Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mycobacterium bovis var. BCG was grown under iron-deficient conditions in the presence and absence of 1% Tween 80. Mycobactin, the iron iron ionophore of mycobacteria, was found solely within the bacteria grown in the absence of Tween, but low concentrations (0.75 mug/ml) of it appeared in the medium in the presence of the surfactant. Both types of medium contain agents, named exochelins, which could solubilize iron. 55Fe added to spent culture media was recovered only chelated to these compounds. Two exochelins were detected, isolated, and purified. Neither were precursors or breakdown products of mycobactin. In the desferri-form, exochelin MB-2, the major component, reversed the inhibitory effect of serum on the growth of BCG, and in their ferri-forms exochelins MB-1, MB-2, and MS (from Mycobacterium smegmatis) stimulated the growth of their producing organism in the presence of serum. Exochelin MB-2 could physically remove iron from ferritin, and BCG used ferritin as a source of iron during growth even when ferritin was separated from the bacteria by a dialysis membrane. As solutions of the exochelins were freely dialyzable, whereas solutions of mycobactin, even in Tween, were not, only exochelin could have been active in this experiment. The exochelins are proposed as the functional extracellular iron-binding agents of BCG and other mycobacteria, the role of mycobactin being confined to that of a cell wall iron transporter.
 ...
PMID:Extracellular iron acquisition by mycobacteria: role of the exochelins and evidence against the participation of mycobactin. 110 22

Excessive hemosiderin-laden perivascular macrophages have been described in the brains of patients with the acquired immunodeficiency syndrome (AIDS) who underwent autopsy; its meaning remains unclear. In the brains of 53 patients with AIDS who consecutively underwent autopsy, we quantified the abnormality, elucidated its relationship to the pathologic features of AIDS, and asked if there was some relationship to endogenous iron storage and transport proteins in brain macrophages and microglia. The number of perivascular siderotic macrophages was significantly increased in patients with AIDS compared with age-matched control subjects. Macrophage siderosis was strongly correlated with the presence of disseminated mycobacterial infection and vacuolar myelopathy at autopsy; a generalized wasting (cachexia) also was related significantly. Many other pathologic abnormalities were not related, including putative human immunodeficiency virus-specific neuropathologic changes such as multinucleated cells and myelin pallor. Activated macrophages and microglial cells in the central nervous system had dense intracytoplasmic accumulation of ferritin (iron storage protein) in AIDS and non-AIDS patients. These results suggest that siderosis of cerebral macrophages is related to an ill-defined nonspecific systemic imbalance associated with the breakdown of abundant stores of endogenous intracellular ferritin. Understanding chronic "secondary" effects of human immunodeficiency virus type 1 infection will become increasingly important as improved survival in patients with AIDS is realized.
 ...
PMID:Siderotic cerebral macrophages in the acquired immunodeficiency syndrome. 158 Jul 55

The weak base ammonium chloride has been previously reported to inhibit lysosomal movements and phagosome-lysosome (Ph-L) fusion in cultured mouse macrophages (M phi), thus reducing delivery, to an intraphagosomal infection, of endocytosed solutes that have concentrated in secondary lysosomes. We have now addressed the question, whether NH4Cl might affect any direct interaction (if it exists) between such infection phagosomes and earlier, nonlysosomal compartments of the endocytic pathway, i.e., solute-containing endosomes. The phagosomes studied were formed after ingestion of the mouse pathogen Mycobacterium microti and the nonpathogenic yeast Saccharomyces cerevisiae; and the endosomes were formed after nonreceptor-mediated endocytosis of electronopaque and fluorescent soluble markers. By electron microscopy, survey of the cell profiles of M phi that had been treated with 10 mM NH4Cl so that Ph-L fusion was prevented, and that displayed many ferritin-labeled endosomes, revealed numerous examples of the fusion of electronlucent endosomes, revealed numerous examples of the fusion of electronlucent vesicles with phagosomes, whether containing M. microti bacilli or S. cerevisiae yeasts. Fusion was recognized by transfer of label and by morphological evidence of fusion in progress. The fusing vesicles were classed as endosomes, not NH4Cl-lysosomes, by their appearance and provenance, and because lysosome participation was excluded by the concurrent, NH4Cl-caused block of Ph-L fusion and associated lysosomal stasis. No evidence of such phagosome-endosome (Ph-E) fusion was observed in profiles from M phi treated with chloroquine, nor in those from normal, untreated M phi. NH4Cl-treated living M phi that had ingested yeasts at 37 degrees C, followed by endocytosis of lucifer yellow at 17 degrees C (to accumulate labeled endosomes and postpone label passing to lysosomes), were then restored to 37 degrees C. Fluorescence microscopy showed that as many as half of the yeast phagosomes (previously unlabeled) rapidly became colored. We inferred that this transfer was from endosomes (by Ph-E fusion) because Ph-L passage was blocked (by the NH4Cl). We conclude that NH4Cl induces Ph-E fusion at the same time as it suppressed Ph-L fusion. We discuss the mechanisms of these concurrent effects and suggest that they are independent; and we consider the implications of NH4Cl opening a direct route for endocytosed molecules to reach an intraphagosomal infection without involving lysosomes.
 ...
PMID:Ammonium chloride, an inhibitor of phagosome-lysosome fusion in macrophages, concurrently induces phagosome-endosome fusion, and opens a novel pathway: studies of a pathogenic mycobacterium and a nonpathogenic yeast. 191 41

We examined 19 patients (17 men) with human immunodeficiency virus (HIV) infection and gastrointestinal symptoms to determine whether those symptoms were due to either a gastrointestinal tract infection or a defect in mucosal absorption because of an enteropathy. The erythrocyte folate and serum vitamin B12 levels were within normal limits in all of the patients. The serum ferritin level was elevated in 12. The xylose absorption test results were abnormal in 8 of the 13 patients able to complete the study. None of the duodenal aspirates yielded a pathogen. Light microscopy revealed nonspecific lymphocytic inflammation without infection in the stomach (in seven patients), the esophagus (in five), the duodenum (in two) and the rectum (in two). However, biopsy specimens were positive for Candida albicans in the esophagus (four patients), cytomegalovirus in the esophagus (one) and the rectum (two), Helicobacter pylori in the antrum (two), Treponema infection in the rectum (two) and Mycobacterium avium-intracellulare in the small intestine (one). Only three patients had a normal series of biopsy specimens. All of the patients had similar ultrastructural changes at the epithelial-stromal junction of the antral glands and in the intestinal crypts. We conclude that abnormal biochemical and endoscopic findings are common in HIV-positive patients with gastrointestinal symptoms. Defects in carbohydrate absorption and ultrastructural changes may be responsible for some aspects of HIV enteropathy.
 ...
PMID:Gastrointestinal function and structure in HIV-positive patients. 220 20

We analyzed the histopathologic findings of arthritis in 3 rat models: adjuvant arthritis induced by active immunization to Mycobacterium tuberculosis (MT) antigens, arthritis produced by passive transfer of an intrinsically arthritogenic line of anti-MT T lymphocytes, and bystander arthritis produced by intraarticular injection of a foreign antigen, ovalbumin, into rats with T lymphocyte line cells specific for the ovalbumin antigen. The histopathology of the tibiotarsal and knee joints was studied by light microscopy and the articular surface of the cartilage by electron microscopy after labeling with cationized ferritin. The lesions in the 3 models of arthritis were compared. In active adjuvant arthritis, inflammatory lesions and cartilage destruction were found as early as 9 days after immunization, and persisted for as long as 11 months. Similar, but somewhat milder, lesions were found in arthritis produced by transfer of anti-MT T lymphocytes. Inflammatory signs were present at 4 days, when there was no evidence of joint edema. Severe inflammatory lesions were found in arthritis induced by transfer of anti-ovalbumin T lymphocytes that was followed by ovalbumin injection into the knee. Pathologic changes were found to be similar in all 3 models. Thus, the changes could be attributed to the action of T lymphocytes, irrespective of whether the target antigen was intrinsic to the joint.
 ...
PMID:Histopathology of arthritis induced in rats by active immunization to mycobacterial antigens or by systemic transfer of T lymphocyte lines. A light and electron microscopic study of the articular surface using cationized ferritin. 244 10

We studied the in vivo killing and degradation of Mycobacterium aurum, a nonpathogenic, acid-fast bacillus, within macrophages after inoculation into the peritoneal cavity of CD-1 mice. The degradative process could be divided in five successive steps that were characterized on ultrastructural and cytochemical grounds and the relative contributions of which were determined by quantitative electron microscopy of samples taken at different times. The main ultrastructural alterations observed during the degradative process were ribosome disaggregation, coagulation of the cytoplasmic matrix, and change in the membrane profile from asymmetric to symmetric, with loss of the polysaccharide components from the outer layer, followed by membrane solubilization and intracellular clearing, followed by digestion of the innermost (peptidoglycan) layer of the cell wall, and at the end of the process, disorganization and collapse of the remaining layers of the cell wall. The correlation between viability and morphology indicated that the first ultrastructural signs of viability loss are cytoplasmic coagulation, change in the membrane geometry, and disappearance of ribosomes. The labeling of lysosomes of peritoneal macrophages with ferritin or by the cytochemical demonstration of inorganic trimetaphosphatase showed that fusion of lysosomes with phagosomes containing mycobacteria occurs in the phagocytes in the mouse peritoneal cavity and is already extensive as soon as 1 h after the inoculation of the bacilli.
 ...
PMID:In vivo killing and degradation of Mycobacterium aurum within mouse peritoneal macrophages. 362 91

Granulomatous lesions of bovine paratuberculosis contained ferritin, lactoferrin, and a small amount of transferrin, as demonstrated by the immunohistochemical method. Macrophages in the normal bovine ileum did not contain lactoferrin and transferrin; however, ferritin was found in individual macrophages of Peyer's patches. These results may help elucidate the relationship between intracellular growth of Mycobacterium paratuberculosis and the presence of iron-binding proteins in the granulomas.
 ...
PMID:Immunohistochemical distribution of ferritin, lactoferrin, and transferrin in granulomas of bovine paratuberculosis. 369 98

Strains H37Ra and H37Rv, attenuated and virulent variants, respectively, of the original human strain H37 of Mycobacterium tuberculosis, were used to infect cultures of mouse peritoneal macrophages. Bacterial viability of each strain was assessed over a 2-week period, and the cellular response to H37Ra during the first week was observed using electron microscopy. Prelabeling of secondary lysosomes with ferritin was used to facilitate the estimation of fusion of the lysosomes with phagosomes containing the bacteria. Streptomycin was excluded from the medium of cell cultures infected with H37Ra. The intracellular viability of strain H37Rv (in the presence of streptomycin) showed a lag during the first week after infection and then rose progressively to a mean figure seven times the starting level. In contrast, the viability of strain H37Ra declined, on the average, to one-fifth of the starting level during the first week; moreover, this decline occurred in the absence of antibiotics. In the second week a variable rise in the viable count took place, usually regaining the starting level. Electron microscopy of macrophages infected with H37Ra revealed a higher proportion of "damaged" bacteria 5 days after infection than at 1 day, in keeping with the decline in viability. Phagosomes containing these "damaged" (and presumed dead) organisms showed virtually universal fusion with prelabeled lysosomes. Phagosomes containing "intact" bacteria of this strain showed a prevalence of fusion varying from 38 to 56%, somewhat higher than the level previously reported for "intact" organisms of H37Rv. Nevertheless, the lysosome-phagosome fusion response to "intact" H37Ra was still far less extensive than that observed previously towards "intact" M. lepraemurium (around 90%). In conclusion, a difference between the macrophage lysosome-phagosome fusion response towards viable organisms of strain H37Ra and to the virulent strain H37Rv was observed, but was not pronounced, and the present findings are in keeping with the increasingly held view that H37Ra should be regarded as a low-virulence or attenuated strain rather than truly avirulent.
 ...
PMID:Strain virulence and the lysosomal response in macrophages infected with Mycobacterium tuberculosis. 421 80

Mycobacterium lepraemurium and M. microti (causal agent of vole tuberculosis) were isolated from tissues of experimentally infected mice and used to infect normal mouse peritoneal macrophage cultures. The cellular response to these bacteria up to 4 days after infection was studied quantitatively by electron microscopy. Prelabeling with ferritin was used to facilitate observation of fusion between secondary lysosomes in the cells and phagosomes containing the bacteria. All bacteria were intraphagosomal, and a high proportion of them was morphologically "intact." Nearly all phagosomes containing morphologically damaged (presumed nonviable) bacteria also contained ferritin, having fused with secondary lysosomes. Fusion of lysosomes had also occurred with most phagosomes containing intact M. lepraemurium but was infrequent with phagosomes containing intact M. microti. This tendency of multiplying mycobacteria of the tubercle type to avoid contact with lysosomal contents has already been reported for M. tuberculosis strain H37Rv. The different intracellular circumstances of the parasites may reflect different means of intracellular survival.
 ...
PMID:Ultrastructural study of the behavior of macrophages toward parasitic mycobacteria. 462 54

Onset and nature of ultrastructural changes in endoneurial vasa nervorum during the pathogenesis of leprosy neuropathy and possibly associated alterations in the "blood-nerve barrier" were investigated, together with perineurial barrier functioning, in mice infected 20-28 months previously with Mycobacterium leprae and in (ageing) non-infected mice. Barriers were tested by i.v. administration of markers (Trypan blue and ferritin) 1-4 days before killing the mice. Twenty-eight months after infection, histopathology of sciatic nerves was comparable to that seen in sensory nerves in clinically early human (borderline-) lepromatous leprosy. Schwann cells and endoneurial macrophages were bacillated, endothelia of endoneurial vessels not, and the perineurium rarely. Many infected mice and all (ageing) controls possessed ultrastructurally and functionally normal endoneurial vessels. Their continuous endothelium with close junctions had prevented marker passage, even when surrounding endoneurial tissue cells were quite heavily bacillated. The perineurium was also normal. By contrast, in infected mice showing hind limb paralysis serious histopathologic involvement and large globi of bacilli intrafascicularly in sciatic nerves, endoneurial blood vessels were abnormal. Open endothelial junctions, extreme attenuation, fenestrations, and luminal protrusions were all features comparable to neural microangiopathy encountered in leprosy patients (Boddingius 1977a, b). The "blood-nerve barrier" clearly had become defective allowing excessive exudation of Trypan blue and ferritin, via four pathways from the vessel lumen, deep into surrounding endoneurial tissues but halted by a normal perineurial barrier. Markers in such "blue" nerves were not found in bacillated or non-bacillated Schwann cells, thus denying significant phagocytotic and lysosomal activities of Schwann cells at this stage of neuropathy. Possible implications of barrier performances for anti-leprosy drug treatment of patients are discussed.
 ...
PMID:Ultrastructural and histophysiological studies on the blood-nerve barrier and perineurial barrier in leprosy neuropathy. 609 79


1 2 3 4 5 Next >>