bluuebunny/crossref_metadata_2025 huggingface dataset:
Seehunde unterscheiden Freund und Feind
Authors: Irsch Wilhelm
Published: June 2004

Dass sich Wale über große Distanzen unter Wasser verständigen können, ist durch eindrucksvolle Tondokumente belegt. Besonders interessant ist, dass einige Meeressäuger diese Laute offenbar durchaus interpretieren können, was nun zumindest für Seehunde (Phoca vitulina) nachgewiesen wurde.
Nanosensoren für Messungen in lebenden Zellen
Authors: Brennicke Axel
Published: June 2004

Bisher war es schwierig, wenn nicht unmöglich, den Stoffwechsel in lebenden Zellen zu beobachten. Jetzt haben Wissenschaftler von der Universität Tübingen ein neues Konzept für Nanosensoren entwickelt, die in Zellen Konzentrationsänderungen einzelner Metabolite exakt anzeigen können.
Moose: Klein, grün, stark
Authors: Frahm Jan‐Peter
Published: June 2004

Seit über 20 Jahren galt das Lebermoos Notothylas orbicularis als verschollen. In Europa waren in den letzten hundert Jahren überhaupt nur acht Funde gemeldet worden, bis ein Botaniker südlich des Vogelbergs 1981 mehrere Pflanzen entdeckte. Einer Gruppe von Wissenschaftlern gelang es nun, die winzige Pflanze auf einem hessischen Stoppelacker wiederzufinden. Der Hintergrund für diese aufwändige Suchaktion nach einer bescheidenen Pflanze: N. orbicularisist eine von 26 Moosarten, die von der Europäischen Union unter Schutz gestellt worden sind. Dass Orchideen, Falken oder Biber geschützt werden, mag ja noch einleuchtend sein, aber warum stellt man Moose unter Naturschutz?
Toxicokinetic assessment of methylphenidate (Ritalin®) enantiomers in pregnant rats and rabbits
Authors: Bakhtiar Ray , Tse Francis L. S.
Published: June 2004

Ritalin® or methylphenidate (MPH) is prescribed for the treatment of attention deﬁcit hyperactivity disorder (ADHD) and narcolepsy. The present report describes the determination of plasma concentrations of d‐threo‐ and l‐threo‐enantiomers of MPH in toxicokinetic (TK) studies in pregnant Wistar Hannover rats and New Zealand white rabbits following repeated daily oral dosing of d,l‐MPH (racemate). A previously reported chiral liquid chromatography tandem mass spectrometric (LC‐MS/MS) method with a lower limit of quantiﬁcation (LLOQ) of 1.09 ng/mL was utilized. Oral (gavage) doses of 7, 25 and 75 mg/kg/day of racemic MPH were selected for the rat study. An over‐proportional increase in exposure was observed with increasing doses of MPH racemate, the effect being more profound with the d‐ than the l‐enantiomer. In contrast, Cmax values of both enantiomers were approximately proportional to the dose. Oral (gavage) doses of 20, 60 and 200 mg/kg were selected for the rabbit study. In general, for the d‐isomer, an over‐proportional increase in exposure was observed with increasing doses of MPH racemate. Conversely, for the l‐isomer, a slight under‐proportionality was detected in exposure with increasing doses of d,l‐MPH. For mean Cmax, while l‐isomer exhibited dose proportionality with increasing doses of MPH racemate, the d‐isomer appeared to be over‐proportional. Herein, the experimental design and observed TK parameters in each study are presented. Copyright © 2004 John Wiley & Sons, Ltd.
A method for determination of dimethyl benzoylphenyl urea (BPU) in human plasma by using LC/UV
Authors: Rudek Michelle A. , Zabelina Yelena , Zhao Ming , Wolff Antonio C. , Baker Sharyn D.
Published: June 2004

Dimethyl benzoylphenyl urea (BPU) inhibited tubulin polymerization, caused microtubule depolymerization in vitro and demonstrated activity against solid tumors. BPU is being tested in phase I clinical trials. A rapid and speciﬁc method using LC/UV has been developed for quantitation of BPU in human heparin‐containing plasma to perform pharmacokinetic and pharmacodynamic studies. BPU is extracted from plasma into acetonitrile:n‐butyl‐chloride using paclitaxel as the internal standard and separated on a Waters Symmetry C18 (3.9 × 150 mm, 5 µm) column with acetonitrile–water mobile phase (70:30, v/v) using isocratic ﬂow at 1 mL/min for a run time of 5 min. Ultraviolet detection was utilized and performed at 225 nm for BPU and paclitaxel. The retention times were 1.9 min for paclitaxel and 4.1 min for BPU. Calibration curves were generated over the range of 0.01–10 µg/mL with coefﬁcient of determination of >0.99. The values for within‐day and between‐day precision were ≤17.0% at the LLOQ and ≤7.4% at the low, medium and high quality controls; accuracy was ±5.4%. Following administration of BPU 320 mg as a weekly oral dose to a patient with advanced solid tumor malignancies, the maximum plasma concentration was 2 µg/mL and concentrations were quantiﬁable up to 168 h after administration. The lower limit of quantitation of 0.01 µg/mL allows for successful measurement of plasma concentrations in patients. Copyright © 2004 John Wiley & Sons, Ltd.
The bioequivalence study of baclofen and lioresal tablets using capillary electrophoresis
Authors: Kowalski Piotr , Chmielewska Aleksandra , Konieczna Lucyna , Olȩdzka Ilona , Zarzycki Paweł K. , Lamparczyk Henryk
Published: June 2004

A simple and robust analytical method for rapid separation and sensitive quantiﬁcation of baclofen in human plasma by capillary electrophoresis technique was developed. Electrophoretic separation was optimized and successfully performed using simple sodium tetraborate aqueous solution. Observed detection limit in biological material was 10 ng. Using UV detection at 200 nm excellent linearity (r = 0.999) was observed over the concentration range from 0.025 to 1.0 µg mL−1. The described method has been validated and applied to the quantitative determination of baclofen in human plasma. The bioavailability of Baclofen (Polpharma) and Lioresal (Novartis) in 18 healthy volunteers was investigated. The results indicate bioequivalence of the reference and Baclofen preparations. Copyright © 2003 John Wiley & Sons, Ltd.
Simultaneous determination of four bufadienolides in human liver by high‐performance liquid chromatography
Authors: Wang Zhaohong , Wen Jiao , Zhang Jizong , Ye Min , Guo Dean
Published: June 2004

A high‐performance liquid chromatographic method for the simultaneous quantitation of four bufadienolides—cinobufotalin, bufalin, cinobufagin and resibufogenin—in human liver was investigated. The procedure involved solid phase extraction of human liver with an Oasis®HLB cartridge coupled with reversed‐phase HPLC and photodiode array detection. Recoveries obtained from spiked liver for the bufadienolides were better than 70%. The linearity was studied up to 1.2 mg/kg and the detection limits of the method were 0.4 ng for cinobufotalin and bufalin and 0.5 ng for cinobufagin and resibufogenin. The developed method was successfully applied to a lethal poisoning case. Copyright © 2004 John Wiley & Sons, Ltd.
Dangerous sports and recreational drug‐use: rationalizing and contextualizing risk
Authors: Larkin Michael , Griffiths Mark D.
Published: June 2004

This article reports upon the Interpretative Phenomenological Analysis (IPA) of a small number of semi‐structured interviews, conducted with persons engaging in either recreational drug‐use (primarily identified here as Ecstasy‐users) or dangerous sports (primarily identified here as bungee‐jumpers). Our analysis focuses upon the manner in which these participants make sense of their initiation and maintenance experiences, and the means by which they understand and make sense of risk. In particular, we draw attention to the distinctions between our participants' rational and contextual reconstructions of risky decisions. These distinctions indicate that our participants are able to draw upon a complex cultural and relational understanding of risk and pleasure, and are thus able to deal quite effectively with the contradictory experience of taking ‘non‐volitional’ action. This exploration of persons' strategies for displacing agency in relation to potentially negative outcomes may have implications for research and practice in related areas. Copyright © 2004 John Wiley & Sons, Ltd.
Identifying violence among women patients attending family practices: the role of research in community change
Authors: Romito Patrizia , de Marchi Margherita , Turan Janet Molzan , Bottaretto Rosa Ciociano , Tavi Michela
Published: June 2004

Violence against women has serious consequences. Although victims use health facilities more frequently than others, violence is still not recognized in most services and in the larger community. This study had three aims: (1) to estimate the prevalence of violence among women patients in primary care, (2) to evaluate the feasibility of asking all women about violence, and (3) to make violence visible, and thereby initiate a process of professional and community change on the issue of violence against women. The study was carried out in a small Italian town, at the initiative of a local family doctor. We conducted a cross‐sectional survey among patients of six family practices and 444 women responded to a self‐administrated questionnaire. Five per cent of respondents experienced physical or sexual violence in the last year, and 25% had experienced it in the past. Nineteen per cent had experienced psychological violence in the last 12 months. Risk factors for current violence were: younger age, being pregnant or with young children, being separated or divorced, or lack of stable employment. Most women were in favour of being asked about violence by their doctor.

The study's results were disseminated in public meetings, with good press coverage. This resulted in a dramatic increase in the visibility of victims of violence, the development of a training course for health professionals, and the creation of the first women's group in the town. Along with advocacy work, the group has prepared a booklet on violence addressing women, and is now raising funds to start an ‘anti‐violence’ telephone line. Overall, the study has become a tool for change within the health services and the community. Copyright © 2004 John Wiley & Sons, Ltd.
The role of informal social support in needs assessment: proposal and application of a model to assess immigrants' needs in the south of Spain
Authors: Hernández‐plaza S. , Pozo C. , Alonso‐Morillejo E.
Published: June 2004

Needs assessment models have been generally focused on the identification and prioritization of needs, analysing formal resources available in the community as possible solutions for existing problems. These kinds of models have assumed that formal services are the primary source of support for individuals in need. However, a great deal of the investigations in the field of Social Psychology have shown that the main source of help and support when facing a problem is not formal organizations, but people's own informal networks. In this article, we therefore propose a needs assessment model that emphasizes the importance of analysing both formal and informal social resources. The application of this model to assess Moroccan immigrants' needs in the south of Spain shows the anticipated low level of utilization of formal services and programmes, one that contrasts with the high use of informal networks as an essential source of social support for this group of immigrants. These results reveal the limitations of traditional needs assessment models, and the importance of incorporating the analysis of informal social support as a key resource for need satisfaction, particularly in the case of immigrant populations. Copyright © 2004 John Wiley & Sons, Ltd.
Is domestic violence a gender issue? Views from a British city1
Authors: Nicolson Paula , Wilson Richard
Published: June 2004

Domestic violence involves the abuse, whether emotional, physical, sexual and/or economic, of one or more family (or ex‐family) members by another family member within the home or wider domestic context. It is typically associated with increasing entrapment, injury, medical complaints, psycho‐social problems and (sometimes) unsuccessful help‐seeking. Research evidence demonstrates that domestic abuse is prolific, prolonged, impacts physically, emotionally and economically upon women and children in particular, over the long‐term including well after they are ‘safe’ from the perpetrator. Furthermore, such abuse is widespread and happens all over the world. The findings reported here are from an observational population survey conducted in one British city to assess awareness of domestic violence. While there appears to be a broadly held and well‐informed definition of what actions constitute domestic violence and why it occurs, there are striking differences in perspective concerning public awareness of the frequency of domestic violence and knowledge of its importance as a safety issue indicating that it is still not seen generally as a serious social problem. Copyright © 2004 John Wiley & Sons, Ltd.
Two 3D Supramolecular Polymers Constructed from an Amino Acid and a High‐Nuclear Ln6Cu24 Cluster Node
Authors: Zhang Jian‐Jun , Sheng Tian‐Lu , Hu Sheng‐Min , Xia Sheng‐Qing , Leibeling Guido , Meyer Franc , Fu Zhi‐Yong , Chen Ling , Fu Rui‐Biao , Wu Xin‐Tao
Published: June 2004

The first successful attempt to construct 3D supramolecular frameworks with high‐nuclear 3d–4f heterometallic clusters as a node is reported. The self‐assembly of Ln3+, Cu2+ and amino acid in solution leads to the formation of two polymers, 35‐nuclear complex {Sm6Cu29} 1 with a primitive cubic net‐like structure and 36‐nuclear complex {Nd6Cu30} 2 with a face‐centred cubic network type structure. Glycine and L‐proline, respectively, were used as ligands. It should be noted that 2 has a chiral framework. X‐ray structure analyses show that 1 crystallizes in the triclinic P$\bar 1$ space group (a=19.6451(8), b=20.4682(8), c=20.7046(8) Å, α=89.453(1), β=66.290(1), γ=68.572(1)°, V=7003.0(5) Å3 and Z=1) and 2 belongs to the cubic P2(1)3 space group (a=b=c=32.4341(3) Å, V=34 119.7(5) Å3 and Z=4). Both complexes utilize Ln6Cu24 octahedral clusters as nodes and trans‐Cu(amino acid)2 groups as bridges. Electrical conductivity measurements reveal that both polymers behave as semiconductors.
The Effect of Fluorination: A Crystallographic and Computational Study of Mesogenic Alkyl 4‐[2‐(Perfluorooctyl)ethoxy]benzoates
Authors: Yano Megumi , Taketsugu Tetsuya , Hori Kayako , Okamoto Hiroaki , Takenaka Shunsuke
Published: June 2004

The series of alkyl 4‐[2‐(perfluorooctyl)ethoxy]benzoates (F8‐n) shows a systematic change of crystal structures depending on the length of the alkyl chain: separate packing of perfluorooctyl (Rf) and alkyl (Rh) chains from each other for shorter (n=2) and longer (n=11) members, alternate packing of Rf and Rh chains for middle (n=6,7) members, and an intermediate type of packing for n=4. Semiempirical MO calculations show slightly repulsive interactions between the Rf chains, and attractive ones between Rf and Rh chains and between Rh and the core of a molecular pair. It is concluded that fluorination determines the molecular shape of the crystal structures by making the chain rigid. It is confirmed that the interactions between Rf chains are small compared with those between other moieties and that they are forced to aggregate owing to the exclusion from other moieties. Thus, the effect is dependent on the geometries and intermolecular interactions of the other moieties.
Silsesquioxane Models for Silica Surface Silanol Sites with Adjacent Siloxide Functionalites and Olefin Polymerization Catalysts Thereof
Authors: Duchateau Robbert , Dijkstra Tessa W. , van Santen Rutger A. , Yap Glenn P. A.
Published: June 2004

Incompletely condensed silsesquioxanes of the type R7Si7O9(O{SiR′2O}n)OH (R = c‐C5H9, c‐C6H11; R′ = Me, Ph; n = 1–4), containing a siloxane ring of variable size and rigidity and a remaining silanol, are described. Compared with a truly isolated silanol [R7Si8O12(OH)], solution and solid state FT‐IR spectra of these compounds show a $\tilde \nu $OH shift of approximately 150 cm−1 to lower frequency, which suggests hydrogen bonding of the silanol with the internal siloxane ring. In agreement with this, the relative ion pair acidities of the silanols in THF, determined by UV/Vis, were lowered by 0.8–1.2 compared with a truly isolated silanol. Density functional theory (DFT) calculations on these systems confirm the presence of intramolecular hydrogen bonding. Possible interaction of the silyl ether functionalities with Lewis acidic metal sites was studied for the neutral gallium‐substituted systems and cationic titanium silsesquioxane complexes, models for an immobilized titanium olefin polymerization catalyst. The electron donating capability of the siloxide functionalities in 1, 6, and 7 is not sufficient to satisfy the electron deficiency of the corresponding gallium silsesquioxane species, which form dimeric structures with a bridging siloxide unit rather than Lewis base adducts with coordinated siloxide functionalities. Metallation of 1 and 4 with [Cp′′Ti(CH2Ph)3] (Cp′′ = η5‐1,3‐C5H3(SiMe3)2) in a 1:1 ratio afforded monomeric titanasilsesquioxanes. To probe the effect of the neighboring siloxane ring on the highly Lewis acidic titanium center, the catalytic activities of the corresponding cationic half‐sandwich complexes were tested in 1‐hexene polymerization. Compared with the catalyst system based on the isolated silanol [(c‐C5H9)7Si8O12OH], the presence of a neighboring siloxane ring causes considerable retardation of the polymerization process but also improves the stability of the catalyst.
Synthesis and Crystal Structure of the Alkaline‐Earth Thallates MnTl2O3+n (M: Ca, Sr).
Authors: Berastegui P. , Eriksson S. , Hull S. , Garcia Garcia F. J. , Eriksen J.
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
The Er—Ni—B System.
Authors: Chaban N. F. , Veremchuk I. V. , Kuz'ma Yu. B.
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
3‐Dimensional Methylammonium and Ammonium Templated Lithiumberyllofluoro Frameworks.
Authors: Gerrard Lee A. , Weller Mark T.
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Solvothermal Syntheses, Crystal Structures, and Thermal Properties of New Manganese Thioantimonates(III): The First Example of the Thermal Transformation of an Amine‐Rich Thioantimonate into an Amine‐Poorer Thioantimonate.
Authors: Schaefer Michael , Naether Christian , Lehnert Nicolai , Bensch Wolfgang
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
The Crystal Growth and Characterization of the Lanthanide‐Containing Double Perovskites Ln2NaIrO6 (Ln: La, Pr, Nd).
Authors: Davis Matthew J. , Mugavero Samuel J. III , Glab Katarzyna I. , Smith Mark D. , zur Loye Hans‐Conrad
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Hydroformylation of Mixed Octenes Using Rhodium—Bulky Phosphonite Complexes with Excellent Catalytic Activity and Stability.
Authors: Jeon Jong‐Ki , Park Young‐Kwon , Kim Ji Man
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Phosphane‐Free Rhodium Catalyst in an Anionic Micellar System for [4 + 2] Annulation of Dienynes.
Authors: Motoda Dai , Kinoshita Hidenori , Shinokubo Hiroshi , Oshima Koichiro
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
SmI2‐Mediated Reduction of γ,γ‐Difluoro‐α,β‐enoates with Application to the Synthesis of Functionalized (Z)‐Fluoroalkene‐Type Dipeptide Isosteres.
Authors: Otaka Akira , Watanabe Junko , Yukimasa Akira , Sasaki Yoshikazu , Watanabe Hideaki , Kinoshita Takayoshi , Oishi Shinya , Tamamura Hirokazu , Fujii Nobutaka
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Syntheses and in vitro Antitumor Activity of 3‐Amino‐N‐(4‐chlorobenzenesulfonyl)guanidine Derivatives Containing N′‐Arylidene Moiety.
Authors: Slawinski J. , Bednarski P. , Reszka P.
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
The Stereoselective Synthesis of Alkenyl‐β‐lactams by Palladium‐Catalyzed [2 + 2] Carbonylative Cycloaddition.
Authors: Troisi Luigino , De Vitis Luisella , Granito Catia , Epifani Erbana
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
N‐Acyl‐2‐benzoxazolinones in Titanium‐Mediated Aldol Reactions.
Authors: Burlingame Mark A. , Mendoza Esteban , Ashley Gary W.
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Synthesis of New Substituted 2,3‐Dihydro‐1,4‐dioxin‐2‐ones and 1,4‐Dioxan‐2‐ones.
Authors: Akopyan S. M. , Khachatryan A. G.
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Microwave‐Assisted Organic Synthesis Using Minivials to Optimize and Expedite the Synthesis of Diverse Purine Libraries.
Authors: Takvorian Amy G. , Combs Andrew P.
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Arylselenovinyl Sulfones. Part 2. Addition of Benzeneselenols to Aryl Ethynyl Sulfones.
Authors: Mannafov T. G. , Berdnikov E. A.
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Glycolamide Esters of 4‐Biphenylacetic Acid as Potential Prodrugs‐Synthetic and Spectral Studies.
Authors: Sharma Pritam Dev , Singh Kamal Jit , Gupta Shivali , Chandiran Senthilkumar
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
From Real World Catalysis to Surface Science and Back: Can Nanoscience Help to Bridge the Gap?
Authors: Freund H.‐J. , Rupprechter G. , Baeumer M. , Risse Th. , Ernst N. , Libuda J.
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Tin(II) and Tin(IV) Complexes with Nitrogen Ligands: Recent Developments
Authors: Singh Ajai K. , Bhandari Sonali
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Neighboring Group Effect of Heteroaromatic Rings
Authors: Kobayashi Tomoshige , Tsuzuki Takeo
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Novel approach for the introduction of a C‐1 oxygenated group on the decalin skeleton: first asymmetric total synthesis of 1S,6S‐dihydroxy‐eudesm‐3‐ene
Authors: Zheng Guojun , Chen Jinchun , Fang Lijing , Guan Yukun , Li Yulin
Published: June 2004

This paper describes a novel approach for the introduction of a C‐1 hydroxyl on the decalin ring system, starting from (−)‐carvone. Utilizing the substratecontrolled Mukaiyama aldol reaction and alkaline cyclization as key steps, the C‐1 oxygenated decalin eudesmane skeleton 2′ and its four isomers were synthesized efficiently. Furthermore, X‐ray structural analysis showed that the claimed structure for the natural product is incorrect. Chirality 16:483–485, 2004. © 2004 Wiley‐Liss, Inc.
Kinetik der isomerisierenden Hydroformylierung von trans‐4‐Octen
Authors: Behr A. , Obst D. , Schulte C.
Published: June 2004

No abstracts.
Bewertungskriterien für die Selbstentzündung von Schüttgütern, Stäuben und porösen Feststoffen
Authors: Krause U. , Lohrer C. , Schmidt M.
Published: June 2004

No abstracts.
Differenzialkreislaufreaktoren zur Gewinnung reaktionskinetischer Daten für festbettkatalytische Reaktionen – Teil 1: Ausführung und Einsatz
Authors: Hesselbarth B. , Adler R.
Published: June 2004

No abstracts.
Explosionsgrenzen von polynären Brenngasgemischen in Luft
Authors: Klaubert M.
Published: June 2004

No abstracts.
Molekulardynamische Simulationen zum Einfluss polycyclischer aromatischer Kohlenwasserstoffe (PAK) auf Phospholipid‐Membranen
Authors: Hoff B. , Herrenbauer M. , Posten C. , Tieleman D. P.
Published: June 2004

No abstracts.
Verteilung von Naturstoffen auf koexistierende Flüssigphasen in Systemen bestehend aus Wasser, einem organischen Lösungsmittel und (nahekritischem) Ethen
Authors: Tuma D. , Freitag J. , Ulanowa T. W. , Maurer G.
Published: June 2004

No abstracts.
Dynamische Messung der Dicke und der mechanischen Eigenschaften von weichen Ablagerungen
Authors: Chew J. Y. M. , Paterson W. R. , Wilson D. I. , Höfling V. , Augustin W.
Published: June 2004

No abstracts.
Vorhersage thermophysikalischer Eigenschaften realer Fluide mit molekularen Modellen
Authors: Stoll J. , Vrabec J. , Hasse H.
Published: June 2004

No abstracts.
Systematische Modularisierung der Simulation mehrskaliger verfahrenstechnischer Prozesse
Authors: Bauer M. , Kolios G. , Eigenberger G.
Published: June 2004

No abstracts.
Explosionsgrenzen von Radiolysegas/Wasserdampf‐Gemischen
Authors: Schröder V. , Beckmann‐Kluge M. , Becker F.
Published: June 2004

No abstracts.
Rohrleitungselemente aus textilverstärkten Verbundwerkstoffen für den chemischen Apparatebau
Authors: Hufenbach W. , Kroll L. , Böhm R. , Langkamp A.
Published: June 2004

No abstracts.
Prozessentwicklung in der Biotechnologie – Ein Rückblick
Authors: Schügerl K.
Published: June 2004

Die Übersicht behandelt einige Probleme der Entwicklung biotechnologischer Prozesse und stellt ihre Lösung an Beispielen dar, die in Kooperation mit der Industrie bearbeitet wurden. Diese Prozesse umfassen die Produktion von Restriktionsendonuclease EcoRI durch rekombinantes E. coli, Penicillin V durch Penicillium chrysogenum, Xylanase durch Aspergillus awamori, Cephalosporin C durch Acremonium chrysogenum, Erythrit durch Moniliella tomentosa var pollinis und alkalische Serin‐Protease durch Bacillus licheniformis. Hierbei werden insbesondere die praktischen Aspekte der Produktentwicklung hervorgehoben.
Adapting the Lung Cancer Symptom Scale (LCSS) to mesothelioma
Authors: Hollen Patricia J. , Gralla Richard J. , Liepa Astra M. , Symanowski James T. , Rusthoven James J.
Published: June 2004

BACKGROUND

The underpinning conceptual model for the Lung Cancer Symptom Scale (LCSS), an instrument used to assess health‐related quality of life in patients with lung cancer, has been described elsewhere. The patient‐rated scale of the LCSS was modified slightly for patients with mesothelioma (LCSS‐Meso), because no other mesothelioma‐specific instrument was available.

METHODS

In the current methodologic study, the authors tested the conceptual model for the LCSS‐Meso. Chemotherapy‐naive patients with unresectable malignant pleural mesothelioma who were participating in two clinical trials of pemetrexed (ALIMTA; Eli Lilly, Indianapolis, IN) completed the scale twice before the start of therapy and once weekly during the trials. Three time points were analyzed: baseline, Day 40, and Day 82. Poisson regression was used to determine the contribution of predictive factors (i.e., symptoms) to the summary items (symptom distress, activity level, and global quality of life).

RESULTS

The model was tested in 495 patients who had malignant pleural mesothelioma. More than 85% of patients reported pain, dyspnea, fatigue, and appetite loss. Pain, dyspnea, and fatigue were significant and stable predictors for all summary items; however, pain had a significant effect on global quality of life only through Day 40. Appetite loss was a significant and stable predictor of activity level and global quality of life. The explained variance for the model was 39–55%.

CONCLUSIONS

Further support for the content validity of the LCSS‐Meso was obtained, as nearly all patients validated that the symptoms described in the scale captured their disease experience. The only exception was the hemoptysis item, which was removed based on the current large normative data set. Support for the construct validity of the LCSS‐Meso also was obtained. For both mesothelioma and lung cancer, the majority of factors within the LCSS model are relevant and have the expected amount of variability. These findings support the use of the LCSS as a sensitive instrument for serial measurement during clinical trials involving patients with lung malignancies. Cancer 2004. © 2004 American Cancer Society.
The risk of venous thromboembolic disease associated with adjuvant hormone therapy for breast carcinoma
Authors: Deitcher Steven R. , Gomes Marcelo P. V.
Published: June 2004

BACKGROUND

Tamoxifen therapy for patients with breast carcinoma is perceived as an independent risk factor for venous thromboembolic events (VTE), but the risk associated with other adjuvant therapies is less well recognized.

METHODS

The authors conducted a computerized PubMed literature search for English‐language articles published between January 1966 and December 2003. Studies were analyzed with regard to trial design, breast carcinoma staging, adjuvant agent, definition of VTE outcomes, method of VTE case ascertainment, and the presence of concomitant VTE risk factors.

RESULTS

Accurate determination of VTE rates was impaired by the universal lack of routine assessments for asymptomatic VTE. Therefore, only the risk of symptomatic VTE could be derived. The risk of VTE was increased twofold to threefold during tamoxifen or raloxifene use for breast carcinoma chemoprevention. It remains unknown whether the risk is increased further in women with inherited hypercoagulable states. In the setting of early‐stage breast carcinoma, the risk of VTE is increased both with tamoxifen use and anastrozole use. Such risk appeared to be lower, albeit not negligible, with anastrozole. Significant methodologic limitations of all available studies in women with advanced‐stage breast carcinoma precluded determination of the true VTE risk associated with different adjuvant hormonal agents and made it nearly impossible to compare the risk between different drugs.

CONCLUSIONS

All agents used for breast carcinoma chemoprevention and adjuvant therapy appear to increase the risk of VTE. Available data were insufficient to support any assumptions that newer hormonal forms of hormone manipulation are safer than tamoxifen in women with advanced breast carcinoma. Cancer 2004. © 2004 American Cancer Society.
Oral capecitabine for the treatment of hepatocellular carcinoma, cholangiocarcinoma, and gallbladder carcinoma
Authors: Patt Yehuda Z. , Hassan Manal M. , Aguayo Alvaro , Nooka Ajay K. , Lozano Richard D. , Curley Steven A. , Vauthey Jean‐Nicolas , Ellis Lee M. , Schnirer Isac I. , Wolff Robert A. , Charnsangavej Chusilp , Brown Thomas D.
Published: June 2004

BACKGROUND

The goal of the current study was to evaluate the efficacy and toxicity of capecitabine in patients with nonresectable hepatobiliary carcinoma.

METHODS

The authors performed a retrospective analysis of all patients with hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), or gallbladder carcinoma (GBC) who were ever treated with oral capecitabine. The medical records of 116 patients with hepatobiliary carcinoma who were treated at The University of Texas M. D. Anderson Cancer Center (Houston, TX) between July 1998 and March 1999 were reviewed.

RESULTS

A total of 63 patients were treated with capecitabine (37 with HCC, 18 with CCA, 8 with GBC). Capecitabine 1000 mg/m2 was administered twice daily for 14 days. Treatment was repeated every 21 days. Each patient received 1–15 treatment cycles. Nine patients (14%)—11% of patients with HCC, 6% of patients with CCA, and 50% of patients with GBC—had either a complete response (CR) or a partial response. A CR was radiologically confirmed in one patient with HCC and in two patients with GBC. The median survival times were 10.1 months (95% confidence interval [CI], 4.5–15.7 months) for patients with HCC, 8.1 months (95% CI, 7.4–8.9 months) for patients with CCA, and 9.9 months (95% CI, 4.4–15.4 months) for patients with GBC. The most common toxicity was hand‐foot syndrome (37%). Grade 3 thrombocytopenia occurred in 8% of patients with HCC. No other significant toxicities were observed. For all patients, response to treatment was positively correlated with survival and decline in tumor markers.

CONCLUSIONS

Capecitabine was found to be safe for patients with hepatobiliary carcinoma, including those with cirrhosis. The antitumor activity of single‐agent capecitabine was most pronounced in patients with GBC, was modest in patients with HCC, and was poor in patients with CCA. Cancer 2004. © 2004 American Cancer Society.
Synovial sarcoma: A retrospective analysis of 271 patients of all ages treated at a single institution
Authors: Ferrari Andrea , Gronchi Alessandro , Casanova Michela , Meazza Cristina , Gandola Lorenza , Collini Paola , Lozza Laura , Bertulli Rossella , Olmi Patrizia , Casali Paolo G.
Published: June 2004

BACKGROUND

The optimal treatment strategy for synovial sarcoma (SS) is subject to debate, and different strategies have been used for pediatric and adult patients. The current retrospective analysis examined a large group of patients of all ages who were treated at a single institution over a 30‐year period.

METHODS

The study included 271 patients who ranged in age from 5 years to 87 years; 255 had localized disease, which was macroscopically resected in 215 cases and deemed unresectable at diagnosis in 40 cases. Chemotherapy was administered to 41% of patients, corresponding to 76% of patients age ≤ 16 years and < 20% of older patients; 28% of patients with macroscopically resected disease received chemotherapy on an adjuvant basis.

RESULTS

The 5‐year event‐free survival rate for the study cohort as a whole was 37%, although this rate varied with age (66%, 40%, and 31% for patients age ≤ 16 years, 17–30 years, and > 30 years, respectively). Chemotherapy was used more commonly for children than for adults. Among patients with surgically resected disease, the 5‐year metastasis‐free survival (MFS) rate was 60% for those who were treated with chemotherapy and 48% for those who were not; the benefit associated with chemotherapy use appeared to be greatest for patients age ≥ 17 years who had tumors measuring > 5 cm (MFS, 47% [chemotherapy] vs. 27% [no chemotherapy]). In the subgroup of patients with measurable disease, the rate of tumor response to chemotherapy was approximately 48%.

CONCLUSIONS

Although the authors await more convincing proof of the efficacy of adjuvant chemotherapy in the treatment of adult soft tissue sarcoma, they recommend that patients with high‐risk SS (tumor size > 5 cm) be the first to be considered for this type of treatment. Cancer 2004. © 2004 American Cancer Society.
Biochemotherapy for melanoma
Authors: Margolin Kim A.
Published: June 2004

Understanding of the mechanisms underlying the activity and limitations of biochemotherapy remains inadequate. The design of new regimens should based on emerging knowledge regarding molecular mechanisms of oncogenesis, cancer cell proliferation and survival, and control apoptosis.

See also pages 596–603.
The prevalence of pituitary adenomas
Authors: Ezzat Shereen , Asa Sylvia L. , Couldwell William T. , Barr Charles E. , Dodge William E. , Vance Mary Lee , McCutcheon Ian E.
Published: June 2004

BACKGROUND

Pituitary adenomas display an array of hormonal and proliferative activity. Once primarily classified according to size (microadenomas, < 1 cm; macroadenomas, ≥ 1 cm), these tumors are now further classified according to immunohistochemistry and functional status. With these additional classifications in mind, the goals of the current study were to determine the prevalence of pituitary adenomas and to explore the clinical relevance of the findings.

METHODS

The authors conducted a metaanalysis of all existing English‐language articles in MEDLINE. They used the search string (pituitary adenoma or pituitary tumor) and prevalence and selected relevant autopsy and imaging evaluation studies for inclusion.

RESULTS

The authors found an overall estimated prevalence of pituitary adenomas of 16.7% (14.4% in autopsy studies and 22.5% in radiologic studies).

CONCLUSIONS

Given the high frequency of pituitary adenomas and their potential for causing clinical pathologies, the findings of the current study suggest that early diagnosis and treatment of pituitary adenomas should have far‐reaching benefits. Cancer 2004. © 2004 American Cancer Society.
Expression of calcium transporters in the retina of the tiger salamander (Ambystoma tigrinum)
Authors: Križaj David , Liu Xiaorong , Copenhagen David R.
Published: June 2004

Changes in intracellular calcium concentration, [Ca2+]i, modulate the flow of visual signals across all stages of processing in the retina, yet the identities of Ca2+ transporters responsible for these changes are still largely unknown. In the current study, the distribution of plasma membrane and intracellular Ca2+ transporters in the retina of tiger salamander, a model system for physiological studies of retinal function, was determined. Plasma membrane calcium ATPases (PMCAs), responsible for high‐affinity Ca2+ extrusion, were highly expressed in the salamander retina. PMCA isoforms 1, 2, and 4 were localized to photoreceptors, whereas the inner retina expressed all four isoforms. PMCA3 was expressed in a sparse population of amacrine and ganglion neurons, whereas PMCA2 was expressed in most amacrine and ganglion cells. Na+/Ca2+ exchangers, a high‐capacity Ca2+ extrusion system, were expressed in the outer plexiform layer and in a subset of inner nuclear and ganglion layer cells. Intracellular Ca2+ store transporters were also represented prominently. SERCA2a, a splice variant of the sarcoplasmic‐endoplasmic Ca2+ ATPase, was found mostly in photoreceptors, whereas SERCA2b was found in the majority of retinal neurons and in glial cells. The predominant endoplasmic reticulum (ER) Ca2+ channels in the salamander retina are represented by the isoform 2 of the IP3 receptor family and the isoform 2 of the ryanodine receptor family. These results indicate that Ca2+ transporters in the salamander retina are expressed in a cell type‐specific manner. J. Comp. Neurol. 475:463–480, 2004. © 2004 Wiley‐Liss, Inc.
Expression and regulation of an FMRFamide‐related neuropeptide gene family in Caenorhabditis elegans
Authors: Kim Kyuhyung , Li Chris
Published: June 2004

FMRFamide (Phe‐Met‐Arg‐Phe‐NH2) and related peptides (FaRPs) have been found throughout the animal kingdom, where they are involved in many behaviors. We previously identified 22 genes comprising the flp gene family that encodes FaRPs in Caenorhabditis elegans; in this paper we report the identification of another flp gene, flp‐23. As a first step toward determining their functional roles in C. elegans, we examined the cell‐specific expression pattern of the flp gene family. Of the 19 flp genes examined, each gene is expressed in a distinct set of cells; these cells include interneurons, motor neurons, and sensory neurons that are involved in multiple behaviors, as well as supporting cells, muscle cells, and epidermal cells. Several flp genes show sex‐specific expression patterns. Furthermore, we find that expression of two flp genes changes in response to the developmental state of the animal. Many neurons express multiple flp genes. To investigate how flp genes are regulated in different neuronal subtypes, we examined flp expression in a small, well‐defined subset of neurons, the mechanosensory neurons. Mutations in the unc‐86 and mec‐3 genes, which are necessary for the production and differentiation of the mechanosensory neurons, result in the complete loss of flp‐4, flp‐8, and flp‐20 expression in mechanosensory neurons. Collectively, these data indicate that members of the flp gene family are likely to influence multiple behaviors and that their regulation can be dependent on the developmental state of the organism. J. Comp. Neurol. 475:540–550, 2004. © 2004 Wiley‐Liss, Inc.
Form and function in the unique inner ear of a teleost: The silver perch (Bairdiella chrysoura)
Authors: Ramcharitar John Umar , Deng Xiaohong , Ketten Darlene , Popper Arthur N.
Published: June 2004

Members of the teleost family Sciaenidae show significant variation in inner ear and swim bladder morphology as well as in the relationship between the swim bladder and the inner ear. In the silver perch (Bairdiella chrysoura), a Stellifer‐group sciaenid, both the saccular and utricular otoliths are enlarged relative to those in other teleosts. Additionally, its swim bladder is two‐chambered, and the anterior chamber surrounds the otic capsule and terminates lateral to the saccules. Structure and function of the auditory system of the silver perch were explored by using gross dissections, scanning electron microscopy, CT scan reconstruction, and auditory brainstem response approach. Several morphological specializations of the auditory system of the silver perch were found, including expansion of the utricular and lagenar otoliths, close proximity between the saccules and the utricles, deeply grooved sulci on the saccular otoliths, two‐planar saccular sensory epithelia, and a unique orientation pattern of sensory hair cell ciliary bundles on the saccular sensory epithelium. It was determined that the silver perch can detect up to 4 kHz, with lowest auditory thresholds between 600 Hz and 1 kHz. Audition in the silver perch is comparable to that in the goldfish (Carassius auratus), a hearing “specialist.” The morphological specializations of the inner ear and swim bladder of the silver perch may be linked to its enhanced hearing capabilities. The findings of this study support the proposal that sciaenids are excellent model species for investigating structure–function relations in the teleost auditory system. J. Comp. Neurol. 475:531–539, 2004. © 2004 Wiley‐Liss, Inc.
The postsynaptic scaffold proteins ProSAP1/Shank2 and Homer1 are associated with glutamate receptor complexes at rat retinal synapses
Authors: Brandstätter Johann Helmut , Dick Oliver , Boeckers Tobias M.
Published: June 2004

The postsynaptic density (PSD) at glutamatergic synapses is a macromolecular complex of various molecules that organize the different glutamate receptors spatially and link them to their appropriate downstream signaling pathways and to the cytoskeleton. Recently, a new family of multidomain proteins called Shanks or ProSAPs (proline‐rich synapse‐associated proteins) has been identified. They are suggested to be central adaptor proteins of the PSD of glutamatergic synapses, bridging different types of glutamate receptor complexes. With immunocytochemistry and light and electron microscopy, we examined the cellular, synaptic, and postnatal developmental expression of ProSAP1/Shank2 at the synapses of rat retina. With double‐labeling experiments and confocal microscopy, we analyzed the association of ProSAP1/Shank2 with proteins specific for glutamatergic, glycinergic, and γ‐aminobutyric acid (GABA)ergic synapses and with proteins known to be involved in the structural and functional organization of PSDs containing N‐methyl‐D‐aspartate receptors [95‐kDa postsynaptic density protein (PSD‐95)], group I metabotropic glutamate receptors (Homer1), and α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionate (AMPA) receptors [glutamate receptor‐interacting protein (GRIP)]. ProSAP1/Shank2 was present postsynaptically at the glutamatergic ribbon synapses of photoreceptor and bipolar cells, and it was absent from glycinergic and GABAergic amacrine cell synapses. The double‐labeling experiments revealed a high rate of colocalization of ProSAP1/Shank2 with Homer1 and PSD‐95, and little colocalization with GRIP. These data suggest that ProSAP1/Shank2 acts as an organizer at PSDs of different glutamatergic retinal synapses. J. Comp. Neurol. 475:551–563, 2004. © 2004 Wiley‐Liss, Inc.
Changes in galanin immunoreactivity in rat lumbosacral spinal cord and dorsal root ganglia after spinal cord injury
Authors: Zvarova K. , Murray E. , Vizzard M.A.
Published: June 2004

Alterations in the expression of the neuropeptide galanin were examined in micturition reflex pathways 6 weeks after complete spinal cord transection (T8). In control animals, galanin expression was present in specific regions of the gray matter in the rostral lumbar and caudal lumbosacral spinal cord, including: (1) the dorsal commissure; (2) the superficial dorsal horn; (3) the regions of the intermediolateral cell column (L1–L2) and the sacral parasympathetic nucleus (L6–S1); and (4) the lateral collateral pathway in lumbosacral spinal segments. Densitometry analysis demonstrated significant increases (P ≤ 0.001) in galanin immunoreactivity (IR) in these regions of the S1 spinal cord after spinal cord injury (SCI). Changes in galanin‐IR were not observed at the L4–L6 segments except for an increase in galanin‐IR in the dorsal commissure in the L4 segment. In contrast, decreases in galanin‐IR were observed in the L1 segment. The number of galanin‐IR cells increased (P ≤ 0.001) in the L1 and S1 dorsal root ganglia (DRG) after SCI. In all DRG examined (L1, L2, L6, and S1), the percentage of bladder afferent cells expressing galanin‐IR significantly increased (4–19‐fold) after chronic SCI. In contrast, galanin expression in nerve fibers in the urinary bladder detrusor and urothelium was decreased or eliminated after SCI. Expression of the neurotrophic factors nerve growth factor (NGF) and brain‐derived neurotrophic factor (BDNF) was altered in the spinal cord after SCI. A significant increase in BDNF expression was present in spinal cord segments after SCI. In contrast, NGF expression was only increased in the spinal segments adjacent and rostral to the transection site (T7–T8), whereas spinal segments (T13–L1; L6–S1), distal to the transection site exhibited decreased NGF expression. Changes in galanin expression in micturition pathways after SCI may be mediated by changing neurotrophic factor expression, particularly BDNF. These changes may contribute to urinary bladder dysfunction after SCI. J. Comp. Neurol. 475:590–603, 2004. © 2004 Wiley‐Liss, Inc.
Cerebellar Purkinje cell loss in aging Hu‐Bcl‐2 transgenic mice
Authors: Zanjani Hadi , Lemaigre‐Dubreuil Y. , Tillakaratne Niranjala J.K. , Blokhin Andrei , McMahon Robert P. , Tobin Allan J. , Vogel Michael W. , Mariani Jean
Published: June 2004

The number of cerebellar Purkinje cells is increased by over 40% in young transgenic mice that overexpress a human Bcl‐2 transgene (Hu‐Bcl‐2). To determine whether the Bcl‐2‐mediated rescue of Purkinje cells persists through life, the numbers of Purkinje cells were estimated in 6‐, 12‐, 18‐, and 24‐month‐old Hu‐Bcl‐2 transgenic mice and age‐matched controls. In addition, the expression of four markers for Purkinje cell differentiation, calbindin (CaBP), the 67‐kDa isoform of glutamic acid decarboxylase (GAD67), γ‐aminobutyric acid transaminase (GABA‐T), and the NMDA‐R1 receptor subtype (NMDA‐NR1) was analyzed in 6‐month‐old Hu‐Bcl‐2 transgenics and controls to determine whether overexpression of Bcl‐2 and rescue from naturally occurring cell death affects the normal differentiation of Purkinje cells. The estimates of Purkinje cell numbers showed that the number of Purkinje cells in the Hu‐Bcl‐2 transgenics declines after 6 months to approach wild‐type values by 18 months. Although the exogenous human BCL‐2 is still expressed in Purkinje cells at 24 months, the expression levels of human BCL‐2 appear to decline significantly after 6 months, suggesting that survival of the supernumary Purkinje cells depends on the sustained overexpression of Bcl‐2. All the Purkinje cells in the Hu‐Bcl‐2 transgenic mice appeared to express normal levels of the differentiation markers analyzed so there was no evidence for a class of Purkinje cells that do not differentiate normally when rescued from naturally occurring cell death. J. Comp. Neurol. 475:481–492, 2004. © 2004 Wiley‐Liss, Inc.