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PubMed1980

The immunologic modulation of morbidity in schistosomiasis. Studies in athymic mice and in vitro granuloma formation.

These studies were designated to test the hypothesis that granulomatous hypersensitivity associated with schistosomiasis, its modulation, and subsequent morbidity are contingent on thymic-dependent lymphocyte function. Studies in athymic mice were integrated with in vitro studies on granuloma formation. Athymic animals tolerate low levels of infection well but are increasingly susceptible to morbidity as the challenge burden increases or becomes associated with simultaneous additional stress such as bacterial infection. In addition, the athymic animals produce smaller granulomas and fail to demonstrate accelerated granuloma formation, the spontaneous modulation of granulomas, or significant resistance to reinfection. These deficiencies could be reversed by thymic reconstitution. In vitro studies indicate that the response to egg antigens was due to the interaction of two subpopulations of T lymphocytes. Studies of "in vitro granuloma formation" augmented the in vivo findings, suggesting that the "in vitro granuloma" represents an excellent analog for delayed hypersensitivities; granuloma production was contingent on a macrophage function and a specific subpopulation of T lymphocytes defined as Ly1+. Granuloma modulation was due to two mechanisms, one contingent on direct suppression by ly2,3+ cells and the other by feedback inhibition requiring Ly,2,3+ cells. These studies suggest the feasibility of combined in vivo and in vitro technology to study the mechanisms of granuloma formation and subsequent morbidity.

Animals↗
PubMed2006

Pulse granulomas detected in gallbladder, fallopian tube, and skin.

CONTEXT: Foreign material typically elicits reactions dominated by multinucleated giant cells. Pulse granulomas are peculiar reactions to particles of food that are characterized by clusters of small to medium-sized hyaline rings. Pulse granulomas are rare and have occupied only the lungs, in association with aspiration, and the alimentary canal, in association with oral pathology, colonic diverticula, and a rectal mass. OBJECTIVE: To report pulse granulomas that occupied previously unrecognized sites and to alert pathologists to the diagnostic pitfall of mistaking pulse granulomas for other entities. DESIGN: We retrospectively reviewed 3 recently encountered cases that involved pulse granulomas in the gallbladder, fallopian tube, and skin. RESULTS: In all cases, pulse granulomas were associated with fistulae involving the gastrointestinal tract. One fistula was clinically occult. Microscopy showed barium-laden histiocytes admixed with hyaline rings, with or without vegetable matter, confirming fistulae involving the gastrointestinal tract. Absence of other features of chronicity, including sarcoid-type granulomas and Langhans-type giant cells, helped to essentially exclude Crohn disease. In 1 case, hyaline rings of pulse granulomas closely resembled hyaline vasculopathy of amyloidosis, diabetes, or hypertension. Surprisingly, polariscopy failed to detect any vegetable matter. In 1 case, negative polariscopy contributed to the difficulty in finding rare vegetable matter. CONCLUSIONS: We demonstrated that pulse granulomas can occur outside the lungs and alimentary canal, and can be associated with fistulae involving the gastrointestinal tract. Awareness of this finding is necessary to avoid confusion with Crohn disease and hyaline vasculopathy. Polariscopy may fail to detect vegetable matter.

Aged↗
PubMedDate not supplied

Distinct B-cell populations are present in hepatic and intestinal Schistosoma mansoni granulomas.

Although it is generally accepted that schistosomal granuloma formation results from a T-cell dependent host response towards the parasite egg, attention has recently been focused on the involvement of B-cells in the induction of schistosome-induced pathology. In this study we investigated the involvement of two functionally different B-cell populations in the formation of the Schistosoma mansoni granuloma: naive and antigen-stimulated B-cells. In liver granulomas two distinct B-cell populations were found, namely unstimulated B-cells at the periphery of the granuloma and antigen-stimulated, syndecan-1 positive B-cells in the inner part near the deposited egg. Intestinal granulomas differed by their relative lack of unstimulated B-cells at the granuloma periphery, but like hepatic granulomas intestinal granulomas also have syndecan-1 positive B-cells. From our results, we conclude that B-cells are important constituents of the S. mansoni granuloma.

Animals↗
PubMed2001

[Granuloma annulare following BCG vaccination].

BACKGROUND: Granuloma annulare following BCG vaccination or tuberculin skin tests is rarely reported in the literature. We describe three cases occurring in patients under the age of 6 years. CASE REPORTS: In the first two cases, granuloma annulare was initially localized at the vaccinal site, then generalized. In the third case, diagnosis was deep granuloma annulare localized far from the initial vaccination site, with recurrence following tuberculin test. In the three cases, diagnosis was made on the basis of clinical and histological elements. DISCUSSION: The relationship between granuloma annulare and BCG may seem evident when the eruption occurs at the vaccinal site, but remains difficult to prove. Diagnosis essentially relies on the absence of other classical etiologies and a compatible delay. When a vaccination such as BCG appears to be the cause of granuloma annulare, a possible cause would be injection trauma or a cell-mediated-delayed-hypersensitivity reaction to a specific antigen contained in the vaccine, leading to development of skin disorders such as granuloma annulare in predisposed subjects. Reports of granuloma annulare following BCG are uncommon but the incidence may be underestimated. In practice, diagnosis of granuloma annulare following BCG or tuberculin skin test cannot be established until BCG dissemination infection is ruled out, a necessary clinical and paraclinical step required in all cases of eruptions following this vaccination. Granuloma annulare is a benign complication requiring no treatment and does not constitute a contraindication for other usual vaccinations.

Adjuvants, Immunologic↗
PubMed2003

Multiple myeloma in remission complicated by bone marrow granulomas.

BACKGROUND: Granulomas are encountered in 1-2% of biopsies performed in various hematological and non-hematological diseases. Almost 50% of bone marrow granulomas are associated with infections and 25% with hematologic disorders, especially lymphoma and multiple myeloma. Toxoplasmosis is reported to induce granulomas in bone marrow inmunosuppressed patients. On the other side, long-term unexplained remissions after conventional treatment in multiple myeloma were mentioned in up to 10% of cases. CASE REPORT: A 56-years-old female patient was diagnosed with IgG(kappa) multiple myeloma in 1992. After 5 years, being still in complete remission, frequent bone marrow epithelioid non-caseating granulomas were noticed in biopsy, without clinical symptomatology or modifications of routine paraclinical examinations. The history revealed no treatments with antiarrhythmic, antihypertensive, anticonvulsivants or nonsteroid antiinflammatory drugs. The serologic tests for other infections or systemic diseases known to induce granulomas were negative, except those for toxoplasma gondii IgG. The treatment with azithromycine and pyrimethamine induced the disappearance of granulomas, simultaneously with an important decrease of anti-toxoplasma IgG antibodies titer. CONCLUSIONS: The bone marrow granulomas provide a valuable histologic clue to opportunistic infections and the bone marrow biopsy is useful for their diagnosis. In the specific case of toxoplasmosis, a recently proposed treatment with azithromycin induced the resolution of the granulomas. Due to the usual lack of specificity of the most bone marrow granulomas, a broad and long-term clinical, histopatological and serological follow-up to establish the etiology should be performed.

Antiprotozoal Agents↗
PubMed1990

Immunosuppression by peritoneal BCG-induced granulomas in mice.

1. Intraperitoneal injection of viable BCG resulted in the formation of peritoneal granulomas in mice. Granuloma-bearing animals presented a specific immunosuppression of delayed-type hypersensitivity (DTH) to BCG. 2. The transplantation of peritoneal granulomas induced by BCG to animals previously sensitized with BCG suppressed the DTH response to this antigen in the recipient animals to the same extent as observed in animals with granulomas induced by the injection of BCG. No suppression was observed in animals transplanted with granulomas induced by either Cytodex or talc. 3. The hypersensitivity reaction to Brucella abortus and the acute inflammatory reaction produced by carrageenin were not affected by granuloma transplantation. 4. Granulomas collected from animals treated with a lethal does of irradiation maintained the capacity to suppress DTH in recipient animals. 5. These results suggest that the response observed in granuloma recipients is modulated by cells within the granuloma.

Animals↗
PubMedDate not supplied

Effect of supernatants of dermal leprosy granulomas on lymphocyte morphology and function.

A comparison has been made of the characteristics of dermal granulomas of tuberculoid and lepromatous leprosy by culturing them in vitro. The granulomas were derived from lesions of untreated patients and their effect was assessed on the morphology and function of lymphocytes derived from peripheral blood of normal individuals. The concentration of proteins released in the supernatants was similar in both the type of granulomas. However, the supernatants from the lepromatous granulomas markedly diminished the viability of lymphocytes when compared with supernatants derived from the tuberculoid granulomas. The supernatants from both the tuberculoid and lepromatous granulomas, contained soluble factors which depressed the 14C-leucine and 3H-thymidine incorporation by lymphocytes. The depression in 3H-thymidine uptake was more pronounced with the supernatants from the lepromatous granulomas while the diminution of 14C-leucine incorporation was more marked with supernatants from the tuberculoid granulomas. The supernatants did not show any migratory inhibitory activity in vitro. When the cells from the granulomas were dispersed and cultured in vitro, only very low concentration of proteins was detectable.

Carbon Radioisotopes↗
PubMed1995

Epithelioid cell granulomas experimentally induced by prototheca in the skin of mice: a light microscopic study.

Prototheca wickerhamii, an achlorophyllous algae, was previously found to induce massive epithelioid cell granulomas in the skin of mice. By means of light microscopy, examination was made of the histological reactions involved in epithelioid cell granulomas induced by intradermal and/or subcutaneous inoculation of Prototheca wickerhamii in BALB/c and ICR mice. Six BALB/c mice showed granuloma nodules while only three of six ICR mice did so. Based on the results of the present and previous studies, BALB/c mice may be considered a strain particularly vulnerable to contracting epithelioid cell granuloma and ICR mice, a resistant strain. In very early lesions at one week following initial prototheca inoculation, cellular infiltration with varying numbers of polymorphonuclear leukocytes, lymphocytes and some macrophages was observed throughout the dermis and subcutaneous fat tissue. In early lesions at one to two months after inoculation, focal granulomas composed of histiocytic cells and/or macrophages were observed. Mast cells were occasionally present among the histiocytic cell infiltrates. In the granulomatous lesions at two to three months, scattered eosinophils and some lymphocytes were seen. Central necrosis, with numerous neutrophils and many endospores surrounded by the granuloma, was often observed. In late stage lesions at six months, massive lymphocyte and plasma cell infiltration surrounding and/or intervening between vacuolated epithelioid cell clusters was evident. Histological reactions in epithelioid cell granuloma and the ultimate course of this disease can be staged from the histological point of view as follows: 1) diffuse inflammation, 2) cell proliferation leading to epithelioid cell formation, 3) hypertrophy of epithelioid cells with consequent formation of cell aggregates and/or organized granuloma and 4) degeneration of granuloma.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1975

Comparative study of proteins extracted form metal-induced allergic and foreign body granulomas in man.

In order to characterize proteins unique to organized epitheloid cells, proteins havebeen sequentially extracted form both foreign body and allergic granulomas in man at varoius times after intradermal injection of beryllium oxide suspension. Treitium-labeled l-tyrosine was injected intralesionally 2 weeks before excision of granulomas. Prolongedextraction with 8 m urea yeilded increases amounts of radioactivie protein form older (8-to 26-week) allergic granulomas but not from 4-to6-week-old or foreign body granulomas (consisting of mononuclear cells and phagocytes). Sephadex G-200 column chromatographyand sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis of the urea extractsfrom 8-week and older allergic granulomas revealed distinct readioactive protein peaks with molecular weights of approximately 172,000 to 208,000. Antisera raised to one of these proteins gave a precipitin line in agar gel diffusion with lines of identity againsturea extracts of several allergic granulomas but not against similiar extracts of foreignbody granulomas. The results suggest synthesis of distinctive high molecular weight proteins in allergic granulomas which may serve as "markers" for organized epitheloid cell granulomas as they transform from mononuclear cells.

Animals↗
PubMed1995

The relationship of granulomas to blood vessels in intestinal Crohn's disease.

It has been suggested that granulomatous vasculitis is a primary mechanism in the production of pathologic changes seen in Crohn's disease. We set out to investigate the relationship of granulomas to blood vessels and to confirm or refute previous reports of granulomatous vasculitis in Crohn's disease. Thirty paraffin embedded tissues from 11 patients with Crohn's disease were selected after examination of H&E stained sections for the presence of granulomas. Using an immunohistochemical method, various monoclonal antibodies were applied to sequential sections from each tissue to demonstrate vascular structures and granulomas. In three patients none of the granulomas occurred in association with blood vessels, in five a small proportion of the granulomas affected blood vessels, and in three granulomatous vasculitis appeared occlusive and significant. A total of 232 granulomas were identified, 22% of which were closely associated with blood vessels, which included both arteries and veins; 16% were perivascular, while 6% were intravascular. Perivascular granulomas did not surround blood vessels or invade the medial layers. They were asymmetric, suggesting that they originated by encroachment of nearby lymphatic or connective tissue granulomas. These results indicate that the granulomas of Crohn's disease are usually not associated with blood vessels; however, there is a minority of patients in whom vascular granulomatous inflammation may be important, although probably as a secondary phenomenon.

Adult↗
PubMed1996

T cell vasoactive intestinal peptide receptor subtype expression differs between granulomas and spleen of schistosome-infected mice.

Granulomas form in the liver and intestines of mice infected with the parasite Schistosoma mansoni. Vasoactive intestinal peptide (VIP) is a neurokine that can modulate aspects of the immune response by acting through receptors within the granuloma. Cloned are two novel VIP receptor (VIPR) mRNAs (VIPR1 and VIPR2) that also bind a second neurokine called pituitary adenylated cyclase-activating polypeptide (PACAP). The objective of this study was to determine if granulomas express either VIPR1 or VIPR2. Using a radioligand-binding assay, it was established that PACAP is as effective as VIP at displacing radiolabeled VIP from splenocytes and granuloma cells, and that most if not all VIPRs in the spleen and granulomas bind PACAP. PCR amplification of reverse transcribed RNA determined that granulomas express both VIPR1 and VIPR2 mRNAs. Gel electrophoresis and nucleotide sequencing confirmed the authenticity of the PCR products. Also, both receptor subtypes were amplified from several granuloma CD4+ T cell lines; yet reverse transcribed RNA from T cell-depleted, dispersed granuloma cells had only VIPR1 RNA. It is notable that reverse transcriptase-PCR detected only VIPR1 in the thymus and spleen, which are organs rich in T lymphocytes. Thus, the granulomas and spleens from mice with schistosomiasis contain cells that display authentic VIP/PACAP receptors. Moreover, these data suggest that T cells in different compartments vary in VIPR subtype expression. VIPR1 and VIPR2 may have different physiologic roles in inflammation.

Animals↗
PubMed1996

In situ analysis of B7-2 costimulatory, major histocompatibility complex class II, and adhesion molecule expression in schistosomal egg granulomas.

Immunopathological damage in schistosomiasis consist of egg granuloma formation, which is a hypersensitivity reaction mediated by antigen-specific CD4+ T helper (Th) lymphocytes. Th cells are dependent on accessory cell-bound co-stimulatory signals for activation. The B7 molecules provide critical costimulation, as in their absence T cells are rendered unresponsive. We investigated the kinetics of B7-2 molecule expression in schistosomal egg granulomas by immunocytochemical analysis in situ. We also monitored major histocompatibility complex (MHC) class II, intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) expression, as well as the presence of macrophages, T cells, and B cells. B7-2 expression was elevated in cells of the large granulomas of the acute (6-1/2 week) infection, and sharply declined thereafter. MHC class II expression was similarly elevated in the acute granulomas, but in contrast to B7-2, remained relatively constant throughout 12 1/2 weeks of infection. Moreover, ICAM-1 and VCAM-1 were expressed in acute and chronic granulomas. However, whereas ICAM-1 was constitutively expressed in normal liver, VCAM-1 was dramatically induced in the livers upon onset of disease. The findings suggest that the acute granulomas are rich in accessory cells with overall phenotypic configurations that support Th-cell activation, although at subsequent times, granulomas contain increasing numbers of B7-poor accessory cells capable of inducing Th-cell unresponsiveness. Thus, cellular interactions in early granulomas may be able to amplify egg-induced immunopathology, whereas interactions taking place in succeeding granulomas appear to precipitate its down-regulation.

Animals↗
PubMed1997

Adult Schistosoma mansoni worms positively modulate soluble egg antigen-induced inflammatory hepatic granuloma formation in vivo. Stereological analysis and immunophenotyping of extracellular matrix proteins, adhesion molecules, and chemokines.

Synchronized liver granulomas were induced by injecting Sepharose beads to which SEA soluble egg antigen (SEA) or the concanavalin A binding fraction of SEA had been coupled into a mesenteric vein in naive, single-sex (35 days) and bisexually (28 days) Schistosoma mansoni-infected and Plasmodium berghei-immunized mice. Stereological analysis revealed that peak granuloma formation was already reached 8 days after injection in single-sex infected mice compared with 16 days in naive animals. No difference in granuloma formation between naive and P. berghei-immunized animals and between unisexually and bisexually S. mansoni-infected mice was observed. This suggests that the positive immunomodulatory effect on the granulomogenesis is worm specific and not likely to be due to arousal of the immune system by unrelated factors, nor is it influenced by the gender or degree of maturation of female worms. At all stages in time, the concanavalin A binding-fraction-induced granulomas reached only 65 to 70% of the volume of SEA-induced granulomas. Immunophenotyping of extracellular matrix proteins around deposited heads revealed that fibronectin was the dominant extracellular matrix protein and that also type I and IV collagen and laminin were deposited. Temporal analysis of the expression of the adhesion molecules ICAM-1, LFA-1, VLA-4, and VLA-6 was performed. Morphological evidence is presented for the role of adhesion molecules in the initiation and maintenance of hepatic granuloma formation. The chemokine monocyte chemoattractant protein-1 was expressed in the granuloma and in hepatic artery branches. From these data, it is concluded that adult S. mansoni worms positively modulate schistosomal hepatic granuloma formation in vivo. Adhesion molecules and chemokines play important roles in schistosomal granuloma formation.

Animals↗
PubMed2000

Observations on multiple sperm granulomas in the rat epididymis following vasectomy.

Seven epididymides of long-term vasectomized rats showing multiple sperm granulomas were studied in serial histological sections. Despite the presence of the multiple granulomas, only two rats showed continuity of the epididymal duct with the central sperm mass of a granuloma. A further three specimens showed breaks in the epididymal epithelium at sites of local distension in the epididymal tail. Granulomas in the epididymal body seem to receive spermatozoa only transiently. The spermatozoa at the center of granulomas in continuity with the epididymal duct showed evenly distributed sperm heads. A number of others showed clumping of spermatozoa, attributed to stagnation of flow and fluid resorption. In many granulomas, folds in the macrophage layer with a connective tissue core rich in lymphocytes and plasma cells projected into the central sperm mass. We conclude that the sperm granuloma is a dynamic structure that shows changes with age and that the sperm granuloma closest to the testis must not be assumed to be the one that is draining the spermatozoa.

Animals↗
PubMed1982

Granulomas in melanoma patients treated with BCG immunotherapy.

Autopsy slides from 22 melanoma patients who received bacille Calmette-Guérin BCG immunotherapy and who had a postmortem examination at the UCLA Center for the Health Sciences were examined for the presence of granulomas. Granulomas were found in six patients (29%) who received BCG but not in a group of 25 melanoma patients who did not have BCG immunotherapy. A number of factors were tested for correlation with the presence of granulomas in the autopsy material. Fifty-five percent of the patients who received BCG by both intralesional and time technique developed granulomas. No patients given BCG by the tine technique alone developed granulomas. No correlation was found between granulomas and the presence of symptoms after the administration of BCG, the duration of BCG immunotherapy, the patient's age, the number of BCG administrations, treatment with immunosuppressive agents, the length of survival after the last BCG administration, the presence of a positive PPD reaction, a positive history for granuloma-forming diseases and tests for immunocompetence. However, these results provide evidence that the route of BCG administration strongly influences the frequency of granulomas in melanoma patients who received BCG immunotherapy.

BCG Vaccine↗
PubMed1985

Primary eosinophilic granuloma of frontal lobe. Diagnostic use of S-100 protein.

Solitary eosinophilic granuloma of the frontal lobe of the brain is a rare lesion. A 30-year-old Jordanian man with a history of recurrent bilateral chronic middle ear infections and tuberculosis presented with focal seizures. A solitary right frontotemporal mass was diagnosed by brain biopsy as an eosinophilic granuloma. Immunoperoxidase stains of virtually all histiocytes in the lesion were strongly positive for S-100. Four cases of eosinophilic granuloma and one of Letterer-Siwe disease were also examined, and virtually all histiocytes demonstrated strong S-100 positivity. In comparison, 24 reactive or infectious granulomas were examined for S-100 staining and most showed complete negativity of histiocytes in granulomas for S-100. This is the first report in the literature that has examined the results of S-100 staining in a large number of reactive or infectious granulomas and compared it with S-100 staining in eosinophilic granuloma. This report illustrates that S-100 can be useful in distinguishing eosinophilic granuloma, generally considered to be part of the larger group of histiocytic disorders known as histiocytosis X, from reactive or infectious granulomatous conditions of similar or confusing histology.

Adult↗
PubMed2005

Propionibacterium acnes-induced hepatic granuloma formation is impaired in mice lacking tetraspanin CD9.

The granuloma is a host defence response to persistent pathogenic irritants. In the process of granuloma formation, the activation, migration, and fusion of macrophages occur locally, but the mechanisms involved remain elusive. Tetraspanins regulate cell migration and fusion by organizing functional molecular complexes in membrane microdomains. Here we investigated the role of tetraspanin CD9 in hepatic granuloma formation. Immunostaining of the liver of untreated wild-type mice showed that CD9 was expressed by vascular endothelial cells and perivenular hepatocytes. When intrahepatic granulomas were induced by intravenous injection of Propionibacterium acnes, hepatocyte CD9 was extensively upregulated, while inflammatory cells constituting granulomas were mostly negative for CD9. Compared with wild-type littermates, CD9-knockout mice showed dissemination of Propionibacterium acnes and reduced number and size of granulomas after the injection. Moreover, production of granuloma-inducing cytokines, TNF-alpha and IFN-gamma, was delayed and chemotactic activity for macrophages was suppressed in the liver of mutant mice. These results suggest that CD9 is one of the proteins that promotes granuloma formation in the liver.

Animals↗
PubMed1982

A biochemical study of the cotton pellet granuloma in the rat. Effects of dexamethasone and indomethacin.

The subcutaneous implantation of a cotton pellet into a rat results in the formation of a granuloma at the site of the implant. The early events comprise an accumulation of fluid and protein-aceous material together with an infiltration of neutrophils. The granuloma formed by day 7 is characterized by the formation of a vascularized fibrous capsule containing fibroblasts and infiltrating mononuclear cells which are rich in N-acetyl-beta-D-glucosaminidase (NAG). Granuloma development was quantitated by dry weight measurements, and its cellular content was measured by assaying activity of NAG and total nucleic acid content. Nucleic acid determinations showed that cell infiltration into the granuloma took place at a virtually constant rate over a 7-day period. In contrast, the NAG activity did not change significantly until after day 5 when a large increase in the amount of enzyme extractable from the granuloma was seen. Systemic treatment of the animal with dexamethasone or indomethacin resulted in an inhibition of granuloma weight gain, NAG activity and nucleic acid levels. The data suggest that the two drugs acted during the early phase of granuloma development at the level of cell infiltration. Both drugs given on days 0-3 alone suppressed granuloma formation, whereas treatment on days 4-7 was without effect.

Acetylglucosaminidase↗