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M J Stadecker

Publications and source records attributed to M J Stadecker.

70 records · Page 4Linked to original sources

Angiotensin-1-converting enzyme activity of murine macrophages isolated from granulomas elicited by eggs of Schistosoma mansoni.

Angiotensin-1-converting enzyme (A1CE) activity was assessed in macrophages isolated from hepatic egg granulomas at 7 and 20 weeks after the infection of mice with Schistosoma mansoni. At 2 h after isolation, granuloma macrophages (GM) from chronically infected mice (20 weeks) displayed significantly higher levels of A1CE than did GM from mice 7 weeks after infection; both of the values were significantly higher than control peritoneal resident macrophages from normal mice. A1CE activity in GM and their respective culture supernatants declined over a 72-h period of in vitro cultivation; however, the decline was abrogated with the addition of dexamethasone to the culture medium. GM from athymic mice displayed significantly higher A1CE activity than did those from normal controls. Our data confirm and extend previous findings of others that GM are a major source of A1CE in murine schistosomiasis and that lymphocyte function may regulate GM A1CE production.

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Induction of immune responses by schistosome granuloma macrophages.

In mice, granuloma formation after Schistosomiasis mansoni infection is known to be a T cell-dependent response to schistosome eggs that peaks at 6 to 8 wk after infection (early) then regresses to a minimum by 20 to 32 wk (late). This decline in host responsiveness, termed modulation, has been attributed to T cell-mediated suppression. We now have investigated the macrophages from either Early or Late schistosome granulomas phenotypically and found no difference in expression of I-A subregion encoded antigens. We also tested granuloma macrophage (Gm) populations in their capacity to induce positive and negative antigen-specific immune responses to the hapten 4-hydroxy-3-nitrophenyl acetyl (NP). As few as 10(3) to 10(4) NP-coupled Early or Late Gm given s.c. were equally capable of inducing MHC-restricted NP-specific delayed-type hypersensitivity (DTH) responses and this DTH-inducing capability was equivalent to that of splenic adherent cell (SAC) controls. Further, both Early and Late Gm were able to generate NP-specific induction-phase suppressor cells (Ts1) when as few as 10(2) NP-coupled Gm were given i.v., the same as NP-SAC controls. Finally, NP-specific effector-phase suppressor cells (Ts3) were equally induced by Early Gm, Late Gm, or SAC controls. Therefore, macrophages derived from Early or Late schistosome granulomas or normal spleens are apparently phenotypically indistinguishable and equally capable, in extremely small quantities, of inducing NP-specific DTH, Ts1, and Ts3 immune responses.

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Ia antigen expression and antigen-presenting function by macrophages isolated from hypersensitivity granulomas.

Macrophages were isolated from granulomas elicited in the liver by the eggs of the trematode Schistosoma mansoni. They were analyzed for the expression of determinants encoded by the I-A subregion of the major histocompatibility complex and for their ability to present antigen in a T cell proliferation assay. Seventy-five to 81% of the macrophages were found to bear I-A antigens after 24 hr in culture; they also were shown to be effective in carrying out antigen-presenting function. Subsequent in vitro cultivation for up to 4 days demonstrated a progressive loss of I-A molecules, which correlated with a corresponding reduction in antigen-presenting capability. The latter was antigen-specific, blocked by monoclonal antibody directed against I-A, and abrogated after depletion of I-A-positive macrophages. Populations of macrophages from hepatic egg granulomas were richer in I-A-positive cells, and were more effective in terms of antigen-presenting capability compared to those obtained from foreign body-type granulomas. These observations suggest a central role for macrophages from infectious granulomas in the induction and maintenance of immunity and hypersensitivity.

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Comparison of pyrimidine and purine nucleoside secretion and nucleoside kinase expression in resident and elicited peritoneal macrophages.

Thymidine was found in culture supernatants from both normal peritoneal macrophages and macrophages elicited in vivo with LPS under conditions in which there was no detectable TK activity. Abrogation of thymidine secretion was observed only when elicited macrophages were cultured in the presence of macrophage growth factor (MGF), whereas resident macrophages continued secreting under similar conditions. Similarly, TK activity was induced with MGF only in elicited, but not in resident, macrophages; LPS added in vitro failed to render resident macrophages susceptible to stimulation by MGF. Tests for adenosine and deoxyadenosine in macrophage supernatants proved that these nucleosides were not secreted by these cells. Although AK was consistently expressed in both resident and elicited macrophages, no significant dAK levels could be detected in either cell population. In contrast to TK, both purine nucleoside kinases could not be modulated or induced with MGF. The data indicate different reactivity to MGF by resident and elicited macrophages and a difference in pyrimidine vs purine nucleoside secretion as well as nucleoside kinase expression by these cells.

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Pleural effusion as a complication of solitary eosinophilic granuloma of the rib.

A 57 year old man presented with a two week history of right sided chest pain. An admission chest x-ray examination revealed a 2 by 1 cm. lytic lesion of the ninth right rib and right sided pleural effusion. The patient underwent a right thoracotomy during which 700 cc. of blood tinged pleural fluid was drained and a 10 cm. segment of the right ninth rib was excised. The rib lesion showed classic features of eosinophilic granuloma of bone. Cytologic examination of the pleural fluid disclosed abundant histiocytes and eosinophils, consistent with eosinophilic granuloma invading the pleural space. This case is unusual because of the age of the patient and the development of a pleural effusion secondary to the rupture of the tumor into the pleural cavity, the latter not previously reported in the literature.

Age Factors↗

The regulation of thymidine secretion by macrophages.

The secretion of thymidine by mononuclear phagocytes was correlated with the activity of the enzyme thymidine kinase (TK). Macrophages cultured in regular tissue culture medium released thymidine and did not express TK. However, when macrophages were incubated with medium conditioned by L cells, they expressed TK, incorporated 3H thymidine into trichloroacetic acid precipitable material, and ceased to secrete the nucleotide. Furthermore, replicating P388/D1 cells were induced to secrete thymidine by inhibiting TK with d-glucosamine. These results have demonstrated an inverse relationship between thymidine secretion and the expression of TK. They suggest that thymidine secretion by macrophages may be attributed to their lack of TK activity.

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The cutaneous basophil response to phytohemagglutinin in chickens.

A cellular infiltrate rich in basophils was observed in chickens in skin sites injected locally with the mitogen PHA. These infiltrating metachromatically granulated cells exhibited features common to mast cells of some species (monolobed nucleus), but also resembled basophils of other species in that they circulated in the blood, and they responded to the PHA mitogen by infiltrating skin test sites. Previous literature suggests that the chicken has a single metachromatic granulated cell and our data support this notion. PHA, a known T cell mitogen, may act by causing the stimulated T lymphocyte to produce a lymphokine that is responsible for the attraction of basophils to the test site.

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Synthesis and release of thymidine by macrophages.

An inhibitor of DNA synthesis and cell proliferation found in macrophage supernatants was subjected to further analysis. The following conclusions were drawn: a. Biochemically, the inhibitor appeared to be thymidine, judging from the migration in three different thin-layer systems and on gel filtration. b. The inhibitor was shown to be synthesized de novo by macrophage monolayers pulsed with a radiolabeled precursor of thymidine such as 14C-formate. c. The amount of inhibitor present in tissue culture fluids proved to be sufficient to block the growth of the EL-4 leukemia cell line in a manner that could be prevented with the addition of 2'-deoxycytidine. The EL-4 line was considerably more sensitive to thymidine blockade than a number of different cells tested.

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Unusual anomaly of the small intestine with malabsorption.

Malabsorption as a complication of anatomic congenital anomalies of the small bowel is uncommon. In this case, malabsorption syndrome in infancy, with features suggestive of coexisting disaccharide intolerance and blind loop syndrome, was the major clinical presentation of a combined anomaly, consisting of a large saccular dilation of the ileum containing heterotropic gastric mucosa, and an adjacent small intramesentric cyst partially lined by small bowel epithelium. Prompt reversal of metabolic and nutritional abnormalities followed surgical resection.

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Comparison of the inactivation of IgM and IgG complement fixation sites by acid and base.

Rabbit IgM antibodies to denatured mammalian or T6 bacteriophage DNA or poly(A)-poly(U) irreversibly lost complement-(C) fixation reactivity on exposure to low pH and reneutralization, with a halving of the complement-fixation titer occurring after treatment at about pH 3. The titers of IgG antibodies to denatured phage DNA, to poly(A)-poly(U), or to hemocyanin were halved only after exposure to pH 2. Inactivation by acid was enhanced by low protein concentrations, incubation at higher temperatures, and by slow reneutralization; under all these conditions it was more extensive with IgM than with IgG. Inactivation of IgM C-fixation activity at pH 2.5 and room temperature was a first order reaction, with a half-time of about 20 min. Both classes retained antigen-binding activity after exposure to pH 2. In the alkaline range, full C-fixation reactivity was retained by both classes after reneutralization from pH 11.5, some loss occurred at pH 12, and total irreversible inactivation occurred by pH 12.5. In the latter case, antigen-binding activity was also lost. The C-fixation inactivation curves in the alkaline range were similar for IgG and IgM antibodies.

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Regulation of immunity and inflammation by mediators from macrophages.

Mononuclear phagocytes secrete a number of materials into the extracellular environment. The materials secreted by phagocytes can be grouped into three categories: a) enzymes affecting extracellular proteins (collagenase, elastase, lysosomal proteases, plasminogen activators), b) materials involved in defense processes (complement proteins, interferons, lysozyme), and c) factors regulating activities of surrounding cells. The latter include lymphostimulatory molecules, a colony-stimulating factor, and inhibitors of cell growth. The conditions for secretion of the materials depend on the activity of the phagocytes. The lymphostimulatory molecules secreted by macrophages exert various effects: 1) an increase in DNA synthesis of lymphocytes, 2) a maturation of early thymocytes to mature T cells, and 3) the differentiation of some B cells to antibody-secreting cells. The mitogenic principle has been partially isolated as a protein of 15,000 to 20,000 daltons. The secretion of lymphostimulatory molecules is increased following uptake of various materials by macrophages or by addition of activated T cells to macrophage cultures.

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The inhibition of cutaneous basophil hypersensitivity reactions by a heterologous anti-guinea pig T cell serum.

Systemic treatment with a heterologous anti-T cell serum of guinea pigs immunized with EA in IFA markedly suppressed CBH reactivity to specific antigen and T cell mitogens, as judged by gross reactivity, histology, and skin histamine. The antiserum produced a marked drop in circulating lymphocytes, mainly at the expense of T cells, as indicated by the ability of surviving lymphocytes to rosette with rabbit RBC. It was postulated that the suppression of CBH reactivity is due to the depletion of T cells, which would have released a factor chemotactic for basophils. The data therefore provide further evidence that cutaneous reactions rich in basophils are primarily dependent on a population of T cells.

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