bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis and Biological Evaluation of Pyrrolo[2,1‐c][1,4]benzodiazepine (PBD) C8 Cyclic Amine Conjugates.
Authors: Masterson Luke A. , Croker Stephen J. , Jenkins Terence C. , Howard Philip W. , Thurston David E.
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Novel Functionalized Trisubstituted Allylboronates via Hosomi—Miyaura Borylation of Functionalized Allyl Acetates.
Authors: Ramachandran P. Veeraraghavan , Pratihar Debarshi , Biswas Debanjan , Srivastava Amit , Reddy M. Venkat Ram
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Fascicularones C and D, Tricyclo[5.4.0.02,5]undecane Sesquiterpenoids from the Liquid Culture of Naematoloma fasciculare.
Authors: Shiono Yoshihito , Wakamatsu Hiroko , Murayama Tetsuya , Ikeda Michimasa
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Asymmetric PTC Alkylation of Glycine Imines: Variation of the Imine Ester Moiety.
Authors: Lygo Barry , Allbutt Bryan
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Synthesis of O‐Aryl N4‐Glycosyl(thiosemicarbazido)phosphonothioates.
Authors: Tsao L. , Chzhou Ch. , Sun Ts. , Koroteev A. M.
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Synthesis of 4‐Amino‐5H‐2,3‐dihydroisothiazole‐1,1‐dioxide Ring Systems on Sugar Templates via Carbanion‐Mediated Sulfonamide Intramolecular Cyclization Reactions (CSIC Protocols) of Glyco‐α‐sulfonamidonitriles.
Authors: Dominguez Laura , Nguyen Van Nhien Albert , Tomassi Cyrille , Len Christophe , Postel Denis , Marco‐Contelles Jose
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
The Absolute Configuration of Methyl Dihydrosterculate: An Unusual Phytofatty Acid Isolated from the Seed Oil of Litchi chinensis.
Authors: Stuart Laura J. , Buist Peter H.
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Thermal Isomerization of Vitamin D3 in Dimethyl Sulfoxide.
Authors: Jin Xiaoling , Yang Xinping , Yang Li , Liu Zhong‐Li , Zhang Fa
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Novel α‐Pyrones Produced by a Marine Pseudomonas sp. F92S91: Taxonomy and Biological Activities.
Authors: Singh Maya P. , Kong Fangming , Janso Jeffrey E. , Arias Daniel A. , Suarez Paola A. , Bernan Valerie S. , Petersen Peter J. , Weiss William J. , Carter Guy , Greenstein Michael
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
The Synthesis and Anticonvulsant Activity of Some ω‐Phthalimido‐N‐phenylacetamide and Propionamide Derivatives.
Authors: Soyer Zeynep , Kilic Fatma Sultan , Erol Kevser , Pabuccuoglu Varol
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Diastereoselective Synthesis and Configuration‐Dependent Activity of (3‐Substituted‐cycloalkyl)glycine Pyrrolidides and Thiazolidides as Dipeptidyl Peptidase IV Inhibitors.
Authors: Ashton Wallace T. , Dong Hong , Sisco Rosemary M. , Doss George A. , Leiting Barbara , Patel Reshma A. , Wu Joseph K. , Marsilio Frank , Thornberry Nancy A. , Weber Ann E.
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Recently Synthesized Class of Vinylphosphonates as Potent Matrix Metalloproteinase (MMP‐2) Inhibitors.
Authors: Al‐Quntar Abed Al‐Aziz , Baum Ofir , Reich Reuven , Srebnik Morris
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Addition to Unsaturated Ligands
Authors: Kurosawa Hideo
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Copper and Silver Derivatives of Scorpionates and Related Ligands
Authors: Pettinari Claudio , Cingolani Augusto , Lobbia Giancarlo Gioia , Marchetti Fabio , Martini Domenico , Pellei Maura , Pettinari Riccardo , Santini Carlo
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Manganese‐Catalyzed Carbomagnesation of Alkynes
Authors: Shinokubo Hiroshi , Oshima Koichiro
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Ionic Liquids: Improved Syntheses and New Products
Authors: Carmichael Adrian J. , Deetlefs Maggel , Earle Martyn J. , Froehlich Ute , Seddon Kenneth R.
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Catalytic Aldehyde Olefinations
Authors: Kuehn Fritz E. , Santos Ana M.
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Combichem: Beads of Light
Authors: Mittoo Stifun , Bradley Mark
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Applications of CO2 in Homogeneous Catalysis
Authors: Jessop Philip G.
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Solid Acid Catalysts for Industrial Condensations of Ketones and Aldehydes with Aromatics
Authors: de Angelis A. , Ingallina P. , Perego C.
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Carboxylate Binding by Guanidiniocarbonyl Pyrroles: From Self‐Assembly to Peptide Receptors
Authors: Schmuck Carsten , Geiger Lars
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Asymmetric Reactions Based on Activation and Structure Control of Molecule — Asymmetric Reaction of Lithiated Nucleophiles
Authors: Tomioka Kiyoshi
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
α‐Campholenic Aldehyde: Versatile Raw Material for Fragrances
Authors: Bajgrowicz Jerzy A. , Gautschi Markus
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Synthesis of Labeled Isomers
Authors: Noel Jean‐Pierre , Loreau Olivier
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
The Mechanisms of Sulfonyl Transfer in Strained Cyclic Sulfonamides
Authors: Wood J. Matthew , Page Michael I.
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Physico‐Chemical Characterization of Drugs and Drug Forms in the Solid State
Authors: Marini A. , Berbenni V. , Bruni G. , Cofrancesco P. , Giordano F. , Villa M.
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Particle Destabilization and Removal from Concentrated Dairy Manure Suspensions
Authors: Dao Thanh H.
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Metalloporphyrins as Efficient Models of Heme Enzymes in Oxidation Reactions
Authors: Vinhado Fabio S. , Martins Patricia R. , Iamamoto Yassuko
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Chemical and Biological Remediation of CCA‐Treated Waste Wood
Authors: Kartal S. Nami , Imamura Yuji
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Electronic Structure and Chemical Reactivity: Density Functional and Information‐Theoretic Perspectives
Authors: Nalewajski Roman F.
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Lateral Diffusion Studied by Pulsed Field Gradient NMR on Oriented Lipid Membranes
Authors: Oraedd Greger , Lindblom Goeran
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Development of a Method for the Measurement of Long‐Range 13C—1H Coupling Constants from HMBC Spectra
Authors: Edden Richard A. E. , Keeler James
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Analysis of Molecular Characteristics of Starch Polysaccharides
Authors: Huber Anton , Praznik Werner
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Aberrant expression of CARM1, a transcriptional coactivator of androgen receptor, in the development of prostate carcinoma and androgen‐independent status
Authors: Hong Heng , Kao Chinghai , Jeng Meei‐Huey , Eble John N. , Koch Michael O. , Gardner Thomas A. , Zhang Shaobo , Li Lang , Pan Chong‐Xian , Hu Zhiqiang , MacLennan Gregory T. , Cheng Liang
Published: May 2004

BACKGROUND

Coactivator‐associated arginine methyltransferase 1 (CARM1) is a transcriptional coactivator of the androgen receptor (AR). It is involved in the regulation of the biologic functions of the AR. It remains to be determined whether CARM1 is involved in prostatic carcinogenesis.

METHODS

The expression of CARM1 in normal prostate epithelium, high‐grade prostatic intraepithelial neoplasia (PIN), and prostate carcinoma tissue was examined in 66 previously untreated patients with prostate carcinomas, as well as 12 patients with hormone‐independent prostate carcinoma, using immunohistochemical methods.

RESULTS

Cell staining was observed in the cytoplasm and the nucleus. In 66 patients without previous hormonal treatment, the percentage of cells that stained positively for CARM1 in benign prostate tissue specimens (mean values: cytoplasm, 23%; nucleus, 16%) was statistically significantly less than the percentage of positively stained cells in PIN (mean values: cytoplasm, 56%; nucleus, 30%; P < 0.001) and in prostatic adenocarcinoma specimens (mean values: cytoplasm, 79%; nucleus, 53%; P < 0.001). The difference between adenocarcinoma and PIN also was statistically significant (P < 0.001). The staining intensity for CARM1 was significantly lower in benign prostate tissue specimens compared with PIN and prostatic adenocarcinoma specimens (P < 0.001). In the 12 patients with androgen‐independent prostatic adenocarcinoma, the expression of CARM1 was significantly increased when compared with patients without previous hormonal treatment. Expression of CARM1 was not correlated with age, Gleason score sum, pathologic stage, lymph node metastasis, extraprostatic extension, surgical margin status, vascular invasion, or perineural invasion.

CONCLUSIONS

The authors found that overexpression of CARM1 was involved in the development of prostate carcinoma as well as androgen‐independent prostate carcinoma. Since CARM1 is functionally different from most other transcriptional coactivators of the AR, it may serve as a new target for the treatment of hormone‐independent prostate carcinoma. Cancer 2004. © 2004 American Cancer Society.
Circulating D‐dimer levels are better predictors of overall survival and disease progression than carcinoembryonic antigen levels in patients with metastatic colorectal carcinoma
Authors: Blackwell Kimberly , Hurẃitz Herbert , Liebérman Grazyna , Novotny William , Snyder Stacey , Dewhirst Mark , Greenberg Charles
Published: May 2004

BACKGROUND

Fibrin formation is required for tumor angiogenesis, metastasis, and invasion. D‐dimer, a fibrin degradation product, is produced when crosslinked fibrin is degraded by plasmin. The current study prospectively examined D‐dimer levels in patients with metastatic colorectal carcinoma treated in a Phase II randomized trial comparing bevacizumab (Avastin, Genentech, South San Francisco, CA) plus 5‐fluorouracil/leucovorin (5‐FU/LV) with 5‐FU/LV alone.

METHODS

At least one circulating D‐dimer level was evaluable in 98 of the 104 previously untreated patients with metastatic colorectal carcinoma in the current trial. Plasma D‐dimer levels were determined using a quantitative immunoassay kit at enrollment, before each treatment, and at the time of trial completion or disease progression.

RESULTS

At trial enrollment, 86 of 104 patients (88%) had elevated D‐dimer levels (> 20 ng/mL), and 86 of 102 patients (84%) had elevated carcinoembryonic antigen (CEA) levels (> 3 ng/mL). Baseline D‐dimer levels were correlated with the following baseline characteristics: CEA (Pearson coefficient, 0.31; P = 0.002), albumin levels (Pearson coefficient, −0.32; P = 0.002), tumor burden (Pearson coefficient, 0.30; P = 0.003), and number of metastatic sites (Pearson coefficient, 0.21; P = 0.04). At the time of progression, plasma D‐dimer levels reached a maximum postbaseline value in 51 of 61 patients (84%), whereas the CEA level was at its maximum postbaseline value in 39 of 55 patients (71%). Baseline D‐dimer levels were a strong predictor of overall survival on univariate analysis (P = 0.008) and multivariate analysis (P = 0.03). Overall, treatment with bevacizumab (5 mg/kg) and baseline D‐dimer levels were the only predictors of overall survival (P < 0.05).

CONCLUSIONS

The current study indicates that fibrin remodeling is an important prognostic feature in metastatic colorectal carcinoma. D‐dimer levels should be incorporated into prognostic models, and D‐dimer may represent a useful biomarker for patients treated with antiangiogenic agents. Cancer 2004. © 2004 American Cancer Society.
Positron emission tomography for unexplained elevation of serum squamous cell carcinoma antigen levels during follow‐up for patients with cervical malignancies
Authors: Chang Ting‐Chang , Law Kim‐Seng , Hong Ji‐Hong , Lai Chyong‐Huey , Ng Koon‐Kwan , Hsueh Suei , See Lai‐Chu , Chang Yu‐Chen , Tsai Chien‐Sheng , Chou Hung‐Hsueh , Huang Kuan‐Gen , Liou Jui‐Der , Lin Cheng‐Tao , Chao Angel , Chen Min‐Yu , Wu Tzu‐I , Ma Shih‐Ya , Yen Tzu‐Chen
Published: May 2004

BACKGROUND

During follow‐up for patients with cervical carcinoma, elevation of serum squamous cell carcinoma antigen (SCC‐Ag) levels in the absence of detectable recurrent lesions presents a diagnostic and therapeutic challenge. In the current prospective study, the authors evaluated the use of fluorine‐18‐labeled fluoro‐2‐deoxy‐D‐glucose (FDG) positron emission tomography (PET) to detect disease recurrence in this setting.

METHODS

Women with cervical carcinoma who experienced complete responses to primary treatment or salvage therapy and who had no evidence of recurrent disease as detected by conventional methods but had serum SCC‐Ag levels ≥ 2.0 ng/mL on 2 consecutive occasions were eligible for the study. PET was performed within 2 weeks after the completion of conventional studies for the assessment of recurrence.

RESULTS

Twenty‐seven consecutive patients were registered for the current study. PET findings were positive for 19 patients: 14 who had a distant lesion or lesions, 2 who had a local lesion or lesions, and 3 who had both local and distant lesions. Of these 19 patients, 17 were confirmed to have recurrent disease; the remaining two were found to be free of disease but had severe anthracosis in the PET‐positive mediastinal lymph nodes. Seven of the eight patients with negative PET findings were not found to have recurrent disease on follow‐up. Overall, PET detected FDG‐avid lesions in 17 (94%; P < 0.001) of the 18 patients with recurrent disease. Seven of these 18 patients received therapy with curative intent; complete control was achieved in 6, four of whom currently are alive and free of disease. The addition of PET in the current setting curbed the use of futile curative therapy and significantly increased overall survival for patients in the current cohort compared with a historical group of 30 consecutive patients who had elevated SCC‐Ag levels as a first sign of recurrence.

CONCLUSIONS

PET expedited the detection of recurrent cervical carcinoma in patients with unexplained elevation of SCC‐Ag levels. Such expedited detection may have positive effects on patient survival. Cancer 2004. © 2004 American Cancer Society.
The utility of computed tomography scans in predicting suboptimal cytoreductive surgery in women with advanced ovarian carcinoma
Authors: Dowdy Sean C. , Mullany Sally A. , Brandt Kathy R. , Huppert Bonnie J. , Cliby William A.
Published: June 2004

BACKGROUND

Computed tomography (CT) scans of the abdomen and pelvis may predict which patients with ovarian carcinoma can undergo optimal cytoreduction at primary surgery. Previous studies have demonstrated that patients with ovarian carcinoma had optimal cytoreduction rates ranging from 50–60%. The authors sought to determine whether these findings applied to a surgical practice with a higher rate of optimal debulking. A predictive model using CT scanning and CA 125 values would allow the authors to determine which patients would be more appropriately treated with neoadjuvant chemotherapy.

METHODS

Preoperative CT scans for patients with Stage III/IV ovarian carcinoma (according to the staging system of the International Federation of Gynecology and Obstetrics) who were treated between 1996 and 2001 were evaluated retrospectively by 2 radiologists for 17 criteria evaluating the extent of disease. Clinical data were extracted from medical records. Residual tumors measuring ≥ 1 cm were considered suboptimal. Logistic regression was used to evaluate which criteria correlated with optimal cytoreduction.

RESULTS

Eighty‐seven patients were identified retrospectively who met entry criteria and had preoperative CT scans of sufficient diagnostic quality. Sixty‐two patients (71%) received optimal cytoreductive surgery and 45 (52%) required aggressive surgical procedures. In a multivariate model, only diffuse peritoneal thickening (DPT) independently predicted suboptimal surgical resection (P = 0.016). However, a model using both DPT and ascites on most CT scans had a positive predictive value of 68% and a sensitivity of 52% for predicting suboptimal cytoreduction.

CONCLUSIONS

The presence of DPT and large‐volume ascites was associated with a very low rate of optimal cytoreduction (32%) in a surgical practice. These patients may be more appropriately treated with neoadjuvant chemotherapy followed by surgical cytoreduction. Cancer 2004. © 2004 American Cancer Society.
Divertor modelling of septum assessment experiments in JET MkIIGB
Authors: Tsitrone E. , Andrew P. , Bonnin X. , Coad P. , Coster D. , Fundamenski W. , Ghendrih P. , Huber A. , Jachmich S. , Kukushkin A. , Loarte A. , Matthews G. , Pitts R. , Rapp J. , Reiter D. , Stamp M. , Wischmeier M. , contributors to the JET EFDA work programme
Published: June 2004

We present results obtained from modeling the septum assessment experiments of the JET MkIIGB divertor with the B2‐Eirene code package. Similar L‐mode discharges have been performed with and without septum, varying density and gas puffing location. High and low inner wall clearance simulations are also compared, as this parameter has been shown experimentally to play an important role in the final density limit. According to the simulations, the neutrals ionization pattern is not affected by the septum, consistent with experiment. The septum does improve the pumped particle flux in the outer divertor, the inner divertor results depending on plasma‐wall clearance, but this only concerns a small fraction of the recycling flux at the targets (less than 2%) and does not influence the overall divertor plasma very much. Comparison between inner and outer gas fuelling with a moderate gas puff rate shows no difference in the simulations without septum, while a slight asymmetry is observed in the simulations with septum, showing that the septum allows acting separately on the inner and outer divertor. We conclude that a neutral flow exists linking outer and inner divertors with particles travelling around the plasma in the main chamber. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Mammary myofibroblastoma: Report of two cases with fine‐needle aspiration cytology and review of the cytology literature
Authors: Odashiro Alexandre N. , Odashiro Miiji Luciana N. , Odashiro Danilo N. , Nguyen Gia‐Khanh
Published: May 2004

Fine‐needle aspirates from two histologically, immunohistochemically, and ultrastructurally confirmed mammary myofibroblastomas (MM) of two elderly women revealed abundant, randomly arranged single and clustered benign spindle‐shaped mesenchymal cells with scant cytoplasm and elongated or oval nuclei displaying a finely granular chromatin pattern and inconspicuous nucleoli. In one case a few cells showed inconspicuous nuclear grooves. The aspirated tumor cells from the other case stained positively with desmin and CD34 antibodies and negatively with cytokeratin and S‐100 protein antibodies, in keeping with an MM. A review of the literature was briefly presented. Diagn. Cytopathol. 2004;30:406–410. © 2004 Wiley‐Liss, Inc.
Identification of cytomegalovirus in a liquid‐based gynecologic sample using morphology, immunohistochemistry, and DNA real‐time PCR detection
Authors: Sekhon Harmanjatinder S. , Press Richard D. , Schmidt Waldemar A. , Hawley Mary , Rader Anne
Published: May 2004

The viral cytopathic effects of cytomegalovirus (CMV) are rarely encountered in conventional cervical vaginal smears and have never been reported in a liquid‐based gynecologic sample (SurePath). We present results of a liquid‐based gynecologic sample (SurePath) from an asymptomatic patient with classic CMV‐associated granular or dense cyanophilic intracytoplasmic and intranuclear inclusion bodies with a clear surrounding zone. These inclusions were immunohistochemically positive for CMV. The patient also had human papilloma virus (HPV)‐associated koilocytes that showed a unique perinuclear immunostaining pattern suggesting coinfection with both CMV and HPV. CMV amplification using real‐time polymerase chain reaction (PCR) of DNA extracted from the liquid‐based sample confirmed the morphologic and immunohistochemical findings of CMV infection. These observations suggest that a liquid‐based preparation can be used to assess CMV infection morphologically, immunohistochemically, and by real‐time PCR. Diagn. Cytopathol. 2004;30:411–417. © 2004 Wiley‐Liss, Inc.
p27Kip1 Expression and grading of breast cancer diagnosed on cytological samples
Authors: Troncone Giancarlo , Migliaccio Ilenia , Caleo Alessia , Palmieri Emiliano A. , Iaccarino Antonino , Sparano Lucianna , Vetrani Antonio , Palombini Lucio
Published: May 2004

The progressive reduction in p27Kip1 (p27) protein immunohistochemical staining with increasing histological grading is a well‐established finding occurring in breast cancer, and its role as diagnostic complement and prognostic marker has been thoroughly evaluated. To clarify whether this test may be applied to breast cytopathology, we performed p27 immunostaining on fresh fine‐needle cytology (FNC) samples from 10 benign and 40 malignant breast lesions. On average, p27 immunostaining was significantly lower in carcinomas than in benign lesions (P < 0.005). In particular, among carcinomas, p27 immunostaining progressively reduced from well‐to poorly differentiated lesions (G1 vs. G2, P < 0.05; G1 vs. G3, P < 0.001; G2 vs. G3; P < 0.001). A similar trend was noted in a subgroup of 20 matched FNCs and histological samples of breast carcinomas, when p27 immunostaining on FNCs was stratified according to the histological grading (G1 vs. G2, P = 0.18; G1 vs. G3, P < 0.05; G2 vs. G3, P < 0.05). In addition, p27 immunostaining on FNCs showed a good positive correlation with that on histology (Spearman R = 0.58; P < 0.01), with a diagnostic concordance between samples of 85%, by using the standard 50% positive cell cutoff. Taken in concert, our data suggest that p27 immunostaining is a reliable marker of tumor cell differentiation in breast cytopathology as well as in histopathology. Accordingly, staining FNCs for p27 may be an useful complement in addition to cytological grading in the preoperative assessment of breast cancer. Diagn. Cytopathol. 2004;30:375–380. © 2004 Wiley‐Liss, Inc.
Papillary thyroid carcinoma with an adenoid cystic pattern: Report of a case with fine‐needle aspiration cytology and immunocytochemistry
Authors: Haji Bahiyah E. , Ahmed Mahmoud S. , Prasad Asha , Omar Moh'd S. , Das Dilip K.
Published: May 2004

Although fine‐needle aspiration (FNA) cytologic features of conventional papillary thyroid carcinoma (PTC) and some of its variants have been documented in the literature, PTC with an adenoid cystic pattern has not so far been described. A 35‐year‐old woman presented with solitary cold nodule in the right lobe of thyroid. FNA smears from the nodule showed features of PTC such as papilliform clusters, monolayered sheets, psammoma bodies, increased frequency of nuclear grooves, and intranuclear cytoplasmic inclusions. In addition, there were areas of follicular formation and light‐pink to deep‐purple hyaline globules with a laminated appearance and surrounded by neoplastic cells, reminiscent of adenoid cystic carcinoma. These globules were present in 53% of the follicles. Immunocytochemical staining for thyroglobulin yielded positive cytoplasmic reaction in the neoplastic cells. Histopathology of the thyroidectomy specimen confirmed the cytodiagnosis of PTC. The hyaline globules were present focally and were light pink to deep purple with a laminated appearance resembling psamomma bodies. The colloid and follicular cells were positive for thyroglobulin but the hyaline globules were negative. Von Kossa staining for calcium revealed positive reaction in the psamomma bodies and some of the hyaline globules, indicating that the globules may be the beginning of psammoma bodies. Thus, FNA cytology was useful in diagnosing an unusual variant of PTC. Diagn. Cytopathol. 2004;30:418–421. © 2004 Wiley‐Liss, Inc.
Invasive mammary carcinoma with osteoclast‐like giant cells diagnosed by fine‐needle aspiration biopsy: Review of the cytologic literature and distinction from other mammary lesions containing giant cells
Authors: Cai Guoping , Simsir Aylin , Cangiarella Joan
Published: May 2004

Invasive carcinoma with osteoclast‐like giant cells is an unusual type of mammary adenocarcinoma with few cases reported in the cytology literature. We present the cytologic findings in a case of invasive cribriform carcinoma of the breast containing osteoclast‐like giant cells diagnosed by fine‐needle aspiration biopsy. The smears displayed three‐dimensional cohesive cluster cells of uniform epithelial cells admixed with numerous multinucleated giant cells that morphologically resembled osteoclasts. Core biopsy confirmed the cytologic diagnosis. Immunohistochemical studies indicated that the multinucleated giant cells were of histocytic origin. Knowledge of the bland cytologic pattern and the admixture of giant cells seen in invasive cribriform carcinoma with osteoclast‐like giant cells should avoid making a false negative diagnosis on aspiration biopsy. Diagn. Cytopathol. 2004;30:396–400. © 2004 Wiley‐Liss, Inc.
Lessons learned from Austrian SEAs
Authors: Aschemann Ralf
Published: May 2004

Since 1998, a number of voluntary strategic environmental assessment (SEA) pilot projects have been completed in Austria. This paper deals with the lessons learned, focusing on three main issues: (i) the involvement of stakeholders and the public; (ii) the methods used in the assessment of environmental impacts and (iii) the impact of SEA on decision making. Based on the analysis, a number of conclusions are drawn and recommendations are given for future SEA in Austria. These particularly include aspects of effective participation, communication, presentation and moderation, early scoping, the use of a limited number of indicators, transparent assessment methods and effective monitoring. Copyright © 2004 John Wiley & Sons, Ltd and ERP Environment.
Interferences in clinical capillary zone electrophoresis of serum proteins
Authors: Bossuyt Xavier
Published: June 2004

Capillary zone electrophoresis (CZE) of serum proteins has become a well‐accepted method for the separation of serum proteins and for the detection of monoclonal proteins in clinical laboratories. As CZE uses ultraviolet detection for direct protein quantification, exogenous ultraviolet‐absorbing substances are a novel challenge, not present in conventional gel‐based methods in which protein is quantified by dye binding. This minireview gives a survey of interfering substances, including iodinated contrast agents and antibiotics.
Forensic DNA typing by capillary electrophoresis using the ABI Prism 310 and 3100 genetic analyzers for STR analysis
Authors: Butler John M. , Buel Eric , Crivellente Federica , McCord Bruce R.
Published: June 2004

DNA typing with short tandem repeat (STR) markers is now widely used for a variety of applications including human identification. Capillary electrophoresis (CE) instruments, such as the ABI Prism 310 and ABI 3100 Genetic Analyzers, are the method of choice for many laboratories performing STR analysis. This review discusses issues surrounding sample preparation, injection, separation, detection, and interpretation of STR results using CE systems. Requirements for accurate typing of STR alleles are considered in the context of what future analysis platforms will need to increase sample throughput and ease of use.
Determination of multiple drugs of abuse in human urine using capillary electrophoresis with fluorescence detection
Authors: Alnajjar Ahmed , Butcher Jared A. , McCord Bruce
Published: June 2004

Methods for separation and determination of multiple drugs of abuse in biological fluids using capillary electrophoresis (CE) with native fluorescence and laser‐induced fluorescence (LIF) detection are described herein. Using native fluorescence, normorphine, morphine, 6‐acetyl morphine (6‐AM), and codeine were analyzed by CE without any derivatization procedure and detected at an excitation wavelength of 245 nm with a cut‐off emission filter of 320 nm, providing a rapid and simple analysis. The detection limits were in the range of 200 ng/mL. For a highly sensitive analysis, LIF detection was also examined using a two‐step precolumn derivatization procedure. In this case, drugs extracted from human urine were first subjected to an N‐demethylation reaction involving the use of 1‐chloroethyl chloroformate (ACE‐Cl) and then derivatized using fluorescein isothiocyanate isomer I (FITC) and analyzed by CE coupled to a LIF detector. Variables affecting this derivatization: yield of demethylation reaction, FITC concentration, reaction time and temperature, were studied. The estimated instrumental detection limits of the FITC derivatives were in the range of 50–100 pg/mL, using LIF detection with excitation and emission wavelengths of 488 nm and 520 nm, respectively. The linearity, reproducibility and reliability of the methods were evaluated. In addition, a comparison of the characteristics for both native fluorescence and LIF detections was also discussed.
Quantitation of reduced glutathione and cysteine in human immunodeficiency virus‐infected patients
Authors: Sbrana Elena , Paladini Adriano , Bramanti Emilia , Spinetti Maria C. , Raspi Giorgio
Published: June 2004

Plasma viral load (VL) values and CD4+ cell count are employed clinically for initiation of therapy in the treatment of patients infected with human immunodeficiency virus (HIV), as previous clinical studies have shown a marked prevalence of acquired immunodeficiency sydrome (AIDS) development in seropositive individuals with VL values over 30 000 copies/mL. Many studies have shown that reduced glutathione (GSH) and cysteine (Cys) deficiency play an important role in the infection. We have developed capillary zone electrophoresis (CZE)‐based assays and have used them to investigate the relationship between plasma and intracellular thiol levels and HIV‐1 viremia in plasma. Blood samples from healthy volunteers and seropositive patients undergoing different antiretroviral regimes were analyzed in the study. The VL assay was based on CZE‐UV detection of viral RNA at 260 nm. Determination of endogenous reduced Cys and GSH was achieved by CZE‐UV detection of their mercurial complexes at 200 nm. We found that a decrease in GSH and Cys levels may be associated with disease progress. In fact, reduced GSH and Cys levels appear progressively reduced with increasing VL.
A critical evaluation of high performance liquid chromatography‐electrospray ionisation‐mass spectrometry and capillary electrophoresis‐ electrospray‐mass spectrometry for the detection and determination of small molecules of significance in clinical and forensic science
Authors: Smyth W. Franklin , Brooks Peter
Published: June 2004

A critical review of applications for the period 2000–2003, taken from the Web of Knowledge database, of the techniques high performance liquid chromatography‐electrospray ionisation‐mass spectrometry (HPLC‐ESI‐MS) and capillary electrophoresis‐electrospray ionisation‐mass spectrometry (CE‐ESI‐MS) to the detection and determination of small molecules of significance in clinical and forensic science is presented. The molecules of mass less than 500 Da are chosen according to selected structural classes in which they give ESI signals primarily as [M+H]+ions although other ions such as [M−H]−, [M+Na]+and [M+NH4]+are also reported. The structural classes are drugs with amine‐containing side chains, drugs withN‐containing saturated ring structures, 1,4‐benzodiazepines, carbohydrates, benzimidazoles, other heterocycles, sulphonylureas, anthracyclines, sulphonamides, penicillins, cephalosporins, tetracyclines, nitrocatechols, steroids, flavonoids, oxazaphosphorines, cannabinols, and miscellaneous molecules. Details are given on the fragmentations, where available, that these ionic species exhibit in‐source and in ion‐trap, triple quadrupole and time‐of‐flight mass spectrometers. The review then gives a critical evaluation of these recent HPLC‐ESI‐MS and CE‐ESI‐MS analytical methods for the detection and determination of small molecules of clinical and forensic significance. Analytical information on, for example, sample concentration techniques, HPLC and CE separation conditions, recoveries from biological media and limits of detection (LODs) are provided.
S‐Adenosyl methionine/S‐adenosyl‐L‐homocysteine ratio determination by capillary electrophoresis employed as a monitoring tool for the antiviral effectiveness of adenosine analogs
Authors: Sbrana Elena , Bramanti Emilia , Spinetti Maria C. , Raspi Giorgio
Published: June 2004

S‐Adenosyl‐L‐homocysteine hydrolase (SAHh) inhibitors have long been used as broad‐range antivirals and have been recently evaluated as an experimental therapy of filovirus infections. In response to the need for a rapid laboratory testing method that could assess antiviral potency in vivo, our group developed a capillary electrophoresis (CE) method for the determination of the S‐adenosyl‐L‐homocysteine (SAH) to S‐adenosyl‐L‐methionine (SAM) ratio. After chloroacetaldehyde derivatization, SAH and SAM were detected using laser‐induced fluorescence detection with a HeCd laser. Separation and quantitation of both SAH and SAM in human plasma were achieved in less than 1 min. The proposed method is rapid and reliable, and could be easily applied to routine monitoring of clinical and preclinical trials subjects.
Capillary electrophoresis combined with microdialysis in the human spinal cord: A new tool for monitoring rapid peroperative changes in amino acid neurotransmitters within the dorsal horn
Authors: Parrot Sandrine , Sauvinet Valérie , Xavier Jean‐Michel , Chavagnac Delphine , Mouly‐Badina Laurence , Garcia‐Larrea Luis , Mertens Patrick , Renaud Bernard
Published: June 2004

A method originally developed for the separation of the three neurotransmitters γ‐aminobutyric acid (GABA), glutamate (Glu) and L‐aspartate (L‐Asp) in microdialysis samples from rat brain (Sauvinet et al., Electrophoresis 2003, 24, 3187–3196) was applied to human spinal dialysates obtained during peroperative microdialysis from patients undergoing surgery against chronic pain. Molecules were tagged on their primary amine function with the fluorogene agent, naphthalene‐2,3‐dicarboxaldehyde (NDA), and, after separation by capillary electrophoresis (CE, 75 mmol/L borate buffer, pH 9.2, containing 70 mmol/L sodium dodecyl sulfate and 10 mmol/L hydroxypropyl‐β‐cyclodextrin, + 25 kV voltage), were detected by laser‐induced fluorescence detection (LIFD) using a 442 nm helium‐cadmium laser. The complete method, including microdialysis sampling and analysis by CE‐LIFD, has been validated for the analysis of human spinal microdialysates. The analytical detection limits were 1, 3.7 and 17 nmol/L for GABA, Glu and L‐Asp respectively. This method allows an accurate measurement of the three amino acid neurotransmitters during an in vivo monitoring performed as rapidly as every minute in the human spinal dorsal horn. In addition, the effect of a brief peroperative electrical stimulation of the dorsal rootlets was investigated. The results obtained illustrate the advantages of combining microdialysis with CE‐LIFD for studying neurotransmitters with such a high sampling rate.
A comparative study of microemulsion electrokinetic capillary chromatography and micellar electrokinetic capillary chromatography for the analysis of UV‐absorbing compounds in human urine
Authors: Melin Virginie , Perrett David
Published: June 2004

Separations of human urine by microemulsion electrokinetic chromatography (MEEKC) and micellar electrokinetic capillary chromatography (MEKC) with respect to resolution, migration times and efficiencies were optimized and compared. The optimised MEEKC and MEKC methods were simple and fast, both of which are excellent characteristics for the complex separations required in clinical and biomedical studies. However, resolution in MEKC was significantly greater than in MEEKC although migration times were 30% faster for the optimised MEEKC method. In addition, a faster analysis method (short‐end injection) specifically for routine screening purposes was also investigated. With both MEEKC and MEKC modes, this provided short separations (less than 4 min for urine) with no major compromise in resolution. In conclusion, we found that MEEKC offered no real advantage over MEKC for urine analysis.
Determination of cefepime in plasma and cerebrospinal fluid by micellar electrokinetic chromatography with direct sample injection
Authors: Tseng Shou‐Hui , Yang Yuan‐Han , Chen Yi‐Ru , Chen Su‐Hwei
Published: June 2004

A simple micellar capillary electrokinetic chromatography (MEKC) with UV detection is described for analysis of cefepime in plasma and cerebrospinal fluid by direct injection without any sample pretreatment. The separation of cefepime from biological matrix was performed at 25°C using a background electrolyte consisting of tris(hydroxymethyl)aminomethane (Tris) buffer with sodium dodecyl sulfate (SDS) as the electrolyte solution. Under optimal MEKC condition, good separation with high efficiency and short analyses time is achieved. Several parameters affecting the separation of the drug were studied, including the pH and concentrations of the Tris buffer and SDS. Using cefazolin as an internal standard, the linear ranges of the method for the determination of cefepime in plasma and cerebrospinal fluid were 1–50 and 1–20 μg/mL, respectively; the detection limits of plasma (signal‐to‐noise ratio = 3; injection, 5 kV, 5 s) and cerebrospinal fluid (signal‐to‐noise ratio = 3; injection, 0.5 psi, 3 s) were 0.2 μg/mL and 0.3 μg/mL, respectively. Application of the proposed method for determination of cefepime in plasma and cerebrospinal fluid collected after intravenous administration of 2 g cefepime in patients with meningitis was demonstrated.
Direct measurement of lithium in whole blood using microchip capillary electrophoresis with integrated conductivity detection
Authors: Vrouwe Elwin X. , Luttge Regina , van den Berg Albert
Published: June 2004

The direct measurement of lithium in whole blood is described. Using microchip capillary electrophoresis (CE) with defined sample loading and applying the principles of column coupling, alkali metals were determined in a drop of whole blood. Blood collected from a finger stick was mixed with anticoagulant and transferred onto the chip without extraction or removal of components. The electrokinetic transport of red blood cells inside the channels was studied to find sample loading conditions suitable for the analysis of lithium without injecting cells into the separation channel. Both bare glass chips and chips coated with polyacrylamide were used showing the behavior of the cells under different electroosmotic flow conditions. In serum a detection limit for lithium of 0.4 mmol/L was reached. Proteins quickly contaminated untreated chip surfaces but devices with coating gave reproducible electropherograms. In addition, potassium and sodium were also detected in the same separation run. To our knowledge, this is the first device to directly measure ions in whole blood with the use of capillary zone electrophoresis on a microchip.
Microfluidic tectonics platform: A colorimetric, disposable botulinum toxin enzyme‐linked immunosorbent assay system
Authors: Moorthy Jaisree , Mensing Glennys A. , Kim Dongshin , Mohanty Swomitra , Eddington David T. , Tepp William H. , Johnson Eric A. , Beebe David J.
Published: June 2004

A fabrication platform for realizing integrated microfluidic devices is discussed. The platform allows for creating specific microsystems for multistep assays in an ad hoc manner as the components that perform the assay steps can be created at any location inside the device via in situ fabrication. The platform was utilized to create a prototype microsystem for detecting botulinum neurotoxin directly from whole blood. Process steps such as sample preparation by filtration, mixing and incubation with reagents was carried out on the device. Various microfluidic components such as channel network, valves and porous filter were fabricated from prepolymer mixture consisting of monomer, cross‐linker and a photoinitiator. For detection of the toxoid, biotinylated antibodies were immobilized on streptavidin‐functionalized agarose gel beads. The gel beads were introduced into the device and were used as readouts. Enzymatic reaction between alkaline phosphatase (on secondary antibody) and substrate produced an insoluble, colored precipitate that coated the beads thus making the readout visible to the naked eye. Clinically relevant amounts of the toxin can be detected from whole blood using the portable enzyme‐linked immunosorbent assay (ELISA) system. Multiple layers can be realized for effective space utilization and creating a three‐dimensional (3‐D) chaotic mixer. In addition, external materials such as membranes can be incorporated into the device as components. Individual components that were necessary to perform these steps were characterized, and their mutual compatibility is also discussed.
Mole Fraction Control of Poly([R]‐3‐hydroxybutyrate‐co‐3‐hydroxyvalerate) (PHB/HV) Synthesized by Paracoccus denitrificans
Authors: Mothes G. , Ackermann J.‐U. , Babel W.
Published: June 2004

Different substrate mixtures of acetic acid and valeric acid were used to synthesize copolymers of poly([R]‐3‐hydroxybutyrate‐co‐3‐hydroxyvalerate) (PHB/HV) with Paracoccus denitrificans under N‐limited conditions. A correlation between the substrate ratio and HV content was found in batch experiments, which seemed to be suitable to produce a number of defined copolymers. In fed‐batch fermentation, such correlation could only be found with carbon substrate mixtures of very restricted composition. Due to the individual substrate consumption rates with this technique, a polymer with 16.5 mol.‐% HV content [w/w] could be reproducibly synthesized. However, under N‐limited chemostatic cultivation conditions it was possible to produce a spectrum of definitely composed copolymers (3.0 %–46.3 mol.‐% HV) from different mixtures of acetic acid and valeric acid.
Membrane Inlet Mass Spectrometry for the on‐line Measurement of Metabolic Fluxes: Case Lysine‐Production by Corynebacterium glutamicum
Authors: Yang T.H. , Wittmann C. , Heinzle E.
Published: June 2004

A miniaturized reactor system with on‐line measurement of respiration rates by membrane inlet mass spectrometry was applied for the on‐line metabolic flux analysis at different phases of a 1.2 L batch culture of lysine‐producing Corynebacterium glutamicum. For this purpose, cells taken from the batch culture were transferred into the 12 mL mini reactor, and incubated for 15 min with [1‐18O]glucose. Quantification of oxygen uptake rate and CO2 mass isotopomer production rates in combination with a simple metabolic model allowed the estimation of the flux partitioning ratio between the pentose phosphate pathway and glycolysis during the process. The relative flux into the pentose pathway increased during growth, and reached maxima at 11 and 17 h cultivation time coinciding with maxima of the differential lysine yield. The developed system is a promising tool for determination of metabolic flux dynamics in industrially relevant batch and fed‐batch cultures.
Physicochemical Conditioning of Dredged Heavy Metal‐Polluted Sediment in Suspension
Authors: Löser C. , Zehnsdorf A. , Voigt K. , Seidel H.
Published: June 2004

The remediation of heavy metal‐polluted aquatic sediment by solid‐bed bioleaching requires a material well permeable to air and water. Freshly dredged sediment is nearly impermeable and needs previous conditioning to make it suitable for solid‐bed leaching. This conditioning – in practice carried out by planting sediment packages with helophytes – comprises water removal by evapotranspiration, abiotic and microbial oxidation of sediment‐borne reduced compounds, acidification, as well as structural changes improving the sediment permeability. The rate of this process seems to be limited by the transport of oxygen into the sediment bed. For a better understanding of the physicochemical processes occurring during conditioning, sediment oxidation was studied in a stirred suspension to minimize transport limitations. Freshly dredged, silty, anoxic, heavy metal‐polluted sediment from the Weisse Elster River (Germany) was suspended in water and then continuously stirred and aerated at 20 °C. Aerobic conditions appeared within a few hours. The redox potential increased from – 400 to + 220 mV, at first very quickly and later more slowly. Sediment‐borne inorganic sulfur compounds were oxidized to sulfate (S0mainly within two days and sulfide within ten days), which reduced the pH from 7.2 to 5.9. A successive oxidation of FeS to Fe(II) sulfate, the oxidation of Fe(II) to Fe(III) followed by Fe(III) oxyhydrate formation caused the dissolved Fe to sharply increase and thereafter rapidly decrease. Ammonium was completely oxidized in a nitrification process to form nitrate, further decreasing the pH to 5.5. The acidification increased the solubility of Mn, Zn, Mg, Ca, and K. The increase in dissolved Mn rules out any oxidation of Mn(II) to Mn(IV) since Mn(IV) would have been insoluble under the prevailing pH and redox conditions. Sediment oxidation did not proceed in a well‐defined, redox‐potential‐directed order, but individual (partly microbially) oxidation processes superimposed each other. Physicochemical conditioning of suspended sediment was completed after 20 days while conditioning in a solid bed would require months or even years. These different rates result from transport limitations in the solid bed. Sediment conditioning in a solid bed could therefore possibly be accelerated by prior sediment aeration.
Data Mining for Bioprocess Optimization
Authors: Rommel S. , Schuppert A.
Published: June 2004

Although developed for completely different applications, the great technological potential of data analysis methods called “data mining” has increasingly been realized as a method for efficiently analyzing potentials for optimization and for troubleshooting within many application areas of process, technology. This paper presents the successful application of data mining methods for the optimization of a fermentation process, and discusses diverse characteristics of data mining for biological processes. For the optimization of biological processes a huge amount of possibly relevant process parameters exist. Those input variables can be parameters from devices as well as process control parameters. The main challenge of such optimizations is to robustly identify relevant combinations of parameters among a huge amount of process parameters. For the underlying process we found with the application of data mining methods, that the moment a special carbohydrate component is added has a strong impact on the formation of secondary components. The yield could also be increased by using 2 m3 fermentors instead of 1 m3 fermentors.