scholarly journals Absence of GP130 cytokine receptor signaling causes extended Stüve-Wiedemann syndrome

2020 ◽  
Vol 217 (3) ◽  
Author(s):  
Yin-Huai Chen ◽  
Giedre Grigelioniene ◽  
Phillip T. Newton ◽  
Jacob Gullander ◽  
Maria Elfving ◽  
...  
Keyword(s):  
Exon Skipping ◽  
Oncostatin M ◽  
Functional Tests ◽  
Loss Of Function ◽  
Genetic Syndrome ◽  
Lung Dysfunction ◽  
Neonatal Lung ◽  
The Common ◽  
Common Signal ◽  
Renal Abnormalities

The gene IL6ST encodes GP130, the common signal transducer of the IL-6 cytokine family consisting of 10 cytokines. Previous studies have identified cytokine-selective IL6ST defects that preserve LIF signaling. We describe three unrelated families with at least five affected individuals who presented with lethal Stüve-Wiedemann–like syndrome characterized by skeletal dysplasia and neonatal lung dysfunction with additional features such as congenital thrombocytopenia, eczematoid dermatitis, renal abnormalities, and defective acute-phase response. We identified essential loss-of-function variants in IL6ST (a homozygous nonsense variant and a homozygous intronic splice variant with exon skipping). Functional tests showed absent cellular responses to GP130-dependent cytokines including IL-6, IL-11, IL-27, oncostatin M (OSM), and leukemia inhibitory factor (LIF). Genetic reconstitution of GP130 by lentiviral transduction in patient-derived cells reversed the signaling defect. This study identifies a new genetic syndrome caused by the complete lack of signaling of a whole family of GP130-dependent cytokines in humans and highlights the importance of the LIF signaling pathway in pre- and perinatal development.

Specific Acute Losses of Vestibular Function in Four Patients following Unilateral Section of One or All Components of the Eighth Cranial Nerve

1974 ◽  
Vol 83 (4) ◽  
pp. 525-536 ◽  
Author(s):  
Earl F. Miller ◽  
Jack L. Pulec ◽  
James G. Wilcox ◽  
Ashton Graybiel
Keyword(s):  
Vestibular Function ◽  
Functional Tests ◽  
Loss Of Function ◽  
High Susceptibility ◽  
Short Term ◽  
Eighth Cranial Nerve ◽  
Common Complaint ◽  
Inner Ear Disease ◽  
Viiith Nerve ◽  
The Common

Functional tests of the specific auricular organs were administered to four patients who had the common complaint of disabling vertigo and tinnitus. Diagnosis of unilateral inner ear disease or disorder was aided by a relative decrease in right- or left-ear response as recorded by certain techniques, while other methods demonstrated undisturbed function. Partial and complete VIIIth nerve sections completely eliminated the tinnitus and severe symptoms of vertigo in each patient, as well as greatly reduced his extremely high susceptibility to motion sickness, although it caused a short-term increase in instability in walking and standing. Specific auricular organ loss of function was related to the side and extent of the surgical interference. Possible clinical implications are discussed.

scholarly journals Postnatally Induced Inactivation of gp130 in Mice Results in Neurological, Cardiac, Hematopoietic, Immunological, Hepatic, and Pulmonary Defects

1998 ◽  
Vol 188 (10) ◽  
pp. 1955-1965 ◽  
Author(s):  
Ulrich A.K. Betz ◽  
Wilhelm Bloch ◽  
Maries van den Broek ◽  
Kanji Yoshida ◽  
Tetsuya Taga ◽  
...  
Keyword(s):  
Leukemia Inhibitory Factor ◽  
Ciliary Neurotrophic Factor ◽  
Oncostatin M ◽  
Receptor Subunit ◽  
Signal Transducer ◽  
Conditional Mutant ◽  
The Common ◽  
Common Signal

The pleiotrophic but overlapping functions of the cytokine family that includes interleukin (IL)-6, IL-11, leukemia inhibitory factor, oncostatin M, ciliary neurotrophic factor, and cardiotrophin 1 are mediated by the cytokine receptor subunit gp130 as the common signal transducer. Although mice lacking individual members of this family display only mild phenotypes, animals lacking gp130 are not viable. To assess the collective role of this cytokine family, we inducibly inactivated gp130 via Cre-loxP–mediated recombination in vivo. Such conditional mutant mice exhibited neurological, cardiac, hematopoietic, immunological, hepatic, and pulmonary defects, demonstrating the widespread importance of gp130-dependent cytokines.

scholarly journals A biallelic mutation in IL6ST encoding the GP130 co-receptor causes immunodeficiency and craniosynostosis

2017 ◽  
Vol 214 (9) ◽  
pp. 2547-2562 ◽  
Author(s):  
Tobias Schwerd ◽  
Stephen R.F. Twigg ◽  
Dominik Aschenbrenner ◽  
Santiago Manrique ◽  
Kerry A. Miller ◽  
...  
Keyword(s):  
Acute Phase Response ◽  
Leukemia Inhibitory Factor ◽  
Oncostatin M ◽  
Homozygous Mutation ◽  
Loss Of Function ◽  
Biallelic Mutation ◽  
Hyper Ige Syndrome ◽  
B Cell Memory ◽  
The Common ◽  
Missense Substitution

Multiple cytokines, including interleukin 6 (IL-6), IL-11, IL-27, oncostatin M (OSM), and leukemia inhibitory factor (LIF), signal via the common GP130 cytokine receptor subunit. In this study, we describe a patient with a homozygous mutation of IL6ST (encoding GP130 p.N404Y) who presented with recurrent infections, eczema, bronchiectasis, high IgE, eosinophilia, defective B cell memory, and an impaired acute-phase response, as well as skeletal abnormalities including craniosynostosis. The p.N404Y missense substitution is associated with loss of IL-6, IL-11, IL-27, and OSM signaling but a largely intact LIF response. This study identifies a novel immunodeficiency with phenotypic similarities to STAT3 hyper-IgE syndrome caused by loss of function of GP130.

The domino gene of Drosophila encodes novel members of the SWI2/SNF2 family of DNA-dependent ATPases, which contribute to the silencing of homeotic genes

Development ◽  
2001 ◽  
Vol 128 (8) ◽  
pp. 1429-1441 ◽  
Author(s):  
M.L. Ruhf ◽  
A. Braun ◽  
O. Papoulas ◽  
J.W. Tamkun ◽  
N. Randsholt ◽  
...  
Keyword(s):  
Polytene Chromosomes ◽  
Gene Mutations ◽  
Polycomb Group ◽  
Protein Isoforms ◽  
Homeotic Genes ◽  
Loss Of Function ◽  
Trithorax Group ◽  
A Subunit ◽  
The Common ◽  
Hematopoietic Disorders

The Drosophila domino gene has been isolated in a screen for mutations that cause hematopoietic disorders. Generation and analysis of loss-of-function domino alleles show that the phenotypes are typical for proliferation gene mutations. Clonal analysis demonstrates that domino is necessary for cell viability and proliferation, as well as for oogenesis. domino encodes two protein isoforms of 3202 and 2498 amino acids, which contain a common N-terminal region but divergent C termini. The common region includes a 500 amino acid DNA-dependent ATPase domain of the SWI2/SNF2 family of proteins, which function via interaction with chromatin. We show that, although domino alleles do not exhibit homeotic phenotypes by themselves, domino mutations enhance Polycomb group mutations and counteract Trithorax group effects. The Domino proteins are present in large complexes in embryo extracts, and one isoform binds to a number of discrete sites on larval polytene chromosomes. Altogether, the data lead us to propose that domino acts as a repressor by interfering with chromatin structure. This activity is likely to be performed as a subunit of a chromatin-remodeling complex.

Basic Clinical Examination of the Foot and Ankle

2020 ◽  
Vol 158 (06) ◽  
pp. 657-660
Author(s):  
Michael Kehrer ◽  
Hendrik Kohlhof ◽  
Desiree Schwetje ◽  
Adnan Kasapovic ◽  
Andreas Kehrer ◽  
...  
Keyword(s):  
Clinical Examination ◽  
Clinical Signs ◽  
Accurate Diagnosis ◽  
Foot And Ankle ◽  
Functional Tests ◽  
Provocation Tests ◽  
Examination Methods ◽  
The Common ◽  
Ankle Complex ◽  
Structured Approach

AbstractSuccessful treatment of foot and ankle diseases requires an accurate diagnosis. In addition to differentiated history taking, clinical examination is the most important component in the diagnosis of foot and ankle diseases. The present video explains the common provocation tests and functional tests that are used in the basic clinical examination of the foot and ankle complex. In addition to general inspection and palpation, the focus is on different diagnostic tests and clinical signs that improve diagnostic accuracy. The present basic clinical examination methods allow a structured approach to clinical issues and can be a good basis, if supplemented by further specific and individual tests.

scholarly journals Oncostatin M, leukaemia-inhibitory factor and interleukin 6 trigger different effects on α1-proteinase inhibitor synthesis in human lung-derived epithelial cells

1998 ◽  
Vol 329 (2) ◽  
pp. 335-339 ◽  
Author(s):  
Joanna CICHY ◽  
Stefan ROSE-JOHN ◽  
James TRAVIS
Keyword(s):  
Epithelial Cells ◽  
Interleukin 6 ◽  
Proteinase Inhibitor ◽  
Human Lung ◽  
Biological Activities ◽  
Oncostatin M ◽  
Inhibitory Factor ◽  
Leukaemia Inhibitory Factor ◽  
Common Signal

Interleukin 6 (IL-6), oncostatin M (OSM) and leukaemia-inhibitory factor (LIF) share a common signal-transducing subunit in each of their receptors and thus mediate an overlapping spectrum of biological activities. Although all of these cytokines stimulate the production of α1-proteinase inhibitor (α1-PI) in hepatocyte-derived cells, only OSM is able to up-regulate levels of this inhibitor in epithelial cells originating from the lung. In this study we characterized human lung-derived epithelial-like HTB58 cells for their ability to synthesize α1-PI after treatment with IL-6, OSM and LIF. The results demonstrate that the resistance of HTB58 cells to the effects of IL-6 and LIF was not because of a lack of their individual functional receptors and suggest that OSM utilizes two different receptors, gp130/LIF receptor and gp130/OSM receptor, in lung-derived epithelial cells.

Euclid and the art of wavelet estimation, Part II: Robust algorithm and field‐data examples

Geophysics ◽  
1997 ◽  
Vol 62 (6) ◽  
pp. 1939-1946 ◽  
Author(s):  
Eike Rietsch
Keyword(s):  
Field Data ◽  
Synthetic Data ◽  
Noise Resistance ◽  
Zero Eigenvalue ◽  
Seismic Line ◽  
Robust Algorithm ◽  
Seismic Wavelet ◽  
Time Zones ◽  
The Common ◽  
Common Signal

In this second part of a two‐part work, a more robust algorithm is derived and used for the estimation of the seismic wavelet as the common signal of two or more seismic traces. It is based on the properties of the eigenvectors with zero eigenvalue of a matrix derived in the first part, whose elements are the samples of the autocorrelation functions and crosscorrelation functions of these seismic traces for a number of lags. The noise resistance of this algorithm is illustrated by means of a synthetic‐data example and then demonstrated on field data. In one field‐data example, the so‐called Euclid wavelet is compared with one derived deterministically by means of an impedance log. The other example relates three quite different Euclid wavelets determined in three different time zones on a seismic line to one another by showing that their differences can be explained by absorption.

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