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Application of peritoneal macrophages to experimentally induced cutaneous wounds of old mice accelerates healing to levels almost comparable to those of untreated young animals. Slightly greater acceleration is observed when macrophages are obtained from young as opposed to old donors. These findings are consistent with a defect in macrophage function as a cause of impaired wound healing in senescence and suggest a possible therapeutic strategy.Macrophages play an important role in wound repair (1) and produce substances that stimulate the synthesis of collagen by fibroblasts (2-4). Furthermore, macrophages produce a substance that causes proliferation of fibroblasts in vitro (5). Activated macrophages have been reported to induce vascular proliferation (6). Although attempts were made to characterize the substances produced by macrophages that enhance wound repair, a simpler way to accelerate the healing process was devised. It consisted of mobilizing the macrophages to the wound area and activating them. The effects of topical application of a variety of substances on the repair process of skin wounds in mice were examined. It was found that promotion of wound repair could be achieved in mice by application of glucan (7). The promotion of wound healing by glucan was evaluated later on single animals, by treating an experimental wound on one rear leg (the wound on the other leg serving as a control) in mice, rats, and guinea pigs. Glucan was found to be effective by accelerating the mobilization of macrophages to the wound (7,8). All these experiments were carried out on young animals or on cells in culture.It is generally accepted that cutaneous wounds heal slower in the elderly as compared with the young. This has been confirmed in clinical studies (9-11) and in experimental investigations on mice and rats (12-16, t, §). Wound healing rate has even been used as a biological marker ofage in mice.T Previous results suggested that altered estrogen or androgen levels or altered sensitivity to these steroids could account, at least partially, for the slower wound repair in old rats (16 clipped and shaved on the back. Four cutaneous wounds were made on each animal by lifting the shaved skin perpendicularly to the length of the mouse and punching twice (once anteriorly on the right side and once posteriorly on the left side) with a leather punch (circumference, 4.7 mm), resulting in two wounds on each side. Wounds were photographed immediately and at subsequent times from a fixed distance with the wound surface perpendicular to the axis of the lens. After development of the film, wound images were projected onto paper at a fixed distance, traced with a pencil, and cut out with sharp scissors. The relative sizes ofthe wounds were assessed by weighing the cut-out paper tracings. Healing was assessed from the mean decrease in wound area for the four wounds on each mouse.Preparation and Application of Peritoneal Macrophages. Mice were anesthetized and 0.5 x 1.0-cm oval incisions were made abdominally. A 20-gau...

Background-Activated macrophages have a significant role in wound healing and damaged tissue repair. We sought to explore the ability of ex vivo activated macrophages to promote healing and repair of the infarcted myocardium. Methods and Results-Human activated macrophage suspension (AMS) was prepared from a whole blood unit obtained from young donors in a closed sterile system and was activated by a novel method of hypo-osmotic shock. The AMS (Ϸ4ϫ10 5 cells) included up to 43% CD14-positive cells and was injected into the ischemic myocardium of rats (nϭ8) immediately after coronary artery ligation. The control group (nϭ9) was treated with saline injection. The human cells existed in the infarcted heart 4 to 7 days after injection, as indicated by histology, human growth hormone-specific polymerase chain reaction, and magnetic resonance imaging (MRI) tracking of iron oxide-nanoparticle-labeled cells.

Summary:Viral infection has been shown to induce aplastic anemia, unidentified types of hepatitis being the most common cause for aplastic anemia-associated viral hepatitis. The survival rate for this group of patients after bone marrow transplantation with stem cells from an HLAmatched sibling is not well known. The aim of this study was to determine the prevalence of hepatitis G virus (HGV) and transfusion transmitted virus (TTV) infection in non-A, non-B, non-C hepatitis associated-aplastic anemia (HAAA) patients, and to define the role of bone marrow transplantation (BMT) as a therapeutic modality for this disease.

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The process of expulsion of the nucleus during the transformation of the late erythroblast to reticulocyte is described. Erythroid clones taken from the spleen of lethally irradiated mice transplanted with syngeneic bone marrow were used. 10-12-day old isolated clones were fixed in glutaraldehyde, then in osmium tetroxide. Ultra-thin sections were stained with uranyl acetate and/or lead citrate before examination. Late (orthochromatic) erythroblasts develop pseudopod-like cytoplasmic protrusions into one of which the nucleus gradually penetrates, being deformed by the extrusion through the relatively narrow passage. During the whole process, mitochondria and vesicular and membranous elements are concentrated in the cytoplasm. Once outside the cell, the nucleus reassumes its rounded form. It is surrounded by a narrow rim of cytoplasm and structurally altered plasma membrane and is connected to the rest of the cell by a bridge. Elongated vacuoles appear within this bridge, with a resulting release of the enveloped nucleus which is soon phagocytized by macrophages; this leaves behind the newly formed reticulocyte. During this process, the cytoplasmic protrusions, the agglomeration of mitochondria, and the mode of separation of the nucleus from the rest of the cell are similar to those occurring in mitotic division.

A highly sensitive antiglobulin test based on rosette formation due to the interaction between IgG bearing red blood cells (RBC) and Fc receptors on K562 cells, was used to study the immunoglobulin molecules present on human senescent RBC. Normal human RBC were separated into young and senescent subpopulations on the basis of age-dependent differences in density by centrifugation on a discontinuous density Percoll gradient, and by flotation on phthalate ester mixtures. The senescent but not the young RBC were found to bear membrane bound IgG. Most of the bound IgG molecules could be specifically eluted by galactose in its alpha-anomeric form. Antigalactosyl (anti-Gal) IgG antibodies with similar reactivity were found to be present in high titres in every one of the 400 normal human sera tested. The natural anti-Gal antibodies isolated from normal sera by affinity chromatography could bind to IgG depleted senescent RBC but not to young RBC. Erythrophagocytosis experiments indicated that the anti-Gal bound to the senescent RBC induced their destruction by macrophages. It is suggested that the natural anti-Gal antibodies interact with cryptic alpha-galactosyl residues which are exposed in the course of the RBC senescence and mediate the removal of these RBC from circulation by cells of the reticuloendothelial system.

Uncomplicated monochorionic twin pregnancies are at substantial risk of stillbirth throughout the third trimester, which is severalfold higher than in dichorionic twin pregnancies. Given the risk of fetal death to the cotwin, these data should inform decisions around timing of delivery in seemingly normal monochorionic twin pregnancies.