Granulomatous Inflammatory Reaction Research Articles

Cell membrane-associated proteoglycans mediate extramedullar myeloid proliferation in granulomatous inflammatory reactions to schistosome eggs.

In chronic murine schistosomiasis, extramedullar myelopoiesis was observed, with proliferation of myeloid cells in liver parenchyma and in periovular granulomas. We have studied the question of whether cells obtained from granulomatous connective tissue may act as myelopoietic stroma, supporting long-term myeloid proliferation. Primary cell lines (GR) were obtained in vitro from periovular granulomas, induced in mouse livers by Schistosoma mansoni infection. These cells were characterized as myofibroblasts, and represent liver connective tissue cells involved in fibro-granulomatous reactions. They were able to sustain survival and proliferation of the multipotent myeloid cell lines FDC-P1 and DA-1 (dependent on interleukin-3 and/or granulocyte-macrophage colony stimulating factor, GM-CSF) without the addition of exogenous growth factors. This stimulation was dependent upon myeloid cell attachment to the GR cell layer; GR cell-conditioned medium had no activity. Primary murine skin fibroblasts could not sustain myelopoiesis. The endogenous growth-factor was identified as GM-CSF by neutralization assays with monoclonal antibodies. The stimulation of myelopoiesis occurred also when GR cells had been fixed with glutardialdehyde. The observed stimulatory activity was dependent upon heparan sulphate proteoglycans (HSPGs) associated with GR cell membranes. It could be dislodged from the cell layer with heparin or a high salt buffer. Our results indicate a molecular interaction between endogenous growth-factor and HSPGs; this interaction may be responsible for the stabilization and presentation of growth factors in myelopoietic stromas, mediating extramedullar proliferation of myeloid cells in periovular granulomas.

Determination of virulence and pathogenesis of a canine strain of Leishmania leishmania infantum in hamsters and dogs

SUMMARY Visceral leishmaniasis was experimentally induced in hamsters by the intracardiac inoculation of 107 amastigotes of Leishmania leishmania infantum of canine origin. At postinoculation (pi) days 7, 21, 42, and 63, hamsters were euthanatized. Body weights and total parasite numbers of the liver and spleen were determined. Gross and histologic evaluations of tissues were done. Dogs also were inoculated IV with 108 amastigotes/kg of body weight. Samples were obtained from dogs prior to infection and at biweekly pi intervals for CBC and serum chemical analysis, for lymphocyte blastogenic assay by use of blood leukocytes, and for ELISA to determine antileishmanial antibody titers. At pi week 12, dogs were necropsied; organ weights, tissue imprints of the liver and spleen, and histologic interpretations of tissues were obtained. Hamsters developed high parasite numbers within 7 days after inoculation, at which time the total parasite numbers in the liver (3.51 × 107 amastigotes) was observed to be approximately 11 times that in the spleen (2.93 × 106). The liver had the highest parasite numbers throughout the infection period. Some infected hamsters became either cachectic and emaciated or ascitic. Two of the 10 infected hamsters died at pi days 54 and 58. Moderate to severe hepatosplenomegaly with granulomatous inflammatory reactions characterized by the presence of varied numbers of parasitized macrophages, giant cells, and hepatic Schaumann bodies were observed in infected hamsters. Infected dogs developed significantly altered hematologic values consisting of mild anemia and moderate leukopenia at pi weeks 8 to 12. Hyperproteinemia characterized by hyperglobulinemia (4.5 g/dl) was noticed at pi week 4. Serum globulin values remained high and increased to > 5.0 g/dl at pi weeks 8, 10, and 12. At pi week 4, ELISA titers were > 16. By pi week 12, all infected dogs had titers > 1,024. The dog with the highest antibody titer had the lowest number of parasites and mild pathologic changes. Evidence of lymphoproliferative response was not noticed up to pi week 12. Similarities between infected hamsters and dogs included the presence of higher parasite numbers in the liver than in other organs. The highest total parasite numbers in the spleen and liver were 1.12 × 109 and 2.86 × 109, respectively. Mild to moderate granulomatous inflammatory reactions were observed in the liver, spleen, thymus, and lymph nodes. Within 12 weeks after inoculation, parasitized macrophages were found in the dermis. The overall results indicate that hamsters are highly susceptible to experimental infection, and that infected hamsters develop findings similar to those in natural human infections. Our findings also indicate that dogs are susceptible and develop high antileishmanial titers that correspond to low parasite numbers. This suggests the possible role of antibody in determining the seriousness of disease.

Granulomatous peritonitis by ascaris

The granulomatous peritonitis by ascaris (GPA) is a rare complication of intestinal ascariasis due to the perforation of the digestive tract by the adult worm, which deposits its ova in free peritoneum; therefore, provoking an intense granulomatous inflammatory reaction. We report a case of an 8-year-old boy with GPA, emphasizing the clinical and diagnostical aspects and the therapeutics procedures.

The effect of therapeutic radiation on canine alveolar ridges augmented with hydroxylapatite

The purpose of this investigation was to evaluate the effect of radiation on hydroxylapatite (HA) implanted subperiosteally for alveolar ridge augmentation in dogs. All bicuspids and molars were extracted from 16 dogs. After 6 weeks, nonporous HA granules were implanted subperiosteally on the alveolar ridge. Following 4 months of healing, 12 dogs (experimental group) underwent therapeutic radiation therapy (Co 60, 4,000 rad [40 Gy]) to the head and neck region. Four dogs were not irradiated and served as controls. Four animals (three experimental and one control) were killed at 5,6,7, and 8 months after HA augmentation. Light microscopic evaluation showed that approximately 25% of HA granules were encased by bone while the others were surrounded by fibrous connective tissue. Dissolution of the HA was observed. Microparticles of HA were phagocytized as part of a granulomatous inflammatory reaction. This reaction decreased significantly as time elapsed after implantation. Osteoclastic activity was seen at the junction of HA and periosteum and as part of bone remodeling. Dissolution of the HA granules and the granulomatous inflammatory reaction were not significantly increased by therapeutic radiation. The radiation did not cause development of dehiscence or osteonecrosis.

Ischemic colitis of the cecum after renal transplantation masquerading as malignant disease

Fourteen years after kidney transplantation and following protracted rejection of the transplant, a patient developed abdominal pain, fever, and leukocytosis. Ultrasound demonstrated a pericolic abscess, and barium enema a deformity of the ascending colon suggesting malignant growth. Colonoscopy showed ulcerative and necrotic lesions of the cecum, and colonic carcinoma was suspected. At surgery, a granulomatous inflammatory reaction with fibrosis involving the kidney transplant and cecum was found. Histological examination revealed ulcerations secondary to ischemic colitis, but no malignancy. Thus, ischemic colitis should be ruled out in cases with a presumptive diagnosis of colonic malignancy at x-ray or endoscopy.

Tissue Response of Fish to Invasion by Larval Pseudoterranova decipiens (Nematoda; Ascaridoidea)

The histopathology of Pseudoterranova decipiens (L3) in experimentally infected rainbow trout (Oncorhynchus mykiss) and naturally infected Atlantic cod (Gadus morhua) was similar. The chronic granulomatous inflammatory reaction included polymorphonuclear neutrophils, macrophages, lymphocytes, epithelioid cells, and fibroblasts. Giant cells were also found but only in the experimentally infected rainbow trout. Mature capsules around the larvae consisted of an inner layer, composed of macrophages which underwent epithelioid transformation and later gradually degenerated, and an outer layer, composed of fibroblasts and collagen fibres. A layer of lipofuscin was adjacent to the parasite in older cod infections but this was absent in all of the newly formed capsules in the experimentally infected rainbow trout.

Potential pathogenicity of Cladosporium tennuisimum, Phaeoisaria clematidis and Ramichloridium subulatum in a mouse model

The potential pathogenicity of one isolate each of Cladosporium tennuisimum, Phaeoisaria clematidis and Ramichloridium subulatum for mice was investigated by intravenous, intraperitoneal and subcutaneous routes of inoculation with saline and mucin suspensions of the organisms. No mice died during the experimental period. Dark nodular lesions were formed in the liver, spleen, kidneys, intestine, stomach, omentum and diaphragm after inoculation through the intravenous and intraperitoneal routes. Gross lesions were produced in the lungs of one mouse inoculated intravenously with R. subulatum. Localised nodular lesions were formed in the subcutis following the subcutaneous route. Tissue response was characterised by granulomatous inflammatory reaction. Fungal elements were confined within the granulomata. Though the fungi showed limited pathogenic potential, they may represent a hazard under conditions of compromised host immunity.

Primate Trabeculectomies With 5-Fluorouracil Collagen Implants

Bilateral trabeculectomies were performed on four normal cynomolgus monkeys. Highly purified bovine skin collagen implants with either 1 mg of 5-fluorouracil or physiologic saline (one each per monkey by randomized, masked assignment) were sutured under the scleral flaps. The randomization code was not broken until all clinical and histopathologic observations had been completed. Six weeks postoperatively, the 5-fluorouracil-treated eyes had more deeply open internal trabeculectomy ostia than the control eyes; however, the intraocular pressures were indistinguishable, the filtering blebs were only minimally different, and half of each group had trace or mild anterior subcapsular lenticular changes. Histologically, a multinucleated foreign body giant cell reaction was evident in all of the collagen implants, but the 5-fluorouracil-treated eyes had less vigorous or delayed reactions compared to the control eyes. The collagen implant appears to be a poor drug delivery system in this model of glaucoma filtering surgery, because it incites a granulomatous inflammatory reaction.

Respiratory Failure Caused by Adiaspiromycosis

Adiaspiromycosis is a rare pulmonary disorder caused by the fungus Emmonsia crescens (or Chrysosporium parvum var crescens). According to the amount of inhaled conidia, man may develop symptomatic disease. After reaching the alveoli, the adiaconidia do not multiply or disseminate, but will induce a granulomatous inflammatory reaction that may lead to fatal respiratory failure. Up to now, only five cases of disseminated pulmonary infection have been documented. This work describes the occurrence, in Brazil, of two further cases of symptomatic disease with diffuse interstitial infiltrates and severe functional impairment. Possible massive infestation during activities in closed and stuffy environments is suggested. The specific diagnosis was troublesome and could not be made by cultures, skin tests or bronchoalveolar lavage. Both patients were successfully treated, but a spontaneous resolution of the process is seriously considered.

Extramedullar proliferation of eosinophil granulocytes in chronic schistosomiasis mansoni is mediated by a factor secreted by inflammatory macrophages

In chronic murine schistosomiasis mansoni, extramedullar myelopoiesis of eosinophils has been described, associated with tissue inflammatory infiltrates and periovular granulomas. It may be experimentally induced by intraperitoneal glass implants in mice with chronic schistosomiasis but not in normal mice or in mice with acute schistosomiasis. In vivo studies showed that this induction depended on macrophages adherent to the implants. In an in vitro test with bone marrow cells, we demonstrated that this eosinophil proliferation was mediated by a factor secreted by the mobilized macrophages. In contrast to murine interleukin-5 (IL-5), which induced both proliferation and differentiation of eosinophils, the studied monokine did not induce their maturation. A potent neutralizing monoclonal antibody for murine IL-5 did not abrogate the stimulatory activity of the monokine, indicating that it is a cytokine distinct from IL-5. These data, together with a quantitation of bone marrow, blood, and peripheral eosinophils, indicated that in chronic schistosomiasis, the systemic medullar supply of eosinophils is supplemented in tissues by their local proliferation, mediated by macrophages mobilized in local granulomatous and diffuse inflammatory reactions.

輸入動物の寄生虫 Ｖ． オオガラゴに見出された舌虫幼虫

We had the opportunity to examine the carcass of a female thicktailed bush baby (Galago crassicaudatus) bred in Tama-Zoo, Tokyo. This carcass was one young galago of 4 head (2 males and 2 females) which were caught at the east part of Africa and died at one month after the importation to Japan at November 1987.As the results of necropsy, 25 encapsulated nymphs of pentastomes were found in or on the parenchyma of the abdominal-wall, diaphragm, mesenteries, liver, lung and spleen, recognized as conspicuous annular worms and coiled within a transparent thin-walled cyst. These measured 4-6 mm in diameter. No other gross lesions were found. The cause of the Galago' s general illness was not ascertained, nor was the source of the pentastomes.The cylindrical nymphs were identified as Armillifer armillatus based on the characteristic pronounced annulations of the integument and by the number of these annulations (16 to 20).At microscopical examination of sections of encysted nymphs in liver and diaphragm, the nymph was enclosed in a fibrous cyst wall and there were a encysted nymph showing prominent acidophilic glands and intestinal tract; the chitinous cuticle was smooth without spins, 6.4 μm thick; subcuticlar glands and muscle fibres were apparent beneath the cuticle. Neither degenerative nor granulomatous inflammatory reactions noted in the adjacent tissue.Nymphal pentastomes are capable of developing in a wide of intermediate hosts.Armillifer armillatus nymphs have been reported from various terrestrial animals, including insectivora, carnivora (lion, dog, leopard, mongoose), rodentia (rat, squirrel), ungulata (antelope), primates (monkey, macaques, galagos, guenons, mangabey, baboons, chimpanzee, man) (Sambon, 1922; Flynn, 1973). Although this parasite occurs naturally only in tropical Africa, when these worms were imported to Japan with these animals, this parasite will be possible to occures the problem as a zoonotic parasites.

Histological Effects of Endocrine Therapy for Prostatic Cancer in Relation to Clinical Course

In order to evaluate histological changes in cases of prostatic cancer following endocrine therapy, 25 extensive specimens were removed from prostates during periods of local control, and were examined with respect to prognosis. Shortly after the commencement of the endocrine therapy, there were noticeable degenerative changes in the cancer cells as well as structural changes such as desquamation of cells and loss of cancer nests. Later than two months from the start of therapy, stromal changes such as fibrosis and scar formation appeared. Coagulation necrosis of tumor tissue, inflammatory cell infiltration and granulomatous reactions were not as prominent. Within the first two months of treatment, the endocrine therapy uniformly affected the cancer tissues to some extent. After then, some showed relapsing viable cells in a part of the tumor, being judged to be no response. The others continued to respond to the therapy. The response was estimated as marked when such therapeutic changes appeared diffusely and profoundly over the tissues removed. Patients with a marked response had a good prognosis, indicating histological evaluation after endocrine therapy to provide a prognostic factor.

Active and latent collagenase activity during reversal of hepatic fibrosis in murine schistosomiasis

In schistosomiasis mansoni, eggs trapped in portal venules of the liver induce a granulomatous inflammatory reaction and subsequently fibrosis. Upon specific schistosomicidal treatment, however, fibrosis undergoes a marked reversal. The features of this process as regards collagen metabolism were examined in mice using praziquantel as the schistosomicidal drug, which was given 68 days after infection. It was found that collagenase activity in the liver, for both latent and active forms, increases rapidly until 5 days after treatment as compared to nontreated infected mice and then diminishes gradually. The hydroxyproline content in liver and (24-hr) urine are also modified, their values decreasing progressively up to 72 days after treatment without, however, reaching values observed in normal mice. Worm death appears to be the triggering stimulus of these events.

Myxidium rhodei (Protozoa. Myxozoa: Myxosporea) in cyprinid fish from NW Spain

Myxidiurn rhodei infection of the kidney of chub Leuciscus cephalus cabeda and boga Chondrostoma polylepis from the Esla River, Spain is described. Prevalence was low. 3.8 % in chub and 1 0 in boga, and intensity relatively high. Affected kidneys exhibited varying degrees of histopathological damage. Spores and plasmodia of the parasite were found mainly in the interstitia, but also in the glomeruli, frequently encapsulated in granulomas with an intense fibrotic reaction. A granulomatous inflammatory reaction with leucocytic infiltration was evident around cysts, affected glomeruli or plasmodia. As a result, much of the kidney tissue became seriously damaged.

Intravesical BCG administration in the guinea pig. A histomorphological study.

Intravesical BCG administration is used as an adjuvant therapy after transurethral resection for superficial bladder cancer in man. The mechanisms of its antitumor activity are not known. The aim of this study was to characterize the histomorphological changes in various organs of the guinea pig after intravesical BCG administration. The BCG preparation used was BCG-RIVM, a Dutch BCG preparation. Instillations were performed in previously undamaged bladders weekly for 6 consecutive weeks and lasted 30 min or 1 h. Different doses were used ranging from 10(3) culturable particles (c.p.) to 5 x 10(7) c.p. of BCG. After 6 weeks, the animals were killed and postmortem examination was performed. The bladder wall, retroperitoneal lymph nodes, spleen, liver, lungs and distant lymph nodes were examined histologically. The BCG therapy, with a dose of 10(6) culturable particles and higher, induced an inflammatory reaction consisting of mononuclear infiltrates in the subepithelial tissue of the bladder wall. In approximately 50% of the animals investigated, the infiltrates were accompanied by non-caseating granulomatous lesions indicated by the presence of epithelioid cells. In general, the epithelial layer of the bladder showed no visible alterations. Similarly, a granulomatous inflammatory reaction was observed in the first retroperitoneal (iliac) lymph nodes draining the bladder. Granulomatous lesions were occasionally also present in liver and lung. In three of the 29 animals investigated, lesions were present both in liver and lungs, and in two of these three animals a granulomatous reaction was observed in the spleen and distant lymph nodes indicating a generalized inflammatory response induced by BCG.(ABSTRACT TRUNCATED AT 250 WORDS)

FISH TUMORS AND ECOLOGICAL SURVEILLANCE: A CAUTIONARY EXAMPLE FROM PORT PHILLIP BAY1

ABSTRACT: Interest in the development of strategies using faunal populations for monitoring chemical contamination of the environment was promoted, in part, by earlier investigations of skin lesions that were mistakenly diagnosed as epidermal papillomas in flatfish from Pacific coastal waters of the northern hemisphere. A survey aimed at exploring chemical pollution effects was also undertaken in the southern hemisphere in Port Phillip Bay, Australia, where over 15,000 fish, involving ten mainly bottom‐feeding species, were sampled. Only two cases of true neoplasia (both in the sand flathead) were found, but there was a high prevalence of cancer‐like growths in certain species of leatherjacket and a low prevalence in spiky globe fish. Morphological analysis proved these to be subacute inflammatory or chronic granulomatous reactions possibly due to parasitic infestation. These findings were discussed in relation to recent work that shows the epidermal papilloma to be a pseudotumor, and the propensity for fish to develop exuberant inflammatory responses to exogenous stimuli which mimic neoplasia.

Epizootiology, pathology, and description of Eustrongylides tubifex (Nematoda: Dioctophymatoidea) in fish

In Guelph Lake, a man-made reservoir in Ontario, Canada, prevalence of larval Eustrongylides tubifex in pumpkinseed (Lepomis gibbosus), rock bass (Ambloplites rupestris), and yellow perch (Perca flavescens) was 12.9% and mean intensity ranged from 1 to 1.8. Larvae were encapsulated on the mesentery of fish. Pumpkinseed and yellow perch were the important fish hosts in Guelph Lake as most larvae in these fish were alive. In contrast, 40% of larvae in rock bass were dead and calcified. Third- and fourth-stage larvae from naturally infected fish are described. Larvae in the three species of fish elicited a granulomatous inflammatory reaction. Attempts to transfer third-stage larvae from experimentally infected oligochaetes and third-stage larvae from naturally infected fish to laboratory-reared pumpkinseed were unsuccessful. Fourth-stage larvae from naturally infected fish were transferred successfully to pumpkinseed. Eutropic lakes such as Guelph Lake are particularly suitable enzootic areas because of the abundant populations of tubificid intermediate hosts and the presence of fish hosts such as pumpkinseed and perch. The advanced stage and development of larvae (to the fourth stage) in fish likely represents an adaptation for a parasite that occurs in a migratory host such as Common Mergansers (Mergus merganser), which frequent Guelph Lake for only about 1 month in spring and fall.

Local reactions of the saponin Quil A and a Quil A containing iscom measles vaccine after intramuscular injection of rats: A comparison with the effect of DPT-polio vaccine

A short-term toxicity study was performed to investigate local reactions and hematological changes after im injection of Quillaia A (Quil A; 50 or 600 μg/ml) an essential component of an immunostimulating complex (iscom), a novel form of a subunit vaccine, and of iscom measles vaccine containing 360 μg Quil A/ml. The effects were compared with those caused by a sterile phosphate-buffered saline solution and by diphtheria-pertussis-tetanus-polio (DPT-polio) vaccine. Groups of six male rats were injected im with 0.25 ml of the test solution: on Day 0 in the left and on Day 7 in the right musculus gastrocnemius. On Day 14 the animals were killed, and the left and right inguinal lymph nodes were weighed. These organs and the left and right musculus gastrocnemius were investigated microscopically. The only hematological changes observed occurred in the group injected with DPT-polio vaccine: a decrease in the Hb value and in the number of erythrocytes and an increase in mean corpuscular hemoglobin content and in the number of leucocytes. The weights of the left and right inguinal lymph nodes were significantly increased in rats injected with DPT-polio vaccine, iscom measles vaccine, and the high dose of Quil A. The most intense granulomatous inflammatory reaction, mainly consisting of activated macrophages, was observed at the injection sites of all animals of the DPT-polio group. Only one animal injected with the iscom measles vaccine showed a moderate inflammatory reaction of the same type. The regional lymph nodes in all animals of both vaccine groups were activated, indicating a good immune response. Quil A in the highest concentration caused in all animals a different type of inflammatory reaction, characterized mainly by a proliferation of fibroblasts. The low-concentration Quil A revealed an inflammatory reaction only in one animal. Considering the absence of local and hematological effects it can be concluded that there are no objections against the use of Quil A in an iscom vaccine at a concentration of 50 μg/ml vaccine.

Pathology of pentastomid infections (Sebekia mississippiensis) in fish.

Differential pathogenesis was observed in two species of fish naturally infected with the pentastome Sebekia mississippiensis. Mosquitofish (Gambusia affinis) showed a mild inflammatory response to developing nymphs, whereas swordtails (Xiphophorus helleri) had an extensive granulomatous inflammatory reaction with accompanying hemorrhage, myositis, and myodegeneration. This suggested that certain species of tropical fish reared in the southeastern United States may be at risk to potentially harmful infections with this parasite.

Complications of Transthoracic Needle Biopsy Decreased with Isobutyl 2-Cyanoacrylate: A Pilot Study

To explore the possibility of performing percutaneous lung biopsy safely in patients mechanically ventilated with positive-end expiratory pressure (PEEP), transthoracic needle biopsy was performed in 16 anesthetized mongrel dogs mechanically ventilated with 10 cm H 2O of PEEP. To obtain the biopsy sample, a 25-gauge “skinny needle” was passed through a 20-gauge sheath and placed up to 6.25 cm deep. After satisfactory samples were obtained, both needles were withdrawn in the control group, but in the treated group, the outer sheath was used to inject 0.5 ml of isobutyl 2-cyanoacrylate to seal the needle track. Pneumothorax was present in 7 (87.5%) of 8 dogs in the control group and in 2 (25%) of 8 dogs in the treated group ( p = .0147). Lung tissue exhibited an apparent foreign-body granulomatous inflammatory reaction. This technique could extend the benefits of transthoracic needle biopsy to mechanically ventilated patients, but further studies to prove the safety of isobutyl 2-cyanoacrylate are necessary.