bluuebunny/crossref_metadata_2025 huggingface dataset:
Ein neues Prinzip zur Darstellung höhergliedriger Ringsysteme, I. Mitteil.: Ringschluß‐Reaktionen bei Sulfonamiden des o‐Phenylendiamins
Authors: Stetter Hermann
Published: May 2007

Es wird ein neues Prinzip zur Darstellung höhergliedriger Ringsysteme beschrieben. Es beruht darauf, daß man von solchen offenkettigen Verbindungen ausgeht, bei denen eine Reaktion zwischen mehreren Molekülen, die zu Polykondensaten führt, aus sterischen Gründen unmöglich ist, während die Ringschluß‐Reaktion sterisch nicht behindert ist. Verbindungen, bei welchen diese sterischen Voraussetzungen erfüllt sind, wurden in den Sulfonamiden des o‐Phenylendiamins gefunden. Durch Kondensation mit α.ω‐Dihalogen‐Verhindungen konnten 7‐, 8‐, 9‐ und 10‐gliedrige Ringe ohne Anwendung des Verdünnungsprinzips dargestellt werden.
Die Molekülschwingungs‐Spektren des Naphthalins und seiner Derivate, I. Mitteil.: Darstellung deuterierter Naphthaline und ihre Raman‐Spektren
Authors: Goubeau Josef , Luther Horst , Feldmann Klaus , Brandes Günter
Published: May 2007

Es wird die Darstellung des Oktadeutero‐naphthalins und des Hexadeutero‐benzols sowie von partiell deuterierten Naphthalinen beschrieben; die Raman‐Spektren dieser Verbindungen werden angegeben.
Zur Strukturspezifität des Vitamins B1, VIII. Mitteilung
Authors: Dornow Alfred , Hargesheimer Alfred
Published: May 2007

Es werden einige Vitamin B1 Analoga und deren Antagonisten beschrieben.
Über einige Derivate des 2.6‐Lutidins
Authors: Mathes Wilhelm , Sauermilch Walter , Klein Theo
Published: May 2007

Es wird über Reaktionsprodukte der katalytischen Oxydation von 2.6‐Lutidin in der Gasphase berichtet, über Versuche zur Darstellung der Pyridin‐aldehyd‐(2)‐carbonsäure‐(6) und über die Cannizzaro‐Reaktion des Pyridin dialdehyds‐(2.6).
Zur Molekülasymmetrie des 4.5‐Dimethyl‐phenanthrens; gleichzeitig ein Beitrag zur metallorganisch geleiteten Synthese von Phenanthren‐Derivaten
Authors: Wittig Georg , Zimmermann Hans
Published: May 2007

Ringschlußoperationen bei optisch aktiven Diphenyl‐Derivaten führten zu optisch inaktivem 4.5‐Dimethyl‐phenanthrenchinon und 4.5‐Dimethyl‐phenanthren.
Notiz über die Identifizierung der Aldosen als deren β‐Phenyl‐äthyl‐mercaptale
Authors: Heweihi Zaki El
Published: May 2007

Es werden die bisher unbekannten β‐Phenyl‐äthyl‐mercaptale der Aldosen und ihre Additionsverbindungen mit Quecksilber (II)‐chlorid dargestellt.
Notiz über die Einwirkung von Jodwasserstoffsäure auf Dehydro‐ergosterylbenzoat‐peroxyd
Authors: Feit Peter
Published: May 2007

Die Bildung des Δ4.6.8.11.22‐Ergostapentaen‐3β‐ol‐benzoats bei der Einwirkung von Jodwasserstoffsäure auf Dehydro‐ergosterylbenzoatperoxyd sowie die analoge Reaktion am Bisdehydro‐cholesteryl‐benzoat‐peroxyd wird beschrieben.
Über den 2.4‐Dioxy‐isophthalaldehyd
Authors: Kuhn Richard , Staab Heinz A.
Published: May 2007

Aus Resorcin und N.N'‐Diphenyl‐formamidin läßt sich durch Schmelzen i. Vak., wobei das gebildete Anilin laufend abdestilliert, der 2.4‐Dioxy‐isophthaladehyd, der bisher nicht leicht zugänglich war, in Ausbeuten von 21–24% d. Th. gewinnen. Sieben Derivate des Dialdehyds werden beschrieben.
Über Einschlußverbindungen, VII. Mitteil.): Zur Struktur der Jodketten in Kanal‐Einschlußverbindungen
Authors: Dietrich Hans V. , Cramer Friedrich
Published: May 2007

Die Struktur der hexagonalen α‐Dextrin‐Jod‐Einschlußverbindung wird auf röntgenographischem Wege untersucht. Die Fourier‐Analyse der eindimensionalen Schichtlinien ergibt das Vorliegen von linearen Jodketten, in denen die Jodatome einen Abstand von 3.06 Ä haben. Die Kettenlänge der Jodketten beträgt etwa 15 Atome.
Über die Kondensation des N.N'‐Diphenylthioharnstoffes mit Malonylchlorid
Authors: Schulte Henda
Published: May 2007

Die Umsetzung von N.N'‐Diphenyl‐thioharnstoff mit Malonylchlorid ohne Lösungsmittel führte zum 6‐Oxy‐4′‐oxo‐2′‐thio‐1′.3′‐diphenyl‐1′.2′.3′.4′‐tetrahydro‐[pyrimidino‐6′.5′ :2.3‐γ‐pyron] sowie zu einer Reihe weiterer Reaktionsprodukte.
Über die Reduktion substituierter Cyanessigsäure‐äthylester (Reduktionen mit LiALH4 VIII. Mitteil.
Authors: Dornow Alfred , Fust Klaus Jürgen
Published: May 2007

Es wird die Reduktion einiger mono‐ bzw. disubstituierter Cyanessigsäure‐äthylester zu den entsprechenden Aminoalkoholen beschrieben und dargelegt, daβ auch die aliphatisch gebundene Carbäthoxy‐Gruppe wie die Keto‐Gruppe bei einigen der angeführten Derivate einer vollständigen Reduktion zu der Methyl‐ bzw. Methylen‐Gruppe unter relativ einfachen Bedingungen unterliegen kann, und daβ bei der Reduktion aliphatischer Nitrile auch sekundäre Amine entstehen können.
Polymethinfarbstoffe, III. Mitteil.) Über vinylen‐homologe Aldehyde der Pyrrolreihe
Authors: Strell Martin , Kreis Fritz
Published: May 2007

Es wird eine Methode zur Darstellung der ersten Glieder von vinylenhomologen Pyrrolaldehyden beschrieben. Diese Verbindungen wurden u.a. charakterisiert durch ihre 2.4‐Dinitro‐phenylhydrazone. Außerdem konnten mit Hilfe dieser Aldehyde neue unsymmetrische Polymethinfarbstoffe dargestellt werden.
Einfluß von Substituenten auf die Farbreaktion von N‐Acetyl‐glucosamin mit p‐Dimethylamino‐benzaldehyd
Authors: Kuhn Richard , Gauhe Adeline , Baer Hans Helmut
Published: May 2007

In 4‐Stellung substituierte N‐Acetyl‐glucosamine geben die Morgan‐Elson‐Reaktion nicht.
Untersuchungen an Steroiden XLI: Darstellung der 1‐Methyl‐3.12‐dioxy ar, AB‐cholansäure aus Desoxycholsäure
Authors: Inhoffen Hans Herloff , Jahnke Heinz , Nehring Peter
Published: May 2007

Die Überführung der Desoxycholsäure in die 1‐Methyl‐3.12‐dioxy‐ar, AB‐cholansäure wird beschrieben.
Herstellung und Reaktionen von 16‐Oxy‐pregnan‐Derivaten
Authors: Heusler Karl , Wettstein Albert
Published: May 2007

Es wird die Aufspaltung des Oxido‐Rings in 16.17α‐Oxido‐20‐ketopregnenen beschrieben, welche jedoch nur unter milden Bedingungen 16β.17α‐disubstituierte Verbindungen liefert. Diese lagern sich außerordentlich leicht zu D‐Homo‐steroiden um, welche z. Tl. mit den kürzlich von H. H. Inhoffen und Mitarbb. als 16β.17α‐Dioxy‐pregnene bzw. ihre Acetate formulierten Stoffen identisch sind. Unter energischen sauren Spaltungsbedingungen entstehen Δ13‐17β‐Methyl‐18‐nor‐17α‐pregnene. Auf Grund des Verhaltens unserer 16β.17α‐disubstituierten Pregnene werden modifizierte Strukturformeln für Nologenin und Pennogenin vorgeschlagen.
Bis‐[2.3‐o‐diphenylen‐tetrazoliumsalze]
Authors: Jerchel Dietrich , Fischer Hans
Published: May 2007

Aus Bis‐tetrazoliumverbindungen entstehen bei Belichtung mit UV‐Licht in glatter Reaktion Bis‐[2.3‐o‐diphenylen‐tetrazoliumsalze]. Durch Reduktion mit Natriumdithionit oder Hydrazin gehen sie in tiefgefärbte Radikale über. Die katalytische Hydrierung führt zu Diphenazonen.
Über die Reaktion des Acetylchlorids mit Arsen (III)‐oxyd und die Bildung des Methylen‐bis‐dichlorarsins
Authors: Gutbier Heiner , Plust Heinz‐Günther
Published: May 2007

Durch massenspektrometrische Untersuchung ergibt sich, daß die Reaktion des Arsen (III)‐oxyds mit Acetylchlorid zu Arsen (III)‐chlorid, Arsentriacetat, Acetanhydrid und in geringem Ausmaß zu Acetato‐arsendichlorid führt. Aus dem Arsentriacetat, dessen Pyrolyse ebenfalls massenspektrometrisch verfolgt wurde, entsteht in Gegenwart von Acetylchlorid, Aluminium (III)‐chlorid und überschüssigem Arsen (III)‐chlorid das Methylen‐bis‐dichlorarsin, dessen Bildungsmechanismus diskutiert wird. Für die Darstellung des Methylen‐bis‐dichlorarsins aus Arsentriacetat wird eine Arbeitsvorschrift mitgeteilt.
Mannich‐Basen als Zwischenprodukte bei der Umsetzung von CH‐aciden Verbindungen mit Formaldehyd und primären oder sekundären aromatischen Aminen zu kernsubstituierten Arylaminen
Authors: Thesing Jan , Zieg Hermann , Mayer Hans
Published: May 2007

Es wird nachgewiesen, daß bei den im sauren Medium zu p‐substituierten Anilinen führenden Umsetzungen von Indol, Antipyrin bzw. β‐Naphthol mit Formaldehyd und Anilin oder Methylanilin zunächst die entspr. Mannich‐Basen entstehen, die dann unter dem Einfluß der Säure mit dem eingesetzten aromatischen Amin zu p‐substituierten Anilinen reagieren.
Progress in the Understanding of Drug–Receptor Interactions, Part 2: Experimental and Theoretical Electrostatic Moments and Interaction Energies of an Angiotensin II Receptor Antagonist (C30H30N6O3S)
Authors: Soave Raffaella , Barzaghi Mario , Destro Riccardo
Published: May 2007

A combined experimental and theoretical charge density study of an angiotensin II receptor antagonist (1) is presented focusing on electrostatic properties such as atomic charges, molecular electric moments up to the fourth rank and energies of the intermolecular interactions, to gain an insight into the physical nature of the drug–receptor interaction. Electrostatic properties were derived from both the experimental electron density (multipole refinement of X‐ray data collected atT=17 K) and the ab initio wavefunction (single molecule and fully periodic calculations at the DFT level). The relevance of S⋅⋅⋅O and S⋅⋅⋅N intramolecular interactions on the activity of1is highlighted by using both the crystal and gas‐phase geometries and their electrostatic nature is documented by means of QTAIM atomic charges. The derived electrostatic properties are consistent with a nearly spherical electron density distribution, characterised by an intermingling of electropositive and ‐negative zones rather than by a unique electrophilic region opposed to a nucleophilic area. This makes the first molecular moment scarcely significant and ill‐determined, whereas the second moment is large, significant and highly reliable. A comparison between experimental and theoretical components of the third electric moment shows a few discrepancies, whereas the agreement for the fourth electric moment is excellent. The most favourable intermolecular bond is show to be an NH⋅⋅⋅N hydrogen bond with an energy of about 50 kJ mol−1. Key pharmacophoric features responsible for attractive electrostatic interactions include CH⋅⋅⋅X hydrogen bonds. It is shown that methyl and methylene groups, known to be essential for the biological activity of the drug, provide a significant energetic contribution to the total binding energy. Dispersive interactions are important at the thiophene and at both the phenyl fragments. The experimental estimates of the electrostatic contribution to the intermolecular interaction energies of six molecular pairs, obtained by a new model proposed by Spackman, predict the correct relative electrostatic energies with no exceptions.
The Mechanism of CX (X=F, Cl, Br, and I) Bond Activation in CX4 by a Stabilized Dialkylsilylene
Authors: Chen Chi‐Hui , Su Ming‐Der
Published: May 2007

The potential‐energy surfaces for the abstraction and insertion reactions of dialkylsilylene with carbon tetrahalides (CX4) have been characterized in detail using density functional theory (B3LYP), including zero‐point corrections. Four CX4 species, CF4, CCl4, CBr4, and CI4, were chosen as model reactants. The theoretical investigations described herein suggest that of the three possible reaction paths, the one‐halogen‐atom abstraction (X abstraction), the one‐CX3‐group abstraction (CX3 abstraction), and the insertion reaction, the X‐abstraction reaction is the most favorable, with a very low activation energy. However, the insertion reaction can lead to the thermodynamically stable products. Moreover, for a given stable dialkylsilylene, the chemical reactivity has been found to increase in the order CF4≪CCl4<CBr4<CI4, that is, the heavier the halogen atom (X), the more facile is its reaction with a stable dialkylsilylene. In particular, halogen abstraction is always predicted to be much more favorable than abstraction of a CX3 group from both energetic and kinetic viewpoints. In brief, electronic as well as steric factors play a crucial role in determining the chemical reactivity of the haloalkane species, kinetically as well as thermodynamically. Our conclusions based on the results of our theoretical investigations are in accordance with available experimental observations. Furthermore, a configuration‐mixing model based on the work of Pross and Shaik has been used to rationalize the computational results. The results obtained allow a number of predictions to be made.
Evidence for a SN2‐Type Pathway for Phosphine Exchange in Phosphine–Phosphenium Cations, [R2PPR′3]+
Authors: Slattery John M. , Fish Cheryl , Green Michael , Hooper Thomas N. , Jeffery John C. , Kilby Richard J. , Lynam Jason M. , McGrady John E. , Pantazis Dimitrios A. , Russell Christopher A. , Willans Charlotte E.
Published: May 2007

Abstraction of a Cl− ion from the P‐chlorophospholes, R4C4PCl (R=Me, Et), produced the PP bonded cations [R4C4PP(Cl)C4R4]+, which reacted with PPh3 to afford X‐ray crystallographically characterised phosphine–phosphenium cations [R4C4P(PPh3)]+ (R=Me, Et). Examination of the 31P‐{1H} NMR spectrum of a solution (CH2Cl2) of [Et4C4P(PPh3)]+ and PPh3 revealed broadening of the resonances due to both free and coordinated PPh3, and importantly it proved possible to measure the rate of exchange between PPh3 and [Et4C4P(PPh3)]+ by line shape analysis (gNMR programmes). The results established second‐order kinetics with ΔS≠=(−106.3±6.7) J mol−1 K−1, ΔH≠=(14.9±1.6) kJ mol−1 and ΔG≠ (298.15 K)=(46.6±2.6) kJ mol−1, values consistent with a SN2‐type pathway for the exchange process. This result contrasts with the dominant dissociative (SN1‐type) pathway reported for the analogous exchange reactions of the [ArNCH2CH2N(Ar)P(PMe3)]+ ion, and to understand in more detail the factors controlling these two different reaction pathways, we have analysed the potential energy surfaces using density functional theory (DFT). The calculations reveal that, whilst phosphine exchange in [Et4C4P(PPh3)]+ and [ArNCH2CH2N(Ar)P(PMe3)]+ is superficially similar, the two cations differ significantly in both their electronic and steric requirements. The high electrophilicity of the phosphorus center in [Et4C4P]+, combined with strong π–π interactions between the ring and the incoming and outgoing phenyl groups of PPh3, favours the SN2‐type over the SN1‐type pathway in [Et4C4P(PPh3)]+. Effective π‐donation from the amide groups reduces the intrinsic electrophilicity of [ArNCH2CH2N(Ar)P]+, which, when combined with the steric bulk of the aryl groups, shifts the mechanism in favour of a dissociative SN1‐type pathway.
Synthesis, Characterization, and Electrochemiluminescence of Luminol‐Reduced Gold Nanoparticles and Their Application in a Hydrogen Peroxide Sensor
Authors: Cui Hua , Wang Wei , Duan Chun‐Feng , Dong Yong‐Ping , Guo Ji‐Zhao
Published: May 2007

It was found that chloroauric acid (HAuCl4) could be directly reduced by the luminescent reagent luminol in aqueous solution to form gold nanoparticles (AuNPs), the size of which depended on the amount of luminol. The morphology and surface state of as‐prepared AuNPs were characterized by transmission electron microscopy, UV/visible spectroscopy, X‐ray photoelectron spectroscopy, FTIR spectroscopy, and thermogravimetric analysis. All results indicated that residual luminol and its oxidation product 3‐aminophthalate coexisted on the surface of AuNPs through the weak covalent interaction between gold and nitrogen atoms in their amino groups. Subsequently, a luminol‐capped AuNP‐modified electrode was fabricated by the immobilization of AuNPs on a gold electrode by virtue of cysteine molecules and then immersion in a luminol solution. The modified electrode was characterized by cyclic voltammetry, electrochemical impedance spectroscopy, and scanning electron microscopy. The as‐prepared modified electrode exhibited an electrochemiluminescence (ECL) response in alkaline aqueous solution under a double‐step potential. H2O2 was found to enhance the ECL. On this basis, an ECL sensor for the detection of H2O2 was developed. The method is simple, fast, and reagent free. It is applicable to the determination of H2O2 in the range of 3×10−7–1×10−3 mol L−1 with a detection limit of 1×10−7 mol L−1 (S/N=3).
Mechanisms for the Dehydrogenation of Alkanes on Platinum: Insights Gained from the Reactivity of Gaseous Cluster Cations, Ptn+n=1–21
Authors: Adlhart Christian , Uggerud Einar
Published: May 2007

Rates for the dihydrogen elimination of methane, ethane, and propane with cationic platinum clusters, Ptn+ (1≤n≤21), were measured under binary collision conditions in a Fourier transform ion cyclotron resonance mass spectrometer (FTICR). The reaction rate for a given cluster, Ptn+, follows the trend k(CH4)<k (C2H6)<k(C3H8). Methane is particular in the sense that reactivity is highly variable; some clusters (n=1–3, 5–9, 11, 12, 15) are very reactive towards methane, while all other clusters react with low efficiency or not at all. For propane, all clusters react efficiently, while the reactivity of ethane lies in‐between that of methane and propane. By necessity, dihydrogen elimination of methane occurs according to a 1,1‐elimination mechanism. Ethane dehydrogenation takes place according to both a 1,1‐ and a 1,2‐mechanism. The difference between the 1,1‐ and 1,2‐mechanisms is well displayed in specifically increased rates for those clusters that were inefficient in the reaction with methane, as well as in the observed selectivity for H2, HD, and D2 elimination in the reaction with [D3]‐1,1,1‐ethane. Some twofold dihydrogen elimination is observed as well. The outcome of reactions with C2H6 in the presence of D2 demonstrates exchange of all hydrogen atoms in [PtnC2H4]+ with deuterium atoms. A potential energy diagram with a high barrier for the second H2 elimination summarizes these observations. For propane twofold dihydrogen elimination is dominating, and for these reactions a far less regiospecific and more random loss of the hydrogens can be inferred, as was demonstrated by the reactions with [D6]‐1,1,1,3,3,3‐propane.
Are MAP Kinases Drug Targets? Yes, but Difficult Ones
Authors: Margutti Simona , Laufer Stefan A.
Published: May 2007

Pharmaceutical companies are facing an increasing interest in new target identification and validation. In particular, extensive efforts are being made in the field of protein kinase inhibitors research and development, and the past ten years of effort in this field have altered our perception of the potential of kinases as drug targets. Therefore, in the drug discovery process, the selection of relevant, susceptible protein kinase targets combined with searches for leads and candidates have become a crucial approach. The success of recent launches of protein kinase inhibitors (Gleevec, Imatinib, Sutent, Iressa, Nexavar, Sprycel) gave another push to this field. Numerous other kinase inhibitors are currently undergoing clinical trials or clinical development. Some questions are nevertheless unanswered, mostly related to the great number of known kinases in the human genome, to their similarity with each other, to the existence of functionally redundant kinases for specific pathways, and also because the connection between particular pathways and diseases is not always clear. The review is leading the reader through a panoramic view of protein kinase inhibition with a major focus on MAPK, successful examples and clinical candidates.
Oxime and Oxime Ether Derivatives of 1,4‐Benzothiazine Related to Oxiconazole
Authors: Milanese Lara , Giacchè Nicola , Schiaffella Fausto , Vecchiarelli Anna , Macchiarulo Antonio , Fringuelli Renata
Published: May 2007

The synthesis, in vitro antifungal activity, and molecular docking experiments of some oxime and oxime ether derivatives of azole 1,4‐benzothiazine are reported herein, with the aim of evaluating the influence of a partially constrained scaffold that is structurally related to Oxiconazole and bearing the 1,4‐benzothiazine moiety, on the inhibition of Candida albicans CYP51.
Antibody‐mediated cell labeling of peripheral T cells with micron‐sized iron oxide particles (MPIOs) allows single cell detection by MRI
Authors: Shapiro Erik M. , Medford‐Davis Laura N. , Fahmy Tarek M. , Dunbar Cynthia E. , Koretsky Alan P.
Published: May 2007

Labeling cells with iron oxide is a useful tool for MRI based cellular imaging. Here it is demonstrated that peripheral rat T cells can be labeled in whole blood, in vitro, with streptavidin‐coated micron‐sized iron oxide particles (MPIOs), achieving iron concentrations as high as 60 pg iron per cell. This is 30 times the amount of labeling reported with ultrasmall particles of iron oxide (USPIOs). Labeling was mediated by use of a biotinylated anti‐CD5 antibody, which is specific for peripheral T cells. Such labeling allowed the in vitro detection of single lymphocytes by MRI, using conditions well suited for in vivo animal work. Electron microscopic analysis demonstrated that MPIOs remained largely extracellular after labeling, with some evidence of intracellular uptake. Cell viability and early and late cytokine release studies showed no significant differences between labeled and unlabeled cells. Therefore, the use of MPIOs for achieving high iron concentrations for cellular MRI is potentially an effective new modality for non‐invasive imaging of lymphocytes. Published in 2007 by John Wiley & Sons, Ltd.
Non‐Hodgkin lymphoma of the breast
Authors: Ganjoo Kristen , Advani Ranjana , Mariappan M. Rajan , McMillan Alex , Horning Sandra
Published: May 2007

BACKGROUND.

Primary lymphoma of the breast has been reported to have a high local and central nervous system recurrence (CNS) rate, suggesting the need for consolidation radiotherapy and CNS prophylaxis. A retrospective study was done to evaluate the institutional experience in this patient population.

METHODS.

In all, 37 patients with lymphoma involving the breast at initial diagnosis and managed at Stanford University from 1981–2005 were included. Diagnostic tissue biopsies were obtained either from the breast mass or an involved lymph node. Treatment and response data, patterns of recurrence, and outcomes were reviewed.

RESULTS.

Diffuse large B cell lymphoma (DLBCL) was the most common histologic subtype seen in 18 of 37 (49%) patients. Follicular and marginal zone subtypes were seen in 38%. Most patients presented with an incidental breast mass in stage IE or IIE. Four (11%) patients presented with bilateral breast involvement, with only 1 patient presenting with CNS disease. DLBCL patients received doxorubicin‐based chemotherapy, with 70% receiving involved field radiotherapy and a single patient receiving intrathecal therapy. No recurrences occurred in the involved breast and a single parenchymal CNS recurrence was recorded. Among the DLBCL patients, the 5‐year progression‐free survival (PFS) was 61%, with a median follow‐up of 3.8 years (range, 5 months to 19 years) and the 5‐year overall survival (OS) was estimated at 82%. Patients with indolent lymphoma had an estimated 5‐year PFS of 76% and an OS of 92%.

CONCLUSIONS.

DLBCL of the breast was successfully treated with doxorubicin‐based chemotherapy alone or with involved field radiotherapy in an estimated 61% of patients at 5 years. A single CNS recurrence was observed in our series of patients, most of whom presented with limited disease. Cancer 2007. © 2007 American Cancer Society.
Micropapillary bladder cancer
Authors: Kamat Ashish M. , Dinney Colin P. N. , Gee Jason R. , Grossman H. Barton , Siefker‐Radtke Arlene O. , Tamboli Pheroze , Detry Michelle A. , Robinson Tracy L. , Pisters Louis L.
Published: May 2007

BACKGROUND

Micropapillary bladder carcinoma is a rare variant of urothelial carcinoma. To improve understanding of this disease, the authors performed a retrospective review of their experience.

METHODS

The authors reviewed the records of 100 consecutive patients with micropapillary bladder cancer who were evaluated at The University of Texas M. D. Anderson Cancer Center.

RESULTS

The mean age of the patients was 64.7 years, with a male:female ratio of 10:1. The TNM stage of disease at the time of presentation was Ta in 5 patients, carcinoma in situ (CIS) in 4 patients, T1 in 35 patients, T2 in 26 patients, T3 in 7 patients, T4 in 6 patients; N+ in 9 patients, and M+ in 8 patients. Kaplan‒Meier estimates of 5‒year and 10‒year overall survival (OS) rates were 51% and 24%, respectively. Bladder‒sparing therapy with intravesical bacillus Calmette–Guerin therapy was attempted in 27 of 44 patients with nonmuscle‒invasive disease; 67% (18 patients) developed disease progression (≥cT2), including 22% who developed metastatic disease. Of 55 patients undergoing radical cystectomy for surgically resectable disease (≤cT4a), 23 received neoadjuvant chemotherapy and 32 were treated with initial cystectomy, with no significant difference noted in stage distribution between the 2 groups. For the 23 patients treated with neoadjuvant chemotherapy, the median OS was 43.2 months with 32% of patients still alive at 5 years. For the 32 patients treated with initial cystectomy, the median survival had not been reached at the time of last follow‒up, with 71% still alive at 5 years.

CONCLUSIONS

Micropapillary bladder cancer is associated with a poor prognosis. Intravesical therapy appears to be ineffective in this disease and patients with surgically resectable disease should be offered early radical cystectomy. Cancer 2007. © 2007 American Cancer Society.
The value of combined‐modality therapy in elderly patients with stage III nonsmall cell lung cancer
Authors: Schild Steven E. , Mandrekar Sumithra J. , Jatoi Aminah , McGinnis William L. , Stella Phillip J. , Deming Richard L. , Jett James R. , Garces Yolanda I. , Allen Katie L. , Adjei Alex A. ,   for the North Central Cancer Treatment Group
Published: May 2007

BACKGROUND.

The objective of this study was to assess the value of combined‐modality therapy in elderly patients by comparing the differences in outcome between patients who received radiotherapy (RT) alone and patients who received RT plus chemotherapy for stage III nonsmall cell lung cancer (NSCLC).

METHODS.

The North Central Cancer Treatment Group performed 2 recent Phase III trials for stage III NSCLC. The first trial, NCCTG 90‐24‐51, included 3 arms: once‐daily RT (QDRT) alone, twice‐daily RT (BIDRT) alone, and concurrent chemotherapy plus BIDRT. The second trial, NCCTG 94‐24‐52, included 2 arms and compared concurrent chemotherapy with either QDRT or BIDRT. The chemotherapy arms of both trials included etoposide and cisplatin administered concurrently with RT. Only the patients aged ≥65 years (elderly) who participated in those trials were included in this analysis.

RESULTS.

Of the 166 elderly patients who were included in this analysis, 37 patients received RT alone, and 129 patients received concurrent chemotherapy plus RT. The median and 5‐year survival rates were 10.5 months and 5.4% for the RT alone group compared with 13.7 months and 14.7% for the RT plus chemotherapy group (log‐rank P = .05). Patients who received RT plus chemotherapy experienced significantly greater severe toxicity (grade ≥3) compared with patients who received RT alone (89.9% vs 32.4%; P < 0.01).

CONCLUSIONS.

Elderly patients who participated in these trials appeared to gain a survival advantage from RT and chemotherapy compared with RT alone. As is the case with younger patients, this benefit came at the cost of additional toxicity. Cancer 2007. © 2007 American Cancer Society.
Multiscale algorithm with patches of finite elements
Authors: Picasso Marco , Rappaz Jacques , Rezzonico Vittoria
Published: May 2007

We develop a discretization and solution technique for elliptic problems whose solutions may present strong variations, singularities, boundary layers and oscillations in localized regions. We start with a coarse finite element discretization with a mesh sizeH, and we superpose to it local patches of finite elements with finer mesh sizeh≪ Hto capture local behaviour of the solution. The two meshes (coarse and patch) are not necessarily compatible. Similar to mesh adaptation methods, the location of the fine patches is identified by ana posteriorierror estimator. Unlike mesh adaptation, no remeshing is involved. We discuss the implementation and illustrate the method on an industrial example. Copyright © 2007 John Wiley & Sons, Ltd.
Predicting parallel application performance via machine learning approaches
Authors: Singh Karan , İpek Engin , McKee Sally A. , de Supinski Bronis R. , Schulz Martin , Caruana Rich
Published: May 2007

Consistently growing architectural complexity and machine scales make the creation of accurate performance models for large‐scale applications increasingly challenging. Traditional analytic models are difficult and time consuming to construct, and are often unable to capture full system and application complexity. To address these challenges, we automatically build models based on execution samples. We use multilayer neural networks, because they can represent arbitrary functions and handle noisy inputs robustly. In this paper we focus on two well‐known parallel applications whose variations in execution times are not well understood: SMG 2000, a semicoarsening multigrid solver, and HPL, an open‐source implementation of LINPACK. We sparsely sample performance data on two radically different platforms across large, multidimensional parameter spaces and show that our models based on these data can predict performance within 2% to 7% of actual application runtimes. Copyright © 2007 John Wiley & Sons, Ltd.
Iron protoporphyrin‐modified monolithic support for on‐line preconcentration of angiotensin prior to CE analysis
Authors: Yone Ángel , Rusell María Lucía , Grasselli Mariano , Vizioli Nora M.
Published: May 2007

An on‐line preconcentration method using a polymeric monolithic support is proposed for the retention of the decapeptide angiotensin I and its subsequent analysis by CZE. Monolithic capillary columns were prepared in fused‐silica (FS) capillaries of 150 μm id by ionizing radiation‐initiated in situ polymerization and cross‐linking of diethylene glycol dimethacrylate and glycidyl methacrylate, and chemically modified with iron protoporphyrin IX (Fe‐ProP). Monolithic microcolumns (8 mm long) were coupled on‐line to the inlet of the separation capillary (FS capillary, 75 μm id ×10 cm from the inlet to the microcolumn and 27 cm from the microcolumn to the detector). Angiotensin I was released from the sorbent by a 50 mM sodium phosphate, pH 2.5/ACN, 75:25 v/v solution and then analyzed by CZE with UV absorption detection at 214 nm. The concentration LOQ (CLOQ) was 0.5 ng/mL. The Fe‐ProP‐derivatized monolithic microcolumn coupled to the separation capillary exhibited a high retention capacity for peptide angiotensin I, and showed as much as 10 000‐fold improvement in concentration sensitivity.
Reduction of Selenium Oxyanions in Wastewater Using Two Bacterial Strains
Authors: Morita M. , Uemoto H. , Watanabe A.
Published: May 2007

The biological reduction of selenium oxyanions is capable of reducing both selenate and selenite to insoluble elemental selenium. In this process, however, bacteria inevitably require expensive chemicals such as yeast extract in almost all cases. Therefore, the reduction of selenium oxyanions with inexpensive alcohol would be more practical. A Pseudomonas sp. strain 4C‐C isolated from a sludge in a wastewater treatment facility was able to reduce selenate to selenite using ethanol as an electron donor for its anaerobic respiration, but could not reduce selenite to elemental selenium. Paracoccus denitrificans JCM‐6892, on the other hand, was observed to be able to reduce selenite to elemental selenium in the presence of ethanol, but not selenate to selenite. Therefore, a mixture containing a suspension of Pseudomonas sp. strain 4C‐C and P. denitrificans JCM‐6892 cells allowed selenate to be reduced to insoluble elemental selenium via selenite in the presence of ethanol and was also capable of reducing nitrate to nitrogen gas. Aiming at simplicity of the recovery process of insoluble elemental selenium, a polymeric gel immobilized mixture of the two bacterial strains was examined using ethanol as an electron donor. The immobilized mixture could therefore reduce not only selenate to elemental selenium, but also nitrate to nitrogen gas in a single step. The gel that immobilized the microbial mixture changed its color during the process to bright red and no red elemental selenium was left in the wastewater. This indicates that the reduced elemental selenium was completely absorbed in the gel. This simple bacterial combination would therefore be effective in the presence of ethanol to reduce selenium oxyanions in various wastewaters containing selenium and the other oxyanions.
Process Design for the Microbial Synthesis of Poly‐β‐hydroxybutyrate (PHB) from Natural Gas
Authors: Listewnik H.‐F. , Wendlandt K.‐D. , Jechorek M. , Mirschel G.
Published: May 2007

A process design for a two‐stage procedure for the production of PHB from natural gas based on the results, obtained on a laboratory and small technical scale, was developed. For this purpose, four bioreactors were dimensioned and interconnected so as to achieve a quasi‐continuous PHB production. A price of 6.35 €/kg PHB was pre‐calculated for the biosynthesis in a plant producing 500 t PHB/year. An extrapolation, which included the incorporation of various downstream procedures to achieve purities dependent on applications, resulted in prices between 11.50 and 14.00 €/kg for the purified final product. Estimations indicate that an expansion of the plant capacity to 5,000 t/year could enable a price reduction of approx. 30–35 %.
Is volatility risk priced in the securities market? Evidence from S&P 500 index options
Authors: Arisoy Yakup Eser , Salih Aslihan , Akdeniz Levent
Published: May 2007

The authors examine whether volatility risk is a priced risk factor in securities returns. Zero‐beta at‐the‐money straddle returns of the S&P 500 index are used to measure volatility risk. It is demonstrated that volatility risk captures time variation in the stochastic discount factor. The results suggest that straddle returns are important conditioning variables in asset pricing, and investors use straddle returns when forming their expectations about securities returns. One interesting finding is that different classes of firms react differently to volatility risk. For example, small firms and value firms have negative and significant volatility coefficients, whereas big firms and growth firms have positive and significant volatility coefficients during high‐volatility periods, indicating that investors see these latter firms as hedges against volatile states of the economy. Overall, these findings have important implications for portfolio formation, risk management, and hedging strategies. © 2007 Wiley Periodicals, Inc. Jrl Fut Mark 27:617–642, 2007
Pulmonary lymphangioleiomyomatosis (LAM): Progress and current challenges
Authors: Goncharova Elena A. , Krymskaya Vera P.
Published: May 2007

Lymphangioleiomyomatosis (LAM), a rare lung disease, is characterized by the progressive proliferation, migration, and differentiation of smooth muscle (SM)‐like LAM cells, which lead to the cystic destruction of the lung parenchyma, obstruction of airways and lymphatics, and loss of pulmonary function. LAM is a disease predominantly affecting women and is exacerbated by pregnancy; only a lung transplant can save the life of a patient. It has been discovered that in LAM, somatic or genetic mutations of tumor suppressor genes tuberous sclerosis complex 1 (TSC1) or TSC2 occur and the TSC1/TSC2 protein complex functions as a negative regulator of the mTOR/S6K1 signaling pathway. These two pivotal observations paved the way for the first rapamycin clinical trial for LAM. The recent discoveries that TSC1/TSC2 complex functions as an integrator of signaling networks regulated by growth factors, insulin, nutrients, and energy heightened the interest regarding this rare disease because the elucidation of disease‐relevant mechanisms of LAM will promote a better understanding of other metabolic diseases such as diabetes, cancer, and cardiovascular diseases. In this review, we will summarize the progress made in our understanding of TSC1/TSC2 cellular signaling and the molecular mechanisms of LAM; we will also highlight some of the lesser explored directions and challenges in LAM research. J. Cell. Biochem. 103: 369–382, 2008. © 2007 Wiley‐Liss, Inc.
Skeletal stem/osteoprogenitor cells: Current concepts, alternate hypotheses, and relationship to the bone remodeling compartment
Authors: Mödder Ulrike I. , Khosla Sundeep
Published: May 2007

Plastic adherent bone marrow stromal cells have become synonymous with skeletal stem cells, and perhaps rightfully so, as these cells have been extremely well characterized over the past four decades, since their original description by Friedenstein. However, although this cell population is useful as an experimental model of precursors for osteoblasts and other mesenchymal lineages, the precise role of bone marrow stromal cells in bone remodeling, fracture repair, or repair of non‐skeletal tissues remains unclear. Moreover, there is a conceptual problem in terms of postulating that these cells are osteoblast precursors at sites of bone remodeling on trabecular surfaces adjacent to red marrow and yet having to posit potentially entirely different mechanisms for the origins of osteoblasts at sites of cortical bone remodeling distant from red marrow. Thus, the identification and characterization in recent years of non‐adherent stem and osteoprogenitor cells in the bone marrow, of similar cells in the peripheral circulation, and of stem/osteoprogenitor cells arising either from the perivascular compartment (pericytes) or within the developing vascular wall itself, has suggested alternative candidate cell populations that may help to resolve the problem of postulating different mechanisms of remodeling in trabecular versus cortical bone. When coupled with our evolving understanding of the bone remodeling compartment (BRC), a closed cavity penetrated by capillaries which appears to be the site of remodeling in both trabecular and cortical bone, it is likely that our conceptual understanding of the fundamental mechanisms of bone remodeling will need to be modified. J. Cell. Biochem. 103: 393–400, 2008. © 2007 Wiley‐Liss, Inc.
PKC‐ζ expression is lower in osteoblasts from arthritic patients: IL1‐β and TNF‐α induce a similar decrease in non‐arthritic human osteoblasts
Authors: Zini Nicoletta , Bavelloni Alberto , Lisignoli Gina , Ghisu Sonia , Valmori Aurelio , Martelli Alberto Maria , Facchini Andrea , Maraldi Nadir Mario
Published: May 2007

Protein kinase C (PKC) is a family of enzymes detected in a diverse range of cell types where they regulate various cellular functions such as proliferation, differentiation, cytoskeletal remodelling, cytokine production, and receptor‐mediated signal transduction. In this study we have analyzed the expression of 11 PKC isoforms (‐α, ‐βI, ‐βII, ‐γ, ‐δ, ‐η, ‐θ, ‐ε, ‐ζ, ‐ι/λ, and ‐µ) in osteoblasts from patients with osteoarthritis (OA) and rheumatoid arthritis (RA) in comparison with osteoblasts from post‐traumatic (PT) patients. By Western blotting analysis, nine isoforms, ‐α, ‐βI, ‐βII, ‐δ, ‐θ, ‐ ε, ‐ζ, ‐ ι/λ, and ‐µ, were detected in osteoblasts. In RA and OA patients, PKC ‐θ and ‐µ were greater expressed whereas PKC‐ε and ‐ζ decreased when compared with normal cells. The subcellular distribution and quantitative differences were confirmed by immuno‐electron microscopy. Furthermore, we demonstrated that treatment with the proinflammatory cytokines, IL‐1β and TNF‐α, significantly decreased PKC‐ζ expression in PT osteoblasts. This suggests that proinflammatory cytokines can modulate the expression of this PKC isoform in osteoblasts in a way which is similar to changes detected in arthritic patients. J. Cell. Biochem. 103: 547–555, 2008. © 2007 Wiley‐Liss, Inc.
Estrogen‐TGFβ cross‐talk in bone and other cell types: Role of TIEG, Runx2, and other transcription factors
Authors: Hawse J. R. , Subramaniam M. , Ingle J. N. , Oursler M. J. , Rajamannan N. M. , Spelsberg T. C.
Published: May 2007

It is well established that E2 and TGFβ have major biological effects in multiple tissues, including bone. The signaling pathways through which these two factors elicit their effects are well documented. However, the interaction between these two pathways and the potential consequences of cross‐talk between E2 and TGFβ continue to be elucidated. In this prospectus, we present known and potential roles of TIEG, Runx2, and other transcription factors as important mediators of signaling between these two pathways. J. Cell. Biochem. 103: 383–392, 2008. © 2007 Wiley‐Liss, Inc.
Whey acidic protein (WAP) regulates the proliferation of mammary epithelial cells by preventing serine protease from degrading laminin
Authors: Nukumi Naoko , Iwamori Tokuko , Kano Kiyoshi , Naito Kunihiko , Tojo Hideaki
Published: May 2007

Whey acidic protein (WAP) is a major whey protein in milk that has structural similarity to the family of serine protease inhibitors with WAP motif domains characterized by a four‐disulfide core. We previously reported that enforced expression of the mouse WAP transgene in mammary epithelial cells inhibits their proliferation in vitro and in vivo by means of suppressing cyclin D1 expression (Nukumi et al., 2004, Dev Biol 274: 31–44). This study was conducted in order to clarify the molecular mechanism of the inhibitory function of WAP in HC11 cells, a mammary epithelial cell line. The assembly of laminin, a component in the extracellular matrix, was much more prominent around WAP‐clonal HC11 cells that stably expressed the WAP transgene than around mock‐clonal HC11 cells, and the proliferation of WAP‐clonal HC11 cells was particularly inhibited in the presence of laminin. A laminin degradation assay demonstrated that WAP inhibited the activity of the pancreatic elastase‐mediated cleavage of laminin B1 and the phosphorylation of ERK1/2. ERK1/2 phosphorylation was blocked by an inhibitor of the epidermal growth factor (EGF) receptor AG1478. Treatment with pancreatic elastase was found to enhance the proliferation of mock‐clonal HC11 cells, but had no effect on that of WAP‐clonal HC11 cells. The proliferation of WAP‐clonal HC11 cells was recovered by the addition of exogenous EGF. We concluded that WAP plays some role in regulating the proliferation of mammary epithelial cells by preventing elastase‐type serine protease from carrying out laminin degradation and thereby suppressing the MAP kinase signal pathway. J. Cell. Physiol. 213:793–800. © 2007 Wiley‐Liss, Inc.
Glucocorticoid induced expression of connective tissue growth factor contributes to lactogenic differentiation of mouse mammary epithelial cells
Authors: Wang Weihan , Morrison Bethanie , Galbaugh Traci , Jose Cynthia C. , Kenney Nicholas , Cutler Mary Lou
Published: May 2007

The response of mammary epithelial cells to basement membrane and stroma induced signals contributes to the degree of differentiation in this tissue. The studies reported here indicate that connective tissue growth factor (CTGF) is highly elevated during lactogenic differentiation of the HC11 mouse mammary epithelial cell line. In addition, CTGF is expressed in the mouse mammary gland during pregnancy and lactation and it is expressed in primary mammary epithelial cell cultures established from pregnant mice. In HC11 cells CTGF is transcriptionally regulated by dexamethasone, but not by estrogen or progesterone, and CTGF expression is not dependent on TGFβ. CTGF contributes to and is required for lactogenic differentiation of HC11 cells, as demonstrated by increased differentiation following expression of plasmid‐encoded CTGF and decreased differentiation following depletion of endogenous CTGF with siRNA. Moreover, HC11 mouse mammary epithelial cells infected with an adenoviral vector encoding CTGF exhibit increased lactogenic differentiation. Plasmid vector‐induced elevation of CTGF levels also increased the level of β1 integrin in HC11 cells. Because the production of stromal factors is an important component of differentiation in mammary epithelial cells, the regulation of CTGF by glucocorticoids may play a critical role in this aspect of the control of differentiation. The studies reported here provide important information on the role of CTGF in mammary epithelial cell differentiation. J. Cell. Physiol. 214:38–46, 2008. © 2007 Wiley‐Liss, Inc.
BMP‐5 expression increases during chondrocyte differentiation in vivo and in vitro and promotes proliferation and cartilage matrix synthesis in primary chondrocyte cultures
Authors: Mailhot Geneviève , Yang Meiheng , Mason‐Savas April , MacKay Carole A. , Leav Irwin , Odgren Paul R.
Published: May 2007

Bone morphogenetic proteins (BMPs) play pivotal roles in bone and cartilage growth and repair. Through phenotypes of short‐ear (se) mice, which have BMP‐5 mutations, a role for BMP‐5 in some specific aspects of skeletogenesis and cartilage growth is known. This report examines BMP‐5 expression in the growth plate and in differentiating cultures of primary chondrocytes, and the effects of addition of BMP‐5 or its inhibition by anti‐BMP‐5 antibody in chondrocyte cultures. By laser capture microdissection and immunohistochemistry, we found that BMP‐5 is expressed in proliferating zone (PZ) chondrocytes and that the expression increases sharply with hypertrophic differentiation. A similar pattern was observed in differentiating cultures of primary chondrocytes, with BMP‐5 expression increasing as cells differentiated, in contrast to other BMPs. BMP‐5 added to cultures increased cell proliferation early in the culture period and also stimulated cartilage matrix synthesis. Also, BMP‐5 addition to the cultures activated phosphorylation of Smad 1/5/8 and p38 MAP kinase and caused increased nuclear accumulation of phospho‐Smads. Anti‐BMP‐5 antibody inhibited the endogenous BMP‐5, reducing cell proliferation and phospho‐Smad nuclear accumulation. Together, the results demonstrate that BMP‐5 is normally an important regulator of chondrocyte proliferation and differentiation. Whether other BMPs may compensate in BMP‐5 loss‐of‐function mutations is discussed. J. Cell. Physiol. 214:56–64, 2008. © 2007 Wiley‐Liss, Inc.
Iron withholding as an innate immune mechanism in the American alligator (Alligator mississippiensis)
Authors: Merchant Mark , Sanders Paige , Dronette Jessica , Mills Kaili , Berken Jennifer
Published: May 2007

Pathogenic microbes require Fe and Zn for growth and proliferation. Upon infection, microbes produce proteins, called sidephores, designed to strip serum divalent metals away from host proteins. Higher vertebrates respond to infection by increasing the expression of proteins that sequester serum iron away from bacteria. As a result, host plasma Fe levels decrease during the initial phases of infection. This study was conducted to determine if the American alligator, an ancient reptile, exhibits the same innate immune mechanism to protect against in vivo microbial proliferation. Intraperitoneal injection of juvenile captive alligators with bacterial lipopolysaccharide (LPS) resulted in a time‐dependent decrease in plasma Fe, as determined by inductively coupled plasma emission spectroscopy. Plasma Fe levels decreased by 5.9, 10.6, and 18.6% relative to untreated control levels at 3, 6, and 12 hr post‐injection, respectively, and remained decreased by 12.0% at 48 hr. Alligators injected with pyrogen‐free saline did not exhibit statistically significant changes in plasma Fe concentrations at any time point observed. In contrast, serum Zn and Cu remained unchanged relative to untreated controls. To insure that the decreases in plasma Fe were not due to the repeated blood collections during the course of the kinetic study, another experiment was conducted in which plasma metals were measured at 24 hr post‐injection. Once again, plasma Fe was reduced by 30.2%, whereas Zn and Cu did not exhibit appreciable changes. These results show that alligators exhibit low plasma Fe levels during an inflammatory response induced by bacterial lipopolysaccharide. J. Exp. Zool. 307A:406–410, 2007. © 2007 Wiley‐Liss, Inc.