scholarly journals Novel mesenchymal and haematopoietic cell isoforms of the SHP-2 docking receptor, PZR: identification, molecular cloning and effects on cell migration

2003 ◽  
Vol 370 (2) ◽  
pp. 537-549 ◽  
Author(s):  
Andrew C.W. ZANNETTINO ◽  
Maria ROUBELAKIS ◽  
Katie J. WELLDON ◽  
Denise E. JACKSON ◽  
Paul J. SIMMONS ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Single Gene ◽  
Transcription Unit ◽  
Erythroid Precursor ◽  
Haematopoietic Cells ◽  
Colony Forming Units ◽  
Cytoplasmic Tails ◽  
Src Homology ◽  
First Time

SHP-2 (Src homology phosphatase type-2) is essential for haematopoietic skeletal and vascular development. Thus the identification of its binding partners is critically important. In the present study, we describe a unique monoclonal antibody, WM78, which interacts with PZR, a SHP-2 binding partner. Furthermore, we identify two novel isoforms of PZR, PZRa and PZRb, derived by differential splicing from a single gene transcription unit on human chromosome 1q24. All are type 1 transmembrane glycoproteins with identical extracellular and transmembrane domains, but differ in their cytoplasmic tails. The PZR intracellular domain contains two SHP-2 binding immunoreceptor tyrosine-based inhibitory motifs (VIY246AQL and VVY263ADI) which are not present in PZRa and PZRb. Using the WM78 monoclonal antibody, which recognizes the common extracellular domain of the PZR isoforms, we demonstrate that the PZR molecules are expressed on mesenchymal and haematopoietic cells, being present on the majority of CD34+CD38+ and early clonogenic progenitors, and at lower levels on CD34+CD38- cells and the hierarchically more primitive pre-colony forming units. Interestingly, we show by reverse transcriptase-PCR that the PZR isoforms are differentially expressed in haematopoietic, endothelial and mesenchymal cells. Both PZR and PZRb are present in CD133+ precursors and endothelial cells, PZRb predominates in mesenchymal and committed myelomonocytic progenitor cells, and all three isoforms occur in erythroid precursor cell lines. Importantly, using SHP-2 mutant (Δ46—110) and SHP-2 rescue of embryonic fibroblasts stably expressing the PZR isoforms, we demonstrate for the first time that PZR, but not PZRa or PZRb, facilitates fibronectin- dependent migration of cells expressing a competent SHP-2 molecule. These observations will be instrumental in determining the mechanisms whereby PZR isoforms regulate cell motility.

scholarly journals MAPK p38alpha Kinase Influences Haematopoiesis in Embryonic Stem Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Kateřina Štefková ◽  
Markéta Hanáčková ◽  
Jan Kučera ◽  
Katarzyna Anna Radaszkiewicz ◽  
Barbora Ambrůžová ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Wild Type ◽  
Colony Forming Unit ◽  
Haematopoietic Cells ◽  
Colony Forming Units ◽  
First Time

The activation of p38alpha kinase mediates cell response to various extracellular factors including many interleukins and growth factors important for haematopoiesis. The role of p38alpha kinase was previously analysed in particular haematopoietic cells. In this study and for the first time, the role of p38alpha kinase in haematopoiesis was studied using a model of continuous haematopoietic development in pluripotent embryonic stem cellsin vitro. The expression of transcripts associated with haematopoiesis and the potential for the formation of specific haematopoietic cell colonies were compared between wild-type and mutant p38alpha gene-depleted cells. The absence of p38alpha kinase led to the inhibition of hemangioblast formation during the first step of haematopoiesis. Later, during differentiation, due to the lack of p38alpha kinase, erythrocyte maturation was impaired. Mutant p38α−/−cells also exhibited decreased potential with respect to the expansion of granulocyte colony-forming units. This effect was reversed in the absence of erythropoietin as shown by colony-forming unit assay in media for colony-forming unit granulocytes/macrophages. p38alpha kinase thus plays an important role in the differentiation of common myeloid precursor cells into granulocyte lineages.

scholarly journals Central precocious puberty in a girl with LEGIUS syndrome: an accidental association?

2021 ◽  
Vol 47 (1) ◽  
Author(s):  
Valentina Orlandi ◽  
Paolo Cavarzere ◽  
Laura Palma ◽  
Rossella Gaudino ◽  
Franco Antoniazzi
Keyword(s):  
Genetic Analysis ◽  
Precocious Puberty ◽  
Central Precocious Puberty ◽  
Neurofibromatosis Type ◽  
Case Presentation ◽  
New Variant ◽  
Legius Syndrome ◽  
Timing Of Puberty ◽  
First Time

Abstract Background Central precocious puberty is a condition characterized by precocious activation of the hypothalamic-pituitary-gonadal axis. It may be idiopathic or secondary to organic causes, including syndromes such as Neurofibromatosis type 1 (NF1). Case presentation We presented a girl of 6 years and 10 months with almost 11 café-au-lait skin macules, without other clinical or radiological signs typical of NF1, and with a central precocious puberty. Genetic analysis evidenced the new variant NM-152594.2:c.304delAp. (Thr102Argfs*19) in SPRED1 gene, which allowed to diagnose Legius syndrome. Conclusions We report for the first time a case of central precocious puberty in a girl with Legius syndrome. The presence of central precocious puberty in a child with characteristic café-au-lait macules should suggest pediatricians to perform genetic analysis in order to reach a definitive diagnosis. Further studies on timing of puberty in patients with RASopathies are needed to better elucidate if this clinical association is casual or secondary to their clinical condition.

scholarly journals EXPRESS: Pulmonary Hypertension Associated With Neurofibromatosis Type 2

2021 ◽  
pp. 204589402110295
Author(s):  
Hirohisa Taniguchi ◽  
Tomoya Takashima ◽  
Ly Tu ◽  
Raphaël Thuillet ◽  
Asuka Furukawa ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Neurofibromatosis Type ◽  
Pulmonary Vascular Remodeling ◽  
Life Threatening ◽  
History Of ◽  
Pulmonary Arterial ◽  
First Time

Although precapillary pulmonary hypertension (PH) is a rare but severe complication of patients with neurofibromatosis type 1 (NF1), its association with NF2 remains unknown. Herein, we report a case of a 44-year-old woman who was initially diagnosed with idiopathic pulmonary arterial hypertension (IPAH) and treated with PAH-specific combination therapy. However, a careful assessment for a relevant family history of the disease and genetic testing reveal that this patient had a mutation in the NF2 gene. Using immunofluorescence and Western blotting, we demonstrated a decrease in endothelial NF2 protein in lungs from IPAH patients compared to control lungs, suggesting a potential role of NF2 in PAH development. To our knowledge, this is the first time that precapillary PH has been described in a patient with NF2. The altered endothelial NF2 expression pattern in PAH lungs should stimulate work to better understand how NF2 is contributing to the pulmonary vascular remodeling associated to these severe life-threatening conditions.

Continuous Ketone Monitoring: A New Paradigm for Physiologic Monitoring

2021 ◽  
pp. 193229682110098
Author(s):  
Jennifer Y. Zhang ◽  
Trisha Shang ◽  
Suneil K. Koliwad ◽  
David C. Klonoff
Keyword(s):  
Interstitial Fluid ◽  
Good Accuracy ◽  
Physiologic Monitoring ◽  
New Paradigm ◽  
Continuous Glucose Monitor ◽  
Sensor Platform ◽  
Wired Enzyme ◽  
First Time

In this issue of JDST, Alva and colleagues present for the first time, development of a continuous ketone monitor (CKM) tested both in vitro and in humans. Their sensor measured betahydroxybutyrate (BHB) in interstitial fluid (ISF). The sensor was based on wired enzyme electrochemistry technology using BHB dehydrogenase. The sensor required only a single retrospective calibration without a need for further adjustments over 14 days. The device produced a linear response over the 0-8 mM range with good accuracy. This novel CKM could provide a new dimension of useful automatically collected information for managing diabetes. Passively collected ISF ketone information would be useful for predicting and managing ketoacidosis in patients with type 1 diabetes, as well as other states of abnormal ketonemia. Although additional studies of this CKM will be required to assess performance in intended patient populations and prospective factory calibration will be required to support real time measurements, this novel monitor has the potential to greatly improve outcomes for people with diabetes. In the future, a CKM might be integrated with a continuous glucose monitor in the same sensor platform.

Insulin-like growth factor type 1 receptor (IGF-1R) exclusive nuclear staining: A predictive biomarker for IGF-1R monoclonal antibody (Ab) therapy in sarcomas

2012 ◽  
Vol 48 (16) ◽  
pp. 3027-3035 ◽  
Author(s):  
Irène Asmane ◽  
Emmanuel Watkin ◽  
Laurent Alberti ◽  
Adeline Duc ◽  
Perrine Marec-Berard ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Growth Factor ◽  
Predictive Biomarker ◽  
Nuclear Staining ◽  
Insulin Like Growth Factor ◽  
Factor Type

Characteristics of ruminant mammary epithelial cells grown in primary culture in serum-free medium

1992 ◽  
Vol 59 (4) ◽  
pp. 491-498 ◽  
Author(s):  
Steven J. Winder ◽  
Alan Turvey ◽  
Isabel A. Forsyth
Keyword(s):  
Monoclonal Antibody ◽  
Mammary Epithelial Cells ◽  
Myoepithelial Cells ◽  
Mammary Epithelial ◽  
Serum Free ◽  
Commercial Medium ◽  
Attachment Factor ◽  
Rat Tail

SummaryCells were obtained from the mammary glands of sheep and cows by collagenase–hyaluronidase digestion. Characterization of cells as epithelial was by reaction with a monoclonal antibody to cytokeratin. A subpopulation of spindle-shaped or stellate cells reacted with a monoclonal antibody to desmin and may be related to myoepithelial cells. The development is described of a simple serum-free culture system for these cells on gels of rat tail (type 1) collagen. A commercial medium (M199) was used, buffered with Hepes and with bovine serum albumin as the sole protein supplement, plus fibronectin for the first 18 h only as an attachment factor. The cell cultures showed stimulated DNA synthesis in response to mitogens on attached gels and also responded as floating cultures to lactogenic hormones with production of α-lactalbumin.

The Cloning and Mapping of ADR6, a Gene Required for Sporulation and for Expression of the Alcohol Dehydrogenase II Isozyme From Saccharomyces cerevisiae

Genetics ◽  
1987 ◽  
Vol 116 (4) ◽  
pp. 531-540
Author(s):  
Aileen K W Taguchi ◽  
Elton T Young
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Alcohol Dehydrogenase ◽  
Single Gene ◽  
Carbon Sources ◽  
Transcription Unit ◽  
Yeast Cells ◽  
Recessive Mutation ◽  
Yeast Saccharomyces Cerevisiae ◽  
Upstream Activating Sequence ◽  
A Site

ABSTRACT The alcohol dehydrogenase II (ADH2) gene of the yeast, Saccharomyces cerevisiae, is not transcribed during growth on fermentable carbon sources such as glucose. Growth of yeast cells in a medium containing only nonfermentable carbon sources leads to a marked increase or derepression of ADH2 expression. The recessive mutation, adr6-1, leads to an inability to fully derepress ADH2 expression and to an inability to sporulate. The ADR6 gene product appears to act directly or indirectly on ADH2 sequences 3' to or including the presumptive TATAA box. The upstream activating sequence (UAS) located 5' to the TATAA box is not required for the Adr6- phenotype. Here, we describe the isolation of a recombinant plasmid containing the wild-type ADR6 gene. ADR6 codes for a 4.4-kb RNA which is present during growth both on glucose and on nonfermentable carbon sources. Disruption of the ADR6 transcription unit led to viable cells with decreased ADHII activity and an inability to sporulate. This indicates that both phenotypes result from mutations within a single gene and that the adr6-1 allele was representative of mutations at this locus. The ADR6 gene mapped to the left arm of chromosome XVI at a site 18 centimorgans from the centromere.

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