Chromosomenabnormitäten und Behandlung mit Imuran® (Azathioprin) nach Nierentransplantationen

Zusammenfassung 19 Patienten, die nach einer Nierentransplantation mit Imuran behandelt wurden, wiesen eine erhöhte Anzahl Chromosomenabnormitäten im Vergleich zu 30 gesunden Kontrollpersonen der gleichen Altersklasse auf. Keine signifikant erhöhte Anzahl an Chromosomenabnormitäten fand sich jedoch bei 7 Patienten, die vor und unter der Imuran-behandlung untersucht wurden. Es wird vermutet, daß die Chromosomenabnormitäten bei den 19 mit Imuran behandelten Patienten wahrscheinlich nicht durch Imuran, sondern durch die Urämie entstanden sind.

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Summary 19 patients treated with Imuran after a renal transplantation showed a high frequency of chromosome abnormalities, compared with 30 healthy control persons in the same age range. No significantly higher frequency of chromosome abnormalities was, however, found in 7 patients examined before and during treatment with Imuran. It is suggested that the chromosome abnormalities found in the 19 patients treated with Imuran were probably not due to Imuran but to Uremia.

     

IMRT/VMAT dose distributions generated for HD® and Millennium® collimators TrueBeam® and Clinac® accelerators

AimThe aim of this study is to answer the question whether the calculated dose distributions for HD and Millennium collimators (Varian Medical Systems) are equivalent for large treatment volumes.BackgroundModern biomedical linacs are equipped with multileaf collimators where leaves can be of different widths. Thinner leaves allow better fit to desired (tumor) shape. At the same time, however, the maximum size of the field that can be obtained with the collimator is also reduced. Varian Medical Systems HD and Millennium collimators can be a good sample. They have 40 cm or 22 cm × 40 cm maximal field size at the isocenter, respectively.Materials and methodsThis paper presents the comparison of selected statistical and dosimetric parameters achieved for treatment plans where the beams for a HD collimator had to be merged because of the size of the tumor volume.Results and discussionAchieved results show that, independently from irradiated volume, there is no statistically significant difference for calculated dose distributions, integral doses, MU values and coefficients evaluating dose distributions for HD and Millennium collimators.ConclusionsResults show that both types of collimators can be used interchangeably for preparing the treatment plans for large tumor volume without quality reduction of the prepared treatment plan.     

Glycosylation profile and biological activity of Remicade® compared with Flixabi® and Remsima®

As biosimilars enter the market, comparisons of product quality are needed. Manufacturing differences may lead to differences in critical quality attributes, which affect efficacy. Therefore, critical quality attributes (structure and biological activity) of Remicade® and of 2 biosimilar products (Flixabi®/Renflexis® and Remsima®/Inflectra®) were determined. We assessed binding to tumor necrosis factor in a fluorescence competitive binding assay; potency in a luciferase reporter gene assay; percentages of galactosylated glycan, afucose plus high mannosylated glycans, and charged glycan; FcγRIIIa (CD16) binding (assessed by 3 methods); and antibody-dependent cell-mediated cytotoxicity (ADCC) in the NK92-CD16a cell line and in peripheral blood mononuclear cells (PBMC). The results of Fab-related activity were similar for all products. Compared with Remicade®, Flixabi® had a lower percentage of charged glycan, and Remsima® had a higher percentage of galactosylated glycan and a lower percentage of afucose plus high mannosylated glycans. Whereas Remsima® and Remicade® are expressed in a Sp2/0 cell line, Flixabi® is expressed in a CHO cell line. Despite this difference, galactosylated glycans from the 3 products were not correlated with the expression system. The results of all 3 methods used in this study indicated that FcγRIIIa binding was lower with Remsima® than with Remicade®. The percentage of ADCC in NK92-CD16a cells was lower with Remsima® and higher with Flixabi® compared with Remicade®, but was similar for all 3 products in PBMC. Surface expression of CD16 was 5.7-fold greater on NK92-CD16a cells than on PBMC. Combined percentages of afucosylated and high mannosylated glycans were positively correlated with FcγRIIIa binding and ADCC in NK92-CD16 cells, while no correlation was observed in PBMC.     

Understanding the pharmacokinetics of Coartem®

Background

During pregnancy, women are more susceptible to Plasmodium falciparum infections and frequently have a higher parasitaemia than non-pregnant women. Several mechanisms are responsible for their increased susceptibility, including down-modulation of immune responses that aid in parasite clearance and sequestration of infected erythrocytes in the placenta. Early in pregnancy, a third mechanism may contribute to higher parasitaemia, since it has been reported that addition of human chorionic gonadotropin (hCG) to in vitro cultures of the NF54-strain of P. falciparum results in increased parasite growth rates. The goal of this study was to further examine the effect of hCG on P. falciparum growth.

Methods

The NF54-3D7, FVO and 7G8 strains of P. falciparum were cultured in vitro with various physiological concentrations of hCG purchased from three sources. Infected erythrocytes were also co-cultured with a human cell line that naturally secretes hCG.

Results

Results from 14 experiments using different combinations of parasite strains and concentrations of hCG from different sources, as well as the co-culture studies, failed to provide convincing evidence that hCG enhances parasite growth in vitro.

Conclusion

Based on these data, it seems unlikely that hCG has a direct effect on the rate of parasite growth early in pregnancy.     

Molecular dynamics studies of the Nafion®, Dow® and Aciplex® fuel-cell polymer membrane systems

The Nafion, Dow and Aciplex systems – where the prime differences lies in the side-chain length – have been studied by molecular dynamics (MD) simulation under standard pressure and temperature conditions for two different levels of hydration: 5 and 15 water molecules per (H)SO₃ end-group. Structural features such as water clustering, water-channel dimensions and topology, and the dynamics of the hydronium ions and water molecules have all been analysed in relation to the dynamical properties of the polymer backbone and side-chains. It is generally found that mobility is promoted by a high water content, with the side-chains participating actively in the H₃O⁺/H₂O transport mechanism. Nafion, whose side-chain length is intermediate of the three polymers studied, is found to have the most mobile polymer side-chains at the higher level of hydration, suggesting that there could be an optimal side-chain length in these systems. There are also some indications that the water-channel network connectivity is optimal for high water-content Nafion system, and that this could explain why Nafion appears to exhibit the most favourable overall hydronium/water mobility. Figure The simulation box for Aciplex with 5 water molecules per sulphonate end-group (yellow spheres). The polymer backbone is black; while side-chains are brown. The water-channel iso-surfaces are represented as blue clouds     

Osteoconductivity and osteoinductivity of NanoFUSE® DBM

Bone graft substitutes have become an essential component in a number of orthopedic applications. Autologous bone has long been the gold standard for bone void fillers. However, the limited supply and morbidity associated with using autologous graft material has led to the development of many different bone graft substitutes. Allogeneic demineralized bone matrix (DBM) has been used extensively to supplement autograft bone because of its inherent osteoconductive and osteoinductive properties. Synthetic and natural bone graft substitutes that do not contain growth factors are considered to be osteoconductive only. Bioactive glass has been shown to facilitate graft containment at the operative site as well as activate cellular osteogenesis. In the present study, we present the results of a comprehensive in vitro and in vivo characterization of a combination of allogeneic human bone and bioactive glass bone void filler, NanoFUSE^® DBM. NanoFUSE^® DBM is shown to be biocompatible in a number of different assays and has been cleared by the FDA for use in bone filling indications. Data are presented showing the ability of the material to support cell attachment and proliferation on the material thereby demonstrating the osteoconductive nature of the material. NanoFUSE^® DBM was also shown to be osteoinductive in the mouse thigh muscle model. These data demonstrate that the DBM and bioactive glass combination, NanoFUSE^® DBM, could be an effective bone graft substitute.     

Reproductive toxicity of BioThrax® in rabbits

BACKGROUND: An increasing number of women are being vaccinated during child-bearing years, including vaccination with BioThrax^® (Anthrax Vaccine Adsorbed, or AVA). As only a limited number of studies exist in humans that have examined the effects of AVA on reproductive health, this study was conducted in order to evaluate the impact AVA vaccination may have on pregnant female rabbits and their offspring. METHODS: Two hundred female rabbits were vaccinated with saline, adjuvant, or AVA twice prior to mating and on one of two occasions during gestation, in order to have exposure to the antigen during organogenesis. Blood samples were collected from does and fetuses/kits to assess the development and in utero transfer of antibodies to Bacillus anthracisprotective antigen (anti-PA IgG). Half of the does underwent Caesarean-sectioning on gestation day 29 and a gross necropsy was performed on both the does and their fetuses. The other half were allowed to naturally deliver and gross necropsy of the does and their kits was performed on lactation day 29. RESULTS: ELISA results showed that anti-PA IgG was generated by the does and passed to the fetuses/kits at detectable levels. CONCLUSIONS: AVA directly, or indirectly through the production of anti-PA IgG, did not appear to have an adverse effect on the pregnant females or their offspring, as measured by mating and fertility indices, natural delivery observations, clinical signs, gross lesions, in utero growth and survival, morphological development, or kit viability. Birth Defects Res (Part B) 86:370–376, 2009. © 2009 Wiley-Liss, Inc.     

Beziehungen zwischen Lage und Teilungsfigur der Kerne und des Protoplasmas einerseits und Wandmicellierung andererseits. Dargestellt an Rippenmeristemen und Spaltöffnungsapparaten

Ohne ZusammenfassungEs ist hier die Stelle, den Professoren Dr. v. Faber und Dr. Bergdold (München), Pilger (Berlin) und Schnarf (Wien) für die freundlichste Überlassung von Frischmaterial aus den dortigen Gewächshäusern zu danken. Zudem bin ich Herrn Professor Dr. Hoefler (Wien) zu großem Danke für die allgemeine Anregung, die Ergebnisse der Protoplasmatik mit denen meiner Kern- und Micellierungsuntersuchungen zu verbinden, verpflichtet. Diese Verbindung dürfte auch noch weiterhin manchen tiefen Einblick in das Zellgeschehen und damit der Entwicklungs- und sonstigen physiologischen Anatomie der Pflanzen zu tun gestatten.     

Apoptin®-induced apoptosis: a review

Apoptin, a protein encoded by an avian virus, induces apoptosis in various cultured human tumorigenic and/ or transformed cell lines, e.g. derived from breast and lung tumor, leukemia, lymphoma, osteosarcoma melanoma, cholangiocarcinoma, and hepatoma. In such cells, Apoptin induces p53-independent apoptosis, and the proto-oncogene Bcl-2 can accelerate this effect. The latter is surprising for, in general, Bcl-2 is known to inhibit e.g., p53-induced apoptosis. On the other hand, in normal non-transformed human cells, Apoptin is unable to induce apoptosis, even when Bcl-2 is over-expressed. In animal models Apoptin-induced apoptosis appears to be a safe and efficient anti-tumor agent. These data, in continuation with the observations that Apoptin is specifically stimulated by Bcl-2 in tumor cells, does not need p53, and is not inhibited by Bcr-Abl in these cells, imply that Apoptin is a potential anti-tumor therapy.     

Pollenfertilität und Pollenschlauchwachstum bei di- und tetraploidem Rotklee

Zusammenfassung Auf Grund zweijähriger blütenbiologischer Untersuchungen wurde festgestellt, daß der tetraploide Rotklee einen etwas höheren Prozentsatz steriler Pollenkörner ausbildet und daß die Pollenkeimung auf künstlichem Medium viel schlechter verläuft als bei den Diploiden. Auf der Narbe dagegen verläuft das Wachstum der Pollenschläuche bei den Tetraploiden schneller. Bei Selbstbestäubung ist das Schlauchwachstum bei den Diploiden verzögerter als bei den Tetraploiden, bei denen es oft zur Selbstbefruchtung kommt. Das unreglmäßige Wachstum und das Platzen der Pollenschläuche ist als eine Erscheinung der Inkompatibilität anzusehen. Ein Zusatz von Griffelgewebe zu künstlichem Agarboden ergab, daß bei Selbstungskombinationen eine Hemmung des Pollenschlauchwachstums nur bei den Diploiden stattfand, keine Hemmung dagegen bei den Tetraploiden beobachtet wurde.Der Prozeß der Pollenkeimung und des Schlauchwachstums wurde beschrieben und diskutiert. Man fand, daß die Pollenkeimung nur dann erfolgt, wenn die Narbe ein entsprechendes Stadium mikroskopisch nachweisbarer Reife erreicht hat.Die tetraploiden Rotkleepflanzen weisen eine große Variabilität in Pollenvitalität und Pollenkeimung auf, eine Selektion erscheint daher erfolgversprechend.Außenfaktoren, wie Feuchtigkeit, Temperatur und Kurztag, haben starken Einfluß auf Pollenkeimung und Schlauchwachstum. Eine Temperatur von 15° hemmt das Pollenschaluchwachstum vollkommen und macht die Befruchtung unmöglich. Kurztag verursacht anormale Blütenbildung und Pollenentwicklung, herabgesetzte Pollenkeimung und-vitalität ist die Folge.Mit 10 Abbildungen     

Assimilations- und Atmungsmessungen an diploiden und polyploiden Zuckerrüben

Ohne ZusammenfassungAuszug aus der Dissertation, Darmstadt 1956. —Meinem verehrten Lehrer, Herrn Prof. Dr.O. Stocker möchte ich für die Überlassung der Arbeit ebenso herzlich danken wie Herrn Prof. Dr.E. Knapp für seine Anregungen und Unterstützungen, sowie die Bereitstellung des Saatgutes.     

Genetik und Klinik der Hämophilie A und B

Haemophilia A and B are caused by various mutations in the factor VIII (FVIII) and factor IX (FIX) genes, respectively. The clinical course of the disease is variable, dependent on the severity of the molecular defect. Nowadays, haemophilia patients can excellently be treated by plasma-derived or recombinant clotting factor concentrates. Thus, bleeding and its consequences can be almost completely prevented with nearly normal quality of life and life expectancy. The most severe complication of this treatment is the formation of antibodies (inhibitors) against the substituted clotting factor. The risk of inhibitor formation correlates significantly with specific mutation types that preclude endogenous factor VIII/IX protein synthesis and can be as high as 20–50%. The information on the expected clinical course is at present the most important indication for FVIII/IX gene analysis. Knowledge of the underlying FVIII/IX gene mutation further allows a reliable and fast carrier diagnosis in female relatives of patients with haemophilia.     

Resistance to glufosinate is proportional to phosphinothricin acetyltransferase expression and activity in LibertyLink® and WideStrike® cotton

Planta - Insertion of the gene encoding phosphinothricin acetyltransferase (PAT) has resulted in cotton plants resistant to the herbicide glufosinate. However, the lower expression and commensurate...     

Advanced assessment of the physicochemical characteristics of Remicade® and Inflectra® by sensitive LC/MS techniques

In this study, we demonstrate the utility of ultra-performance liquid chromatography coupled to mass spectrometry (MS) and ion-mobility spectrometry (IMS) to characterize and compare reference and biosimilar monoclonal antibodies (mAbs) at an advanced level. Specifically, we focus on infliximab and compared the glycan profiles, higher order structures, and their host cell proteins (HCPs) of the reference and biosimilar products, which have the brand names Remicade® and Inflectra®, respectively. Overall, the biosimilar attributes mirrored those of the reference product to a very high degree. The glycan profiling analysis demonstrated a high degree of similarity, especially among the higher abundance glycans. Some differences were observed for the lower abundance glycans. Glycans terminated with N-glycolylneuraminic acid were generally observed to be at higher normalized abundance levels on the biosimilar mAb, while those possessing α-linked galactose pairs were more often expressed at higher levels on the reference molecule. Hydrogen deuterium exchange (HDX) analyses further confirmed the higher-order similarity of the 2 molecules. These results demonstrated only very slight differences between the 2 products, which, interestingly, seemed to be in the area where the N-linked glycans reside. The HCP analysis by a 2D-UPLC IMS-MS approach revealed that the same 2 HCPs were present in both mAb samples. Our ability to perform these types of analyses and acquire insightful data for biosimilarity assessment is based upon our highly sensitive UPLC MS and IMS methods.     

Endopolyploidie und Ertrag bei diploiden und tetraploiden Zuckerrüben

Zusammenfassung Die Regression des Rübengewichts von diploiden und tetraploiden Zuckerrüben auf den tatsächlichen Ploidiegrad des Mesophylls, der sich aus der meristematischen Ploidiestufe und der Endopolyploidie zusammensetzt, wurde in einem nassen Jahr unter Feldbedingungen geprüft. Am wenigsten leisteten die Pflanzen mit dem höchsten Endopolyploidiegrad. Die Diploiden mit geringer bis mittlerer Endopolyploidie befriedigten im Mittel gleich gut, aber unter den Tetraploiden brachten nur die Pflanzen mit der kleinsten oder einer nur wenig höheren Tendenz zur Endopolyploidisierung den höchsten Ertrag. Das beste Rübengewicht wurde sowohl bei Diploiden als auch bei Tetraploiden mit etwa tetraploidem, im vorhergehenden Trockenjahr bei Diploiden sogar mit vorwiegend diploid gebliebenem Mesophyll erreicht. Deshalb erscheint es nützlich, bei tetraploiden Zukkerrüben gegen die Endopolyploidisierung zu züchten. Die genetischen Vorteile der Tetraploidie bleiben erhalten, während der Nachteil der großen Zellen verschwinden kann.

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Endopolyploidy and yield in diploid and tetraploid sugar beets

Summary The root weight of diploid and tetraploid sugar beets as related to the actual degree of ploidy of the mesophyll, a combination of meristematic level and subsequent endopolyploidization, was investigated under field conditions in a wet year. Plants with highest endopolyploidy showed the lowest yield. Diploids with low to intermediate endopolyploidy were about equally satisfactory, but among the tetraploids only those plants with the lowest tendency toward endopolyploidization exhibited maximum yield. The highest yield was produced by both diploids and tetraploids with about tetraploid mesophyll, in the preceding dry year this was achieved by diploids with predominantly diploid mesophyll. It seems, therefore, useful in tetraploid sugar beets to breed against endopolyploidization. The genetic advantages of tetraploidy are retained while the disadvantage of large cell size may be eliminated.