bluuebunny/crossref_metadata_2025 huggingface dataset:
Late (> 48 hr) myocardial infarction after PTCA: Clinical and angiographic characteristics of infarction related or not to the angioplasty site
Authors: Rodés Josep , Tanguay Jean‐François , Bertrand Olivier F. , Malekianpour Mehrdad , Lespérance Jacques , Côté Gilles , Théroux Pierre
Published: August 2002

Since late myocardial infarctions after percutaneous coronary interventions have not been well characterized, we intended to evaluate the characteristics of myocardial infarctions occurring > 48 hr after balloon angioplasty of native coronary arteries or saphenous vein grafts. The Montreal Heart Institute database (1985–1996) was interrogated for all patients readmitted with a diagnosis of MI more than 48 hr after successful percutaneous transluminal coronary angioplasty (PTCA). We compared the clinical, procedural, and angiographic variables between MIs related or not to the index PTCA site. One hundred and ninety‐three patients presented with late myocardial infarction (MI) following balloon angioplasty. The median time elapsed between PTCA and MI was 55 days compared to 968 days when MI was unrelated to the PTCA site. MIs related to the PTCA site were more likely non–Q‐wave (76% vs. 35%, P = 0.0001) with less marked CK‐MB rise. Angiography showed less complex lesions (63% vs. 90%, P = 0.001) and better thrombolysis in myocardial infarction (TIMI) grade flow (TIMI II to III, 66% vs. 56%, P = 0.01) when the culprit lesion was at the PTCA site. Independent predictors of MI at the PTCA site were vein graft dilation, female sex, and residual stenosis post‐PTCA. Myocardial infarctions occurring late after PTCA have a distinct time course and present specific characteristics according to their relationship or not to the previously dilated site. Cathet Cardiovasc Intervent 2001;53:155–162. © 2001 Wiley‐Liss, Inc.
Three‐year follow‐up after rotational atherectomy for the treatment of diffuse in‐stent restenosis: Predictors of major adverse cardiac events
Authors: Radke Peter W. , vom Dahl Juergen , Hoffmann Rainer , Klues Heinrich G. , Hosseini Massud , Janssens Uwe , Hanrath Peter
Published: August 2002

Restenosis remains the major limitation of coronary stent implantation, especially in diffuse forms of in‐stent restenosis. In this study, rotablation (RA) with adjunct angioplasty of in‐stent restenosis was performed in 84 patients. Clinical follow‐up and control angiography were obtained 6‐month postprocedure. The rate of recurrent restenosis after rotablation for in‐stent restenosis at 6‐month angiographic follow‐up was 45%, resulting in a rate of major adverse cardiac events of 35%. At 3‐year follow‐up, the cumulative event‐free survival rate was 57% for the entire population. The only predictor of MACE at 3‐year clinical follow‐up by multivariate logistic regression analysis was in‐stent lesion length. RA for the treatment of diffuse in‐stent restenosis is thereby characterized by high procedural success rates and recurrent angiographic restenosis in 45% of patients with diffuse lesions. Major adverse cardiac events occur most likely within the first 6 months postprocedure. Three years after rotablation of in‐stent restenosis, 43% of patients had experienced at least one major adverse cardiac event. Cathet Cardiovasc Intervent 2001;53:334–340. © 2001 Wiley‐Liss, Inc.
Inadvertent stent extraction six months after implantation by an entrapped cutting balloon
Authors: Harb Tareq S. , Ling Frederick S.
Published: August 2002

We report a case of extraction of a restenosed aorto‐ostial stent by an entrapped cutting balloon that had inadvertently been passed through a protruding stent cell. Cathet Cardiovasc Intervent 2001;53:415–419. © 2001 Wiley‐Liss, Inc.
Initial results of the quanam drug eluting stent (QuaDS‐QP‐2) registry (BARDDS) in human subjects
Authors: de la Fuente Luis M. , Miano Jorge , Mrad Jorge , Penaloza Eduardo , Yeung Alan C. , Eury Robert , Froix Michael , Fitzgerald Peter J. , Stertzer Simon H.
Published: August 2002

Thirty‐two patients presenting with varied coronary syndromes and anatomy were treated with a new coronary multisleeve drug delivery coronary stent (QuaDS‐QP‐2) containing up to 4,000 μg of a taxol‐derived lipophilic microtubule inhibitor (QP2). The device was successfully implanted in 32 patients who have been followed for up to 2 years. Twenty‐five patients have undergone stress ECHO or SPECT Thallium and all are currently asymptomatic. Thirteen patients have already been restudied angiographically, by IVUS and/or by SPECT Thallium testing and are detailed in this report. Angiographic, IVUS, and SPECT Thallium have been controlled at a mean of 11.2 months (range, 6–15 months) in this 13‐patient cohort. Although all 13 QuaDS‐QP‐2 (QDES) stents were angiographically and IVUS patent, two reinterventions have been required in the 32‐patient study group thus far, both relate to either new disease or to distal, small‐vessel disease beyond the stent. There was no evidence of significant proliferation in the QDES devices. On the basis of this preliminary data and a European pilot study, a controlled randomized trial (SCORE) is currently in progress in western Europe. Cathet Cardiovasc Intervent 2001;53:480–488. © 2001 Wiley‐Liss, Inc.
Long‐term clinical safety and efficacy of NIROYAL vs. NIR intracoronary stent
Authors: Harding Scott A. , McKenna Charles J. , Flapan Andrew D. , Boon Nicholas A.
Published: August 2002

Research in vitro and in animal models suggested that gold electroplating of stents can attenuate neointimal hyperplasia and reduce thrombogenicity. The objective of this study was to evaluate the safety and efficacy of the gold‐coated NIROYAL stent in the treatment of stenosed coronary arteries and bypass grafts. We retrospectively studied 181 consecutive patients undergoing deployment of NIR (n = 87) or NIROYAL (n = 94) coronary stents in a single tertiary referral center from July 1997 to December 1998. Mean follow‐up duration for the NIR and NIROYAL patient groups were 11.6 and 11.4 (range, 3–12) months, respectively. Stent thrombosis rates were 3/87 (3%) in the NIR and 0/94 (0%) in the NIROYAL group (P = 0.07). The need for target lesion revascularization (TLR) in the NIR patient group was 8/87 (9%) compared to 11/94 (12%) in the NIROYAL patient group (P = 0.6). The overall MACE rates for the NIR and NIROYAL patient groups were 24/87 (28%) and 22/94 (23%), respectively (P = 0.5). The present study, hence, implies equivalence between the stainless steel NIR and the gold‐plated NIROYAL stent with no significant difference in immediate and long‐term clinical performance profiles. Cathet Cardiovasc Intervent 2001;54:141–145. © 2001 Wiley‐Liss, Inc.
Subarachnoidal hemorrhage following carotid stenting with the distal‐balloon protection
Authors: Al‐Mubarak Nadim , Roubin Gary S. , Vitek Jiri J. , Iyer Sriram S. , New Gishel , Leon Martin B.
Published: August 2002

A 61‐year‐old man underwent carotid stenting with the distal‐balloon protection system for symptomatic carotid artery stenosis. During the procedure, progressive elevation of the systolic blood pressure occurred, reaching a peak of 220 mm Hg immediately following deflation of the distal balloon. This was associated with severe headaches and progressive deterioration in the mental status to a coma. Head CT scan showed massive subarachnoidal hemorrhage contralateral to the stented side and a secondary intracerebral hemorrhage. Despite immediate successful blood pressure control, his condition deteriorated and he died 2 days later. Cathet Cardiovasc Intervent 2001;54:521–523. © 2001 Wiley‐Liss, Inc.
Sequence search algorithms for single pass sequence identification: does one size fit all?
Authors: Cara Woodwark K. , Hubbard Simon J. , Oliver Stephen G.
Published: August 2002

Bioinformatic tools have become essential to biologists in their quest to understand the vast quantities of sequence data, and now whole genomes, which are being produced at an ever increasing rate. Much of these sequence data are single‐pass sequences, such as sample sequences from organisms closely related to other organisms of interest which have already been sequenced, or cDNAs or expressed sequence tags (ESTs). These single‐pass sequences often contain errors, including frameshifts, which complicate the identification of homologues, especially at the protein level. Therefore, sequence searches with this type of data are often performed at the nucleotide level. The most commonly used sequence search algorithms for the identification of homologues are Washington University's and the National Center for Biotechnology Information's (NCBI) versions of the BLAST suites of tools, which are to be found on websites all over the world. The work reported here examines the use of these tools for comparing sample sequence datasets to a known genome. It shows that care must be taken when choosing the parameters to use with the BLAST algorithms. NCBI's version of gapped BLASTn gives much shorter, and sometimes different, top alignments to those found using Washington University's version of BLASTn (which also allows for gaps), when both are used with their default parameters. Most of the differences in performance were found to be due to the choices of default parameters rather than underlying differences between the two algorithms. Washington University's version, used with defaults, compares very favourably with the results obtained using the accurate but computationally intensive Smith–Waterman algorithm. Copyright © 2001 John Wiley & Sons, Ltd.
Asymmetric induction in the [4+2]cycloaddition of cyclopentadiene and furan to chiral derivatives of fumaric acid
Authors: Kucharska Anna , Gorczyńska Renata , Chapuis Christian , Jurczak Janusz
Published: August 2002

[4+2]Cycloaddition reactions of cyclopentadiene (1a) and furan (1b) to N,N′‐fumaroyldi[(2R)‐bornane‐10,2‐sultam] (2) and to N,N′‐fumaroyldi[(2R)‐bornane‐10,2‐(2′‐phenyl‐pyrazol‐3′‐one)] (3) are presented. A correlation between the solvent polarity and the logarithm of the diastereoisomer ratio (dr) was found for the uncatalyzed [4+2]cycloaddition of 1a to 3. Chirality 13:631–633, 2001. © 2001 Wiley‐Liss, Inc.
Alkylating agents from sugars: Synthesis of chlorambucil derivatives carried by chiral glycosyl glycerols derived from D‐Glucosamine
Authors: Iglesias‐Guerra Fernando , Candela José I. , Blanco Eugenia , Alcudia Felipe , Vega‐Pérez José M.
Published: August 2002

Chlorambucilamide derivatives involving chiral glycosyl glycerols derived from D‐glucosamine were synthesized in good yield by coupling the chlorambucil moiety to the amino group of ω‐amino‐(ω‐1)‐hydroxyalkyl 2‐acylamino‐4,6‐O‐benzylidene‐2‐deoxy‐β‐D‐glucopyranosides, and subsequent hydrolysis of the benzylidene group. The starting material was easily available from 2‐acetamido‐2‐deoxy‐D‐glucose. The bonding of 2,3,4,6‐tetra‐O‐pivaloyl‐β‐D‐galactopyranosylamine to chlorambucil by formation of an amide function is also described. Chirality Chirality 14:199–203, 2002. © 2002 Wiley‐Liss, Inc.
Synthesis and stereochemistry of dispiro substituted pyridazines: Application of ellipticity‐absorbance ratio spectra for proving enantiomeric relationship by HPLC‐CD/UV detection
Authors: Beke Gyula , Gergely András , Szász György , Szentesi Aletta , Nyitray József , Barabás Orsolya , Harmath Veronika , Mátyus Péter
Published: August 2002

The aim of our study was to synthesize vinylic and pyrido‐fused pyridazines with a spirano moiety and to investigate their stereochemistry by spectroscopic and HPLC analyses. The vinylic compounds 5 were obtained by Knoevenagel condensation of cyclohexylidene malonates 1 with pyridazinecarbaldehyde 2. Compound 5b exhibits geometric isomerism identified by NMR, HPLC, and X‐ray methods. The thermal rearrangement reactions of compounds 5 easily led to the pyridopyridazine derivatives 6. In the case of 6b, possessing both central and axial chirality, both diastereomers and the respective enantiomers were detected. Their stereochemical relationships could be determined by HPLC‐CD/UV analyses with application of anisotropy spectra in a novel way. Chirality 14:365–371, 2002. © 2002 Wiley‐Liss, Inc.
Evaluation of the contribution to enantioselectivity of quinine and quinidine scaffolds in chemically and physically mixed chiral selectors
Authors: Franco Pilar , Klaus Philipp M. , Minguillón Cristina , Lindner Wolfgang
Published: August 2002

Three “dimeric” C9‐carbamates of quinine (QN) and quinidine (QD), that is, QN‐QN, QD‐QD, and QN‐QD (chemically prepared mixture of the two cinchona‐derived subunits), separated by an ethylene spacer were synthesized and used as chiral selectors for HPLC and capillary electrophoresis (CE) for the resolution of chiral acids. The chiral recognition abilities of these dimers and of several physically prepared mixtures thereof were compared in order to estimate the contribution of every cinchona scaffold to the overall enantioselectivity. The diverse phenomena observed in nonaqueous capillary electrophoresis (NACE), either using the selector added to the background electrolyte (BGE) in the total filling or partial filling mode, led us to rationalize, taking into account the relative mobilities of the chiral selectors in the capillary. The chromatographic and electrophoretic properties were compared with those of the corresponding “monomeric” QN and QD carbamates. Chirality 13:177–186, 2001. © 2001 Wiley‐Liss, Inc.
First direct discrimination of chiral phosphorus thionate (P=S) derivatives by multinuclear magnetic resonance spectroscopy in the presence of a chiral dirhodium complex
Authors: Rockitt Sven , Duddeck Helmut , Omelanczuk Jan
Published: August 2002

Enantiomeric ratios of compounds with P=S functionalities can be determined by 1H, 13C, and 31P NMR spectroscopic inspection of their diastereomeric complexes with (r)‐Rh2(MTPA)4 (MTPA‐H ≡ methoxytrifluoromethylphenylacetic acid; Mosher's acid). This is the first facile and rapid spectroscopic method for chiral recognition in this class of compounds. Whereas complexation shifts Δδ are moderate or even negligible, significant signal dispersions Δν can be observed. Some rationalization about the complexation mode is presented. The NMR spectral characteristics of the free P=S compounds 1–9 are described in detail. Chirality 13:214–222, 2001. © 2001 Wiley‐Liss, Inc.
Solid‐phase synthesis of chiral stationary phases based on 2,4,5,6‐tetrachloro‐1,3‐dicyanobenzene derivatives spaced from N‐3,5‐dinitrobenzoyl α‐amino acids: Comparative study of their resolution efficacy
Authors: Kontrec Darko , Abatangelo Anna , Vinković Vladimir , Šunjić Vitomir
Published: August 2002

Two new chiral stationary phases, 3‐[5‐chloro‐1,3‐dicyano‐2,4‐[2′‐(N′‐1,3‐dinitrobenzoyl‐D‐phenylglycinyl) aminoethyl]aminophen‐1‐yl] aminopropyl silica (CSP‐1) and 3‐[5‐chloro‐1,3‐dicyano‐2,4‐[2′‐(N′‐1,3‐dinitrobenzoyl‐L‐leucinyl) aminoethyl] aminophen‐1‐yl] aminopropyl silica (CSP‐2), were prepared by solid‐phase synthesis. They comprise chiral unit, 3,5‐dinitrobenzoyl derivative of the amino acid, D‐PhGly or L‐Leu, bound via spacer 1,2‐diaminoethane to 2,4‐positions of the persubstituted benzene ring, derived from compound 1, and possess pseudo‐C2 symmetry. Preparation of model compounds 6 and 7 confirmed the structure of chiral selectors, which comprise π‐donor persubsituted aromatic ring and two strong π‐acceptor 3,5‐dinitrobenzoyl amido units. CD spectra of model selectors 6 and 7, run in DMSO above 250 nm, exhibit negative exciton coupling (EC) between π‐acceptor and π‐donor chromophores, C1 symmetric model compound 8 exhibited much weaker EC and 9, devoid of π‐donor unit, does not exhibit any significant CD. Combined π‐donor and π‐acceptor properties enable the new CSPs to separate a broad range of racemates. The columns with CSP‐1 and CSP‐2 were tested for the separation of 22 racemates by HPLC with two different mobile phase systems and the results are compared with those obtained by using a structurally related commercial column. Chirality 13:294–301, 2001. © 2001 Wiley‐Liss, Inc.
Absolute stereochemistry of guaianolides, of matricin and its epimers, of yarrow proazulenes, and of chamazulene carboxylic acid
Authors: Imming Peter , Goeters Susanne , Pawlitzki Gregor , Hempel Bernd
Published: August 2002

Known determinations of the absolute configuration of guaianolides were collected and found to be few. The absolute configurations of guaianolides rest on the assumption that 7‐H always has α‐orientation. For matricin, only the relative configuration was determined. On the basis of a detailed study of the NMR spectra of matricin and its epimers, and of synthetic, NMR, and CD studies with its decomposition product, chamazulene carboxylic acid, we were able to reconfirm the accepted 3S,3aR,4S,9R,9aS,9bS configuration of matricin. Chirality 13:337–341, 2001. © 2001 Wiley‐Liss, Inc.
Novel asymmetric oxy‐michael addition reaction of the chiral ketones to the achiral γ‐ or δ‐hydroxy‐α,β‐unsaturated carbonyl compounds
Authors: Watanabe Hidenori , Machida Kaori , Itoh Daisuke , Nagatsuka Haruki , Kitahara Takeshi
Published: August 2002

A novel asymmetric oxy‐Michael addition reaction was developed. In the presence of a catalytic amount of base, chiral ketones 1 and 2, derived from D‐glucose and D‐fructose, respectively, reacted with ω‐hydroxy enones or enoates 3a–e, 17 and 21 to form the hemiacetal‐derived alkoxide which underwent stereoselective intramolecular Michael addition to give cyclic acetals. Although the stereoselectivities in the formation of the five‐membered acetal rings were modest, six‐membered ring formation proceeded with high stereoselectivity and the utility of the reaction was demonstrated by a simple syntheses of natural products. Chirality 13:379–385, 2001. © 2001 Wiley‐Liss, Inc.
Dynamics of the Dictyostelium Arp2/3 complex in endocytosis, cytokinesis, and chemotaxis
Authors: Insall Robert , Müller‐Taubenberger Annette , Machesky Laura , Köhler Jana , Simmeth Evelyn , Atkinson Simon J. , Weber Igor , Gerisch Günther
Published: August 2002

The Arp2/3 complex is a ubiquitous and important regulator of the actin cytoskeleton. Here we identify this complex from Dictyostelium and investigate its dynamics in live cells. The predicted sequences of the subunits show a strong homology to the members of the mammalian complex, with the larger subunits generally better conserved than the smaller ones. In the highly motile cells of Dictyostelium, the Arp2/3 complex is rapidly re‐distributed to the cytoskeleton in response to external stimuli. Fusions of Arp3 and p41‐Arc with GFP reveal that in phagocytosis, macropinocytosis, and chemotaxis the complex is recruited within seconds to sites where actin polymerization is induced. In contrast, there is little or no localization to the cleavage furrow during cytokinesis. Rather the Arp2/3 complex is enriched in ruffles at the polar regions of mitotic cells, which suggests a role in actin polymerization in these ruffles. Cell Motil. Cytoskeleton 50:115–128, 2001. © 2001 Wiley‐Liss, Inc.
Enhanced diagonal peak suppression in three‐dimensional TROSY‐type 15N‐resolved 1HN1HN NOESY spectra
Authors: Meissner Axel , Sørensen Ole Winneche
Published: August 2002

A new method for enhanced diagonal peak suppression in the three‐dimensional TROSY–NOESY experiment is presented. The main source of residual diagonal signals in the conventional technique is spin flips of the passive 15N spins during the 1H1H NOESY mixing period. The new pulse sequence does not suppress this pathway, but it generates peaks at the positions of the relaxation‐induced artifacts with opposite phase of the artifacts so that cancellation occurs. The new technique is demonstrated using an 15N‐labeled protein sample, Neural Cell Adhesion Molecule (NCAM) 213–308 in H2O at 500 MHz. © 2002 John Wiley & Sons, Inc. Concepts Magn Reson 14: 1–8, 2002
BirdcageBuilder: Design of specified‐geometry birdcage coils with desired current pattern and resonant frequency
Authors: Chin Chih‐Liang , Collins Christopher M. , Li Shizhe , Dardzinski Bernard J. , Smith Michael B.
Published: August 2002

A simple method for birdcage coil design (high pass, low pass, and band pass) is presented. Rather than iteratively approaching the Larmor resonant frequency with known capacitances and calculated inductances, a more versatile approach to birdcage coil design is developed and validated, in which the necessary capacitances are calculated using a desired current pattern, a calculated inductance, and a predetermined resonant frequency. In order to expedite coil design for experienced and novice coil builders, a computer program (BirdcageBuilder) is also implemented based on this method. Experimental results show that the calculated capacitances and actual capacitances for several existing birdcage coils are in good agreement. © 2002 Wiley Periodicals, Inc. Concepts in Magnetic Resonance (Magn Reson Engineering) 15: 156–163, 2002
Residual dipolar couplings in protein NMR
Authors: Brunner Eike
Published: August 2002

Partial molecular alignment leads to an incomplete averaging of anisotropic magnetic interactions such as the magnetic dipole–dipole interaction, the chemical shift anisotropy, or the electric quadrupole interaction. The resulting so‐called “residual” anisotropic magnetic interactions currently become increasingly important in biomolecular NMR spectroscopy. In particular, residual dipolar couplings turn out to be extremely useful novel parameters for protein structure determination. The basic principles of this new methodology are discussed in the present review and recent applications are demonstrated. Different alignment mechanisms leading to partial orientation of protein molecules in solution are considered in detail. The influence of magnetic and electric fields applied to isotropic protein solutions is discussed. Various magnetically orienting media which can be admixed to protein solutions are described and compared. Experiments for the measurement of residual dipolar couplings in proteins and advantageous strategies for the use of residual dipolar couplings in structure calculations are reviewed. © 2001 John Wiley & Sons, Inc. Concepts Magn Reson 13: 238–259, 2001
Serum squamous cell carcinoma antigen is a useful biologic marker in patients with inverted papillomas of the sinonasal tract
Authors: Yasumatsu Ryuji , Nakashima Torahiko , Kuratomi Yuichiro , Hirakawa Naoya , Azuma M.S. Kaoru , Tomita Kichinobu , Cataltepe Sule , Silverman Gary A. , Clayman Gary L. , Komiyama Sohtaro
Published: August 2002

BACKGROUND

Inverted papilloma (IP) is a frequent benign sinonasal tumor that is characterized histologically by squamous metaplasia, epithelial acanthosis, and hyperplasia of the nasal epithelium. Because of its high recurrence rate and malignant transformation potential, careful long‐term follow up is necessary.

METHODS

The purpose of the current report was to study the expression of squamous cell carcinoma (SCC) antigen in sinonasal IPs and to evaluate the usefulness of SCC antigen as a biologic marker for the follow‐up of patients with sinonasal IP. The expression of SCCA1 in three sinonasal IP cases, three sinonasal SCC cases, and cases of normal nasal epithelium were examined by Western blot analysis, and the SCCA1 expression pattern in 31 IP specimens and 4 carcinoma in IP specimens were evaluated immunohistochemically. The serum levels of SCC antigen in 11 patients with sinonasal IP also were analyzed.

RESULTS

SCCA1 was overexpressed in all three sinonasal IP tissues compared with sinonasal SCC tissues or normal nasal epithelium. SCCA1 cytoplasmic immunoreactivity was detected in the suprabasal epidermal keratinocytes of all 31 sinonasal IP cases. In the four carcinoma in IP specimens, SCCA1 expression in the papillomatous lesion was more intense than in the cancerous lesion. The serum SCC antigen level was high in 10 of 11 patients with IP (91%) and significantly decreased after surgical resection of the tumors.

CONCLUSIONS

The results of the current study indicate that SCCA1 frequently is overexpressed and may play a biologic role in the development of sinonasal IPs. Serum SCC antigen may be a useful biologic marker in patients with sinonasal IP. Cancer 2002;94:152–8. © 2002 American Cancer Society.
Phase II trial of irinotecan in combination with amifostine in patients with advanced colorectal carcinoma
Authors: Delioukina Maria L. , Prager Diane , Parson Mandy , Hecht J. Randolph , Rosen Peter , Rosen Lee S.
Published: August 2002

BACKGROUND

Irinotecan is effective in patients with advanced colorectal carcinoma in both first‐line and salvage settings but its use can be limited by serious side effects. Amifostine has been shown to reduce the incidence of cisplatin‐induced cumulative renal toxicity in patients with advanced ovarian carcinoma and nonsmall cell lung carcinoma. In the current pilot Phase II trial, the authors examined the potential role of amifostine as a protective agent against irinotecan‐induced diarrhea and myelosuppression and evaluated an every‐2‐weeks regimen as an alternative schedule for the administration of irinotecan in patients with previously treated metastatic colorectal carcinoma.

METHODS

All patients received amifostine, 740 mg/m2, followed by irinotecan, 250 mg/m2, every 2 weeks. A 6‐week cycle of chemotherapy (every 2 weeks for 3 treatments) was chosen to assess toxicity and response. The main objective of the current study was to evaluate the impact of amifostine on gastrointestinal and hematologic toxicity.

RESULTS

A total of 22 patients entered the current study. Six of these 22 patients (27%) had WHO Common Toxicity Criteria Grade 3 or 4 diarrhea, including 2 patients (9%) with Grade 4 diarrhea. Eight of 22 patients (36.3%) developed Grade 3 or 4 neutropenia (Grade 4 in 4 of the 22 patients [18%]). Dose reduction was required in 25% of the treatment cycles. Five of the 22 patients (23%) withdrew from the trial due to amifostine toxicity. Of the 15 patients who were evaluable for response, 4 patients (26.6%) had achieved a partial response and 9 (60%) had stable disease as their best response.

CONCLUSIONS

The combination of irinotecan with amifostine in patients with previously treated metastatic colorectal carcinoma did not appear to reduce irinotecan toxicity. Amifostine did not appear to interfere with the cytotoxic effect of irinotecan. The results of the current study did demonstrate efficacy and safety of the every‐2‐weeks irinotecan schedule that was comparable to other established regimens and these results support its feasibility as a reasonable alternative in this disease setting. Cancer 2002;94:2174–9. © 2002 American Cancer Society.

DOI 10.1002/cncr.10432
Spatiotemporal expression patterns of slit and robo genes in the rat brain
Authors: Marillat Valérie , Cases Oliver , Nguyenf‐Ba‐Charvet Kim Tuyen , Tessier‐Lavigne Marc , Sotelo Constantino , Chédotal Alain
Published: August 2002

Diffusible chemorepellents play a major role in guiding developing axons toward their correct targets by preventing them from entering or steering them away from certain regions. Genetic studies in Drosophila revealed a repulsive guidance system that prevents inappropriate axons from crossing the central nervous system midline; this repulsive system is mediated by the secreted extracellular matrix protein Slit and its receptors Roundabout (Robo). Three distinct slit genes (slit1, slit2, and slit3) and three distinct robo genes (robo1, robo2, rig‐1) have been cloned in mammals. However, to date, only Robo1 and Robo2 have been shown to be receptors for Slits. In rodents, Slits have been shown to function as chemorepellents for several classes of axons and migrating neurons. In addition, Slit can also stimulate the formation of axonal branches by some sensory axons. To identify Slit‐responsive neurons and to help analyze Slit function, we have studied, by in situ hybridization, the expression pattern of slits and their receptors robo1 and robo2, in the rat central nervous system from embryonic stages to adult age. We found that their expression patterns are very dynamic: in most regions, slit and robo are expressed in a complementary pattern, and their expression is up‐regulated postnatally. Our study confirms the potential role of these molecules in axonal pathfinding and neuronal migration. However, the persistence of robo and slit expression suggests that the couple slit/robo may also have an important function in the adult brain. J. Comp. Neurol. 442:130–155, 2002. © 2002 Wiley‐Liss, Inc.
Guidance of dopaminergic neuritic growth by immature astrocytes in organotypic cultures of rat fetal ventral mesencephalon
Authors: Johansson Saga , Strömberg Ingrid
Published: August 2002

Astrocytes, with their many functions in producing and controlling the environment in the brain, are of great interest when it comes to studying regeneration after injury and neurodegenerative diseases such as in grafting in Parkinson's disease. This study was performed to investigate astrocytic guidance of growth derived from dopaminergic neurons using organotypic cultures of rat fetal ventral mesencephalon. Primary cultures were studied at different time points starting from 3 days up to 28 days. Cultures were treated with either interleukin‐1β (IL‐1β), which has stimulating effects on astrocytic proliferation, or the astrocytic inhibitor cytosine arabinoside (Ara‐C). Tyrosine hydroxylase (TH)‐immunohistochemistry was used to visualize dopaminergic neurons, and antibodies against glial fibrillary acidic protein (GFAP) and S100β were used to label astrocytes. The results revealed that a robust TH‐positive nerve fiber production was seen already at 3 days in vitro. These neurites had disappeared by 5 days. This early nerve fiber outgrowth was not guided by direct interactions with glial cells. Later, at 7 days in vitro, a second wave of TH‐positive neuritic outgrowth was clearly observed. GFAP‐positive astrocytic processes guided these neurites. TH‐positive neurites arborized overlying S100β‐positive astrocytes in an area distal to the GFAP‐positive astrocytic processes. Treatment with IL‐1β resulted in an increased area of TH‐positive nerve fiber network. In cultures treated with Ara‐C, neither astrocytes nor outgrowth of dopaminergic neurites were observed. In conclusion, this study shows that astrocytes play a major role in long‐term dopaminergic outgrowth, both in axonal elongation and branching of neurites. The long‐term nerve fiber growth is preceded by an early transient outgrowth of dopamine neurites. J. Comp. Neurol. 443:237–249, 2002. © 2002 Wiley‐Liss, Inc.
Extracellular matrix glycoproteins inhibit neurite production by cultured neurons
Authors: De‐Miguel Francisco F. , Vargas Javier , Arias Clorinda , Escamilla Carolina
Published: August 2002

We have analyzed the role of extracellular matrix glycoproteins in the formation of a bipolar outgrowth pattern of identified leech neurons in culture. Adult anterior pagoda (AP) neurons cultured on the inner surface of the ganglion capsules that surround central nervous system, generate two processes oriented in opposite directions. This pattern differs from those produced by these neurons cultured on other substrates, and is similar to the pattern of developing AP neurons at embryonic day 10. We used different lectins to identify subsets of glycoproteins in the extracellular matrix (ECM) of the capsules and to study their contribution to the formation of the bipolar outgrowth pattern. ECM glycoproteins binding to peanut agglutinin (PNA) or Galanthus nivalis aglutinin (GNA) lectins were detected in ganglion capsules and in ganglion extracts that had been separated by electrophoresis and blotted to nitrocellulose membranes. Four protein bands bound to PNA lectin and six other bands, including laminin subunits, bound to GNA lectin. Other lectins failed to recognize any of the proteins. For AP neurons cultured on capsules, addition of PNA lectin to the culture medium produced a dose‐dependent increase in the number of primary neurites without affecting their shape, length or number of branch points. However, PNA lectin used as substrate did not affect sprouting of AP neurons. Our results suggest that PNA‐binding extracellular matrix glycoproteins regulate the formation of the bipolar pattern of AP neurons by inhibiting the formation of neurites. J. Comp. Neurol. 443:401–411, 2002. © 2002 Wiley‐Liss, Inc.
Colocalization of γ‐aminobutyric acid‐like immunoreactivity and catecholamines in the feeding network of Aplysia californica
Authors: Díaz‐Ríos Manuel , Oyola Eduardo , Miller Mark W.
Published: August 2002

Functional consequences of neurotransmitter coexistence and cotransmission can be readily studied in certain experimentally favorable invertebrate motor systems. In this study, whole‐mount histochemical methods were used to identify neurons in which γ‐aminobutyric acid (GABA)‐like immunoreactivity (GABAli) was colocalized with catecholamine histofluorescence (CAh; FaGlu method) and tyrosine hydroxylase (TH)‐like immunoreactivity (THli) in the feeding motor circuitry (buccal and cerebral ganglia) of the marine mollusc Aplysia californica. In agreement with previous reports, five neurons in the buccal ganglia were found to exhibit CAh. These included the paired B20 buccal‐cerebral interneurons (BCIs), the paired B65 buccal interneurons, and an unpaired cell with projections to both cerebral‐buccal connectives (CBCs). Experiments in which the FaGlu method was combined with the immunohistochemical detection of GABA revealed double labeling of all five of these neurons. An antibody generated against TH, the rate‐limiting enzyme in the biosynthesis of catecholamines, was used to obtain an independent determination of GABA‐CA colocalization. Biocytin backfills of the CBC performed in conjunction with TH immunohistochemistry revealed labeling of the rostral B20 cell pair and the unpaired CBI near the caudal surface of the right hemiganglion. THli was also present in a prominent bilateral pair of caudal neurons that were not stained with CBC backfills. On the basis of their position, size, shape, and lack of CBC projections, the lateral THli neurons were identified as B65. Double‐labeling immunohistochemical experiments revealed GABAli in all five buccal THli neurons. Finally, GABAli was observed in individual B20 and B65 neurons that were identified using electrophysiological criteria and injected with a marker (neurobiotin). Similar methods were used to demonstrate that a previously identified catecholaminergic cerebral‐buccal interneuron (CBI) designated CBI‐1 contained THli but did not contain GABAli. Although numerous THli and GABAli neurons and fibers were present in the cerebral and buccal ganglia, additional instances of their colocalization were not observed. These findings indicate that GABA and a catecholamine (probably dopamine) are colocalized in a limited number of interneurons within the central pattern generator circuits that control feeding‐related behaviors in Aplysia. J. Comp. Neurol. 445:29–46, 2002. © 2002 Wiley‐Liss, Inc.
Functional aspects of dopamine metabolism in the putative prefrontal cortex analogue and striatum of pigeons (Columba livia)
Authors: Bast Tobias , Diekamp Bettina , Thiel Christiane , Schwarting Rainer K.W. , Güntürkün Onur
Published: August 2002

Dopamine (DA) in mammalian associative structures, such as the prefrontal cortex (PFC), plays a prominent role in learning and memory processes, and its homeostasis differs from that of DA in the striatum, a sensorimotor region. The neostriatum caudolaterale (NCL) of birds resembles the mammalian PFC according to connectional, electrophysiological, and behavioral data. In the present study, DA regulation in the associative NCL and the striatal lobus parolfactorius (LPO) of pigeons was compared to uncover possible differences corresponding to those between mammalian PFC and striatum. Extracellular levels of DA and its metabolites (homovanillic acid [HVA], dihydroxyphenylacetic acid [DOPAC]) and the serotonin metabolite 5‐hydroxyindoleacetic acid (5‐HIAA) were investigated by in vivo microdialysis of urethane‐anesthetized pigeons under basal conditions and after systemic administration of D‐amphetamine. DA was reliably determined only in LPO dialysates, and DA metabolite levels were significantly higher in LPO than in NCL. The HVA/DOPAC ratio, indicating extracellular lifetime of DA, was more than twice as high in NCL than in LPO dialysates. After amphetamine, DA increased in LPO while still being undetectable in NCL, and DA metabolites decreased in both regions. 5‐HIAA slightly decreased in NCL dialysates. Amphetamine effects were delayed in NCL compared with the striatum. In conclusion, effects of amphetamine on the pigeon's ascending monoamine systems resemble those found in mammals, suggesting similar regulatory properties. The neurochemical differences between NCL and LPO parallel those between associative regions, such as PFC and dorsal striatum in mammals. They may reflect weaker regulation of extracellular DA, favoring DAergic volume transmission, in associative than striatal forebrain regions. J. Comp. Neurol. 446:58–67, 2002. © 2002 Wiley‐Liss, Inc.
Distribution and terminal arborizations of cutaneous mechanoreceptors in the glabrous finger pads of the monkey
Authors: Paré Michel , Smith Allan M. , Rice Frank L.
Published: August 2002

Recent electrophysiological studies demonstrated that neurons in the somatosensory cortex of monkeys respond to tangential forces applied to glabrous skin. To unravel the peripheral basis for this cortical response, we determined the distribution of presumptive low‐threshold mechanoreceptors innervating the distal finger pads of monkeys. Endings were reconstructed in immunolabeled serial sections imaged by epifluorescence and confocal microscopy. Although classically implicated as cutaneous stretch receptors, no Ruffini corpuscles were found in the glabrous skin. Ruffini‐like endings were only detected at the base of the finger nails. Pacinian corpuscles were sparsely distributed in the deep dermis. Meissner corpuscles (MCs) in dermal papillary ridges had a comparably high density in the thumb, index, and fifth fingers. Each MC was innervated by several large‐caliber axons. Within the limits of our reconstructions, some of these axons terminated in only one MC, whereas others innervated several MCs. Merkel endings covered about 80% of the base of the intermediate epidermal ridges that form the pattern of fingerprints. In some cases, the distal tip of a Merkel‐related axon gave rise to a several terminal branches that supplied endings to tightly circumscribed (30–70 μm) clusters of Merkel cells. In other cases, the nodes of axons gave rise to en passant branches that formed extended chains of endings among Merkel cells spread over territories up to 300 μm long. Based on their relatively diffuse distributions, the axons that innervate multiple MCs or the axons with en passant Merkel terminations seem most suited to transduce tangential forces. J. Comp. Neurol. 445:347–359, 2002. © 2002 Wiley‐Liss, Inc.
Cellular basis for the effects of substance P in the periaqueductal gray and dorsal raphe nucleus
Authors: Commons Kathryn G. , Valentino Rita J.
Published: August 2002

Substance P (SP) is known to act at supraspinal sites to influence pain sensitivity as well as to promote anxiety. The effects of SP could be mediated in part by actions in the periaqueductal gray (PAG) and the dorsal raphe nucleus (DRN), adjoining mesencephalic cell groups that are strategically positioned to influence both nociception and mood. Previous studies have indicated that SP regulates both enkephalin and serotonin neurotransmission in these brain regions. To determine the mechanism underlying the effects of SP in the PAG and DRN, the distribution of the principal receptor for SP, the neurokinin 1 (NK1) receptor, was examined with respect to other neurotransmitter markers. PAG neurons that had NK1 receptor immunolabeling were interdigitated with and received contacts from enkephalin‐containing neurons. However, only a few (16/144; 11%) neurons with NK1 receptor also contained enkephalin immunoreactivity after colchicine treatment. In the DRN, dendrites containing NK1 receptor were selectively distributed in the dorsomedial subdivision. The majority (132/137; 96%) of these dendrites did not contain immunoreactivity for the serotonin‐synthesizing enzyme tryptophan hydroxylase. In contrast, neuronal profiles with NK1 receptor in both the PAG and the DRN often contained immunolabeling for glutamate. Light and electron microscopic examination revealed that 48–65% of cell bodies and dendrites with NK1 receptor were dually immunolabeled for glutamate. These data suggest that SP directly acts primarily on glutamatergic neurons in the PAG and DRN. To a lesser extent, enkephalin‐containing neurons may be targeted. Through these actions, it may subsequently influence activity of larger populations of neurons containing enkephalin as well as serotonin. This circuitry could contribute to, as well as coordinate, effects of SP on pain perception and mood. J. Comp. Neurol. 447:82–97, 2002. © 2002 Wiley‐Liss, Inc.
Comparison of unilateral and bilateral intrastriatal 6‐hydroxydopamine‐induced axon terminal lesions: Evidence for interhemispheric functional coupling of the two nigrostriatal pathways
Authors: Roedter Alexandra , Winkler Christian , Samii Madjid , Walter Gerhard F. , Brandis Almuth , Nikkhah Guido
Published: August 2002

Partial lesions of the nigrostriatal dopamine system can be induced reliably by the intrastriatal injection of 6‐hydroxydopamine (6‐OHDA) and are considered to be analogous to the early stages of human Parkinson's disease. Previous studies have established a clear correlation between different doses and placements of the 6‐OHDA toxin and the degree of neurodegenerative changes and behavioral impairments. In the present study, the influence of the interdependence between the two nigrostriatal systems in both hemispheres on the effects on sensorimotor behavioral performances after terminal 6‐OHDA lesions was investigated. The behavioral effects were correlated to the extent of nigral dopamine neuron cell and striatal tyrosine‐hydroxylase (TH)‐positive fiber loss. Sprague‐Dawley rats receiving unilateral intrastriatal 6‐OHDA injections (4 × 5 μg) exhibited a 30–70% reduction in striatal TH‐positive fiber density along an anterior‐posterior gradient, an 80% loss of nigral dopamine neurons and a mild degree of behavioral impairments as revealed by amphetamine‐induced rotational asymmetry, and a reduced performance in the stepping and postural balance tests. When the same amount of toxin was injected twice into both hemispheres (2 × 4 × 5 μg), additional behavioral deficits were observed, consisting of a significant, but temporary, weight loss, a stable reduction in general locomotor activity and explorational behavior, and a long‐term deficit in skilled forelimb use. This is interesting in light of the morphological findings, in which uni‐ and bilaterally lesioned animals did not differ significantly in the extent of TH‐immunoreactive fiber and dopamine neuron loss within the nigrostriatal system in each lesioned hemisphere. These results indicate that the interdependent regulation of the two nigrostriatal systems may provide some compensatory support for the function and behavioral performance of the lesioned side via the normal unlesioned side, which is lost in animals with bilateral lesions of the nigrostriatal system. Therefore, this model of uni‐ and bilateral partial lesions of the nigrostriatal system, as characterized in the present study, may foster further exploration of compensatory functional mechanisms active in the early stages of Parkinson's disease and promote development of novel neuroprotective and restorative strategies. J. Comp. Neurol. 432:217–229, 2001. © 2001 Wiley‐Liss, Inc.
Odorants as cell‐type specific activators of a heat shock response in the rat olfactory mucosa
Authors: Carr Virginian McMillan , Menco Bert Ph.M. , Yankova Maya P. , Morimoto Richard I. , Farbman Albert I.
Published: August 2002

Heat shock, or stress, proteins (HSPs) are induced in response to conditions that cause protein denaturation. Activation of cellular stress responses as a protective and survival mechanism is often associated with chemical exposure. One interface between the body and the external environment and chemical or biological agents therein is the olfactory epithelium (OE). To determine whether environmental odorants affect OE HSP expression, rats were exposed to a variety of odorants added to the cage bedding. Odorant exposure led to transient, selective induction of HSP70, HSC70, HSP25, and ubiquitin immunoreactivities (IRs) in supporting cells and subepithelial Bowman's gland acinar cells, two OE non‐neuronal cell populations involved with inhalant biotransformation, detoxification, and maintenance of overall OE integrity. Responses exhibited odor specificity and dose dependency. HSP70 and HSC70 IRs occurred throughout the apical region of supporting cells; ubiquitin IR was confined to a supranuclear cone‐shaped region. Electron microscopic examination confirmed these observations and, additionally, revealed odor‐induced formation of dense vesicular arrays in the cone‐like regions. HSP25 IR occurred throughout the entire supporting cell cytoplasm. In contrast to classical stress responses, in which the entire array of stress proteins is induced, no increases in HSP40 and HSP90 IRs were observed. Extended exposure to higher odorant doses caused prolonged activation of the same HSP subset in the non‐neuronal cells and severe morphological damage in both supporting cells and olfactory receptor neurons (ORNs), suggesting that non‐neuronal cytoprotective stress response mechanisms had been overwhelmed and could no longer adequately maintain OE integrity. Significantly, ORNs showed no stress responses in any of our studies. These findings suggest a novel role for these HSPs in olfaction and, in turn, possible involvement in other normal neurophysiological processes. J. Comp. Neurol. 432:425–439, 2001. © 2001 Wiley‐Liss, Inc.
Neuronal plasticity and formation of new synaptic contacts follow pyramidal lesions and neutralization of Nogo‐A: A light and electron microscopic study in the pontine nuclei of adult rats
Authors: Blöchlinger Stefan , Weinmann Oliver , Schwab Martin E. , Thallmair Michaela
Published: August 2002

Regeneration and compensatory sprouting are limited after lesions in the mature mammalian central nervous system in contrast to the developing central nervous system (CNS). After neutralization of the growth inhibitor Nogo‐A, however, massive sprouting and rearrangements of fiber connections occurred after unilateral pyramidal tract lesions in adult rats: Corticofugal fibers from the lesioned side crossed the midline of the brainstem and innervated the contralateral basilar pontine nuclei. To determine whether these newly sprouted fibers formed synaptic contacts, we analyzed the corticofugal fibers in the basilar pontine nuclei contralateral to the lesion by light and electron microscopy 2 weeks after pyramidotomy and treatment with the Nogo‐A‐inhibiting monoclonal antibody IN‐1 (mAb IN‐1). The mAb IN‐1, but not a control antibody, led to structural changes in the basilar pons ipsilateral and contralateral to the lesion site. Fibers sprouted across the pontine midline and terminated topographically. They established asymmetric synaptic contacts with the characteristics of normal corticopontine terminals. These results show that adult CNS fibers are able to sprout and to form new synaptic contacts after a lesion when a growth‐permissive microenvironment is provided. J. Comp. Neurol. 433:426–436, 2001. © 2001 Wiley‐Liss, Inc.