bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of NOGA catheter stability during the entire cardiac cycle by means of a special needle‐tipped catheter
Authors: Lessick Jonathan , Kornowski Ran , Fuchs Shmuel , Ben‐Haim Shlomo A.
Published: August 2002

The NOGA system maps regional myocardial function and delivers local catheter‐based therapeutics, requiring stability and precise localization of the catheter tip throughout the cardiac cycle. A special catheter having a retractable needle at its tip was used to compare tip stability with and without needle insertion into the myocardium, assuming this prevents catheter slippage. For multiple sites in seven pig left ventricles, we recorded sets of three consecutive point locations: pre‐, post‐, and during needle insertion. In‐point location stability (LocStab), defined as the mean displacement between catheter tip trajectories of two consecutive cardiac cycles at a specific point, did not differ among the three groups of points (mean, 1.33 ± 0.61 mm; P = 0.37 by ANOVA), indicating that trajectories are equally stable and repeatable with or without needle insertion. Between‐point LocStab(p1,p2), i.e., displacement between the trajectories of two different points (p1 and p2) at the same location, was not increased when p1 = a needle insertion point and p2 = a noninsertion point, compared to both p1,p2 = noninsertion points, suggesting that slippage of noninsertion points is negligible. In conclusion, catheter tip trajectories at any location are highly stable throughout the cardiac cycle. Cathet Cardiovasc Intervent 2001;52:400–406. © 2001 Wiley‐Liss, Inc.
Use of a percutaneous arterial suture device (Perclose) in patients undergoing percutaneous balloon aortic valvuloplasty
Authors: Michaels Andrew D. , Ports Thomas A.
Published: August 2002

Percutaneous balloon aortic valvuloplasty has been used as a therapeutic option for patients with severe aortic stenosis who are not candidates for aortic valve replacement. This procedure has been limited by both the high rate of aortic valve restenosis and high procedural morbidity related chiefly to the large femoral arteriotomies required. The purpose of this study was to assess the feasibility and vascular complication rate using the “Preclose” technique in patients undergoing balloon aortic valvuloplasty. We evaluated the immediate and 30‐day results in 18 consecutive patients undergoing this procedure. Angiographically significant peripheral vascular disease was present in 39% of cases. Aortic balloon dilation produced significant decreases in the mean aortic valve pressure gradient from 55 ± 20 mmHg to 30 ± 22 mmHg (P < 0.001). Closure of the arteriotomy with an 8F (10F in 1 case) Perclose device led to immediate hemostasis in all patients. Perclose of the contralateral femoral arterial site with a 6F device was attempted in 50%, all of which were successful. The mean length of bed rest was 4.5 ± 0.9 hr. No procedural was observed. No patient had a local vascular complication, and no patient required blood product transfusion after the procedure. The use of the “Preclose” technique for closure of femoral arteriotomies after balloon aortic valvuloplasty is feasible and associated with a low rate of periprocedural and short‐term vascular complications. Cathet Cardiovasc Intervent 2001;53:445–447. © 2001 Wiley‐Liss, Inc.
Transcatheter closure of a posttraumatic ventricular septal defect with an Amplatzer occluder device
Authors: Bauriedel Gerhard , Redel Dierk A. , Schmitz Christoph , Welz Armin , Schild Hans Heinz , Lüderitz Berndt
Published: August 2002

Cardiac traumatization may lead to severe complications. Transcatheter closure of a postraumatic ventricular septal defect (VSD) was successfully done using an Amplatzer septal occluder in a man who had previously undergone surgery for myocardial fissure and mitral valve dysfunction. In selected cases, the percutaneous approach may be a valuable option to close muscular VSDs. Cathet Cardiovasc Intervent 2001;53:508–512. © 2001 Wiley‐Liss, Inc.
Intravascular ultrasound diagnosis of cystic adventitial degeneration of the popliteal artery: A case report
Authors: Foster Malcolm T. , Collins John T. , Morgan Jeffry P.
Published: August 2002

The diagnosis of cystic adventitial degeneration (CAD) is difficult. We present the first case in which intravascular ultrasound (IVUS) correctly identified CAD of the popliteal artery when duplex sonography and angiography were inconclusive. Cathet Cardiovasc Intervent 2001;53:527–529. © 2001 Wiley‐Liss, Inc.
Transcatheter creation of an atrial septal defect using radiofrequency perforation
Authors: Justino Henri , Benson Lee N. , Nykanen David G.
Published: August 2002

Transseptal perforation using radiofrequency energy was performed successfully in a patient with congenital heart disease and a thickened interatrial septum. This was followed by balloon dilatation of the atrial septal defect. Radiofrequency is presented as a alternative to standard transseptal needle puncture. Cathet Cardiovasc Intervent 2001;54:83–87. © 2001 Wiley‐Liss, Inc.
Local delivery of c‐myc neutrally charged antisense oligonucleotides with transport catheter inhibits myointimal hyperplasia and positively affects vascular remodeling in the rabbit balloon injury model
Authors: Kipshidze Nicholas , Keane Eamon , Stein David , Chawla Paramjith , Skrinska Victor , Shankar Latha Raja , Khanna Ashwani , Komorowski Richard , Haudenschild Christian , Iversen Patrick , Leon Martin B. , Keelan Michael H. , Moses Jeffrey
Published: August 2002

Myointimal hyperplasia after percutaneous transluminal coronary angioplasty (PTCA) is a key component of the process of restenosis. The c‐myc is a critical cell‐cycle division protein involved in the formation of neointima. We evaluated the long‐term impact of local delivery of c‐myc neutrally charged antisense oligonucleotides (Resten‐NG) on myointimal hyperplasia after PTCA in a rabbit model. PTCA was performed in the iliac arteries of 25 New Zealand white rabbits, using a Transport\T catheter at 8 atm for 30 sec, three times; 500 μg Resten‐NG (n = 11) or saline (n = 14) was delivered to the PTCA site at 2 atm with the outer balloon for 2 min. The diet was supplemented with 0.25% cholesterol for 10 days before and 60 days after PTCA. Angiography was performed at harvest, and vessels were fixed in formalin, processed, and stained with hematoxylin and eosin (H&E) and Movat. Quantitative angiography showed that local delivery of antisense c‐myc at PTCA reduced late luminal loss from 1.8 ± 0.30 mm in control animals to 0.90 ± 0.30 mm in the treatment group (P = 0.001). Histological analysis by planimetry showed that intimal areas were 1.67 ± 0.44 mm2 and 0.82 ± 0.32 mm2 in the control and antisense delivery groups, respectively (P < 0.05). We conclude that local delivery of Resten‐NG inhibited myointimal hyperplasia after PTCA in cholesterol‐fed rabbits for up to 60 days. Cathet Cardiovasc Intervent 2001;54:247–256. © 2001 Wiley‐Liss, Inc.
A novel quantitative method for evaluating diffuse in‐stent narrowing at follow‐up angiography
Authors: Ishii Yasuhiro , van Weert Anton W.M. , Hekking Ellen , de Marie Karen , ter Horst Jeroen , Oemrawsingh Pranobe V. , Reiber Johan H.C.
Published: August 2002

A new quantitative parameter, diffuse index (DI), was proposed to evaluate objectively whether in‐stent restenosis is diffuse or focal in nature. A total of 343 patients (346 lesions) with Wiktor‐GX, AVE MS‐II, or JOMED stents were evaluated at follow‐up angiography. According to the QCA‐CMS definition, lesion length is derived from the 100% reference diameter function (RDF). By moving the RDF downward, the lesion length, LL(x), at each percentage x of the RDF can be calculated. We have defined the DI by the ratio of this calculated length LL(x) and the total stent length, SL, in other words, DI = [LL(x)/SL]. The percentage plaque area (% PA) was calculated by dividing the plaque area by the sum of the plaque area and luminal area within the stent. An excellent correlation was found between the DI at 88% RDF and the % PA in all three stents (r > 0.88). The individual correlation curves were nearly identical, independent of the type of stent. Furthermore, based on the overall data, the combination of a DI > 0.8 and % PA > 30% correlated with a high incidence of subsequent major adverse cardiac events (13/25 = 52%). From these data, it can be concluded that the diffuse index is a new objective quantitative parameter to describe whether in‐stent restenosis is of focal or diffuse nature. Cathet Cardiovasc Intervent 2001;54:309–317. © 2001 Wiley‐Liss, Inc.
Percutaneous stenting of acquired thoracic aorta occlusive disease
Authors: Pienvichit Pavit , Piemonte Thomas C.
Published: August 2002

We report on successful treatment of acquired atherosclerotic coarctation of the thoracic aorta with self‐expanding stents via percutaneous approach. The technique and equipment used in the case are discussed. Cathet Cardiovasc Intervent 2001;54:350–354. © 2001 Wiley‐Liss, Inc.
Featured Organism: Schizosaccharomyces pombe, the fission yeast
Authors: Wixon Jo
Published: August 2002

Schizosaccharomyces pombe, the fission yeast, has long been a crucial model for the study of the eukaryote cell cycle. We take a look at this important yeast, whose genome has recently been completed, featuring comments from Valerie Wood, Jürg Bähler, Ramsay McFarlane, Susan Forsburg, Iain Hagan and Paul Nurse on the implications of having the complete sequence and future prospects for pombe genomics. Copyright © 2002 John Wiley & Sons, Ltd.

Summary

• Fission yeast; reproduces by medial fission rather than budding

• 13.8Mb genome, as three chromosomes

• Genome sequence completed, ∼5000 genes

• ∼10% of the predicted genes are orphans

• No signs of whole genome duplication like that seen in S. cerevisiae

• Evolutionarily very distant to S. cerevisiae
NMR and parity nonconservation. Experimental requirements to observe a difference between enantiomer signals
Authors: Robert J.‐B. , Barra A.L.
Published: August 2002

The possibility of observing a difference in the high‐resolution NMR spectra of two enantiomers as due to parity nonconservation is discussed. Proposals to minimize the NMR linewidths are presented. It is concluded that, using the ultra‐ high‐resolution technique, a difference could be observed with high Z value spin one‐ half nuclei such as Pt, T1, Xe. Other nuclei can also be considered. Chirality 13:699–702, 2001. © 2001 Wiley‐Liss, Inc.
Direct chiral separation of unnatural amino acids by high‐performance liquid chromatography on a ristocetin a‐bonded stationary phase
Authors: Török Gabriella , Pëter Antal , Armstrong Daniel W. , Tourwë Drik , Töth Gëza , Säpi Jänos
Published: August 2002

Direct high‐performance liquid chromatographic chiral separation of numerous underivatized unnatural amino acids on a ristocetin A‐bonded chiral stationary phase used in the reversed‐phase and in the polar organic chromatographic modes is reported. The effects of different parameters such as mobile phase composition, temperature, and the structure of the analytes on the selectivity in both chromatographic modes are discussed. By variation of the parameters, the separation of the stereoisomers was optimized and, as a result, baseline resolution was achieved in most cases. Chirality 13:648–656, 2001. © 2001 Wiley‐Liss, Inc.
Novel direct access to enantiomerization barriers from peak profiles in enantioselective dynamic chromatography: Enantiomerization of dialkyl‐1,3‐allenedicarboxylates
Authors: Trapp Oliver , Schurig Volker
Published: August 2002

The axially chiral allenes dimethyl‐1,3‐allenedicarboxylate1and diethyl‐1,3‐allenedicarboxylate2show characteristic plateau formation during enantioselective GC separation on the chiral stationary liquid phase Chirasil‐β‐Dex. The elution profiles, obtained from temperature‐dependent dynamic GC (DGC) experiments (1: 100–140°C;2: 110–150°C) were evaluated with the recently derived approximation function (AF)$k_1^{approx} = f(t^{A}_{R}, t_R^B, w^A_h, h_{plateau}, N)$to yield the enantiomerization rate constant directlyk1. These values were compared with those obtained by computer‐aided simulation with ChromWin. The Eyring activation parameters of the experimental interconversion profiles were determined to be: ΔG#(298.15 K) = 103.6 ± 0.9 kJ mol−1, ΔH#= 44.7 ± 0.4 kJ mol−1, ΔS#= −198 ± 7 J K1mol−1for dimethyl‐1,3‐allenedicarboxylate1, and ΔG#(298.15 K) = 103.5 ± 1.1 kJ mol−1, ΔH#= 44.7 ± 0.5 kJ mol−1, ΔS#= −197 ± 9 J K−1mol−1for diethyl‐1,3‐allenedicarboxylate2. The approximation function (AF) presented here allows the fast determination of rate constantsk1and activation barriers of enantiomerization ΔG#from chromatographic parameters without extensive computer simulation. Chirality 14:465–470, 2002. © 2002 Wiley‐Liss, Inc.
CEOs' power and corporate performance transitions
Authors: Chaganti Rajeswararao , Damanpour Fariborz , Mankelwicz John M.
Published: August 2002

This study addresses the question, How does CEO power affect, and respond to, corporate performance transitions over time? Drawing on insights culled from the top management and organizational life‐cycle literature, we assumed that CEO power rises and falls in tandem with a firm's upward or downward performance cycles. However, our examination of four CEO “power characteristics”—structural, ownership, expert, and prestige—at 38 major U.S. corporations over a period of 12 years showed, instead, that CEOs' power (1) rises and falls within both upward and downward performance transitions and (2) does not rise and fall in a steady, monotonic fashion. In fact, some dimensions of CEO power are clearly more tied than others to changes in firm performance, and shifts in CEO power can also be linked to either the early or the late part of each transition cycle. These results have several implications for competitive intelligence (CI) professionals: First, the four power characteristics seem to behave independently of each other and seem to influence performance in their own unique ways. Each characteristic seems to play a very special role in the scheme of things and contribute uniquely to our understanding of performance transitions. Because of the special role that each power characteristic assumes in driving a firm's performance, CI professionals must track all four power indicators (and not simply any one of the indicators) to fully comprehend the performance changes. © 2001 John Wiley & Sons, Inc.
The science, not art, of business intelligence
Authors: O'Guin Michael C. , Ogilvie Timothy
Published: August 2002

The intelligence process starts with management articulating the need for information that will allow it to make a critical decision. As our case study demonstrates, effective business intelligence results not from luck, but from a systematic process. The intelligence analyst deduces a target's most likely actions or intentions using a hypothesis‐based approach. This approach allows the analyst to form and test a theory about the target's actions. Testing a set of hypotheses causes the analysis to identify, plan, and seek out market signals that betray a competitor's actions. By implementing the intelligence plan, the analyst is able to collect the necessary facts to deduce a competitor's actions, allowing his or her company a decisive advantage in the marketplace. © 2001 John Wiley & Sons, Inc.
Transient production of α‐smooth muscle actin by skeletal myoblasts during differentiation in culture and following intramuscular implantation
Authors: Springer Matthew L. , Ozawa Clare R. , Blau Helen M.
Published: August 2002

α‐smooth muscle actin (SMA) is typically not present in post‐embryonic skeletal muscle myoblasts or skeletal muscle fibers. However, both primary myoblasts isolated from neonatal mouse muscle tissue, and C2C12, an established myoblast cell line, produced SMA in culture within hours of exposure to differentiation medium. The SMA appeared during the cells' initial elongation, persisted through differentiation and fusion into myotubes, remained abundant in early myotubes, and was occasionally observed in a striated pattern. SMA continued to be present during the initial appearance of sarcomeric actin, but disappeared shortly thereafter leaving only sarcomeric actin in contractile myotubes derived from primary myoblasts. Within one day after implantation of primary myoblasts into mouse skeletal muscle, SMA was observed in the myoblasts; but by 9 days post‐implantation, no SMA was detectable in myoblasts or muscle fibers. Thus, both neonatal primary myoblasts and an established myoblast cell line appear to similarly reprise an embryonic developmental program during differentiation in culture as well as differentiation within adult mouse muscles. Cell Motil. Cytoskeleton 51:177–186, 2002. © 2002 Wiley‐Liss, Inc.
In vivo localization of centrin in the green alga Chlamydomonas reinhardtii
Authors: Ruiz‐Binder Nayma E. , Geimer Stefan , Melkonian Michael
Published: August 2002

The green alga Chlamydomonas reinhardtii has been used as a model system to study flagellar assembly, centriole assembly, and cell cycle events. These processes are dynamic. Therefore, protein targeting and protein‐protein interactions should be evaluated in vivo. To be able to study dynamic processes in C. reinhardtii in vivo, we have explored the use of the green fluorescent protein (GFP). A construct containing a fusion of centrin and GFP was incorporated into the genome as a single copy. The selected clone shows expression in 25–50% of the cells. Centrin‐GFP was targeted in vivo to the nuclear basal body connectors and the distal connecting fibers. At the electron microscopic level, it was also localized to the flagellar transitional regions. EM data of transformants indicate that there are some abnormalities in the centrin‐containing structures. The transitional region consists of only the transverse septum or has lesions in the H‐piece. The distal connecting fibers are thinner and their characteristic crossbands seem to be incomplete. Deflagellation is not affected since more than 95% of the cells deflagellate. Also basal body segregation is not affected since cells with an abnormal flagellar number were not detected. Functional studies of the centrin‐GFP fusion show the characteristic calcium‐induced mobility shift in SDS‐PAGE. Immunofluorescence revealed that during cell division, centrin‐GFP remains associated with the basal bodies. In vivo localization of the fusion protein during cell division shows that in metaphase centrin‐GFP appears as two opposing spots located close to the spindle poles. The distance between the spots increases as the cells progress through anaphase and then decreases during telophase. GFP is a useful tool to study dynamic processes in the cytoskeleton of C. reinhardtii. Cell Motil. Cytoskeleton 52:43–55, 2002. © 2002 Wiley‐Liss, Inc.
Electromagnetic wave compression and radio frequency homogeneity in NMR solenoidal coils: Computational approach
Authors: Engelke Frank
Published: August 2002

The homogeneity of the radio frequency (RF) magnetic field in the region of the NMR sample is prerequisite for good performance in many NMR experiments. When calculating such fields, the quasistationary approximation is valid for wavelengths that are large compared to the physical dimensions of the NMR coil, but it no longer applies for the geometrical dimensions of NMR coils at high frequencies. The present study investigates electromagnetic fields in solenoidal coils. Considering the electromagnetic field derivable from first principles allows us to systematically study the effects that originate from the finiteness of the wavelength compared to the physical size of solenoidal coils employed in NMR probes. There are three major effects that occur: the wavelength in the coil is generally different from the wavelength in free space, even for an absent sample; the dielectric properties of the NMR sample have an additional influence on the electromagnetic field distribution inside the coil; and the circuit surrounding the coil leads to a wave reflection that affects the RF magnetic field distribution originating from the superposition of forward and backward traveling waves. The results allow the derivation of principal conclusions for the characterization of NMR solenoidal coils. © 2002 Wiley Periodicals, Inc. Concepts in Magnetic Resonance (Magn Reson Engineering) 15: 129–155, 2002
Echo planar spectroscopic imaging
Authors: Mulkern Robert V. , Panych Lawrence P.
Published: August 2002

Echo planar spectroscopic imaging (EPSI) allows for mapping one spatial dimension and the spectroscopic dimension in a single readout. Modern clinical magnetic resonance imaging scanners are becoming widely equipped with echo planar imaging gradient capabilities. Thus there exists an enormous potential for EPSI to facilitate clinical magnetic resonance spectroscopy. Here, a pedagogical analysis of how the spectral and spatial encoding occur within EPSI is provided along with demonstrations of the technique and a discussion of the inherent signal‐to‐noise limitations. © 2001 John Wiley & Sons, Inc. Concepts Magn Reson 13: 213–237, 2001
p53 mutation analysis for definite diagnosis of multiple primary lung carcinoma
Authors: van Rens Marcel Th. M. , Eijken Erik J. E. , Elbers Johannes R. J. , Lammers Jan‐W. J. , Tilanus Marcel G. J. , Slootweg Pieter J.
Published: August 2002

BACKGROUND

The detection of a second tumor in patients with lung carcinoma raises the question whether this lesion is a metastasis or a second primary lung carcinoma. Patients cannot always be categorized satisfactorily according the criteria of multiple lung carcinoma proposed by Martini and Melamed. This may result in an inadequate treatment schedule in individual patients. Because p53 mutations can be used as clonal marker, the authors investigated whether p53 mutation analysis can differentiate between primary lung carcinomas and metastatic disease.

METHODS

Sixty‐four tumors in 31 patients with synchronous and metachronous lung tumors were investigated by p53 mutation analysis.

RESULTS

In 21 patients, the tumors showed different p53 mutations, and therefore a definite diagnosis of multiple primary lung carcinoma was made. One of these patients did not meet the criteria of Martini and Melamed. In two other patients not matching these criteria, identical mutations were demonstrated in both tumors, indicating the presence of metastatic disease. In eight patients, analysis was not conclusive or possible.

CONCLUSIONS

p53 mutation analysis can be a useful tool to confirm or rule out multiple primary lung carcinoma, and the results confirm the criteria of Martini and Melamed. However, in patients not meeting these criteria, the diagnosis of multiple lung carcinoma still has to be considered, and metastatic disease has to be ruled out. P53 mutation analysis can be helpful for this purpose. Cancer 2002;94:188–96. © 2002 American Cancer Society.
Active chemotherapy for collecting duct carcinoma of the kidney
Authors: Milowsky Matthew I. , Rosmarin Alyssa , Tickoo Satish K. , Papanicolaou Nicholas , Nanus David M.
Published: August 2002

BACKGROUND

Collecting (Bellini) duct carcinoma (CDC) of the kidney is associated with an aggressive course and an extremely poor prognosis. To the authors' knowledge, there are no standard treatment regimens and neither immunotherapy nor chemotherapy have been found to be effective.

METHODS

In the current study, the authors report a 49‐year‐old man who presented with a 7.0 cm × 6.0 cm renal mass with extensive regional, paraaortic, and left supraclavicular lymphadenopathy. Radical nephrectomy revealed a CDC. The patient was treated with doxorubicin, 50 mg/m2 (Day 1), and gemcitabine, 2000 mg/m2 (Day 1), (AG) every 2 weeks with granulocyte–colony‐stimulating factor (GCSF) support.

RESULTS

The left supraclavicular lymphadenopathy significantly decreased in size after the first cycle. Computed tomography (CT) scan after the third cycle revealed a significant (68%) reduction in the tumor volume. Toxicity was comprised of only CTC version 2.0, 1998; Grade 1 nausea and fatigue. After Cycle 6, a repeat CT scan demonstrated minimal disease progression. Based on recent Phase II data of an active regimen comprised of AG alternating with ifosfamide, paclitaxel, and cisplatin (ITP) in patients with transitional cell carcinoma, the patient was treated with ifosfamide, 1500 mg/m2 (Days 1–3); paclitaxel, 175 mg/m2 (Day 1); and cisplatin, 35 mg/m2 (Days 1 and 2), every 4 weeks with GCSF support. After two cycles of ITP, the patient developed disease progression in bone and received palliative radiation therapy. Follow‐up CT scan demonstrated new liver metastases. The patient received palliative care without further chemotherapy and died approximately 10 months after the initial diagnosis of CDC.

CONCLUSIONS

Immunohistologic and molecular analyses indicate that CDC more closely resembles transitional cell carcinoma than renal cell carcinoma. Chemotherapy regimens used to treat advanced transitional cell carcinoma such as AG should be evaluated as first‐line therapy for CDC. Cancer 2002;94:111–6. © 2002 American Cancer Society.
Loss of E‐cadherin expression resulting from promoter hypermethylation in oral tongue carcinoma and its prognostic significance
Authors: Chang Hsiao Wen , Chow Vivian , Lam King Yin , Wei William Ignace , Wing Yuen Anthony Po
Published: August 2002

BACKGROUND

E‐cadherin is expressed on the surface of normal epithelial cells. Loss of E‐cadherin expression has been found in cancers and is postulated to facilitate tumor cell dissociation and metastasis. This study evaluated the role of promoter dense methylation in the downregulation of E‐cadherin expression in oral tongue carcinoma.

METHODS

E‐cadherin expression of 109 oral tongue carcinomas (93 primary tumors, 7 locally recurrent tumors, and 9 metastatic lymph nodes) was evaluated by immunohistochemical staining of tumor tissues. The methylation status of the CpG islands at the promoter region of E‐cadherin which flanked five HpaII (methylation sensitive restriction enzyme) digestion sites were evaluated by methylation sensitive polymerase chain reaction in 86 tumors (70 primary tumors, 7 locally recurrent tumors, and 9 metastatic lymph nodes).

RESULTS

Underexpression of E‐cadherin was found in 83% of primary tumors, 86% of recurrent tumors, and 89% of nodal metastases. Hypermethylated E‐cadherin promoter was found in 64% of primary tumors, 71% of recurrent tumors, and 67% of nodal metastases. Downregulation of E‐cadherin expression was found to be related to promoter hypermethylation. Consistently weak expression of E‐cadherin by promoter hypermethylation was observed in primary tumors, their corresponding metastatic lymph nodes, and recurrent tumors. Downregulation of E‐cadherin expression was a significant poor prognostic factor for survival.

CONCLUSIONS

Methylation of CpG sites at the promoter region played a key role in the inhibition of E‐cadherin expression in both primary oral tongue carcinomas and their corresponding recurrences and nodal metastases. The resulting downregulation of E‐cadherin expression had adverse effects on the prognosis of patients who were treated by primary surgery. Cancer 2002;94:386–92. © 2002 American Cancer Society.
Severe interstitial pneumonitis associated with docetaxel administration
Authors: Read William L. , Mortimer Joanne E. , Picus Joel
Published: August 2002

BACKGROUND

Interstitial pneumonitis has not been reported as a toxicity of docetaxel. The authors report the presentation and natural history of four patients who developed a severe interstitial pneumonitis after receiving docetaxel.

METHODS

The hospital and outpatient records of patients treated with docetaxel were reviewed to identify whether any of these patients required an evaluation for respiratory problems.

RESULTS

Four patients developed an interstitial pneumonitis that could be explained only as a toxicity of docetaxel. None had metastatic disease to the lung, and all had normal liver function before receiving chemotherapy. The patients presented with acute dyspnea and fever within 1–2 weeks of receiving docetaxel. All developed progressive interstitial infiltrates and respiratory failure that required mechanical ventilation. An exhaustive workup for other causes of pneumonitis was negative. Broad‐spectrum antibiotics and corticosteroids were ineffective. Two patients died of complications related to the pulmonary process. The two survivors required ventilatory support for more than 21 days. The clinical and pathologic findings of these patients are presented.

CONCLUSIONS

Interstitial pneumonitis is a rare and potentially fatal complication of docetaxel treatment. Prolonged ventilatory support is appropriate in patients with a favorable prognosis. Cancer 2002;94:847–53. © 2002 American Cancer Society.

DOI 10.1002/cncr.10263
A prospective study evaluating the response of patients with unrelieved cancer pain to parenteral opioids
Authors: Enting Roelien H. , Oldenmenger Wendy H. , van der Rijt Carin C. D. , Wilms Erik B. , Elfrink Erna J. , Elswijk Ineke , Sillevis Smitt Peter A. E.
Published: August 2002

BACKGROUND

The initiation of continuous parenteral (subcutaneous or intravenous) opioids or a change of opioid (opioid rotation) are treatment options for patients who fail on oral or transdermal opioids. There are insufficient data on the efficacy of these strategies, and comparative data are unavailable.

METHODS

The authors prospectively evaluated the efficacy of the start of parenteral opioids in 100 patients with cancer pain who failed on conventional opioids. Pain intensity was rated at rest and during movement from 0 to 10 and was categorized as mild (0–4), moderate (5–6), or severe (7–10): Clinically important pain control was defined as a decrease ≥ 2 points in pain intensity and pain intensity < 7. Pain control was evaluated on the second day and again when a clinical decision was made to continue or change parenteral opioid treatment after a median of 6 days. The presence of side effects (absent, mild, moderate, or severe) was evaluated.

RESULTS

The mean pain intensity at rest decreased significantly from 6.3 to 4.4 at 48 hours and to 3.4 at the end of treatment. The mean pain intensity during movement decreased significantly from 8.4 to 5.7 at 48 hours and to 4.6 at the end of treatment. Clinically important pain control at rest was seen in 52% of patients at 48 hours, in 71% of patients at the end of treatment; and clinically important pain control during movement was seen in 43% of patients at 48 hours and in 61% of patients at the end of treatment. The proportion of patients with mild pain increased significantly both at rest and during movement. Side effects were present in 78% of patients, and they resolved completely in 32% of patients. The median intravenous morphine equivalent dose increased from 80 mg per day to 135 mg per day at 48 hours and to 201 mg per day at the end of treatment. Results were not different for opioid rotation or for change of route only, nor did the start of antitumour treatment influence the results. In 34% of patients, it was decided to rotate to a second‐line parenteral opioid or to start either spinal analgesia or a sedation procedure after a median of 6 days. During follow‐up, 18% of patients who were dismissed with parenteral opioids (and 6% of all patients) needed a further change of treatment.

CONCLUSIONS

Parenteral opioids improved the balance between analgesia and side effects in patients with cancer pain who failed on conventional opioids, with an important improvement seen in 71% of patients. On the basis of this study, it is concluded that parenteral opioids are a good alternative to spinal opioids. Furthermore, it is suggested that a change of route alone is as effective as opioid rotation. Cancer 2002;94:3049–56. © 2002 American Cancer Society.

DOI 10.1002/cncr.10518
Fas (CD95/APO‐1) and Fas ligand expression in normal pancreas and pancreatic tumors
Authors: Bernstorff Wolfram V. , Glickman Jonathan N. , Odze Robert D. , Farraye Francis A. , Joo Hong G. , Goedegebuure Peter S. , Eberlein Timothy J.
Published: August 2002

BACKGROUND

Fas (CD95/APO‐1) and Fas ligand (FasL) play key roles in immunologic homeostasis and immune privilege and may regulate normal cell turnover. Earlier studies had suggested that FasL‐positive pancreatic carcinoma cell lines can induce apoptosis in T cells, thereby evading host immune surveillance. In the current study the authors have characterized the expression of Fas and FasL in the normal pancreas and in pancreatic neoplasia.

METHODS

Pancreatic resection specimens with ductal‐type adenocarcinoma or intraductal dysplasia (n = 41), nonductal pancreatic neoplasms (n = 5), and chronic pancreatitis (n = 4) were examined for Fas and FasL expression by immunohistochemistry. The results in invasive adenocarcinoma were compared to those for benign ducts and intraductal dysplasia, and correlated with clinicopathologic features of the tumors and with patient survival.

RESULTS

Fas was expressed in the normal pancreatic ducts and in intraductal dysplasia in a mixed membrane/cytoplasmic pattern. In all cases of invasive ductal‐type adenocarcinoma, membranous Fas could not be detected; cytoplasmic Fas staining was reduced or completely lost. Loss of Fas expression in pancreatic ductal‐type adenocarcinomas significantly correlated with poorer differentiation and extrapancreatic spread of the tumors and was associated with a shorter overall survival. FasL expression was present in the normal pancreatic ducts as well as in islet cells and was maintained in all pancreatic tumors.

CONCLUSIONS

These results implicate the Fas pathway in the regulation of physiologic cell turnover and immune privilege in the normal pancreas and indicate that loss of Fas expression is correlated with malignant transformation and biologic aggressiveness in pancreatic adenocarcinomas. This may represent a mechanism by which pancreatic tumor cells become resistant to apoptosis and escape immune surveillance in vivo. Cancer 2002;94:2552–60. © 2002 American Cancer Society.

DOI 10.1002/cncr.10549
Functional circuitry involved in the regulation of whisker movements
Authors: Hattox Alexis M. , Priest Catherine A. , Keller Asaf
Published: August 2002

Neuroanatomical tract‐tracing methods were used to identify the oligosynaptic circuitry by which the whisker representation of the motor cortex (wMCx) influences the facial motoneurons that control whisking activity (wFMNs). Injections of the retrograde tracer cholera toxin subunit B into physiologically identified wFMNs in the lateral facial nucleus resulted in dense, bilateral labeling throughout the brainstem reticular formation and in the ambiguus nucleus as well as predominantly ipsilateral labeling in the paralemniscal, pedunculopontine tegmental, Kölliker‐Fuse, and parabrachial nuclei. In addition, neurons in the following midbrain regions projected to the wFMNs: superior colliculus, red nucleus, periaqueductal gray, mesencephalon, pons, and several nuclei involved in oculomotor behaviors. Injections of the anterograde tracer biotinylated dextran amine into the wMCx revealed direct projections to the brainstem reticular formation as well as multiple brainstem and midbrain structures shown to project to the wFMNs. Regions in which retrograde labeling and anterograde labeling overlap most extensively include the brainstem parvocellular, gigantocellular, intermediate, and medullary (dorsal and ventral) reticular formations; ambiguus nucleus; and midbrain superior colliculus and deep mesencephalic nucleus. Other regions that contain less dense regions of combined anterograde and retrograde labeling include the following nuclei: the interstitial nucleus of medial longitudinal fasciculus, the pontine reticular formation, and the lateral periaqueductal gray. Premotoneurons that receive dense inputs from the wMCx are likely to be important mediators of cortical regulation of whisker movements and may be a key component in a central pattern generator involved in the generation of rhythmic whisking activity. J. Comp. Neurol. 442:266–276, 2002. © 2001 Wiley‐Liss, Inc.
Upregulation of Kv 1.4 protein and gene expression after chronic spinal cord injury
Authors: Edwards Lori , Nashmi Raad , Jones Owen , Backx Peter , Ackerley Cameron , Becker Larry , Fehlings Michael G.
Published: August 2002

After spinal cord injury (SCI), white matter tracts are characterized by demyelination and increased sensitivity to the K+ channel blocker 4‐aminopyridine (4‐AP). These effects appear to contribute to neurological impairment after SCI, although the molecular changes in K+ channel subunit expression remain poorly understood. We examined changes in gene expression of the 4‐AP‐sensitive voltage‐gated K+ channel Kv 1.4 after chronic SCI in the rat. Quantitative immunoblotting showed that Kv 1.4 protein was significantly increased at 6 weeks, but not at 1 week, after SCI in spinal cord white matter. Kv 1.4 was localized to astrocytes, oligodendrocytes, and oligodendrocyte progenitor cells but not to axons in both the normal and the injured spinal cord white matter. Because glial cells proliferate after SCI, we used immunogold electron microscopy to quantify Kv 1.4 protein in individual glial cells and found a sixfold increase of Kv 1.4 in cells of the oligodendrocyte lineage after chronic injury. Finally, quantitative in situ hybridization showed that Kv 1.4 mRNA was significantly upregulated in spinal cord white matter, but not gray matter, after SCI. In summary, we show that Kv 1.4 is expressed in glial cells and not in axons in the rat spinal cord white matter and that its expression is markedly increased in cells of the oligodendrocyte lineage after chronic SCI. Given that K+ channels play a role in glial cell proliferation, cells exhibiting changes in Kv 1.4 expression may represent proliferating oligodendroglia in the chronically injured spinal cord. J. Comp. Neurol. 443:154–167, 2002. © 2002 Wiley‐Liss, Inc.
Differential distribution of spermidine/spermine‐like immunoreactivity in neurons of the adult rat brain
Authors: Laube Gregor , Bernstein Hans‐Gert , Wolf Gerald , Veh Rüdiger W.
Published: August 2002

The polyamines spermidine and spermine are small, widely distributed polycations. In the brain, they confer rectification properties upon inwardly rectifying potassium channels and Ca2+‐permeable α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole‐propionate (AMPA)/kainate receptors and also modify functional properties of N‐methyl‐D‐aspartate receptors. Therefore, functional roles of spermidine/spermine in the adult brain will depend on the colocalization of the spermidine/spermine‐sensitive receptors/channels and the polyamines either in the same or in closely associated cell types. We previously immunocytochemically demonstrated a prominent localization of spermidine/spermine in glial cells, especially astrocytes (Laube and Veh [ 1997] Glia 19:171–179). In contrast to the commonly accepted assumption of a ubiquitous distribution of polyamines in various cell types, in neurons of the rat brain, we detected a highly diverse spermidine/spermine‐like immunoreactivity. The immunoreactivity in neurons and neuropil throughout the rat brain is listed according to intensity in arbitrary groups. The strongest neuronal staining was observed in the hypothalamic paraventricular, supraoptic, and accessory neurosecretory nuclei. Strong cytoplasmic staining was also evident in some motor and somatosensory areas such as the Me5 nucleus of the mesencephalic trigeminal tract, the nucleus ruber, and the large motor neurons of the spinal cord ventral horn. In contrast, in most cortical and hippocampal regions spermidine/spermine‐like immunoreactivity in neurons was relatively weak, whereas in these areas, the labeling pattern was dominated by a diffuse neuropil labeling. In addition to spermidine/spermine immunocytochemistry, ornithine decarboxylase labeling was performed and the resulting labeling patterns were compared. The prominent localization of spermidine/spermine in neurosecretory neurons might point to a functional role different from channel/receptor modification. In these neurons, polyamines might be involved in secretory processes. J. Comp. Neurol. 444:369–386, 2002. © 2002 Wiley‐Liss, Inc.
Mast cells in Wallerian degeneration: Morphologic and ultrastructural changes
Authors: Esposito Barbara , De Santis Amedeo , Monteforte Rossella , Baccari Gabriella Chieffi
Published: August 2002

The morphologic and ultrastructural changes of mast cells were followed in degenerating distal and regenerating proximal stumps of frog brachial nerve during Wallerian degeneration. Quantitative analysis included determination of both number and size of mast cells. The mast cell response to injury consisted of an early and a late phase. In the early phase, there was an increase in mast cell numbers in the proximal site of the lesion and a release of Alcian blue material consistent with mediator release. This phase of mast cell activation may be related, through the secretion of biogenic agents such as heparin and histamine, to the increase of endoneurial vessel size and vascular permeability, providing access for macrophages and mast cell precursors. The later phase, which peaked at 40 days after transection in the degenerating distal stump, consisted in the degranulation of the mast cells. These mast cells, closely associated with macrophages and degenerating Schwann cells, released secretory granules into the endoneurial microenvironment. These degranulating mast cells, through the released acid hydrolases, may contribute along with macrophages and Schwann cells, to the degradation of myelin debris. At the same time, mast cells appeared filled with granular content in the regenerating proximal segment. Therefore, we suggest that mast cells in peripheral nerves may play an important role in nerve degenerating and regenerating mechanisms through the secretion of diffusible molecules. J. Comp. Neurol. 445:199–210, 2002. © 2002 Wiley‐Liss, Inc.
Distribution and synaptic connectivity of neuropeptide Y‐immunoreactive amacrine cells in the rat retina
Authors: Oh Su‐Ja. , D'Angelo Iona , Lee Eun‐Jin , Chun Myung‐Hoon , Brecha Nicholas C.
Published: August 2002

Neuropeptide Y (NPY) is a potent bioactive peptide that is widely expressed in the nervous system, including the retina. Here we show that specific NPY immunoreactivity was localized to amacrine and displaced amacrine cells in the rat retina. Immunoreactive cells had a regular distribution across the retina and an overall cell density of 280 cells/mm2 in the inner nuclear layer (INL) and 90 cells/mm2 in the ganglion cell layer (GCL). In the INL, most immunoreactive cells were characterized by small cell bodies and fine processes that appeared to ramify primarily in stratum 1 of the inner plexiform layer (IPL). A few cells in the INL also ramified in stratum 3 of the IPL. In the GCL, small to medium immunoreactive cells appeared to ramify primarily in stratum 5 of the IPL. A few immunoreactive processes, originating from somata in the INL and processes in the IPL, ramified in the OPL. NPY‐immunoreactive cells contained GABA immunoreactivity, and some amacrine cells also contained tyrosine hydroxylase immunoreactivity. NPY‐immunostained processes were most frequently presynaptic to nonimmunostained amacrine and ganglion cell processes and postsynaptic to nonimmunostained amacrine cell processes and cone bipolar cell axonal terminals. These findings indicate that NPY immunoreactivity is present in two populations of amacrine cells, one located in the INL and the other in the GCL, and that these cells mainly form synaptic contacts with other amacrine cells. These observations suggest that NPY‐immunoreactive cells participate in multiple circuits mediating visual information processing in the inner retina. J. Comp. Neurol. 446:219–234, 2002. © 2002 Wiley‐Liss, Inc.
Retinofugal projections in the short‐tailed opossum (Monodelphis domestica)
Authors: Kahn Dianna M. , Krubitzer Leah
Published: August 2002

In the current investigation, retinofugal projections to midbrain and thalamic nuclei of Monodelphis domestica were investigated using wheat‐germ agglutinin conjugated to horseradish peroxidase (WGA‐HRP). Large intraocular injections of WGA‐HRP were placed into the eye, and patterns of labeled axon terminals were related to nuclear boundaries in tissue that was stained for Nissl or reacted for cytochrome oxidase (CO). Our results demonstrate that the major projection from the retina is to the contralateral dorsal lateral geniculate nucleus (LGNd) and the superior colliculus (SC). Connections were also observed with the contralateral pretectal nucleus (PRT), the lateral posterior nucleus (LP), and the ventral division of the lateral geniculate nucleus (LGNv). Ipsilateral connections were with the LGNv and LGNd. These findings are consistent with reports in other marsupials as well as with studies in a number of eutherian mammals. Thus, there appears to be a common pattern of retinofugal projections that all mammals share, probably due to retention from a common ancestor. However, some features such as a lack of ipsilateral input to the SC (which are absent only in certain species like Monodelphis, platypus, and echidnas) may represent a primitive state retained from a common ancestor. When comparisons of retinofugal connections and LGNd organization are made across taxa, three types of organization are observed: a homogenous LGNd with a high degree of binocular overlap of projections; a partially differentiated LGNd with some segregation of eye‐specific inputs; and a fully segregated structure with a large degree of segregation of eye‐specific inputs. We discuss the factors that contribute to the organization observed in extant mammals and conclude that phylogeny and lifestyle appear to be the underlying factors contributing to the organization of the LGNd. J. Comp. Neurol. 447:114–127, 2002. © 2002 Wiley‐Liss, Inc.
Developmental regulation of CPG15 expression in Xenopus
Authors: Nedivi Elly , Javaherian Ashkan , Cantallops Isabel , Cline Hollis T.
Published: August 2002

Mechanisms controlling dendritic arbor formation affect the establishment of neuronal circuits. Candidate plasticity gene 15 (CPG15) is a glycosylphosphatidyl inositol (GPI)‐linked activity‐induced protein that has been shown to function as an intercellular signaling molecule that can promote the morphological and physiological development of the Xenopus retinotectal system. A thorough understanding of CPG15 function requires knowledge of the spatiotemporal expression of the endogenous protein. We therefore cloned Xenopus cpg15 and used RNA in situ hybridization and immunohistochemistry to determine the pattern of CPG15 expression. cpg15 mRNA and CPG15 protein are first detectable in the developing spinal cord and become widespread as development proceeds. CPG15 is expressed in sensory regions of the brain, including the visual, auditory, and olfactory systems. Within the retina, CPG15 is only expressed in retinal ganglion cells. CPG15 protein is concentrated in axon tracts, including retinal axons. These data support a model in which CPG15 expressed in retinal ganglion cells is trafficked to retinal axons, where it modulates postsynaptic dendritic arbor elaboration, and synaptic maturation. J. Comp. Neurol. 435:464–473, 2001. © 2001 Wiley‐Liss, Inc.