Biomedical subjects
C E Corbett
Publications and source records attributed to C E Corbett.
Characterization of the receptor for insulin-like growth factor on Leishmania promastigotes.
Insulin-like growth factor (IGF)-I constitutively present in the skin is one of the first growth factors that Leishmania parasites encounter after transmission to the vertebrate host. We have previously shown that IGF-I is a potent growth-promoting factor for Leishmania parasites. IGF-I binds specifically to a single-site putative receptor at the parasite membrane, triggering a cascade of phosphorylation reactions. In the present article we characterize the receptor for IGF-I on Leishmania (Leishmania) mexicana promastigotes. The receptor is a monomeric glycoprotein with a molecular mass of 65 kDa and is antigenically related to the alpha chain of human type 1 IGF-I receptor. Upon IGF-I stimulation the receptor undergoes autophosphorylation on tyrosine residues with activation of its signaling pathway. Activation of the IGF-I receptor also leads to phosphorylation of an 185-kDa molecule that is homologous to the substrate of the insulin receptor present in human cells, the insulin receptor substrate 1 (IRS-1).
Cell-mediated immune response in megacolon from patients with chronic Chagas' disease.
PURPOSE: The mechanisms that control chronic infection in vivo and the immunologic mechanisms involved in the pathogenesis of chagasic megacolon are not completely characterized. Although autoimmunity may play a role in the pathogenesis of Chagas' disease, recent studies, both in mice and in humans, suggest a positive association of tissue parasitism, inflammation, and severity of lesions. The aim of this study was to evaluate the role of inflammatory cells and the subclasses of lymphocytes involved in neuropathic lesions in the colon of patients who underwent resection for advanced megacolon. METHODS: Specimens from 23 patients were selected based on histopathologic analysis. Paraffin-embedded tissue blocks were sectioned and evaluated by immunohistochemistry for cluster of differentiation 3, cluster of differentiation 8, cluster of differentiation 20, and natural killer cell antibodies by an avidin-biotin peroxidase method. RESULTS: Almost all myenteric plexuses were damaged, characterized by degenerative changes, necrosis of ganglion cells, and inflammatory response. Mild lymphocytic infiltration around degenerated and normal ganglion cells was observed in all cases. Collagen fibers and mononuclear cells surrounded some ganglion cells. Most of the inflammatory cells were lymphocytes, identified as cluster of differentiation 3-positive cells. Cluster of differentiation 8-positive lymphocytes were associated with degenerated ganglion cells. Natural killer cell antibodies were detected in a lower proportion of cells and were distributed between muscle layers or in proximity to the myenteric plexus. All these findings were also observed in the submucosal plexus. Cluster of differentiation 20-positive lymphocytes were not present in muscle layers or in the vicinity of either plexus. CONCLUSION: Pathogenesis of the megacolon is based on a continuous process of ganglion cell damage with participation of T lymphocytes expressing cluster of differentiation 8 and natural killer cell membrane antigens. B lymphocytes do not take part in the chronic inflammatory reaction.
Detection of specific antibody isotypes and subtypes before and after treatment of American visceral leishmaniasis.
Sera from patients with American visceral leishmaniasis (AVL) were studied before and after treatment based on their antibody isotypes and subtypes. The study was comprised of 33 Brazilian patients with well-defined diagnosis of AVL and 39 clinically healthy individuals. Antileishmanial antibody isotypes and subtypes were observed in almost all patients, except IgA that was detected in about 63% of them. The sensitivity and specificity of the immunofluorescence assay in the detection of antibody isotypes (IgG and IgM) and subtypes (IgG1, IgG2, IgG3, and IgG4) were high with no statistical difference, ranging from 0.937 to 1.000 and from 0.954 to 1.000, respectively. All IgG antibodies and its subtypes had their levels reduced after treatment. However, the IgG4 had an early decay and its conversion to negative was significantly high in children. Moreover, the profile of IgG4 before treatment corresponded to a unimodal curve that shifted to a patent bimodal curve after treatment, indicative of therapeutic success. Thus, the IgG4 shows to be a suitable immunological marker for the assessment of chemotherapy in AVL patients or communities. Our findings suggest that IgG4 correlates with IL-4 that also decreases after therapy.
Insulin-like growth factor (IGF)-I affects parasite growth and host cell migration in experimental cutaneous leishmaniasis.
While the control or progression of leishmaniasis depends on host immune responses, the initial inflammatory process represents a key event. This process involves the participation of several cytokines and growth factors induced during inflammation as well as factors already present at the site of infection such as insulin-like growth factor (IGF)-I. We have previously demonstrated a potential role for IGF-I in experimental cutaneous leishmaniasis based on the significant increase in lesion size seen in mice injected with Leishmania promastigotes preactivated with IGF-I. In the present study we show that preactivation of Leishmania (Leishmania) amazonensis promastigotes with IGF-I induces an increase in the actual number of parasites at the lesion site from seven days postinfection, in addition to a more intense inflammatory infiltrate. There was a higher numerical density of polymorphonuclear neutrophils from 3 to 24 h, and of mononuclear cells from 48 h of infection onward. A higher density of polymorphonuclear neutrophils and mononuclear cells harboring parasites was also observed. The most important observation, however, was that more parasites per cell were present, revealing that IGF-I appears to favour parasite growth within the macrophages. These results strongly suggest an important role for IGF-I in the development of cutaneous leishmaniasis, where it influences both the inflammatory process and parasite growth.
Sternal osteomyelitis caused by mycobacterium tuberculosis: case report and review of the literature.
Sternal osteomyelitis caused by Mycobacterium tuberculosis is rare; since the advent of modern antituberculous therapy, a limited number of detailed cases have been reported. Most patients were relatively young, free of underlying disease, and lived in a country in which tuberculosis is endemic. The disease presented indolently with sternal pain and swelling. Extrasternal disease is detectable in less than half. Diagnosis was based on histologic examination of infected tissues and mycobacterial cultures. Most patients recovered after surgical debridement and combination drug therapy. Tuberculous sternal osteomyelitis should be considered in patients with sternal pain and swelling.
Leishmania (Viannia) panamensis/Leishmania (Leishmania) amazonensis--a warning.
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The role of natural killer cells in the early period of infection in murine cutaneous leishmaniasis.
In order to study the role of natural killer (NK) cells during the early period of Leishmania infection, BALB/c mice were selectively and permanently depleted of NK cells by injection with 90Sr and subsequently infected with Leishmania (Leishmania) amazonensis (HSJD-1 strain). 90Sr is known to selectively deplete NK cells, leaving an intact T- and B-cell compartment and preserving the ability to produce both interferon alpha and IL-2. This method of depletion has advantages when compared with depletion using anti-NK cell monoclonal antibodies because the effect is permanent and neither activates complement nor provokes massive cell death. In the present study, after one month of treatment with 90Sr, the depletion of NK cells was shown by a more than ten-fold reduction in the cytotoxic activity of these cells: 2 x 10(6) spleen cells from NK-depleted animals were required to reach the same specific lysis of target cells effected by 0.15 x 10(6) spleen cells from normal control animals. The histopathology of the skin lesion at 7 days after Leishmania infection showed more parasites in the NK cell-depleted group. This observation further strengthens a direct role of NK cells during the early period of Leishmania infection.
Insulin-like growth factor I is a growth-promoting factor for Leishmania promastigotes and amastigotes.
Leishmaniases are diseases caused by protozoa of the genus Leishmania that affect more than 20 million people in the world. The initial phase of the infection is fundamental for either the progression or control of the disease. The Leishmania parasites are injected in the skin as promastigotes and then, after been phagocytized by the host macrophages, rapidly transform into amastigotes. In this phase different nonspecific cellular and humoral elements participate. We have shown previously that insulin-like growth factor (IGF)-I that is constitutively present in the skin induces growth of Leishmania promastigotes. In the present paper we show further evidence for the importance of this factor: (i) IGF-I also can induce a growth response in Leishmania (Leishmania) mexicana amastigotes; (ii) IGF-I binds specifically to a putative single-site receptor on both promastigotes and amastigotes; (iii) IGF-I induces a rapid tyrosine phosphorylation of parasite proteins with different molecular mass in promastigotes and amastigotes of L. (L.) mexicana; and, finally, (iv) the cutaneous lesion in the mice when challenged by IGF-I-preactivated Leishmania (Viannia) panamensis is increased significantly because of inflammatory process and growth of parasites. We thus suggest that IGF-I is another important host factor participating in the Leishmania-host interplay in the early stage during the establishment of the infection and presumably also in the later stages.
Epidemiology of ventilator-acquired pneumonia based on protected bronchoscopic sampling.
We performed a prospective observational cohort study of the epidemiology and etiology of nosocomial pneumonia in 358 medical ICU patients in two university-affiliated hospitals. Protected bronchoscopic techniques (protected specimen brush and bronchoalveolar lavage) were used for diagnosis to minimize misclassification. Risk factors for ventilator-associated pneumonia were identified using multiple logistic regression analysis. Twenty-eight cases of pneumonia occurred in 358 patients for a cumulative incidence of 7.8% and incidence rates of 12.5 cases per 1, 000 patient days and 20.5 cases per 1,000 ventilator days. Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa, and Hemophilus species made up 65% of isolates from the lower respiratory tract, whereas only 12.5% of isolates were enteric gram-negative bacilli. Daily surveillance cultures of the nares, oropharynx, trachea, and stomach demonstrated that tracheal colonization preceded ventilator-associated pneumonia in 93.5%, whereas gastric colonization preceded tracheal colonization for only four of 31 (13%) eventual pathogens. By multiple logistic regression, independent risk factors for ventilator- associated pneumonia were admission serum albumin <= 2.2 g/dl (odds ratio [OR] 5.9; 95% confidence interval [CI] 2.0-17.6; p = 0.0013), maximum positive end-expiratory pressure >= 7.5 cm H2O (OR, 4.6; 95% CI, 1.4 to 15.1; p = 0.012), absence of antibiotic therapy (OR, 6.7; 95% CI, 1.8 to 25.3; p = 0.0054), colonization of the upper respiratory tract by respiratory gram-negative bacilli (OR, 3.4; 95% CI, 1.1 to 10.1; p = 0.028), pack-years of smoking (OR, 2.3 for 50 pack-years; 95% CI, 1. 2 to 4.2; p = 0.012), and duration of mechanical ventilation (OR, 3. 4 for 14 d; 95% CI, 1.5 to 7.8; p = 0.0044). Several of these risk factors for ventilator-associated pneumonia appear amenable to intervention.
Colon polyps in Schistosoma haematobium schistosomiasis.
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Insulin-like growth factor-1 is a growth promoting factor for Leishmania promastigotes.
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The role of complement in the acute inflammatory process in the skin and in host-parasite interaction in hamsters inoculated with Leishmania (Leishmania) chagasi.
Tecidual reaction at the inoculation site of L. (L.)chagasi promastigotes in hamsters depleted and non-depleted of complement was studied within 2, 6, 12, 24, 48 and 72 hours of infection. The inflammatory reaction was characterized by early predominance of polymorphonuclear cells (PMN) at 2, 6 and 12 hours of infection, mixed infiltrate of PMN and mononuclear cells (MN) at 24 hours, followed by predominance of MN at 48 and 72 hours after infection. The group depleted of complement showed a higher number of PMN at 2 hours and lower numbers of MN at 72 hours after infection (P < 0.0001). In the depleted group the phagocytosis by PMN was lower at 2 and 24 hours and by MN was lower at 24, 48 and 72 hours after infection. Electron microscopy showed extracellular intact and degenerated parasites, and lysed intracellular parasites, in PMN; and, rarely, preserved intracellular parasites in MN at 2, 6 and 12 hours after infection. The groups examined at 24, 48 and 72 hours of infection showed only cellular and parasite debris in mononuclear inflammatory cells. C3b deposits were detected by immunofluorescence in the interstitium and in the cytoplasm of inflammatory cells in non-depleted group at 2, 6 and 12 hours of infection. No immunoglobulin was detected in either group. Visceralization was detected 240 days after infection. The complement system has an important role in the inflammatory reaction and phagocytosis. The ultrastructural findings showed that the escape of the parasite probably occurs soon after inoculation.
Case report: empyema with hydropneumothorax and bacteremia caused by Clostridium sporogenes.
Clostridia species are rare causes of pleuropulmonary infections. This report describes an immunocompromised patient who had a renal transplant, had multiple risk factors for anaerobic pleuropulmonary infection, and developed an acute empyema with hydropneumothorax that was associated with Clostridium sporogenes bacteremia. Therapy included antibiotics and surgical drainage of the empyema. Species identification of clostridia can usually be limited to whether the species is perfringens or nonperfringens because the majority of clinically significant clostridial infections are caused by Clostridium perfringens. Increased cost and consumption of time limits the usefulness of species identification of nonperfringens species. However, the identification of clostridia species that are known to be associated with specific underlying diseases or known to have variable and unpredictable antibiotic susceptibilities may affect patient management. The role of the laboratory in identifying such anaerobic isolates is discussed.
Adenovirus parotitis in patients with AIDS.
Adenoviruses are well documented as opportunistic pathogens in patients with immunocompromising conditions, including human immunodeficiency virus (HIV) infection. We recently diagnosed adenovirus infection of the parotid gland in two patients with AIDS. Viral cultures and electron microscopic examinations of parotid tissue were positive in both cases. Adenovirus infection should be considered in the differential diagnosis of parotid swelling in HIV-infected patients.
Regression of diffuse intralobular liver fibrosis associated with visceral leishmaniasis.
Diffuse intralobular fibrosis of the liver is rare in cases of New World visceral leishmaniasis. A patient with this disease from a newly endemic area in the northernmost area of the Brazilian Amazon region was studied. Hypertrophy and hyperplasia of the phagocytic mononuclear cell system were observed, with parasitism and Disse's space fibrosis diffusely involving the liver. This description is based on a biopsy carried out after seven days of treatment with Glucantime. Another biopsy performed almost two years later showed no fibrosis, no Kupffer cell hypertrophy and hyperplasia, and no parasitism. The mechanism of fibrosis and regression is discussed.
Histopathology of lymphoid organs in experimental leishmaniasis.
Hamsters (Mesocricetus auratus) were inoculated with L. (L.) chagasi and killed on days 7, 15, 30, 45 and 60 after infection. The lymphoid organs developed initial proliferation of the B lymphocyte zone with recovery by the 60th day group when pyroninophilic cells were prominent. The T lymphocyte area showed a progressive selective decrease of lymphocytes and cellular density with cellular pleomorphism including macrophages, plasma cells and reticular cells. The mean volume of the white pulp increased with the lymphoid follicle hyperplasia but returned to its initial level by day 60. The main red pulp change was marked hyperplasia of the phagocytic mononuclear cells containing parasites from the 30th day of infection onward. These changes are compatible with the humoral and cellular immunoresponse found in patients with visceral leishmaniasis (VL).
Haemobartonella-like microorganism infection in AIDS patients: ultrastructural pathology.
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