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Query: UMLS:C0344329 (collapse)
 28,634 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Passive immunization with monoclonal antibodies (MAbs) specific for the major capsular polysaccharide of Cryptococcus neoformans alters the course of murine cryptococcosis. During studies of passive immunization for treatment of murine cryptococcosis, we noted the occurrence of an acute, lethal toxicity. Toxicity was characterized by scratching, lethargy, respiratory distress, collapse, and death within 20 to 60 min after injection of antibody. The toxic effect was observed only in mice with a cryptococcal infection and was reduced or absent in the early and late stages of disease. The clinical course and histopathology were consistent with those for shock. There was considerable variation between mouse strains in susceptibility to toxicity. Swiss Webster mice from the Charles River colony were most susceptible, followed by C3H/He, BALB/c, and C57BL/6 mice. DBA/2 mice and Swiss Webster mice from the Simonsen colony were resistant. Acute toxicity was mimicked by injection of preformed complexes of MAb and purified polysaccharide. The toxic effect was also produced by injection of MAbs into mice that were preloaded with polysaccharide. The toxic effect was not blocked by treatment of mice with chloropheniramine or anti-tumor necrosis factor alpha antibodies or by depletion of complement components via pretreatment with cobra venom factor. Toxicity was reduced by treatment of mice with high doses of epinephrine, dexamethasone, or chlorpromazine. Finally, the toxic effect was completely blocked by treatment of mice with the platelet-activating factor antagonist WEB 2170 BS or by pretreatment of mice with the liposome-encapsulated drug dichloromethylene diphosphonate, a procedure which depletes macrophages from the spleen and liver.
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PMID:Acute lethal toxicity following passive immunization for treatment of murine cryptococcosis. 912 64

Mouse strains have been divided into 'tasters' and 'non-tasters' based on their relatively high and low preference, respectively, for low concentrations of sucrose and saccharin. These phenotypic differences appear to be due to a polymorphism in the gene at the Sac locus encoding for the T1R3 taste receptor selectively affecting the functionality of the T1R2+3 heterodimer. To psychophysically examine whether these phenotypes are due to sensory sensitivity as opposed to hedonic responsiveness, we measured taste signal detection of sucrose, glucose, and glycine by Sac taster (C57BL/6J and SWR/J) and non-taster (129P3/J and DBA/2J) strains in an operant conditioning paradigm using a gustometer. The taster mice had lower detection thresholds for sucrose and glucose compared with the non-taster mice. The detection thresholds corresponded well with reported responsiveness to low concentrations of these sugars in two-bottle intake tests suggesting that the Sac taster phenotype has a sensory basis and is not simply a matter of strain differences in the hedonic evaluation of weak intensities of the stimuli. Taster status did not entirely account for the strain differences in detection thresholds for glycine, a 'sweet' tasting amino acid. Collapsed across strains, detection thresholds for sucrose and glucose were highly correlated with each other (r = 0.81), but only modestly correlated with those for glycine (r < or = 0.43). This suggests that stimulus processing of glycine in the perithreshold intensity domain can be dissociated from that of sucrose and glucose. The mechanism underlying this difference may be related to the ability of glycine to bind with the T1R1+3 heterodimer.
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PMID:Stimulus processing of glycine is dissociable from that of sucrose and glucose based on behaviorally measured taste signal detection in Sac 'taster' and 'non-taster' mice. 1533 88

The etiology of primary open angle glaucoma, a leading cause of age-related blindness, remains poorly defined, although elevated intraocular pressure (IOP) contributes to the disease progression. To better understand the mechanisms causing elevated IOP from aqueous humor circulation, we pursued proteomic analyses of trabecular meshwork (TM) from glaucoma and age-matched control donors. These analyses demonstrated that Cochlin, a protein associated with deafness disorder DFNA9, is present in glaucomatous but absent in normal TM. Cochlin was also detected in TM from the glaucomatous DBA/2J mouse preceding elevated IOP but found to be absent in three other mouse lines that do not develop elevated IOP. Histochemical analyses revealed co-deposits of Cochlin and mucopolysaccharide in human TM around Schlemm's canal, similar to that observed in the cochlea in DFNA9 deafness. Purified Cochlin was found to aggregate after sheer stress and to induce the aggregation of TM cells in vitro. Age-dependent in vivo increases in Cochlin were observed in glaucomatous TM, concomitant with a decrease in type II collagen, suggesting that Cochlin may disrupt the TM architecture and render components like collagen more susceptible to degradation and collapse. Overall, these observations suggest that Cochlin contributes to elevated IOP in primary open angle glaucoma through altered interactions within the TM extracellular matrix, resulting in cell aggregation, mucopolysaccharide deposition, and significant obstruction of the aqueous humor circulation.
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PMID:Proteomics reveal Cochlin deposits associated with glaucomatous trabecular meshwork. 1557 65

Bacillus anthracis lethal toxin (LT) causes vascular collapse and high lethality in BALB/cJ mice, intermediate lethality in C57BL/6J mice, and no lethality in DBA/2J mice. We found that adrenalectomized (ADX) mice of all three strains had increased susceptibility to LT. The increased susceptibility of ADX-DBA/2J mice was not accompanied by changes in their macrophage sensitivity or cytokine response to LT. DBA/2J mice showed no change in serum corticosteroid levels in response to LT injection, while BALB/cJ mice showed a fivefold increase in serum corticosterone. However, LT inhibited dexamethasone (DEX)-induced glucocorticoid receptor gene activation to similar extents in all three strains. DEX treatment did not rescue ADX mice from LT-mediated mortality. Surprisingly, oral DEX treatment also sensitized adrenally intact DBA/2J mice to LT lethality at all doses tested and also exacerbated LT-mediated pathogenesis and mortality in BALB/cJ mice. Aldosterone did not protect ADX mice from toxin challenge. These results indicate that susceptibility to anthrax LT in mice depends on a fine but easily perturbed balance of endocrine functions. Thus, the potentially detrimental consequences of steroid therapy for anthrax must be considered in treatment protocols for this disease.
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PMID:Endocrine perturbation increases susceptibility of mice to anthrax lethal toxin. 1597 15

The role of ribosome biogenesis in erythroid development is supported by the recognition of erythroid defects in ribosomopathies in both Diamond-Blackfan anemia and 5q- syndrome. Whether ribosome biogenesis exerts a regulatory function on normal erythroid development is still unknown. In the present study, a detailed characterization of ribosome biogenesis dynamics during human and murine erythropoiesis shows that ribosome biogenesis is abruptly interrupted by the drop of rDNA transcription and the collapse of ribosomal protein neo-synthesis. Its premature arrest by RNA polI inhibitor, CX-5461 targets the proliferation of immature erythroblasts. We also show that p53 is activated spontaneously or in response to CX-5461 concomitantly to ribosome biogenesis arrest, and drives a transcriptional program in which genes involved in cell cycle arrest, negative regulation of apoptosis and DNA damage response were upregulated. RNA polI transcriptional stress results in nucleolar disruption and activation of ATR-CHK1-p53 pathway. Our results imply that the timing of ribosome biogenesis extinction and p53 activation are crucial for erythroid development. In ribosomopathies in which ribosome availability is altered by unbalanced production of ribosomal proteins, the threshold of ribosome biogenesis down-regulation could be prematurely reached and together with pathological p53 activation prevents a normal expansion of erythroid progenitors.
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PMID:p53 activation during ribosome biogenesis regulates normal erythroid differentiation. 3281 41