scholarly journals Persistent Human KIT Receptor Signaling Disposes Murine Placenta to Premature Differentiation Resulting in Severely Disrupted Placental Structure and Functionality

2020 ◽  
Vol 21 (15) ◽  
pp. 5503
Author(s):  
Franziska Kaiser ◽  
Julia Hartweg ◽  
Selina Jansky ◽  
Natalie Pelusi ◽  
Caroline Kubaczka ◽  
...  
Keyword(s):  
Giant Cell ◽  
Tumor Formation ◽  
Placental Lactogen ◽  
Common Mutation ◽  
Trophoblast Giant Cell ◽  
Placental Development ◽  
Humanized Mouse Model ◽  
Kit Receptor ◽  
Hematopoietic Disorders ◽  
The Impact

Activating mutations in the human KIT receptor is known to drive severe hematopoietic disorders and tumor formation spanning various entities. The most common mutation is the substitution of aspartic acid at position 816 to valine (D816V), rendering the receptor constitutively active independent of ligand binding. As the role of the KIT receptor in placental signaling cascades is poorly understood, we analyzed the impact of KITD816V expression on placental development using a humanized mouse model. Placentas from KITD816V animals present with a grossly changed morphology, displaying a reduction in labyrinth and spongiotrophoblast layer and an increase in the Parietal Trophoblast Giant Cell (P-TGC) layer. Elevated differentiation to P-TGCs was accompanied with reduced differentiation to other Trophoblast Giant Cell (TGC) subtypes and by severe decrease in proliferation. The embryos display growth retardation and die in utero. KITD816V-trophoblast stem cells (TSC) differentiate much faster compared to wild type (WT) controls. In undifferentiated KITD816V-TSCs, levels of Phosphorylated Extracellular-signal Regulated Kinase (P-ERK) and Phosphorylated Protein Kinase B (P-AKT) are comparable to wildtype cultures differentiating for 3–6 days. Accordingly, P-TGC markers Placental Lactogen 1 (PL1) and Proliferin (PLF) are upregulated as well. The results reveal that KIT signaling orchestrates the fine-tuned differentiation of the placenta, with special emphasis on P-TGC differentiation. Appropriate control of KIT receptor action is therefore essential for placental development and nourishment of the embryo.

The effect of surgery in tenosynovial giant cell tumours as measured by patient-reported outcomes on quality of life and joint function

2019 ◽  
Vol 101-B (3) ◽  
pp. 272-280 ◽  
Author(s):  
F. G. M. Verspoor ◽  
M. J. L. Mastboom ◽  
G. Hannink ◽  
W. T. A. van der Graaf ◽  
M. A. J. van de Sande ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Giant Cell ◽  
Diffuse Type ◽  
Joint Function ◽  
Population Means ◽  
Sf 36 ◽  
Patient Reported ◽  
The Impact

Aims The aim of this study was to evaluate health-related quality of life (HRQoL) and joint function in tenosynovial giant cell tumour (TGCT) patients before and after surgical treatment. Patients and Methods This prospective cohort study run in two Dutch referral centres assessed patient-reported outcome measures (PROMs; 36-Item Short-Form Health Survey (SF-36), visual analogue scale (VAS) for pain, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)) in 359 consecutive patients with localized- and diffuse-type TGCT of large joints. Patients with recurrent disease (n = 121) and a wait-and-see policy (n = 32) were excluded. Collected data were analyzed at specified time intervals preoperatively (baseline) and/or postoperatively up to five years. Results A total of 206 TGCT patients, 108 localized- and 98 diffuse-type, were analyzed. Median age at diagnosis of localized- and diffuse-type was 41 years (interquartile range (IQR) 29 to 49) and 37 years (IQR 27 to 47), respectively. SF-36 analyses showed statistically significant and clinically relevant deteriorated preoperative and immediate postoperative scores compared with general Dutch population means, depending on subscale and TGCT subtype. After three to six months of follow-up, these scores improved to general population means and continued to be fairly stable over the following years. VAS scores, for both subtypes, showed no statistically significant or clinically relevant differences pre- or postoperatively. In diffuse-type patients, the improvement in median WOMAC score was statistically significant and clinically relevant preoperatively versus six to 24 months postoperatively, and remained up to five years’ follow-up. Conclusion Patients with TGCT report a better HRQoL and joint function after surgery. Pain scores, which vary hugely between patients and in patients over time, did not improve. A disease-specific PROM would help to decipher the impact of TGCT on patients’ daily life and functioning in more detail. Cite this article: Bone Joint J 2019;101-B:272–280.

scholarly journals The impact of Temporal Artery Biopsy for the diagnosis of Giant Cell Arteritis in clinical practice in a tertiary University Hospital

2019 ◽  
Author(s):  
E Kaltsonoudis ◽  
E Pelechas ◽  
A Papoudou-Bai ◽  
E.T. Markatseli ◽  
M Elisaf ◽  
...  
Keyword(s):  
Giant Cell Arteritis ◽  
Giant Cell ◽  
Laboratory Data ◽  
Unknown Origin ◽  
Temporal Artery ◽  
University Hospital ◽  
Temporal Artery Biopsy ◽  
Acute Phase Reactants ◽  
Anemia Of Chronic Disease ◽  
The Impact

ABSTRACTBackgroundTemporal artery biopsy (TAB) is useful in assisting with giant cell arteritis (GCA) diagnosis but lacks sensitivity. The aim of our study was to assess the diagnostic impact of TAB histology in patients with suspected GCA on hospital admission.MethodsA prospectively maintained database was queried for all TABs performed between 1-1-2000 until 31-12-2017 at the University Hospital of Ioannina. Thus, inclusion criteria were made on the grounds of every patient that underwent a TAB during the above-mentioned period, regardless of demographic, clinical and laboratory data.ResultsTwo hundred forty-five TABs were included (149 females and 96 males), with a mean age of 64.5 (±3.5) years. The mean symptoms duration until admission to the hospital was 8.6 (±1.3) weeks and all had elevated acute phase reactants on admission. The reasons of admission were fever of unknown origin (FUO) in 114 (46.5%) patients, symptoms of polymyalgia rheumatica (PMR) in 84 (34.3%), new headache in 33 (13.5%), anemia of chronic disease (ACD) in 8 (3.32%) and eye disturbances in 6 (2.5%) patients. Positive results were found in 49 (20%) TABs. More specifically, in 14% of patients with FUO, 21% in those with PMR, while in patients with a new headache the percentage was 27%. Finally, 5 out of 6 (83.3%) of patients with ocular symptoms and only one (12.5%) of those suffering from ACD. Visual manifestations and FUO are correlated with a positive TAB.ConclusionIt seems that TAB is useful in assisting with GCA diagnosis, but lacks sensitivity.

scholarly journals Giant cell tumor formation due to metallosis after open latarjet and partial shoulder resurfacing

2020 ◽  
Vol 12 (2) ◽  
Author(s):  
Matthew Wolfson ◽  
Patrick Curtin ◽  
Emily J. Curry ◽  
Sandra Cerda ◽  
Xinning Li
Keyword(s):  
Giant Cell Tumor ◽  
Giant Cell ◽  
Shoulder Arthroplasty ◽  
Total Shoulder Arthroplasty ◽  
Tumor Formation ◽  
Cell Tumor ◽  
History Of ◽  
Pectoralis Major Transfer ◽  
Post Traumatic ◽  
Traumatic Arthritis

Shoulder metallosis with giant cell tumor formation is rarely seen in shoulder surgery. With an increase in shoulder arthroplasty and complex revision shoulder surgeries, clinicians should have an index of suspicion for possible metallosis in patients that presents with unexplained persistent pain with metal components on both the glenoid and humeral side. This case describes a 43-yearold female with a history of six prior shoulder surgeries who presented with shoulder metallosis and giant cell tumor formation after a screw from her open Latarjet procedure began rubbing against her Hemicap implant. She successfully underwent a revision total shoulder arthroplasty for post traumatic arthritis with pectoralis major transfer for her chronic subscapularis rupture and had complete symptom resolution.

scholarly journals The impact of temporal artery biopsy for the diagnosis of giant cell arteritis in clinical practice in a tertiary university hospital

PLoS ONE ◽  
2019 ◽  
Vol 14 (3) ◽  
pp. e0210845 ◽  
Author(s):  
Evripidis Kaltsonoudis ◽  
Eleftherios Pelechas ◽  
Alexandra Papoudou-Bai ◽  
Theodora E. Markatseli ◽  
Moses Elisaf ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Giant Cell Arteritis ◽  
Giant Cell ◽  
Temporal Artery ◽  
University Hospital ◽  
Temporal Artery Biopsy ◽  
The Impact

scholarly journals Poorly controlled diabetes mellitus alters placental structure, efficiency, and plasticity

2020 ◽  
Vol 8 (1) ◽  
pp. e001243
Author(s):  
Jackson Nteeba ◽  
Kaela M Varberg ◽  
Regan L Scott ◽  
Mikaela E Simon ◽  
Khursheed Iqbal ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Fetal Development ◽  
Trophoblast Invasion ◽  
Ambient Conditions ◽  
Placental Development ◽  
Junctional Zone ◽  
Pregnant Rat ◽  
Elevated Glucose ◽  
The Impact

IntroductionThe hemochorial placenta provides a critical barrier at the maternal–fetal interface to modulate maternal immune tolerance and enable gas and nutrient exchange between mother and conceptus. Pregnancy outcomes are adversely affected by diabetes mellitus; however, the effects of poorly controlled diabetes on placental formation, and subsequently fetal development, are not fully understood.Research design and methodsStreptozotocin was used to induce hyperglycemia in pregnant rats for the purpose of investigating the impact of poorly controlled diabetes on placental formation and fetal development. The experimental paradigm of hypoxia exposure in the pregnant rat was also used to assess properties of placental plasticity. Euglycemic and hyperglycemic rats were exposed to ambient conditions (~21% oxygen) or hypoxia (10.5% oxygen) beginning on gestation day (gd) 6.5 and sacrificed on gd 13.5. To determine whether the interaction of hyperglycemia and hypoxia was directly altering trophoblast lineage development, rat trophoblast stem (TS) cells were cultured in high glucose (25 mM) and/or exposed to low oxygen (0.5% to 1.5%).ResultsDiabetes caused placentomegaly and placental malformation, decreasing placental efficiency and fetal size. Elevated glucose disrupted rat TS cell differentiation in vitro. Evidence of altered trophoblast differentiation was also observed in vivo, as hyperglycemia affected the junctional zone transcriptome and interfered with intrauterine trophoblast invasion and uterine spiral artery remodeling. When exposed to hypoxia, hyperglycemic rats showed decreased proliferation and ectoplacental cone development on gd 9.5 and complete pregnancy loss by gd 13.5. Furthermore, elevated glucose concentrations inhibited TS cell responses to hypoxia in vitro.ConclusionsOverall, these results indicate that alterations in placental development, efficiency, and plasticity could contribute to the suboptimal fetal outcomes in offspring from pregnancies complicated by poorly controlled diabetes.

scholarly journals Embryotoxic impact of Zika virus in a rhesus macaque in vitro implantation model†

2020 ◽  
Vol 102 (4) ◽  
pp. 806-816 ◽  
Author(s):  
Lindsey N Block ◽  
Matthew T Aliota ◽  
Thomas C Friedrich ◽  
Michele L Schotzko ◽  
Katherine D Mean ◽  
...  
Keyword(s):  
Rhesus Macaque ◽  
Pregnancy Outcomes ◽  
Zika Virus ◽  
Negative Impact ◽  
Culture Media ◽  
Blastocyst Formation ◽  
Placental Development ◽  
Zikv Infection ◽  
The Impact

Abstract Zika virus (ZIKV) infection is associated with adverse pregnancy outcomes in humans, and infection in the first trimester can lead to miscarriage and stillbirth. Vertical and sexual transmissions of ZIKV have been demonstrated, yet the impact of infection during the initial stages of pregnancy remains unexplored. Here we defined the impact of ZIKV on early embryonic and placental development with a rhesus macaque model. During in vitro fertilization (IVF), macaque gametes were inoculated with a physiologically relevant dose of 5.48log10 plaque-forming units (PFU) of Zika virus/H.sapiens-tc/PUR/2015/PRVABC59_v3c2. Exposure at fertilization did not alter blastocyst formation rates compared to controls. To determine the impact of ZIKV exposure at implantation, hatched blastocysts were incubated with 3.26log10, 4.26log10, or 5.26log10 PFU, or not exposed to ZIKV, followed by extended embryo culture for 10 days. ZIKV exposure negatively impacted attachment, growth, and survival in comparison to controls, with exposure to 5.26log10 PFU ZIKV resulting in embryonic degeneration by day 2. Embryonic secretion of pregnancy hormones was lower in ZIKV-exposed embryos. Increasing levels of infectious virus were detected in the culture media post-exposure, suggesting that the trophectoderm is susceptible to productive ZIKV infection. These results demonstrate that ZIKV exposure severely impacts the zona-free blastocyst, whereas exposure at the time of fertilization does not hinder blastocyst formation. Overall, early stages of pregnancy may be profoundly sensitive to infection and pregnancy loss, and the negative impact of ZIKV infection on pregnancy outcomes may be underestimated.

scholarly journals The Role of Epigenetics in Placental Development and the Etiology of Preeclampsia

2019 ◽  
Vol 20 (11) ◽  
pp. 2837 ◽  
Author(s):  
Clara Apicella ◽  
Camino S. M. Ruano ◽  
Céline Méhats ◽  
Francisco Miralles ◽  
Daniel Vaiman
Keyword(s):  
Maternal Blood ◽  
Placental Development ◽  
Post Translational Modifications ◽  
Epigenetic Marks ◽  
Placental Function ◽  
Non Coding Rna ◽  
The Impact ◽  
Long Non Coding Rna ◽  
Potential Use

In this review, we comprehensively present the function of epigenetic regulations in normal placental development as well as in a prominent disease of placental origin, preeclampsia (PE). We describe current progress concerning the impact of DNA methylation, non-coding RNA (with a special emphasis on long non-coding RNA (lncRNA) and microRNA (miRNA)) and more marginally histone post-translational modifications, in the processes leading to normal and abnormal placental function. We also explore the potential use of epigenetic marks circulating in the maternal blood flow as putative biomarkers able to prognosticate the onset of PE, as well as classifying it according to its severity. The correlation between epigenetic marks and impacts on gene expression is systematically evaluated for the different epigenetic marks analyzed.

Role of epidermal growth factor (EGF) and its receptor in the development of the human placenta

1995 ◽  
Vol 7 (6) ◽  
pp. 1465 ◽  
Author(s):  
T Maruo ◽  
H Matsuo ◽  
T Otani ◽  
M Mochizuki
Keyword(s):  
Egf Receptor ◽  
Placental Lactogen ◽  
Immunocytochemical Staining ◽  
Placental Development ◽  
Ki 67 ◽  
Serum Free ◽  
C Cell ◽  
Serum Free Condition ◽  
And Function

To elucidate the role of EGF in human placental development, effects of EGF on the proliferation and differentiation of trophoblasts were investigated. Explants of trophoblastic tissues obtained from 4-5 week or 6-12 week placentas were, respectively, cultured with or without EGF, in the presence or absence of triiodo-L-thyronine (T3) in a serum-free condition. The proliferative activity was examined by immunocytochemical staining with an antibody Ki-67, and the differentiated function was assessed by the ability to secrete human chorionic gonadotrophin (hCG) and human placental lactogen (hPL). In 4-5 week placentas, EGF and EGF receptor were localized in cytotrophoblast (C-cell), and EGF augmented the proliferation of C-cell without affecting the ability to secrete hCG and hPL. In contrast, in 6-12 week placentas, EGF and EGF receptor were localized in syncytiotrophoblast (S-cell), and EGF stimulated the secretion of hCG and hPL without affecting the proliferation of C-cell. In situ hybridization with c-erb B probe revealed that c-erb B mRNA is expressed in the S-cell after 6 weeks' gestation. Column chromatography of the serum-free media obtained by 5-day culture of early placental tissues resulted in the elution of immunoreactive EGF. The addition of T3 (10(-8) mol L(-1)) resulted in increased secretion of immunoreactive EGF by placental explants. These findings suggest that EGF acts as an autocrine factor in regulating early placental growth and function in synergy with thyroid hormone.

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