We demonstrate that it is possible to observe single fluorescent molecules using a standard fluorescence microscope with mercury lamp excitation and an inexpensive cooled charge-coupled device (CCD) ...camera. With this equipment, we have been able to observe single molecules of tetramethyl-rhodamine, rhodamine 6G, fluorescein isothiocyanate and green fluorescent protein. Immobilized molecules were observed both in air and in aqueous solution.
Soon after the canonization of St. Carlo Borromeo, Cardinal Benedetto Giustiniani commissioned Lorenzo Garbieri to create three paintings for one of the chapels in the newly-erected Barnabite church ...of San Paolo Maggiore in the center of Bologna, with scenes taken from the new saint's life. This was the first chapel to be decorated in the church. Here, as will be argued below, one may find the seeds of what eventually became common in representations of the saint: Barnabite propaganda meant to accentuate not only the saint himself and his important altruistic deeds, but also the order's part in those deeds, as well as the connections between the saint and the Barnabites. An emphasis is given to the Barnabites' participation in the very deeds that became associated with the saint and through which he became known during his lifetime as a living saint. Publication Abstract
Pharmacokinetic interactions often occur as a result of activity changes of drug-metabolizing and transporting proteins, especially cytochrome P450 (CYP) isoenzymes and P-glycoprotein (P-gp). The ...activity of these enzymes and drug transporters can be enhanced or inhibited by synthetic drugs as well as by natural products. Since the number of herb-drug interactions has increased in recent years, systematic in vitro screenings and more clinical studies to identify such interactions were proposed for herbal medicinal products. However, previous results regarding this issue are not only contradictory but also of less predictability. One reason for the discrepancies could be the lack of validation of the recommended in vitro tests. Furthermore, it has to be considered that pharmacokinetic drug interactions are not only mediated by herbal medicines but also by several foods, beverages and life-style products. Since herbal medicines are considered to have a broad therapeutic range, a preventive risk assessment for pharmacokinetic drug interactions should first be realized for synthetic drugs with a narrow therapeutic index. Efforts to identify all possible interactions will lead to limitless investigations and to inconsistent decisions.
Malignant melanoma is increasing in incidence in this country. Metastatic disease generally responds poorly to most chemotherapy drugs. Immunologic and biologic agents have shown some activity in ...this disease. Interleukin 4 (IL-4) is a cytokine produced by activated T-lymphocytes with pluripotent activities including growth inhibition of various tumor cell lines in vitro and immune- mediated tumor growth inhibition in in vivo animal tumor models. In this phase II trial, patients with advanced malignant melanoma with no prior systemic therapy for metastatic disease and Southwest Oncology Group performance status 0-1 were treated with recombinant human IL-4 at a dose of 5 micrograms/kg/day by daily subcutaneous injection days 1-28 followed by a 7-day rest period, after which the cycle was repeated. Thirty-six patients were registered to this study. Two patients were ineligible by study criteria. Among the 34 eligible patients, there was 1 complete response, 0 partial responses, 2 stable/no responses, 27 increasing disease/progression, 1 early death, and 3 patients whose assessment was inadequate to determine response. The overall estimated response rate was 3% (1 of 34) with a 95% confidence interval 0.1-15%. The duration of the complete response is 421+ days. Thirty-one of the 34 eligible patients have died. The estimated median survival is 6 months (95% confidence interval 4-9 months). The most common toxicities were elevated liver function tests, nausea/vomiting/diarrhea, malaise/fatigue, edema, headache, myalgias/arthralgias, and fever/chills. Despite promising preclinical growth inhibitory and immunomodulatory effects, IL-4 in this dose and schedule showed only low antitumor activity. Alternative methods and routes of administration or combinations of IL-4 with other cytokines might produce greater antitumor effects.
Bacterial surface layer proteins have been utilized as combined vaccine carrier/adjuvants and offer a number of advantages in these applications. The crystalline protein arrays contain functional ...groups in precisely defined orientations for coupling of haptens. Conventional applications of S-layer vaccines do not cause observable trauma or side effects. Depending on the nature of the S-layer preparations, antigenic conjugates will induce immune responses of a predominantly cellular or predominantly humoral nature. Immune responses to S-layer-hapten conjugates are also observed following oral/nasal application. In the present contribution, the status of investigations with S-layer conjugates in three main immunological projects is reviewed. In a project aimed at immunotherapy of cancer, conjugates of S-layer with small, tumor-associated oligosaccharides have been found to elicit hapten-specific DTH responses. An enlarged program of chemical synthesis has now been initiated to prepare a complete set of mucin-derived, tumor-associated oligosaccharides and their chemically modified analogues for elicitation of cell-mediated immune responses to certain tumors in humans. In another application, oligosaccharides derived from capsules of Streptococcus pneumoniae type 8 have been linked to S-layer proteins and have been found to elicit protective antibody responses in animals. Most recently, allergen S-layer conjugates have been prepared with the intention to suppress the TH2-directed, IgE-mediated allergic responses to Bet nu 1, the major allergen of birch pollen. In the former two applications, the S-layer vaccine technology appears to offer the versatility needed to direct vaccination responses toward predominant control by TH1 or TH2 lymphocytes to meet the different therapeutic or prophylactic requirements in each case. In the third application, work has progressed to a preliminary stage only.
Zusammenfassung
Hintergrund
Ghrelin und andere Peptidhormone des Gastrointestinaltrakts beeinflussen Stoffwechselprozesse und die Motilität des Verdauungstraktes. Viele dieser Peptidhormone wirken ...zusätzlich über eine Bindung an spezifische Rezeptoren im zentralen Nervensystem (ZNS) auf Prozesse wie Gedächtnisfunktion, Stimmung, Belohnungsverhalten und Schlaf. Die Ausschüttung der Peptidhormone des Gastrointestinaltrakts wird über unterschiedliche Mechanismen gesteuert. Der N. vagus spielt hierbei eine wichtige Rolle.
Fragestellung
Ziel dieses Artikels ist es, den Zusammenhang zwischen gastrointestinalen Peptidhormonen (insbesondere dem im Magen gebildeten Peptidhormon Ghrelin) und den Erkrankungen REM-Schlaf-Verhaltensstörung und M. Parkinson darzustellen.
Ergebnisse
Klinische und neuropathologische Untersuchungen legen eine vagale Dysfunktion bei den beiden Erkrankungen M. Parkinson und REM-Schlaf-Verhaltensstörung (einem möglichen frühen Stadium der Parkinson Erkrankung) nahe. Peptidhormone des Gastrointestinaltrakts spielen auch aufgrund der Modulation von Prozessen im ZNS eine Rolle für neurologische Erkrankungen wie REM-Schlaf-Verhaltensstörung und M. Parkinson. In eigenen Arbeiten konnten wir zeigen, dass sich das postprandiale Ausschüttungsmuster von Ghrelin und pankreatischem Polypeptid von Patienten mit REM-Schlaf-Verhaltensstörung und M. Parkinson ähnelt und beide Patientengruppen sich von gesunden Kontrollpersonen unterscheiden. Diese Befunde unterstützen die Annahme, dass der REM-Schlaf-Verhaltensstörung und dem M. Parkinson eine gemeinsame Pathologie im neuroendokrinen System zugrunde liegt.
Schlussfolgerungen
Experimentelle Daten zeigen, dass einige der im Gastrointestinaltrakt gebildeten Peptidhormone eine neuroprotektive Wirkung haben. Da beispielsweise Ghrelin-Agonisten in anderen Indikationen bereits klinisch getestet werden, könnten Peptidhormone mittelfristig auch Bedeutung für neuroprotektive Therapiestrategien bei den beiden oben angegebenen Erkrankungen erlangen.
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