scholarly journals Piperacillin-Induced Immune Hemolytic Anemia in an Adult with Cystic Fibrosis

2010 ◽  
Vol 2010 ◽  
pp. 1-5 ◽  
Author(s):  
Mahesh Bandara ◽  
David B. Seder ◽  
George Garratty ◽  
Regina M. Leger ◽  
Jonathan B. Zuckerman
Keyword(s):  
Cystic Fibrosis ◽  
Hemolytic Anemia ◽  
Rare Complication ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Drug Induced ◽  
Immune Hemolytic Anemia ◽  
Antiglobulin Test ◽  
Cf Transmembrane Conductance Regulator ◽  
Positive Direct

We report a case of drug-induced immune hemolytic anemia (DIIHA) in an adult female with cystic fibrosis (CF), complicating routine treatment of a pulmonary exacerbation with intravenous piperacillin-tazobactam. Workup revealed a positive direct antiglobulin test (DAT) due to red blood cell (RBC)-bound IgG and C3 and piperacillin antibodies detectable in the patient's serum. The potential influence of CF transmembrane conductance regulator mutations on the severity of DIIHA is discussed. This report illustrates the importance of early identification of DIIHA, a rare complication of a commonly utilized medication in CF.

Association of positive direct antiglobulin test (DAT) with nonreactive eluate and drug-induced immune hemolytic anemia (DIHA)

2020 ◽  
pp. 103015
Author(s):  
Cristiane da Silva Rodrigues de Araújo ◽  
Bruna Accorsi Machado ◽  
Tamaris Fior ◽  
Júlia Mognon Mattiello ◽  
Mosseli Meinhart ◽  
...  
Keyword(s):  
Hemolytic Anemia ◽  
Direct Antiglobulin Test ◽  
Drug Induced ◽  
Immune Hemolytic Anemia ◽  
Antiglobulin Test ◽  
Positive Direct

scholarly journals ASSOCIATION OF POSITIVE DIRECT ANTIGLOBULIN TEST WITH NONREACTIVE ELUATE AND DRUG-INDUCED IMMUNE HEMOLYTIC ANEMIA

2020 ◽  
Vol 42 ◽  
pp. 382
Author(s):  
C.S.R. Araújo ◽  
J.M. Mattiello ◽  
L.L. Brittes ◽  
M. Meinhart ◽  
P. Bortolotti ◽  
...  
Keyword(s):  
Hemolytic Anemia ◽  
Direct Antiglobulin Test ◽  
Drug Induced ◽  
Immune Hemolytic Anemia ◽  
Antiglobulin Test ◽  
Positive Direct

scholarly journals Drug-induced immune hemolytic anemia (Direct Antiglobulin Test positive)

2013 ◽  
Vol 69 (2) ◽  
pp. 190-192 ◽  
Author(s):  
R.S. Sarkar ◽  
J. Philip ◽  
R.S. Mallhi ◽  
Neelesh Jain
Keyword(s):  
Hemolytic Anemia ◽  
Direct Antiglobulin Test ◽  
Drug Induced ◽  
Immune Hemolytic Anemia ◽  
Antiglobulin Test

scholarly journals VX-809 corrects folding defects in cystic fibrosis transmembrane conductance regulator protein through action on membrane-spanning domain 1

2013 ◽  
Vol 24 (19) ◽  
pp. 3016-3024 ◽  
Author(s):  
Hong Yu Ren ◽  
Diane E. Grove ◽  
Oxana De La Rosa ◽  
Scott A. Houck ◽  
Pattarawut Sopha ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Chloride Transport ◽  
Genetic Disorder ◽  
Missense Mutations ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Regulator Protein ◽  
Folding Defect ◽  
Membrane Spanning ◽  
Cf Transmembrane Conductance Regulator

Cystic fibrosis (CF) is a fatal genetic disorder associated with defective hydration of lung airways due to the loss of chloride transport through the CF transmembrane conductance regulator protein (CFTR). CFTR contains two membrane-spanning domains (MSDs), two nucleotide-binding domains (NBDs), and a regulatory domain, and its channel assembly requires multiple interdomain contacts. The most common CF-causing mutation, F508del, occurs in NBD1 and results in misfolding and premature degradation of F508del-CFTR. VX-809 is an investigational CFTR corrector that partially restores CFTR function in people who are homozygous for F508del-CFTR. To identify the folding defect(s) in F508del-CFTR that must be repaired to treat CF, we explored the mechanism of VX-809 action. VX-809 stabilized an N-terminal domain in CFTR that contains only MSD1 and efficaciously restored function to CFTR forms that have missense mutations in MSD1. The action of VX-809 on MSD1 appears to suppress folding defects in F508del-CFTR by enhancing interactions among the NBD1, MSD1, and MSD2 domains. The ability of VX-809 to correct F508del-CFTR is enhanced when combined with mutations that improve F508del-NBD1 interaction with MSD2. These data suggest that the use of VX-809 in combination with an additional CFTR corrector that suppresses folding defects downstream of MSD1 may further enhance CFTR function in people with F508del-CFTR.

scholarly journals Maturation and function of cystic fibrosis transmembrane conductance regulator variants bearing mutations in putative nucleotide-binding domains 1 and 2.

1991 ◽  
Vol 11 (8) ◽  
pp. 3886-3893 ◽  
Author(s):  
R J Gregory ◽  
D P Rich ◽  
S H Cheng ◽  
D W Souza ◽  
S Paul ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Amino Acid ◽  
Functional Activity ◽  
Nucleotide Binding ◽  
Missense Mutations ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Fluorescence Measurements ◽  
Cf Transmembrane Conductance Regulator ◽  
Altered Proteins

One feature of the mutations thus far found to be associated with the disease cystic fibrosis (CF) is that many of them are clustered within the first nucleotide-binding domain (NBD) of the CF transmembrane conductance regulator (CFTR). We sought to discover the molecular basis for this clustering by introducing into the two NBDs of CFTR mutations either mimicking amino acid changes associated with CF or altering residues within highly conserved motifs. Synthesis and maturation of the mutant CFTR were studied by transient expression in COS cells. The ability of the altered proteins to generate cyclic AMP-stimulated anion efflux was assessed by using 6-methoxy-N-(sulfopropyl) quinolinium (SPQ) fluorescence measurements in HeLa cells expressing mutated plasmids. The results show that (i) all CF-associated mutants, with one exception, lack functional activity as measured in the SPQ assay, (ii) mutations in NBD1 are more sensitive to the effects of the same amino acid change than are the corresponding mutations in NBD2, (iii) cells transfected with plasmids bearing CF-associated mutations commonly but not exclusively lack mature CFTR, (iv) NBD mutants lacking mature CFTR fail to activate Cl- channels, and (v) the glycosylation of CFTR, per se, is not required for CFTR function. We reason that the structure of NBD1 itself or of the surrounding domains renders it particularly sensitive to mutational changes. As a result, most NBD1 mutants, but only a few NBD2 mutants, fail to mature or lack functional activity. These findings are consistent with the observed uneven distribution of CFTR missense mutations between NBD1 and NBD2 of CF patients.

scholarly journals Dysfunctional cystic fibrosis transmembrane conductance regulator inhibits phagocytosis of apoptotic cells with proinflammatory consequences

2009 ◽  
Vol 297 (4) ◽  
pp. L677-L686 ◽  
Author(s):  
R. William Vandivier ◽  
Tiffany R. Richens ◽  
Sarah A. Horstmann ◽  
Aimee M. deCathelineau ◽  
Moumita Ghosh ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Rho Kinase ◽  
Negative Regulator ◽  
Apoptotic Cells ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Altered Expression ◽  
Proinflammatory Mediators ◽  
Downstream Effector ◽  
Cf Transmembrane Conductance Regulator

Cystic fibrosis (CF) is caused by mutated CF transmembrane conductance regulator (CFTR) and is characterized by robust airway inflammation and accumulation of apoptotic cells. Phagocytosis of apoptotic cells (efferocytosis) is a pivotal regulator of inflammation, because it prevents postapoptotic necrosis and actively suppresses release of a variety of proinflammatory mediators, including IL-8. Because CF is associated with accumulation of apoptotic cells, inappropriate levels of IL-8, and robust inflammation, we sought to determine whether CFTR deficiency specifically impairs efferocytosis and its regulation of inflammatory mediator release. Here we show that CFTR deficiency directly interferes with efferocytosis by airway epithelium, an effect that is not due to altered binding of apoptotic cells to epithelial cells or altered expression of efferocytosis receptors. In contrast, expression of RhoA, a known negative regulator of efferocytosis, is substantially increased in CFTR-deficient cells, and inhibitors of RhoA or its downstream effector Rho kinase normalize efferocytosis in these cells. Impaired efferocytosis appears to be mediated through an amiloride-sensitive ion channel, because amiloride restores phagocytic competency in CFTR-deficient cells. Finally, ineffective efferocytosis in CFTR-deficient cells appears to have proinflammatory consequences, because apoptotic cells enhance IL-8 release by these cells, but not by wild-type controls. Therefore, in CF, dysregulated efferocytosis may lead to accumulation of apoptotic cells and impaired regulation of the inflammatory response and, ultimately, may suggest a new therapeutic target.

scholarly journals Elevation of hepatic sulphotransferase activities in mice with resistance to cystic fibrosis

2002 ◽  
Vol 364 (1) ◽  
pp. 115-120 ◽  
Author(s):  
Josie L. FALANY ◽  
Heather GREER ◽  
Timea KOVACS ◽  
Eric J. SORSCHER ◽  
Charles N. FALANY
Keyword(s):  
Cystic Fibrosis ◽  
Mouse Liver ◽  
Northern Blot Analysis ◽  
Transmembrane Conductance Regulator ◽  
Male Mice ◽  
Transmembrane Conductance ◽  
Female Adult ◽  
Cf Transmembrane Conductance Regulator ◽  
Different Levels

The severity of intestinal disease in the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) (-/−) mice has been reported to co-segregate with gene loci which contain the genes for hydroxysteroid sulphotransferase (SULT). Because of the potential involvement of steroid hormones in CF, we investigated levels of steroid SULT activity in the livers of CFTR mice to determine whether the levels of SULT activity correlate with the occurrence or severity of CF. To elucidate the possible role of SULT activity in ameliorating the deleterious effects of CF in CFTR (-/−) mice, we determined the levels of phenol SULT (PST), hydroxysteroid SULT [dehydroepiandrosterone (DHEA)-ST] and oestrogen SULT (EST) activity in control CFTR (+/+), heterozygous CFTR (+/−) and homozygous CFTR (-/−) mice, which survive to adulthood. The level of PST activity was not significantly different between any of the groups of mice, regardless of sex or genotype. Although DHEA-ST activity was significantly higher in female mice than in male mice, there was no difference in DHEA-ST activity that could be correlated with genotype. In contrast with PST and DHEA-ST activities, we found that some male and all female adult CFTR (-/−) mice had elevated, dramatically different levels of EST from both CFTR (+/+) and CFTR (+/−) mice. Results from these SULT activity experiments were confirmed by Northern-blot analysis of mouse-liver RNA. Subsequent studies with preweanling mice revealed no differences in the levels of EST that could be correlated with genotype. Thus this study indicates that EST is elevated significantly in CFTR (-/−) mice which survive to adulthood and provides important biochemical information that EST levels may be protective in CF.

scholarly journals Cystic Fibrosis Transmembrane Conductance Regulator Modulator Therapy: A Review for the Otolaryngologist

2020 ◽  
Vol 34 (4) ◽  
pp. 573-580
Author(s):  
Saangyoung E. Lee ◽  
Zainab Farzal ◽  
M.Leigh Anne Daniels ◽  
Brian D. Thorp ◽  
Adam M. Zanation ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Respiratory Compromise ◽  
Basic Understanding ◽  
Epithelial Cultures ◽  
Cf Transmembrane Conductance Regulator ◽  
Cystic Fibrosis Transmembrane ◽  
Cftr Modulators ◽  
Initial Results

Background Cystic fibrosis (CF) is a genetic disease that may result in multiple systemic disorders and potentially fatal severe respiratory compromise. However, the advent of CF transmembrane conductance regulator (CFTR) modulators has changed the management of CF for patients with select mutations. Although clinical trials have highlighted increased pulmonary function and decreased exacerbations as a result of these novel therapies, their effect on the sinuses has not been well-described. Objective Our objective is to review the CFTR modulators to provide otolaryngologists, physicians who frequently care for patients with CF, a basic understanding of these drugs and their effects on chronic rhinosinusitis (CRS) in patients with CF. Methods The clinically approved and available CFTR modulators and specific indications for their use are reviewed. Additionally, a systematic review of these therapies and effects on CRS in CF was performed. Results Four Food and Drug Administration approved CFTR modulators are available for patients with CF. Current drugs are approved for gating, residual function, or F508del mutations. Multiple reports describe CFTR modulators’ increase in transepithelial ion transport in nasal epithelial cultures; however, clinical studies regarding effects of these modulators on sinonasal health are limited to 5 studies that present new data of the effects of CFTR modulators in CRS. Conclusions CFTR modulators have changed management of CF. Initial studies of these medications demonstrate promising results in CF; however, there is a paucity of literature describing the effect of CFTR modulators on CF-associated CRS, although initial results are encouraging.

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