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At least 19 recordsLinked to original sources
PubMed2001

The first clone.

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Bioethics↗
PubMed2001

Beating the ban.

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Cloning, Organism↗
PubMed2001

Tracking oligodendrocytes during development and regeneration.

Over the past decade, advances in strategies to tag cells have opened new avenues for examining the development of myelin-forming glial cells and for monitoring transplanted cells in animal models of myelin insufficiency. The strategies for labelling glial cells have encompassed a range of genetic modifications as well as methods for directly attaching labels to cells. Genetically modified oligodendrocytes have been engineered to express enzymatic (e.g., beta-galactosidase, alkaline phosphatase), naturally fluorescent (e.g., green fluorescent protein), and antibiotic resistance (e.g., neomycin, zeomycin) reporters. Genes have been introduced in vivo and in vitro with viral or plasmid vectors to somatically label glial cells. To generate germ-line transmission of tagged oligodendrocytes, transgenic mice have been created both by direct injection into mouse fertilized eggs and by "knock-in" of reporters targetted to myelin gene loci in embryonic stem cells. Each experimental approach has advantages and limitations that need to be considered for individual applications. The availability of tagged glial cells has expanded our basic understanding of how oligodendrocytes are specified from stem cells and should continue to fill in the gaps in our understanding of how oligodendrocytes differentiate, myelinate, and maintain their myelin sheaths. Moreover, the ability to select oligodendrocytes by virtue of their acquired antibiotic resistance has provided an important new tool for isolating and purifying oligodendrocytes. Tagged glial cells have also been invaluable in evaluating cell transplant therapies in the nervous system. The tracking technologies that have driven these advances in glial cell biology are continuing to evolve and present new opportunities for examining oligodendrocytes in living systems. Microsc. Res. Tech. 52:766-777, 2001. Published 2001 Wiley-Liss, Inc.

Animals↗
PubMed1994

Photodynamic therapy and cancer of the esophagus.

Esophageal carcinoma usually is diagnosed at an advanced, incurable stage. In patients with good operative risk, surgery is still considered the ideal treatment. Patients with coexisting major medical conditions in whom resective surgery is precluded may benefit from several therapeutic options, including photodynamic therapy (PDT) with porfimer sodium (Photofrin; manufactured by Lederle Parenterals, Carolina, Puerto Rico, under license from Quadra Logic Technologies, Inc, Vancouver, British Columbia, Canada), dilation, thermal destruction, Nd:YAG laser ablation, injection therapy, and placement of prosthetic tubes. Photodynamic therapy with porfimer sodium is thought to have a direct toxic effect on malignant cells via the production of singlet oxygen, which damages the microvasculature of the tumor and renders it ischemic. The 630 nm wavelength used for clinical PDT exhibits the greatest relative degree of light penetration into tissue, with corresponding activation of retained photosensitizer. The efficacy of PDT with porfimer sodium is closely related to stage of disease. It should be emphasized that PDT has been shown to be potentially curative in patients with early, noninvasive tumors of both squamous and glandular (adenocarcinoma) histologies. Eighty-three patients with esophageal carcinoma were treated using PDT. At presentation, 60% of patients had recurrence following previous radiotherapy or chemotherapy. Patients with less advanced disease had a better response to PDT with regard to relief of dysphagia and prolongation of survival. Photodynamic therapy was found to be more useful than Nd:YAG laser therapy for high, upper third lesions, especially circumferential ones. For tumors larger than 8 cm, PDT was twice as effective as Nd:YAG laser therapy in establishing prolonged lumen patency, especially for adenocarcinomas. Photodynamic therapy appears to have the added advantages of fewer treatments and less pain. The role of PDT in gastrointestinal malignancies continues to evolve.

Adenocarcinoma↗
PubMed1998

Inhibitors of tryptase for the treatment of mast cell-mediated diseases.

Human tryptase is a structurally unique and mast cell specific trypsin-like serine protease. Recent biological and immunological investigations have implicated tryptase as a mediator in the pathology of numerous allergic and inflammatory conditions including rhinitis, conjunctivitis, and most notably asthma. A growing body of data further implicates tryptase in certain gastrointestinal, dermatological, and cardiovascular disorders as well. The recent availability of potent, and selective tryptase inhibitors, though, has facilitated the validation of this protease as an important therapeutic target as well. Herein, we describe the design and potency of four classes of selective tryptase inhibitors, of which the first three types are synthetic and the fourth is natural in origin: 1) peptidic inhibitors (e.g., APC-366), 2) dibasic inhibitors (i.e., pentamidine-like), 3) Zn(2+)-mediated inhibitors (i.e., BABIM-like), and 4) heparin antagonists (e.g., lactoferrin). These inhibitors have been tested in the airways and skin of allergic sheep. Aerosol administration of tryptase inhibitors from each structural class 30 minutes before, and 4 hours and 24 hours after allergen challenge, abolishes late phase bronchoconstriction and airway hyperresponsiveness in a dose-dependent manner. Moreover, intradermal injection of APC-366 blocks the cutaneous response to antigen. These studies provide the essential proof-of-concept for the further pursuit of tryptase inhibitors for the treatment of asthma, and perhaps other allergic diseases. Results from clinical studies with the first generation tryptase inhibitor APC-366, currently in phase II trials for the treatment of asthma, provide additional support for a pathological role for tryptase in this disease. Notable advances in the area of tryptase inhibitor design at Axys Pharmaceuticals, Inc. include a novel, zinc-mediated, serine protease inhibitor technology (described herein), and the discovery of a unique class of extremely potent and selective dibasic tryptase inhibitors. Independently, an X-ray crystal structure of active tryptase tetramer complexed with 4-amidinophenyl pyruvic acid has been reported. It is anticipated that these discoveries will further accelerate the design of structurally novel tryptase inhibitors as well as the development of new drugs for the treatment of mast cell tryptase-mediated disorders.

Animals↗