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Biomedical subjects

E Meerovitch

Publications and source records attributed to E Meerovitch.

At least 19 recordsLinked to original sources

Entamoeba histolytica: chemoattractant activity for gerbil neutrophils in vivo and in vitro.

The kinetics of the host's cellular response in the peritoneal cavity of gerbils toward axenic pathogenic and nonpathogenic Entamoeba histolytica strains were examined. Amebae contained in diffusion chambers or free in the peritoneum elicited a neutrophilic response accompanied by decreased levels of macrophages and lymphocytes. Pathogenic amebae (IP:0682:1 strain) elicited a neutrophilic response greater than the nonpathogenic DKB and "entamoeba-like" Laredo amebae. The neutrophil eliciting factor was found in high levels in disrupted freeze-thawed amebae (53% elicited neutrophils vs 8% for control), glutaraldehyde fixed amebae (45%) and amebic membranes (65%), and low levels in conditioned amebic medium (15%) and the supernatant fraction of amebae (16%). The factor was heat stable to high temperature (100 C for 30 min) and at various pH (6 to 9). The neutrophil eliciting factor in amebic membranes was lowered following pretreatment for 30 min with 1% immune and nonimmune gerbil or human sera (34-48% lowered neutrophil response vs control), acidic pH (less than 3, 69%), proteolytic digestion [trypsin (68%) and alpha-chymotrypsin (72%), 100 micrograms/ml], and 2% Triton X-100 (75%). Peritoneal neutrophils isolated following stimulation with amebic membranes or thioglycollate medium demonstrated higher chemotaxis in vitro toward live pathogenic amebae and amebic membranes (IP:0682:1 strain) compared to either the supernatant fraction or the nonpathogenic DKB or Laredo amebae. The results of this study indicate that membrane bound proteins of pathogenic amebae are chemotactic for gerbil neutrophils which may be important in the pathogenesis and pathology of amebiasis.

Animals↗

In vitro and in vivo interaction between trophozoites of Entamoeba histolytica and gerbil lymphoid cells.

The in vitro and in vivo antiamoebic cytotoxic effects of peritoneal exudate cells and mesenteric lymph node lymphocytes of gerbils with cecal amoebiasis or those immunized with amoebic extract were investigated. A differential effect of the lymphoid cells against trophozoites of nonpathogenic and pathogenic strains of Entamoeba histolytica was observed. Nonpathogenic amoebae were more susceptible to killing by lymphoid cells than pathogenic amoebae in vitro and in vivo in infected or immunized animals. These data suggest that during the course of cecal amoebiasis in gerbils, a differential stimulation or depletion of cytotoxic cells in the lymphoreticular tissues occurs, resulting in an impaired cell-mediated immune response.

Animals↗

Entamoeba histolytica: early progressive pathology in the cecum of the gerbil (Meriones unguiculatus).

The early formation of amebic cecal lesions in the gerbil (Meriones unguiculatus) was studied sequentially from 1 to 10 days post-inoculation. The earliest response of the cecal mucosa towards trophozoites of Entamoeba histolytica was local release of interglandular and goblet cell mucin. Trophozoites adhered to the surface epithelium or were trapped in the luminal mucus in the absence of epithelial cell damage. Focal mucosal erosion occurred later, and was preceded by crypt hyperplasia, edema and hemorrhaging of the lamina propria. The interglandular epithelial cells were cytolysed or were sloughed off into the lumen. Amebic mucosal erosion was accompanied by trophozoite entry in the crypts, but rarely into the lamina propria. The inflammatory cellular infiltrate was diffuse, and neutrophils were found in the lumen in contact with trophozoites. The findings of this study suggest that trophozoites of E. histolytica do not actively penetrate or invade the interglandular epithelium, but rather, that amebae are permitted to invade as a result of the destruction of the epithelium. Mucus depletion and the mucosal inflammation, probably in response to the adsorption of amebic toxins, preceded epithelial erosions.

Amebiasis↗

Entamoeba histolytica: electrophoretic isoenzyme patterns of strains and their virulence in the cecum of gerbils (Meriones unguiculatus).

Six strains of Entamoeba histolytica isolated from humans were characterized by their electrophoretic isoenzyme patterns and by virulence in the cecum of Mongolian gerbils (Meriones unguiculatus). Amebae from symptomatic cases of amebiasis were found to belong to zymodeme group II, whereas strains isolated from asymptomatic infections belonged to zymodeme groups I or V. Strains recently isolated from symptomatic cases of amebiasis were highly invasive in the cecum of gerbils. The most prominent pathologic changes present in these infections were the destruction of the interglandular epithelium, crypt hyperplasia and trophozoite invasion of the crypts and submucosa. Strains from asymptomatic carriers were of low or moderate invasiveness in the animal model. Two of the carrier strains expressing a zymodeme group I pattern caused diffuse or transient focal erosions of the interglandular epithelium in some animals. Trophozoites of carrier strains did not invade the crypts nor cause sloughing of the surface epithelium. Presence of colonic lesions was correlated with passage of motile trophozoites in the feces. The severity of histologically demonstrable lesions in the cecum of gerbils was positively correlated with the isoenzyme patterns characteristic of the more virulent amebic strains.

Animals↗

Entamoeba histolytica: lymphoreticular changes in gerbils (Meriones unguiculatus) with experimentally induced cecal amebiasis.

Antibody responses and changes in the lymphoreticular tissues of gerbils with experimental cecal amebiasis were studied from 5 to 60 days PI. Changes in the cecum consisted of lymphoid follicle hyperplasia and depletion of lymphocytes, followed by follicle atrophy and histiocytosis. Mesenteric lymphadenopathy, and histologic alterations in the lymph nodes paralleled the progressive development of amebic cecal lesions. Early in the infection (5 to 10 days PI) mesenteric lymph nodes showed cortical follicle hyperplasia, blastogenesis in the paracortical areas (PCA) and intense lymphoblast and plasma cell activity in the medullary cords. At 20 to 30 days PI, the cortical follicles, the PCA and the medulla were depleted of lymphocytes and there was histiocytosis throughout the organ. At 60 days PI, lymphocyte repopulation took place in the PCA, and cortical follicles had active germinal centers. Spleen follicles did not increase in number as the infection progressed, but became hyperplastic. Antibody titers to ameba were low throughout the cecal infection but rose whenever amebic metastasis to the liver occurred. The results of this study indicate that lymphocytes from the submucosal lymphoid follicles and the draining lymph nodes may control the pathogenesis of the infection. Lymphoreticular tissue alterations could result from antigenic stimulation and migration of cells to the sites of infection.

Animals↗

Primates as a source of Entamoeba histolytica, their zymodeme status and zoonotic potential.

A survey of 17 species of non-human captive primates in Quebec, Canada, revealed that 40% of the animals were infected with the protozoan Entamoeba histolytica. Isoenzyme analysis of lysates prepared from cultured amebic isolates showed them to belong to either a zymodeme III or VIII, and therefore, characteristic of non-pathogenic strains of E. histolytica from humans. These isolates were also of low virulence in gerbil ceca. Serum samples from infected and uninfected primates had negative titres for E. histolytica and all the animals appeared to be healthy.

Amebiasis↗

The pathology of experimentally induced cecal amebiasis in gerbils (Meriones unguiculatus). Liver changes and amebic liver abscess formation.

The pathogenesis of experimentally induced cecal amebiasis in gerbils (Meriones unguiculatus) was studied from 5 to 60 days after inoculation. Ulcerative lesions were noted 10 to 60 days after inoculation. The sequential development of lesions was asynchronous and progressed from destruction of the interglandular epithelium and of glandular crypt elements to loss of mucosa and formation of granulomatous lesions in the submucosa involving the muscularis mucosae. Pathologic changes in the liver correlated with the formation of ulcerative cecal lesions. Subacute hepatic changes showed lymphocytic portal infiltrate, Kupffer cell hyperplasia, multinucleated giant cells, granuloma formation, and sinusoidal mononuclear and granulocytic infiltrates. Metastatic amebic liver abscesses occurred as early as 10 days after inoculation, and small abscesses were found in the portal areas of the right liver lobe. The sequential development and pathologic manifestation of the infection and the usefulness of the gerbil for the study of human intestinal amebiasis are discussed.

Amebiasis↗

Entamoeba histolytica: antibody responses and lymphoreticular changes in gerbils (Meriones unguiculatus) in response to experimental liver abscess and amebic extract infection.

Antibody responses and histological changes in hepatic lymph nodes and spleen of gerbils (Meriones unguiculatus) during the course of experimental hepatic amebiasis (5-60 days), or in those injected with extracts of Entamoeba histolytica, are described. Lymph node and spleen responses in infected animals paralleled the proliferation of the amebic liver abscess. However, spleen follicle responses were similar in animals that received low or high doses of the amebic extract and differed histologically from those with amebic liver abscess. Liver abscesses, up to 30 days postinfection (pi), doubled in weight between 10 and 15 and between 20 and 30 days pi. Early changes (10 days pi) in the lymphoreticular tissues were characterized by increased size and weight of the organs, hyperplastic follicles, and blastogenesis in the T-dependent areas. At 20 and 30 days pi, the size of spleen follicles increased and there was depletion of lymphocytes from the periarterial area (PAA), as well as gross extension of the red pulp, accompanied by extramedullary erythropoiesis and megakaryocytosis. The paracortical areas (PCA) of lymph nodes were depleted of lymphocytes and histiocytosis throughout the organ, and there was intense plasma cell activity in the medulla. At 60 days pi, lymphocyte repopulation was noted in the PCA and PAA; germinal centers were depleted of blast cells and the spleen red pulp had contracted. Antiamebic antibody titers were low throughout the infection. Changes in the cellularity of the lymphoid organs are discussed in relation to the proliferation of the amebic liver abscesses in infected animals and in those which were injected with the amebic extract.

Animals↗

Lectin-induced agglutination of trophozoites of different species and strains of Entamoeba.

In vitro agglutinability of trophozoites of three Entamoeba histolytica strains, cultivated under axenic conditions in the presence of concanavalin A (Con A), was shown to be related to the degree of their pathogenicity for experimental animals and of the concentration of Con A. Seven strains of E. invadens tested also agglutinated in the presence of Con A, and the degree of agglutination was proportional to the concentration of the lectin. Three strains of E. histolytica-like "Laredo-type" amebae, a strain of E. terrapinae, and a strain of E. moshkovskii agglutinated very slightly, only in the presence of the highest concentration of Con A tested.

Agglutination↗

The Mongolian gerbil (Meriones unguiculatus) as an experimental host for Entamoeba histolytica.

Experimentally induced cecal and hepatic amebiasis was studied in the Mongolian gerbil (Meriones unguiculatus). Axenically cultivated Entamoeba histolytica trophozoites were inoculated into the cecum or the liver after laparotomy. Cecal infections were characterized by intense inflammation and distortion of the tissue. The intensity of the infection, measured by a standard method of scoring, was consistently high from 10 to 30 days postinoculation (p.i.). In tissue sections, disruption of the interglandular epithelium and presence of amebic ulcers and of large numbers of trophozoites were most noticeable 10 days p.i. In older infections there was cecal hypertrophy and crypt hyperplasia but only few amebae were seen. Amebic liver abscesses were well tolerated by gerbils and no mortality occurred. Growth of liver abscesses increased exponentially as the duration of the infection progressed from 5 to 30 days p.i. Liver abscesses were always confined to the inoculated liver lobe, and metastases did not occur. Early liver granulomas were discrete with well-defined walls. The abscesses had a fibrous wall and amebae were seen at their inner aspect. Older liver granulomas were coalesced, forming a single cavitary abscess with intense cellular infiltrate. Gerbils of all ages tested were equally susceptible to liver infections although larger abscesses were obtained in younger adult animals (60-80 days old). The Mongolian gerbil is proposed as a suitable animal model for experimental amebiasis because both the intestinal and hepatic aspects of the disease can be studied in it.

Animals↗

The pathogenesis of experimentally induced amebic liver abscess in the gerbil (Meriones unguiculatus).

Sequential development and pathology of experimentally induced amebic liver abscess in the gerbil (Meriones unguiculatus) were studied from 1 to 60 days after inoculation. Early lesions were characterized by an acute inflammatory response, which became granulomatous at 5 days. Early granulomas were discrete, with well-defined fibrohistiocytic walls. Trophozoite dissemination as a result of fibrolysis of granuloma wall was confined to the liver parenchyma. The granulomatous cellular infiltrate (less than 20 days) was characterized by granulocytes and histiocytes; older granulomas (greater than 30 days) were composed of lymphocytic infiltrate, plasma cells, and a few granulocytes, and were characterized by the absence of epithelioid histiocytes. The degree of pathologic change adjacent to liver granulomas followed the sequential development of the amebic liver abscess. Severe changes observed were portal canal lymphocytic infiltration, the presence of foreign body giant cells, periportal fibrosis, proliferation of bile duct epithelium, and hepatocyte anisonucleosis and ballooning degeneration. The pathogenesis of the infection and the usefulness of the gerbil model for the study of human amebiasis are discussed.

Animals↗

Passive transfer of immunity against hepatic amoebiasis in the hamster by cells.

The role of passive cell-mediated transfer of immunity in hepatic amoebiasis in hamsters was studied. The transfer of peritoneal cells from hamsters vaccinated against or protected from hepatic amoebiasis and from those with hepatic amoebiasis, as well as of spleen cells from vaccinated or protected, but not from infected hamsters, conferred immunity against hepatic amoebiasis in recipient normal hamsters. Treatment of the spleen cells from protected hamsters with anti T-cell serum abolished their ability to transfer immunity. It appears that the effector mechanism in this system is T-cell dependent.

Animals↗

Role of macrophages in host defense against hepatic amoebiasis in hamsters.

The role of macrophages in hepatic amoebiasis in hamsters has been investigated by means of antimacrophage serum prepared in rabbits. Animals treated with normal rabbit serum or antimacrophage serum, as well as untreated controls, were inoculated intrahepatically with 10(5) axenic trophozoites of Entamoeba histolytica. In hamsters treated with antimacrophage serum before intrahepatic inoculation of amoebae, the mean weight of the metastatic foci was significantly greater than in normal rabbit serum-treated or untreated controls. Treatment of hamsters with antimacrophage serum both before and after administration of amoebae not only increased significantly the size of the abscess in the liver but also allowed dissemination of metastatic foci to other organs.

Animals↗

Comparative studies on the pattern of infection with Giardia spp. in mongolian gerbils.

Mongolian gerbils (Meriones unguiculatus) were inoculated with known numbers of Giardia cysts isolated from humans, beavers and mice. The pattern of cyst release in the feces was studied for a period of 35 days. After a latent period of 5 days, animals infected with G. muris release cysts in their feces every day until day 14. Gerbils infected with human or beaver isolates released cysts in their feces intermittently for 30 days. These results indicated that the mode of cyst release in these animals was characteristic of the parasite, and was independent of the host. Mongolian gerbils acquire complete resistance upon homologous species challenge but demonstrate only partial protection when challenged with a different species of Giardia. We concluded that the Mongolian gerbil model could be useful in epidemiological studies for two reasons: it can be used for determination of cyst viability, and for the identification of the etiological agent.

Animals↗

The anti-neoplastic effect of trichinellosis in a syngeneic murine model.

C57BL/6 male mice with chronic trichinellosis, and age-matched uninfected control mice, were inoculated with B16 melanoma cells. Tumour development was inhibited in the infected animals. In the infected tumour-bearing mice, the tumor induction intervals were longer and the tumour size was subsequently smaller than in the control mice. Moreover, when the number of tumour cells in the inoculum was less than that required to produce 100% tumour incidence in the uninfected mice (less than 1 x 10(4) cells), significantly more of the mice with an infection of 2 months duration remained tumour-free. These results were significant at the P less than 0.05 level.

Animals↗

Macrophage requirement for host defence against experimental hepatic amoebiasis in the hamster.

The role of macrophages in hepatic amoebiasis in hamsters has been investigated by means of their treatment with bacille Calmette-Guérin (BCG) for activation, and with silica for elimination of these cells. Silica-treated animals inoculated intrahepatically with 1 x 10(5) trophozoites of Entamoeba histolytica developed amoebic abscesses in the liver and more metastases to other organs than control animals, and this effect was silica-dose-dependent. In contrast, BCG-treated animals developed significantly smaller abscesses in the liver and fewer metastatic foci. These data suggest that macrophages are involved in host defence against the establishment of amoebic liver abscess and metastatic dissemination of amoebae.

Animals↗