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PubMed1987

Interleukin 1 and prostaglandin production by cells of the mononuclear phagocyte system isolated from mycobacterial granulomas.

A study has been made of the activity of interleukin 1 (IL-1) and prostaglandins (PGs) in the culture supernatants from unstimulated and lipopolysaccharide (LPS)-stimulated mycobacteria-induced granuloma cells. Both epithelioid cells from bacillus Calmette-Guerin (BCG)-induced granulomas and macrophages from Mycobacterium leprae-induced granulomas, separated on a fluorescence-activated cell sorter using monoclonal antibody specific to guinea pig macrophages, spontaneously secreted low levels of IL-1 (assayed by thymocyte comitogenic and fibroblast mitogenic activities) into culture supernatants. However, culture supernatants from LPS-stimulated epithelioid cells showed significantly higher IL-1 activity than those from unstimulated cells. In contrast, LPS stimulation of M. leprae granuloma macrophages failed to enhance IL-1 production. Nevertheless, IL-1 activity in the culture supernatants from stimulated mycobacterial granuloma cells of both types was much lower than that from LPS-stimulated peritoneal exudate macrophage culture supernatants. There was no detectable amount of prostaglandin E2 (PGE2) in the culture supernatants from both unstimulated and LPS-stimulated BCG- and M. leprae-induced granuloma cells in comparison to much higher levels of PGE2 produced by unstimulated (0.28-6.2 ng/ml) or LPS-stimulated (greater than 15 ng/ml) peritoneal exudate macrophages. However, BCG granuloma cells either secreted prostaglandin F2 alpha (PGF2 alpha) spontaneously or produced comparable levels of PGF2 alpha to those from peritoneal exudate macrophages on stimulation, while M. leprae granuloma macrophages produced much lower levels of PGF2 alpha.

Animals↗
PubMed1992

Vasectomy and spermatic granuloma in hamsters.

Fifty-eight hamsters were bilaterally vasectomized either 1, 2, 3 or 6 months before experimentation. Fifty-five sham-vasectomized hamsters served as control. Cauda epididymal fluid was obtained by micropuncture. The effect of vasectomy on the incidence of spermatic granuloma was studied. The data were analyzed according to the presence or absence of granuloma after vasectomy and were compared with the data of their respective control. The incidence of granuloma increased with the duration of vasectomy and reached 92.8% at the end of 6 months after operation. Distension of the epididymis increased to a maximum at 1 month, but recovered to nearly normal irrespective of the existence of granuloma. The weight of the testis, spermatocrit and sperm density significantly decreased, and the percentage of abnormal sperm in the cauda and caput increased markedly in the absence of granuloma compared with their respective tract with granuloma or control. The testes in both the group with and without granuloma showed marked atrophy 6 months after vasectomy. The concentration of carnitine in the cauda epididymal plasma was significantly reduced from 2-6 months. The possible protective effect of a granuloma formation is discussed.

Animals↗
PubMed1989

Comparison of lipid accumulation and metabolism in carrageenan-induced granulomas to aorta and blood monocytes of normal and cholesterol-fed rabbits.

New Zealand rabbits (six each) were either maintained on a standard chow diet (ND) or the chow diet supplemented with cholesterol/peanut oil (HD) for 2 weeks. After 2 weeks, each animal had 15 ml of a 1% carrageenan gel injected subcutaneously into the midabdominal area. Rabbits were maintained on the diets for an additional 4 weeks. At sacrifice, blood was collected both for serum and for monocyte isolation and granulomas and aorta were excised. Tissues were assayed for lipid composition and lipid metabolism. Electron and light microscopies were performed on granuloma tissue. Granulomas from ND animals did not stain with oil red O. Granulomas from HD animals had homogenous oil red O staining indicating lipid accumulation. Granulomas from both ND and HD animals consisted of macrophages. Macrophages from ND rabbits accumulated follicular carrageenan but not lipid, while HD macrophages had the appearance of foam cells. Granuloma lipid content and metabolism closely paralleled the aorta and blood monocytes. The HD tissue had increased acylCoA:cholesterol acetyltransferase (ACAT) activity and lipid composition changes reflective of the atherosclerotic process. ND granulomas had no elevation of lipid content or ACAT. The carrageenan-induced granulomas provide a useful model for studying the biochemical and morphologic changes characteristic of arteries undergoing atherogenic change.

Animals↗
PubMed1986

T-cell independent transfer of organized granuloma formation.

A direct role for delayed hypersensitivity in organized granuloma formation has been emphasized in the literature, but some clinical and experimental studies have suggested a more complicated relationship. In order to further evaluate T-cell function in cutaneous granulomatous inflammation, hepatic granulomas isolated from athymic mice with schistosomiasis were grafted into the skin of athymic and euthymic mice. Granulomas developed in athymic mice, as seen previously after transplantation of euthymic hepatic granulomas, indicating that granulomas develop in the skin without T-cell function. However, the granulomas in athymic mice skin were smaller and lacked eosinophils and mast cells, whereas the athymic mouse granulomas grafted in euthymic mice skin were larger, better organized, and associated with tissue eosinophilia. These findings suggest that granuloma initiation itself is T-cell independent, but that T-cell participation enhances the granulomatous reaction.

Animals↗
PubMed2004

Identifying control mechanisms of granuloma formation during M. tuberculosis infection using an agent-based model.

Infection with Mycobacterium tuberculosis is a major world health problem. An estimated 2 billion people are presently infected and the disease causes approximately 3 million deaths per year. After bacteria are inhaled into the lung, a complex immune response is triggered leading to the formation of multicellular structures termed granulomas. It is believed that the collection of host granulomas either contain bacteria resulting in a latent infection or are unable to do so, leading to active disease. Thus, understanding granuloma formation and function is essential for improving both diagnosis and treatment of tuberculosis. Granuloma formation is a complex spatio-temporal system involving interactions of bacteria, specific immune cells, including macrophages, CD4+ and CD8+ T cells, as well as immune effectors such as chemokine and cytokines. To study this complex dynamical system we have developed an agent-based model of granuloma formation in the lung. This model combines continuous representations of chemokines with discrete agent representations of macrophages and T cells in a cellular automata-like environment. Our results indicate that key host elements involved in granuloma formation are chemokine diffusion, prevention of macrophage overcrowding within the granuloma, arrival time, location and number of T cells within the granuloma, and an overall host ability to activate macrophages. Interestingly, a key bacterial factor is its intracellular growth rate, whereby slow growth actually facilitates survival.

Chemokines↗
PubMed1996

Granulomas in murine schistosomiasis mansoni have a somatostatin immunoregulatory circuit.

The role of somatostatin (SRIF) in controlling the granulomatous inflammatory response to infection with the parasite Schistosoma mansoni was explored in mice. The murine granulomas contain SRIF-14. Immunoreactive SRIF and prepro SRIF localize in the cytoplasmic granules of macrophages within the granulomas. The granulomas contain mRNA for prepro SRIF and are not innervated. The production of SRIF by the inflammatory cells appears to be inducible. The granulomas contain mRNA for the SRIF receptors sst2A and sst2B, which are expressed mainly on CD4- T lymphocytes and bind SRIF-14 with high affinity. Antigens from the schistosome eggs stimulate granuloma T lymphocytes to produce cytokines. Interferon-gamma (IFN-gamma) is one such cytokine made by CD4+ T lymphocytes. SRIF-14 suppresses antigen-induced IFN-gamma production from granuloma cells, and this effect is blocked by anti-sst2 antibody. SRIF was shown to inhibit IFN-gamma-induced immunoglobulin G2a (lgG2a) synthesis in murine schistosomiasis. SRIF also blocks substance P (SP)-stimulated IFN-gamma and lgG2a secretion. Schistosome-infected animals treated with the SRIF analog octreotide form smaller granulomas that secrete substantially less IFN-gamma and lgG2a. Unpublished observations suggest that SRIF does not modulate schistosome egg antigen- or concanavalin A-stimulated granuloma lymphocyte proliferation in murine schistosomiasis. In conclusion, SRIF may be an important factor in the control of the granulomatous inflammatory response in murine schistosomiasis.

Animals↗
PubMed2000

Teflon granuloma after microvascular decompression for trigeminal neuralgia.

BACKGROUND: Our purpose was to research the factors that may induce Teflon granuloma in trigeminal neuralgia patients who have undergone microvascular decompression (MVD) procedures, to propose methods for the early diagnosis of Teflon granuloma, and provide suggestions for reducing this complication. METHODS: From 1985 to 1996, 89 trigeminal neuralgia patients underwent MVD with Teflon felt to separate the offending vessels and the trigeminal nerve. Ten patients had secondary explorations for recurrent symptoms. Five patients developed recurrent facial pain associated with facial numbness within a certain period after the first operation. We reviewed the onset and site of the initial symptoms, the duration of the symptoms, the operative findings and methods, and the results of the operations. In the reoperative patients, we analyzed the initial and secondary symptoms after the first operation, and the time to relapse. We compared the operative findings and methods in these operations. RESULTS: The operative findings in the 10 patients with recurrence were Teflon granuloma in five patients, arterial loop compression in three patients, venous compression in one patient, and negative exploration in one patient. The Teflon granuloma patients all complained of facial numbness after the first MVD operation. The incidence of Teflon granuloma after MVD was 5.6% (5/89). CONCLUSION: The Teflon felt used in the MVD procedure can produce complications. It is not absolutely inert when used in MVD procedures. When it contacts the tentorium and/or dura, an inflammatory giant-cell foreign body reaction can be induced. In the future, we should search for other implants to replace the Teflon felt. However, until new materials are found, we suggest that the Teflon felt be kept away from the tentorium and dura and placed completely within the CSF cisterna. We can diagnose Teflon granuloma early with enhanced CT and/or MRI, especially in patients with new facial numbness symptoms after Teflon MVD procedures. The results of reexploration of Teflon granulomas are more satisfactory than a negative exploration or venous compression. We may be able to decrease the incidence of Teflon granuloma. We should be more aggressive in performing reexploration in these recurrent patients.

Adult↗
PubMed1977

Sperm granuloma and reversibility of vasectomy.

Ninety-two consecutive patients who had undergone bilateral vasectomy 1 month to 28 years earlier were studied at the time of vasectomy reversal for sperm output, dilatation of the vas-deferens lumen, and sperm granuloma. Thirty-nine men had unilateral or bilateral sperm granuloma. The presence of of a sperm granuloma virtually assured normal sperm in the vas fluid no matter how long ago the vasectomy was performed. In the absence of a sperm granuloma, the interval since vasectomy had an important influence on the quality of vas fluid. The presence of a sperm granuloma was associated with significantly less dilatation of vas-deferens lumen at the testicular end. The site of the vasectomy and the amount of vas deferens removed did not influence sperm quality. A sperm granuloma on only one side resulted in normal spermatozoa in the vas fluid on that side, whereas the side without the sperm granuloma had abnormal spermatozoa or no spermatozoa in the vas fluid. It is concluded that when sperm granuloma follows vasectomy it vents the high pressure otherwise created by vasectomy and prevents disruption of sperm output in the vas fluid.

Adult↗
PubMed1983

Non-specific granuloma of the larynx. A 10-year review of 63 patients.

During the 10 years from 1971 to 1980, 63 cases of non-specific granuloma of the larynx were examined at the Department of Otolaryngology, Kurume University Hospital. Of the entire 63 cases, 51 were intubation granulomas, 5, contact granulomas and 7, granulomas of unknown etiology. A review of the clinical records of these patients was completed. The results are summarized as follows; 1) In intubation granulomas, there was a significant preponderance of females over males (43 to 8). The age ranged from 9 to 72 years. The lesion was bilateral in 21 cases and unilateral in 30. All the granulomas but one were located at the cartilaginous portion. Twenty-one (75%) of the 28 cases which were surgically treated got healed, 6 (21%) developed a recurrence and 1 was lost to follow up. 2) All 5 patients with contact granulomas were males. Their lesions were unilateral. Three patients were surgically treated. Two of these 3 had no recurrence while the other developed a recurrence, which disappeared following conservative treatments. One patient was successfully treated with conservative modalities. 3) Granulomas of unknown etiology were found in 5 males and 2 females. Their age ranged from 19 to 70 years. The lesion was unilateral in all 7 cases. Three patients were surgically treated. Two of these 3 required repeated surgeries. One patient was successfully treated by means of conservative therapy.

Adolescent↗
PubMed1996

Granulomas and hepatitis C.

Hepatitis C (HCV) is associated with a number of characteristic histological features. A recent paper has identified an increased frequency of granulomas in resection specimens from cases of HCV. We have carried out a retrospective study of 155 cases of HCV to assess the frequency of granulomas in biopsy specimens. We had two control groups: 151 cases of hepatitis B (HBV) and 129 cases of alcohol induced liver disease. Granulomas were found in 14 cases of HCV (10%), three cases of HBV (2%) and three cases of alcohol induced liver disease (2%). Granulomas were significantly commoner in cases of HCV than in the other two groups. Of the 14 cases of HCV, the granulomas could be ascribed to another cause in seven cases. When the analysis was carried out, excluding those granulomas which could be ascribed to another cause, they were still significantly commoner in cases of HCV. We conclude that granulomas are more frequent in HCV but that in half of cases in which they are found another cause can be identified. This means that if granulomas are seen in association with hepatitis C another aetiology should be sought before ascribing them to HCV.

Granuloma↗
PubMed2001

Tissue granuloma structure-function in experimental visceral leishmaniasis.

In experimental visceral leishmaniasis in normal mice (BALB/c, C57BL/6) acquired resistance to Leishmania donovani, a protozoan which targets tissue macrophages, depends upon T cells, Th1 cell-type cytokine generation and activated mononuclear phagocytes. In the intact host, initial control and eventual resolution of L. donovani hepatic infection in normal mice is expressed by and accomplished within well-formed, mature tissue granulomas. In the liver, these immunologically active, inflammatory structures are assembled around a core of fused, parasitized resident macrophages (Kupffer cells) which come to be encircled by both cytokine-secreting T cells and influxing leishmanicidal blood monocytes. This pro-host defense granuloma structure-function relationship, in which histologically mature granulomas provide the microenvironment for intracellular L. donovani killing, however, is only one of seven which have been identified through experimental modifications in this model. This report reviews these structure-function relationships and illustrates the broad spectrum of additional possible responses. These responses range from structurally intact granulomas which provide no antileishmanial function (the 'ineffective' granuloma), to enlarged granulomas which show enhanced parasite killing (the 'hypertrophied' granuloma), to effective antileishmanial activity in the absence of any tissue reaction (the 'invisible' granuloma).

Animals↗
PubMed2001

The Schistosoma mansoni egg-derived r38 peptide-induced Th1 response affects the synchronous pulmonary but not the asynchronous hepatic granuloma growth.

The p38 peptide derived from Schistosoma mansoni egg-antigens (SEA) is a preferential inducer of the Th1 response. In the present study, we investigated whether induction of a p38-specific Th1 or Th2 response can influence granuloma development in infected or sensitized mice. Mice sensitized with SEA/IL-12 3 weeks after infection but before worm oviposition commenced developed Th1 cytokine responses and had significantly reduced hepatic granuloma size. Similar immunization with p38/IL-12 induced a strong peptide-specific Th1, mixed SEA-specific Th1/Th2 responses without effect on hepatic granuloma development. Presentation of p38 with alum or alum/IL-12 mixture enhanced Th2 cytokine responses and hepatic granuloma sizes. In the synchronized pulmonary model, sensitization of naïve mice with p38/IL-12 induced a strong Th1 cytokine production to p38 and SEA, led to a moderate increase in granuloma growth at days 4 and 8 following egg injection and actually promoted the resolution of the lesion by day 16. Sensitization with p38 in alum induced Th2 cytokine production and generated the largest granulomas whereas the p38/alum/IL-12 sensitized group showed intermediate results in cytokine production and granuloma growth. Thus, in infected mice, the p38 induced strong Th1 response was insufficient to cross-regulate the evolving Th2 environment that generated large granulomas.

Animals↗
PubMed2002

Breast implant-related silicone granulomas: the literature and the litigation.

Formation of a granuloma is a common tissue response to the presence of a variety of foreign materials. A silicone granuloma is, by definition, a type of tissue reaction elicited occasionally by silicone. Granulomas of this sort have not engendered a great deal of attention in the scientific literature since their first description in 1964, and they were considered by most surgeons through the 1980s to be an incidental finding of little or no consequence. Since it is tangible and readily visible to juries, the silicone granuloma became a frequent issue in breast implant litigation in the 1990s. Although most other complaints in this litigation have been subjective or causally unrelated to silicone, the presence of a granuloma has been used as a basis of local complication claims and, more creatively, as a mechanism for hypothetical systemic disease occurrence. This review examines the basic science and the clinical literature pertaining to breast implant-related silicone granulomas, viewing them in a context of current clinical thought and frequent issues of litigation. Clinically apparent silicone granulomas are a relatively rare complication of breast implant placement and surgical resection is indicated when they are symptomatic or of diagnostic concern. There is no evidence in the peer-reviewed scientific literature to support frequent plaintiff theories in litigation that silicone granulomas play some role in implant-related systemic disease. In fact, the very existence of such diseases, themselves, is equally unsubstantiated.

Breast Implants↗
PubMed2004

Eosinophilic granuloma of the atlas presenting as torticollis in a child.

STUDY DESIGN: This report describes a case of successful surgical treatment of eosinophilic granuloma of the atlas in a 3.5-year-old boy who presented with torticollis. OBJECTIVE: The purpose of this report was to illustrate the rare clinical presentation of eosinophilic granuloma in the atlas. SUMMARY OF BACKGROUND DATA: Eosinophilic granuloma, a benign solitary lesion that commonly affects children, has a variable clinical course. Although eosinophilic granuloma has been reported to occur in the cervical spine, there have been only five reported cases of eosinophilic granuloma affecting the atlas. The management of eosinophilic granuloma ranges from observation and immobilization of the cervical spine to surgical excision. METHODS: The tumor was located on the left lateral mass of the atlas. Biopsy and curettage were performed through an oblique incision through the posterior border of the sternocleidomastoid muscle. A histopathologic evaluation confirmed the diagnosis of eosinophilic granuloma. RESULTS: The patient tolerated the procedure with no complications, and his torticollis has completely resolved. CONCLUSION: Eosinophilic granuloma of the atlas initially presented in this patient as torticollis. Biopsy for confirmation of diagnosis and curettage for treatment provided a successful outcome in this patient. We suggest biopsy of the lesion and histopathologic evaluation to confirm the diagnosis in atypical cases.

Cefazolin↗
PubMed1985

Effect of captopril on transplanted schistosome egg granulomas in skin.

Groups of athymic nude (nu/nu) and littermate (nu/+) mice received transplants into skin of hepatic egg granulomas isolated from Schistosoma mansoni-infected nu/+ mice. Some were fed captopril, an angiotensin-converting enzyme inhibitor, and other animals served as controls. Lesions were removed at 2, 4, and 6 weeks after implantation and prepared for light and electron microscopy. The number of new egg granulomas repopulated by recipient cells was compared by counting more than 100 eggs per specimen, randomly, double blind, and the effects of captopril on developing granulomas were determined. Results in nude mice indicated a trend for increasing granuloma takes with time in captopril-treated animals compared to controls, especially in mice who started therapy 2 weeks after transplantation. In nu/+ recipients the differences were more striking and statistically significant at 2 and 6 weeks after grafting. The granulomas in treated mice in both groups were larger than those in controls, but the cellular composition in the granulomas that developed were similar. New granulomas consisted mainly of eosinophils and mixed-function macrophages, although some purely secretory macrophages also were seen. The findings demonstrate that captopril ingestion enhanced granulomatous inflammation induced by skin transplantation of schistosome egg granulomas and significantly increased isograft takes. The results may have relevance for treating cutaneous diseases like sarcoidosis with captopril.

Animals↗
PubMed1994

Granulomatous hypersensitivity to Schistosoma mansoni EGG antigens in human schistosomiasis. IV. A role for prostaglandin-induced inhibition of in vitro granuloma formation.

The prostaglandins (PG) are known to regulate immune cell function(s) and participate in the progression of both acute and chronic inflammatory reactions. Using an in vitro model of Schistosoma mansoni egg-induced hypersensitivity granulomas, we have delineated the role of immune complexes (IC) in the induction and release of PG and their inhibitory effects on granuloma development. The hypersensitivity-type granuloma reaction to soluble egg antigen (SEA) was examined using a model of in vitro granuloma formation. Our results show that granuloma formation was dramatically suppressed by the addition to the granuloma cultures of IC, PGE1, PGE2, while PGF2 alpha had no significant effect. The inhibition of the PG function was achieved by the introduction of anti-PG antibodies that blocked suppression of granuloma formation. It appears in this model system that IC may inhibit the activity of granuloma formation by stimulating the monocyte-macrophage lineage to release inhibitory mediators. Our results suggest that the prostaglandins E series may be important in the generation and maintenance of suppression of the granulomatous inflammatory response to S. mansoni egg antigens.

Animals↗
PubMedDate not supplied

Abscess-forming granulomatous lymphadenitis: histological typing of suppurative granulomas and clinicopathological findings with special reference to cat scratch disease.

In order to clarify the histological and immunohistochemical characteristics of suppurative granuloma in abscess-forming granulomatous lymphadenitis (AGL), and the relation between AGL and cat scratch disease (CSD), 36 cases of AGL were studied. The combined results showed that there were two types of suppurative granulomas. The suppurative granulomas histologically revealed small lymphocytes of predominantly T cell phenotype distributed among the epithelioid histiocytes bordering central necrotic areas in the suppurative granulomas. These suppurative granulomas could be further subdivided into two groups, mainly those with and without the intermingling of large transformed cells of B-cell phenotypes: Type B granuloma with large transformed B cells and Type A without large transformed B cells. Both types of granulomas were observed in a varying degree in most cases. According to the predominant type of granulomas, 36 patients with AGL were further classified into two groups: Group I of Type A dominance and Group II of Type B dominance. Warthin-Starry (WS) silver stain positive bacteria, which are said to be a causative agent of CSD, were present in about 50% of both groups. No Brown-Hopps' Gram-positive bacteria, fungus, toxoplasma, Chlamydia or Bacillus Calmette-Guérin antigen were found in any case. Clinically, there was no significant difference between these two groups. On the other hand, the detection of WS-positive bacteria seemed to have some relationship with the duration of disease and the history of exposure to cats, and 70% of AGL cases occurred in autumn without a single concurrent epidemic.

Adolescent↗
PubMed1985

Eosinophils in the cellular infiltrate of granuloma annulare.

Eosinophils have been described in the infiltrates of granuloma annulare, but their frequency, distribution and extent are not well documented. We found eosinophils in 18/45 (40%) cases of granuloma annulare, without significant variation relating to histologic sub-pattern. Eosinophils were seen in over half the cases of deep granuloma annulare and in over one-third of the cases of superficial granuloma annulare. This study demonstrates the lack of specificity of eosinophils in differentiating superficial granuloma annulare from deep granuloma annulare, granuloma annulare from necrobiosis lipoidica, and granuloma annulare from occasional clinical simulants which histologically show eosinophils, such as arthropod bite reactions.

Diagnosis, Differential↗