scholarly journals The Hypothesis of the Prolonged Cell Cycle in Turner Syndrome

2021 ◽  
Author(s):  
Francisco Álvarez-Nava
Keyword(s):  
Cell Cycle ◽  
Turner Syndrome ◽  
Low Birthweight ◽  
Sex Chromosome ◽  
Heart Diseases ◽  
Cellular Growth ◽  
Proliferating Cells ◽  
Cycle Frequency ◽  
Increased Risk ◽  
New Findings

Turner syndrome (TS) is a chromosomal disorder that is caused by a missing or structurally abnormal second sex chromosome. Subjects with TS are at an increased risk of developing intrauterine growth retardation, low birthweight, short stature, congenital heart diseases, infertility, obesity, dyslipidemia, hypertension, insulin resistance, type 2 diabetes mellitus, metabolic syndrome, and cardiovascular diseases (stroke and myocardial infarction). The underlying pathogenetic mechanism of TS is unknown. The assumption that X chromosome-linked gene haploinsufficiency is associated with the TS phenotype is questioned since such genes have not been identified. Thus, other pathogenic mechanisms have been suggested to explain this phenotype. Morphogenesis encompasses a series of events that includes cell division, the production of migratory precursors and their progeny, differentiation, programmed cell death and integration into organs and systems. The precise control of the growth and differentiation of cells is essential for normal development. The cell cycle frequency and the number of proliferating cells are essential in cell growth. 45,X cells have a failure to proliferate at a normal rate, leading to a decreased cell number in a given tissue during organogenesis. A convergence of data indicates an association between a prolonged cell cycle and the phenotypical features in Turner syndrome. This review aims to examine old and new findings concerning the relationship between a prolonged cell cycle and TS phenotype. These studies reveal a diversity of phenotypic features in TS that could be explained by reduced cell proliferation. The implications of this hypothesis for our understanding of the TS phenotype and its pathogenesis are discussed. It is not surprising that 45,X monosomy leads to cellular growth pathway dysregulation with profound deleterious effects on both embryonic and later stages of development. The prolonged cell cycle could represent the beginning of the pathogenesis of TS, leading to a series of phenotypic consequences in embryonic/fetal, neonatal, pediatric, adolescence, and adulthood life.

Expression of Cell Cycle Regulatory Proteins and Analysis of Apoptosis in Normal Nasal Mucosa and in Nasal Polyps

2005 ◽  
Vol 19 (6) ◽  
pp. 549-553 ◽  
Author(s):  
Werner Garavello ◽  
Paola Viganò ◽  
Marco Romagnoli ◽  
Lorenza Sordo ◽  
Emilio Berti ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Nasal Mucosa ◽  
Nasal Polyps ◽  
Normal Mucosa ◽  
Cellular Growth ◽  
Regulatory Proteins ◽  
Biological Behavior ◽  
Proliferating Cells ◽  
Ki 67 ◽  
Sequence Of Events

Background The etiopathogenesis of nasal polyps still is to be clarified. Although hyperplasia is a typical feature of these pathological processes, little attention has been paid to specific aspects of cellular growth in polyps. We have evaluated the expression and localization of some of the regulatory proteins that direct the cell through the specific sequence of events culminating in mitosis or apoptosis in nasal polyps. Methods Twenty samples of nasal polyps and 20 samples of normal nasal mucosa have been analyzed for apoptotic index by detecting the DNA 3’ OH ends deriving from DNA fragmentation. Moreover, they have been evaluated by immunohistochemical staining for expression of Ki-67, cyclins A and B1, p53, p21, p27, murine double minute clone 2, and Bcl-2. Results We have identified a greater proportion of proliferating cells in the lining epithelial cells of the polyps when compared with the normal mucosa as stained with anti–Ki-67 antibodies. An overexpression of p53, MDM2, and Bcl-2 and an increased apoptosis were observed in nasal polyps compared with the normal mucosa, whereas no variation of p27 expression was observed. The p21 and cyclins A and B1 were rarely expressed in both pathological and normal tissue. Conclusion The p53-based control system of cell cycle progression appears to be altered in nasal polyps, potentially leading to an abrogation of the DNA damage checkpoint. Evaluation of the expression of the regulatory proteins that direct the cells throughout their cycle in nasal polyps may allow a better understanding of the biological behavior and clinical outcome of these benign pathological entities.

scholarly journals Care of girls and women with Turner syndrome: beyond growth and hormones

2017 ◽  
Vol 6 (4) ◽  
pp. R39-R51 ◽  
Author(s):  
Caroline Culen ◽  
Diana-Alexandra Ertl ◽  
Katharina Schubert ◽  
Lisa Bartha-Doering ◽  
Gabriele Haeusler
Keyword(s):  
Turner Syndrome ◽  
Psychosocial Development ◽  
Sex Chromosome ◽  
Psychosocial Care ◽  
Adult Care ◽  
Increased Risk ◽  
Optimal Screening ◽  
Age Appropriate ◽  
Physical Features

Turner syndrome (TS), although considered a rare disease, is the most common sex chromosome abnormality in women, with an incident of 1 in 2500 female births. TS is characterized by distinctive physical features such as short stature, ovarian dysgenesis, an increased risk for heart and renal defects as well as a specific cognitive and psychosocial phenotype. Given the complexity of the condition, patients face manifold difficulties which increase over the lifespan. Furthermore, failures during the transitional phase to adult care result in moderate health outcomes and decreased quality of life. Guidelines on the optimal screening procedures and medical treatment are easy to find. However, recommendations for the treatment of the incriminating psychosocial aspects in TS are scarce. In this work, we first reviewed the literature on the cognitive and psychosocial development of girls with TS compared with normal development, from disclosure to young adulthood, and then introduce a psychosocial approach to counseling and treating patients with TS, including recommendations for age-appropriate psychological diagnostics. With this work, we aim to facilitate the integration of emphasized psychosocial care in state-of-the-art treatment for girls and women with TS.

scholarly journals Prevalence and Physical Distribution of SRY in the Gonads of a Woman with Turner Syndrome: Phenotypic Presentation, Tubal Formation, and Malignancy Risk

2017 ◽  
Vol 88 (3-4) ◽  
pp. 291-297 ◽  
Author(s):  
Tamar G. Baer ◽  
Christopher E. Freeman ◽  
Claudia Cujar ◽  
Mahesh Mansukhani ◽  
Bahadur  Singh ◽  
...  
Keyword(s):  
Turner Syndrome ◽  
Y Chromosome ◽  
Sex Chromosome ◽  
Heterogeneous Distribution ◽  
Gonadal Tissue ◽  
Malignancy Risk ◽  
Monosomy X ◽  
Increased Risk ◽  
A Cell ◽  
Chromosome Material

Although monosomy X is the most common karyotype in patients with Turner syndrome, the presence of Y chromosome material has been observed in about 10% of patients. Y chromosome material in patients with Turner syndrome poses an increased risk of gonadoblastoma and malignant transformation. We report a woman with a diagnosis of Turner syndrome at 12 years of age, without signs of virilization, and karyotype reported as 46,X,del(X)(q13). At 26 years, cytogenetic studies indicated the patient to be mosaic for monosomy X and a cell line that contained a du­plicated Yq chromosome. Bilateral gonadectomy was performed and revealed streak gonads, without evidence of gonadoblastoma. Histological analysis showed ovarian stromal cells with few primordial tubal structures. FISH performed on streak gonadal tissue showed a heterogeneous distribution of SRY, with exclusive localization to the primordial tubal structures. DNA extraction from the gonadal tissue showed a 6.5% prevalence of SRY by microarray analysis, contrasting the 86% prevalence in the peripheral blood sample. This indicates that the overall gonadal sex appears to be determined by the majority gonosome complement in gonadal tissue in cases of sex chromosome mosaicism. This case also raises questions regarding malignancy risk associated with Y prevalence and tubal structures in gonadal tissue.

Y chromosome in Turner syndrome: detection of hidden mosaicism and the report of a rare X;Y translocation case

2014 ◽  
Vol 26 (8) ◽  
pp. 1176 ◽  
Author(s):  
Adriana Valéria Sales Bispo ◽  
Pollyanna Burégio-Frota ◽  
Luana Oliveira dos Santos ◽  
Gabriela Ferraz Leal ◽  
Andrea Rezende Duarte ◽  
...  
Keyword(s):  
Turner Syndrome ◽  
Y Chromosome ◽  
Sex Chromosome ◽  
Genetic Disorder ◽  
In Situ Hybridisation ◽  
Normal Female ◽  
Fluorescence In Situ Hybridisation ◽  
Partial Monosomy ◽  
Chromosome Mosaicism ◽  
Increased Risk

Turner syndrome (TS) is a common genetic disorder in females associated with the absence of complete or parts of a second sex chromosome. In 5–12% of patients, mosaicism for a cell line with a normal or structurally abnormal Y chromosome is identified. The presence of Y-chromosome material is of medical importance because it results in an increased risk of developing gonadal tumours and virilisation. Molecular study and fluorescence in situ hybridisation approaches were used to study 74 Brazilian TS patients in order to determine the frequency of hidden Y-chromosome mosaicism, and to infer the potential risk of developing malignancies. Additionally, we describe one TS girl with a very uncommon karyotype 46,X,der(X)t(X;Y)(p22.3?2;q11.23) comprising a partial monosomy of Xp22.3?2 together with a partial monosomy of Yq11.23. The presence of cryptic Y-chromosome-specific sequences was detected in 2.7% of the cases. All patients with Y-chromosome-positive sequences showed normal female genitalia with no signs of virilisation. Indeed, the clinical data from Y-chromosome-positive patients was very similar to those with Y-negative results. Therefore, we recommend that the search for hidden Y-chromosome mosaicism should be carried out in all TS cases and not be limited to virilised patients or carriers of a specific karyotype.

Neuroradiology Manifestations of Li-Fraumeni Syndrome: Epidemiology, Genetics, Imaging Findings, and Management

Neurographics ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 228-235
Author(s):  
S. Naganawa ◽  
T. Donohue ◽  
A. Capizzano ◽  
Y. Ota ◽  
J. Kim ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Soft Tissue Sarcomas ◽  
Suppressor Gene ◽  
Imaging Findings ◽  
Li Fraumeni Syndrome ◽  
Increased Risk ◽  
Li Fraumeni ◽  
Risk Of Cancer

Li-Fraumeni syndrome is a familial cancer predisposition syndrome associated with germline mutation of the tumor suppressor gene 53, which encodes the tumor suppressor p53 protein. Affected patients are predisposed to an increased risk of cancer development, including soft-tissue sarcomas, breast cancer, brain tumors, and adrenocortical carcinoma, among other malignancies. The tumor suppressor gene TP53 plays an important, complex role in regulating the cell cycle, collaborating with transcription factors and other proteins. The disruption of appropriate cell cycle regulation by mutated TP53 is considered to be the cause of tumorigenesis in Li-Fraumeni syndrome. Appropriate surveillance, predominantly by using MR imaging, is used for early malignancy screening in an effort to improve the survival rate among individuals who are affected. Patients with Li-Fraumeni syndrome are also at increased risk for neoplasm development after radiation exposure, and, therefore, avoiding unnecessary radiation in both the diagnostic and therapeutic settings is paramount. Here, we review the epidemiology, genetics, imaging findings, and the current standard surveillance protocol for Li-Fraumeni syndrome from the National Comprehensive Cancer Network as well as potential treatment options.Learning Objective: Describe the cause of second primary malignancy among patients with Li-Fraumeni syndrome.

scholarly journals Adolescent, Pregnant, and HIV-Infected: Risk of Adverse Pregnancy and Perinatal Outcomes in Young Women from Southern Mozambique

2021 ◽  
Vol 10 (8) ◽  
pp. 1564
Author(s):  
Clara Pons-Duran ◽  
Aina Casellas ◽  
Azucena Bardají ◽  
Anifa Valá ◽  
Esperança Sevene ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Maternal Morbidity ◽  
Low Birthweight ◽  
Negative Binomial ◽  
Perinatal Outcomes ◽  
Sub Saharan Africa ◽  
P Value ◽  
Increased Risk ◽  
Adverse Pregnancy ◽  
The Impact

Sub-Saharan Africa concentrates the burden of HIV and the highest adolescent fertility rates. However, there is limited information about the impact of the interaction between adolescence and HIV infection on maternal health in the region. Data collected prospectively from three clinical trials conducted between 2003 and 2014 were analysed to evaluate the association between age, HIV infection, and their interaction, with the risk of maternal morbidity and adverse pregnancy and perinatal outcomes in women from southern Mozambique. Logistic regression and negative binomial models were used. A total of 2352 women were included in the analyses; 31% were adolescents (≤19 years) and 29% HIV-infected women. The effect of age on maternal morbidity and pregnancy and perinatal adverse outcomes was not modified by HIV status. Adolescence was associated with an increased incidence of hospital admissions (IRR 0.55, 95%CI 0.37–0.80 for women 20–24 years; IRR 0.60, 95%CI 0.42–0.85 for women >25 years compared to adolescents; p-value < 0.01) and outpatient visits (IRR 0.86, 95%CI 0.71–1.04; IRR 0.76, 95%CI 0.63–0.92; p-value = 0.02), and an increased likelihood of having a small-for-gestational age newborn (OR 0.50, 95%CI 0.38–0.65; OR 0.43, 95%CI 0.34–0.56; p-value < 0.001), a low birthweight (OR 0.40, 95%CI 0.27–0.59; OR 0.37, 95%CI 0.26–0.53; p-value <0.001) and a premature birth (OR 0.42, 95%CI 0.24–0.72; OR 0.51, 95%CI 0.32–0.82; p-value < 0.01). Adolescence was associated with an increased risk of poor morbidity, pregnancy and perinatal outcomes, irrespective of HIV infection. In addition to provision of a specific maternity care package for this vulnerable group interventions are imperative to prevent adolescent pregnancy.

scholarly journals Severe haemophilia A in a preterm girl with Turner syndrome: case report – a diagnostic and therapeutic challenge for a paediatrician (Part 2)

2021 ◽  
Vol 47 (1) ◽  
Author(s):  
Berendt Agnieszka ◽  
Wójtowicz-Marzec Monika ◽  
Wysokińska Barbara ◽  
Kwaśniewska Anna
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Family History ◽  
Factor Viii ◽  
Turner Syndrome ◽  
Factor Viii Inhibitor ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Prolonged Bleeding ◽  
Increased Risk

Abstract Background Haemophilia A is an X-linked genetic condition which manifests itself mainly in male children in the first 2 years of life, during gross motor skill development. This disorder is rare in females. The clinical manifestation of severe haemophilia in preterm infants poses a great challenge to the therapeutic team. As extreme prematurity is linked to an increased risk of central nervous system or gastrointestinal bleeding, a well-informed and balanced treatment from the first days of life is crucial to prevent long-term damage. Haemophilia is most commonly caused by inheriting defective genes, and can also be linked to skewed X inactivation and Turner syndrome. The coincidental occurrence of haemophilia A and Turner syndrome is extremely rare, with only isolated cases described to date. Hence, a multidisciplinary approach is needed. Case presentation The authors report on a preterm girl (gestational age 28 weeks) diagnosed with haemophilia and Turner syndrome. The first manifestation of haemophilia was prolonged bleeding from injection sites on the second day of life. Indeterminate aPTT and factor VIII level < 1% confirmed the diagnosis of haemophilia A. Dysmorphic features which did not match the typical clinical picture of haemophilia, the female sex, and a negative paternal family history led to the diagnosis of Turner syndrome. While in hospital, the girl received multiple doses of recombinant factor VIII in response to prolonged bleedings from the injection sites and from a nodule on the girl’s head, and before and after retinal laser photocoagulation. No central nervous system or abdominal cavity bleeding was observed. The substitutive therapy was complicated by the development of factor VIII inhibitor (anti-factor VIII (FVIII) antibodies). Treatment was continued with recombinant factor VIIa. This article aims at demonstrating the complexity of the diagnostics and treatment of a preterm child with two genetic disorders. Conclusions Haemophilia should always be considered in the differential diagnosis of prolonged bleeding, even in patients with a negative family history. In the case of coinciding atypical phenotypic features, further diagnostics for another genetic disease are recommended. Infant care should follow current care standards, while considering certain individual features.

scholarly journals Centrosome Dynamics and Its Role in Inflammatory Response and Metastatic Process

Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 629
Author(s):  
Massimo Pancione ◽  
Luigi Cerulo ◽  
Andrea Remo ◽  
Guido Giordano ◽  
Álvaro Gutierrez-Uzquiza ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Rho Gtpases ◽  
Human Cancer ◽  
Genetic Disorders ◽  
Cell Cycle Checkpoint ◽  
Animal Cells ◽  
Normal Tissues ◽  
Checkpoint Pathway ◽  
New Findings ◽  
Cycle Checkpoint

Metastasis is a process by which cancer cells escape from the location of the primary tumor invading normal tissues at distant organs. Chromosomal instability (CIN) is a hallmark of human cancer, associated with metastasis and therapeutic resistance. The centrosome plays a major role in organizing the microtubule cytoskeleton in animal cells regulating cellular architecture and cell division. Loss of centrosome integrity activates the p38-p53-p21 pathway, which results in cell-cycle arrest or senescence and acts as a cell-cycle checkpoint pathway. Structural and numerical centrosome abnormalities can lead to aneuploidy and CIN. New findings derived from studies on cancer and rare genetic disorders suggest that centrosome dysfunction alters the cellular microenvironment through Rho GTPases, p38, and JNK (c-Jun N-terminal Kinase)-dependent signaling in a way that is favorable for pro-invasive secretory phenotypes and aneuploidy tolerance. We here review recent data on how centrosomes act as complex molecular platforms for Rho GTPases and p38 MAPK (Mitogen activated kinase) signaling at the crossroads of CIN, cytoskeleton remodeling, and immune evasion via both cell-autonomous and non-autonomous mechanisms.

scholarly journals Ano1 as a regulator of proliferation

2011 ◽  
Vol 301 (6) ◽  
pp. G1044-G1051 ◽  
Author(s):  
Jennifer E. Stanich ◽  
Simon J. Gibbons ◽  
Seth T. Eisenman ◽  
Michael R. Bardsley ◽  
Jason R. Rock ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Slow Wave ◽  
Interstitial Cells Of Cajal ◽  
Primary Cultures ◽  
Channel Blockers ◽  
Proliferating Cells ◽  
Stromal Tumors ◽  
Whole Mount ◽  
Cells Of Cajal ◽  
Regular Medium

Ano1 is a recently discovered Ca2+-activated Cl− channel expressed on interstitial cells of Cajal (ICC) that has been implicated in slow-wave activity in the gut. However, Ano1 is expressed on all classes of ICC, even those that do not contribute to generation of the slow wave, suggesting that Ano1 may have an alternate function in these cells. Ano1 is also highly expressed in gastrointestinal stromal tumors. Mice lacking Ano1 had fewer proliferating ICC in whole mount preparations and in culture, raising the possibility that Ano1 is involved in proliferation. Cl− channel blockers decreased proliferation in cells expressing Ano1, including primary cultures of ICC and in the pancreatic cancer-derived cell line, CFPAC-1. Cl− channel blockers had a reduced effect on Ano1(−/−) cultures, confirming that the blockers are acting on Ano1. Ki67 immunoreactivity, 5-ethynyl-2′-deoxyuridine incorporation, and cell-cycle analysis of cells grown in low-Cl− media showed fewer proliferating cells than in cultures grown in regular medium. We confirmed that mice lacking Ano1 had less phosphorylated retinoblastoma protein compared with controls. These data led us to conclude that Ano1 regulates proliferation at the G1/S transition of the cell cycle and may play a role in tumorigenesis.

scholarly journals The Small Subunit Processome Is Required for Cell Cycle Progression at G1

2004 ◽  
Vol 15 (11) ◽  
pp. 5038-5046 ◽  
Author(s):  
Kara A. Bernstein ◽  
Susan J. Baserga
Keyword(s):  
Cell Cycle ◽  
Ribosome Biogenesis ◽  
Cell Cycle Progression ◽  
Small Subunit ◽  
Cellular Growth ◽  
Yeast Cells ◽  
G1 Phase ◽  
Relay Cell ◽  
Ssu Processome ◽  
Nucleolar Rna

Without ribosome biogenesis, translation of mRNA into protein ceases and cellular growth stops. We asked whether ribosome biogenesis is cell cycle regulated in the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe, and we determined that it is not regulated in the same manner as in metazoan cells. We therefore turned our attention to cellular sensors that relay cell size information via ribosome biogenesis. Our results indicate that the small subunit (SSU) processome, a complex consisting of 40 proteins and the U3 small nucleolar RNA necessary for ribosome biogenesis, is not mitotically regulated. Furthermore, Nan1/Utp17, an SSU processome protein, does not provide a link between ribosome biogenesis and cell growth. However, when individual SSU processome proteins are depleted, cells arrest in the G1 phase of the cell cycle. This arrest was further supported by the lack of staining for proteins expressed in post-G1. Similarly, synchronized cells depleted of SSU processome proteins did not enter G2. This suggests that when ribosomes are no longer made, the cells stall in the G1. Therefore, yeast cells must grow to a critical size, which is dependent upon having a sufficient number of ribosomes during the G1 phase of the cell cycle, before cell division can occur.

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