bluuebunny/crossref_metadata_2025 huggingface dataset:
Methyl CpG‐binding proteins and transcriptional repression*
Authors: Wade Paul A.
Published: August 2002

Since its discovery, methylation of DNA in mammalian cells has been correlated with transcriptional repression and with specialized chromatin structures. Recently, considerable progress has been reported in the identification of protein factors with a highly conserved DNA interaction surface, termed the methyl CpG‐binding domain or MBD. A subset has been biochemically linked to histone deacetylases, suggesting a molecular mechanism for the functional properties of methylated DNA. Despite several obvious attractions, the connection between MBD proteins and histone deacetylases fails to explain all the existing data. In fact, the biochemistry and DNA‐binding properties of most MBD family members have not been adequately described and considerable evidence exists for alternative mechanisms in the repression of methylated loci. Null mutations have been generated in mice for several MBD family members, the phenotypes of the mutant animals raise important questions regarding the functions of the MBD family. Here, I review the biochemistry, DNA‐binding properties, and genetics of the MBD proteins that are linked to transcriptional repression, namely, MeCP2, MBD1, MBD2, and MBD3. Several models to account for the functional properties of methylated DNA are presented. BioEssays 23:1131–1137, 2001. © 2001 John Wiley & Sons, Inc.
The molecular machinery for lysosome biogenesis*
Authors: Mullins Chris , Bonifacino Juan S.
Published: August 2002

The lysosome serves as a site for delivery of materials targeted for removal from the eukaryotic cell. The mechanisms underlying the biogenesis of this organelle are currently the subject of renewed interest due to advances in our understanding of the protein sorting machinery. Genetic model systems such as yeast and Drosophila have been instrumental in identifying both protein and lipid components of this machinery. Importantly, many of these components, as well as the processes in which they are involved, are proving conserved in mammals. Other recently identified components, however, appear to be unique to higher eukaryotes. BioEssays 23:333–343, 2001. Published 2001 John Wiley & Sons, Inc.
Cancer: the evolved consequence of a destabilized genome
Authors: Anderson Garth R. , Stoler Daniel L. , Brenner Bruce M.
Published: August 2002

The genome is a stable repository of vastly intricate genetic information developed over eons of evolution; this information is replicated at the highest fidelity and expressed within each cell at the highest selectivity. Non‐leukemia cancers break this standard; the intricate genetic information qualitatively and progressively deteriorates, resulting in a somatic Darwinian free‐for‐all. In a process lasting several years, a genomically heterogeneous population replicates from a single cell that originally lost the ability to preserve its genomic integrity. Cells selected for their abilities to proliferate and spread, while evading host defenses, inexorably expand their numbers. The clinical consequences of this become severe, as the genomically diverse cell population that evolves contains members that can evade most therapeutic approaches aimed at “the tumor cell”. BioEssays 23:1037–1046, 2001. © 2001 John Wiley & Sons, Inc.
NMR solution structure of the isolated Apo Pin1 WW domain: Comparison to the x‐ray crystal structures of Pin1
Authors: Kowalski Jennifer A. , Liu Kai , Kelly Jeffery W.
Published: August 2002

The NMR solution structure of the isolated Apo Pin1 WW domain (6–39) reveals that it adopts a twisted three‐stranded antiparallel β‐sheet conformation, very similar to the structure exhibited by the crystal of this domain in the context of the two domain Pin1 protein. While the B factors in the apo x‐ray crystal structure indicate that loop 1 and loop 2 are conformationally well defined, the solution NMR data suggest that loop 1 is quite flexible, at least in the absence of the ligand. The NMR chemical shift and nuclear Overhauser effect pattern exhibited by the 6–39 Pin1 WW domain has proven to be diagnostic for demonstrating that single site variants of this domain adopt a normally folded structure. Knowledge of this type is critical before embarking on time‐consuming kinetic and thermodynamic studies required for a detailed understanding of β‐sheet folding. © 2002 John Wiley & Sons, Inc. Biopolymers 63: 111–121, 2002
Significance of location of enzymes on their release during microbial cell disruption
Authors: Balasundaram B. , Pandit A.B.
Published: August 2002

The release kinetics of the enzyme invertase and alcohol dehydrogenase from yeast and penicillin acylase from E. coli during disruption using various techniques has been investigated. The disruption techniques used were sonication, high‐pressure homogenization, and hydrodynamic cavitation. The first‐order‐release kinetics was applied for the determination of release rate of these enzymes and total soluble proteins. Location factor (LF) values were calculated using these release rates. The location of the enzymes as given by the values of location factor coincided well with those reported in the literature. Varying values of location factor for the same enzyme by different disruption techniques gave some indications about the selectivity of release of a target enzyme by different disruption techniques. Varying values of location factor for the same enzyme with the use of a particular equipment or disruption technique at different conditions reveals the degree to which the cell is disrupted. Few plausible applications of this location factor concept have been predicted and these speculations have been examined. This location factor concept has been used for monitoring the heat‐induced translocation of ADH and location of penicillin acylase during the growth period of E. coli cells. © 2001 John Wiley & Sons, Inc. Biotechnol Bioeng 75: 607–614, 2001.
Metabolic flux modeling of detoxification of acetic acid by Ralstonia eutropha at slightly alkaline pH levels
Authors: Yu Jian , Wang Jianping
Published: August 2002

Ralstonia eutropha grows on and produces polyhydroxyalkanoates (PHAs) from fermentation acids. Acetic acid, one major organic acid from acidogenesis of organic wastes, has an inhibitory effect on the bacterium at slightly alkaline pH (6 g HAc/L at pH 8). The tolerance of R. eutropha to acetate, however, was increased significantly up to 15 g/L at the slightly alkaline pH level with high cell mass concentration. A metabolic cell model with five fluxes is proposed to depict the detoxification mechanism including mass transfer and acetyl‐CoA formation of acetic acid and the formation of three final metabolic products, polyhydroxybutyrate (PHB), active biomass, and CO2. The fluxes were measured under different conditions such as cell mass concentration, acetic acid concentration, and medium composition. The experimental results indicate that the acetate detoxification by high cell mass concentration is attributed to the increased fluxes at high extracellular acetate concentrations. The fluxes could be doubled to reduce and hence detoxify the accumulated intracellular acetate anions. © 2001 John Wiley & Sons, Inc. Biotechnol Bioeng 73: 458–464, 2001.
Simultaneous determination of ondansetron and tropisetron in human plasma using HPLC with UV detection
Authors: Bauer Steffen , Störmer Elke , Kaiser Rolf , Tremblay Pierre‐Benoit , Brockmöller Jürgen , Roots Ivar
Published: August 2002

A rapid and sensitve HPLC method for the simultaneous quantitation of ondansetron and tropisetron, two serotonin (5‐HT) receptor antagonists frequently used in treatment and prevention of nausea and emesis, is described. The procedure involves liqid–liquid extraction of human plasma with dichloromethane coupled with reversed‐phase HPLC and UV detection. The lower limits of quantification (LOQ) were 0.62 ng/mL for ondansetron and 1.25 ng/mL or tropisetron. Intra‐ and inter‐assay coefficients of variation ranged from 1.5 to 7.5% and 5.3 to 13.7%, respectively. The sensitivity and precision were sufficient for determination of plasma concentrations after therapeutic administration of both drugs and the method can be used for the estimation of pharmacokinetic parameters. Copyright © 2002 John Wiley & Sons, Ltd.
Pathways to industrial environmental improvement in the East Asian newly industrializing economies
Authors: Rock Michael T.
Published: August 2002

After the adoption of ‘grow first clean up later’ environmental strategies, governments in the East Asian newly industrializing economies (NIEs) turned to environmental ‘clean‐up’ by enacting landmark environmental legislation, creating command and control environmental agencies and promulgating tough air and water emissions standards. Available evidence suggests there is wide variability in the performance of these new environmental regulatory agencies.

Most attribute this variability to differences in ‘political will’. However, why have some governments among the East Asian NIEs been able to muster the ‘political will’ to impose duties on industrial polluters while others have not?

This paper answers this question by summarizing a larger study (Rock, 2002) which examines the ‘politics of industrial pollution’ control in six East Asian NIEs. Each case study is based on extensive interviews, the collection of data on the effectiveness of pollution management policies, and the integration of both with the political economy literature on each economy. Copyright © 2002 John Wiley & Sons, Ltd. and ERP Environment
Fractal analysis of lumbar vertebral cancellous bone architecture
Authors: Feltrin G.P. , Macchi V. , Saccavini C. , Tosi E. , Dus C. , Fassina A. , Parenti A. , De Caro R.
Published: August 2002

Osteoporosis is characterized by bone mineral density (BMD) decreasing and spongy bone rearrangement with consequent loss of elasticity and increased bone fragility. Quantitative computed tomography (QCT) quantifies bone mineral content but does not describe spongy architecture. Analysis of trabecular pattern may provide additional information to evaluate osteoporosis. The aim of this study was to determine whether the fractal analysis of the microradiography of lumbar vertebrae provides a reliable assessment of bone texture, which correlates with the BMD. The lumbar segment of the spine was removed from 22 cadavers with no history of back pain and examined with standard x‐ray, traditional tomography, and quantitative computed tomography to measure BMD. The fractal dimension, which quantifies the image fractal complexity, was calculated on microradiographs of axial sections of the fourth lumbar vertebra to determine its characteristic spongy network. The relationship between the values of the BMD and those of the fractal dimension was evaluated by linear regression and a statistically significant correlation (R = 0.96) was found. These findings suggest that the application of fractal analysis to radiological analyses can provide valuable information on the trabecular pattern of vertebrae. Thus, fractal dimensions of trabecular bone structure should be considered as a supplement to BMD evaluation in the assessment of osteoporosis. Clin. Anat. 6:414–417, 2001. © 2001 Wiley‐Liss, Inc.
Dual Enrollment Options: Columbus State Community College Model for Successful Implementation
Authors: Jordan Tammi
Published: August 2002

Ohio Senate Bill 140 was enacted in 1989 to allow dual enrollment. The legislative intent and components are reviewed in this chapter, followed by an overview of criteria and procedures at Columbus State Community College. Methods that foster student success and growth are also discussed.
CO2 angiography
Authors: Huber Philip R. , Leimbach Mark E. , Lewis W. Lance , Marshall J. Jeffrey
Published: August 2002

Iodinated contrast agents are routinely used in procedures to diagnose and treat peripheral vascular disease. Despite the development of low‐osmolar contrast agents and premedication techniques, these agents are still associated with contrast‐induced nephropathy and allergic reactions in some individuals. To overcome these problems, carbon dioxide angiography has been developed as an alternative to standard iodinated contrast angiography in certain patient populations. The technology of digital subtraction angiography has greatly improved the image quality of CO2 angiography. Understanding the unique properties of CO2, the techniques for its use, and its associated limitations and complications will allow interventional cardiologists to expand their treatments of atherosclerotic peripheral vascular disease. Cathet Cardiovasc Intervent 2002;55:398–403. © 2002 Wiley‐Liss, Inc.
SMART: The microstent's ability to limit restenosis trial
Authors: Heuser Richard , Lopez Alejandro , Kuntz Richard , Reduto Lawrence , Badger Rodney , Coleman Patrick , Whitlow Patrick , Iannone L. A. , Safian Robert , Yeung Alan , Moses Jeffrey
Published: August 2002

In this randomized, prospective, multicenter trial (n = 661) of patients with de novo or restenotic coronary lesions, 330 patients received the MicroStent® II (MSII), and 331 received the Palmaz‐Schatz® (PS) stent. The short‐term procedural success rates were 94.4% and 95.7%, respectively (P = 0.47). The 30‐day cumulative incidence of major adverse events [death, myocardial infarction, CVA, target lesion revascularization (TLR)] was 6.4% for the MSII and 4.5% for the PS stent (P = 0.31). The in‐stent binary restenosis rate at 6 months was 25.2% for the MSII and 22.1% for the PS stent (P = 0.636). Using Kaplan‐Meier estimates, the incidence of clinically driven TLR was 8.9% for the MSII and 9.2% for the PS stent at 180 days; at 270 days, it was 12.8% and 12.1%, respectively (P = 0.83). MSII and the PS stents were comparable with respect to short‐term procedural success, complications, and late clinical and angiographic restenosis. Cathet Cardiovasc Intervent 2001;52:269–277. © 2001 Wiley‐Liss, Inc.
Safety and efficacy of suture‐mediated closure after percutaneous coronary interventions
Authors: Rinder Morton R. , Tamirisa Praveen K. , Taniuchi Megumi , Kurz Howard I. , Mumm Kimberly , Lasala John M.
Published: August 2002

Percutaneous coronary interventions (PCI) performed with concomitant use of heparin and platelet inhibitors are safe procedures with reported vascular complication rates of approximately 6.1%. EPILOG investigators demonstrated that utilizing a low‐dose heparin regimen with abciximab, along with early sheath removal, vascular access‐related bleeding was significantly lower than that reported in EPIC. Recently, a suture‐mediated closure (SMC) device has been reported to be safe, appears effective, and may improve patient comfort by allowing early ambulation. We conducted a retrospective analysis (January 1999 to March 2000) of complication frequencies among PCI patients who underwent SMC and those who had manual compression (non‐SMC). Furthermore, we compared the overall rates of complications to patients who underwent PCI prior to the introduction of SMC (1995–1998). When comparing the current cohort to the historical cohort, there was a significant decrease in the number of retroperitoneal bleeds (0.3% vs. 0.9%; P = 0.003), hematomas (5% vs. 9%; P < 0.001), pseudoaneurysms (1.2% vs. 2.7%; P < 0.001), and need for vascular surgery (0.9% vs. 2.8%; P < 0.001). There was no difference in the number of arterio‐venous fistulas and a slight increase in transfusion needs (12% vs. 10%; P = 0.03). Within the current cohort, there was no difference in the vascular complications between SMC and non‐SMC PCI patients, although there were lower rates of pseudoaneurysms (0.5% vs. 1.8%; P = 0.02) and transfusion requirements (72/880 vs. 132/874; P < 0.001). These results suggest that the complication rates for SMC are not different and may be lower when compared to non‐SMC patients after PCI. At our institution, the practice of early sheath removal and less aggressive heparin dosing has led to a decrease in vascular complication rates and a 66% reduction in vascular surgeries on post‐PCI patients. Because of the limitations of retrospective analyses, further studies will be necessary to confirm these findings. Cathet Cardiovasc Intervent 2001;54:146–151. © 2001 Wiley‐Liss, Inc.
Factors associated with abuse in residential child care institutions
Authors: Colton Matthew
Published: August 2002

Confidence in the public care system in the United Kingdom (UK) has been shaken by numerous and widespread scandals surrounding the abuse of children and young people, particularly those in residential child care institutions. This paper examines factors associated with such abuse, including: failings in relation to staff recruitment, training, and supervision; ineffective management and systems of accountability; the development of inappropriate institutional cultures; public ambivalence towards children in care; the slow footed response to the threat posed to children and young people by dangerous men and other youngsters in care; and the long‐term policy failure to develop coherent and integrated systems of child welfare in the UK. Copyright © 2002 John Wiley & Sons, Ltd.
Two‐dimensional separation of [7]helicene enantiomers on Cu(111)
Authors: Ernst K.‐H. , Kuster Y. , Fasel R. , Müller M. , Ellerbeck U.
Published: August 2002

The adsorption of heptahelicene, a helically shaped polyaromatic hydrocarbon (C30H18), on a Cu(111) surface was studied by means of thermal desorption mass spectrometry (TDMS) and low energy electron diffraction (LEED) at temperatures between 130–1,000 K under ultrahigh vacuum (UHV) conditions. The molecule in the monolayer remains intact up to 400 K. Above that temperature it decomposes in several steps into carbon and hydrogen, desorbing subsequently as H2. In the saturated monolayer of the racemate the enantiomers are separated into two different domains on the surface which are mirror images of each other. After adsorption of one enantiomer only, no mirror domains were observed. Chirality 13:675–678, 2001. © 2001 Wiley‐Liss, Inc.
Effect of beta radiation on the crystallization of sodium chlorate from water: A new type of asymmetric synthesis
Authors: Mahurin Shannon , McGinnis Michael , Bogard J.S. , Hulett L.D. , Pagni Richard M. , Compton Robert N.
Published: August 2002

Sodium chlorate is an achiral molecule that crystallizes from water in the chiral space group P213. In the absence of chiral perturbations, a random distribution of (+) and (−) crystals is obtained. Kondepudi2 has shown that constantly stirring an evaporating NaClO3 solution gives mostly either (+) or (−) crystals. Repeating this experiment many times gives equal numbers of (+) and (−) sets of crystals. Herein we report that when evaporating aqueous NaClO3 is subjected to beta particles from an Sr‐90 source, an asymmetric distribution of (+) and (−) crystals favoring the (+) crystals is obtained. The beta particles are energetic polarized electrons that are approximately 80% of left‐handed helicity. By a poorly understood mechanism, the spin polarized electrons produce chiral nucleating sites that favor formation of the (+)‐NaClO3 crystals. Exposure of the evaporating solution instead to energetic positrons from an Na‐22 source yields mainly (−)‐NaClO3 crystals. Polarized positrons are of predominantly right‐handed helicity. One may conclude that the chirality of the radiation is correlated with the chirality of the crystals being generated. Chirality 13:636–640, 2001. © 2001 Wiley‐Liss, Inc.
Lymphomas of the breast
Authors: Domchek Susan M. , Hecht Jonathan L. , Fleming Mark D. , Pinkus Geraldine S. , Canellos George P.
Published: August 2002

BACKGROUND

The involvement of the breast by lymphoma is a rare form of extralymph node lymphoma and represents either primary disease or systemic involvement. The authors hypothesized that screening mammography may influence the detection of lymphomatous involvement of the breast.

METHODS

All patients (n = 81 patients) who were diagnosed with lymphomatous involvement of the breast at the study institution between 1988 and 1999 were evaluated retrospectively.

RESULTS

Clinical information was available for 73 patients who could be classified into three major groups according to their diagnosis: primary breast lymphoma (PBL) (44%), breast involvement from disseminated disease at the time of initial diagnosis (29%), and recurrence of preexisting lymphoma to the breast (27%). The majority of PBL were of intermediate or high grade, and the majority of disseminated lymphomas involving the breast were of low grade. Lymphomatous recurrence to the breast was slightly more likely to be of intermediate grade rather than low grade. In 91% of patients, the diagnosis of lymphoma was made after the evaluation of a palpable mass. All patients who were identified after the evaluation of an abnormal screening mammogram (9%) had low‐grade lymphomas. Of the 32 patients with PBL, screening mammography discovered only 1. Nineteen percent of patients with PBL also had a history of an autoimmune disorder.

CONCLUSIONS

These findings suggest that screening mammography has not altered substantially the detection of breast lymphoma. The clinical outcome of patients with breast lymphoma is dependent on histology and appears to parallel that of patients with lymphoma of similar histology involving other sites. Cancer 2002;94:6–13. © 2002 American Cancer Society.
The prognostic value of immunohistochemically detected CD44v3 and CD44v6 expression in patients with surgically staged vulvar carcinoma
Authors: Hefler Lukas A. , Concin Nicole , Mincham David , Thompson Jane , Swarte Nikkie B. , van Eijkeren Marion A. , Sie‐Go Daisy M.D.S. , Hammond Ian , McCartney Anthony J. , Tempfer Clemens B. , Speiser Paul
Published: August 2002

BACKGROUND

Isoforms of the adhesion molecule CD44 are involved in carcinogenesis and the metastatic cascade of tumor cells by increasing the affinity of malignant cells to their extracellular matrix. Preliminary data with respect to the prognostic value of the CD44 isoforms CD44v3 and CD44v6 in patients with vulvar carcinoma showed promising results. The current multicenter study aimed to determine the prognostic value of CD44v3 and CD44v6 in patients with surgically staged vulvar carcinoma.

METHODS

Expression of CD44v3 and CD44v6 in vulvar carcinoma tissue was assessed by immunohistochemistry. Immunohistochemic staining was performed according to established protocols. Results were correlated to clinical data.

RESULTS

A positive CD44v3 and CD44v6 staining was detected in 33.3% (33 out of 99) and 39.4% (39 out of 99) of the tumor samples, respectively. Overexpression of CD44v6 was associated with an impaired prognosis with respect to disease‐free survival (P = 0.01) and overall survival (P = 0.04). Multivariate analysis showed that CD44v6 provided prognostic information with respect to disease‐free survival (P = 0.001) and overall survival (P = 0.005) independently of the two established prognosticators, tumor stage and groin lymph node involvement. Overexpression of CD44v3 had no impact on patient survival.

CONCLUSIONS

The current multicenter study, involving a large series of patients with surgically staged vulvar carcinoma, allowed for multivariate survival analysis and showed that CD44v6 confers prognostic information in addition to that provided by the established clinicopathologic parameters of tumor stage and lymph node status. Cancer 2002;94:125–30. © 2002 American Cancer Society.
31Phosphorus‐magnetic resonance spectroscopy to assess histologic tumor response noninvasively after isolated limb perfusion for soft tissue tumors
Authors: Kettelhack Christoph , Wickede Minette v. , Vogl Thomas , Schneider Ulrike , Hohenberger Peter
Published: August 2002

BACKGROUND

In patients with unresectable soft tissue sarcoma of the extremities, isolated limb perfusion (ILP) has been reported to result in significant tumor regression enabling limb‐sparing resection in the majority of patients. However, clinical tumor response as evaluated by imaging and histopathology (extent of tumor necrosis) often differ significantly. The current study was initiated to evaluate prospectively the role of 31phosphorus‐magnetic resonance spectroscopy (31P‐MRS) in the noninvasive assessment of histologic response in patients treated with ILP.

METHODS

Thirty‐two patients with locally advanced and unresectable soft tissue tumors (sarcoma in 28 patients and bulky melanoma in 4 patients) were treated by ILP with recombinant human tumor necrosis factor‐α and melphalan or with cytostatics. 31P‐MRS was performed prior to treatment and at regular intervals after ILP until definite tumor resection. Clinical response parameters according to the World Health Organization as well as the histopathologic necrosis rate of the resection specimen were correlated with changes in the energy‐rich phosphorous metabolites phosphocreatine (PCR); α‐, β‐, γ‐adenosine triphosphate (ATP); phosphomonoesters (PME); and inorganic phosphate (Pi).

RESULTS

Clinically, 15 of 32 patients (response rate [RR] of 47%) demonstrated a partial response (PR). The ratios of PME/PCR and PME/β‐ATP decreased significantly after ILP in comparison with preoperative values (P < 0.001). The changes in the PME/β‐ATP ratio were significantly different between clinical responders and nonresponders (P < 0.02) in contrast with the PME/PCR ratios (P < 0.09). Histologic necrosis of > 90% (pathologic (p) PR) was present in 17 resection specimens, 7 of which demonstrated no clinical response. Seven tumors demonstrated a pathologic complete response (pCR). When combining PR, pPR, and pCR (RR of 68%), 31P‐MRS was able to predict response with a specificity of 94% and a sensitivity of 68% (P < 0.006, by the chi‐square test).

CONCLUSIONS

The considerable difference between clinical and pathologic RR after ILP underlines the shortcomings of established response criteria. Utilizing changes in PME/β‐ATP ratios, 31P‐MRS is a highly specific tool with which to predict histologic response in this setting. This finding may be of major value in those patients in whom the decision to perform a major resection or amputation must be made for local tumor control. Cancer 2002;94:1557–64. © 2002 American Cancer Society.

DOI 10.1002/cncr.10361
Cerebrospinal fluid concentrations of vincristine after bolus intravenous dosing
Authors: Kellie Stewart J. , Barbaric Draga , Koopmans Pauline , Earl John , Carr Deborah J. , de Graaf Siebold S. N.
Published: August 2002

BACKGROUND

Vincristine (VCR) is used widely in oncology practice, and regular dosing is commonly associated with the development of sensorimotor or autonomic neuropathies. However, the incidence of VCR‐related central nervous system (CNS) toxicity is comparatively low, suggesting that the blood‐brain barrier may limit drug penetration into the brain parenchyma. This study determined whether measurable concentrations of VCR could be detected in the cerebrospinal fluid (CSF), as a surrogate marker of brain parenchyma penetration, after bolus intravenous injection in children without primary CNS pathology.

METHODS

The authors studied 17 pediatric patients ages 2.5–14.1 years (median, 6.8 years) with acute lymphoblastic leukemia or non‐Hodgkin lymphoma without evidence of leptomeningeal disease. Patients received VCR 1.5 mg/m2 by intravenous bolus injection followed at varying intervals by lumbar puncture for scheduled intrathecal methotrexate administration under general anesthesia. Paired VCR concentrations in both plasma and CSF were measured in each patient simultaneously at times ranging from 8 minutes to 146 minutes after the VCR injection. Three patients were studied twice. The paired samples were stored at −40 °C until analysis using a high performance liquid chromatography assay with a sensitivity of 0.1 μg/L in CSF and 0.4 μg/L in plasma.

RESULTS

Plasma VCR concentrations ranged from 2.2 μg/L to 91.2 μg/L. No measurable VCR concentrations were detected in the CSF samples.

CONCLUSIONS

Measurable concentrations of VCR in CSF are not achieved after the administration of standard intravenous bolus doses of VCR. The current observations are consistent with the relative rarity of VCR‐related CNS neurotoxicity compared with the commonly observed sensorimotor and autonomic neuropathies. These findings suggest that the penetration of VCR into the brain parenchyma of patients with a relatively intact blood‐brain barrier is low and that VCR may have a limited role in the CNS‐directed therapy of these patients. Cancer 2002;94:1815–20. © 2002 American Cancer Society.

DOI 10.1002/cncr.10397
Malignant placental site trophoblastic tumor
Authors: Xue Wei‐Cheng , Guan Xin‐Yuan , Ngan Hextan Y. S. , Shen Dan‐Hua , Khoo Ui‐Soon , Cheung Annie N. Y.
Published: August 2002

BACKGROUND

Placental site trophoblastic tumor (PSTT) is a rare form of gestational trophoblastic neoplasm composed predominantly of intermediate trophoblast. Most showed benign behavior whereas 10–15% of PSTTs were clinically malignant with later recurrence and metastasis. Currently, there are no reliable means to predict clinical outcome, and cytogenetic information is scanty.

METHODS

The clinicopathologic features of two cases of malignant PSTT were analyzed. Cytogenetic analysis was performed by comparative genomic hybridization (CGH) and chromosome in situ hybridization (CISH) using frozen tissue and paraffin embedded sections, respectively.

RESULTS

Both patients were 32 years old at time of diagnosis. One patient with PSTT presented with menorrhagia, and the other presented with symptoms of missed abortion. Elevated serum human chorionic gonadotropin (HCG) was detected in both patients. Histologic examination showed the typical features of PSTT with high mitotic count (> 5/10 high‐power fields). Ovarian and lung metastasis occurred in both patients. Immunohistochemical staining revealed an equal distribution of HCG and human placental lactogen. Cytogenetic studies by CISH showed that karyotypes of these two malignant PSTTs were diploid. Analysis of the tumor tissue by CGH did not show any changes in DNA copy numbers.

CONCLUSIONS

The authors' study indicated that the two metastasizing PSTTs had balanced diploid karyotype. The malignant behavior of PSTTs may be not related to the DNA copy number changes. Such cytogenetic study may be useful in distinguishing metastatic PSTT from choriocarcinoma. Cancer 2002;94:2288–94. © 2002 American Cancer Society.

DOI 10.1002/cncr.10424
HER‐2/neu is overexpressed infrequently in patients with prostate carcinoma
Authors: Lara Primo N. , Meyers Frederick J. , Gray Carl R. , Gandour Edwards Regina , Gumerlock Paul H. , Kauderer Caren , Tichauer Garrett , Twardowski Przemyslaw , Doroshow James H. , Gandara David R.
Published: August 2002

BACKGROUND

The overexpression of HER‐2/neu is found in 20–30% of patients with breast carcinoma and is an adverse prognostic factor. HER‐2 overexpression also has been reported in up to 60% of patients with hormone‐refractory prostate carcinoma (HRPC) and was correlated with shortened survival. Trastuzumab (Herceptin®) is a humanized monoclonal antibody that binds to the HER‐2 receptor and has antitumor activity in patients with HER‐2‐overexpressing breast carcinoma. The authors report the results of HER‐2 screening from a Phase II trial of chemotherapy with trastuzumab and docetaxel in patients with HER‐2‐overexpressing prostate carcinoma.

METHODS

Archival paraffin embedded tumor tissue was obtained from potentially eligible patients and was screened for HER‐2 expression by immunohistochemistry (IHC) using a specialized test kit. Shed HER‐2 antigen in serum also was determined using an enzyme‐linked immunosorbent assay (ELISA). HER‐2 gene amplification was assessed by fluorescent in situ hybridization (FISH). Patients with IHC scores of 2+ or 3+ were considered to have HER‐2 overexpression and were eligible for the trial. To date, 62 patients with HRPC have been screened.

RESULTS

The median patient age was 72 years, and Gleason scores were < 5 in 1 patient, 5–7 in 24 patients, > 7 in 23 patients, and not specified in 14 patients. IHC HER‐2 expression was 0 in 28 patients, 1+ in 14 patients, 2+ in 4 patients, and 3+ in 1 patient. Fifteen patients had either suboptimal tissue (13 patients) for interpretation or had pending results (2 patients). Therefore, 8% of all patients screened (5 of 62 patients) had HER‐2 overexpression by IHC. Quantitative ELISA for shed HER‐2 was available in 32 patients; this level was elevated (> 15 ng/mL) in only 2 patients, and neither had HER‐2 expression by IHC. Of the 5 patients with 2+ or 3+ HER‐2 expression by IHC, none had elevated shed HER‐2 antigen levels by ELISA. FISH for HER‐2 amplification was performed on 12 specimens; 5 of these specimens were uninterpretable due to specimen artifact, and none of the remaining 7 specimens had HER‐2 amplification, defined as a ratio > 1. Patient age and Gleason score were not correlated with HER‐2 status.

CONCLUSIONS

Unlike breast carcinoma and contrary to prior reports, HER‐2 overexpression by IHC in archival prostate tissue from patients who eventually developed hormone‐ refractory disease was infrequent. There did not appear to be any correlation between HER‐2 overexpression by IHC and shed HER‐2 antigen levels in serum by ELISA in this tumor type. Whether trastuzumab possesses single‐agent activity or modulates chemotherapy response in tumor types other than breast carcinoma remains to be determined. Cancer 2002;94:2584–9. © 2002 American Cancer Society.

DOI 10.1002/cncr.10526
How many nodes must be examined to accurately stage gastric carcinomas?
Authors: Bouvier Anne‐Marie , Haas Olivier , Piard Françoise , Roignot Philippe , Bonithon‐Kopp Claire , Faivre Jean
Published: August 2002

BACKGROUND

There are few population based data about lymphadenectomy practices in resections for stomach carcinoma. The aim of the current study was to describe these practices and to determine how many nodes must be examined in order to accurately stage gastric carcinoma.

METHODS

The current study included all patients (749 patients total) with TNM Stage I, II, or III resected gastric carcinoma diagnosed over a 21 year period (1976–1996) in a well‐defined French population. A model of the relationship between the proportion of positive nodes and the number of examined nodes was performed. The relationship between the proportion of positive nodes and the number of nodes examined was modeled to determine the number of nodes beyond which the proportion of N+ tumors no longer changed.

RESULTS

The average number of examined lymph nodes was 8.4 per patient. More than 15 lymph nodes were examined in 17.6% of patients. Under 10 examined nodes, the proportion of N+ classified tumors significantly decreased with the number of examined nodes, whereas it remained stable beyond this value. The type of gastrectomy and patient age were the two factors independently associated with the resection of at least 10 nodes, whereas the diagnosis period was not associated. After adjustment for the type of surgical resection, three variables independently influenced the prognosis of TNM Stage I or II tumors: extension within the gastric wall (extension T3/T4 vs. T1/T2; odds ratio [OR] = 2.05, P < 0.001), age at diagnosis (age ≥ 70 years vs. < 70 years; OR = 4.06, P < 0.001), and the number of examined nodes (10 resected lymph nodes vs. 0–9; OR = 0.57, P < 0.001).

CONCLUSIONS

The current study strongly suggests that staging is not reliable when fewer than 10 lymph nodes are examined. The number of examined lymph nodes should be used as a stratification criterion in clinical trials and as an adjustment variable in survival studies. Cancer 2002;94:2862–6. © 2002 American Cancer Society.

DOI 10.1002/cncr.10550
African‐American ethnicity, socioeconomic status, and breast cancer survival
Authors: Newman Lisa A. , Mason James , Cote David , Vin Yael , Carolin Kathryn , Bouwman David , Colditz Graham A.
Published: August 2002

BACKGROUND

African‐American women are at increased risk for breast cancer mortality compared with white American women, and the extent to which socioeconomic factors account for this outcome disparity is unclear.

METHODS

A MEDLINE search was conducted to identify published studies that used a Cox proportional hazards regression model to evaluate the outcome of African‐American women and white American women with breast carcinoma after adjusting for socioeconomic status. A meta–analysis was performed using specialized statistical software; the random‐effects method of statistical evaluation was used because of the a priori impression that the studies reviewed would be at least moderately heterogeneous in study design and patient populations.

RESULTS

The initial literature search yielded 3962 studies. Fourteen studies met all criteria for inclusion in the meta–analysis, resulting in a sample size of 10,001 African‐American patients and 42,473 white American patients with breast carcinoma. There was substantial variation in the method used for defining socioeconomic status. Summary statistics revealed a significant odds ratio of 1.22 (95% confidence interval, 1.13–1.30) for the adverse effect of African‐American ethnicity on breast cancer mortality. Subset meta–analyses yielded similar results, supporting the robustness of this finding.

CONCLUSIONS

This meta–analysis revealed that African‐American ethnicity is an independent predictor of a worse breast cancer outcome. The pooled analysis has added strength because of the aggregate sample size and indicates that the true biologic and/or therapeutic determinants of disparities in breast cancer outcome for different ethnic groups and for different socioeconomic strata are incompletely understood. Cancer 2002;94:2844–54. © 2002 American Cancer Society.

DOI 10.1002/cncr.10575
Pale cytochrome oxidase stripes in V2 receive the richest projection from macaque striate cortex
Authors: Sincich Lawrence C. , Horton Jonathan C.
Published: August 2002

Once the visual pathway reaches striate cortex, it fans out to a number of extrastriate areas. The projections to the second visual area (V2) are known to terminate in a patchy manner. V2 contains a system of repeating pale‐thin‐pale‐ thick stripes of cytochrome oxidase (CO) activity. We examined whether the patchy terminal fields arising from primary visual cortex (V1) projections are systematically related to the CO stripes in V2. Large injections of an anterograde tracer, [3H]proline, were made into V1 of both hemispheres in 5 macaques. The resulting V2 label appeared in layers 2–6, with the densest concentration in layer 4. In 21/29 injections, comparison of adjacent flatmount sections processed either for autoradiography or CO activity showed that the heaviest [3H]proline labeling was located in pale CO stripes. In 7/29 injections, there was no clear enrichment of labeling in the CO pale stripes. In 1 injection, the proline label correlated with dark CO stripes. On a fine scale, CO levels vary within V2 stripes, giving them an irregular, mottled appearance. In all stripe types, the density of proline label would often wax and wane in opposing contrast to these local fluctuations in CO density. Our data showed that V1 input is generally anti‐correlated with the intensity of CO staining in V2, with strongest input to pale stripes. It is known that the pulvinar projects preferentially to dark stripes. Therefore, V2 receives interleaved projections from V1 and the pulvinar. Because these projections favor different stripe types, they may target separate populations of neurons. J. Comp. Neurol. 447:18–33, 2002. © 2002 Wiley‐Liss, Inc.
Larval electroreceptors in the epidermis of mormyrid fish: I. Tuberous organs of type A and B
Authors: Bensouilah Mourad , Schugardt Christian , Roesler Ritva , Kirschbaum Frank , Denizot Jean‐Pierre
Published: August 2002

Two types of larval electroreceptors, type A and B, are described in the epidermis of the head of larvae of three mormyrid species, Campylomormyrus cassaicus, Mormyrus rume proboscirostris and Pollimyrus isidori, bred in captivity. In each of these electroreceptor organs, a single sensory cell is found inside an intraepidermal cavity, sitting on a platform of accessory cells. The cavity is filled with microvilli originating both from the sensory cell and from the epidermal covering cells lining the intraepidermal cavity. These two types of tuberous larval electroreceptors differ in their distribution in the epidermis of the head, in the composition of their accessory cells, and by their innervation. The innervation found in type B organs is similar to that already described for electroreceptors of adult mormyrids. The sensorineural junction is composed of primary afferent terminal boutons, which contact the base of the sensory cell. Opposite each terminal bouton, a ribbon‐like synaptic bar surrounded by vesicles is found in the cytoplasm of the sensory cell. In contrast, the base of the sensory cell in type A larval electroreceptors is not contacted by nervous terminal boutons, but instead forms closed appositions with specialized prolongations of accessory cells of the platform. The base of the sensory cell presents membrane evaginations, with hemispheric synaptic structures and few synaptic vesicles. These two types of electroreceptor organs degenerate at the time of the degeneration of the larval electric organ and the functional differentiation of the adult electric organ. The functional role of two tuberous electroreceptor types is examined. J. Comp. Neurol. 447:309–322, 2002. © 2002 Wiley‐Liss, Inc.
Distribution of the zinc transporter ZnT‐1 in comparison with chelatable zinc in the mouse brain
Authors: Sekler Israel , Moran Arie , Hershfinkel Michal , Dori Amir , Margulis Ariel , Birenzweig Nurit , Nitzan Yuval , Silverman William F.
Published: August 2002

Zinc maintains a diverse array of functions in the mammalian central nervous system as a key component of numerous enzymes, via its role in the activation of transcription factors, and as a neuroregulator, modulating neuronal receptors such as N‐methyl‐D‐aspartate and γ‐aminobutyric acid. Zinc has a dark side, however, with massive influx of Zn2+ to neurons considered to be a key factor in neuronal death secondary to ischemia and seizure. Several different putative zinc transporters, ZnT‐1–4, have recently been identified and characterized. Among them, ZnT‐1 has been suggested to play a key role in reducing cellular Zn2+ toxicity. In the present study, we describe the regional and cellular distribution of ZnT‐1 in the adult mouse brain using an antibody raised against the C‐terminal domain of mouse ZnT‐1. The distribution of ZnT‐1 was compared to that of chelatable Zn2+, visualized by means of neoTimm histochemistry or N‐(6‐methoxy‐8‐quinolyl)‐p‐toluene‐sulfonamide (TSQ) histofluorescence. Extracts from various brain regions specifically stained a 60‐kDa peptide corresponding to the expected molecular weight of ZnT‐1. The expression of ZnT‐1 was highest in the cerebral cortex and cerebellum, moderate in the hippocampus, hypothalamus, and olfactory bulb, and lowest in the striatum and septum. In brain sections, ZnT‐1‐immunoreactive neurons, in particular principle neurons, in the somatosensory cortex, hippocampus, and olfactory bulb, were closely related to synaptic Zn2+. Robust ZnT‐1 immunoreactivity was also observed in cerebellar Purkinje cells. Although the function of the protein in these cells is unclear, in the forebrain, ZnT‐1 is strikingly present in cells and regions where significant Zn2+ homeostasis is required. This finding suggests a protective role for neuronal ZnT‐1 in the context of both normal and pathophysiological activity. J. Comp. Neurol. 447:201–209, 2002. © 2002 Wiley‐Liss, Inc.
Distribution and morphology of nigral axons projecting to the thalamus in primates
Authors: François Chantal , Tande Dominique , Yelnik Jerome , Hirsch Etienne C.
Published: August 2002

This study presents an analysis of the distribution and organization pattern of axons originating from the substantia nigra pars reticulata and projecting to the thalamus in monkeys. Biotin dextran amine was iontophoretically injected into different parts of the substantia nigra pars reticulata of monkeys (African green monkeys and macaques). In whatever part of the substantia nigra the injection was made, numerous axonal endings were found to be distributed within different thalamic regions: the ventral anterior nucleus and mainly its magnocellular part, the most ventromedial part of the ventral lateral nucleus, and the mediodorsal and parafascicular nuclei. Moreover, the nigrothalamic projection appeared to be topographically organized. Ten anterogradely labeled axons were reconstructed from serial sections. The axons terminated in three to six terminal fields per axon located in a relatively small portion of only one thalamic region. These terminal fields were variable in size and comprised 4–43 very thin, varicose branches. They consisted either of different axonal branches of the same axon or of different axons and covered 10–31 thalamic cell bodies. These findings demonstrate that the overall morphological organization of individual nigral axons is complex and allows single axons to influence thalamic neurons via a combination of divergent, convergent, and amplification processes. J. Comp. Neurol. 447:249–260, 2002. © 2002 Wiley‐Liss, Inc.
Nr‐CAM expression in the developing mouse nervous system: Ventral midline structures, specific fiber tracts, and neuropilar regions
Authors: Lustig Marc , Erskine Lynda , Mason Carol A. , Grumet Martin , Sakurai Takeshi
Published: August 2002

Nr‐CAM is a member of the L1 subfamily of cell adhesion molecules (CAMs) that belong to the immunoglobulin superfamily. To explore the role of Nr‐CAM in the developing nervous system, we prepared specific antibodies against both chick and mouse Nr‐CAM using recombinant Fc fusion proteins of chick Nr‐CAM and mouse Nr‐CAM, respectively. First, we show the specificity of the new anti‐chick Nr‐CAM antibody compared with a previously employed antibody using the expression patterns of Nr‐CAM in the chick spinal cord and floor plate and on commissural axons, where Nr‐CAM has been implicated in axon guidance. Using the anti‐mouse Nr‐CAM antibody, we then studied the expression patterns of Nr‐CAM in the developing mouse nervous system along with the patterns of two related CAMs, L1, which labels most growing axons, and TAG‐1, which binds to Nr‐CAM and has a more restricted distribution. Major sites that are positive for Nr‐CAM are specialized glial formations in the ventral midline, including the floor plate in the spinal cord, the hindbrain and midbrain, the optic chiasm, and the median eminence in the forebrain. Similar to what is seen in the chick spinal cord, Nr‐CAM is expressed on crossing fibers as they course through these areas. In addition, Nr‐CAM is found in crossing fiber pathways, including the anterior commissure, corpus callosum, and posterior commissure, and in nondecussating pathways, such as the lateral olfactory tract and the habenulointerpeduncular tract. Nr‐CAM, for the most part, is colocalized with TAG‐1 in all of these systems. Based on in vitro studies indicating that the Nr‐CAM‐axonin‐1/TAG‐1 interaction is involved in peripheral axonal growth and guidance in the spinal cord [Lustig et al. (1999) Dev Biol 209:340–351; Fitzli et al. (2000) J Cell Biol 149:951–968], the expression patterns described herein implicate a role for this interaction in central nervous system axon growth and guidance, especially at points of decussation. Nr‐CAM also is expressed in cortical regions, such as the olfactory bulb. In the hippocampus, however, TAG‐1‐positive areas are segregated from Nr‐CAM‐positive areas, suggesting that, in neuropilar regions, Nr‐CAM interacts with molecules other than TAG‐1. J. Comp. Neurol. 434:13–28, 2001. © 2001 Wiley‐Liss, Inc.