scholarly journals Postnatal Cytoarchitecture and Neurochemical Hippocampal Dysfunction in Down Syndrome

2021 ◽  
Vol 10 (15) ◽  
pp. 3414
Author(s):  
David G. Moreno ◽  
Emma C. Utagawa ◽  
Nicoleta C. Arva ◽  
Kristian T. Schafernak ◽  
Elliott J. Mufson ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Pyramidal Cell ◽  
Hippocampal Neurons ◽  
Cellular Proliferation ◽  
Hippocampal Neurogenesis ◽  
Granule Cell Layer ◽  
Postnatal Life ◽  
Ki 67 ◽  
Basal Dendrites ◽  
Calbindin D

Although the prenatal hippocampus displays deficits in cellular proliferation/migration and volume, which are later associated with memory deficits, little is known about the effects of trisomy 21 on postnatal hippocampal cellular development in Down syndrome (DS). We examined postnatal hippocampal neuronal profiles from autopsies of DS and neurotypical (NTD) neonates born at 38-weeks’-gestation up to children 3 years of age using antibodies against non-phosphorylated (SMI-32) and phosphorylated (SMI-34) neurofilament, calbindin D-28k (Calb), calretinin (Calr), parvalbumin (Parv), doublecortin (DCX) and Ki-67, as well as amyloid precursor protein (APP), amyloid beta (Aβ) and phosphorylated tau (p-tau). Although the distribution of SMI-32-immunoreactive (-ir) hippocampal neurons was similar at all ages in both groups, pyramidal cell apical and basal dendrites were intensely stained in NTD cases. A greater reduction in the number of DCX-ir cells was observed in the hippocampal granule cell layer in DS. Although the distribution of Calb-ir neurons was similar between the youngest and oldest NTD and DS cases, Parv-ir was not detected. Conversely, Calr-ir cells and fibers were observed at all ages in DS, while NTD cases displayed mainly Calr-ir fibers. Hippocampal APP/Aβ-ir diffuse-like plaques were seen in DS and NTD. By contrast, no Aβ1–42 or p-tau profiles were observed. These findings suggest that deficits in hippocampal neurogenesis and pyramidal cell maturation and increased Calr immunoreactivity during early postnatal life contribute to cognitive impairment in DS.

scholarly journals Characterization of Cytokines and Proliferation Marker Ki67 in Chronic Rhinosinusitis with Nasal Polyps: A Pilot Study

Medicina ◽  
2021 ◽  
Vol 57 (6) ◽  
pp. 607
Author(s):  
Rudolfs Janis Viksne ◽  
Gunta Sumeraga ◽  
Mara Pilmane
Keyword(s):  
Connective Tissue ◽  
Chronic Rhinosinusitis ◽  
Nasal Polyps ◽  
Cellular Proliferation ◽  
Rank Correlation ◽  
Control Group ◽  
Relative Distribution ◽  
Proliferation Marker ◽  
Ki 67 ◽  
Stimulation Of

Background and Objectives: Chronic rhinosinusitis (CRS) is a condition that affects as much as 10.9% of the population and, along with presence of nasal polyps, is associated with significant morbidity and decreased quality of life. Studies on molecular pathways that have been activated in nasal polyp tissue are mainly based on cytokine concentration detection. Therefore, our aim is to investigate the complex appearance, relative distribution and interlinks of IL-1, IL-4, IL-6, IL-7, IL-8, IL-10, IL-12 and Ki 67 in chronic rhinosinusitis with nasal polyps (CRSwNP) affected human nasal mucosa. Materials and Methods: Samples of nasal polyps were obtained from 12 patients with previously diagnosed CRSwNP and no prior surgery. Control group consisted of samples from 17 otherwise healthy individuals with isolated nasal septum deviation. Tissues were stained for IL-1, IL-4, IL-6, IL-7, IL-8, IL-10, IL-12 and Ki67 immunohistochemically. Non-parametric statistic, Mann–Whitney U test and Spearman’s rank correlation coefficient were used. Results: All factors, except connective tissue cytokine IL-10 and proliferation marker Ki-67, had increased presence in connective tissue and decreased presence in epithelium of nasal polyps when compared to controls. Very strong and strong positive correlations between factors were observed. Conclusions: Decreased appearance of IL-1α, IL-4, IL-6, IL-7, IL-8, IL-10, IL-12 positive structures in the nasal epithelium with selective increase of IL-1α and IL-12 in nasal subepithelial connective tissue characterize the cytokine endotype with dysfunctional epithelial barrier and local stimulation of immune response in the connective tissue in case of chronic rhinosinusitis with polyps. Decrease of IL-6 in both—epithelium and connective tissue with strong correlation between it and IL-7 and IL-10 in connective tissue suggests significant stimulation of this regulatory cytokine and, possibly, the important role in pathogenesis of the development in nasal polyps. Correlations between Ki67 and cytokines indicate possible involvement of IL-4, IL-7 and IL-12 in regulation of cellular proliferation.

scholarly journals Mice lacking β-carotene-15,15’-dioxygenase exhibit reduced serum testosterone, prostatic androgen receptor signaling, and prostatic cellular proliferation

2016 ◽  
Vol 311 (6) ◽  
pp. R1135-R1148 ◽  
Author(s):  
Joshua W. Smith ◽  
Nikki A. Ford ◽  
Jennifer M. Thomas-Ahner ◽  
Nancy E. Moran ◽  
Eric C. Bolton ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Cellular Proliferation ◽  
Serum Testosterone ◽  
Cell Number ◽  
Immunofluorescent Staining ◽  
Receptor Signaling ◽  
Ki 67 ◽  
Androgen Receptor Signaling ◽  
Testosterone Levels ◽  
Β Carotene

β-Carotene-15,15’-dioxygenase (BCO1) cleaves dietary carotenoids at the central 15,15’ double bond, most notably acting on β-carotene to yield retinal. However, Bco1 disruption also impacts diverse physiological end points independent of dietary carotenoid feeding, including expression of genes controlling androgen metabolism. Using the Bco1−/− mouse model, we sought to probe the effects of Bco1 disruption on testicular steroidogenesis, prostatic androgen signaling, and prostatic proliferation. Male wild-type (WT) and Bco1−/− mice were raised on carotenoid-free AIN-93G diets before euthanasia between 10 and 14 wk of age. Weights of the prostate and seminal vesicles were significantly lower in Bco1−/− than in WT mice (−18% and −29%, respectively). Serum testosterone levels in Bco1−/− mice were significantly reduced by 73%. Bco1 disruption significantly reduced Leydig cell number and decreased testicular mRNA expression of Hsd17b3, suggesting inhibition of testicular testosterone synthesis. Immunofluorescent staining of the androgen receptor (AR) in the dorsolateral prostate lobes of Bco1−/− mice revealed a decrease in AR nuclear localization. Analysis of prostatic morphology suggested decreases in gland size and secretion. These findings were supported by reduced expression of the proliferation marker Ki-67 in Bco1−/− prostates. Expression analysis of 200 prostate cancer- and androgen-related genes suggested that Bco1 loss significantly disrupted prostatic androgen receptor signaling, cell cycle progression, and proliferation. This is the first demonstration that Bco1 disruption lowers murine circulating testosterone levels and thereby reduces prostatic androgen receptor signaling and prostatic cellular proliferation, further supporting the role of this protein in processes more diverse than carotenoid cleavage.

Ki-67/MIB-1 and Recurrence in Pituitary Adenoma

2021 ◽  
Author(s):  
Kent Tadokoro ◽  
Colten Wolf ◽  
Joseph Toth ◽  
Cara Joyce ◽  
Meharvan Singh ◽  
...  
Keyword(s):  
Systematic Review ◽  
Pituitary Adenoma ◽  
Recurrence Rate ◽  
Pituitary Adenomas ◽  
Cellular Proliferation ◽  
Published Data ◽  
Ki 67 ◽  
Institutional Data ◽  
Mib 1

Abstract Objectives Ki-67/MIB-1 is a marker of cellular proliferation used as a pathological parameter in the clinical assessment of pituitary adenomas, where its expression has shown utility in predicting the invasiveness of these tumors. However, studies have shown variable results when using Ki-67/MIB-1 association with recurrence. The purpose of this study is to determine if a high Ki-67/MIB-1 labeling index (LI) is predictive of recurrence in pituitary adenomas. Methods A retrospective chart review was performed for patients undergoing pituitary adenoma resection with at least 1 year of follow-up. Additionally, systematic data searches were performed and included studies that correlated recurrence rate to Ki-67/MIB-1 LI. Our institutional data were included in a synthesis with previously published data. Results Our institutional review included 79 patients with a recurrence rate of 26.6%. We found that 8.8% of our patients had a high Ki-67/MIB-1 LI (>3%); however, high Ki-67/MIB-1 was not associated with recurrence. The systematic review identified 244 articles and 49 full-text articles that were assessed for eligibility. Quantitative analysis was performed on 30 articles including our institutional data and 18 studies reported recurrence by level of Ki-67/MIB-1 LI. Among studies that compared Ki-67/MIB-1 ≥3 vs. <3%, 10 studies reported odds ratios (OR) greater than 1 of which 6 were statistically significant. A high Ki-67/MIB-1 had higher odds of recurrence via the pooled odds ratio (OR = 4.15, 95% confidence interval [CI]: 2.31–7.42). Conclusion This systematic review suggests that a high Ki-67/MIB-1 should prompt an increased duration of follow-up due to the higher odds of recurrence of pituitary adenoma.

Abstract 1414: Pim-1 Stimulates Cardiac Progenitor Cell Proliferation And Asymmetric Division

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Christopher T Cottage ◽  
Savilla Tuck ◽  
Kimberlee Fischer ◽  
Natalie Gude ◽  
John Muraski ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Cell Fate ◽  
Cellular Proliferation ◽  
Gene Promoter ◽  
Asymmetric Division ◽  
Postnatal Growth ◽  
Chain Gene ◽  
Ki 67 ◽  
Population Number ◽  
Mechanistic Basis

Cardiac progenitor cells (CPCs) blunt cardiomyopathic damage and increase survival following adoptive transfer into hearts subjected to myocardial infarction (MI), but the initial survival, persistence, and long term engraftment of the donated cell population remains problematic. Previous studies from our group have demonstrated that transgenes driven by the α -myosin heavy chain gene promoter are expressed in the CPC population allowing for enhanced proliferation and survival. This study details a genetic engineering strategy to augment the salutary effects of CPCs through the use of a serine/threonine kinase named Pim-1 that promotes cellular proliferation and survival. Transgenic mice created with cardiac-specific Pim-1 overexpression (Pim-wt) exhibit enhanced Pim-1 activity in both cardiomyocytes and CPCs, both of which show increased proliferative activity assessed using BrdU or Ki-67 markers relative to non-transgenic (NTG) controls. However, CPC population number was not increased in the Pim-wt hearts during normal postnatal growth or after infarction challenge, suggesting that Pim-1 expression promotes asymmetric division resulting in maintenance of the CPC pool as well as expansion of the cardiomyocyte population. Localization and quantitation of cell fate determinants Numb and α -adaptin by confocal microscopy were employed to assess levels of asymmetric division in the CPC population. Polarization of Numb in mitotic phospho-histone positive cells demonstrates asymmetric division in 65% of the CPC population in hearts of Pim-wt mice versus 26% in NTG hearts after infarction challenge. Similarly, Pim-wt hearts had fewer cells with uniform α -adaptin staining indicative of symmetrically dividing CPCs, with in 36% of the CPCs versus vs. 73% in NTG sections. These findings define a mechanistic basis for enhanced myocardial regeneration in transgenic mice overexpressing Pim-1 kinase in the myocardial lineage cells.

scholarly journals Cellular Proliferation Index between Carcinoma Ex-Pleomorphic Adenoma and Pleomorphic Adenoma

2015 ◽  
Vol 26 (4) ◽  
pp. 416-421 ◽  
Author(s):  
Fernanda Viviane Mariano ◽  
Ana Flávia Costa ◽  
Rogério Oliveira Gondak ◽  
Antonio Santos Martins ◽  
André Del Negro ◽  
...  
Keyword(s):  
Minimally Invasive ◽  
Pleomorphic Adenoma ◽  
Cellular Proliferation ◽  
Sarcomatoid Carcinoma ◽  
Proliferation Index ◽  
Carcinoma Ex Pleomorphic Adenoma ◽  
Proliferative Index ◽  
Salivary Duct ◽  
Ki 67 ◽  
Duct Carcinoma

<p>Carcinoma ex pleomorphic adenoma (CXPA) has been considered an interesting model of carcinogenesis, presenting various histological subtypes and invasiveness phase. The objective was to determine the proliferative index of CXPA and comparing to pleomorphic adenoma (PA). Thirty six cases of CXPA (36 PA) and 22 areas of PA in CXPA (residual PA) were studied by Ki-67 expression. All CXPA cases were classified according to invasiveness phase (intracapsular, minimally and frankly invasive) and histopathological subtypes. Data was statistically analyzed by Wilcoxon, Mann-Whitney and Kruskal-Wallis tests. CXPA included 5 intracapsular, 9 minimally invasive and 22 frankly invasive cases. Fifteen cases corresponded to salivary duct carcinoma, 7 to adenocarcinoma NOS, 7 myoepithelial, 5 epithelial-myoepithelial, one case of squamous cell and one case of sarcomatoid carcinoma. The Ki-67 index of PA and residual PA were significantly lower than CXPA. Intracapsular and minimally invasive showed smaller proliferative index than frankly invasive. Considering the subtypes of CXPA, there was not a statistic difference among them. Ki-67 is a useful marker in the differential diagnosis of PA and CXPA, even when in the early invasive phase.</p>

scholarly journals Ki-67 expression in mature B-cell neoplasms: a flow cytometry study

2018 ◽  
Vol 64 (6) ◽  
pp. 525-529 ◽  
Author(s):  
Natália Marcondes ◽  
Flavo Fernandes ◽  
Gustavo Faulhaber
Keyword(s):  
Flow Cytometry ◽  
B Cell ◽  
Cellular Proliferation ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Ki 67 ◽  
Large B Cell Lymphoma ◽  
Flow Cytometry Study ◽  
Mantle Cell ◽  
Surface Staining

SUMMARY OBJECTIVE: Ki-67 is a nuclear protein associated with cellular proliferation in normal or leukemic conditions that can help identify more aggressive diseases and is usually evaluated with immunohistochemistry. The aim of this was to assess Ki-67 expression on mature B-cell neoplasms samples with flow cytometry immunophenotyping. METHOD: After surface staining with CD19 and CD45, intracellular staining for Ki-67 was performed in leukemic mature B-cells. Ki-67 expression was evaluated with flow cytometry. RESULTS: Ki-67 expression was higher in mantle cell lymphoma, Burkitt lymphoma, and diffuse large B-cell lymphoma cases. It was also associated with CD38 mean fluorescence intensity. CONCLUSIONS: Ki-67 expression evaluated by flow cytometry can be a useful tool in the diagnosis of mature B-cell neoplasms. More studies are needed to validate Ki-67 assessment with flow cytometry immunophenotyping.

Ts65Dn, a Mouse Model of Down Syndrome, Exhibits Increased GABAB-Induced Potassium Current

2007 ◽  
Vol 97 (1) ◽  
pp. 892-900 ◽  
Author(s):  
Tyler K. Best ◽  
Richard J. Siarey ◽  
Zygmunt Galdzicki
Keyword(s):  
Down Syndrome ◽  
Mouse Model ◽  
Hippocampal Neurons ◽  
Single Channel ◽  
Extra Chromosome ◽  
Functional Expression ◽  
Chromosome 21 ◽  
Fluctuation Analysis ◽  
Response Curves ◽  
Girk Channel

Down syndrome (DS) is the most common nonheritable cause of mental retardation. DS is the result of the presence of an extra chromosome 21 and its phenotype may be a consequence of overexpressed genes from that chromosome. One such gene is Kcnj6/Girk2, which encodes the G-protein-coupled inward rectifying potassium channel subunit 2 (GIRK2). We have recently shown that the DS mouse model, Ts65Dn, overexpresses GIRK2 throughout the brain and in particular the hippocampus. Here we report that this overexpression leads to a significant increase (∼2-fold) in GABAB-mediated GIRK current in primary cultured hippocampal neurons. The dose response curves for peak and steady-state GIRK current density is significantly shifted left toward lower concentrations of baclofen in Ts65Dn neurons compared with diploid controls, consistent with increased functional expression of GIRK channels. Stationary fluctuation analysis of baclofen-induced GIRK current from Ts65Dn neurons indicated no significant change in single-channel conductance compared with diploid. However, significant increases in GIRK channel density was found in Ts65Dn neurons. In normalized baclofen-induced GIRK current and GIRK current kinetics no difference was found between diploid and Ts65Dn neurons, which suggests unimpaired mechanisms of interaction between GIRK channel and GABAB receptor. These results indicate that increased expression of GIRK2 containing channels have functional consequences that likely affect the balance between excitatory and inhibitory neuronal transmission.

scholarly journals Haploinsufficiency of the psychiatric risk gene Cyfip1 causes abnormal postnatal hippocampal neurogenesis through microglial and Arp2/3 mediated actin dependent mechanisms

2018 ◽  
Author(s):  
Niels Haan ◽  
Laura J Westacott ◽  
Jenny Carter ◽  
Michael J Owen ◽  
William P Gray ◽  
...  
Keyword(s):  
Genetic Risk ◽  
Hippocampal Neurons ◽  
Hippocampal Neurogenesis ◽  
Actin Dynamics ◽  
Biological Processes ◽  
Risk Gene ◽  
A Cell ◽  
Adult Born Neurons ◽  
Newborn Neurons ◽  
And Migration

AbstractGenetic risk factors can significantly increase chances of developing psychiatric disorders, but the underlying biological processes through which this risk is effected remain largely unknown. Here we show that haploinsufficiency of Cyfip1, a candidate risk gene present in the pathogenic 15q11.2(BP1-BP2) deletion may impact on psychopathology via abnormalities in cell survival and migration of newborn neurons during postnatal hippocampal neurogenesis. We demonstrate that haploinsufficiency of Cyfip1 leads to increased numbers of adult born hippocampal neurons due to reduced apoptosis, without altering proliferation. We confirm this is due to a cell autonomous failure of microglia to induce apoptosis through the secretion of the appropriate factors. Furthermore, we show an abnormal migration of adult-born neurons due to altered Arp2/3 mediated actin dynamics. Together, our findings throw new light on how the genetic risk candidate Cyfip1 may influence the hippocampus, a brain region with strong evidence for involvement in psychopathology.

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