The serial cultivation of human diploid cell strains.

The limited in vitro lifetime of human diploid cell strains

The discovery that mammalian cells have the ability to synthesize the free radical nitric oxide (NO) has stimulated an extraordinary impetus for scientific research in all the fields of biology and medicine. Since its early description as an endothelial-derived relaxing factor, NO has emerged as a fundamental signaling device regulating virtually every critical cellular function, as well as a potent mediator of cellular damage in a wide range of conditions. Recent evidence indicates that most of the cytotoxicity attributed to NO is rather due to peroxynitrite, produced from the diffusion-controlled reaction between NO and another free radical, the superoxide anion. Peroxynitrite interacts with lipids, DNA, and proteins via direct oxidative reactions or via indirect, radical-mediated mechanisms. These reactions trigger cellular responses ranging from subtle modulations of cell signaling to overwhelming oxidative injury, committing cells to necrosis or apoptosis. In vivo, peroxynitrite generation represents a crucial pathogenic mechanism in conditions such as stroke, myocardial infarction, chronic heart failure, diabetes, circulatory shock, chronic inflammatory diseases, cancer, and neurodegenerative disorders. Hence, novel pharmacological strategies aimed at removing peroxynitrite might represent powerful therapeutic tools in the future. Evidence supporting these novel roles of NO and peroxynitrite is presented in detail in this review.

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Nitric Oxide and Peroxynitrite in Health and Disease

▪ Abstract At the interface between the innate and adaptive immune systems lies the high-output isoform of nitric oxide synthase (NOS2 or iNOS). This remarkable molecular machine requires at least 17 binding reactions to assemble a functional dimer. Sustained catalysis results from the ability of NOS2 to attach calmodulin without dependence on elevated Ca2+. Expression of NOS2 in macrophages is controlled by cytokines and microbial products, primarily by transcriptional induction. NOS2 has been documented in macrophages from human, horse, cow, goat, sheep, rat, mouse, and chicken. Human NOS2 is most readily observed in monocytes or macrophages from patients with infectious or inflammatory diseases. Sustained production of NO endows macrophages with cytostatic or cytotoxic activity against viruses, bacteria, fungi, protozoa, helminths, and tumor cells. The antimicrobial and cytotoxic actions of NO are enhanced by other macrophage products such as acid, glutathione, cysteine, hydrogen peroxide, or superoxid...

Nitric oxide and macrophage function

http://theory.bio.uu.nl/immbio/Marks91.pdf

By-passing immunization: Human antibodies from V-gene libraries displayed on phage

While neutralization tests in embryonated eggs have been described by a number of authors, the methods on the whole have been based on the quantitative ability of an immune serum to suppress the pocklike lesions produced by the free virus, and in only a few instances (Bumet and Galloway, 1934; Keogh, cited in Bumet, 1936; Higbie and Howitt, 1935) has death or survival of the embryos been used as a criterion of neutralizing capacity. Since the Venezuelan equine encephalomyelitis virus is highly and uniformly lethal for chick embryos (Koprowski and Lennette, 1944), the possibility was considered that a neutralization test in this species, based on alterations of the lethal end point of the virus by a serum, might perhaps prove to be more sensitive than the usual intracerebral test in mice. Serum-virus mixtures, accordingly, were tested by parallel inoculation into eggs and mice, and a comparison of the results is presented here.

Comparative Sensitivity of Venezuelan Equine Encephalomyelitis Virus Neutralization Tests in Chick Embryos and in Mice.

Methods in virology. Vol. II.

The present invention relates to a method for the generation of transgenic Brassica oleracea plants, in particular transgenic Cruciferae (also known as Brassicaceae) plants. The present invention also provides a method for the production of heterologous proteins using a Cruciferae-based plant system, for example pharmaceutical and/or recombinant proteins. In particular the invention also relates to a method for the production of transgenic collard and cauliflower, and to the large scale production of pharmaceutical and/or therapeutic production, such as production of Cruciferae-based vaccine production.

Cruciferae-based plant system for the generation and production of recombinant proteins and vaccines

From the early 1990s the recombinant DNA technology led researchers to explore plants as a novel source for antigen expression. The concept of production edible vaccines in plants has been recognized to be attractive for its safety, simplicity and low farming cost (Mason et al 1992). The latter might be especially valid for developing countries where classical ways of vaccination often encounter various limitations. Plants are potentially useful for delivering vaccines as it is widely known that plants themselves produce a variety of medically valuable compounds. There are two well established systems for antigen expression in plant.

Biotechnological Approaches to Making Vaccine in Plants

A process for the synthesis and delivery of bioactive compounds, compounds that have a therapeutic, biochemical, or immunologic effect on an animal, such as human. In the process, an endophytic microorganism is genetically altered so that it synthesizes the bioactive compound. A plant may be infected with the genetically altered microorganism and used as an oral delivery system.

Hilary Koprowski

Papers

Comparative Sensitivity of Venezuelan Equine Encephalomyelitis Virus Neutralization Tests in Chick Embryos and in Mice.

Methods in virology. Vol. II.

Cruciferae-based plant system for the generation and production of recombinant proteins and vaccines

Biotechnological Approaches to Making Vaccine in Plants

Synthesis of immunologic, therapeutic and prophylactic compounds by endophytic microorganisms