Berger Memorial : a Jewish funeral home

Project (B. Arch.)--University of Kansas, Architecture and Urban Design, 1969

Peeking Inside the Black Box: One Institution\u27s Experience Developing Policy for Unrepresented Patients

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Zanvil Alexander Cohn 1926-1993

Zanvil Alexander Cohn, an editor of this Journal since 1973, died suddenly on June 28, 1993. Cohn is best known as the father of the current era of macrophage biology. Many of his scientific accomplishments are recounted here, beginning with seminal studies on the granules of phagocytes that were performed with his close colleague and former editor of thisJournaI, James Hirsch. Cohn and Hirsch identified the granules as lysosomes that discharged their contents of digestive enzymes into vacuoles containing phagocytosed microbes. These findings were part of the formative era of cell biology and initiated the modern study of endocytosis and cell-mediated resistance to infection. Cohn further explored the endocytic apparatus in pioneering studies of the mouse peritoneal macrophage in culture. He described vesicular inputs from the cell surface and Golgi apparatus and documented the thoroughness of substrate digestion within lysosomal vacuoles that would only permit the egress of monosaccharides and amino acids. These discoveries created a vigorous environment for graduate students, postdoctoral fellows, and junior and visiting faculty. Some of the major findings that emerged from Cohn’s collaborations included the radioiodination of the plasma membrane for studies of composition and turnover; membrane recycling during endocytosis; the origin of the mononuclear phagocyte system in situ; the discovery of the dendritic cell system of antigen-presenting cells; the macrophage as a secretory cell, including the release of proteases and large amounts of prostaglandins and leukotrienes; several defined parameters of macrophage activation, especially the ability of T cell-derived lymphokines to enhance killing of tumor cells and intracellular protozoa; the granule discharge mechanism whereby cytotoxic lymphocytes release the pore-forming protein perforin; the signaling of macrophages via myristoylated substrates of protein kinase C; and a tissue culture model in which monocytes emigrate across tight endothelial junctions. In 1983, Cohn turned to a long-standing goal of exploring host resistance directly in humans. He studied leprosy, focusing on the disease site, the parasitized macrophages of the skin. He injected recombinant lymphokines into the skin and found that these molecules elicited several cell-mediated responses. Seeing this potential to enhance host defense in patients, Cohn was extending his clinical studies to AIDS and tuberculosis. Zanvil Cohn was a consummate physician-scientist who nurtured the relationship between cell biology and infectious disease. He guided with a warm but incisive manner the careers of many individuals. He was deeply committed to several institutions of biomedical research; to medicine in the developing world; to The Rockefeller University, especially its programs for graduate study and patient-oriented research; and to the energy and spirit of this Journal

An appreciation of Ralph Marvin Steinman (1943–2011)

Ralph Steinman, an editor at the Journal of Experimental Medicine since 1978, shared the 2011 Nobel Prize in Physiology or Medicine for his discovery of dendritic cells (DCs) and their role in immunity. Ralph never knew. He died of pancreatic cancer on September 30, 3 days before the Nobel announcement. Unaware of his death at the time of their announcement, the Nobel Committee made the unprecedented decision that his award would stand. Ralph was the consummate physician-scientist to the end. After his diagnosis, he actively participated in his 4.5 years of treatments, creating experimental therapies using his own DCs in conjunction with the therapies devised by his physicians, all the while traveling, lecturing, and most of all pursuing new investigations in his laboratory. For 38 years—from his discovery of DCs to his Nobel Prize—Ralph pioneered the criteria and methods used to identify, isolate, grow, and study DCs. He and his colleagues demonstrated that DCs are initiators of immunity and regulators of tolerance. In his most recent studies, Ralph was harnessing the specialized features of DCs to design improved vaccines. The following synopsis describes some of his seminal discoveries

The changing immunology of organ transplantation

The engrafted organ becomes a chimera as the recipient's leukocytes station themselves in the transplant. Remarkably, the recipient becomes chimeric as well, in a reverse migration involving immune cells from the graft. Interactions between donor and recipient cells are tolerogenic-a process with implications for the goal of graft acceptance with minimal immunosuppression

Ralph M. Steinman: Research and Career

General information about Dr. Ralph Steinman and his Nobel Prize winning research.https://digitalcommons.rockefeller.edu/steinman-nobel/1000/thumbnail.jp

Anatomy of germinal centers in mouse spleen, with special reference to \u27follicular dendritic cells\u27

Lymphocyte proliferation in germinal centers (GC\u27s) is thought to be triggered by antigen retained extracellularly on the surface of special \u27dendritic\u27 cells. The anatomy and function of these cells have not been studied directly or in detail. We therefore examined mouse spleen GC\u27s developing in response to sheep erythrocyte stimulation. We found that distinctive \u27follicular dendritic cells\u27 (FDC\u27s) were present in both the GC and adjacent mantle region of secondary follicles. The large, irregularly shaped nucleus, containing little heterochromatin, allowed for the light microscope (LM) identification of FDC\u27s. By EM, the cell was stellate in shape sending out long, thin sheets of cytoplasm which could fold and coil into complex arrays. The processes were coated extracellularly by an amorphous electron-dense material of varying thickness, as well as particulates including variable numbers of virions. The FDC cytoplasm lacked organelles of active secretory and endocytic cells, such as well-developed rough endoplasmic reticulum (RER) and lysosomes. These anatomical features readily distinguished FDC\u27s from other cell types, even those that were extended in shape. To pursue these descriptive findings, we injected three electron-dense tracers i.v. and sacrificed the mice 1 h-10 days thereafter. Colloidal carbon, colloidal thorium dioxide (cThO2), and soluble horseradish perixidase (HRP) were actively sequestered into the vacuolar system of macrophages but were interiorized only in trace amounts by FDC\u27s. Therefore, FDC\u27s are not macrophages by cytologic and functional criteria. FDC\u27s did display a unique property. Both colloidal carbon and thorium dioxide, which are nonimmunogens, could be visualized extracellularly on the cell surface for several days. The meaning of this is unclear, but the association of colloid with FDC\u27s appeared to slow the movement of particulates through the extracellular space into the GC proper. FDC\u27s were not readily identified in splenic white pulp lacking GC\u27s. They must develop de novo then, possibly from novel dendritic cells that we have identified in vitro