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M J Stadecker

Publications and source records attributed to M J Stadecker.

At least 55 records · Page 3Linked to original sources
PubMed1991

Spirochetes in atrophic skin lesions accompanied by minimal host response in a child with Lyme disease.

Acrodermatitis chronica atrophicans, which has rarely been observed in the United States, is a late skin manifestation of Lyme borreliosis. A 12-year-old girl who spent summers on Cape Cod presented with a 2-year history of hyperpigmentation and atrophy of the skin on the hands, wrists, and ankles. The skin biopsy specimen of an affected area showed mild dermal fibrosis, a few inflammatory cells, and spirochetes morphologically compatible with Borrelia burgdorferi. An IgG antibody response to B. burgdorferi could be elicited by immunoblotting, but not by enzyme-linked immunosorbent assay. We conclude that this patient had chronic Lyme borreliosis manifested only by indolent infection of the skin.

Acrodermatitis↗
PubMed1991

Propranolol ameliorates the development of portal-systemic shunting in a chronic murine schistosomiasis model of portal hypertension.

We investigated the role of early portal hypotensive pharmacotherapy in preventing the development of portal-systemic shunting in a portal hypertensive model of chronic murine schistosomiasis induced by infecting C3H mice with 60 cercariae of Schistosoma mansoni. Propranolol was administered in drinking water to 20 animals for a period of 6 wk at a dose of 10 mg.kg-1d-1, starting at 5 wk of schistosomal infection. 32 age-matched mice with chronic schistosomal infection served as controls. All animals were studied 11 wk after the infection. Compared with controls the portal pressure (10.8 +/- 0.40 mmHg) was significantly lower (P less than 0.001) in the propranolol-treated animals (7.9 +/- 0.80 mmHg). Portal-systemic shunting was decreased by 79%, from 12.2 +/- 3.34% in controls to 2.5 +/- 0.99% in the propranolol group (P less than 0.05). Portal venous inflow was reduced by 38% in the propranolol treated animals (2.50 +/- 0.73 ml/min; n = 6) compared with controls (4.00 +/- 0.34 ml/min; n = 8; P less than 0.05). The worm burden, the granulomatous reaction, the collagen content of the liver, and the serum bile acid levels were not significantly different between the two groups of animals. These results demonstrate that in chronic liver disease induced by schistosomiasis, the development of portal-systemic shunting can be decreased or prevented by the reduction of flow and pressure in the portal system.

Animals↗
PubMed1990

Induction of T helper cell unresponsiveness to antigen by macrophages from schistosomal egg granulomas. A basis for immunomodulation in schistosomiasis?

The present studies were undertaken in an effort to understand the role of mononuclear phagocytes in the regulation of the T cell-mediated granulomatous inflammatory response in experimental murine schistosomiasis mansoni. We report that macrophages from schistosomal egg granulomas did not efficiently stimulate, but rather induced marked proliferative unresponsiveness to Ag in an IL-2-producing, I-Ek-restricted, CD4+ Th cell clone specific for pigeon cytochrome c. The unresponsive state of the T cells was achieved after incubation with granuloma macrophages in the presence of the specific Ag fragment 81-104, but not with either of them independently, and was, similarly, restricted by the I-Ek molecule. Equivalent amounts of peritoneal macrophages from schistosome-infected, but not from normal mice, were also effective in inducing T cell unresponsiveness. We postulate that granuloma macrophages, and potentially other accessory cells in schistosome-infected individuals, are similarly capable of inducing anergy in egg Ag-specific Th cells, and that the resulting inhibited T cell reactivity, which translates into failure of lymphokine secretion and of clonal expansion, represents a major basis of the immunologic down-regulation (immunomodulation) of granulomatous hypersensitivity, characteristically seen in this disease.

Animals↗
PubMed1990

Thyroid-derived epithelial cells acquire alloantigen-presenting capabilities following X-irradiation and class II antigen induction.

This work was undertaken to further define the antigen-presenting capabilities of thyroid epithelial cells, as this is of paramount importance with regard to their potential to trigger autoimmune thyroiditis. For this purpose we developed the murine cloned thyroid-derived epithelial cell line M.5 which, as previously reported, could be induced to express class II antigens with interferon (IFN)-gamma, but failed to stimulate a primary mixed leukocyte reaction. We now show that M.5 cells acquired alloantigen-presenting function, under conditions in which their replication was arrested by X-irradiation, during a 4-day period of exposure to UV-inactivated reovirus, or to IFN-gamma, for induction of class II antigens. The allostimulatory function by M.5 cells could not be explained on the basis of enhanced class II antigen expression, as equivalent numbers of M.5 cells, irradiated after the 4-day exposure to reovirus, or to IFN-gamma, expressed higher amounts of class II antigens, but did not stimulate a primary mixed leukocyte reaction. Early X-irradiation appeared to induce in the class II-expressing M.5 cells a co-stimulatory signal needed for T cell proliferation, similar to that otherwise provided by phorbol esters in this system. Preservation of alloantigen-presenting function by M.5 cells following fixation indicated that this co-stimulatory activity did not reside in a soluble molecule. We surmise that M.5 epithelial cells must provide a least two signals in order to be able to stimulate lymphocyte populations. Consequently, the mode and conditions of epithelial cell activation may determine whether these cells acquire the capacity to serve as antigen-presenting cells, and ultimately whether or not they are able to induce autoimmune disease.

Animals↗
PubMed1989

Direct induction of Ia antigen on murine thyroid-derived epithelial cells by reovirus.

The ability of thyroid follicular epithelial cells (TFEC) to act as APC is linked to the expression of class II (Ia) molecules of the MHC. The cloned murine thyroid-derived epithelial cell line M.5 was used to demonstrate the potential effects of virus in the direct induction of Ia molecules on TFEC. Membrane binding and replication of reovirus type 1 in TFEC was demonstrated using fluorescein-labeled antireovirus antibody and fluorescence microscopy. One consequence of the interaction between reovirus and M.5 cells was the induction of Ia Ag and augmented class I molecule expression in M.5 cells. The levels of Ia expression at three days after reovirus binding were amplified 17.3-fold over controls and were 2-fold less than that seen upon treatment of M.5 cells with IFN-gamma. Supernatant transfer experiments showed that the induction of Ia expression was directly linked to the binding of virus to M.5 cells, and was not dependent upon virus replication or the presence of IFN. These results indicate that early events of reovirus binding or receptor internalization on TFEC initiate a signaling process which results in the induction of class II and augmentation of class I MHC protein levels on the cell surface.

Adhesiveness↗
PubMed1989

Schistosoma mansoni: the host immune response to egg antigens. I. Partial characterization of cellular and humoral responses to pI fractions of soluble egg antigens.

Soluble egg Ag (SEA) were separated according to charge by agarose-IEF (A-IEF) in order to partially characterize those antigenic determinants that may elicit the granulomatous response in schistosomiasis mansoni. Coomassie blue-stained A-IEF gels of SEA showed that this technique was able to resolve multiple isobands. A-IEF gels were sliced into 18 or 36 fractions from anode to cathode, and the SEA components from the isoelectric point (pI) fractions were eluted from gels in a manner that allowed for their direct utilization in both cellular and in humoral immunoassays. Only Ag in two distinct pI ranges consistently elicited lymphoproliferative responses, with the major stimulatory fractions being in the acid (3.5 to 5.0) range. Lymphocytes from mice infected for 10 wk had higher proliferative responses to both SEA and fractionated Ag in this acid pI range when compared to lymphocytes from mice infected for 25 wk; however, the latter had an enhanced response to Ag with a pI range of 6.2 to 6.4. In contrast to the cellular responses, the corresponding sera from these mice, or from schistosome-infected patients, recognized Ag in all pI fractions as determined by ELISA. However, although protective and nonprotective mAb (which recognize an egg Ag that cross-reacts with a 38-kDa schistosomular Ag) bound to most acidic fractions, only the nonprotective mAb (which also recognize determinants on keyhole limpet hemocyanin), bound, in addition, to fractions in the basic range. Finally, the m.w. of Ag in the various pI fractions were determined by SDS-PAGE analysis.

Animals↗
PubMed1989

Schistosomal egg granuloma-derived fibroblast-stimulating factor is apparently distinct from interleukin-1.

We have previously reported that egg granulomas isolated from livers of Schistosoma mansoni-infected euthymic mice in vitro elaborate a factor(s) that stimulates a variety of fibroblast responses including fibroblast proliferation and enhanced synthesis of extracellular matrix proteins. We have postulated that these factors play a role in the pathogenesis of hepatic fibrosis in schistosomiasis mansoni. Serum-free supernatants from egg granuloma cultures also stimulate thymocyte proliferation in an assay that defects interleukin-1 (IL-1). Thymocytes and fibroblasts are stimulated to proliferate by the same fractions of egg granuloma culture supernatant separated by gel filtration, isoelectric focusing, and ion-exchange chromatography. This suggested that granuloma-derived IL-1 is responsible for the observed fibroblast stimulation. Here we report that the ability of granuloma culture supernatants to stimulate the IL-1-sensitive D10.G4.1 cells but not fibroblasts is removed by treatment with immobilized anti-IL-1 antibody. We also observed that dialyzed culture supernatants from egg granulomas obtained from infected congenitally athymic (nude) mice also stimulate fibroblast proliferation. Treatment with anti-IL-1 antibody did not abrogate this response. In contrast to our experience with egg granulomas isolated from euthymic mice, IL-1- and fibroblast-stimulating activity could be separated by gel filtration and isoelectric focusing. We conclude that the fibroblast growth-stimulating activities elaborated by egg granulomas from S. mansoni-infected euthymic and athymic mice may be different but both appear to be distinct from IL-1.

Animals↗
PubMed1989

Resistance to reinfection in experimental murine schistosomiasis: role of porto-hepatic hemodynamics.

Experiments were conducted to evaluate critically, and independently of the immune system, the possible role of hemodynamic mechanisms in resistance to schistosomal reinfection. The effects of a challenge schistosomal infection were compared in groups of mice which were either previously infected with schistosomiasis, vaccinated with irradiated cercariae, or underwent partial portal vein ligation for the induction of portal hypertension and porto-systemic shunting. Following infection with 60 cercariae, the appearance of portal hypertension preceded by approximately 2 weeks the development of porto-systemic shunting, which reached maximal values 11 weeks postinfection. Such a primary infection conferred on C3H mice an estimated 90% protection to a 2nd infection, measured by the reduction of worm burden. Worm burdens were also reduced in vaccinated and ligated animals as compared to normal controls. The protection amounted to 30% and 56%, respectively, in the C3H strain and 63% and 75-85%, respectively, in the C57Bl/6 strain. Reduction in worm burden in the ligated animals is believed to be due to the extrahepatic porto-systemic vascular shunts. Hemodynamic as well as immunological factors may account for the resistance to reinfection observed in chronic murine schistosomiasis.

Animals↗
PubMed1988

Schistosoma mansoni: the basis for the antischistosomal effect of cyclosporine A.

A potent antiparasitic effect against a broad range of microorganisms is now known to follow the administration of cyclosporine A (CSA) to a variety of mammalian species and birds. Even though in the case of Schistosoma mansoni a direct antischistosomal effect by CSA has been in principle ruled out, this possible mechanism of action has not been previously explored in depth. In this paper we show that (a) concentrations of CSA of as low as 1 microgram/ml are schistosomulicidal in vitro as determined by morphological criteria, (b) mice receiving antischistosomal regimens in vivo exhibit serum concentrations of CSA that are within the range of toxic doses in vitro, (c) schistosomulicidal concentrations of CSA are maintained in vivo for sufficiently long periods of time to secure parasite death, (d) the antischistosomal activity of heat-inactivated mouse sera closely correlates with their levels of CSA, and (e) independent of the site of administration, CSA offers protection against a schistosomal infection in vivo only when present in the serum. The data strongly support the contention that CSA has a direct effect on the early forms of Schistosoma mansoni, and suggest that interference with a survival mechanism, perhaps common to several parasites, represents one likely mode of action.

Animals↗
PubMed1988

Metastatic sweat gland carcinoma in an adolescent: a case report.

Sweat gland carcinomas are rare tumors that metastasize frequently. The diagnosis is seldom suspected prior to histologic examination. A long interval between onset of the disease and diagnosis is characteristic of the disorder. The benign clinical and histologic appearance of some of these tumors can obscure their full malignant potential. This report illustrates an unusual instance of sweat gland carcinoma metastatic to bone carcinoma in an adolescent. This case stresses the necessity for those involved in the care of the foot to be familiar with a condition of this type.

Adenocarcinoma↗
PubMed1987

Characterization and antigen-presenting function of a murine thyroid-derived epithelial cell line.

We have developed and evaluated the antigen-presenting function of a murine thyroid-derived epithelial cell line M.5 in order to further investigate the possible role of the thyroid follicular epithelium in the inductive phase of autoimmune thyroiditis. M.5 cells did not express class II major histocompatibility complex encoded (Ia) antigens constitutively, but these could be readily induced with interferon-gamma. We found that Ia expressing M.5 cells were ineffective in stimulating T cell proliferation when tested in a 4-day primary mixed leukocyte reaction (MLR). However, significant T cell stimulation was obtained when phorbol myristate acetate (PMA) was added either to the M.5-T cell co-cultures, or for a brief period to the M.5 cells prior to adding the responder T cells. Cytofluorographic analysis of M.5 cells disclosed that PMA did not significantly alter the expression of Ia antigens. Additional experiments indicated that interleukin 1 (IL-1) was unlikely to represent the co-stimulatory factor generated by PMA. This was based on the observations that M.5 cells failed to secrete significant IL-1 either spontaneously, or in the presence of various stimuli, and that murine recombinant IL-1 failed to substitute for PMA in the activation of T cells. The nature of the co-stimulatory signal is as yet unknown. We conclude from these experiments that a pure population of thyroid-derived epithelial cells may be able to function, under the described circumstances, as antigen presenting cells.

Animals↗
PubMed1987

The effects of phorbol ester on alloantigen presentation.

B cells and Ia+ thyroid cells fail to stimulate alloreactive T cells in a primary mixed leukocyte reaction (MLR) and fail to activate some allo-class II (I-A) reactive T cell hybridomas. We now demonstrate that B cells can specifically stimulate a primary MLR in combination with the phorbol ester, PMA, but not with interleukin 1 (IL 1) or calcium ionophore. The primary MLR induced with B cells plus PMA can be blocked by either monoclonal anti-I-A or anti-L3T4 antibodies. In contrast, thyroid cells that can be induced to express Ia antigens after incubation with interferon-gamma fail to stimulate a primary MLR even in the presence of PMA or IL 1. We confirmed these observations by using the alloreactive T cell hybridoma, HTB-9.3, which does not react to stimulator B cells. In the presence of PMA, however, this I-Ab-specific hybridoma line was able to respond to relevant but not to control stimulator B cells. Furthermore, the response of HTB-9.3 to B cells plus PMA was also blocked by anti-I-A or anti-L3T4 antibody. In contrast to B cells, Ia+ thyroid cells could not activate HTB-9.3 even in the presence of PMA or IL 1. The data indicate that for primary class II restricted allo-responses, B cells provide signals that can be complemented with the phorbol ester PMA, whereas Ia+ thyroid cells do not, suggesting the existence of additional requirements for T cell activation.

Animals↗
PubMed1987

Murine thyroid follicular epithelial cells can be induced to express class II (Ia) gene products but fail to present antigen in vitro.

To determine whether thyroid follicular epithelial cells (TFEC) might be involved in the induction of autoimmune thyroiditis, they were tested for their potential to express Ia antigens, and for their ability to present antigen in vitro. Results showed that Ia antigens, absent on normal TFEC, could be readily induced with interferon gamma, as detected by immunofluorescence. Maximal expression of Ia antigens in over 50% of TFEC was observed after 4 days of culture in the presence of IFN-gamma, and was quantitatively comparable to spleen cells by cytofluorometric analysis. Moreover, primary TFEC in culture secreted thyroglobulin (tg) and interleukin 1. However, TFEC consistently failed to stimulate various populations of T cells. These included lymph node cells sensitized to tg, a T-cell clone specific for azo-benzene-arsonate tyrosine (ABA), and a hybridoma specific for beef insulin. Likewise, Ia-positive TFEC did not stimulate T-cell hybridomas restricted to the class II alloantigen I-Ab, while stimulating a hybridoma specific for the class I alloantigen Kb. T-cell unresponsiveness could not be explained by inhibitory activity of TFEC, released either into the culture supernatant or exerted by cell contact. The data indicate that Ia-positive TFEC failed to serve as class II-restricted antigen-presenting cells (APC) in vitro and thus argue against a primary role for these cells in the inductive phase of thyroiditis.

Animals↗
PubMed1987

Subclinical syringoma coexisting with basal cell carcinoma.

We report three cases of clinically unapparent syringoma found incidentally on horizontal frozen tissue sections from patients undergoing Mohs micrographic excision of basal cell carcinoma (BCC). In the first case, the syringoma and BCC were admixed; in the other two cases, they were seen in close approximation to one another. In all cases, the tumors were detected on the faces of elderly women. The potential existence of a benign syringoma in association with BCC should be borne in mind, particularly in connection with Mohs micrographic excision. These tumors must be distinguished from one another in order to avoid excessive surgery beyond adequate resection of the basal cell carcinoma.

Adenoma↗
PubMed1984

Distribution and kinetics of mononuclear phagocytes in granulomas elicited by eggs of Schistosoma mansoni.

Previous work has shown that cell suspensions from egg granulomas of Schistosoma mansoni-infected mice contain populations of both I-A-positive and -negative granuloma macrophages (GMs). The present study was undertaken to investigate the distribution of I-A-bearing macrophages within the granulomas, as well as the kinetics of I-A antigen expression by these cells in vivo. Cryostat sections of liver tissue from infected animals, stained with monoclonal anti-I-A antibodies, demonstrated the presence of I-A-positive GMs in peripheral areas of the granulomas, whereas I-A-negative cells concentrated in their centers. For investigation of their expression of I-A antigen, dispersed GMs were studied at time intervals after subjecting infected mice to lethal doses of total body irradiation. I-A half-life on GMs in vivo was estimated to be 2 days, based both on visual detection by immunofluorescence and functionally on the ability of GMs to perform as antigen-presenting cells. Autoradiographic studies, performed on infected liver tissue obtained 1 hour after in vivo administration of tritiated thymidine, showed that macrophages predominantly replicated in peripheral areas of the schistosomal egg granulomas. After longer intervals, however, labeled cells were seen in more central areas of the granuloma, suggesting an overall cell flux from the periphery to the center. These findings indicate that macrophages express I-A antigens in peripheral areas of the granulomas, where macrophage replication and recruitment from the bone marrow take place. They suggest that I-A expression occurs during a limited period of time in "young" macrophages, which later may convert to an I-A-negative phenotype.

Animals↗
PubMed1984

Characterization of mononuclear phagocytes in schistosomal egg granulomas of athymic mice.

Macrophages from schistosomal egg granulomas of athymic mice (nu/nu GM) and their euthymic littermates (nu/+ GM) were analyzed phenotypically for the expression of antigens encoded by the I-A subregion of the major histocompatibility complex and for their ability to perform as antigen-presenting cells. Only 11 to 15% of nu/nu GM expressed I-A antigens as compared to 61.5 to 75% of nu/+ GM. Although both populations of cells appeared to be equally effective as antigen-presenting cells appropriately sensitized lymphocytes in the presence of specific antigens--soluble schistosomal egg antigen (SEA) and human gamma-globulin (HGG)--only nu/nu GM, but not nu/+ GM, were found to stimulate I-A-restricted proliferation of schistosome-sensitized T cell populations in the absence of SEA added in vitro. Furthermore, nu/nu GM but not nu/+ GM were shown to exhibit significant proliferative capacity in vitro, but this phenomenon could not account for the observed difference in SEA-independent T cell stimulation. Finally, culture supernatants from nu/nu GM displayed significant thymocyte-stimulating activity, consistent with interleukin 1, which was not observed in nu/+ GM. These findings point to significant differences between nu/nu GM and nu/+ GM, which may be part of an adaptive mechanism of granulomatous reactivity in the absence of a competent T cell system.

Animals↗
PubMed1984

Fibroblast stimulation in schistosomiasis. V. Egg granuloma macrophages spontaneously secrete a fibroblast-stimulating factor.

Isolated intact egg granulomas from the liver of Schistosoma mansoni-infected mice have been previously shown to elaborate factors in vitro that can stimulate fibroblasts for biological functions that are of potential importance in the pathogenesis of hepatic fibrosis in schistosomiasis. We report here that cell cultures obtained from monodispersed granuloma cell suspensions, and specifically enriched for macrophages (95% to 100%) spontaneously elaborated fibroblast proliferation-stimulating activity in vitro. These cells possessed functional and phenotyptic characteristics of activated macrophages. In contrast, control peritoneal macrophages from uninfected mice lacked such phenotypic characteristics, and did not spontaneously elaborate fibrogenic activity in vitro. The granuloma macrophage activity was present, pre-formed within the isolated cells, and was continuously elaborated during 72 hr of incubation. By gel infiltration chromatography (Sephacryl S-200 sf), fibroblast-stimulating activity was identified in two pooled fractions, one with estimated molecular radius (Mr) of 46 kd to 57 kd and the other with Mr of 10 kd to 16 kd. Preparative isoelectric focusing in granular gel of crude macrophage culture supernatants identified peak activity in fractions with pI approximately 5. Two different serine esterase inhibitors had no effect on the ability of crude granuloma macrophage supernatants to stimulate fibroblast proliferation. Whereas crude and chromatographed fractions of granuloma macrophage supernatant were active for fibroblasts, they had minimal or no interleukin 1 (IL 1) activity when tested in a thymocyte proliferation assay. In contrast, resident peritoneal macrophages from the same infected mice spontaneously secreted substantial IL 1 and fibroblast-stimulating activity in vitro. We conclude that egg granuloma macrophages are activated in vivo to secrete fibrogenic molecules functionally distinct from IL 1, which might contribute to the pathogenesis of hepatic fibrosis in schistosomiasis.

Animals↗