Kent G. Osborn

Bio: Kent G. Osborn is an academic researcher from University of California, San Diego. The author has contributed to research in topics: Extracellular matrix & Decellularization. The author has an hindex of 12, co-authored 21 publications receiving 1141 citations. Previous affiliations of Kent G. Osborn include University of California, Davis.

Safety and Efficacy of an Injectable Extracellular Matrix Hydrogel for Treating Myocardial Infarction

Abstract: New therapies are needed to prevent heart failure after myocardial infarction (MI). As experimental treatment strategies for MI approach translation, safety and efficacy must be established in relevant animal models that mimic the clinical situation. We have developed an injectable hydrogel derived from porcine myocardial extracellular matrix as a scaffold for cardiac repair after MI. We establish the safety and efficacy of this injectable biomaterial in large- and small-animal studies that simulate the clinical setting. Infarcted pigs were treated with percutaneous transendocardial injections of the myocardial matrix hydrogel 2 weeks after MI and evaluated after 3 months. Echocardiography indicated improvement in cardiac function, ventricular volumes, and global wall motion scores. Furthermore, a significantly larger zone of cardiac muscle was found at the endocardium in matrix-injected pigs compared to controls. In rats, we establish the safety of this biomaterial and explore the host response via direct injection into the left ventricular lumen and in an inflammation study, both of which support the biocompatibility of this material. Hemocompatibility studies with human blood indicate that exposure to the material at relevant concentrations does not affect clotting times or platelet activation. This work therefore provides a strong platform to move forward in clinical studies with this cardiac-specific biomaterial that can be delivered by catheter.

Simian AIDS: isolation of a type D retrovirus and transmission of the disease

Abstract: A type D retrovirus related to but distinct from Mason-Pfizer monkey virus was isolated in vitro from the blood of two rhesus monkeys (Macaca mulatta) with simian acquired immunodeficiency syndrome (SAIDS). Three juvenile rhesus monkeys that were injected intravenously with tissue culture fluids containing this virus developed SAIDS after 2 to 4 weeks.

Enzyme-Responsive Nanoparticles for Targeted Accumulation and Prolonged Retention in Heart Tissue after Myocardial Infarction.

Abstract: A method for targeting to and retaining intravenously injected nanoparticles at the site of acute myocardial infarction in a rat model is described. Enzyme-responsive peptide-polymer amphiphiles are assembled as spherical micellar nanoparticles, and undergo a morphological transition from spherical-shaped, discrete materials to network-like assemblies when acted upon by matrix metalloproteinases (MMP-2 and MMP-9), which are up-regulated in heart tissue post-myocardial infarction.

PLD3 and PLD4 are single-stranded acid exonucleases that regulate endosomal nucleic-acid sensing.

Abstract: The sensing of microbial genetic material by leukocytes often elicits beneficial pro-inflammatory cytokines, but dysregulated responses can cause severe pathogenesis. Genome-wide association studies have linked the gene encoding phospholipase D3 (PLD3) to Alzheimer's disease and have linked PLD4 to rheumatoid arthritis and systemic sclerosis. PLD3 and PLD4 are endolysosomal proteins whose functions are obscure. Here, PLD4-deficient mice were found to have an inflammatory disease, marked by elevated levels of interferon-γ (IFN-γ) and splenomegaly. These phenotypes were traced to altered responsiveness of PLD4-deficient dendritic cells to ligands of the single-stranded DNA sensor TLR9. Macrophages from PLD3-deficient mice also had exaggerated TLR9 responses. Although PLD4 and PLD3 were presumed to be phospholipases, we found that they are 5' exonucleases, probably identical to spleen phosphodiesterase, that break down TLR9 ligands. Mice deficient in both PLD3 and PLD4 developed lethal liver inflammation in early life, which indicates that both enzymes are needed to regulate inflammatory cytokine responses via the degradation of nucleic acids.

Harrison's Principles of Internal Medicine

Abstract: The 11th edition of Harrison's Principles of Internal Medicine welcomes Anthony Fauci to its editorial staff, in addition to more than 85 new contributors. While the organization of the book is similar to previous editions, major emphasis has been placed on disorders that affect multiple organ systems. Important advances in genetics, immunology, and oncology are emphasized. Many chapters of the book have been rewritten and describe major advances in internal medicine. Subjects that received only a paragraph or two of attention in previous editions are now covered in entire chapters. Among the chapters that have been extensively revised are the chapters on infections in the compromised host, on skin rashes in infections, on many of the viral infections, including cytomegalovirus and Epstein-Barr virus, on sexually transmitted diseases, on diabetes mellitus, on disorders of bone and mineral metabolism, and on lymphadenopathy and splenomegaly. The major revisions in these chapters and many

Remodelling the extracellular matrix in development and disease.

Abstract: The extracellular matrix (ECM) is a highly dynamic structure that is present in all tissues and continuously undergoes controlled remodelling. This process involves quantitative and qualitative changes in the ECM, mediated by specific enzymes that are responsible for ECM degradation, such as metalloproteinases. The ECM interacts with cells to regulate diverse functions, including proliferation, migration and differentiation. ECM remodelling is crucial for regulating the morphogenesis of the intestine and lungs, as well as of the mammary and submandibular glands. Dysregulation of ECM composition, structure, stiffness and abundance contributes to several pathological conditions, such as fibrosis and invasive cancer. A better understanding of how the ECM regulates organ structure and function and of how ECM remodelling affects disease progression will contribute to the development of new therapeutics.

Neurological manifestations of the acquired immunodeficiency syndrome (AIDS): experience at UCSF and review of the literature.

Abstract: In this review of the acquired immunodeficiency syndrome (AIDS) the authors have evaluated a total of 352 homosexual patients with AIDS or generalized lymphadenopathy managed at the University of California San Francisco (UCSF) between 1979 and 1984. Of an initial unselected group of 318 patients 124 (39%) were neurologically symptomatic and 1/3 already had their neurological complaints at the time of presentation. An additional 210 AIDS patients with neurological symptoms have been reported in the literature. Thus a total of 366 neurologically symptomatic patients with AIDS or lymphadenopathy are reviewed. Central nervous system (CNS) complications encountered in 315 patients included the following viral syndromes: subacute encephalitis (54) atypical aseptic meningitis (21) herpes simplex encephalitis (9) progressive multifocal leukoencephalopathy (6) viral myelitis (3) and varicella-zoster encephalitis (1). Non-viral infections were caused by Toxoplasma gondii (103) Cryptococcus neoformans (41) Candida albicans (6) Mycobacteria (6) Treponema pallidum (2) coccidiodomycosis (1) Mycobacterium tuberculosis (1) Aspergillus fumigatus (1) and Escherichia coli (1). Neoplasms included primary CNS lymphoma (15) systemic lymphoma with CNS involvement (12) and metastatic Kaposis sarcoma (3). Cerebrovascular complications were seen in 4 patients with hemorrhage and 5 with infarction. 5 patients in the UCSF series had multiple intracranial pathologies including 2 cases of simultaneous Toxoplasma gondii infections and primary CNS lymphoma 2 cases of coexistent Toxoplasma gondii and viral infections and 1 case of combined Toxoplasma gondii and atypical mycobacterial infection. Cranial or peripheral nerve complications seen in 51 patients included cranial nerve syndromes secondary to chronic inflammatory polyneuropathy (5) lymphoma (5) and Bells palsy (5). Peripheral nerve syndromes included chronic inflammatory polyneuropathy (5) distal symmetrical neuropathy (13) herpes zoster radiculitis (6) persistent myaligias (2) myopathy (2) and polymyositis (1). In light of the protean behavior of AIDS and the problems related to the clinical and radiological and serological diagnosis of the unusual and varied associated nervous system diseases patients with AIDS and neurological complaints require a rigorous and detailed evaluation. The authors experience suggests that biopsy of all CNS space-occupying lesions should be performed for tissue diagnosis prior to the institution of other therapies. (authors)

Neurological manifestations of the acquired immunodeficiency syndrome (AIDS): Experience at UCSF and review of the literature

Abstract: In this review of the acquired immunodeficiency syndrome (AIDS), the authors have evaluated a total of 352 homosexual patients with AIDS or generalized lymphadenopathy managed at the University of California, San Francisco (UCSF), between 1979 and 1984. Of an initial unselected group of 318 patients, 124 (39%) were neurologically symptomatic, and one-third already had their neurological complaints at the time of presentation. An additional 210 AIDS patients with neurological symptoms have been reported in the literature. Thus, a total of 366 neurologically symptomatic patients with AIDS or lymphadenopathy are reviewed. Central nervous system (CNS) complications, encountered in 315 patients, included the following viral syndromes: subacute encephalitis (54), atypical aseptic meningitis (21), herpes simplex encephalitis (nine), progressive multifocal leukoencephalopathy (six), viral myelitis (three), and varicella-zoster encephalitis (one). Non-viral infections were caused by Toxoplasma gondii (103), Cryptococcus neoformans (41), Candida albicans (six), Mycobacteria (six), Treponema pallidum (two), coccidioidomycosis (one), Mycobacterium tuberculosis (one), Aspergillus fumigatus (one), and Escherichia coli (one). Neoplasms included primary CNS lymphoma (15), systemic lymphoma with CNS involvement (12), and metastatic Kaposi's sarcoma (three). Cerebrovascular complications were seen in four patients with hemorrhage and five with infarction. Five patients in the UCSF series had multiple intracranial pathologies, including two cases of simultaneous Toxoplasma gondii infections and primary CNS lymphoma, two cases of coexistent Toxoplasma gondii and viral infections, and one case of combined Toxoplasma gondii and atypical mycobacterial infection. Cranial or peripheral nerve complications, seen in 51 patients, included cranial nerve syndromes secondary to chronic inflammatory polyneuropathy (five), lymphoma (five), and Bell's palsy (five). Peripheral nerve syndromes included chronic inflammatory polyneuropathy (12), distal symmetrical neuropathy (13), herpes zoster radiculitis (six), persistent myalgias (two), myopathy (two), and polymyositis (one). In light of the protean behavior of AIDS and the problems related to the clinical, radiological, and serological diagnosis of the unusual and varied associated nervous system diseases, patients with AIDS and neurological complaints require a rigorous and detailed evaluation. The authors' experience suggests that biopsy of all CNS space-occupying lesions should be performed for tissue diagnosis prior to the institution of other therapies.

Selective tropism of lymphadenopathy associated virus (LAV) for helper-inducer T lymphocytes.

Abstract: Lymphadenopathy associated virus ( LAV ) has been isolated from patients with the acquired immunodeficiency syndrome (AIDS) or lymphadenopathy syndrome. Since the immune deficiency in AIDS seems to be primarily related to the defect of the helper-inducer T lymphocyte subset, the possibility that LAV is selectively tropic for this subset was investigated. Fractionation of T lymphocytes was achieved by cellular affinity chromatography with monoclonal antibodies. In a hemophilic patient who was a healthy carrier of LAV , reverse transcriptase activity and virus particles detected by electron microscopy were found only in cultures of helper-inducer lymphocytes. When infected with LAV in vitro, lymphocyte subsets from normal individuals yielded similar results. Virus production was associated with impaired proliferation, modulation of T3-T4 cell markers, and the appearance of cytopathic effects. The results provide evidence for the involvement of LAV in AIDS.