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Biomedical subjects

C E Corbett

Publications and source records attributed to C E Corbett.

At least 37 records · Page 2Linked to original sources

Comparative and sequential histopathology of Plasmodium chabaudi-infected Balb/c mice.

1. Rodent experimental models have been useful to study severe malaria but few serial and controlled studies have been conducted. In the present investigation, we describe the histopathology of lethal and non-lethal rodent malaria induced by Plasmodium berghei and P. chabaudi. P. berghei malaria shows a uniformly lethal course, while P. chabaudi malaria produces a non-lethal acute infection with recovery and periodical recrudescences. Sequential histopathological changes were also characterized in P. chabaudi malaria to determine the evolution of the lesions. 2. P. berghei-infected mice have a more severe organ involvement and lower blood regenerative changes than P. chabaudi-infected mice. Two patterns of organ involvement were observed by comparing the two infections. The first is related to nonspecific parasitized red blood cell clearance by liver and spleen. The second is related to specific changes due to a specific parasite strain interaction with the host, such as those found in the lungs. 3. Sequential changes in P. chabaudi-infected mice were characterized by perihepatocytic reticulin fiber deposition during the recovery from infection, which faded in subsequent stages. Other organs had a similar regressive evolution, except splenic lymphoid tissue which underwent histological restoration or even hypertrophy after depletion in the acute stage. No brain or heart lesions were observed in either model during the acute and subsequent stages. 4. P. chabaudi infection, whose histopathology is described here for the first time, should be useful as a non-lethal experimental model to study the evolution of histopathological alterations in malaria.

Animals↗

Experimental visceral leishmaniasis: sequential events of granuloma formation at subcutaneous inoculation site.

Hamsters were inoculated with IO7 Leishmania (Leishmania) chagasi amastigotes in the hind footpads and killed at 7, 15, 30, 45, 60, 75 and 90 days after infection. We observed mononuclear inflammatory infiltrates with many parasites on the 7th and 15th days of infection. On the 30th day there was early granuloma formation. After 45 days the lesion was characterized by well defined epithelioid granuloma with multinuclear giant cells whose cytoplasm showed Schaumann bodies. Non-particulate antigenic material was present in the macrophage cytoplasm and between the lamellae of the Schaumann bodies. Granuloma formation has an important role for the control of infection at the inoculation site. The results indicate that dissemination of the infection must occur in the first 45 days, before granuloma formation has taken place.

Animals↗

A case of multiple lesion mucocutaneous leishmaniasis caused by Leishmania (Viannia) braziliensis infection.

A case of leishmaniasis with multiple lesions due to Leishmania (Viannia) braziliensis infections was diagnosed in a male patient from north-east Brazil. The skin lesions were nodular and pustular and progressed to ulcers. Skin and the oral mucosae were also affected. The behaviour in culture and hamsters of the parasite recovered from a skin lesion was similar to other strains of L. (V.) braziliensis and the strain was characterized by monoclonal antibodies as belonging to serodeme I of this species. The histopathology of the skin lesions of the patient and hamster were of an inflammatory nature which extended through the dermis; leishmania in the tissues were more easily detected by the immunoenzymatic PAP method.

Adult↗

Liver parenchymal cell parasitism in human visceral leishmaniasis.

Liver parenchymal cell parasitism with the amastigotes form of L. donovani was detected by electron microscopy in human visceral leishmaniasis. Endocytosis was considered to be the mechanism by which the leishmania entered the cell. Evidence of well preserved parasites within hepatocytes suggest this parasitism as a possible reservoir for recrudescence.

Humans↗

Cytoadherence in human falciparum malaria as a cause of respiratory distress.

The ultrastructure of three cases of fatal human falciparum malaria was studied in order to identify the cytoadherence of the endothelial cells in relation to parasitized red blood cells and septal interstitial changes which could be related to respiratory distress. Two cases showed marked endothelial oedema narrowing the capillary lumen with areas of adherence preferentially related to knobs, accompanied by septal interstitial oedema. One case showed no endothelial cells oedema, no knobs in parasitized red blood cells with no cytoadherence, no septal interstitial oedema and no respiratory distress. Cytoadherence seems to be the mechanism responsible for the septal pulmonary changes in severe falciparum malaria.

Animals↗

Baseline volume data of human liver parenchymal cell.

Normal human liver fragments obtained through intra surgical needle biopsies from five selected hospital cases were fixed in glutaraldehyde and subsequently in osmium tetroxide and embedded in Araldite. These samples were studied in semithin sections under light microscopy. Stereological methods applied on photomicrographs were used to estimate the hepatocyte nuclear volume, the nuclear and cytoplasmic volume densities as well as the hepatocyte numerical density in the liver intermediate lobular zone. The average absolute volume of the mean hepatocyte in the intermediate lobular zone is 2850 +/- 99.9 microns 3. In one cubic centimeter of this zone there are 233 x 10(6) +/- 81.57 parenchymal cells.

Biopsy, Needle↗

Sequence of protective epitopes of streptococcal M proteins shared with cardiac sarcolemmal membranes.

Synthetic peptide fragments spanning the entire amino acid sequence of pep M5 were used to detect epitopes cross-reactive with heart tissue components other than myosin. Heart-cross-reactive pep M5 antibodies were affinity purified by absorption to and elution from purified sarcolemmal membranes. Only one of the synthetic peptides, SM5(164-197)C, inhibited reactivity of the affinity-purified antibodies with pep M5 by ELISA. SM5(164-197)C linked to KLH evoked both opsonic and heart-cross-reactive antibodies in rabbits. In addition to type 5, the immune sera opsonized M types 6, 18, 19, and 49 streptococci. The antisera reacted strongly with isolated cardiac sarcolemmal membranes by immunofluorescence. In Western blots of cardiac tissue, the anti-SM5(164-197)C reacted with a 40 kDa protein but not with myosin. The reaction was inhibited by pep M5 and SM5(164-197)C but not by any of the other peptides spanning pep M5. The cross-reactive anti-SM5(164-197)C affinity purified on sarcolemmal membranes opsonized types 5, 6, and 19 but not type 24 streptococci. These results indicate that SM5(164-197)C contains heart-cross-reactive, opsonic epitopes that are shared among heterologous serotypes of group A streptococci.

Amino Acid Sequence↗

Ultrastructure of the lung in falciparum malaria.

We describe a case of fatal falciparum malaria, with severe pulmonary insufficiency in the absence of fluid overload or cardiac failure. At autopsy the most striking change was a marked pulmonary interstitial edema. The endothelial cell was the most altered structure, showing marked cytoplasmic swelling which narrowed the capillary lumen. Monocytes were also found occupying the capillary lumen. The edematous interstitium also showed macrophages with endocytes and malarial pigment. There was no disseminated intravascular coagulation or other terminal complications. The patient's respiratory insufficiency seems not to have derived from the complications usually associated with the fatal malaria but from malaria-induced alveolar septal changes.

Endothelium↗

Histopathological and ultrastructural aspects of interstitial pneumonitis of experimental visceral leishmaniasis.

Golden hamsters inoculated with Leishmania donovani developed interstitial pneumonitis. Three developmental phases were characterized: exudative, cellular and fibrotic. From the sequence of events, a relationship between the types of cellular proliferation and the appearance of fibrosis could be established. The participation of septal interstitial cells with lipid inclusions (ICLI) in the process and their possible role in the development of fibrosis was demonstrated.

Animals↗

Interstitial pneumonitis in human visceral leishmaniasis.

The involvement of the lung in 13 cases of human visceral leishmaniasis was studied. Interstitial pneumonitis with mononuclear cells was found in 76.8% of the cases; 53.8% also had foci of septal fibrosis. Leishmania were seen within macrophages in 3 cases only. However, all 10 interstitial pneumonitis cases showed PAP-positive material using specific L. donovani (MHOM/BR/72/LD 46) antiserum. 3 cases with no interstitial pneumonitis were PAP-negative. A short discussion about clinical aspects and the course of the disease is presented.

Autopsy↗

Insulin-like growth factor-I induces phosphorylation in Leishmania (Leishmania) mexicana promastigotes and amastigotes.

Protein phosphorylation controls major steps of proliferation and differentiation in eukaryotic cells. However there are few studies done in protozoa particularly when being triggered by external stimuli. In this paper we have examined the tyrosine- and serine/threonine-phosphorylated proteins in both promastigote and amastigote-like forms of Leishmania (Leishmania) mexicana stimulated with insulin-like growth factor (IGF)-I. Stimulation with IGF-I induces major tyrosine phosphorylation of a 185-kDa protein in promastigotes and 60- and 40-kDa proteins in amastigotes. Analysis of total phosphorylation revealed additional sets of phosphorylated proteins: a 110-kDa protein band in promastigotes and two other proteins of 120 and 95 kDa in the amastigote-like forms. To further analyze the IGF-I-mediated response we compared it with the phosphorylation pattern obtained with a known inducer of protein kinase C, phorbol myristate acetate. This analysis showed overlapping phosphorylation of most of the proteins but mainly of the 185- and 110-kDa proteins in the promastigotes and the 95-, 60- and 40-kDa proteins in the amastigote-like forms. We thus conclude that there are phosphorylation-dependent pathways in Leishmania parasites induced by IGF-I that are stage-specific.

Animals↗