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

Production of recombinant anthrax toxin receptor (ATR/CMG2) fused with human Fc in planta.

Infection of normal human melanocyte and nevus cultures with an adenovirus 12-Simian Virus 40 hybrid virus (Ad12-SV40) produced transformed cells that expressed SV40-T antigen. The Ad12-SV40 cells exhibited rapid cell proliferation to high cell densities and efficient growth in soft agar, but none of 15 transformed melanocyte and nevus cultures formed tumors when injected s.c. or under the renal capsule into athymic nude mice. While the Ad12-SV40-transformed cells lost certain properties associated with the melanocytic phenotype, i.e., pigmentation, tyrosinase activity and melanosome content, the expression of melanoma-associated antigens, including nerve growth factor receptor, p97 melanotransferrin, and chondroitin sulfate proteoglycan, remained stable. The transformed melanocytes acquired the ability to express HLA-DR antigen, which is found on nevus and melanoma cells. Total ganglioside patterns in Ad12-SV40-transformed cells changed to reflect more advanced stages of tumor progression. Transformed melanocytes, like nevus and melanoma cells, showed increased GD3 content and transformed nevus cells increased GD2 which is a feature of malignant melanoma cells. Ad 12-SV40-transformed human melanocytes and nevus cells are useful tools for studying tumor progression under experimental conditions.

Transformation of normal human melanocytes and non-malignant nevus cells by adenovirus 12-SV40 hybrid virus.

The present invention discloses novel methods for producing foreign polypeptides in a host plant using recombinant viruses through functional complementation systems. The methods involve constructing suitable recombinant viral vectors that are capable of systemic infection and infecting the host plants with one or more recombinant viral vectors. The methods are also directed to infecting a host plant that is transgenic for expressing replicase genes of a virus, wherein the transgenic plant expressing a virus replicase genes complements the virus replicase function. The invention also discloses a method for producing a full-length antibody in a host plant using viral vectors.

Production of biomedical peptides and proteins in plants using plant virus vectors

A fusion capsid protein comprising a plant virus capsid protein fused to an antigenic polypeptide is used as a molecule for presentation of that polypeptide to the immune system of an animal such as a human. The plant virus capsid protein is that of an alfalfa mosaic virus (AlMV) or ilarvirus.

Hilary Koprowski

Papers

Production of recombinant anthrax toxin receptor (ATR/CMG2) fused with human Fc in planta.

Transformation of normal human melanocytes and non-malignant nevus cells by adenovirus 12-SV40 hybrid virus.

Production of biomedical peptides and proteins in plants using plant virus vectors

Polypeptides fused with alfalfa mosaic virus or ilarvirus capsid

Specific detection of antibodies in cancer patients following immunotherapy with anti-idiotype.