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Biomedical subjects

G A Ackerman

Publications and source records attributed to G A Ackerman.

At least 19 recordsLinked to original sources
PubMed2006

A history of biological disasters of animal origin in North America.

This paper examines past occurrences in North America relevant to the possibility of biological disasters with animal origins. With respect to naturally occurring animal disease outbreaks, North America, while not as adversely affected by epizootics as other regions, has had its fair share of such outbreaks of both 'traditional' and emerging animal diseases. The traditional category includes such diseases as anthrax, classical swine fever, bluetongue, brucellosis, foot and mouth disease, and the family of equine encephalomyelitis viruses. The emerging diseases include relatively more recent culprits such as postweaning multisystemic wasting syndrome, poultry enteritis mortality syndrome, and newly discovered examples of the transmissible spongiform encephalopathies. Additionally, several serious diseases of human beings that involve animal vectors or reservoirs occur naturally in North America or have emerged in recent decades; these include plague, hantavirus, monkeypox, West Nile virus and avian-derived influenza. At the same time, there have been very few intentional attacks on livestock using biological agents and no recorded cases in North America of animals intentionally being used to transmit disease to humans. According to the historical record, therefore, naturally occurring emerging zoonoses probably constitute the greatest threat in terms of biological disasters with animal origins. However, some of the general trends in terrorist activity, such as the intensification of activities by animal rights extremists against facilities undertaking animal research, mean that the possibility of intentional animal-related biological disasters should not be discounted.

Animal Diseases↗
PubMed2006

It is hard to predict the future: the evolving nature of threats and vulnerabilities.

This paper describes the evolving nature of threats and vulnerabilities associated with biological disasters with animal origins, and introduces some of the pitfalls and opportunities associated with anticipating future threats. Evolving threats and vulnerabilities include continued deforestation and encroachment on virgin habitats, the effects of globalisation on trade and transportation, the increased interdependence and social vulnerability of modern society, the commingling of intensive agriculture and traditional farming methods, the periodic appearance of pandemics and epizootics, and indications that numerous human actors are displaying an increasing interest in and capability of using biological agents as weapons. These developments must be viewed in the context of various impediments to accurately gauging future threats, such as the appearance of new elements that depart from current trends and the inherent difficulty in anticipating human, and especially terrorist, behaviour. The paper concludes with some broad recommendations for structuring a policy response to the threat in an environment of uncertainty about the future.

Bioterrorism↗
PubMed1989

Activation and deactivation of guinea pig peritoneal eosinophils during chronic polymyxin B stimulation.

Eosinophils exhibit different levels of oxidative metabolism depending on their site of origin and various host factors that may influence metabolism. The present study examined the time course of eosinophil oxidative metabolism in animals undergoing chronic peritoneal stimulation. Eosinophils were purified from the peritoneal exudates of guinea pigs stimulated with weekly polymyxin B and saline peritoneal lavage. 14C-1- and 14C-6-glucose oxidation and H2O2 production were measured at week 0 and at various time points throughout 43 weeks of stimulation. Baseline oxidative metabolism of eosinophils was relatively high throughout the time course, but then declined sharply after 32 weeks. These "deactivated" cells that were recovered after 32 weeks also failed to respond to phorbol myristate acetate (PMA) or opsonized zymosan. Electron microscopy did not reveal significant differences between deactivated eosinophils and cells from earlier time points. These findings document the time course of eosinophil activation and deactivation in this model and suggest that metabolic heterogeneity of eosinophils can occur over time in response to a chronic stimulus.

Animals↗
PubMed1985

Stimulation of normal rat bone marrow fibroblast proliferation by sera from leukemic Fischer rats.

Fibroblast hyperplasia and accumulation of fibrous material in the bone marrow of patients with idiopathic (primary) or secondary myelofibrosis (MF) is believed to result from a reaction by marrow fibroblasts to an altered marrow microenvironment, the alteration being potentiated by abnormal hemic cells. We investigated the hypothesis that humoral factors might contribute to fibroblast overgrowth in MF by using an animal model, aged Fischer rats, where MF frequently occurs with leukemia. Sera from leukemic rats and leukemic cell conditioned media (CM) were assayed for enhancement of normal rat marrow fibroblast proliferation in a culture system where fibroblasts form discrete, adherent colonies. Our results demonstrated that: leukemic sera induced a 170% increase in total fibroblast colony numbers and a 325% increase in colonies containing more than 80 cells, stimulation of fibroblast growth was leukemia related since sera from rats with transplanted leukemia enhanced marrow fibroblast proliferation, leukemic cell CM did not contain a growth factor for marrow fibroblasts, sera from leukemic rats and 2-mercaptoethanol were additive in enhancing marrow fibroblast proliferation and probably act by different mechanisms, and leukemic rat sera was less effective as a colony-stimulating factor than normal rat sera, a condition mimicked when leukemic and normal spleen CM were compared. This is the first time that a serum component has been implicated in the pathogenesis of MF; our work may contribute to understanding the mechanism involved when MF occurs as a complication of leukemia.

Animals↗
PubMed1984

Growth characteristics, morphology, and phospholipid composition of human type II pulmonary alveolar cells grown in a collagen-free microenvironment.

Human lung epithelial cells have been isolated and maintained in pure culture and characterized during their time in culture. Any residual fibroblasts were removed by selective trypsinization within the first 48 h in culture and the residual epithelial cells from the primary culture grew to confluent density. The epithelial cells at Passage 2 or greater were serially subpassaged when cultures reached ca. 80% confluency. This procedure permitted us to conduct biochemical and structural studies of starting materials and subsequent population doublings. Electron microscope evaluation of both initial monolayers and cell suspensions showed cultures to be composed of a single cell type. These cells had microvilli on their free or apical surface. Subsequent population doubling level 1 up to 5 exhibited the same structures. They contained lamellar inclusions, which are typical of Type II alveolar epithelial cells. Fetal lung (age 18 to 20 wk) cell suspensions processed for electron microscopy before culturing showed cells to be undifferentiated, epithelial-like with small microvilli along cell borders, and with desmosomes at cell junctions. Lamellar inclusions were not observed in these cells. Ultrastructural studies of the cultured epithelial cells demonstrated that the lamellar inclusions had a slightly positive reaction when tested for acid phosphatase. Phospholipid analysis of these lung epithelial cells showed a phospholipid composition consistent with that found in surfactant-containing Type II cells. Cultured epithelial cells stained with phosphine 3-R demonstrated a green fluorescent cytoplasm and nucleus with brightly fluorescent yellow-orange perinuclear particles. The preceding characterization of these cells leads us to conclude that they exhibit structural and biochemical features commensurate with Type II epithelial cells from human lung. Moreover, these selection techniques applied to the isolation of human lung Type II cells from the tissue permit us to study the differentiative function of these cells routinely under conditions of growth in vitro.

Acid Phosphatase↗
PubMed1984

Insulin complex binding to human peripheral and mitogen-stimulated lymphocytes.

Surface labeling and internalization of insulin was demonstrated ultrastructurally with human peripheral lymphocytes and with "activated"/transformed lymphocytes from mitogen-treated cultures using the colloidal gold-labeled insulin-bovine serum albumin (GIA) procedure. The majority of peripheral lymphocytes bound only limited amounts of the insulin complex, while approximately 15% of the lymphocyte population bound modest to comparatively large quantities of the labeled hormone. Quantitative labeling data indicated a skewed GIA labeling continuum for peripheral lymphocytes rather than separate, distinct populations. Sequential labeling studies with the GIA complex followed by either the ferritin-conjugated goat anti-human immunoglobulin or the E-rosette techniques indicated that insulin labeling was neither T nor B cell specific, since extremes of GIA labeling were found in both populations. Many, but not all, circulating lymphocytes with elevated insulin binding had morphological features suggestive of "active" cells, viz., larger cell, nuclear, nucleolar, and Golgi sizes, dispersed chromatin, and greater numbers of polysomes than lymphocytes having minimal GIA labeling. Both phytohemagglutinin (PHA), a T-cell mitogen, and pokeweed mitogen (PWM), a B/T cell mitogen, induced an increase in mean GIA labeling of cultured lymphoid cells as compared to non-mitogen-treated controls. The majority of mitogen-transformed "blast-like" cells had more extensive insulin labeling than nontransformed small (medium)-size lymphocytes, although an overlap in labeling densities was noted in these two groups. PHA induced a slight increase in mean surface GIA labeling of the nontransformed lymphocyte population at 48 and 72 hr of culture as compared to similar cells in non-mitogen-treated controls and PWM cultures. We interpret these findings as indicating the emergence of increased numbers of insulin binding sites on lymphocytes, both those in the circulation and in mitogen-treated cultures, during the early response (activation) to functional and/or metabolic modulations of the cell; this surface change does not appear to be directly related to blastogenic transformation.

Binding Sites↗
PubMed1983

The stimulation of rat bone marrow fibroblast colony formation by 2-mercaptoethanol.

The definition of the function of bone marrow stromal cells in the regulation of hematopoiesis has been complicated by the limited growth of these cells in vitro. We have demonstrated that the addition of 2-mercaptoethanol to rat bone marrow cultures enhances bone marrow fibroblast proliferation as evidenced by a 2-fold increase in the total number of fibroblast colonies and a 5-fold increase in the number of these colonies which contain more than 80 cells. We also present evidence suggesting that enhancement of fibroblast growth may not be due to direct action of 2-mercaptoethanol, but may result from the activation of a serum component. The results from this study should facilitate further research into the function of bone marrow fibroblasts in the regulation of hematopoietic cell differentiation.

Animals↗
PubMed1983

Surface localization of wheat germ agglutinin and concanavalin A binding sites on normal human blood cells: an ultrastructural histochemical study.

In order to determine the extent and variations in surface concavanalin A (CON A) and wheat germ agglutinin (WGA) labeling of different varieties of normal blood cells, gluraraldehyde-fixed human blood cells were exposed to CON A-gold labeled horseradish peroxidase (CON A-HRP-G) and WGA-gold labeled ovomucoid (WGA-OVO-G) histochemical methods. The resultant particulate reaction product permitted assessment of binding and number of gold particles per micrometer of cell surface. Particle counts and data were subjected to statistical analysis. Six subjects (three female and three male) were used and compared in this study. In spite of moderate variations in surface labeling of the various types of leukocytes, erythrocytes and platelets within a given subject, determinations of mean labeling values for similar cell varieties proved quite similar between subjects with the given lectin. WGA and CON A had substantially different labeling densities on the various hemic cells. WGA surface labeling of all types of hemic cells, with the exception of platelets, showed far more labeling than was found with CON A. WGA mean labeling of the grouped subjects was significantly higher for each variety of leukocyte than for either erythrocytes or platelets although this distinction was not always evident in an individual subject. With CON A, mean labeling density for each of hemic cell types showed significant differences between each of the hemic cell varieties. Erythrocytes had only minimal CON A binding while monocyte and platelet populations represented the most reactive of the hemic cells. No difference was noted between corresponding cell varieties in the female vs. male subjects.

Antigens, Surface↗
PubMed1982

Corticosteroid alteration of human monocyte to macrophage differentiation.

Human monocyte to macrophage differentiation in vitro is associated morphologically with an increased cell size, an increased number of lysosomes, and rough endoplasmic reticulum. Functional changes associated with monocyte to macrophage differentiation include increased tumoricidal activity and increased cell protein, acid phosphatase, and 5'-nucleotidase. Hydrocortisone succinate (HCS) at 2.5 microM markedly altered monocyte to macrophage differentiation: HCS inhibited the development of tumoricidal activity and the increased levels of cell protein, acid phosphatase, and 5'-nucleotidase. By transmission electron microscopy, macrophages incubated with HCS failed to develop an increased complement of lysosomes and developed an increased number of membrane-bound electron lucent vacuoles. Dexamethasone inhibited the development of tumoricidal activity at a 10-fold lower concentration than HCS. HCS also markedly inhibited monocyte 3H-uridine incorporation. Mechanisms of HCS alteration of monocyte differentiation are discussed. These data suggest that corticosteroid alteration of monocyte differentiation may be a mechanism of HCS immunosuppression in vivo.

Adrenal Cortex Hormones↗
PubMed1981

Histochemical evidence for the differential surface labeling, uptake, and intracellular transport of a colloidal gold-labeled insulin complex by normal human blood cells.

A colloidal gold-labeled insulin-bovine serum albumin (GIA) reagent has been developed for the ultrastructural visualization of insulin binding sites on the cell surface and for tracing the pathway of intracellular insulin translocation. When applied to normal human blood cells, it was demonstrated by both visual inspection and quantitative analysis that the extent of surface labeling, as well as the rate and degree of internalization of the insulin complex, was directly related to cell type. Further, the pathway of insulin (GIA) transport via round vesicles and by tubulo-vesicles and saccules and its subsequent fate in the hemic cells was also related to cell variety. Monocytes followed by neutrophils bound the greatest amount of labeled insulin. The majority of lymphocytes bound and internalized little GIA, however, between 5-10% of the lymphocytes were found to bind considerable quantities of GIA. Erythrocytes rarely bound the labeled insulin complex, while platelets were noted to sequester large quantities of the GIA within their extracellular canalicular system. GIA uptake by the various types of leukocytic cells appeared to occur primarily by micropinocytosis and by the direct opening of cytoplasmic tubulo-vesicles and saccules onto the cell surface in regions directly underlying surface-bound GIA. Control procedures, viz., competitive inhibition of GIA labeling using an excess of unlabeled insulin in the incubation medium, preincubation of the GIA reagent with an antibody directed toward porcine insulin, and the incorporation of 125I-insulin into the GIA reagent, indicated the specificity and selectivity of the GIA histochemical procedure for the localization of insulin binding sites.

Adult↗
PubMed1980

Growth and ultrastructural characterization of proliferating human keratinocytes in vitro without added extrinsic factors.

Routine in vitro cultivation of human epithelial cells derived from foreskin and free of contaminating fibroblasts has been achieved without the addition of conditioned medium or extrinsic factors. Epithelial cell populations could be serially subpassaged and exhibited modulating responses at PDL5 to culture conditions as the cells passed from phase 1 through phase 2 of their life span. The cell population in early phase 2 gave rise to tissue sheets that exhibited characteristics typical of human foreskin epidermis including the formation of distinct cellular layers, viz. strata basalis, spinosum, granulosum and corneum. Typical keratohyaline granules were not observed in the epithelial cells although a distinct cornified layer was evident. Ultrastructurally, desmosomes and tonofilaments were readily apparent. Thus, the procedure detailed in this study will produce highly differentiated fibroblast-free epidermal sheets reaching several centimeters in size and which can be removed from the substratum as a single sheet of organized epidermis. The epithelial cells could be cultured through 20 +/- 3 PDL, whereas fibroblast cultures derived from foreskin cultures exhibited 40 +/- 5 PDL and mixed cell cultures of foreskin were carried through 43 +/- 5 PDL.

Cells, Cultured↗
PubMed1980

Surface distribution of monosialoganglioside GM1 on human blood cells and the effect of exogenous GM1 and neuraminidase on cholera toxin surface labeling. A quantitative immunocytochemical study.

The cholera toxin-colloidal gold-labeled IgG-F(ab')2 anticholera toxin ultrastructural immunocytochemical procedure was used for the localization of GM1 monosialoganglioside on the surface of human blood cells. The number of gold particles per micron of cell surface was counted and the data subjected to statistical analysis. Cholera toxin (CT) binding characteristics assessed in several subjects showed consistent labeling patterns for the various hemic cells, although some quantitative differences were noted in surface labeling densities between subjects. Neutrophils were invariably the most heavily labeled of the hemic cells, while lymphocytes, erythrocytes, and platelets exhibited only limited CT labeling. Exposure of hemic cells to neuraminidase induced a major increase in surface CT labeling that proved to be directly related to cell type and differed in many respects with the CT labeling pattern noted in nonenzyme treated cells. Newly exposed CT binding sites attributed to "masked" GM1 and/or to neuraminidase-transformed GD1a or GT1 gangliosides, showed that the number of new binding sites were nearly twice as abundant on platelet and monocyte sufaces as on the surfaces of neutrophil, lymphocyte, and erythrocyte populations. However, ratios of new CT binding sites to those normally available for CT binding were approximately 10:1 for erythrocytes, approximately 3--7:1 for lymphocytes, monocytes, and platelets, and approximately 1:1 for the neutrophil group. Exogenous GM1 was incorporated into the cell surface of the hemic cells in a differential manner. Platelets showed a dramatic increase in surface CT labeling, viz. approximately 12- to 20-fold, compared to that of other hemic cells; however, neutrophil and erythrocyte GM1 uptake was limited. Our studies have demonstrated that distinct differences exist in the extent of surface CT labeling of the various types of blood cells. They further indicated that the ability of the cell surface to incorporate exogenous GM1 may represent a differential expression of the physiochemical properties of the surface of the individual cell types.

Adult↗
PubMed1980

Differential expression of surface monosialoganglioside GM1 in various hemic cell lines of normal human bone marrow. A quantitative immunocytochemical study using the cholera toxin-gold-labeled anti-cholera toxin procedure.

The cholera toxin-colloidal gold-labeled IgG-F(ab')2 anti-cholera toxin ultrastructural immunocytochemical procedure has been used for the localization of GM1 monosialogangliosides on the surface of human bone marrow cells. The number of gold particles per micron of cell surface was counted and the data subjected to statistical analysis. Cholera toxin (CT) binding characteristics assessed in several subjects showed consistent labeling patterns for the various types of marrow cells, although minor quantitative differences were noted in surface labeling densities between subjects. Surface labeling was nonuniformly distributed along the cell membrane of the marrow cells and label clusters or domains were commonly noted. Data analysis indicated that CT labeling was related to cell type, to cell lineage, and to the stage of maturation. Mature neutrophils were the most reactive of the marrow cells and the CT labeling of this cell series increased stepwise from the promyelocyte stage to the segmented neutrophil. A similar pattern occurred during eosinophil maturation and the maturation of the monocyte. A different labeling pattern was found during the differentiation of the erythrocytic cell series with low labeling of proerythroblasts increasing modestly to the early normoblast stage and then decreasing during the final phase of maturation. Exposure to neuraminidase prior to the immunocytochemical sequence induced a major increase in surface CT labeling of the various types of marrow cells, as was particularly evident for the platelet, promyelocyte, myelocyte, monocyte, promonocyte, and erythrocyte cell groups. The data indicated that the number of cryptic GM1 and/or higher gangliosides exposed by neuraminidase in the cell membrane varied during cell differentiation and was directly related to specific cell types. Exogenous GM1 also was demonstrated to be incorporated into the surface of the bone marrow cells in a differential manner and the extent of incorporation was found to be related to specific cell types and to their stage of maturation.

Antitoxins↗
PubMed1980

The ultrastructural immunocytochemical demonstration of erythropoietin receptors on developing erythrocytic cells of fetal mouse liver.

In spite of the severe restrictions imposed by the lack of high purity erythropoietin (Ep) and Ep specific antiserum wer have attempted to demonstrate presumptive Ep binding sites on the surface of developmental forms of erythrocytic cells of the mouse fetal liver using ultrastructural immunocytochemical methodology. Cells were exposed to exogenous Ep of differing potencies and concentrations and subsequently incubated in an Ep antiserum. The Ep-Ep-antiserum complex was then visualized with a gold-labeled IgG reagent. Limited surface labeling was noted on the developing erythrocytic cells and the evaluation of the mean surface labeling densities of the erythrocytic cell series indicated that the extent of labeling was related to the stage of maturation. Early polychromatophilic erythroblasts proved to be the most heavily labeled of the erythrocytic cells followed by the basophilic erythroblast, proerythroblast and late polychromatophilic erythroblasts respectively; normoblasts, reticulocytes and erythrocytes exhibited, at most, only minimal labeling. In addition, we have been able to demonstrate several primitive cells in the fetal liver which exhibited extensive surface labeling when compared with the developing erythrocytic cells. These cells may represent the erythroid precursors of the fetal liver.

Animals↗
PubMed1980

Triglycerides, lipid droplets, and lysosomes in aorta smooth muscle cells during the control of cell proliferation with polyunsaturated fatty acids and vitamin E.

The effects of 8,11,14-eicosatrienoic acid [20:3 (n--6)], 5,8,11,14-eicosatetraenoic acid [20:4 (n--6)], and alpha-tocopherol (vitamin E) on the morphology of smooth muscle cells from the guinea pig were studied in tissue culture. Cells were examined by phase and contrast interference microscopy, histochemistry, and transmission electron microscopy for the appearance of lipid droplets and lysosomes. The addition of 120 microM 20:3 (n--6) to the media produces large increases in the number of both lipid droplets and lysosomes. The addition of 10 microM vitamin E to the media has no effect on the morphology of smooth muscle cells. Large increases in the number of both lipid droplets and lysosomes are produced when vitamin E is added together with 20:3 (n--6). Thus, vitamin E has no effects on the morphologic changes induced by 20:3 (n--6). Lipid analyses showed that 80 per cent of the fatty acid taken into the cells is incorporated into triglyceride. Phospholipids incorporated about 17 per cent of the labeled fatty acid while cholesteryl esters, free fatty acids, and a polar neutral lipid fraction each incorporated less than 1 per cent of the labeled fatty acids. Gas liquid chromatography showed that the labeled fatty acid is recovered from the triglyceride fraction with little chain elongation and desaturation. Vitamin E has not effect on the uptake and distribution of labeled fatty acid in smooth muscle cells. 20:3 (n--6) and 20:4 (n--6) are inhibitors of cell proliferation when they are added to cells seeded at low cell density. 20:3 (n--6) has no effect on cell proliferation when it is added to a confluent monolayer which is subsequently split and grown at low cell density. Lipid droplets disappear as these pretreated cells grow. Vitamin E in the presence or absence of fatty acid enhances cell proliferation. The vitamin E and pretreatment studies show that cell proliferation is not related directly to triglyceride accumulation, the formation of lipid droplets, or enhanced lysosomal enzyme activity.

Acid Phosphatase↗
PubMed1979

Distribution of wheat germ agglutinin binding sites on normal human and guinea pig bone marrow cells: an ultrastructural histochemical study.

The wheat germ agglutinin-gold labeled ovomucoid (WGA-Ovo-G) method has been employed in the ultrastructural localization of WGA surface receptor sites on gluteraldehyde-fixed normal human and guinea pig bone marrow cells. The number of gold particles per micron of cell surface were counted and data subjected to statistical analysis. WGA labeling of the bone marrow cells was found to be quite heavy and evenly distributed along the cell surface. Only macrophages, in both species, and a number of lymphocytes in the guinea pig exhibited limited WGA labeling. Comparison of morphologically similar cell types in human and guinea pig marrow indicated that WGA receptor sites were more abundant on the guinea pig hemic cells. WGA surface labeling was found to be not only related to cell type and to animal species but, in some instances, varied with the stage of maturation of a given cell line; viz., neutrophilic cell series in both man and guinea pig and erythrocytic cell series in the guinea pig.

Animals↗