Search PubMed⌕ Search

Biomedical subjects

A M Dannenberg

Publications and source records attributed to A M Dannenberg.

At least 55 records · Page 3Linked to original sources
PubMed1981

Persistence of protein, carbohydrate and was components of tubercle bacilli in dermal BCG lesions.

Dermal tuberculous lesions were produced in rabbits with Bacille Calmette Guèrin and biopsied on days 4, 14, 21, 35, and 56. Frozen sections prepared from the biopsy specimens were stained by the peroxidase-antiperoxidase immunocytochemical technique with antisera against whole tubercle bacilli and antisera against the protein B, polysaccharide I, and wax D fractions of tubercle bacilli. In the primary lesions, protein B was often undetectable at 21 days, and polysaccharide I was often undetectable at 35 days. Wax D disappeared more slowly than the other bacillary components evaluated, and some wax D was still found at 56 days (if the lesions had not completely healed). Antisera against intact tubercle bacilli produced results similar to those produced by antiserum against wax D. These studies suggest that the chronicity of tuberculous lesions is due, at least in part, to the persistence of the wax D-like component of tubercle bacilli.

Animals↗
PubMed1980

Macrophage functional heterogeneity in vivo. Macrolocal and microlocal macrophage activation, identified by double-staining tissue sections of BCG granulomas for pairs of enzymes.

BCG lesions were produced in the skin of rabbits, and biopsies were performed at 7, 21, and 42 days, when they were developing, maximal in size, and almost healed, respectively. Tissue sections were prepared and stained histochemically for several enzymes. The percentage of cells stained for a given enzyme and the distribution of such cells within lesions of various ages were determined. Seven-day BCG lesions contained few esterase- and beta-galactosidase-positive macrophages, but 21-day lesions contained many, especially in the viable and nonviable tuberculous granulation tissue at the edge of the now prominent caseous necrotic center. Both 7-day and 21-day lesions contained many acid phosphatase- and cathepsin-D-positive macrophages, which were numerous in the more peripheral parts of the lesion, where little or no necrosis was present. Enzyme patterns in 42-day lesions resembled those in 21-day lesions. The role of each of these enzymes in the development and regression of the BCG lesion is unknown. Nonetheless, these studies clearly demonstrate that this macrophage population is heterogeneous and that macrophages carry out different functions in different parts of the lesion at different times. Histochemical techniques were developed to stain two enzymes in the same tissue section. The first stain usually contained a naphthol substrate and produced a red color; the second stain contained an indoxyl substrate and produced a blue color. A cell staining with both was colored purple. The peroxidase-antiperoxidase immunocytochemical technique for cathepsin D (producing a red color) was also employed. 1) Red esterase (hydrolyzing naphthol AS-D acetate) and beta-galactosidase, and 2) red esterase and blue esterase (hydrolyzing 5-bromo-4-chloro-indoxyl acetate), probably the same enzyme, were usually present in the same macrophage. In contrast, each of the following enzyme pairs was usually present in a different macrophage: 3) cathepsin D and beta-galactosidase, 4) cathepsin D and blue esterase, 5) acid phosphatase and beta-galactosidase, and 6) acid phosphatase and blue esterase. Roughly 10% of the macrophages stained for one enzyme existed side by side with macrophages stained for a different enzyme. These results suggest that local macrophage activation is under two levels of control. The first, macrolocal control, would determine the overall enzyme distribution in the lesion; whereas the second, microlocal control, would determine enzyme distribution on a cell-by-cell basis, ie, how two neighboring macrophages can each be rich in a different enzyme.

Animals↗
PubMed1979

The antinflammatory effects of glucocorticosteroids. A brief review of the literature.

The effects of glucocorticosteroids on immune and inflammatory responses are reviewed. The steroids seem to change the number or function of cell receptors for regulating agents, so that in areas of inflammation: (a) blood vessels dilate less, (b) lymphocytes proliferate less, (c) all leukocytes infiltrate less, (d) macrophages become less activated (digesting and secreting less), and (e) fibroblasts produce less collagen and ground substance. In addition, the corticosteroids seem to alter the response of cells to various signals from their receptors by affecting the prostaglandin system, cyclic nucleotides, and perhaps other internal mediators.

Bacterial Infections↗
PubMed1979

Macrophages in immunity to syphilis: suppressive effect of concurrent infection with Mycobacterium bovis BCG on the development of syphilitic lesions and growth of Treponema pallidum in tuberculin-positive rabbits.

Paired groups of male rabbits were challenged with Treponema pallidum and Mycobacterium bovis BCG. One group had been sensitized to BCG by inoculation 3 weeks before challenge. All animals were challenged intradermally at multiple sites with T. pallidum alone, BCG alone, and both organisms into the same sites. The resulting lesions were followed clinically and histologically. BCG lesions enlarged more rapidly in sensitized rabbits, but they were otherwise no different from those in the controls. T. pallidum lesions enlarged and regressed simultaneously in both groups, but in the BCG-sensitized animals they became twice as large as those in the unsensitized rabbits. Mixed BCG-T. pallidum lesions showed the greatest differences in the two groups of animals. Like the pure BCG lesions, they enlarged more rapidly in the sensitized rabbits but began to recede after 1 week. The corresponding lesions in the controls enlarged more slowly and reached their maximum size after 3 weeks when the receding lesions in the sensitized animals were much smaller. The most marked histological-histochemical difference between the two groups of animals was in the number and activation of macrophages. These cells were more numerous in the mixed lesions of BCG-sensitized animals than in similar lesions of the controls and more activated as determined by beta-galactosidase staining. Although sparsely distributed, activated macrophages were more numerous in the pur T. pallidum lesions of sensitized animals than in those of control animals. Silver-stained sections revealed fewer treponemes in mixed lesions of sensitized animals than in the mixed lesions of control animals. Quantitation of treponemes in pure T. pallidum versus mixed lesions was determined in two groups of rabbits challenged intratesticularly. The total number of treponemes per testis in the mixed lesions of BCG-sensitized rabbits was significantly less than the number in the mixed lesions of control animals, and also less than the number in pure T. pallidum lesions of both groups of animals.

Animals↗
PubMed1979

Histochemical demonstration of enzyme activities in plastic and paraffin embedded tissue sections.

Histochemical staining for enzymes is usually performed on frozen sections. This report lists the longer incubation times required to demonstrate esterase, acid phosphatase, beta-galactosidase, and cytochrome oxidase in plastic embedded and ruotine paraffin embedded tissues. The sections embedded in plastic, i.e. water soluble methacrylate (Polyscience's JB-4) and cut at 2 micrometers, were far superior to frozen sections and paraffin embedded sections both in tissue detail and in the localization of the histochemical reaction product.

Acid Phosphatase↗
PubMed1979

Quantitative histological changes produced in the tracheal mucosa of young chickens by the inhalation of sulfur dioxide in low concentrations.

Chickens were exposed to SO2 in relatively low concentrations (3.4 to 18.5 parts per million (ppm)) for 1 to 14 days. A portion of their tracheas was embedded in water-soluble methacrylate, cut at 2 micrometer and stained with hematoxylin and eosin, Wright's stain, methyl green-pyronin, Alcian blue - periodic and Schiff, and for acid phosphatase. An increase was found in (a) the mucosa to wall ratio; (b) the number of mucosal cells in mitosis; (c) the number of macrophages, lymphocytes, plasma cells, and neutrophils in the epithelium and lamina propria; and (d) the number of these infiltrating cells which contained acid phosphatase. The number of mucus- and seromucus- secreting cells and vasoamine-containing cells were sometimes increased, but not consistently. The percentage of cells containing sialidase-sensitive sialomucins was elevated, and percentage of cells containing neutral mucins was reduced. These changes were only partly related to the SO2 concentration and the duration of SO2 exposure, in that increasing amounts of SO2 did not always cause increasing changes in the mucin composition. Evidently, the altered mucins sometimes protected against further mucin modification.

Acid Phosphatase↗
PubMed1978

The effect of cortisone on the accumulation, activation, and necrosis of macrophages in tuberculous lesions.

Rabbits were injected intramuscularly with cortisone acetate (2 mg/kg) on alternate days. Six days after the first injection these rabbits and controls were injected intradermally in multiple sites with BCG (the vaccine strain of tubercle bacillus). Periodically, over the next 2 months, the resulting lesions were measured and surgically biopsied, and the animals were tuberculin-tested. Macrophage activation in the BCG lesions was evaluated histochemically by staining for beta-galactosidase activity. Both BCG lesions (and tuberculin reactions) in the cortisone-treated group were considerably smaller than those in the control group. Cortisone was highly effective in reducing the number of infiltrating mononuclear cells (MN), the amount of caseous necrosis and ulceration, and the percent of NM that were beta-galactosidase-positive. The decreased activation and reduced number of macrophages readily explains the increased susceptibility to tuberculosis found amoung patients receiving glucocorticosteroids. In the BCG lesions, the local decrease in the number and function of leukocytes probably explains the decreased tissue necrosis. Such antiinflammatory effects of corticosteroids may offset, in selected antimicrobial-treated cases, the hormone's detrimental effect on host resistance to infectious agents.

Animals↗
PubMed1978

Extracellular hydrolytic enzymes of rabbit dermal tuberculous lesions and tuberculin reactions collected in skin chambers.

To evaluate extracellular hydrolytic enzymes in an in vivo system, plastic chambers were glued over rabbit dermal BCG lesions in various stages of development, after the central epithelium was removed with a scalpel. They were filled with tissue culture medium and left in place 2 days. The following enzymes in the fluid were assayed: collagenase (an enzyme secreted but not stored in macrophages); lysozyme (both secreted and stored); DNase and RNase (released on cell death and possibly regurgitated but not secreted); and, as a control, lactic dehydrogenase (released only on cell death). Tissue sections were prepared and studied histologically for the type of cell infiltrate, for beta-galactosidase (our marker enzyme for macrophage activation), and for necrosis. At 11 and 18 days of age the BCG lesions were largest and the number of activated macrophages in the chamber beds was highest. At this time the levels of the five enzymes assayed in the chamber fluids reached their peaks, tuberculin hypersensitivity was well developed, and the bacilli components would still be plentiful. In general, the chamber fluids from 11- and 18-day BCG lesions contained higher enzyme levels than chamber fluids from tuberculin reactions. Active collagenase was only detected in fluids from such BCG lesions. Evidently, the serum in the chamber fluids was sufficient to inhibit the lower amounts of collagenase probably released from smaller BCG lesions and tuberculin reactions (and from the 2-week polystyrene lesions that were also evaluated). These studies demonstrate that in chronic inflammatory reactions, both acid-acting and neutral-acting hydrolytic enzymes are released extracellularly. Tissue components would be hydrolyzed locally wherever the acid-acting hydrolytic enzymes encounter a drop in pH and wherever the concentration of neutral-acting hydrolytic enzymes exceeds the concentration of their inhibitors.

Animals↗
PubMed1977

Histochemical studies relating the activation of macrophages to the intracellular destruction of tubercle bacilli.

Dermal tuberculous lesions, both primary and those of reinfection, were produced in rabbits with 14C-labeled BCG and biopsied once at various times. Macrophage activation was evaluated by the indolyl histochemical test for beta-galatosidase, the number of bacilli in macrophages by acid-fast staining, and the breakdown of bacilli by autoradiography. After the rabbits became tuberculin positive, the stongly activated macrophage population contained a) fewer parasitized cell, b) fewer bacilli in each parasitized cell, and c) more "free" 14C-label (not associated with intact bacilli) than the weakly activated macrophage population. These results suggest that the more highly activated macrophages had destroyed many of the bacilli that they once contained and that their power to do so was enhanced by immunologic mechanisms.

Animals↗
PubMed1976

Turnover of tritiated-thymidine-labeled mononuclear cells in tuberculous lesions of rabbits: a comparison of primary dermal BCG lesions and those of reinfection.

Rabbits were infected or reinfected intradermally in multiple sites with BCG. One day before the BCG infection they were injected iv with a single pulse of tritiated thymidine (3HT). At various times thereafter, the BCG lesions were biopsied and evaluated for 3HT-labeled mononuclear cells (MN), which are mostly macrophages but include some lymphocytes. Periodically Old Tuberculin (OT) was infected intradermally, creating MN traps, which were biopsied and evaluated 1 day after their onset. These traps monitor the population of 3HT-labeled MN in the blood stream that readily enters sites of inflammation. During the first 5 days after the 3HT pulse, a higher percentage of labeled MN accumulated in tuberculin traps on rabbits reinfected with BCG than in traps on rabbits with primary infection. The high percentage of labeled MN in the former was probably due to the more intense inflammation cuased by preexisting tuberculin hypersensitivity. By 8 days after the 3HT pulse, a lower percentage of labeled MN had accumulated in BCG lesions of reinfection than in primary BCG lesions. Evidently the presence of delayed hypersensitivity increased the turnover of MN in tuberculous lesions. By 15 days after the 3HT pulse, the percentage of 3HT-labeled MN was much higher in BCG lesions than in 1-day traps, suggesting that such MN had accumulated in the lesions over a period of several days.

Animals↗
PubMed1976

Mononuclear cell turnover in chronic inflammation: studies on tritiated thymidine-labeled cells in blood, tuberculin traps, and dermal BCG lesions of rabbits.

Rabbits were injected intradermally in multiple sites with BCG. Four days after the BCG injection, they were injected intravenously with a single pulse of tritiated thymidine (3H-TdR) at various times thereafter, the BCG lesions were biopsied and evaluated for 3H-TdR-labeled mononuclear cells (MN). Periodically, Old Tuberculin (OT) was injected intradermally, creating MN traps which were biopsied and evaluated 1 day after their onset. 3H-TdR-labeled cells were also evaluated in samples of blood. During the first 8 days after the 3H-TdR pulse, the labeled MNs represent short-lived cells, i.e., recently dividing monocytes and lymphocytes. During this time, the percentage of labeled MNs in the blood, in the traps, and in the BCG lesions rose and fell together. This result suggests that the majority of the MNs in the BCG lesions had a turnover rate of about a week. By 12 days and afterward, the percentage of MNs labeled by 3H-TdR in the blood was higher than that in the BCG lesions which was in turn higher than that in the traps. At this time the circulating MN population probably contained labeled long-lived lymphocytes that did not enter inflammatory sites (the traps) as readily as the short-lived lymphocytes. The labeled MNs remaining in the BCG lesions probably did not divide and dilute out their 3H-TdR label as readily as those that were trapped from the bone marrow via the blood. The percentage of MNs labeled with 3H-TdR in the traps had decreased to about one-fifteenth of its peak value by 12 days, suggesting that the bone marrow's supply of labeled MNs was depleted at this time, except for the few cells labeled as a result of 3H-TdR reutilization.

Animals↗