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  • 1
    ISSN: 0730-2312
    Keywords: anticoagulants ; blood coagulation enzymes ; elastase ; emphysema ; isocoumarins ; molecular modeling ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Isocoumarins are potent mechanism-based heterocyclic irreversible inhibitors for a variety of serine proteases. Most serine proteases are inhibited by the general serine protease inhibitor 3,4-dichloroisocoumarin, whereas isocoumarins containing hydrophobic 7-acylamino groups are potent inhibitors for human leukocyte elastase and those containing 7-alkylureidogroups are inhibitors for porcine pancreatic elastase. Isocoumarins containing basic side chains that resemble arginine are potent inhibitors for trypsin-like enzymes. A number of 3-alkoxy-4-chloro-7-guanidinoisocoumarins are potent inhibitors of bovine thrombin, human factor Xa, human factor XIa, human factor XIIa, human plasma kallikrein, porcine pancreatic kallikrein, and bovine trypsin. Another cathionic derivative, 4-chloro-3-(2-isothiureidoethoxy) isocoumarin, is less reactive toward many of these enzymes but is an extremely potent inhibitor of human plasma kallikrein. Several guanidinoisocoumarins have been tested as anticoagulants in human plasma and are effective at prolonging the prothrombin time. The mechanism of inhibition by this class of heterocyclic inactivators involves formation of an acyl enzyme by reaction of the active site serine with the isocoumarin carbonyl group. Isocoumarins with 7-amino or 7-guanidino groups will then decompose further to quinone imine methide intermediates, which react further with an active site residue (probably His-57) to form stable inhibited enzyme derivatives. Isocoumarins should be useful in further investigations of the physiological function of serine proteases and may have future therapeutic utility for the treatment of emphysema and coagulation disorders.
    Additional Material: 9 Ill.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 159 (1967), S. 159-169 
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Horseradish peroxidase was injected into the spleens of mice and the animals were sacrificed ten minutes after injection. The tissues were reacted with 3-3′ diaminobenzidine hydrochloride and the distribution of the reaction product was studied with both the light and electron microscope. The peroxidase was localized between epithelial cells up to the region of the tight junction and within vacuoles in the absorptive cells Granules ranging in size from ca. 40A to 600A were observed in the cytoplasm of epithelial cells in numbers far in excess of that found in control specimens. It appeared that the diffuse light brown staining observed in epithelial cells with the light microscope could be attributed to large numbers of granules of reaction product free in the cytoplasm. When corn oil was given by stomach tube and an intravascular injection of perioxidase was given ten minutes later, absorbed lipid was found to pass from interepithelial cell spaces to lamina propria at the same time that peroxidase was traversing the same compartments in the reverse direction. Hence, it was shown that exogenous peroxidase and probably other substances of vascular origin required for the metabolism of epithelial cells are exposed to both the basal and lateral epithelial cell membranes, even when absorbed lipid is traversing the same spaces in the opposite direction.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 213 (1985), S. 464-472 
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: White Leghorn chicken eggs, specific pathogen free, were treated with the organophosphate insecticide dicrotophos and the early defects thus induced were characterized histologically. Eggs were incubated for 24, 48, 72, or 96 hr, injected with doses of dicrotophos ranging from 250 μg to 2.0 mg per egg, and observed after an additional 48 hr of incubation. Treated embryos displayed general developmental retardation as well as unilateral retardation of the cranial sense organs, the youngest embryos being most severely affected. Many embryos injected with insecticide at 24 hr, and all but one injected at 48 or 72 hr, displayed notochordal folding, usually restricted to the cervical region; most of these also showed deformities of the adjacent spinal cord. Other defects, seen on a less consistent basis, included branching of the neural canal in the lumbar region, bifurcation of the neural epiphysis, deformation of the lens vesicle, and distention of the major blood vessels. The incidence and severity of epiphyseal, lens, and vascular defects were greatest among embryos treated at 24 hr, whereas notochordal and both types of neural defects were greatest among those treated at 48 hr. The incidence and severity of the abnormalities diminished with increasing age such that by 96 hr the only defect noted was a weak notochordal folding in one embryo. To a lesser extent, incidence and severity were dose-related also. Histological similarities between embryos displaying vascular distention and recently dead treated embryos suggested that this abnormality is a precursor to death. All defects were associated with the presence of the insecticide at the time the affected structures were undergoing initial or early morphogenesis or else the deposition of a supportive sheath, suggesting these activities as targets of the teratogen.
    Additional Material: 17 Ill.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 216 (1986), S. 528-533 
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Gravimetric determination of total bone water space was used as an index of available bone marrow space in mice following various specific stressors, i.e., splenectomy, hypoxia, bone fracture, and estrone-induced osteosclerosis. Data was corrected for bone weight and was reported as specific bone marrow volume (total bone water space/mg dry bone × 100).A direct relationship was observed between specific bone marrow volume and medullary hemopoietic activity induced by stress. Absolute and/or relative marrow space increased following splenectomy, hypoxia, and fracture. Osteosclerotic animals shift most hemopoietic activity from marrow to spleen, and splenectomized osteosclerotic animals become anemic. Both intact and splenectomized hypoxic animals develop increased specific bone marrow volume and successfully compensate for hypoxia with enhanced erythropoiesis. Animals sustaining a fracture callus increase both specific bone marrow volume and hemopoietic activity at the callus without an increase in hemopoietic demand.Increased specific bone marrow volume extends the marrow bone interface, where primitive stem cells accumulate, while expanding marrow stromal space, where stem cells lodge, proliferate and differentiate. Therefore, it would appear that availability of competent marrow space may play an integral part in passively permitting hematopoiesis and in determining hemopoietic reserve capacity.Stem cell migration increases during intensified hemopoietic demand, which also may be related to available marrow space. Mice have a low medullary hemopoietic reserve capacity; subsequently, when available medullary hematopoietic stroma becomes occupied, stem cells are more likely to migrate from the marrow to extra-medullary sites where they mature before entering the circulating pool.
    Additional Material: 2 Tab.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Lactoferrin (Lf) in blood and/or marrow neutrophils was semiquantified using indirect immunofluorescence technique in nine mammalian species. Neutrophil iron-binding reactivity (NFeBR), which corresponds primarily to Lf, was also visualized and semiquantified using functional cytochemical (FeNTA-AF) technique at the light microscopic level in these nine and in an additional fifteen mammalian species, and in selected species at the ultrastructural level. Neutrophil immunoreactive Lf was positively correlated with total cellular and granule content of NFeBR among these nine species, and with previously reported concentrations of neutrophil Lf quantified by radioimmunoassay. Relative levels of Lf in neutrophil extracts from rat, hamster, and human were confirmed using SDS-polyacrylamide gel electrophoresis and immunoblotting. Relatively high levels of immunoreactive neutrophil Lf and/or NFeBR were observed in carnivores (ten species) and primates (six species). Among rodents (five species), the levels were variable, and the artiodactyls (four species) studied had low levels. These results demonstrate that neutrophil Lf levels vary widely among mammalian species. In addition, FeNTA-AF technique provides a rapid means of evaluating animals for relative quantities of neutrophil Lf.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 212 (1985), S. 161-166 
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Discovery of components of the renin-angiotensin system (RAS) in the adenohypophysis of several species has prompted speculation concerning the location and possible function of a pituitary RAS. Although both renin and angiotensin II have been localized within the rat adenohypophysis, their colocalization has not been previously demonstrated within the same cells. In the present study, immunohistochemical staining by the avidin-biotin-peroxidase complex technique was used to demonstrate the coexistence of renin and angiotensin II in adenohypophyseal cells identified morphologically and immunocytochemically as gonadotrophs. These results support the existence of an adenohypophyseal RAS, at least part of which is under intracellular control. The influence of this system on control of fluid balance, blood pressure, and the secretion of other hypophyseal hormones is discussed.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 0002-9106
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Macrophages and cells of the plasmocyte series were studied in the rat's spleen during the primary and secondary immune responses to particulate antigen. Evidence is presented to suggest that the plasma cell precursors are located in the marginal zones surrounding the lymphoid nodules and that less than one day following injection of antigen, these cells migrate into the nodules, where mitosis and subsequent differentiation into hemocytoblasts occurs in the presence of nodular macrophages. The hemocytoblasts then migrate across the marginal zone into the red pulp where differentiation into mature plasma cells occurs in the presence of red pulp macrophages. It is suggested that the initiation of the antibody-forming process occurs in the lymphoid nodules where marginal zone cells come into close contact with the marginal metalophils or with germinal center macrophages. The process initiating the migration of cells from the marginal zone to the nodules is unknown.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 0002-9106
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Spleens from neonatally thymectomized and nonthymectomized young rats were studied histologically and histochemically to elucidate the development of the splenic immune system with and without thymus.In intact animals primitive germinal center activity could be elicited with antigen as early as 13 days of age. More definitive germinal centers lacking tingible body macrophages were observed at 18 days of age. Germinal centers containing tingible body macrophages did not develop until 35 days of age in response to antigenic stimulation. This coincided with maximal development of the marginal zone of medium-sized lymphocytes and the mature development of nodular macrophages possessing strong acid phosphatase activity.Neonatally thymectomized rats developed marginal zones and germinal centers similar to control littermates when the young animals were maintained on tetracycline. Thymectomized animals not given tetracycline showed disturbances in splenic development. These are discussed.The results suggest that the thymus may be critical to the immune system in rats from birth to about 30 days of age but is not essential to its function beyond this period. Marginal zone lymphocytes and germinal center cells proliferate normally and mature to the plasma cell stage in the absence of a thymus if the animals are maintained on tetracycline beyond this critical age.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 124 (1985), S. 207-212 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The mechanisms of action of extracellular mitogens for normal human bronchial epithelial cells (NHBE) were investigated by observing their effects on selected biochemical pathways when the cells were incubated in serum-free media. We find that (a) epidermal growth factor (EGF) stimulates ornithine decarboxylase (ODC) activity and the rate of cell division without stimulating cAMP; (b) alone, pituitary extract (PEX) does not stimulate ODC activity, cAMP levels, or cell division; (c) when PEX is added to medium containing EGF there is a further increase in both ODC activity and the rate of cell division, again with no increase in cAMP levels; (d) in contrast, alone, L-epinephrine (EPI) stimulates an increase in both ODC and cAMP but does not stimulate cell division; (e) when EPi is added to medium containing both EGF and PEX a further increase in the rate of cell division is noted; (f) the specific inhibitor of ODC, α- (difluoromethyl)-ornithine (DMFO), also inhibits NHBE cell proliferation; and (g) the β-adrenergic receptor antagonist propranolol inhibits the mitogenic action and ODC induction by EPI observed under condition e. We conclude that an increase in ODC activity is necessary but not sufficient for an increase in proliferation of NHBE cells. In contrast, cAMP stimulation is not necessary for an increase in NHBE cell division. However, in the presence of undefined factors in PEX, increases in cAMP levels result in a synergistic increase in the rate of EGF-stimulated clonal growth. By correlating the biochemical pathways invoked by EGF, PEX, EPI, and combinations thereof with their mitogenic actions, we have better defined the role each of these different mitogens plays in stimulating epithelial cell division.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 129 (1986), S. 73-81 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
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