non‐PS liposome or saline treatment had no effects. We conclude that necrosis occurs secondary to apoptosis in LPS‐treated lung model and that this development is not the result of direct insult by LPS. Instead, our results and previous studies suggest that inefficient clearance of apoptotic cells by macrophages contributes, at least in part, to the levels of apoptosis and necrosis induced by LPS. Because necrosis is associated with cell damage and release of histotoxic contents, this development is likely to play a role in determining the severity and duration of lung toxicity induced by endotoxin. © 2002 Wiley‐Liss, Inc.
β‐estradiol stimulation of DNA synthesis requires different PKC isoforms in HepG2 and MCF7 cells
Authors: Marino Maria , Distefano Enza , Caporali Simona , Ceracchi Gianna , Pallottini Valentina , Trentalance Anna
Published: August 2002

The role exerted by protein kinase C (PKC) on estrogen‐induced DNA synthesis has been investigated in hepatic and mammary gland cells, HepG2 and MCF7. 17‐β‐estradiol stimulated DNA synthesis in HepG2 and MCF7 cells, maximal effect occurring at 10 nM. DNA synthesis stimulation was prevented by anti‐estrogen ICI 182,780 and by inhibitor of PKC, Ro 31‐8220. The rapid estradiol effects in MCF7 cells were determined by following the inositol trisphosphate (IP3) production and PKC‐α membrane translocation. After estradiol treatment the increase of IP3 production, prevented by anti‐estrogen or by phospholipase C (PLC) inhibitor (neomycin), was present in MCF7 cells. In MDA cells, devoid of estrogen receptor, no effect was observed. The PKC‐α presence on the membranes appeared unchanged in MCF7 cells. The PLC inhibitors, neomycin and U73,122, and PKC‐α down regulator, phorbol 12‐myristate 13‐acetate (PMA), were able to prevent estradiol‐induced DNA synthesis in hepatoma cells, but ineffective in mammary cells; wortmannin, an inhibitor of phosphoinositide 3‐kinases (PI3‐K), blocked DNA synthesis in both cell lines. These data show that β‐estradiol, via an estrogen receptor‐mediated mechanism, activates more signal transduction pathways, and consequently different PKC isoforms in two responsive cell lines. In both cell lines PI3‐K/PKC pathway is functional to the estrogen regulation of DNA synthesis, whereas in HepG2 cells the parallel involvement of the PLC/PKC‐α pathway is present. The reported results indicate that the DNA synthesis stimulation by β‐estradiol requires the estrogen receptor and utilises one or more activated pathways in dependence on the cell equipment. © 2001 Wiley‐Liss, Inc.
High‐level extracellular production of penicillin acylase by genetic engineering of Escherichia coli
Authors: Lin Wen‐Jer , Huang Shin‐Wei , Chou C Perry
Published: August 2002

The extracellular production of penicillin acylase (PAC) in genetically engineered Escherichia coli by coexpression of the brp gene encoding bacteriocin release protein (BRP) and the pac gene was demonstrated. Cell physiology was affected while PAC was released into the medium, depending on the strategy for brp expression. The performance for the production and release of PAC was optimized by taking several culture parameters, including host, inducer (mitomycin C) concentration, and induction timing for brp expression, into consideration. The effect of PAC release on inclusion body formation was also investigated. It was observed that the amount of inclusion bodies was significantly affected by brp expression. A reason for the limitation of PAC production and a strategy for resolving this problem are proposed.

© 2001 Society of Chemical Industry
Use of the axial dispersion model to describe the O3 and O3 /H2O2 advanced oxidation of alachlor in water
Authors: Beltrán Fernando J , González Manuel , Acedo Benito , Rivas Javier
Published: August 2002

Experiments on alachlor degradation by ozonation alone and combined with hydrogen peroxide using different surface waters have been conducted in a reactor bubble column and a kinetic model of the advanced oxidation process has been proposed. Variables studied were the nature of the surface water (four surface waters were treated), pH (3.5–9.7) and hydrogen peroxide to ozone mass ratio at the column inlet (0.1–1.85 g g−1). Data on residence time distribution, rate constants and the absorption kinetic regime were considered to prepare the kinetic model, which was also based on the axial dispersion model of non‐ideal flow. The model gives good predictions of alachlor and hydrogen peroxide conversions and the fraction of dissolved ozone (deviations were lower than ±15%) although it fails, in some cases, to yield accurate estimates of the observed experimental trends of concentrations in water at the reactor column outlet. The calculated results were close to those obtained from the more classical N well‐mixed tanks‐in‐series model (deviations with this model were lower than ±20%). It is concluded that quantitative deviations from experimental observations were likely due to the lack of rate data on ozone reactions with organic matter present in the surface waters investigated.

© 2002 Society of Chemical Industry
Sonographic appearances of galactoceles
Authors: Sawhney Sukhpal , Petkovska Liljana , Ramadan Salwa , Al‐Muhtaseb Sayeed , Jain Rajeev , Sheikh Mehraj
Published: August 2002

Purpose

The aim of this study was to investigate and summarize the sonographic appearances of galactoceles.

Methods

We retrospectively reviewed the sonograms and clinical records of 10 patients with galactoceles who had been examined over a 5‐year period to evaluate breast lumps that had occurred during lactation or the puerperium.

Results

Sonograms from all patients showed well‐defined lesions with thin, echogenic walls. The internal appearances of the lesions included homogeneous contents with medium‐level echoes in 6 patients and heterogeneous contents with fluid clefts and anechoic rims in 4 patients. Focal echogenic areas with distal shadowing were seen in 2 patients. Most of the lesions showed some distal acoustic enhancement, depending on the internal contents. The diagnosis of a galactocele was established by needle aspiration in 9 patients and by excision biopsy in 1 patient. Needle aspiration alone was therapeutic in 8 patients.

Conclusions

Galactoceles can have a wide range of sonographic appearances and can mimic other lesions of the breast, both benign and malignant. The clues to the diagnosis are recent childbirth and lactation and the presence of a well‐defined lesion with some distal acoustic enhancement. Needle aspiration of the lesion is both a diagnostic tool and an effective treatment in most patients with galactoceles. © 2002 John Wiley & Sons, Inc. J Clin Ultrasound 30:18–22, 2002.
Comparison of the sonographic features of acalculous and calculous submandibular sialadenitis
Authors: Ching Alex Sik‐Chung , Ahuja Anil T. , King Ann D. , Tse Gary Man‐Kit , Metreweli Constantine
Published: August 2002

Objective

The purpose of this study was to compare the sonographic features of acalculous and calculous sialadenitis of the submandibular gland.

Methods

A retrospective review of sonograms of the neck was performed in 25 patients with submandibular sialadenitis: 8 with acalculous and 17 with calculous disease. The submandibular glands were assessed for size, shape, border, and echogenicity; presence of dilated ducts or other intraglandular lesions; inflammatory changes in adjacent tissues; lymphadenopathy; and involvement of other salivary glands.

Results

In the group with acalculous sialadenitis, 4 (50%) of the 8 patients had unilateral disease, and 11 (92%) of 12 glands were rounded. In all cases (100%), multiple hypoechoic lesions were diffusely distributed throughout the submandibular glands against a heterogeneous parenchymal background. The lesions ranged from 3 to 15 mm and were oval or round. Confluent lesions were noted in 2 glands (17%). There was no sonographic evidence of duct dilatation, calculi, or abnormal lymph nodes. All patients with calculous sialadenitis had unilateral disease; 9 had a main duct calculus (53%), 7 had intraglandular calculi (41%), and 1 had both (6%). In 14 (82%) of 17 glands, normal shape was maintained, and 11 (65%) of 17 had duct dilatation.

Conclusions

Acalculous submandibular sialadenitis differs from the calculous form of the disease. The former has characteristic sonographic features, including a round gland with numerous hypoechoic lesions in a heterogeneous parenchymal background. Sonographic imaging in conjunction with fine‐needle aspiration is useful for detection of this disorder. © 2001 John Wiley & Sons, Inc. J Clin Ultrasound 29:332–338, 2001.
Scanning electron microscopic observation of microvasculature in periodontium
Authors: Matsuo Masato , Takahashi Kazuto
Published: August 2002

In this study, vascular resin cast models in the periodontium of beagle dogs were prepared and three‐dimensional observation of the relationship between the gingiva and periodontal ligament (PDL) vascular network was performed. After the perfusion of Ringer's solution and fixative, synthetic resin was injected from the inferior alveolar arteries. Soft tissue was digested by proteinase solution and specimens were examined under scanning electron microscope (SEM). The gingival vascular network (GVN) in the region facing the teeth consisted of sulcular and junctional epithelium. The vascular network of the sulcular epithelium (SE) had a renal glomerulus‐like form and the junctional epithelium (JE) consisted of squamous mesh. The gingival sulcular fluid exudated from the vascular network directly beneath the JE, and leukocytes permeated from the vascular network beneath the epithelium. Thus, we considered that the GVN performs an important function in the protection against the inflammation. Periodontal ligament had a polygonal mesh vascular network that was anastomosed to the venous plexus of alveolar bone through Volkmann's canals (VC). When occlusal force was applied, the blood in the periodontal vessels flowed out through VC into the bone marrow, and when the force was removed, it flowed backward into the PDL. This blood transfer acted as an absorber against occlusal force. Our findings suggest that the blood vessels of the gingiva perform an important function in defending against inflammation, while the blood vessels of the PDL play a key role in absorbing occlusal force. Microsc. Res. Tech. 56:3–14, 2002. © 2002 Wiley‐Liss, Inc.
Oocyte growth and follicular hierarchy may be locally controlled by an inhibin‐like protein in the lizard Podarcis sicula
Authors: Limatola Ermelinda , Manzo Clotilde , Manzo Sonia , Monti Maria Gaia , Rosanova Patrizia , Romano Maurizio
Published: August 2002

The lizard Podarcis shows an ovarian annual cycle with three to four ovulatory waves between April and July (reproductive period). In August to September, a refractory stage occurs, followed by a nonreproductive period (October to March), during which the oocytes undergo slow growth and prepare themselves for vitellogenesis and ovulation. In the reproductive period, only a certain number of oocytes start growing, giving rise to a follicular hierarchy, which is controlled by still unknown mechanisms. In the present paper, immunoreactive inhibin was detected in previtellogenetic follicles of the reproductive period, and in particular, in the pyriform cells of the follicular epithelium. As the follicle grew and the pyriform cells disappeared, immunostaining shifted to the oocyte cytoplasm. The smaller follicles did not show any immunoreactivity. In the nonreproductive period, no follicles were labeled. We conclude that in the reproductive period, inhibin characterizes the follicles destined to ovulation and might be one of the main factors controlling follicular hierarchy. J. Exp. Zool. 292:96–102, 2002. © 2002 Wiley‐Liss, Inc.
Knowledge facts, knowledge fiction: the role of ICTs in knowledge management for development
Authors: Van Der Velden Maja
Published: August 2002

What happens when corporate knowledge management monoculture meets the diverse international development sector? This paper finds that development agencies have too readily adopted approaches from the Northern corporate sector that are inappropriate to development needs. These approaches treat knowledge as a rootless commodity, and information and communications technology as a key knowledge tool. Alternative approaches are required, that focus on the knower and on the context for creating and sharing knowledge. ICT tools need to support this approach, helping people develop appropriate or alternative scenarios and improving the accessibility of information and knowledge for people with different cultural, social, or educational backgrounds. Copyright © 2002 John Wiley & Sons, Ltd.
Cyclopentadienyl technetium (99mTc) tricarbonyl piperidine conjugates: biodistribution and imaging studies
Authors: Saidi Mouldi , Kothari K. , Pillai M. R. A. , Hassan Amri , Sarma H. D. , Chaudhari P. R. , Unnikrishnan T. P. , Korde A. , Azzouz Zohra
Published: August 2002

Synthesis of organometallic complexes of 99mTc using the precursor ligands N‐methylpiperidino‐4[(bispentahaptocyclopentadienyl)iron] carboxylate and N‐(isopropyl)‐piperidino‐4[(bispentahaptocyclopentadienyl)iron]carboxylate is described. The labelling method involved reaction of the ligands with 99mTcO in the presence of Mn(CO)5Br in dimethyl formamide at 150°C for 1 h in an oil bath. The purification of the complexes was carried out by preparative TLC using ethery/n‐butyl methyl amine (95:5) solvent system. The purified complexes were characterized by HPLC using acetonitrile:water (80:20) solvent system in a PRP‐1 column in which both the complexes were eluted as single peaks. Biodistribution studies carried out in rats showed 2.4±0.14 and 1.1±0.42% of the injected activity in the brain tissue 5 min p.i. for cytectrene I and II, respectively. The brain to blood activity ratio was >15:1 for both the complexes at 5 min p.i. Scintigraphic studies in rabbits showed significant uptake of the activity in the brain with fast clearance from blood. The complexes warrant further investigation as agents for brain imaging. Copyright © 2001 John Wiley & Sons, Ltd.
Effect of IL‐1β‐induced macromolecular depletion on residual quadrupolar interaction in articular cartilage
Authors: Borthakur Arijitt , Shapiro Erik M. , Beers Jennifer , Kudchodkar Sagar , Kneeland J. Bruce , Reddy Ravinder
Published: August 2002

Purpose

Sodium multiple‐quantum filtered (MQF) NMR spectroscopy may potentially be used to measure proteoglycan (PG) depletion in cartilage caused by osteoarthritis (OA). The purpose of this work was to quantify the effect of interleukin‐1 (IL‐1β)‐induced macromolecule depletion on the residual quadrupolar interaction (RQI) of sodium in bovine cartilage plugs.

Materials and Methods

Fifteen 8‐mm‐diameter cartilage plug specimens were cored from the articular surface of fresh bovine patellae. All plugs were kept in culture media and nine of the plugs were subjected to interleukin‐1 (IL‐1β)‐induced degeneration of cartilage for 4, 6, and 7 days. Sodium NMR spectra were obtained from each sample with a 1‐cm‐diameter solenoid coil in a 2T whole‐body magnet interfaced to a custom‐built spectrometer. We employed a previously described theoretical model to analyze triple‐quantum filtered (TQF) and double‐quantum filtered magic angle (DQFMA) spectra obtained from normal cartilage and cartilage treated with IL‐1β. The model assumes a static Gaussian distribution of the RQI frequency, ωQ, in the sample. TQF and DQFMA spectra from each sample were fitted with the appropriate signal expressions to determine σ (the root mean square (RMS) ωQ), T2f, and T2s. An inversion‐recovery sequence was used to determine T1 of each plug. A spectrophotometric assay was used to determine the amount of PG depleted from each plug. Histology was performed to visualize the PG loss in cartilage plugs. We defined σ as the measure of changes in macroscopic order in the tissue.

Results

Simulated spectra from the theoretical model were in excellent agreement with the experimental data. We were able to determine the relaxation times as well as σ of each specimen from their corresponding fits. T2f ranged between
2.26–3.50 msec, decreasing with increased PG loss. Over the range of PG depletion investigated, T2s increased from 12.3 msec to 14.9 msec, and T1 increased from 16 msec to 21 msec, while σ decreased from 180 Hz to 120 Hz. The order of macromolecules in the cartilage tissue decreased substantially with PG loss. Histology sections clearly showed qualitative visualization of the PG loss in cartilage following treatment with IL‐1β.

Conclusion

We demonstrated that IL‐β‐induced macromolecule depletion in cartilage not only changes the relaxation characteristics of sodium but also changes RQI of the tissue. Using MQF sodium spectroscopy we quantified the changes in σ and showed that loss of macromolecules reduces the degree of order in the tissue. J. Magn. Reson. Imaging 2002;15:315–323. © 2002 Wiley‐Liss, Inc.
Comparison of fat suppression strategies in 3D spiral coronary magnetic resonance angiography
Authors: Börnert Peter , Stuber Matthias , Botnar René M. , Kissinger Kraig V. , Manning Warren J.
Published: August 2002

Purpose

In the present study, the impact of the two different fat suppression techniques was investigated for free breathing 3D spiral coronary magnetic resonance angiography (MRA). As the coronary arteries are embedded in epicardial fat and are adjacent to myocardial tissue, magnetization preparation such as T2‐preparation and fat suppression is essential for coronary discrimination.

Material and Methods

Fat‐signal suppression in three‐dimensional (3D) thin‐ slab coronary MRA based on a spiral k‐space data acquisition can either be achieved by signal pre‐saturation using a spectrally selective inversion recovery pre‐pulse or by spectral‐spatial excitation. In the present study, the performance of the two different approaches was studied in healthy subjects.

Results

No significant objective or subjective difference was found between the two fat suppression approaches.

Conclusion

Spectral pre‐saturation seems preferred for coronary MRA applications due to the ease of implementation and the shorter cardiac acquisition window. J. Magn. Reson. Imaging 2002;15:462–466. © 2002 Wiley‐Liss, Inc.
MR pattern of hyperacute cerebral hemorrhage
Authors: Wintermark Max , Maeder Philippe , Reichhart Marc , Schnyder Pierre , Bogousslavsky Julien , Meuli Reto
Published: August 2002

Magnetic resonance (MR) pattern of cerebral hemorrhage relates mainly to the relaxation and susceptibility effects of iron‐containing hemoglobin degradation products, as well as to their intra‐ or extracellular location. The purpose of this article is to report two acute stroke patients who underwent thrombolytic therapy and developed hyperacute cerebral hemorrhage during their admission cerebral MR survey. They constitute the earliest MR appearance of hyperacute intracerebral bleeding reported in the literature, featuring increased diffusion properties and persistent susceptibility effect on perfusion‐weighted imaging (PWI)‐series. J. Magn. Reson. Imaging 2002;15:705–709. © 2002 Wiley‐Liss, Inc.
The introduction of MR in the nordic countries with special reference to Norway: Central control versus local initiatives
Authors: Smith Hans‐Jørgen
Published: August 2002

The introduction of MR technology in Norway differed from that in Denmark, Finland and Sweden. In the latter countries, decisions were made at county or local level while in Norway the process was steered by the government and the national health authorities. For several reasons the steering was not very successful, and the intention of buying one MR unit ended with the purchase of five units. As a counter‐reaction, for seven years only university hospitals were allowed to purchase MR equipment. In 1993, the strict regulations were abolished, and during the succeeding years all four Nordic countries experienced similar exponential growth in the number of MR units. J. Magn. Reson. Imaging 2001;13:639–644. © 2001 Wiley‐Liss, Inc.
Improved mapping of pharmacologically induced neuronal activation using the IRON technique with superparamagnetic blood pool agents
Authors: Chen Yin‐Ching I. , Mandeville Joseph B. , Nguyen Tuong V. , Talele Anjali , Cavagna Friedrich , Jenkins Bruce G.
Published: August 2002

The use of functional magnetic resonance imaging (fMRI) techniques for evaluation of pharmacologic stimuli has great potential for understanding neurotransmitter dynamics for a number of brain disorders, such as drug abuse, schizophrenia, epilepsy, or neurodegeneration. Unfortunately, blood oxygenation level‐dependent (BOLD) imaging at common fields strengths, such as 1.5 or 3 T, has very low sensitivity and contrast‐to‐noise ratios (CNRs). We demonstrate here the utility of using an intravascular superparamagnetic iron oxide contrast agent with a long plasma half‐life for evaluation of hemodynamic changes related to dopaminergic stimuli using amphetamine or the cocaine analog 2β‐carbomethoxy‐3β‐(4‐fluorophenyl)tropane (CFT). We refer to this technique as increased relaxation with iron oxide nanoparticles (IRON). Results obtained here show that even at field strengths as high as 4.7 T, one can obtain increases in CNR by factors of 2–3 over BOLD imaging that lead to greater than an order of magnitude increase in statistical power with greatly increased sensitivity to hemodynamic changes in brain regions difficult to observe using BOLD imaging. Furthermore, use of the intravascular contrast agent allows for a meaningful physiologic parameter to be measured (relative cerebral blood volume (rCBV)), compared to conventional BOLD imaging. J. Magn. Reson. Imaging 2001;14:517–524. © 2001 Wiley‐Liss, Inc.
Cross‐checking of nanoelectrospray ionization mass spectrometry and computer simulation for the evaluation of the interaction strength of non‐covalently bound enkephalins in solution
Authors: Ishikawa Keiichiro , Nakamura Takako , Koga Yoshinori
Published: August 2002

Nanoelectrospray ionization mass spectrometry (nanoESI‐MS) and computer simulation were applied to the characterization of non‐covalent interactions of [Leu5]‐enkephalin (LE) and its optical isomers, [D‐Tyr1, Leu5]‐enkephalin (Y‐LE), [D‐Phe4, Leu5]‐enkephalin (F‐LE) and [D‐Tyr1, D‐Phe4, Leu5]‐enkephalin (YF‐LE). The dimer formation tendencies of the optical isomers of LE were evaluated by nanoESI‐MS using quadruply deuterated LE (H2N‐Tyr‐(2,2‐d2)Gly‐(2,2‐d2)Gly‐Phe‐Leu‐COOH, d4‐LE) as an internal standard. The relative interaction strengths of the optical isomers of LE were estimated to be Y‐LE < F‐LE < LE < YF‐LE. Geometry optimization calculations were performed for interactions in vacuo and in water using a semi‐empirical SCF method (PM3). The initial coordinate of the dimer structure of LE was taken from that obtained from single‐crystalline x‐ray diffraction analysis. Estimates of the interaction strengths of the dimer complexes were based on the heats of formation of a dimer complex (Hd) and the corresponding monomers (Hm) using the equation ΔH = Hd − 2Hm. The values of ΔH obtained from the calculations for interactions in water decreased in the order Y‐LE > F‐LE > LE > YF‐LE. Since the smaller values of ΔH correspond to stronger interactions between peptides, the results from computer simulations were qualitatively consistent with those obtained from the nanoESI experiments. The possibility of cross‐checking these independent techniques was demonstrated using medium‐sized molecules of biological importance. The agreement of the results from the two techniques suggested that nanoESI experiments, at least qualitatively, reflected the relative interaction strengths of non‐covalently bound enkephalins in aqueous solution. Copyright © 2001 John Wiley & Sons, Ltd.
Tuning compounds for electrospray ionization/in‐source collision‐induced dissociation and mass spectra library searching
Authors: Weinmann Wolfgang , Stoertzel Mylène , Vogt Susanne , Svoboda Michal , Schreiber André
Published: August 2002

Tuning compounds for positive and negative electrospray ionization (ESI) were tested for the tuning of in‐source collision‐induced dissociation (ESI/CID) with three types of SCIEX API instruments (API 365, 2000 and 3000) in the single‐quadrupole mode. The vacuum interfaces of these instruments differ slightly in geometry, but the principles of ionization and solvent evaporation by nebulizer and curtain gases, orifice and skimmer are identical. For comparison of in‐source CID, breakdown curves of haloperidol, paracetamol, metronidazole and metamizole were acquired by increasing the orifice voltages. The API 2000 and 3000 required higher orifice voltages than did the API 365 to induce a similar degree of fragmentation of the protonated or deprotonated molecules to characteristic fragment ions. This increase of orifice voltage could be demonstrated with each of the four compounds tested by a shift of the maxima of the breakdown curves to higher orifice voltages. A procedure with three collision energy (CE) levels for drug identification with a mass spectra library set up with an API 365 therefore required an adjustment of the orifice voltages to higher values when being transferred to an API 2000 or API 3000. The corresponding orifice voltages for the three instruments were 20/50/80 V (API 365), 30/90/130 V (API 2000) and 40/80/120 V (API 3000). However, a change in orifice voltage of ±10 V (with the API 2000 and 3000) hardly influenced the fit values of a library search for each single CE level. For adjusting orifice voltages with different instruments, a tuning procedure with haloperidol and paracetamol is presented. With this tuning procedure an ESI/CID mass spectra library set up for API 365 and API 150 could also be used for drug identification with an API 2000 and an API 3000 with good library search results. Copyright © 2001 John Wiley & Sons, Ltd.
Enterovirus sequences resembling coxsackievirus A2 detected in stool and spleen from a girl with fatal myocarditis
Authors: Bendig Justin W.A. , O'Brien Patrick S. , Muir Peter , Porter Helen J. , Caul E. Owen
Published: August 2002

A 10‐year‐old girl who died suddenly was found at post mortem to have myocarditis. Virus could not be cultured from post‐mortem stool, spleen or heart but enterovirus RNA was detected in stool and spleen by PCR, and the stool caused flaccid paralysis in newborn suckling mice. A 654 base pair (bp) sequence from the capsid‐coding region of the viral genome was amplified from an affected mouse and sequenced. Using this sequence, strain‐specific nested primers were designed and used to amplify viral sequences directly from stool and spleen. These sequences were identical to each other and to that obtained from the infected mouse, and most closely resembled Coxsackievirus A2, an uncommon serotype rarely associated with myocarditis. Testing spleen tissue may be useful in etiological investigation of suspected viral myocarditis. PCR proved more sensitive than suckling mouse inoculation in detecting this Coxsackievirus, but a combination of both methods was required for genotypic characterization. J. Med. Virol. 64:482–486, 2001. © 2001 Wiley‐Liss, Inc.
Pyramidal and extrapyramidal involvement in experimental infection of cynomolgus monkeys with enterovirus 71
Authors: Nagata Noriyo , Shimizu Hiroyuki , Ami Yasushi , Tano Yoshio , Harashima Ayako , Suzaki Yuriko , Sato Yuko , Miyamura Tatsuo , Sata Tetsutaro , Iwasaki Takuya
Published: August 2002

Among the enteroviruses, polioviruses and enterovirus 71 (EV71) are two major neurotropic viruses causing serious neurological manifestations. While polioviruses are being eradicated globally by vaccination, EV71 still has the potential to cause a large outbreak such as that in Taiwan in 1998, in which there were many fatalities. In this study, we determined the neurovirulence of EV71 by neuropathological analysis of cynomolgus monkeys after experimental infection with five EV71 strains, which were isolated from individual patients with fatal encephalitis; meningitis; and hand, foot, and mouth disease. After intraspinal inoculation, the monkeys developed neurological manifestations within 1–6 days post‐inoculation, irrespective of the inoculated strains. These manifestations included not only pyramidal tract signs such as flaccid paralysis, but also extrapyramidal tract signs such as tremor and ataxia. Histological and viral examinations confirmed virus replication in the spinal cord, brainstem, cerebellar cortex, and dentate nuclei, and cerebrum. The strains isolated during the 1970s and 1990s showed no particular differences with respect to neurotropism. Thus, it is clear that EV71 has a wider neurotropism than that of polioviruses. J. Med. Virol. 67:207–216, 2002. © 2002 Wiley‐Liss, Inc.
Nitric oxide‐induced programmed cell death in human neuroblastoma cells is accompanied by the synthesis of Egr‐1, a zinc finger transcription factor
Authors: Cibelli Giuseppe , Policastro Vincenza , Rössler Oliver G. , Thiel Gerald
Published: August 2002

Nitric oxide (NO) is cytotoxic for human SH‐SY5Y neuroblastoma cells. While nuclear condensation was visible in cells treated with nitric oxide donors, we observed that the plasma membrane remained intact, indicating that NO induced apoptotic cell death. We analyzed the NO‐induced apoptotic signaling cascade in SH‐SY5Y cells and observed a striking increase in early growth response (Egr)‐1 promoter activity as a result of NO‐induced cell death. Likewise, we detected an activation of the transcriptional activation potential of the ternary complex factor Elk1, a key transcriptional regulator of serum response element‐driven gene transcription. Egr‐1 is a zinc finger transcription factor that couples extracellular signals to long‐term responses by altering expression of Egr‐1 target genes. The Egr‐1 5′‐flanking region contains five serum response elements (SRE) that function as genetic elements for stimulus‐transcription coupling. Moreover, these SREs are binding sites for Elk1, suggesting that NO activated Egr‐1 gene transcription via activation of Elk1. The NO‐induced biosynthesis of Egr‐1 was confirmed by Western blot analysis and an NO‐dependent increase in the transcriptional activation potential of Egr‐1 was observed. The fact that NO‐induced neuronal cell death is accompanied by the biosynthesis of Egr‐1 suggests that Egr‐1 may be an integral part of the NO triggered apoptotic signaling cascade. © 2002 Wiley‐Liss, Inc.
Trafficking of axonal K+ channels: Potential role of Hsc70
Authors: Clay John R. , Kuzirian Alan
Published: August 2002

Voltage‐gated potassium ion channels in axons underlie the repolarization phase of the membrane action potential and help to set the resting potential. In addition to being present in the axolemma, they are also found in axoplasm in small vesicles, 30–50 nm in diameter, which may serve as a reserve pool of K+ channel protein (Clay and Kuzirian [2000] J Neurobiol 45:172–184). We have developed a novel technique for extracting these vesicles from axoplasm, which relies on the ability of Texas red to bind to them, thereby reducing their buoyancy so that they are amenable to pelleting by ultracentrifugation (Clay and Kuzirian [2000] J Neurobiol 45:172–184). The mechanism underlying this process may be binding of Texas red to Hsc70, which is primarily a cytosolic protein. However, a small portion of it is located on the surface of vesicles. Kinesin is also on the vesicle surface. This protein is membrane bound in our in vitro vesicle preparation when solutions that do not contain MgATP are added to extruded axoplasm. The addition of MgATP to the solution appears to release a significant amount of kinesin from the vesicles, possibly by the Hsc70‐MgATP catalysis mechanism recently proposed by Tsai et al. Published 2002 Wiley‐Liss, Inc.
NID67, a small putative membrane protein, is preferentially induced by NGF in PC12 pheochromocytoma cells
Authors: Vician Linda , Silver Abigail L. , Farias‐Eisner Robin , Herschman Harvey R.
Published: August 2002

In an effort to identify genes involved in neuronal differentiation, we have used representational difference analysis (RDA) to clone cDNAs that are preferentially induced by nerve growth factor (NGF) vs. epidermal growth factor (EGF) in PC12 pheochromocytoma cells. We now report the cloning of a previously unknown primary response gene, NID67. In addition to a robust induction by NGF and FGF, both of which cause PC12 cells to differentiate, NID67 is strongly induced by forskolin, A23187 and ATP. EGF, TPA and KCl induce NID67 only weakly. NID67 mRNA is most abundant in heart, ovary and adrenal. Modest levels are present in most brain regions, testis, thyroid, thymus, pituitary, kidney and intestine; little NID67 is present in skeletal muscle and cerebellum. The NID67 cDNA contains a 180 bp open reading frame (ORF) that encodes a 60 amino acid protein. The central 29 amino acids are very hydrophobic and very likely comprise a transmembrane domain. Mouse and human NID67 cDNAs contain an ORF similar to NID67; the rat and human protein sequences are 85% identical whereas the rat and mouse sequences are 92% identical. In vitro transcription and translation reactions confirmed that the ORF we identified produces a 6000 Da protein product. Several small membrane proteins are similar to NID67; they contain a transmembrane domain and little more. All of these proteins participate in forming or regulating ion channels. NID67 may play a similar role in cellular physiology. J. Neurosci. Res. 64:108–120, 2001. © 2001 Wiley‐Liss, Inc.
Modification of the porphyrin chromophore by ring fusion: identifying trends due to annelation of the porphyrin nucleus
Authors: LASH TIMOTHY D.
Published: August 2002

The effects exerted by fused aromatic rings on the UV-vis spectra of porphyrins are surveyed. Modified porphyrin chromophores with fused benzene, 1,2-naphthalene, 9,10-phenanthrene or phenanthroline rings are surprisingly little affected even when a maximum number of ring fusions are incorporated. Linearly annealed naphtho- or anthraporphyrins show large red shifts to the Q bands but the Soret absorptions are weakened and undergo only minor bathochromic shifts. Fluoranthoporphyrins give multiple bands in the Soret region, but the Q band region is virtually unaffected by this tetracyclic ring system. On the other hand, metal chelates of fluoranthoporphyrins show surprisingly strong bands near 600 nm. Benzothiadiazole rings split and weaken the Soret band, but the Q bands region is unexceptional. However, metal coordination again produces relatively intense bands near 600 nm. The most significant results were obtained for porphyrins with fused acenaphthylene rings. Monoacenaphthoporphyrins (41) have three Soret bands at 387, 431 and 454 nm, and the longest wavelength Q band is shifted to 658 nm. opp-Diacenaphthoporphyrin (43) further shifts these bands with two Soret absorbances at 443 and 470 nm, and an additional strong peak is observed at 692 nm. The metal complexes of these systems also show strong bands between 602 and 656 nm. Still larger effects are produced by tetraacenaphthoporphyrin (47), the dication for which in trifluoroacetic acid (TFA)–chloroform has a Soret absorption at 528 nm. Tetraaryltetraacenaphthoporphyrins (48) are even more red shifted, showing Soret bands between 556 and 570 nm for the free bases and 565 to 588 nm for the related dications. The lead(II) chelate for tetraphenylporphyrin (48a) shows an additional 'hyper' spectral shift that brings the Soret band to 604 nm, and this effect can also be achieved by introducing four meso-phenylethynyl substituents onto the tetraacenaphthoporphyrin nucleus (49). In addition, by combining these two factors for the lead(II) chelate of 49, a record-breaking value for the Soret band of 642 nm can be achieved. Spectral shifts due to ring annelation in porphyrin analogues are also discussed, including those for oxybenziporphyrins, oxypyriporphyrins, carbaporphyrins and sapphyrins.