Detection of Sialic Acids and Gangliosides with Special Reference to 9-O-Acetylated Species in Basaliomas and Normal Human Skin

Basal cell carcinomas and normal skin were examined in relation to the abnormal expression of gangliosides. The content of gangliosides with 9-O-acetylated sialic acids of 26 sample pairs was analyzed by a microtiter assay using influenza C virus as well as by fluorimetric high-performance liquid chromatography of the sialic acids released. The 9-O-acetylation levels were significantly (up to 56-fold) higher in basal cell carcinoma tissues than in the skin surrounding basal cell carcinomas. Slightly elevated amounts of O-acetylated gangliosides were also seen in the skin marginal to the basaliomas. The ganglioside composition of four sets of pooled samples of basal cell carcinoma and one pool of normal skin were studied by high-performance thin-layer chromatography and immune high-performance thin-layer chromatography using monoclonal antibodies against 9-O-acetyl GD3. The lipid-bound sialic acid content of normal skin was 0.029 μg dry weight, whereas in nodular basal cell carcinomas it was approximately twice as much. Several O-acetylated sialic acids were seen by high-performance liquid chromatography analysis, but N-acetyl-9-O-acetylneuraminic acid prevailed. Only in the tumor ganglioside fraction, a small amount of N-glycolylneuraminic acid was found. The 9-O-acetylated gangliosides with mainly 9-O-acetyl-GD3 can be considered as tumor-associated antigens or markers for basal cell carcinomas. This finding about tumor-associated carbohydrates may contribute to new strategies in current tumor diagnosis and therapy

Solubilization, Activation and Partial Purification of a Sialidase from Horse Liver

Using sialyl-methylumbelliferyl -glycoside as substrate, sialidase in horse liver was detected as a membrane-bound enzyme. A yield of about 50% of sialidase activity was found in supernatant when solubilized in 0.1 M sodium-phosphate buffer pH 5.5, containing 0.15 M NaCl, 0.25 M sucrose, and 0.5% Triton X-100. Sialidase in the solubilisate could be activated by incubating in acidic pH at 37 oC. Incubation of this solubilized enzyme at 37 oC for 1.5 h at pH 5.0 led to 10% increase of activity and to the precipitation of about 50% of contaminating protein. Using cation-exchange chromatography on S-Sepharose FF and affinity chromatography on p-aminophenyl oxamic acid-agarose following solubilization and activation, about 6% of total sialidase activity was recovered with the purification factor of about 500. The pH and temperature optimum were measured at pH 4.3 and between 37-45 oC, respectively. Neu5Ac2en was a strong inhibitor, while p-aminophenyl oxamic acid had only a weak inhibitory effect

Analysis of monosaccharides, fatty constituents and rare O-acetylated sialic acids from gonads of the starfish Asterias rubens

Abstract A previous study (Bergwerff et al., Biochimie 74 (1992

A generic questionnaire framework supporting psychological studies with smartphone technologies

Many psychological studies are performed with specifically tailored ‘‘paper & pencil’’-questionnaires. Such a paper-based approach usually results in a massive workload for evaluating and analyzing the collected data afterwards, e.g., to transfer data to electronic worksheets or any statistics software. To relieve researchers from such manual tasks and to improve the efficiency of data collection processes, we realized smart device applications for existing psychological questionnaires (e.g., the KINDEX, PDS, or CAPS questionnaire). Based on these applications, we were able to demonstrate the usefulness of smart devices (e.g., smartphones or tablets) for mobile data collection in the context of psychological questionnaires. Although the implemented applications already have shown several advantages in respect to data collection and analysis, they have not been suitable for psychological studies in the large scale yet, e.g., due to the high maintenance efforts for the psychologists. More precisely, changes to a questionnaire or its structure still must be accomplished by computer scientists, since its implementation is hard-coded. What is needed instead is an easy-to-use and self-explaining framework for creating, running, and evolving the questionnaires of psychological studies on mobile and smart devices. In this context, supporting the complete questionnaire lifecycle is essential, i.e., IT support for creating, using, evaluating, and archiving questionnaires is required to assist end-users having no programming background. We present our generic questionnaire framework, which encompasses the following three parts: a questionnaire configurator to create the questions and questionnaires, a way of integrating mobile devices to deploy, run and log questionnaires, and a middleware enabling a secure data exchange. Finally, we discuss how smartphone technology and mobile devices can be used to suitably support psychologists in their daily work with questionnaires. As major benefit of the framework, better data quality, shorter evaluation cycles, and significant decreases in workload will result

Efficacy of Chondroprotective Food Supplements Based on Collagen Hydrolysate and Compounds Isolated from Marine Organisms †

Osteoarthritis belongs to the most common joint diseases in humans and animals and shows increased incidence in older patients. The bioactivities of collagen hydrolysates, sulfated glucosamine and a special fatty acid enriched dog-food were tested in a dog patient study of 52 dogs as potential therapeutic treatment options in early osteoarthritis. Biophysical, biochemical, cell biological and molecular modeling methods support that these well-defined substances may act as effective nutraceuticals. Importantly, the applied collagen hydrolysates as well as sulfated glucosamine residues from marine organisms were strongly supported by both an animal model and molecular modeling of intermolecular interactions. Molecular modeling of predicted interaction dynamics was evaluated for the receptor proteins MMP-3 and ADAMTS-5. These proteins play a prominent role in the maintenance of cartilage health as well as innate and adapted immunity. Nutraceutical data were generated in a veterinary clinical study focusing on mobility and agility. Specifically, key clinical parameter (MMP-3 and TIMP-1) were obtained from blood probes of German shepherd dogs with early osteoarthritis symptoms fed with collagen hydrolysates. Collagen hydrolysate, a chondroprotective food supplement was examined by high resolution NMR experiments. Molecular modeling simulations were used to further characterize the interaction potency of collagen fragments and glucosamines with protein receptor structures. Potential beneficial effects of collagen hydrolysates, sulfated glycans (i.e., sulfated glucosamine from crabs and mussels) and lipids, especially, eicosapentaenoic acid (extracted from fish oil) on biochemical and physiological processes are discussed here in the context of human and veterinary medicine

The sialic acid-dependent nematocyst discharge process in relation to its physical-chemical properties is a role model for nanomedical diagnostic and therapeutic tools

Formulas derived from theoretical physics provide important insights about the nematocyst discharge process of Cnidaria (Hydra, jellyfishes, box-jellyfishes and sea-anemones). Our model description of the fastest process in living nature raises and answers questions related to the material properties of the cell- and tubule-walls of nematocysts including their polysialic acid (polySia) dependent target function. Since a number of tumor-cells, especially brain-tumor cells such as neuroblastoma tissues carry the polysaccharide chain polySia in similar concentration as fish eggs or fish skin, it makes sense to use these findings for new diagnostic and therapeutic approaches in the field of nanomedicine. Therefore, the nematocyst discharge process can be considered as a bionic blue-print for future nanomedical devices in cancer diagnostics and therapies. This approach is promising because the physical background of this process can be described in a sufficient way with formulas presented here. Additionally, we discuss biophysical and biochemical experiments which will allow us to define proper boundary conditions in order to support our theoretical model approach. PolySia glycans occur in a similar density on malignant tumor cells than on the cell surfaces of Cnidarian predators and preys. The knowledge of the polySia-dependent initiation of the nematocyst discharge process in an intact nematocyte is an essential prerequisite regarding the further development of target-directed nanomedical devices for diagnostic and therapeutic purposes. The theoretical description as well as the computationally and experimentally derived results about the biophysical and biochemical parameters can contribute to a proper design of anti-tumor drug ejecting vessels which use a stylet-tubule system. Especially, the role of nematogalectins is of interest because these bridging proteins contribute as well as special collagen fibers to the elastic band properties. The basic concepts of the nematocyst discharge process inside the tubule cell walls of nematocysts were studied in jellyfishes and in Hydra which are ideal model organisms. Hydra has already been chosen by Alan Turing in order to figure out how the chemical basis of morphogenesis can be described in a fundamental way. This encouraged us to discuss the action of nematocysts in relation to morphological aspects and material requirements. Using these insights, it is now possible to discuss natural and artificial nematocyst-like vessels with optimized properties for a diagnostic and therapeutic use, e.g., in neurooncology. We show here that crucial physical parameters such as pressure thresholds and elasticity properties during the nematocyst discharge process can be described in a consistent and satisfactory way with an impact on the construction of new nanomedical devices

Weideochsenmast ohne Kraftfutter

Bei Weidehaltung von Rindern ist die Besatzdichte ein wesentliches Kriterium für die erzielbare Einzeltierleistung und die Flächenproduktivität. Bei Kurzrasenweidehaltung besteht zwischen Tierbesatz und Aufwuchshöhe ein Zusammenhang. In der vorliegenden Arbeit wurde der Einfluss der Weideaufwuchshöhe bei Kurzrasenweidehaltung auf die Mastleistung und Flächenproduktivität in der Ochsenmast ohne Kraftfutterergänzung im Berggebiet Österreichs untersucht. In der 2. Mitteilung (Steinwidder et al., 2019b) wird auf die Schlachtleistung, Fleischqualität und Wirtschaftlichkeit eingegangen. Der Versuch wurde in zwei Durchgängen mit insgesamt 24 Fleckviehochsen, aufgeteilt auf jährlich 3 Versuchsgruppen, von 225 kg bis 700 kg Lebendgewicht durchgeführt. In der Gruppe „kurz“ wurde eine Weideaufwuchshöhe vom 5,0, in der Gruppe „mittel“ von 6,5 und in der Gruppe lang von 8,0 cm angestrebt. Die Aufwuchshöhe jeder Dauergrünlandfläche wurde wöchentlich mit dem Rising Plate Pasture Meter erfasst und die Weideflächengröße dementsprechend im Vegetationsverlauf vergrößert. Nach der ersten Weideperiode wurden die Ochsengruppen im Winter jeweils in Tretmistboxen gehalten und mit Grassilage gefüttert und kamen danach wiederum auf die entsprechenden Kurzrasenweideflächen. Mit Ausnahme von vier Tieren der Gruppe „kurz“, welche bis zur Erreichung des Mastendgewichts nochmals im Herbst aufgestallt werden mussten, kamen alle Ochsen in der zweiten Weideperiode zur Schlachtung. Der Nährstoffgehalt der Weidefutterproben der drei Weide-Aufwuchsgruppen unterschied sich nur geringfügig, der durchschnittliche Rohproteingehalt lag bei 20% und die durchschnittliche Energiekonzentration bei 10,7 MJ ME. Mit zunehmender Aufwuchshöhe nahmen jedoch die Futterverluste zu, ging die Homogenität der Pflanzenbestandesnutzung zurück und wurden Weidepflegemaßnahmen vermehrt erforderlich. Das Schlachtalter der Tiere lag im Mittel bei 26,4 (kurz), 24,8 (mittel) bzw. 24,2 (lang) Monaten. In der Versuchsdauer bzw. den Tageszunahmen wurden an der Signifikanzgrenze liegende Gruppenunterschiede festgestellt (P-Werte 0,06 bzw. 0,07). Die Tageszunahmen der Gruppe kurz (864 g) lagen tendenziell unter jener der Gruppen mittel (950 g) und lang (935 g). Der Flächenbedarf je Tier war in der Gruppe lang signifikant höher als in den Gruppen kurz und mittel. In der Flächenleistung (Lebendgewichtszuwachs/ha) fielen die Tiere der Gruppe lang mit 492 kg/ha signifikant von den anderen beiden Gruppen (kurz 612 kg/ha bzw. mittel 606 kg/ha) ab. Jene Versuchsgruppen, welche die höchsten täglichen Zunahmen erreichten, erzielten nicht die höchste Flächenleistung

Multiple Myeloma Treatment in Real-world Clinical Practice : Results of a Prospective, Multinational, Noninterventional Study

Funding Information: The authors would like to thank all patients and their families and all the EMMOS investigators for their valuable contributions to the study. The authors would like to acknowledge Robert Olie for his significant contribution to the EMMOS study. Writing support during the development of our report was provided by Laura Mulcahy and Catherine Crookes of FireKite, an Ashfield company, a part of UDG Healthcare plc, which was funded by Millennium Pharmaceuticals, Inc, and Janssen Global Services, LLC. The EMMOS study was supported by research funding from Janssen Pharmaceutical NV and Millennium Pharmaceuticals, Inc. Funding Information: The authors would like to thank all patients and their families and all the EMMOS investigators for their valuable contributions to the study. The authors would like to acknowledge Robert Olie for his significant contribution to the EMMOS study. Writing support during the development of our report was provided by Laura Mulcahy and Catherine Crookes of FireKite, an Ashfield company, a part of UDG Healthcare plc, which was funded by Millennium Pharmaceuticals, Inc, and Janssen Global Services, LLC. The EMMOS study was supported by research funding from Janssen Pharmaceutical NV and Millennium Pharmaceuticals, Inc. Funding Information: M.M. has received personal fees from Janssen, Celgene, Amgen, Bristol-Myers Squibb, Sanofi, Novartis, and Takeda and grants from Janssen and Sanofi during the conduct of the study. E.T. has received grants from Janssen and personal fees from Janssen and Takeda during the conduct of the study, and grants from Amgen, Celgene/Genesis, personal fees from Amgen, Celgene/Genesis, Bristol-Myers Squibb, Novartis, and Glaxo-Smith Kline outside the submitted work. M.V.M. has received personal fees from Janssen, Celgene, Amgen, and Takeda outside the submitted work. M.C. reports honoraria from Janssen, outside the submitted work. M. B. reports grants from Janssen Cilag during the conduct of the study. M.D. has received honoraria for participation on advisory boards for Janssen, Celgene, Takeda, Amgen, and Novartis. H.S. has received honoraria from Janssen-Cilag, Celgene, Amgen, Bristol-Myers Squibb, Novartis, and Takeda outside the submitted work. V.P. reports personal fees from Janssen during the conduct of the study and grants, personal fees, and nonfinancial support from Amgen, grants and personal fees from Sanofi, and personal fees from Takeda outside the submitted work. W.W. has received personal fees and grants from Amgen, Celgene, Novartis, Roche, Takeda, Gilead, and Janssen and nonfinancial support from Roche outside the submitted work. J.S. reports grants and nonfinancial support from Janssen Pharmaceutical during the conduct of the study. V.L. reports funding from Janssen Global Services LLC during the conduct of the study and study support from Janssen-Cilag and Pharmion outside the submitted work. A.P. reports employment and shareholding of Janssen (Johnson & Johnson) during the conduct of the study. C.C. reports employment at Janssen-Cilag during the conduct of the study. C.F. reports employment at Janssen Research and Development during the conduct of the study. F.T.B. reports employment at Janssen-Cilag during the conduct of the study. The remaining authors have stated that they have no conflicts of interest. Publisher Copyright: © 2018 The AuthorsMultiple myeloma (MM) remains an incurable disease, with little information available on its management in real-world clinical practice. The results of the present prospective, noninterventional observational study revealed great diversity in the treatment regimens used to treat MM. Our results also provide data to inform health economic, pharmacoepidemiologic, and outcomes research, providing a framework for the design of protocols to improve the outcomes of patients with MM. Background: The present prospective, multinational, noninterventional study aimed to document and describe real-world treatment regimens and disease progression in multiple myeloma (MM) patients. Patients and Methods: Adult patients initiating any new MM therapy from October 2010 to October 2012 were eligible. A multistage patient/site recruitment model was applied to minimize the selection bias; enrollment was stratified by country, region, and practice type. The patient medical and disease features, treatment history, and remission status were recorded at baseline, and prospective data on treatment, efficacy, and safety were collected electronically every 3 months. Results: A total of 2358 patients were enrolled. Of these patients, 775 and 1583 did and did not undergo stem cell transplantation (SCT) at any time during treatment, respectively. Of the patients in the SCT and non-SCT groups, 49%, 21%, 14%, and 15% and 57%, 20%, 12% and 10% were enrolled at treatment line 1, 2, 3, and ≥ 4, respectively. In the SCT and non-SCT groups, 45% and 54% of the patients had received bortezomib-based therapy without thalidomide/lenalidomide, 12% and 18% had received thalidomide/lenalidomide-based therapy without bortezomib, and 30% and 4% had received bortezomib plus thalidomide/lenalidomide-based therapy as frontline treatment, respectively. The corresponding proportions of SCT and non-SCT patients in lines 2, 3, and ≥ 4 were 45% and 37%, 30% and 37%, and 12% and 3%, 33% and 27%, 35% and 32%, and 8% and 2%, and 27% and 27%, 27% and 23%, and 6% and 4%, respectively. In the SCT and non-SCT patients, the overall response rate was 86% to 97% and 64% to 85% in line 1, 74% to 78% and 59% to 68% in line 2, 55% to 83% and 48% to 60% in line 3, and 49% to 65% and 36% and 45% in line 4, respectively, for regimens that included bortezomib and/or thalidomide/lenalidomide. Conclusion: The results of our prospective study have revealed great diversity in the treatment regimens used to manage MM in real-life practice. This diversity was linked to factors such as novel agent accessibility and evolving treatment recommendations. Our results provide insight into associated clinical benefits.publishersversionPeer reviewe