bluuebunny/crossref_metadata_2025 huggingface dataset:
Teratogenic effects of bis‐diamine on the developing myocardium
Authors: Okamoto Nobuhiko , Nakagawa Masao , Fujino Hidetoshi , Nishijima Setsuko , Hanato Takashi , Narita Tsutomu , Takeuchi Yoshihiro , Imanaka‐Yoshida Kyoko
Published: March 2004

BACKGROUND

Bis‐diamine induces conotruncal anomalies and disproportional ventricular development in rat embryos when administered to the mother. To evaluate the mechanisms of disproportional ventricular development in the anomalous heart, we analyzed the morphology of the embryonic heart and investigated cardiomyocytic DNA synthesis and apoptosis.

METHODS

A single dose of 200 mg of bis‐diamine was administered to pregnant rats Wistar on day 9.5 of pregnancy. The embryos were removed on each embryonic day from 10.5 to 18.5. Expression of cardiotrophin‐1 and hepatocyte growth factor was investigated on the sections, and cardiotrophin‐1, hepatocyte growth factor and myocyte enhancer factor 2 mRNA expression was examined by reverse transcriptase–polymerase chain reaction. Myocardial DNA synthesis was investigated using 5‐bromo‐2′‐deoxyuridine and the labeling index was calculated for each heart. Apoptosis was also analyzed using TUNEL reaction and electrophoresis of DNA fragmentation.

RESULTS

The embryos treated with bis‐diamine had conotruncal anomalies associated with thin left ventricular wall in the later stage. The labeling index on embryonic day 15.5 and 16.5 was significantly lower than those in the controls. Hepatocyte growth factor and cardiotrophin‐1 mRNA expression was upregulated on embryonic day 12.5 and 15.5 in bis‐diamine–treated hearts. Fewer apoptotic cells were detected in the hearts of bis‐diamine–treated embryos than in control hearts from embryonic day 14.5 to 16.5.

CONCLUSIONS

The ventricular disproportion in the bis‐diamine–treated heart may be caused by the early myocardial differentiation delay and poor proliferation and reduced apoptosis associated with anomalous circulatory condition in the later stage. Birth Defects Research (Part A), 2004. © 2004 Wiley‐Liss, Inc.
Human head exposure to a 37 Hz electromagnetic field: Effects on blood pressure, somatosensory perception, and related parameters
Authors: Ghione Sergio , Del Seppia C. , Mezzasalma L. , Emdin M. , Luschi P.
Published: March 2004

Previous studies have shown that exposure to an electromagnetic field (EMF) of 37 Hz at a flux density of 80 μT peak enhances nociceptive sensitivity in mice. Here we examined the effects on pain sensitivity and some indexes of cardiovascular regulation mechanisms in humans by measuring electrical cutaneous thresholds, arterial blood pressure, heart rate and its variability, and stress hormones. Pain and tolerance thresholds remained unchanged after sham exposure but significantly decreased after electromagnetic exposure. Systolic blood pressure was significantly higher during electromagnetic exposure and heart rate significantly decreased, both during sham and electromagnetic exposure, while the high frequency (150–400 mHz) component of heart rate variability, which is an index of parasympathetic activity, increased as expected during sham exposure but remained unchanged during electromagnetic exposure. Cortisol significantly decreased during sham exposure only. These results show that exposure to an EMF of 37 Hz also alters pain sensitivity in humans and suggest that these effects may be associated with abnormalities in cardiovascular regulation. Bioelectromagnetics 25:167–175, 2004. © 2004 Wiley‐Liss, Inc.
In situ synthesis of oligonucleotide microarrays
Authors: Gao Xiaolian , Gulari Erdogan , Zhou Xiaochuan
Published: March 2004

This contribution presents a brief overall look of the methods for the preparation of various types of DNA microarrays and a thorough examination of the methods for in situ synthesis of oligonucleotide microarrays. © 2004 Wiley Periodicals, Inc. Biopolymers, 2004
Invasive cleavage reactions on DNA‐modified diamond surfaces
Authors: Lu Manchun , Knickerbocker Tanya , Cai Wei , Yang Wensha , Hamers Robert J. , Smith Lloyd M.
Published: March 2004

Recently developed DNA‐modified diamond surfaces exhibit excellent chemical stability to high‐temperature incubations in biological buffers. The stability of these surfaces is substantially greater than that of gold or silicon surfaces, using similar surface attachment chemistry. The DNA molecules attached to the diamond surfaces are accessible to enzymes and can be modified in surface enzymatic reactions. An important application of these surfaces is for surface invasive cleavage reactions, in which target DNA strands added to the solution may result in specific cleavage of surface‐bound probe oligonucleotides, permitting analysis of single nucleotide polymorphisms (SNPs). Our previous work demonstrated the feasibility of performing such cleavage reactions on planar gold surfaces using PCR‐amplified human genomic DNA as target. The sensitivity of detection in this earlier work was substantially limited by a lack of stability of the gold surface employed. In the present work, detection sensitivity is improved by a factor of ∼100 (100 amole of DNA target compared with 10 fmole in the earlier work) by replacing the DNA‐modified gold surface with a more stable DNA‐modified diamond surface. © 2004 Wiley Periodicals, Inc. Biopolymers, 2004
Efficient strategies for the conjugation of oligonucleotides to antibodies enabling highly sensitive protein detection
Authors: Kozlov Igor A. , Melnyk Peter C. , Stromsborg Katie E. , Chee Mark S. , Barker David L. , Zhao Chanfeng
Published: March 2004

Three methods for the conjugation of oligonucleotides to antibodies and the subsequent application of these conjugates to protein detection at attomole levels in immunoassays are described. The methods are based on chemical modification of both antibody and oligonucleotide. Aldehydes were introduced onto antibodies by modification of primary amines or oxidation of carbohydrate residues. Aldehyde‐ or hydrazine‐modified oligonucleotides were prepared either during phosphoramidite synthesis or by post‐synthesis derivatization. Conjugation between the modified oligonucleotide and antibody resulted in the formation of a hydrazone bond that proved to be stable over long periods of time under physiological conditions. The binding activity of each antibody–oligonucleotide conjugate was determined to be comparable to the corresponding unmodified antibody using a standard sandwich ELISA. Each oligonucleotide contained a unique DNA sequence flanked by universal primers at both ends and was assigned to a specific antibody. Highly sensitive immunoassays were performed by immobilizing analyte for each conjugate onto a solid support with cognate capture antibodies. Binding of the antibody–oligonucleotide conjugate to the immobilized analyte allowed for amplification of the attached DNA. Products of amplification were visualized using gel electrophoresis, thus denoting the presence of bound analyte. The preferred conjugation method was used to generate a set of antibody–oligonucleotide conjugates suitable for high‐sensitivity protein detection. © 2004 Wiley Periodicals, Inc. Biopolymers, 2004
Optical spectroscopic differentiation of various equilibrium denatured states of horse cytochrome c
Authors: Xu Qi , Keiderling Timothy A.
Published: March 2004

Thermal unfolding of cytochrome c (cyt c) from several states has been studied using equilibrium spectroscopic techniques. CD in the uv, vibrational circular dichroism, infrared, and uv‐vis absorption spectra measured at various temperatures, pHs, salt concentrations, and GuHCl concentrations are used to show the conformational as well as heme structural differences between native and various denatured states. The difference in thermal denaturation behaviors of cyt c starting from acid denatured, molten globule (MG), and the A and native states are explored. Different final high temperature states were observed for cytochrome c unfolding from four different initial states (native, MG, A, and acid denatured state) by electronic CD, Fourier transform infrared (FTIR), and vibrational CD (VCD). Consistent with this, different thermal unfolding pathways for the MG and A states are suggested by the FTIR and VCD data for this process. © 2004 Wiley Periodicals, Inc. Biopolymers, 2004
Characterization of collagen‐like heterotrimers: Implications for triple‐helix stability
Authors: Berisio Rita , Granata Vincenzo , Vitagliano Luigi , Zagari Adriana
Published: March 2004

This article deals with the effects of proline hydroxylation on collagen triple‐helix stability, an issue that is still under discussion. To investigate the structural determinants of triple‐helix stabilization by hydroxyproline (Hyp), we here characterized spectroscopically triple‐helix heterotrimers containing both chains of (Pro–Pro–Gly)10 and (Pro–Hyp–Gly)10. Results are discussed in relation to the various triple‐helix stabilization mechanisms. © 2004 Wiley Periodicals, Inc. Biopolymers, 2004
Preliminary results of intraperitoneal chemohyperthermia with oxaliplatin in peritoneal carcinomatosis of colorectal origin
Authors: Elias D , Pocard M , Sideris L , Edè C , Ducreux M , Boige V , Lasser P
Published: March 2004

Promising preliminary data
Tissue integration and biomechanical behaviour of contaminated experimental polypropylene and expanded polytetrafluoroethylene implants
Authors: Bellón J M , García-Carranza A , García-Honduvilla N , Carrera-San Martín A , Buján J
Published: March 2004

Background

Infection is one of the most devastating complications following implantation of a prosthetic material. The aim of this study was to compare the behaviour of two biomaterials contaminated with Staphylococcus aureus or Staphylococcus epidermidis, used to repair abdominal wall defects.

Methods

Defects (7 × 5 cm) were created in the anterior abdominal wall of 60 white New Zealand rabbits and repaired using polypropylene or expanded polytetrafluoroethylene (ePTFE) prostheses. The site of repair had been previously inoculated with 106 colony-forming units/ml S. aureus or S. epidermidis. Seven and 30 days after implantation, prosthetic specimens were examined by light and scanning electron microscopy, and immunohistochemical and biomechanical analysis.

Results

No significant differences with respect to controls were observed in the S. epidermidis groups. Two animals inoculated with S. aureus died. S. aureus induced the appearance of denuded areas exposing the filaments in the polypropylene prostheses, whereas the ePTFE prostheses showed zones of erosion, disorganized tissue, haemorrhage and necrosis. The biomechanical strength of the contaminated implants was unaltered.

Conclusion

Integration within host tissue was affected in the setting of S. aureus infection but the tensile strength of contaminated prostheses was not significantly reduced.
Prognostic significance of peritoneal minimal residual disease in gastric cancer detected by reverse transcription–polymerase chain reaction
Authors: Oyama K , Terashima M , Takagane A , Maesawa C
Published: March 2004

Background

A sensitive method for detecting minimal residual disease in the peritoneal cavity by quantifying carcinoembryonic antigen (CEA) mRNA using real-time quantitative reverse transcription–polymerase chain reaction (RQ-RT–PCR) was developed. The clinical value of the method for predicting peritoneal recurrence in patients with gastric cancer was evaluated.

Method

A total of 195 patients with gastric cancer and 20 with asymptomatic cholecystolithiasis were included in the study. CEA mRNA expression in peritoneal washings (p-CEA mRNA) was measured by RQ-RT–PCR and normalized to glyceraldehyde-3-phosphate dehydrogenase mRNA expression. The cut-off level of p-CEA mRNA for gastric cancer was determined by examining p-CEA mRNA levels in patients with asymptomatic cholecystolithiasis.

Results

Fifty-five (28·2 per cent) of the 195 patients were p-CEA mRNA positive. The rate of p-CEA mRNA positivity correlated significantly with clinicopathological factors. In 163 patients who underwent curative surgery, overall survival and disease-free survival were significantly poorer in p-CEA mRNA-positive patients than in p-CEA mRNA-negative patients (P < 0·001). Cox regression analysis revealed that only p-CEA mRNA was a significant independent prognostic factor (P = 0·034). Multivariate logistic regression analysis showed that p-CEA mRNA was a significant independent risk factor for peritoneal recurrence (P = 0·027).

Conclusion

These results suggest that p-CEA mRNA is a reliable prognostic factor and predictor of peritoneal recurrence in gastric cancer.
Value of updating a systematic review in surgery using individual patient data
Authors: McCormack K , Grant A , Scott N
Published: March 2004

Background

Previous research has highlighted the advantages of individual patient data (IPD) meta-analyses. However, they are resource intensive and take considerable time to complete. The aim of this study was to determine whether the extra investment is justified by greater accuracy or usefulness by means of a case study in surgery.

Methods

An updated review using IPD, where possible, was compared with an earlier version based on aggregate published data to determine whether there were statistically significant changes in estimates of effectiveness for hernia recurrence and persisting pain. Differences related to the type of laparoscopic repair, the type of open repair and methodological quality were also explored.

Results

The results for hernia recurrence changed little. However, the IPD update led to divergent conclusions for persisting pain. The published data implied a statistically significant benefit in favour of open repair, whereas the IPD result implied a statistically significant benefit in favour of laparoscopic repair (P < 0·001). Methodological quality did not account for this difference.

Conclusion

Updating of systematic reviews using IPD can be conducted successfully in surgery. This example led to little change in estimates of effectiveness for hernia recurrence but yielded qualitatively different estimates for persisting pain, an outcome rarely included in the published reports.
Haemodynamic effect of intermittent pneumatic compression of the leg after infrainguinal arterial bypass grafting
Authors: Delis K T , Husmann M J , Szendro G , Peters N S , Wolfe J H N , Mansfield A O
Published: March 2004

Background

Intermittent pneumatic compression (IPC) may increase blood flow through infrainguinal arterial grafts, and has potential clinical application as blood flow velocity attenuation often precedes graft failure. The present study examined the immediate effects of IPC applied to the foot (IPCfoot), the calf (IPCcalf) and to both simultaneously (IPCfoot+calf) on the haemodynamics of infrainguinal bypass grafts.

Methods

Eighteen femoropopliteal and 18 femorodistal autologous vein grafts were studied; all had a resting ankle : brachial pressure index of 0·9 or more. Clinical examination, graft surveillance and measurement of graft haemodynamics were conducted at rest and within 5 s of IPC in each mode using duplex imaging. Outcome measures included peak systolic (PSV), mean (MV) and end diastolic (EDV) velocities, pulsatility index (PI) and volume flow in the graft.

Results

All IPC modes significantly enhanced MV, PSV, EDV and volume flow in both graft types; IPCfoot+calf was the most effective. IPCfoot+calf enhanced median volume flow, MV and PSV in femoropopliteal grafts by 182, 236 and 49 per cent, respectively, and attenuated PI by 61 per cent. Enhancement in femorodistal grafts was 273, 179 and 53 per cent respectively, and PI attenuation was 63 per cent.

Conclusion

IPC was effective in improving infrainguinal graft flow velocity, probably by reducing peripheral resistance. IPC has the potential to reduce the risk of bypass graft thrombosis.
Validation of POSSUM scoring systems for audit of major hepatectomy
Authors: Lam C-M , Fan S-T , Yuen A W-C , Law W-L , Poon K
Published: March 2004

Background

The aim of the study was to validate the use of Physiological and Operative Severity Score in the enUmeration of Mortality and morbidity (POSSUM) and Portsmouth (P) POSSUM scoring systems to predict postoperative mortality in a group of Chinese patients who had a major hepatectomy for hepatocellular carcinoma.

Methods

A retrospective analysis was performed on data collected prospectively over a 6-year interval from January 1997 to December 2002. The mortality risks were calculated using both the POSSUM and the P-POSSUM equations.

Results

Two hundred and fifty-nine patients underwent major hepatectomy; there were 17 (6·6 per cent) postoperative deaths. Of 32 preoperative and intraoperative variables studied, age, smoking habit, serum creatinine concentration, American Society of Anesthesiologists grade, and physiological and operative severity scores were found to be significant factors predicting mortality. On multivariate analysis only the physiological and operative severity scores were independent variables. The POSSUM system overpredicted mortality risk (14·2 per cent) and there was a significant lack of fit in these patients (χ2 = 14·1, 3 d.f., P = 0·003). The mortality rate predicted by P-POSSUM was 4·2 per cent and showed no significant lack of fit (χ2 = 7·6, 3 d.f., P = 0·055), indicating that it predicted outcome effectively. A new logistic equation was derived from the present patient data set that requires testing prospectively.

Conclusion

P-POSSUM significantly predicted outcome in Chinese patients who had major hepatectomy for hepatocellular carcinoma. A modified disease-specific equation requires further testing.
Development of solid‐phase extraction method and its application for determination of hydrochlorothiazide in human plasma using HPLC
Authors: Zendelovska Dragica , Staﬁlov Trajče , Miloševski Petar
Published: March 2004

A high‐performance liquid chromatographic method was developed, validated and applied for the determination of hydrochlorothiazide in human plasma. The effects of mobile phase composition, buffer concentration, mobile phase pH and concentration of organic modiﬁers on retention of hydrochlorothiazide and internal standard were investigated. The method involves solid‐phase extraction on RP‐select B cartridges followed by isocratic reversed‐phase chromatography on a Hibar Lichrospher 100 RP‐8 column with UV detection at 230 nm. The recovery, selectivity, linearity, precision and accuracy of the method were evaluated from spiked human plasma samples. Limit of quantiﬁcation was 10 ng mL−1. The method has been implemented to monitor hydrochlorothiazide levels in patient samples. Copyright © 2004 John Wiley & Sons, Ltd.
Rapid analysis of MMI270B, an inhibitor of matrix metalloproteases in human plasma by liquid chromatography–tandem mass spectrometry: matrix interference in patient samples
Authors: Majumdar Tapan K. , Vedananda Sunanda , Tse Francis L. S.
Published: March 2004

A high‐throughput method was developed and validated for the quantitative determination of MMI270B, an inhibitor of matrix metalloprotease (MMP) enzymes, in human plasma. The method was based on reverse‐phase chromatographic separation of the analyte from plasma extract followed by atmospheric pressure chemical ionization (APCI) and tandem mass spectrometry in the selected reaction monitoring mode (SRM). Extraction was performed using simple protein ﬁltration in the 96‐well plate format to increase the throughput of the method. Optimised chromatographic separation in a short column (30 × 4.6 mm i.d.) coupled with positive APCI mode of ionization followed by selective SRM mode of detection yielded clean chromatograms with minimal signal suppression. The chromatographic conditions resolved isobaric interference peaks observed in samples from patients dosed with MMI270B. The standard curve was linear (r = 0.997) within the concentration range of 1.04 (lower limit of quantiﬁcation) to 1040 ng/mL using 0.1 mL of human plasma. The accuracy of the method varied from 93.6 to 103% with a precision of 2.17–6.71% over the concentration range. The method was simple, rapid, and robust with an analyte recovery of >98%. Copyright © 2003 John Wiley & Sons, Ltd.
Liquid chromatography‐tandem mass spectrometry for the determination of a new oxazolidinone antibiotic DA‐7867 in human plasma
Authors: Ji Hye Young , Lee Hye Won , Chang Seung Goo , Lee Jong Jin , Rhee Jae Keol , Kim Won Bae , Lee Hye Suk
Published: March 2004

A liquid chromatography‐tandem mass spectrometric (LC/MS/MS) method for the determination of a new ox‐azolidinone antibiotic DA‐7867, (S)‐[N‐3‐(4‐(2‐(1‐methyl‐5‐tetrazolyl)‐pyridine‐5‐yl)‐3‐ﬂuorophenyl)‐2‐oxo‐5‐oxazolidinyl]methyl acetamide, in human plasma was developed. DA‐7867 and internal standard, linezolid, were extracted from human plasma with ethyl acetate at acidic pH. A reverse‐phase LC separation was performed on Luna C8 column with the mixture of acetonitrile–ammonium formate (10 mm, pH 4.5; 35:65, v/v) as mobile phase. The analytes were determined using an electrospray ionization tandem mass spectrometry in the multiple‐reaction‐monitoring mode. The lower limits of quantiﬁcation for DA‐7867 was 2.5 ng/mL. The single liquid–liquid extraction quantitatively recovered DA‐7867 and internal standard from plasma samples at the ranges of 82.2–86.7%. DA‐7867 was stable in blank human plasma at room temperature for 24 h and following three freeze–thaw cycles. Copyright © 2003 John Wiley & Sons, Ltd.
Determination of the uronic acid composition of seaweed dietary ﬁbre by HPLC
Authors: Sánchez‐Machado D. I. , López‐Cervantes J. , López‐Hernández J. , Paseiro‐Losada P. , Simal‐Lozano J.
Published: March 2004

A high‐performance liquid chromatographic (HPLC) method is described for determination of the ratio of β‐d‐mannuronic acid to α‐l‐guluronic acid (M/G ratio) in dietary ﬁbre of edible seaweeds. Total dietary ﬁbre (TDF) content was determined gravimetrically. The TDF fraction was hydrolysed with 12 m and 1 m H2SO4, then neutralized with AG 4 × 4 resin. The uronic acids were separated in a Tracer Extrasil SAX 5 µm column (25 cm × 4 mm) at 35°C, with 2 mm KH2PO4 containing 5% methanol as mobile phase at a ﬂow rate of 1.5 mL/min. The detection wavelength was UV 210 nm. The chromatographic identiﬁcations of β‐d‐mannuronic acid and α‐l‐guluronic acid were conﬁrmed by liquid chromatography–mass spectrometry (LC‐MS). The method precision was 1.4% for β‐d‐mannuronic acid and 3.5% for α‐l‐guluronic acid. The method was used to determine M/G ratio in canned seaweeds (Saccorhiza polyschides and Himanthalia elongata) and in dried seaweeds (H. elongata, Laminaria ochroleuca, Undaria pinnatiﬁda, Palmaria sp. and Porphyra sp.). Copyright © 2003 John Wiley & Sons, Ltd.
Determination of abamectin and doramectin in sheep faeces using HPLC with ﬂuorescence detection
Authors: Kolar Lucija , Kužner Jernej , Eržen Nevenka Kožuh
Published: March 2004

An analytical procedure for the determination of abamectin and/or doramectin in sheep faeces has been developed. Avermectins were extracted from sheep faeces with acetonitrile, clean‐up using solid phase extraction (SPE) and analysed by high performance liquid chromatography (HPLC) with ﬂuorescence detection after derivatization with N‐methylimidazole.

The method has a low detection limit (1.0 ng/g of moist sheep faeces), low quantiﬁcation limit (2.5 ng/g of moist sheep faeces), good recovery in the range 66.4–80.8% for abamectin and 67.7–85.5% for doramectin as well as good repeatability (>85%). The method is applicable to the study of the time proﬁle of excretion in sheep faeces and also for ecotoxicological studies of both avermectins. Copyright © 2003 John Wiley & Sons, Ltd.
Simultaneous determination of amphetamine derivatives in human urine after SPE extraction and HPLC‐UV analysis
Authors: Soares M. E. , Carvalho M. , Carmo H. , Remião F. , Carvalho F. , Bastos M. L.
Published: March 2004

Amphetamine derivatives are a class of compounds increasingly abused as recreational drugs in various regions of the world. Although d‐amphetamine (AMPH) and 3,4‐methylenedioxymethamphetamine (MDMA, ecstasy) are among the most commonly used, the abuse of other designer drugs such as 4‐bromo‐2,5‐dimethoxyphenethylamine (2C‐B) and 4‐methylthioamphetamine (4‐MTA) and their involvement in acute intoxications has been increasingly reported. There is evidence that abusers ingest these compounds either alone or in combination and the respective monitoring is important for both legal and health care purposes in hospital emergency. In the present study a simple and clean solid‐phase extraction procedure from urine of AMPH and MDMA, and their major metabolites p‐hydroxyamphetamine (OH‐AMPH) and methylenedioxyamphetamine (MDA) and 2C‐B and 4‐MTA was developed. Analysis was performed by HPLC‐UV and the precision of the technique was between 2.9 and 5.3% for all compounds. For the overall procedure, the precision values were between 3.3 and 5.9%. Recoveries obtained from spiked urines at three concentration levels were better than 84 ± 4% for the six compounds. The limit of detection of the method for the compounds (between 5.3 and 84.0 ng) enables their identiﬁcation in urine after ingestion of fatal and non‐fatal doses. The main advantages of the present method lie in its simple, clean and reliable SPE extraction method of the six amphetamine derivatives from urine followed by their simultaneous detection and quantiﬁcation by liquid chromatography with UV detection. Copyright © 2004 John Wiley & Sons, Ltd.
Biodegradation and bioaccumulation of fenitrothion in rat liver
Authors: Roy Shalini , Roy Sharmila , Kumar Reena , Sharma C. B. , Pereira Ben. J.
Published: March 2004

The biodegradation of fenitrothion O,O‐dimethyl‐O‐(3‐methyl‐4‐nitro phenyl) phosphorothioate was investigated in rat liver after administration of various doses (5 mg/100 g body weight and 20 mg/100 g body weight) in acute treatment and 1 mg/100 g body weight in chronic treatment. High performance liquid chromatography of the pesticide and its metabolites formed in liver in acute treatment showed time‐dependent sequential conversion of pesticide into three major metabolites within 24 h. These metabolites were separated and puriﬁed to homogenity by HPLC and characterized by IR spectroscopy as O,O‐dimethyl‐O‐(3‐methyl‐4‐amino phenyl) phsophorothioate (metabolite 1), O,O‐dimethyl phosphorothioate (metabolite II) and O,O‐dimethyl phosphate (metabolite III) in the ﬁrst dose (5 mg/100 g body weight). Metabolite II was found to be different in the second dose (20 mg/100 g body weight) and identiﬁed as O,O‐dimethyl O‐3‐methyl‐4‐amino phenyl phosphate. The results with the ﬁrst dose indicated reduction of the nitro group in fenitrothion as step I followed by hydrolytic clevage of the P‐O‐aryl bond in metabolite I and oxidative desulphurylation of metabolite II. At higher dose (20 mg/100 g body weight) oxidative desulphurylation takes place as step II followed by hydrolysis of metabolite II. The bioaccumulation of fenitrothion within 60 days during chronic treatment showed no metabolite but continuous reduction in fenitrothion concentration, indicating excretion of pesticide and its products in urine and in faeces. Copyright © 2004 John Wiley & Sons, Ltd.
Detailed anatomy of the abdomen and pelvis of the visible human female
Authors: Bajka M. , Manestar M. , Hug J. , Székely G. , Haller U. , Groscurth P.
Published: March 2004

We report on a virtual anatomical preparation of the abdomen and pelvis of the Visible Human Female (VHF) for laparoscopic surgery training. The detailed cross‐sectional image data set from the U.S. National Library of Medicine was used as the basis to build an exemplary model of the female abdomen and pelvis. Segmentation software was developed to delineate organ outlines and more than 300 structures of interest, including organs, blood vessels, bones, muscles, and ligaments, have been segmented and three‐dimensionally reconstructed. Analyzing the normal anatomy we found several variations and pathologies of the VHF, such as missing muscles (gemellus superior, psoas minor), additional veins as well as spondylophytes (vertebral column, pubic bone), and colon diverticula. The complete data set may be viewed on the home page of the project (http://www.vision.ee.ethz.ch/projects/Lasso/start.html). Clin. Anat. 17:252–260, 2004. © 2004 Wiley‐Liss, Inc.
New views of male pelvic anatomy: Role of computer‐generated 3D images1
Authors: Venuti Judith M. , Imielinska Celina , Molholt Pat
Published: March 2004

There is considerable controversy concerning the role of cadaveric dissection in teaching gross anatomy and the potential of using 3D computer‐generated images to substitute for actual laboratory dissections. There are currently few high‐quality 3D virtual models of anatomy available to evaluate the utility of computer‐generated images. Existing 3D models are frequently of structures that are easily examined in three dimensions by removal from the cadaver, i.e., the heart, skull, and brain. We have focused on developing a 3D model of the pelvis, a region that is conceptually difficult and relatively inaccessible for student dissection. We feel students will benefit tremendously from 3D views of the pelvic anatomy. We generated 3D models of the male pelvic anatomy from hand‐segmented color Visible Human Male cryosection data, reconstructed and visualized by Columbia University's in‐house 3D Vesalius™ Visualizer.1 These 3D models depict the anatomy of the region in a realistic true‐to‐life color and texture. They can be used to create 3D anatomical scenes, with arbitrary complexity, where the component anatomical structures are displayed in correct 3D anatomical relationships. Moreover, a sequence of 3D scenes can be defined to simulate actual dissection. Structures can be added in a layered sequence from the bony framework to build from the “inside‐out” or disassembled much like a true laboratory dissection from the “outside‐in.” These 3D reconstructed anatomical models can provide views of the structures from new perspectives and have the potential to improve understanding of the anatomical relationships of the pelvic region (http://www.cellbiology.lsuhsc.edu/People/Faculty/Venuti_Figures/movie_index.html). Clin. Anat. 17:261–271, 2004. © 2004 Wiley‐Liss, Inc.
Non‐parametric statistical methods for multivariate calibration model selection and comparison
Authors: Thomas Edward V.
Published: March 2004

Model selection is an important issue when constructing multivariate calibration models using methods based on latent variables (e.g. partial least squares regression and principal component regression). It is important to select an appropriate number of latent variables to build an accurate and precise calibration model. Inclusion of too few latent variables can result in a model that is inaccurate over the complete space of interest. Inclusion of too many latent variables can result in a model that produces noisy predictions through incorporation of low‐order latent variables that have little or no predictive value. Commonly used metrics for selecting the number of latent variables are based on the predicted error sum of squares (PRESS) obtained via cross‐validation. In this paper a new approach for selecting the number of latent variables is proposed. In this new approach the prediction errors of individual observations (obtained from cross‐validation) are compared across models incorporating varying numbers of latent variables. Based on these comparisons, non‐parametric statistical methods are used to select the simplest model (least number of latent variables) that provides prediction quality that is indistinguishable from that provided by more complex models. Unlike methods based on PRESS, this new approach is robust to the effects of anomalous observations. More generally, the same approach can be used to compare the performance of any models that are applied to the same data set where reference values are available. The proposed methodology is illustrated with an industrial example involving the prediction of gasoline octane numbers from near‐infrared spectra. Published in 2004 by John Wiley & Sons, Ltd.
Fault‐tolerant spectroscopic data evaluation based on extended principal component regression correcting for spectral drifts and uncalibrated spectral features
Authors: Vogt F. , Mizaikoff B.
Published: March 2004

Chemometric algorithms are commonly applied in spectroscopy for deriving concentrations of chemicals from spectra. In order to ensure correct concentration results, the background spectrum must be stable and all absorbers present in unknown samples must have been contained in the calibration set. Recently, standard principal component regression (PCR) has been improved in two ways, correcting either for spectral drifts or for uncalibrated spectral features. In this study a combination of both correction approaches named secured pseudo PCR (spPCR) is presented which provides substantially improved concentration results even if the spectra are simultaneously affected by drifts and uncalibrated features. Additionally, spPCR extracts estimates of the spectrum of the uncalibrated absorbers and the drift spectrum. Hence systematic disturbances can be analyzed and a facile tool for allocating their origin is provided. Copyright © 2004 John Wiley & Sons, Ltd.
Towards Ordered Architectures: Self‐Assembly and Stepwise Procedures to the Hexameric Metallomacrocycles [Arylbis(terpyridinyl)6FeII6−n‐RuIIn] (n=0,2,3,5)
Authors: Newkome George R. , Cho Tae Joon , Moorefield Charles N. , Mohapatra Prabhu P. , Godínez Luis A.
Published: March 2004

Hexameric metallomacrocycles are a new class of ordered rigid‐macromolecules which possess unique structural, electronic, and physical characteristics. Directed‐ and self‐assembly methods for the construction of these stable bis(terpyridine)‐based materials are investigated by using both FeII and RuII as the coordinating metals. These heterometallomacrocycles and their homocounterparts are structurally compared, and their attendant electrochemical properties are analyzed and evaluated. These studies demonstrate the potential to create stable, nanoscale, doughnut‐shaped, molecular assemblies with envisioned ramifications for energy storage and release, as well as nanoscale molecular electronic and magnetic devices.
Magneto‐Structural Characterization of Metallocene‐Bridged Nitronyl Nitroxide Diradicals by X‐Ray, Magnetic Measurements, Solid‐state NMR Spectroscopy, and Ab Initio Calculations
Authors: Sporer Christian , Heise Henrike , Wurst Klaus , Ruiz‐Molina Daniel , Kopacka Holger , Jaitner Peter , Köhler Frank , Novoa Juan J. , Veciana Jaume
Published: March 2004

Crystallization of ferrocene and ruthenocene substituted in the 1‐ and 1′‐positions by two nitronyl nitroxide radicals gave the new crystal phases β‐1 (besides the known phase α‐1), α‐2, and β‐2 whose structures were determined by X‐ray analysis. In β‐1 the radical moieties adopt transoid positions, whereas two different cisoid conformations are adopted by α‐2 and β‐2. These conformations result from inter‐ and intramolecular hydrogen bonds, respectively. All compounds experience antiferromagnetic interactions, and J/kB values up to −7 K have been found by fitting the experimental magnetic susceptibilities to a modified Bleaney–Bowers equation. The solid diradicals α‐1, β‐1, α‐2, and β‐2 as well as the ferrocene 3, which was substituted by a unique nitronyl nitroxide, were investigated by 13C and 1H NMR spectroscopy with magic angle spinning. The carbon signals cover a range of 2000 ppm, and are well resolved such that the structure could be confirmed. Conversion of the signal shifts into spin densities disclosed the mechanisms by which spin delocalization from the nitronyl nitroxide substituents to the metallocene core occurs. The spin density distribution in α‐1, β‐1, and 3 was also predicted by DFT calculations. There is good agreement between the experimental and theoretical trends of the spin delocalization. The magnetic interactions were discussed in the light of intramolecular spin transfer and its dependence on geometric constraints, demonstrating that the 1,1′‐metallocenylene bridge is not a robust magnetic coupler.
DFT Description of the Electronic Structure and Spectromagnetic Properties of Strongly Correlated Electronic Systems: NiII, CuII and ZnIIo‐Dioxolene Complexes
Authors: Bencini Alessandro , Carbonera Chiara , Totti Federico
Published: March 2004

The spectroscopic and magnetic properties of dioxolene complexes of zinc, copper and nickel were studied by DFT calculations on model complexes of formulas [(NH3)4MII(SQ)]+ (M=Zn, Ni; SQ=semiquinonato) and [(NH3)2CuII(SQ)]+. Standard approaches such as time‐dependent DFT (TDDFT), the Slater transition state (STS), and broken symmetry (BS) were found to be unable to completely account for the physical properties of the systems, and complete active space‐configuration interaction (CAS‐CI) calculations based on the Kohn–Sham (KS) orbitals was applied. The CAS‐CI energies, properly corrected with multireference perturbation theory (MR‐PT), were found to be in good agreement with experimental data. We present here a calculation protocol that has a low CPU cost/accuracy ratio and seems to be very promising for interpreting the properties of strongly correlated electronic systems in complexes of real chemical size.
Ginkgolides and Glycine Receptors: A Structure–Activity Relationship Study
Authors: Jaracz Stanislav , Nakanishi Koji , Jensen Anders A. , Strømgaard Kristian
Published: March 2004

Ginkgolides from the Ginkgo biloba tree are diterpenes with a cage structure consisting of six five‐membered rings and a unique tBu group. They exert a variety of biological properties. In addition to being antagonists of the platelet activating factor receptor (PAFR), it has recently been shown that native ginkgolides are potent and selective antagonists of the inhibitory glycine receptor. Forty new ginkgolide derivatives have been prepared in good to high yields on milligram scales and investigated for their antagonistic properties at homomeric α1 glycine receptors, thus providing the first structure–activity relationship study of ginkgolides at glycine receptors. A high‐throughput screening assay showed that native ginkgolide C was the most potent ligand, and that manipulation of any of the hydroxyl groups led to loss of activity at α1 glycine receptors.
Structure and Lithium Dynamics of Li2AuSn2—A Ternary Stannide with Condensed AuSn4/2 Tetrahedra
Authors: Wu Zhiyun , Mosel Bernd D. , Eckert Hellmut , Hoffmann Rolf‐Dieter , Pöttgen Rainer
Published: March 2004

The new stannide Li2AuSn2 was prepared by reaction of the elements in a sealed tantalum tube in a resistance furnace at 970 K followed by annealing at 720 K for five days. Li2AuSn2 was investigated by X‐ray diffraction on powders and single crystals and the structure was refined from single‐crystal data: Z=4, I41/amd, a=455.60(7), c=1957.4(4) pm, wR2=0.0681, 278 F2 values, 10 parameters. The gold atoms display a slightly distorted tetrahedral tin coordination with AuSn distances of 273 pm. These tetrahedra are condensed through common corners leading to the formation of two‐dimensional AuSn4/2 layers. The latter are connected in the third dimension through SnSn bonds (296 pm). The lithium atoms fill distorted hexagonal channels formed by the three‐dimensional [AuSn2] network. Modestly small 7Li Knight shifts are measured by solid‐state NMR spectroscopy that are consistent with a nearly complete state of lithium ionization. The noncubic local symmetry at the tin site is reflected by a nuclear electric quadrupolar splitting in the 119Sn Mössbauer spectra and a small chemical shift anisotropy evident from 119Sn solid‐state NMR spectroscopy. Variable‐temperature static 7Li solid‐state NMR spectra reveal motional narrowing effects at temperatures above 200 K, revealing lithium atomic mobility on the kHz time scale. Detailed lineshape as well as temperature‐dependent spin lattice relaxation time measurements indicate an activation energy of lithium motion of 27 kJ mol−1.
Stereocontrolled Synthesis of the C21–C38 Fragment of the Unnatural Enantiomer of the Antibiotic Nystatin A1
Authors: Berkenbusch Thilo , Brückner Reinhard
Published: March 2004

The C21–C38 fragment all‐trans‐41 of the unnatural enantiomer 1 of nystatin A1 was prepared starting from the N‐propionyl oxazolidinone 9. Aldol adduct ent‐8 (ee > 96 %) derived in two steps was hydroborated with (thexyl)BH2. Oxidative work‐up and treatment with acid furnished δ‐lactone 4. It contains the complete stereotetrade of the target molecule. The α,β‐unsaturated ester 28 was reached after another four steps. It should be a precursor for the polyene moieties of a variety of polyol,polyene macrolides. Illustrating that, the α,β‐unsaturated aldehyde 29 obtained from 28 and DIBAL was extended by 10 C atoms in four steps yielding the C21–C38 segment 41. The latter set of transformations included the regio‐ and stereoselective Claisen rearrangement 32→35.
Oxasmaragdyrin–Ferrocene and Oxacorrole–Ferrocene Conjugates: Synthesis, Structure, and Nonlinear Optical Properties
Authors: Venkatraman Sundararaman , Kumar Rajeev , Sankar Jeyaraman , Chandrashekar Tavarekere K. , Sendhil Kaladevi , Vijayan C. , Kelling Alexandra , Senge Mathias O.
Published: March 2004

Ferrocenyl macrocyclic conjugates involving 22π oxasmaragdyrins and 18π oxacorroles have been synthesized and characterized. The direct covalent linkage of the ferrocenyl moiety to the meso position of the macrocycle is achieved by simple oxidative coupling of appropriate precursors with trifluoroacetic acid as catalyst. The electronic coupling between the ferrocenyl moiety and the macrocyclic π system is apparent from: a) the red shifts (293–718 cm−1) of the Soret and Q‐bands in the electronic absorption spectra of ferrocenyl conjugates; b) the shift of oxidation potentials (50–130 mV) of both the ferrocene and the corrole rings to the positive potentials; and c) considerable shortening of the CC bond which connects the ferrocene and the meso‐carbon atom of the macrocycle. The single‐crystal X‐ray structure of oxasmaragdyrin–ferrocene conjugate 9 reveals the planarity of the 22π skeleton with very small deviations of the meso‐carbon atoms. The meso‐ferrocenyl substituent has a small dihedral angle of 38°, making way for mixing of the molecular orbitals of the ferrocene and the macrocycle. However, the other two meso substituents are almost perpendicular to the mean plane, defined by the three meso carbon atoms. Classical CH⋅⋅⋅O and nonclassical CH⋅⋅⋅π interactions lead to a two‐dimensional supramolecular network. Ferrocene–smaragdyrin conjugate 9 bonds to a chloride ion in the protonated form and a rhodium(i) ion in the free base form. Nonlinear optical measurements reveal a larger nonlinear refractive index (−5.83×10−8 cm2 W−1) and figure of merit (2.28×10−8 cm3 W−1) for the rhodium smaragdyrin–ferrocene conjugate 19 than for the others, suggesting its possible application in optical devices.
Strategy for Enantio‐ and Diastereoselective Syntheses of All Possible Stereoisomers of 1,3‐Polyol Arrays Based on a Highly Catalyst‐Controlled Epoxidation of α,β‐Unsaturated Morpholinyl Amides: Application to Natural Product Synthesis
Authors: Tosaki Shin‐ya , Horiuchi Yoshihiro , Nemoto Tetsuhiro , Ohshima Takashi , Shibasaki Masakatsu
Published: March 2004

We describe a new strategy for enantio‐ and diastereoselective syntheses of all possible stereoisomers of 1,3‐polyol arrays. This strategy relies on a highly catalyst‐controlled epoxidation of α,β‐unsaturated morpholinyl amides promoted by the Sm–BINOL–Ph3AsO (1:1:1) complex, followed by a conversion of morpholinyl amides into ketones and diastereoselective ketone reduction. Highly enantio‐ (up to >99 % ee) or diastereoselective (up to >99.5:0.5) epoxidation was achieved using 5–10 mol % of the Sm complex to afford synthetically very useful, nearly optically pure α,β‐epoxy morpholinyl amides. Stereoselectivity of the epoxidation was controlled by the chirality of BINOL with overwhelming inherent diastereofacial preference for the substrate. Combination with the syn‐ and anti‐selective ketone reduction with the highly catalyst‐controlled epoxidation allowed for an iterative strategy for the syntheses of all possible stereoisomers of 1,3‐polyol arrays. Eight possible stereoisomers of 1,3,5,7‐tetraol arrays were synthesized with high to excellent stereoselectivity. Moreover, the efficiency of the present strategy was successfully demonstrated by enantioselective syntheses of several 1,3‐polyol/α‐pyrone natural products, for example, cryptocaryolone diacetate.
X‐chromosome loss of heterozygosity frequently occurs in gastrinomas and is correlated with aggressive tumor growth
Authors: Chen Yuan‐Jia , Vortmeyer Alexander , Zhuang Zhengping , Gibril Fathia , Jensen Robert T.
Published: March 2004

BACKGROUND

Recent studies have shown that tumor growth, rather than hormone overproduction, is the leading cause of death among patients with gastrinomas and other malignant gastrointestinal endocrine tumors. No patient/laboratory characteristics accurately predict which tumors will exhibit aggressive growth. Furthermore, little is known regarding the molecular pathogenesis of these tumors. X‐chromosome loss of heterozygosity (LOH) occurs in some nonendocrine tumors, and its presence can be associated with aggressive growth/decreased survival. Data on X‐chromosome LOH in gastrointestinal endocrine tumors are conflicting. Therefore, the purpose of the current study was to determine whether X‐chromosome LOH occurred in gastrinomas and, if so, whether it was correlated with tumor growth, tumor behavior, and/or prognosis.

METHODS

X chromosome allelotyping was performed using 12 microsatallite markers spaced throughout the chromosome using DNA from leukocytes and microdissected gastrinoma specimens from 16 female patients. The presence of X‐chromosome LOH was analyzed for correlations with clinical and laboratory tumor characteristics as well as tumor growth characteristics.

RESULTS

Nine gastrinoma specimens (56%) had X‐chromosome LOH, ranging from 6% to 23% at the 12 different loci studied. X‐chromosome LOH was significantly associated with aggressive postoperative tumor growth, increased primary tumor size, and pancreatic primaries. In 6 tumor specimens, LOH occurred on Xp22.1–22.3 over a 28.4‐centimorgan region.

CONCLUSIONS

X‐chromosome LOH was common in gastrinoma specimens from female patients, and its presence was found to be a potentially useful molecular/genetic prognostic factor for aggressive growth. Cancer 2004;100:1379–87. Published 2004 American Cancer Society.
Chromophobe renal cell carcinoma
Authors: Peyromaure Michaël , Misrai Vincent , Thiounn Nicolas , Vieillefond Annick , Zerbib Marc , Flam Thierry A. , Debré Bernard
Published: March 2004

BACKGROUND

Chromophobe renal cell carcinoma (CRCC) is often associated with a favorable prognosis. However, to the authors' knowledge, only few clinical data are available regarding this variant of tumor. In the current study, the authors report their experience with CRCC over the last 14 years.

METHODS

Since 1989, 61 patients have been treated at the study institution for CRCC. Tumor characteristics and patient outcome were analyzed retrospectively. Data were obtained from the patients' medical records.

RESULTS

The mean age of the patients was 58 years. Of the 61 tumors, 68.8% were discovered incidentally. The mean tumor size was 6.9 cm. Fifty‐seven patients (93.4%) were treated with radical nephrectomy and 4 patients (6.6%) underwent partial nephrectomy. According to the 1997 TNM classification, the pathologic tumor stage was T1 in 65.6% of cases, T2 in 31.1% of cases, and T3a in 3.3% of cases. All tumors were staged as N0M0. Nuclear grade was low (1 or 2) in 88.5% of cases. In no case of CRCC was a sarcomatoid component observed. At a mean follow‐up of 49.5 months (range, 5–135 months), no patient had experienced tumor recurrence or disease progression, and none had died of renal carcinoma.

CONCLUSIONS

In the authors' experience, CRCC carries an excellent prognosis, possibly due to the high rate of low‐stage and low‐grade tumors. Cancer 2004;100:1406–10. © 2004 American Cancer Society.