scholarly journals An Unexpected Infection in Loss-of-function Mutations in STAT3: Malignant Alveolar Echinococcosis in Liver

2020 ◽  
Author(s):  
Sule Haskologlu ◽  
Figen Dogu ◽  
Gulnur Gollu Bahadır ◽  
Setenay Akyuzluer ◽  
Ergin Ciftci ◽  
...  
Keyword(s):  
Alveolar Echinococcosis ◽  
Immunoglobulin E ◽  
Fungal Infections ◽  
Parasitic Infections ◽  
Loss Of Function ◽  
Recurrent Pneumonia ◽  
Tissue Abnormalities ◽  
Transcription 3 ◽  
Slow Growing ◽  
Very High

Loss-of-function (LOF) mutations in signal transducer and activator of transcription 3 (STAT3) gene causes autosomal dominant hyper immunoglobulin E syndrome (AD-HIES or Job’s Syndrome), a rare and complex primary immunodeficiency (PID) syndrome characterized by increased levels of IgE (>2000 IU/mL), eosinophilia, recurrent staphylococcal skin abscesses, eczema, recurrent pneumonia, skeletal and connective tissue abnormalities. Although bacterial and fungal infections are common in AD-HIES, susceptibility to parasitic infections has not been reported. Alveolar echinococcosis (AE), a zoonosis caused by the growth of the Echinococcus multilocularis (EM) metacestode, mimics slow-growing liver cancer. The mortality rate of AE is very high when it is diagnosed late or under-treated. Here, we report a 14-year-old boy with AE infections of the liver and the lung resulting in liver failure and diagnosed as STAT3-LOF. To our knowledge, the association between these two conditions has not been reported in the literature before.

scholarly journals Bi-allelic Loss-of-Function Mutations in the NPR-C Receptor Result in Enhanced Growth and Connective Tissue Abnormalities

2018 ◽  
Vol 103 (2) ◽  
pp. 288-295 ◽  
Author(s):  
Eveline Boudin ◽  
Tjeerd R. de Jong ◽  
Tim C.R. Prickett ◽  
Bruno Lapauw ◽  
Kaatje Toye ◽  
...  
Keyword(s):  
Connective Tissue ◽  
Allelic Loss ◽  
Loss Of Function ◽  
Tissue Abnormalities

scholarly journals Tumor Suppressor LKB1 Inhibits Activation of Signal Transducer and Activator of Transcription 3 (STAT3) by Thyroid Oncogenic Tyrosine Kinase Rearranged in Transformation (RET)/Papillary Thyroid Carcinoma (PTC)

2007 ◽  
Vol 21 (12) ◽  
pp. 3039-3049 ◽  
Author(s):  
Dong Wook Kim ◽  
Hyo Kyun Chung ◽  
Ki Cheol Park ◽  
Jung Hwan Hwang ◽  
Young Suk Jo ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Tumor Suppressor ◽  
Thyroid Carcinoma ◽  
Malignant Tumors ◽  
Kinase Domain ◽  
Signal Transducer ◽  
Papillary Thyroid ◽  
Loss Of Function ◽  
Amino Acid Region ◽  
Transcription 3

Abstract The tumor suppressor LKB1 (STK11) is a cytoplasmic/nuclear serine/threonine kinase, defects in which cause Peutz-Jeghers syndrome (PJS) in humans and animals. Recent studies showed that loss of function of LKB1 is associated with sporadic forms of lung, pancreatic, and ovarian cancer. In cancer cells, LKB1 is inactivated by two mechanisms: mutations in its central kinase domain or complete loss of LKB1 expression. Inactivation of LKB1 is associated with progression of PJS and transformation of benign polyps into malignant tumors. This study examines the effect of LKB1 on regulation of STAT3 and expression of transcriptional targets of STAT3. The results show that LKB1 inhibits rearranged in transformation (RET)/papillary thyroid carcinoma (PTC)-dependent activation of signal transducer and activator of transcription 3 (STAT3), which is mediated by phosphorylation of STAT3 tyrosine 705 by RET/PTC. Suppression of STAT3 transactivation by LKB1 requires the kinase domain but not the kinase activity of LKB1. The centrally located kinase domain of LKB1 is an approximately 260-amino-acid region that binds to the linker domain of STAT3. Chromatin immunoprecipitation studies indicate that expression of LKB1 reduces the binding of STAT3 to its target promoters and suppresses STAT3-mediated expression of Cyclin D1, VEGF, and Bcl-xL. Knockdown of LKB1 by specific small interfering RNA led to an increase in STAT3 transactivation activity and promoted cell proliferation in the presence of RET/PTC. Thus, this study suggests that LKB1 suppresses tumor growth by inhibiting RET/PTC-dependent activation of oncogenic STAT3.

scholarly journals Bilateral angiomyolipoma of the kidney in patient with tuberous sclerosis

2005 ◽  
Vol 133 (9-10) ◽  
pp. 433-437
Author(s):  
Radoje Colovic ◽  
Natasa Colovic ◽  
Nikica Grubor ◽  
Vladimir Radak ◽  
Marijan Micev ◽  
...  
Keyword(s):  
Tuberous Sclerosis ◽  
Complete Loss ◽  
Hla Typing ◽  
Uneventful Recovery ◽  
Loss Of Function ◽  
Kidney Tumors ◽  
Benign Nature ◽  
The Right ◽  
Slow Growing

Angiomyolipomas are relatively frequent tumors of the kidney. It is believed that about 10 million people worldwide have such a tumor. About 1/10 of these 10 million are patients who suffer from tuberous sclerosis. The tumors are frequently bilateral, slow growing, and usually a symptomatic, as well as being rare in children. Due to the benign nature of angiomyolipomas, surgical treatment and embolisation of the tumors are generally not recommended, unless renal function is endangered, the symptoms are severe, or the kidney in question becomes completely dysfunctional. This is particularly the case in patients with tuberous sclerosis in whom these tumors are either already bilateral or may become so. We present a 24-year-old woman with tuberous sclerosis in whom bilateral kidney tumors were diagnosed 7 years earlier and in whom we carried out a left nephrectomy of a 5300 gram angiomyolipoma, which caused pain and complete loss of function. Although timorous, the right kidney was functional, so it was left untouched. After an uneventful recovery, a close follow-up was recommended, as well as HLA typing, as it is highly probable that the right kidney will gradually become inadequate or completely dysfunctional, so that haemodialysis and/or kidney transplantation along with nephrectomy will become necessary.

scholarly journals Evaluation of a Particle-enhanced Turbidimetric Immunoassay for the Measurement of Immunoglobulin E in an ILab 900 Analyzer

1999 ◽  
Vol 45 (9) ◽  
pp. 1557-1561
Author(s):  
Sandra Guaita ◽  
Josep MA Simó ◽  
Natàlia Ferré ◽  
Jorge Joven ◽  
Jordi Camps
Keyword(s):  
General Chemistry ◽  
Detection Limit ◽  
Immunoglobulin E ◽  
Parasitic Infections ◽  
Attractive Alternative ◽  
Allergic Reactions ◽  
Automated Assay ◽  
Serum Assay ◽  
Microparticle Enzyme Immunoassay ◽  
Turbidimetric Immunoassay

Abstract Background: The measurement of immunoglobulin E (IgE) in serum is widely used in the diagnosis of allergic reactions and parasitic infections. We describe here a fully automated assay for human IgE suitable for routine application in a general chemistry analyzer. Methods: We used an ILab 900® analyzer. This instrument automates a particle-enhanced immunoturbidimetric assay with an analysis time of 9 min. Results: The assay was linear in the range 4–1000 kIU/L (r = 0.9998). The intra- and interassay CVs at 57, 235, and 434 kIU/L were <3.5% and <7.4%, respectively. The detection limit was 4 kIU/L. Hemoglobin (≤16 g/L), bilirubin (≤250 μmol/L), and myeloma paraproteins did not interfere with the assay. The assay showed good correlation with a microparticle enzyme immunoassay (r = 0.998) with a mean difference between methods of −6 ± 26 kIU/L. Conclusion: The new automated serum assay for IgE is an attractive alternative that avoids the need for dedicated instrumentation.

scholarly journals 1376. Antifungal Activity of Cerium Nitrate Against Fungal Isolates Associated with Combat-Related Injuries Including Burns

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S422-S422
Author(s):  
Heather Pomerantz ◽  
Miriam Beckius ◽  
Dana Blyth ◽  
Kevin S Akers ◽  
David R Tribble ◽  
...  
Keyword(s):  
Fungal Infections ◽  
Mucor Circinelloides ◽  
Cerium Nitrate ◽  
Time Dependent ◽  
Candida Spp ◽  
Burn Care ◽  
Fungal Isolates ◽  
Time Kill ◽  
Slow Growing

Abstract Background Fungal infections are a critical cause of morbidity and mortality in burn patients. In addition to debridement and systemic antifungal therapy, various topical adjuncts have been used, and topical burn care is a key component of infection prevention and treatment. Cerium nitrate (CN) has been used in combination with silver sulfadiazine (SS) in burn care. Previous studies showed that CN had bacteriostatic activity, and suggested anti-biofilm activity against Candida biofilms. In this study, we evaluated the in vitro activity of CN against fungal isolates associated with combat-related injuries. Methods The efficacy of CN was evaluated against 14 mold (three Aspergillus spp., two Fusarium spp., five different mucormycetes, two Bipolaris spp., one Alternaria spp., one Exophiala spp.) and 21 Candida spp. isolates collected as part of the Trauma Infectious Disease Outcomes Study. Fungicidal activity of various concentrations of CN (2.2%, 1%, 0.5% and 0.2%) was determined using an established time-kill assay. Standard conidia/cell suspensions were prepared according to Clinical and Laboratory Standards Institute guidelines and then exposed to the CN solutions for 24 hours. At different times (0, 5, 15, 30 minutes, 1, 1.5, 3, 6, 12, and 24 hours) aliquots were plated and incubated at 35ºC. Colony forming unit (CFU) counts were determined after 24 hours incubation or after an appropriate time for slow growing molds. Results All mold isolates had persistent growth at 24 hours with most having no significant change in colony counts over the 24-hour period. The only exception was Mucor circinelloides, which appeared to have a time-dependent reduction in CFUs at 24 hours for all CN concentrations. Exophiala did not grow as well in CN solutions compared with the control (mean 65 vs. 28.2 CFUs with a difference of mean 37.4 CFUs, P = 0.0001), but this was not time or concentration dependent. All yeast species showed a time-dependent killing after 6–12 hours. Conclusion CN demonstrated time-dependent killing of the yeasts. However, very little activity was observed against the tested molds. Since CN is often used in combination with SS there might be a synergistic effect against molds. Further research will evaluate higher concentrations of CN and its toxicity for cells and tissue. Disclosures All authors: No reported disclosures.

Atopic dermatitis without serum immunoglobulin E elevation or loss‐of‐function filaggrin gene mutation in a patient with X‐linked agammaglobulinemia

2019 ◽  
Vol 47 (1) ◽  
pp. 58-60
Author(s):  
Emi Yamazaki ◽  
Katsuko Kikuchi ◽  
Yoji Sasahara ◽  
Michihiro Kono ◽  
Masashi Akiyama ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Gene Mutation ◽  
Immunoglobulin E ◽  
Serum Immunoglobulin ◽  
Loss Of Function

scholarly journals Fungal and Parasitic Infections of the Eye

2000 ◽  
Vol 13 (4) ◽  
pp. 662-685 ◽  
Author(s):  
Stephen A. Klotz ◽  
Christopher C. Penn ◽  
Gerald J. Negvesky ◽  
Salim I. Butrus
Keyword(s):  
Fungal Infections ◽  
Penetrating Trauma ◽  
Ocular Tissue ◽  
Endogenous Endophthalmitis ◽  
Parasitic Infections ◽  
Candida Spp ◽  
Dimorphic Fungi ◽  
Contact Lens Wear ◽  
Adjacent Structures ◽  
Lens Wear

SUMMARY The unique structure of the human eye as well as exposure of the eye directly to the environment renders it vulnerable to a number of uncommon infectious diseases caused by fungi and parasites. Host defenses directed against these microorganisms, once anatomical barriers are breached, are often insufficient to prevent loss of vision. Therefore, the timely identification and treatment of the involved microorganisms are paramount. The anatomy of the eye and its surrounding structures is presented with an emphasis upon the association of the anatomy with specific infection of fungi and parasites. For example, filamentous fungal infections of the eye are usually due to penetrating trauma by objects contaminated by vegetable matter of the cornea or globe or, by extension, of infection from adjacent paranasal sinuses. Fungal endophthalmitis and chorioretinitis, on the other hand, are usually the result of antecedent fungemia seeding the ocular tissue. Candida spp. are the most common cause of endogenous endophthalmitis, although initial infection with the dimorphic fungi may lead to infection and scarring of the chorioretina. Contact lens wear is associated with keratitis caused by yeasts, filamentous fungi, and Acanthamoebae spp. Most parasitic infections of the eye, however, arise following bloodborne carriage of the microorganism to the eye or adjacent structures.

Parasitology: today and tomorrow

1987 ◽  
Vol 65 (4) ◽  
pp. 812-822
Author(s):  
D. F. Mettrick
Keyword(s):  
New Technologies ◽  
Control Point ◽  
Experimental Studies ◽  
High Standard ◽  
Cellular Biology ◽  
Parasitic Infections ◽  
Host Parasite ◽  
Canadian Research ◽  
Very High

Parasites have, over the centuries, been responsible for high mortalities among humans and domestic and wild animals. The presence of parasitic infections has made vast areas of the world uninhabitable for both humans and animals. Major strengths of Canadian parasitology include wildlife parasitology, systematics, and taxonomy. Experimental studies in parasitology are limited; in particular the subdisciplines of parasite molecular and cellular biology, biochemistry, immunology, and neurobiology are very limited. There is concern that we will not be able to maintain the quality of Canadian research in parasitology, particularly in the emerging new technologies. It is greatly to the credit of those early Canadian parasitologists, who laid the foundations for today's advances in parasitology, that a relatively small group of approximately 100 professional parasitologists has today reached a very high standard of parasitological research. The next 25 years will be an exciting period as new insights allow us to further understand the complexity of host–parasite relationships. The development of new vaccines, drugs, and vector control point to significant reductions in parasitic infections.

STAT3 is required for IL-21–induced secretion of IgE from human naive B cells

Blood ◽  
2008 ◽  
Vol 112 (5) ◽  
pp. 1784-1793 ◽  
Author(s):  
Danielle T. Avery ◽  
Cindy S. Ma ◽  
Vanessa L. Bryant ◽  
Brigitte Santner-Nanan ◽  
Ralph Nanan ◽  
...  
Keyword(s):  
B Cells ◽  
Immunoglobulin E ◽  
Interferon Γ ◽  
Fundamental Difference ◽  
Interleukin 4 ◽  
Loss Of Function ◽  
Serum Ige ◽  
Human B Cells ◽  
Stat3 Mutations

Abstract The production of immunoglobulin E (IgE) is tightly regulated. This is evidenced by the fact that it comprises less than 0.0001% of serum Ig, and aberrant production causes atopic conditions, including allergy, rhinitis, and anaphylaxis. Interleukin-4 (IL-4) is a well-characterized inducer of IgE by human and murine B cells, whereas interferon-γ can antagonize this effect. IL-21 has also been recognized for its ability to suppress IL-4–induced IgE production by murine B cells. Here, we identified IL-21 as an inducer of IgE production by CD40L-stimulated human naive B cells. Furthermore, there was a striking synergy between IL-4 and IL-21 on inducing IgE secretion by CD40L-stimulated human B cells, such that the levels detected under these conditions exceeded those induced by IL-4 or IL-21 alone by more than 10-fold. IL-21 induced activation of STAT3 and analysis of B cells from patients with loss-of-function STAT3 mutations revealed that the ability of IL-21 to induce IgE secretion, and augment that driven by IL-4, was STAT3-dependent. These findings highlight a fundamental difference between the regulation of IgE production by human and murine B cells and have implications for the dysregulated production of IgE in conditions characterized by extremely high levels of serum IgE.

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