bluuebunny/crossref_metadata_2025 huggingface dataset:
PDDG/PM3 and PDDG/MNDO: Improved semiempirical methods
Authors: Repasky Matthew P. , Chandrasekhar Jayaraman , Jorgensen William L.
Published: December 2002

Two new semiempirical methods employing a Pairwise Distance Directed Gaussian modification have been developed: PDDG/PM3 and PDDG/MNDO; they are easily implemented in existing software, and yield heats of formation for compounds containing C, H, N, and O atoms with significantly improved accuracy over the standard NDDO schemes, PM5, PM3, AM1, and MNDO. The PDDG/PM3 results for heats of formation also show substantial improvement over density functional theory with large basis sets. The PDDG modifications consist of a single function, which is added to the existing pairwise core repulsion functions within PM3 and MNDO, a reparameterized semiempirical parameter set, and modified computation of the energy of formation of a gaseous atom. The PDDG addition introduces functional group information via pairwise atomic interactions using only atom‐based parameters. For 622 diverse molecules containing C, H, N, and O atoms, mean absolute errors in calculated heats of formation are reduced from 4.4 to 3.2 kcal/mol and from 8.4 to 5.2 kcal/mol using the PDDG modified versions of PM3 and MNDO over the standard versions, respectively. Several specific problems are overcome, including the relative stability of hydrocarbon isomers, and energetics of small rings and molecules containing multiple heteroatoms. The internal consistency of PDDG energies is also significantly improved, enabling more reliable analysis of isomerization energies and trends across series of molecules; PDDG isomerization energies show significant improvement over B3LYP/6‐31G* results. Comparison of heats of formation, ionization potentials, dipole moments, isomer, and conformer energetics, intermolecular interaction energies, activation energies, and molecular geometries from the PDDG techniques is made to experimental data and values from other semiempirical and ab initio methods. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 1601–1622, 2002
Prediction of β‐sheet topology and disulfide bridges in polypeptides
Authors: Klepeis J. L. , Floudas C. A.
Published: December 2002

An ab initio method has been developed to predict β architectures in polypeptides. The approach predicts the topology of β‐sheets and disulfide bridges through a novel superstructure‐based mathematical framework originally established for chemical process synthesis problems. Two types of superstructure are introduced, both of which emanate from the principle that hydrophobic interactions drive the formation of a β‐structure. The mathematical formulation of the problem results in a set of integer linear programming (ILP) problems that can be solved to global optimality to identify the optimal β‐configuration. These (ILP) models can also predict a ranked ordered list of the best, second‐best, third‐best, etc., topologies of β‐sheets and disulfide bridges. The approach is shown to perform very well for several benchmark polypeptide systems, as well as polypeptides exhibiting challenging nonsequential β‐sheet topologies folds (56 to 187 amino acids). © 2002 Wiley Periodicals, Inc. J Comput Chem 24: 191–208, 2003
Molecules for materials: Germanium hydride neutrals and anions. Molecular structures, electron affinities, and thermochemistry of GeHn/GeH (n = 0–4) and Ge2Hn/Ge2H (n = 0–6)
Authors: Li Qian‐Shu , Lü Rui‐Hua , Xie Yaoming , Schaefer Henry F.
Published: December 2002

The GeHn (n = 0–4) and Ge2Hn (n = 0–6) systems have been studied systematically by five different density functional methods. The basis sets employed are of double‐ζ plus polarization quality with additional s‐ and p‐type diffuse functions, labeled DZP++. For each compound plausible energetically low‐lying structures were optimized. The methods used have been calibrated against a comprehensive tabulation of experimental electron affinities (Chemical Reviews 102, 231, 2002). The geometries predicted in this work include yet unknown anionic species, such as Ge2H−, Ge2H, Ge2H, Ge2H, and Ge2H. In general, the BHLYP method predicts the geometries closest to the few available experimental structures. A number of structures rather different from the analogous well‐characterized hydrocarbon radicals and anions are predicted. For example, a vinylidene‐like GeGeH structure is the global minimum of Ge2H. For neutral Ge2H4, a methylcarbene‐like HGë‐GeH3 is neally degenerate with the trans‐bent H2GeGeH2 structure. For the Ge2H anion, the methylcarbene‐like system is the global minimum. The three different neutral‐anion energy differences reported in this research are: the adiabatic electron affinity (EAad), the vertical electron affinity (EAvert), and the vertical detachment energy (VDE). For this family of molecules the B3LYP method appears to predict the most reliable electron affinities. The adiabatic electron affinities after the ZPVE correction are predicted to be 2.02 (Ge2), 2.05 (Ge2H), 1.25 (Ge2H2), 2.09 (Ge2H3), 1.71 (Ge2H4), 2.17 (Ge2H5), and −0.02 (Ge2H6) eV. We also reported the dissociation energies for the GeHn (n = 1–4) and Ge2Hn (n = 1–6) systems, as well as those for their anionic counterparts. Our theoretical predictions provide strong motivation for the further experimental study of these important germanium hydrides. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 1642–1655, 2002
Placenta: Regularization of neovascularization. Microvascularization pattern of the rabbit term placenta
Authors: Del Mar Yllera Maria , Alexandre‐Pires Graça Maria , Cifuentes Jose Manuel
Published: December 2002

Mammalian blastocyst produces membranes that gradually attach in the endometrial epithelium and establish a close relationship between fetal and maternal circulatory systems for physiologic exchange. This fact results in the formation of a combined organ, the placenta. Placentation includes extensive neovascularization in maternal and embryonic placental tissues. Recent studies, particularly of genetically altered mice, have greatly improved our understanding of the molecular basis of the development of the vascular system. Numerous factors have been implicated in the regulation of the neovascularization process of the placenta. The aim of this article is to highlight briefly the pattern circulation of the rabbit term placenta as an example of the microvascularization of hemochorial placenta typical of humans and to summarize the main factors responsible for modulating the growth of decidual placental vessels and the vasculogenesis of the basal plate. Microsc. Res. Tech. 60:38–45, 2003. © 2002 Wiley‐Liss, Inc.
The Poisson–Boltzmann equation for biomolecular electrostatics: a tool for structural biology
Authors: Fogolari F. , Brigo A. , Molinari H.
Published: December 2002

Electrostatics plays a fundamental role in virtually all processes involving biomolecules in solution. The Poisson–Boltzmann equation constitutes one of the most fundamental approaches to treat electrostatic effects in solution. The theoretical basis of the Poisson–Boltzmann equation is reviewed and a wide range of applications is presented, including the computation of the electrostatic potential at the solvent‐accessible molecular surface, the computation of encounter rates between molecules in solution, the computation of the free energy of association and its salt dependence, the study of pKa shifts and the combination with classical molecular mechanics and dynamics. Theoretical results may be used for rationalizing or predicting experimental results, or for suggesting working hypotheses. An ever‐increasing body of successful applications proves that the Poisson–Boltzmann equation is a useful tool for structural biology and complementary to other established experimental and theoretical methodologies. Copyright © 2002 John Wiley & Sons, Ltd.
Essential motions in a fungal lipase with bound substrate, covalently attached inhibitor and product
Authors: Peters Günther H. , Bywater Robert P.
Published: December 2002

As an aid to understanding the influence of dynamic fluctuations during esterolytic catalysis, we follow protein flexibility at three different steps along the catalytic pathway from substrate binding to product clearance via a covalently attached inhibitor, which represents a transition‐state mimic. We have applied a classical approach, using molecular dynamics simulations to monitor protein dynamics in the nanosecond regime. We filter out small amplitude fluctuations and focus on the anharmonic contributions to the overall dynamics. This ‘essential dynamics’ analysis reveals different modes of response along the pathway suggesting that binding, catalysis and product clearance occur along different energy surfaces. Motions in the enzyme with a covalently attached ligand are more complex and occur along several eigenvectors. The magnitudes of the fluctuations in these individual subspaces are significantly smaller than those observed for the substrate and product molecules, indicating that the energy surface is shallow and that a relatively large number of conformational substates are accessible. On the other hand, substrate binding and product release occur at distinct modes of the protein flexibility suggesting that these processes occur along rough energy surfaces with only a few minima. Detailed energetic analyses along the trajectories indicated that in all cases binding is dominated by van der Waals interactions. The carboxylate form of the product is stabilized by a tight hydrogen bond network involving in particular Ser82, which may be a potential cause of product inhibition. Considerations such as these should aid the understanding of mechanisms of substrate, inhibitor or product recognition and could become of importance in the design of new substrates or inhibitors for enzymes. Copyright © 2002 John Wiley & Sons, Ltd.
Protein–protein interactions: mechanisms and modification by drugs
Authors: Veselovsky A. V. , Ivanov Yu. D. , Ivanov A. S. , Archakov A. I. , Lewi P. , Janssen P.
Published: December 2002

Protein–protein interactions form the proteinaceous network, which plays a central role in numerous processes in the cell. This review highlights the main structures, properties of contact surfaces, and forces involved in protein–protein interactions. The properties of protein contact surfaces depend on their functions. The characteristics of contact surfaces of short‐lived protein complexes share some similarities with the active sites of enzymes. The contact surfaces of permanent complexes resemble domain contacts or the protein core. It is reasonable to consider protein–protein complex formation as a continuation of protein folding. The contact surfaces of the protein complexes have unique structure and properties, so they represent prospective targets for a new generation of drugs. During the last decade, numerous investigations have been undertaken to find or design small molecules that block protein dimerization or protein(peptide)–receptor interaction, or on the other hand, induce protein dimerization. Copyright © 2002 John Wiley & Sons, Ltd.
Survey of the year 2001 commercial optical biosensor literature
Authors: Rich Rebecca L. , Myszka David G.
Published: December 2002

We have assembled references of 700 articles published in 2001 that describe work performed using commercially available optical biosensors. To illustrate the technology's diversity, the citation list is divided into reviews, methods and specific applications, as well as instrument type. We noted marked improvements in the utilization of biosensors and the presentation of kinetic data over previous years. These advances reflect a maturing of the technology, which has become a standard method for characterizing biomolecular interactions. Copyright © 2002 John Wiley & Sons, Ltd.
Brownian dynamics of interactions between aldolase mutants and F‐actin
Authors: Lowe Stephen L. , Atkinson Derek M. , Waingeh Victor F. , Thomasson Kathryn A.
Published: December 2002

Previous Brownian dynamics (BD) simulations (Ouporov IG, Knull HR and Thomasson KA 1999. Biophys. J. 76: 17–27) of complex formation between rabbit aldolase and F‐actin have identified three lysine residues (K288, K293 and K341) on aldolase and acidic residues (DEDE) at the N‐terminus of actin as important to binding. BD simulations of computer models of aldolase mutants with any of these lysine residues replaced by alanine show reduced binding energy; the greatest effect of a single substitution is for K341A, and replacement of all three lysines greatly reduces binding. BD simulations of wild‐type rabbit aldolase vs altered F‐actin show that binding is decreased if any one of the four N‐terminal acidic residues is replaced by alanine and binding is greatly reduced if three or more of the N‐terminal acidic residues are replaced; none of the four actin residues appear more critical for binding than the others. Copyright © 2002 John Wiley & Sons, Ltd.
Wavelet statistics of functional MRI data and the general linear model
Authors: Müller Karsten , Lohmann Gabriele , Zysset Stefan , von Cramon D. Yves
Published: December 2002

Purpose

To improve the signal‐to‐noise ratio (SNR) of functional magnetic resonance imaging (fMRI) data, an approach is developed that combines wavelet‐based methods with the general linear model.

Materials and Methods

Ruttimann et al. (1) developed a wavelet‐based statistical procedure to test wavelet‐space partitions for significant wavelet coefficients. Their method is applicable for the detection of differences between images acquired under two experimental conditions using long blocks of stimulation. However, many neuropsychological questions require more complicated event‐related paradigms and more experimental conditions. Therefore, in order to apply wavelet‐based methods to a wide range of experiments, we present a new approach that is based on the general linear model and wavelet thresholding.

Results

In contrast to a monoresolution filter, the application of the wavelet method increased the SNR and showed a set of clearly dissociable activations. Furthermore, no relevant decrease of the local maxima was observed.

Conclusion

Wavelet‐based methods can increase the SNR without diminishing the signal amplitude, while preserving the spatial resolution of the image. The anatomical localization is strongly improved. J. Magn. Reson. Imaging 2003;17:20–30. © 2002 Wiley‐Liss, Inc.
MR tagging of human lungs using hyperpolarized 3He gas
Authors: Owers‐Bradley John R. , Fichele Mr Stanislao , Bennattayalah Abdelmalek , Smith McGloin Colin J. , Bowtell Richard W. , Morgan Paul S. , Moody Alan R.
Published: December 2002

Purpose

To evaluate the use of spin‐tagging in conjunction with hyperpolarized gas imaging for monitoring lung ventilation and gas diffusion.

Methods and Materials

Images were taken at 0.15 T using single shot RARE, with hyperpolarized 3He gas prepared by the metastability exchange technique. Sinusoidal modulation of the longitudinal magnetization (tag) was produced by two 90‐degree rf pulses separated by a gradient pulse. The diffusion of 3He gas in the lungs was measured by monitoring the decay of the tags. This study was conducted on a 25‐year‐old, male, healthy volunteer.

Results

Clear tags in hyperpolarized 3He gas both in vivo and in vitro were generated. The relative movement of the lung compared to a static, partial breath‐hold was measured following inspiration or expiration. The diffusion coefficient of 3He in the lungs was found to be 0.02 ± 0.005 cm2seconds‐1.

Conclusion

The spin‐tagging of hyperpolarized 3He in the lungs is possible, and allows regional lung movements to be measured following inspiration and expiration. It also allows quantification of the diffusion of the 3He gas. J. Magn. Reson. Imaging 2003;17:142–146. © 2002 Wiley‐Liss, Inc.
Clinical blood flow quantification with segmented k‐space magnetic resonance phase velocity mapping
Authors: Chatzimavroudis George P. , Zhang Haosen , Halliburton Sandra S. , Moore James R. , Simonetti Orlando P. , Schvartzman Paulo R. , Stillman Arthur E. , White Richard D.
Published: December 2002

Purpose

To evaluate the accuracy of segmented k‐space magnetic resonance phase velocity mapping (PVM) in quantifying aortic blood flow from through‐plane velocity measurements.

Materials and Methods

Two segmented PVM schemes were evaluated, one with seven lines per segment (seg‐7) and one with nine lines per segment (seg‐9), in twenty patients with cardiovascular disease. A non‐segmented (non‐seg) PVM acquisition was also performed to provide the reference data.

Results

There was agreement between the aortic flow curves acquired with segmented and non‐segmented PVM. The calculated systolic and total flow volume per cycle from the seg‐7 and the seg‐9 scans correlated and agreed with the flow volumes from the non‐seg scans (differences < 5%). Sign tests showed that there were no statistically significant differences (P‐values < 0.05) between the segmented and the non‐segmented PVM measurements. Seg‐9, which was the fastest among the three sequences, provided adequate spatial and temporal resolution (> 10 phases per cycle).

Conclusion

Segmented k‐space PVM shows great clinical potential in blood flow quantification. J. Magn. Reson. Imaging 2003;17:65–71. © 2002 Wiley‐Liss, Inc.
Assessment of aorto‐iliac disease with magnetic resonance angiography using arterial phase 3‐d gradient‐echo and interstitial phase 2‐d fat‐suppressed spoiled gradient‐echo sequences
Authors: Venkataraman Shambhavi , Semelka Richard C. , Weeks Susan , Braga Larissa , Vaidean Georgeta
Published: December 2002

Purpose

To evaluate magnetic resonance angiography (MRA) of the pelvis for the examination of the aorto‐iliac system using arterial phase 3‐D gradient echo and interstitial phase 2‐D fat‐suppressed spoiled gradient‐echo (SGE), with comparison to surgery and angiography.

Materials and Methods

Ninety MR angiograms performed on 79 consecutive patients were analyzed, retrospectively, for the presence of narrowing, aneurysm, and dissection. Comparisons were made with angiography and surgery in 50 examinations, and a weighted kappa statistic test was applied to assess agreement. MR examinations were performed at 1.5T 3‐D fast imaging in steady state precession (FISP) acquired immediately, and fat‐suppressed SGE in the interstitial phase following gadolinium administration.

Results

MRA had overall sensitivities of 100% at aortic segments, 100% at common iliac, 93.8% at external, and 95.7% at internal iliac, and specificities of 100% at aortic segments, 89.7% at common iliac, 95.2% at external iliac, and 88.7% at internal iliac in detection of vascular disease. The agreement of MRA with the angiography and surgery yielded a weighted kappa statistic of 0.97 at the aortic, 0.94 at the common, 0.85 at the external, and 0.82 at the internal iliac segments.

Conclusion

This study demonstrates an excellent performance of MRA in the evaluation of aorto‐iliac arterial system and almost perfect agreement with angiography and surgery at all vascular levels. J. Magn. Reson. Imaging 2003;17:43–53. © 2002 Wiley‐Liss, Inc.
Regional chemotherapy is indicated after surgical resection of colorectal metastases to the liver: A debate
Authors: Khushalani Nikhil I. , McKinley Brian Patrick , Gibbs John F. , Leichman Cynthia Gail , Petrelli Nicholas J.
Published: December 2002

Surgical resection for selected patients with hepatic metastases from colorectal cancer can cure approximately one‐fourth of these patients. The addition of regional chemotherapy as an attempt to improve this statistic has been extensively investigated in clinical trials. As part of a multidisciplinary educational program, a series of debates on various topics in oncology are held at the Roswell Park Cancer Institute, Buffalo, New York, involving the medical, surgical, and radiation oncology departments. One such debate focused on the use of regional chemotherapy after potentially curative resection of hepatic metastases from colorectal cancer. The representative medical and surgical oncology fellows (N.I.K. and B.P.M.), with guidance from their respective mentors (C.G.L., J.F.G., and N.J.P.), presented concise reviews from the literature arguing for and against the use of regional chemotherapy in this setting. They appear as Parts 1 and 2 in this article. This exercise is purely educational and does not in any way reflect the opinion or the clinical practice of the authors. J. Surg. Oncol. 2003;82:65–72. © 2002 Wiley‐Liss, Inc.
Downregulation of putative tumor suppressor gene TSC‐22 in human brain tumors
Authors: Shostak Katherina O. , Dmitrenko Vladimir V. , Garifulin Oleg M. , Rozumenko Vladimir D. , Khomenko Olexiy V. , Zozulya Yuriy A. , Zehetner Günther , Kavsan Vadym M.
Published: December 2002

Background and Objectives

Our objective was to identify differentially expressed genes involved in the pathogenesis of glioblastoma multiforme (GBM).

Methods

Screening of arrayed human fetal brain and human postnatal brain cDNA libraries was performed by differential hybridization with glioblastoma multiforme and human normal brain cDNAs.

Results

Repeated differential hybridization of more than 100 cDNA clones selected by primary screening and analysis of RNA from adult normal brain and glial tumors showed 16 nucleotide sequences differentially expressed between normal brain and brain tumors. Among others, decreased content in astrocytic tumors was determined for TSC‐22 mRNA corresponding to cDNA in the ICRFp507J1041 clone from human fetal brain cDNA library. Northern blot hybridization of RNA from different human brain tumors showed very low amounts of TSC‐22 mRNA in most investigated samples of GBM, anaplastic astrocytoma, and some other tumors. Complete lack of expression of TSC‐22 occurred in one sample of anaplastic astrocytoma, as well as in meningioma, brain sarcoma, sarcomatous meningioma, and oligodendroglioma. The differential expression of TSC‐22 gene was confirmed by semiquantitative RT‐PCR in 15 samples of astrocytomas WHO grade II–IV and three samples of normal brain.

Conclusions

Significantly decreased levels of TSC‐22 mRNA in human brain and salivary gland tumors and antiproliferative role of TSC‐22 strongly suggest a tumor suppressor role for TSC‐22. J. Surg. Oncol. 2003;82:57–64. © 2002 Wiley‐Liss, Inc.
Prognostic significance of biomarkers in squamous cell carcinoma of the tongue: Multivariate analysis
Authors: Vora Hemangini H. , Shah Neelam G. , Patel Devendra D. , Trivedi Trupti I. , Chikhlikar Priya R.
Published: December 2002

Background and Objectives

Expression of a panel of biomarkers, such as p53, Bcl‐2, Cyclin D1, c‐myc, p21ras, c‐erb B2, cytokeratin‐19 (CK‐19), and factor VIII–related antigen (FVIII‐RA), was studied together in anterior tongue tumors from the oral cavity and in posterior tongue tumors from the oropharynx of patients with early‐ and locally advanced‐stage disease, to evaluate their prognostic value.

Methods

The expression of the above‐mentioned biomarkers was studied by immunohistochemical localization.

Results

In this study, 18%, 26%, 62%, 75%, 73%, 50%, and 29% of the tumors exhibited p53, Bcl‐2, Cyclin D1, c‐myc, p21ras, c‐erb B2, and CK‐19 expression, respectively. Twenty percent of the tumors had a microvessel count of >0.0. The expression of these biomarkers was also correlated with clinicopathologic parameters. In early‐stage patients with a tobacco habit, who showed borderline significance for relapse‐free survival by Kaplan‐Meier survival analysis, this turned out to be significant, with the general linear model univariate survival analysis. In the total group, disease stage emerged as the most significant prognostic factor, followed by c‐myc, when Cox forward stepwise regression and general linear model multivariate survival analysis were performed. However, Cyclin D1, which was significant by Cox forward stepwise regression analysis, lost its significance by general linear model multivariate analysis. In patients with early‐stage disease, MVC, which was a significant predictor of disease relapse by Cox forward stepwise regression analysis, lost its significance by general linear model analysis because of small number of patients. In patients with locally advanced tongue cancer, multivariate survival analysis of individual biomarkers by both Cox forward stepwise regression and general linear model analysis indicated c‐myc expression to be strongly indicative of poor prognosis. However, multivariate analysis of individual markers along with a combination of markers showed that only by Cox forward stepwise regression analysis did the combined expression of markers c‐myc, Cyclin D1, and p21ras emerge as a significant independent prognosticator.

Conclusions

Overall stage emerged as the most significant prognostic indicator of disease outcome. Tobacco habit also affected relapse‐free survival in patients with early‐stage disease. However, immunostaining of c‐myc in the tumors of locally advanced‐stage tongue cancer patients might be a potential adjunct to clinical stage in the pathologic evaluation of tongue specimens. J. Surg. Oncol. 2003;82:34–50. © 2002 Wiley‐Liss, Inc.
Prognostic significance of the size of cancer nests in metastatic lymph nodes in human esophageal cancers
Authors: Komori Takamichi , Doki Yuichiro , Kabuto Toshiyuki , Ishikawa Osamu , Hiratsuka Masahiro , Sasaki Yo , Ohigashi Hiroaki , Murata Kohei , Yamada Terumasa , Miyashiro Isao , Mano Masayuki , Ishiguro Shingo , Imaoka Shingi
Published: December 2002

Background

Postoperative survival of patients with esophageal cancers after curative surgery is strongly affected by the presence of lymph node metastasis. The number and location of lymph node metastases have been evaluated and graded, but the clinical significance of their size has not been well investigated.

Methods

Of 322 esophageal cancer patients who underwent curative operations with radical lymph node dissection, 170 (53%) had lymph node metastasis. A total of 784 metastatic lymph nodes were obtained, and the area of the cancer nests was measured microscopically in the cross section. The data from each patient included the area of the largest cancer nest in the positive nodes (Nmax), classified as Na (<4 mm2), Nb (4–25 mm2), Nc (25–100 mm2), or Nd (>100 mm2).

Results

The 170 patients were classified according to the Nmax value: Na, 31 (18.2%); Nb, 35 (20.5%); Nc, 49 (28.8%); and Nd, 55 (32.4%). The 5‐year survival rate was 77.7% in patients without lymph node metastasis and 35.4% in those with lymph node metastasis. When classified by Nmax, the 5‐year survival rate was 77.8% for Na, 63.9% for Nb, 18.8% for Nc, and 12.8% for Nd. There was no significant difference in the survival rate between Na patients and those without lymph node metastasis. Nmax showed significant correlation with the primary tumor size, depth of tumor invasion, and number and location of metastatic lymph nodes, but not with histologic type or primary tumor location. In multivariate analysis, the Nmax value, the number of lymph node metastases and depth of tumor invasion were independent prognostic factors, while the location of the lymph node metastases was not statistically significant.

Conclusions

The area of the largest cancer nest in the lymph nodes was one of the most significant prognostic factors for esophageal cancers. This estimation is objective and reproducible and may be of great importance when deciding the therapeutic modality for patients with esophageal cancers. J. Surg. Oncol. 2003;82:19–27. © 2002 Wiley‐Liss, Inc.
Anal sphincter preservation in locally advanced low rectal adenocarcinoma after preoperative chemoradiation therapy and coloanal anastomosis
Authors: Luna‐Pérez Pedro , Rodríguez‐Ramírez Saúl , Hernández‐Pacheco Freddi , Gutiérrez de la Barrera Marcos , Fernández Raúl , Labastida Sonia
Published: December 2002

Background and Objectives

Standard treatment of rectal adenocarcinoma located 3–6 cm above anal verge is abdominoperineal resection. The objective was to evaluate feasibility, morbidity, and functional results of anal sphincter preservation after preoperative chemoradiation therapy and coloanal anastomosis in patients with rectal adenocarcinoma located between 3 and 6 cm above the anal verge.

Methods

This study included 17 males and 15 females with a mean age of 54.8 ± 15.4 years. Tumors were located at a mean of 4.7 ± 1.1 cm above the anal verge. The mean tumor size was 4.6 ± 1.5 cm. All patients received the scheduled treatment. Twenty‐two patients underwent coloanal anastomosis with the J pouch; 10 underwent straight anastomosis. Average surgical time was 328.7 ± 43.8 min, and the average intraoperative hemorrhage was 471.5 ± 363.6 ml. The mean distal surgical margin was 1.3 ± 0.6 cm. Five patients (15.6%) received a blood transfusion.

Results

Major complications included coloanal anastomotic leakage (three); pelvic abscess (three), and coloanal stenosis (two). Tumor stages were as follows: T0–2,N0,M0 = 12; T3,N0,M0 = 9; T1–3,N+,M0 = 9, and T1–3,N0–3,M+ = 2. Diverting stomas were closed in 30 patients. Median follow‐up was 25 months. Recurrences occurred in four patients and were local and distant (n = 1) and distant (n = 3). Anal sphincter function was perfect (n = 20), incontinent to gas (n = 3), occasional minor leak (n = 2), frequent major soiling (n = 3), and colostomy (n = 2).

Conclusions

In patients with locally advanced rectal cancer located 3–6 cm from anal verge who are traditionally treated with abdominoperineal resection, preservation of anal sphincter after preoperative chemoradiation therapy plus complete rectal excision with coloanal anastomosis is feasible and is associated with acceptable morbidity and no mortality. J. Surg. Oncol. 2003;82:3–9. © 2002 Wiley‐Liss, Inc.
Enhancement of integrins by interleukin‐1α, and their relationship with metastatic and invasive behavior of human pancreatic ductal adenocarcinoma cells
Authors: Sawai Hirozumi , Takeyama Hiromitsu , Yamamoto Minoru , Furuta Akiyoshi , Funahashi Hitoshi , Okada Yuji , Sato Mikinori , Tanaka Moritsugu , Manabe Tadao
Published: December 2002

Background and Objectives

Adhesion and invasion of tumor cells to extracellular matrix (ECM) proteins play an important role in tumor metastasis formation. We investigated the enhancement of adhesive and invasive behavior to ECM proteins of human pancreatic cancer cells by interleukin‐1α (IL‐1α) to examine the mechanism of adhesion and invasion of metastatic human pancreatic cancer cells to ECM proteins.

Methods

The enhancement of integrin subunits by IL‐1α was examined by cellular enzyme‐linked immunosorbent assay (CELISA) in two metastatic human pancreatic cancer cell lines (BxPC‐3 and SW1990) and two nonmetastatic pancreatic cancer cell lines (PaCa‐2 and PANC‐1). In addition, assays of cancer cell adhesion and invasion to ECM proteins were performed to investigate whether increased integrin expression affected the invasive interaction between cancer cells and the putative integrin ECM ligands.

Results

Expression of the α6 subunit by metastatic cancer cells was enhanced by IL‐1α. Metastatic cancer cells also exhibited preferential adherence and invasion to laminin compared with nonmetastatic cancer cells, and this was enhanced by IL‐1α.

Conclusions

The enhancement of α6β1‐integrin by Il‐1α acting through IL‐1RI, as well as the expression of α6β1‐integrin, plays an important role in metastasis formation in pancreatic cancer. J. Surg. Oncol. 2003;82:51–56. © 2002 Wiley‐Liss, Inc.
Lymphocytic infiltration surrounding liver metastases from colorectal cancer
Authors: Okano Keiichi , Maeba Takashi , Moroguchi Akito , Ishimura Ken , Karasawa Yukihiko , Izuishi Kunihiko , Goda Fuminori , Usuki Hisashi , Wakabayashi Hisao , Maeta Hajime
Published: December 2002

Background and Objectives

Tumor infiltrating lymphocytes (TILs) have been recognized as a tumor‐host reaction in various primary neoplasms. Although several studies reported TILs surrounding metastatic liver tumors, to the authors' knowledge few evaluations of the clinical significance of such features in patients with colorectal liver metastases have been carried out.

Methods

Forty‐one patients who underwent initial hepatic resection for liver metastases from colorectal cancer were studied. Lymphocytic infiltration surrounding metastatic liver tumor was graded as weak or dense according to the mean number of TILs from 10 high‐power microscopic fields (≤50 or >50/HPF).

Results

Dense lymphocytic infiltration between the metastatic tumor and hepatic parenchyma was seen in 18 of 41 patients (44%). Histologically, tumor invasion of the portal vein was rare in patients with dense TILs (12%) compared with patients with weak TILs (36%). Patients with dense TILs survived longer than patients with weak TILs after hepatic resection (P = 0.013). Multivariate analysis using the Cox proportional hazard model identified this pathological variable as a significant independent prognostic factor after hepatic resection.

Conclusions

The extent of lymphocytic infiltration between the metastatic nodule and hepatic parenchyma may reflect host defensive activity in the liver and is closely related to prognosis in patients who underwent hepatic resection for liver metastases from colorectal cancer. J. Surg. Oncol. 2003;82:28–33. © 2002 Wiley‐Liss, Inc.
Role of metastasectomy in the management of thyroid carcinoma: The NIH experience
Authors: Pak Ho , Gourgiotis Loukas , Chang Wen‐I , Guthrie Lori C. , Skarulis Monica C. , Reynolds James C. , Merino Maria J. , Schrump David S. , Libutti Steven K. , Alexander H. Richard , Sarlis Nicholas J.
Published: December 2002

Background and Objectives

We studied the impact of metatasectomy on disease outcome in 29 advanced nonmedullary thyroid carcinoma (ThyrCa) patients who were operated on between 1969 and 2001 at NIH to further define its role in the management of this malignancy.

Methods

Data were extracted by retrospective chart review. A Kaplan‐Meyer survival curve was constructed, and comparative stratification for various parameters was performed.

Results

During 47 surgeries, the following lesions were resected from mid‐mediastinum/hila, 17; lung parenchyma, 12; skeleton, 14; kidneys, 2; and brain, 2. All patients received multiple radioiodine (RAI) treatments. External‐beam radiotherapy, chemotherapy and other palliative measures were used in selected patients. Six patients (21%) died within 74.7 ± 54.7 months after the first distant metastasectomy. The outcome of the remaining patients was as follows: complete remission, 3; partial remission, 10; and 10: progressive disease, 10, with a follow‐up of 175 patient‐years. Metastasectomy led to a decrease of 38% in thyroglobulin levels in 23 patients. Cumulative survival rates were 78.5 ± 8.4% at 5 years and 50.2 ± 12.5% at 10 years (mean ±SEM) after initial distant metastasectomy.

Conclusions

Our data show that extensive targeted metastasectomy in the setting of a tertiary center can be beneficial to patients with disseminated ThyrCa with persistent or recurrent distant disease, when used in conjunction with nonsurgical treatment modalities. J. Surg. Oncol. 2003;82:10–18. © 2002 Wiley‐Liss, Inc.
Capturing pressure‐dependence in automated mechanism generation: Reactions through cycloalkyl intermediates
Authors: Matheu David M. , Green William H. , Grenda Jeffrey M.
Published: December 2002

Chemical kinetic mechanisms for gas‐phase processes (including combustion, pyrolysis, partial oxidation, or the atmospheric oxidation of organics) will often contain hundreds of species and thousands of reactions. The size and complexity of such models, and the need to ensure that important pathways are not left out, have inspired the use of computer tools to generate such large chemical mechanisms automatically. But the models produced by existing computerized mechanism generation codes, as well as a great many large mechanisms generated by hand, do not include pressure‐dependence in a general way. This is due to the difficulty of computing the large number of k(T, P) estimates required.

Here we present a fast, automated method for computing k(T, P) on‐the‐fly during automated mechanism generation. It uses as its principal inputs the same high‐pressure‐limit rate estimation rules and group‐additivity thermochemistry estimates employed by existing computerized mechanism‐generation codes, and automatically identifies the important chemically activated intermediates and pathways. We demonstrate the usefulness of this approach on a series of pressure‐dependent reactions through cycloalkyl radical intermediates, including systems with over 90 isomers and 200 accessible product channels. We test the accuracy of these computer‐generated k(T, P) estimates against experimental data on the systems H + cyclobutene, H + cyclopentene, H + cyclohexene, C2H3 + C2H4, and C3H5 + C2H4, and make predictions for temperatures and pressures where no experimental data are available. © 2002 Wiley Periodicals, Inc. Int J Chem Kinet 35: 95–119, 2003
Polymethylene tetraamine backbone as template for the development of biologically active polyamines
Authors: Melchiorre Carlo , Antonello Alessandra , Banzi Rita , Bolognesi Maria Laura , Minarini Anna , Rosini Michela , Tumiatti Vincenzo
Published: December 2002

The concept that polyamines may represent a universal template in the receptor recognition process is embodied in the design of ligands for different biological targets. As a matter of fact, the insertion of different pharmacophores onto the polymethylene tetraamine backbone can tune both affinity and selectivity for any given receptor. The application of this approach provided a prospect of modifying benextramine (1) structure to achieve specific recognition of muscarinic receptors that led to the discovery of methoctramine (2), which is widely used as a pharmacological tool for muscarinic receptor characterization. In turn, appropriate structural modifications performed on the structure of methoctramine led to the discovery of new polyamines endowed with high affinity and selectivity for (a) muscarinic receptor subtypes, (b) Gi proteins, and (c) muscle‐type nicotinic receptors. Thus, polyamines tripitramine (9) and spirotramine (33), among others, were designed, which were shown to be highly selective for muscarinic M2 and M1 receptors, respectively. Several polyamines have been discovered, which inhibit noncompetitively a closed state of the nicotinic receptor. These ligands, such as 66, resulted in important tools for elucidating the mode and site of interaction of polyamines with the ion channel. It was discovered that reducing the flexibility of the diaminohexane spacer of methoctramine led to polyamines, such as 70, which are endowed with a biological profile significantly different from that of the prototype. Most likely, tetraamine (70) is a potent activator of Gi proteins. Finally, the universal template approach formed the basis for modifying benextramine (1) structure to the design of ligands, which display affinity for acetylcholinesterase and muscarinic M2 receptors. Thus, these polyamines, such as caproctamine (78), could have potential in the investigation of Alzheimer disease. © 2002 Wiley Periodicals, Inc. Med Res Rev, 23, No. 2, 200–233, 2003
αv vitronectin receptors in vascular‐mediated disorders
Authors: Mousa Shaker A.
Published: December 2002

Various integrin antagonist candidates including antibodies, cyclic peptides, peptidomimetics, and non‐peptides have been clinically evaluated and shown to successfully modulate certain disease processes. This review will focus on the key role of the αv integrin (αvβ3 and αvβ5) in vascular disorders such as restenosis and angiogenesis‐mediated disorders. © 2002 Wiley Periodicals, Inc. Med Res Rev, 23, No. 2, 190–199, 2003
Microscopic vs. Endoscopic assisted harvesting and transplantation of free groin flaps: A comparative experimental study in the rat model
Authors: El‐Shazly Mohamed M. , Kamel Assem H. , El‐Sonbaty Mostafa A. , Zaki Mohamed S. , Baumeister Ruediger G.
Published: December 2002

Advances in video technology can now permit the surgeon to view a microsurgical field on a video monitor without the necessity of physically looking through the microscope eyepieces. In this project, we investigated the possibility of the performance of rat groin free‐flap harvesting and transplantation with the visual assistance of the endoscope, and compared it with the conventional operating microscope, not for its replacement but as an alternative operating tool that may be preferred by a younger generation of microsurgeons or in certain operative and financial situations. Although there were not many technical differences between the microscope and the endoscope, we recorded significantly shorter operative, harvesting, and transplantation times by using the endoscope. The endoscope seems to be a promising new tool in performing microsurgery, with better handling and greater physical comfort for the surgeon. It is reliable, time‐efficient, and cost‐effective. © 2002 Wiley‐Liss, Inc. MICROSURGERY 22:347–351 2002
Effect of allopurinol, superoxide‐dismutase, and hyperbaric oxygen on flap survival
Authors: Prada Flavia S. , Arrunategui Gino , Alves Marcos C. , Ferreira Marcos C. , Zumiotti Arnaldo V.
Published: December 2002

The effect of allopurinol, superoxide‐dismutase, and hyperbaric oxygen was compared on axial pattern skin flap survival. An abdominal flap based on the inferior epigastric pedicle was raised in rats for this purpose. Three experimental groups were studied. In the first group, adult male Wistar rats received 50 mg/kg I.P. of allopurinol. The second received 20,000 I.U./kg of superoxide‐dismutase. The third group was submitted to hyperbaric oxygen therapy. The flaps were exposed to 8‐h warm ischemia. Flap survival was evaluated on postoperative day 7. All flaps survived, and the mean survival areas were 63.53%, 83.03%, and 55.98%, respectively, in the allopurinol, superoxide‐dismutase, and hyperbaric groups. The percentage of flap necrosis was significantly smaller in all experimental groups when compared to controls (P < 0.05). It was clear that the superoxide‐dismutase group had better results on axial pattern ischemic skin flap survival, under the tested conditions. The tested methods improved flap survival to ischemic injury, and the flap designed is a reliable model for further investigations. © 2002 Wiley‐Liss, Inc. MICROSURGERY 22:352–360 2002
Averaging a transport equation with small diffusion and oscillating velocity
Authors: Bourgeat A. , Jurak M. , Piatnitski A. L.
Published: December 2002

A complete asymptotic expansion is constructed for the transport equation with diffusion term small with respect to the convection. Error estimates are obtained by using matched asymptotic expansion technique and building all the boundary layer terms in time and in space, necessary for obtaining an accurate error estimate. Copyright © 2003 John Wiley & Sons, Ltd.
The elastic echo problem
Authors: Mabrouk Mongi , Helali Zouheir
Published: December 2002

We consider a homogeneous isotropic unbounded linear elastic medium Ω⊂ℝ3, having a free boundary Γ. A forcing f(t,x) creates an incident displacement field u0(t,x). This primary field is scattered by Γ giving rise to a secondary field or echo, for which we determine the asymptotic behaviour in time. These results are obtained via the use of an tension of the time‐dependent scattering theory of C. Wilcox. Copyright © 2003 John Wiley & Sons, Ltd.
A FEM–DtN formulation for a non‐linear exterior problem in incompressible elasticity
Authors: Gatica Gabriel N. , Gatica Luis F. , Stephan Ernst P.
Published: December 2002

In this paper, we combine the usual finite element method with a Dirichlet‐to‐Neumann (DtN) mapping, derived in terms of an infinite Fourier series, to study the solvability and Galerkin approximations of an exterior transmission problem arising in non‐linear incompressible 2d‐elasticity. We show that the variational formulation can be written in a Stokes‐type mixed form with a linear constraint and a non‐linear main operator. Then, we provide the uniqueness of solution for the continuous and discrete formulations, and derive a Cea‐type estimate for the associated error. In particular, our error analysis considers the practical case in which the DtN mapping is approximated by the corresponding finite Fourier series. Finally, a reliable a posteriori error estimate, well suited for adaptive computations, is also given. Copyright © 2003 John Wiley & Sons, Ltd.
Uniform boundedness of the magnetic field in a resistive plasma
Authors: Núñez Manuel
Published: December 2002

While the magnetic energy in a plasma can be easily bounded by classical energy inequalities, the behaviour of the maximum of the magnetic field is less clear. In fact, the field in chaotic flows appears to concentrate in progressively smaller regions of the domain, so that conceivably it could grow there without limit. However, we prove that as long as the magnetic energy and the plasma remain bounded, so does the magnetic field. The dependence of these bounds on the main plasma parameters is analysed. Copyright © 2003 John Wiley & Sons, Ltd.
Cytoskeletal dynamics underlying collateral membrane protrusions induced by neurotrophins in cultured Xenopus embryonic neurons
Authors: Gibney Jean , Zheng James Q.
Published: December 2002

The establishment and refinement of neuronal connections depend on dynamic modification of the morphology and physiology of developing axons in response to extrinsic factors. In embryonic cultures of Xenopus spinal neurons, acute application of brain‐derived neurotrophic factor (BDNF) induced rapid collateral protrusion of filopodium‐like microspikes and lamellipodia along the neurite processes, leading to a morphologic alternation of the neuron. Both types of membrane protrusions contained high concentrations of actin filaments and depended on the polymerization of the actin cytoskeleton. Immunofluorescent staining, however, revealed the presence of microtubules (MTs) in lamellipodia induced by BDNF. These MTs appeared to have arisen from debundling of MTs in the neurite shaft at the protrusion sites, splaying and extending in the rapidly protruding lamellipodia. Inhibition of microtubule polymerization by nocodazole largely abolished the formation of lamellipodia but not of microspikes. Taken together, our results suggest that collateral sprouting of microspikes and lamellipodia involve distinctly different cytoskeletal mechanisms. Although the actin cytoskeleton is solely responsible for microspike formation, cooperative efforts by microtubules and actin filaments are essential for lamellipodial protrusion in response to extrinsic factors. © 2002 Wiley Periodicals, Inc. J Neurobiol 54: 393–405, 2003
Multilevel block factorizations in generalized hierarchical bases
Authors: Chow Edmond , Vassilevski Panayot S.
Published: December 2002

This paper studies the use of a generalized hierarchical basis transformation at each level of a multilevel block factorization. The factorization may be used as a preconditioner to the conjugate gradient method, or the structure it sets up may be used to define a multigrid method. The basis transformation is performed with an averaged piecewise constant interpolant and is applicable to unstructured elliptic problems. The results show greatly improved convergence rate when the transformation is applied for solving sample diffusion and elasticity problems. The cost of the method, however, grows and can get very high with the number of non‐zeros per row. Published in 2002 by John Wiley & Sons, Ltd.