scholarly journals A Comprehensive Modeling Procedure for the Human Granulopoietic System: Over-all View and Summary of Data

Blood ◽  
1973 ◽  
Vol 42 (2) ◽  
pp. 303-313 ◽  
Author(s):  
Leslie E. Blumenson
Keyword(s):  
Peripheral Blood ◽  
Marrow Cell ◽  
Cell Types ◽  
Cellular Level ◽  
Laboratory Research ◽  
Modeling Procedure ◽  
Cellular Events ◽  
Rapid Pace ◽  
The One ◽  
Comprehensive Modeling

Abstract Understanding of the granulopoietic system in both normal and diseased states might be assisted by the use of a quantitative modeling procedure that relates the underlying cellular events of granulopoiesis studied in the laboratory to the marrow and peripheral blood picture as it might be seen in the clinic. In this way, the modeling procedure could become both an adjunct to ongoing laboratory research, as well as a means for rationally deciding on modes of treatment for pathologic conditions. The depth and rapid pace of modern granulopoietic research require that the modeling procedure be, on the one hand, detailed enough to permit the inclusion of the pertinent events at the cellular level as they are known today, while on the other hand, remain flexible enough to permit both the modification of any part and the possibility of seeing the predicted consequences of this modification for both the normal and diseased states. A detailed procedure was developed for an hour-by-hour description of the interrelationship of the kinetics of the various marrow cell types with the events in the peripheral blood and tissue spaces. The model was extended to include the toxic effects of a drug (5-fluorouracil) administered according to the protocol of an actual trial with cancer patients, and the temporal pattern of the predicted effects of the drug on the peripheral blood count was compared with that found in the clinic.

scholarly journals Transcriptomic Changes of Murine Visceral Fat Exposed to Intermittent Hypoxia at Single Cell Resolution

2020 ◽  
Vol 22 (1) ◽  
pp. 261
Author(s):  
Abdelnaby Khalyfa ◽  
Wesley Warren ◽  
Jorge Andrade ◽  
Christopher A. Bottoms ◽  
Edward S. Rice ◽  
...  
Keyword(s):  
Intermittent Hypoxia ◽  
Cell Types ◽  
Cellular Level ◽  
Cellular Heterogeneity ◽  
Transcriptional Networks ◽  
Metabolic Dysfunction ◽  
Rna Seq ◽  
Obstructive Sleep ◽  
Differential Expressed Gene ◽  
Key Aspects

Intermittent hypoxia (IH) is a hallmark of obstructive sleep apnea (OSA) and induces metabolic dysfunction manifesting as inflammation, increased lipolysis and insulin resistance in visceral white adipose tissues (vWAT). However, the cell types and their corresponding transcriptional pathways underlying these functional perturbations are unknown. Here, we applied single nucleus RNA sequencing (snRNA-seq) coupled with aggregate RNA-seq methods to evaluate the cellular heterogeneity in vWAT following IH exposures mimicking OSA. C57BL/6 male mice were exposed to IH and room air (RA) for 6 weeks, and nuclei from vWAT were isolated and processed for snRNA-seq followed by differential expressed gene (DEGs) analyses by cell type, along with gene ontology and canonical pathways enrichment tests of significance. IH induced significant transcriptional changes compared to RA across 14 different cell types identified in vWAT. We identified cell-specific signature markers, transcriptional networks, metabolic signaling pathways, and cellular subpopulation enrichment in vWAT. Globally, we also identify 298 common regulated genes across multiple cellular types that are associated with metabolic pathways. Deconvolution of cell types in vWAT using global RNA-seq revealed that distinct adipocytes appear to be differentially implicated in key aspects of metabolic dysfunction. Thus, the heterogeneity of vWAT and its response to IH at the cellular level provides important insights into the metabolic morbidity of OSA and may possibly translate into therapeutic targets.

scholarly journals Immunologic abnormalities in an animal model of chronic hypoplastic marrow failure induced by busulfan

Blood ◽  
1978 ◽  
Vol 51 (4) ◽  
pp. 601-610 ◽  
Author(s):  
CA Pugsley ◽  
IJ Forbes ◽  
AA Morley
Keyword(s):  
B Lymphocytes ◽  
Peripheral Blood ◽  
Blood Cells ◽  
Cell Injury ◽  
Cell Types ◽  
Peripheral Blood Lymphocytes ◽  
Delayed Type Hypersensitivity ◽  
Splenic Lymphocytes ◽  
Hypoplastic Marrow ◽  
Experimental Murine Model

Abstract The immunology of chronic hypoplastic marrow failure (CHMF, aplastic anemia) was studied in an experimental murine model of the disease induced by busulfan. B lymphocytes of peripheral blood, spleen, and bone marrow were reduced to 30%–40% and T lymphocytes of thymus, spleen, marrow, and blood were decreased to 20%–70% of control values. IgG and IgM antibody titer to sheep red blood cells were reduced to one- third of control levels, and splenic IgG, but not IgM, plaque-forming cells were fewer on day 7 after antigen stimulation. The proliferative responses to phytohemagglutinin or concanavalin A were reduced in cultures of peripheral blood lymphocytes, splenic lymphocytes, and thymocytes, and cutaneous delayed-type hypersensitivity induced by dinitrofluorobenze was not detected in mice with CHMF. The results demonstrate disturbance of a variety of cellular and humoral functions and suggest that the disturbance was due to quantitative and possibly qualitative abnormalities of the cell types subserving these functions. The results suggest that residual cell injury, the lesion underlying experimental CHMF, is not confined to the myeloid stem cell but also involved cells of the lymphoid series.

scholarly journals Identification of a C3bi-specific membrane complement receptor that is expressed on lymphocytes, monocytes, neutrophils, and erythrocytes

1982 ◽  
Vol 155 (1) ◽  
pp. 96-110 ◽  
Author(s):  
GD Ross ◽  
JD Lambris
Keyword(s):  
Peripheral Blood ◽  
Myeloid Cell ◽  
Fluid Phase ◽  
Cell Types ◽  
Peripheral Blood Lymphocytes ◽  
Polymorphonuclear Cells ◽  
Coated Particles ◽  
Blood Lymphocytes ◽  
T Cell Antigens ◽  
D Region

Cells expressing a membrane C receptor (CR(3)) specific for C3b-inactivator- cleaved C3b (C3bi) were identified by rosette assay with C3bi-coated sheep erythrocytes (EC3bi) or C3bi-coated fluorescent microspheres (C3bi-ms). C3bi- ms, probably because of their smaller size, bound to a higher proportion of cells than did EC3bi. C3bi-ms bound to greater than 90 percent of mature neutrophils, 85 percent of monocytes, 92 percent of erythrocytes, and 12 percent of peripheral blood lymphocytes. Binding of C3bi-ms to neutrophils, monocytes, and erythrocytes was inhibited by fluid-phase C3bi, Fab anti-C3c, or Fab anti-C3d but was not inhibited by F(ab')(2) anti-CR(1) (C3b receptor) or F(ab')(2) anti-CR(2) (C3d receptor) nor by fluid-phase C3b, C3c, or C3d. This indicated that monocytes, neutrophils, and erythrocytes expressed C3bi receptors (CR(3)) that were separate and distinct from CR(1) and CR(2) and specific for a site in the C3 molecule that was only exposed subsequently to cleavage of C3b by C3b inactivator and that was either destroyed, covered, or liberated by cleavage of C3bi into C3c and C3d fragments. Lymphocytes differed from these other cell types in that they expressed CR2 in addition to CRa. Lymphocyte C3bi-ms rosettes were inhibited from 50 to 84 percent by F(ab')(2)-anti-CR(2) or fluid-phase C3d, whereas C3d-ms rosettes were inhibited completely by F(ab')(2) anti-CR(2), fluid-phase C3bi, or fluid- phase C3d. Thus, with lymphocytes, C3bi was bound to CR(3), and in addition was bound to CR(2) by way of the intact d region of the C3bi molecule. In studies of the acquisition of C receptors occurring during myeloid cell maturation, the ability to rosette with C3bi-coated particles was detected readily with immature low-density cells, whereas this ability was nearly undetectable with high density mature polymorphonuclear cells. This absence of C3bi binding to polymorphs was not due to a loss of the CR(3) but instead was due to the maturation-linked acquisition of the abiity to secrete elastase that cleaved reagent particle-bound C3bi into CR(3)-unreactive C3d. Neither neutrophils nor monocytes bound C3d-coated particles at any stage of maturation. Assay of CR(3) with mature neutrophils required inhibition of neutrophil elastase with either soybean trypsin inhibitor or anti-elastase antibodies, and the amounts of these elastase inhibitors required to allow EC3bi rosette formation increased with neutrophil maturation. Because lymphocytes bound C3bi to CR(2) as well as to CR(3), specific assay of lymphocyte CR(3) required saturation of membrane CR(2) with Fab' anti-CR(2) before assay for rosettes with C3bi-ms. Only 3.5 percent of anti-CR(2)- treated peripheral blood lymphocytes bound C3bi-ms. Therefore, among normal blood lymphocytes the majority of the 12 percent C3bi-ms-binding cells expressed only CR(2) (8.5 percent), and the small proportion of C3bi-ms- binding cells that expressed CR(3) (3.5 percent) represented a distinct subset from the CR2(+) cells. Double-label assay indicated that 3.0 percent out of 3.5 percent of these CR(3)-bearing lymphocytes were B cells because they expressed membrane immunoglobulins. Of the remaining CR(3)(+) cells, 0.2 percent expressed either Leu-1 or 3A1 T cell antigens, and 0.6 percent expressed the OKM-1 monocyte-null lymphocyte determinant.

Total progeny in a multitype critical age dependent branching process with immigration

1974 ◽  
Vol 11 (3) ◽  
pp. 458-470 ◽  
Author(s):  
Howard J. Weiner
Keyword(s):  
Limit Theorem ◽  
Branching Process ◽  
Cell Types ◽  
Dimensional Case ◽  
One Dimensional ◽  
Age Dependent ◽  
Total Progeny ◽  
Critical Age ◽  
The One ◽  
Branching Process With Immigration

In a multitype critical age dependent branching process with immigration, the numbers of cell types born by t, divided by t2, tends in law to a one-dimensional (degenerate) law whose Laplace transform is explicitily given. The method of proof makes a correspondence between the moments in the m-dimensional case and the one-dimensional case, for which the corresponding limit theorem is known. Other applications are given, a possible relaxation of moment assumptions, and extensions are indicated.

Aging of the Retina: Molecular and Metabolic Turbulences and Potential Interventions

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Laura Campello ◽  
Nivedita Singh ◽  
Jayshree Advani ◽  
Anupam K. Mondal ◽  
Ximena Corso-Diaz ◽  
...  
Keyword(s):  
Healthy Aging ◽  
Cell Types ◽  
Lifestyle Changes ◽  
Annual Review ◽  
Past Century ◽  
Publication Date ◽  
Vision Science ◽  
Human Lifespan ◽  
Cellular Events ◽  
Age Related

Multifaceted and divergent manifestations across tissues and cell types have curtailed advances in deciphering the cellular events that accompany advanced age and contribute to morbidities and mortalities. Increase in human lifespan during the past century has heightened awareness of the need to prevent age-associated frailty of neuronal and sensory systems to allow a healthy and productive life. In this review, we discuss molecular and physiological attributes of aging of the retina, with a goal of understanding age-related impairment of visual function. We highlight the epigenome–metabolism nexus and proteostasis as key contributors to retinal aging and discuss lifestyle changes as potential modulators of retinal function. Finally, we deliberate promising intervention strategies for promoting healthy aging of the retina for improved vision. Expected final online publication date for the Annual Review of Vision Science, Volume 7 is September 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Signaling pathways have an inherent need for noise to acquire information

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Eugenio Azpeitia ◽  
Eugenio P. Balanzario ◽  
Andreas Wagner
Keyword(s):  
Signaling Pathways ◽  
Information Acquisition ◽  
Cellular Level ◽  
Kinetic Properties ◽  
Positive Role ◽  
Binding Interactions ◽  
Reversible Binding ◽  
Wide Range ◽  
The One ◽  
Parameter Values

Abstract Background All living systems acquire information about their environment. At the cellular level, they do so through signaling pathways. Such pathways rely on reversible binding interactions between molecules that detect and transmit the presence of an extracellular cue or signal to the cell’s interior. These interactions are inherently stochastic and thus noisy. On the one hand, noise can cause a signaling pathway to produce the same response for different stimuli, which reduces the amount of information a pathway acquires. On the other hand, in processes such as stochastic resonance, noise can improve the detection of weak stimuli and thus the acquisition of information. It is not clear whether the kinetic parameters that determine a pathway’s operation cause noise to reduce or increase the acquisition of information. Results We analyze how the kinetic properties of the reversible binding interactions used by signaling pathways affect the relationship between noise, the response to a signal, and information acquisition. Our results show that, under a wide range of biologically sensible parameter values, a noisy dynamic of reversible binding interactions is necessary to produce distinct responses to different stimuli. As a consequence, noise is indispensable for the acquisition of information in signaling pathways. Conclusions Our observations go beyond previous work by showing that noise plays a positive role in signaling pathways, demonstrating that noise is essential when such pathways acquire information.

scholarly journals Cellular, molecular, and therapeutic characterization of pilocarpine-induced temporal lobe epilepsy.

2021 ◽  
Author(s):  
Rammohan Shukla ◽  
Nicholas D Henkel ◽  
Marissa A Smail ◽  
Xiaojun Wu ◽  
Heather A Enright ◽  
...  
Keyword(s):  
Machine Learning ◽  
Bayesian Inference ◽  
Pyramidal Neurons ◽  
Predictive Biomarkers ◽  
Cell Types ◽  
Cellular Level ◽  
Hippocampal Subfields ◽  
Synaptic Changes ◽  
Discovery Method

We probed a transcriptomic dataset of pilocarpine-induced TLE using various ontological, machine-learning, and systems-biology approaches. We showed that, underneath the complex and penetrant changes, moderate-to-subtle upregulated homeostatic and downregulated synaptic changes associated with the dentate gyrus and hippocampal subfields could not only predict TLE but various other forms of epilepsy. At the cellular level, pyramidal neurons and interneurons showed disparate changes, whereas the proportion of non-neuronal cells increased steadily. A probabilistic Bayesian network demonstrated an aberrant and oscillating physiological interaction between oligodendrocytes and interneurons in driving seizures. Validating the Bayesian inference, we showed that the cell types driving the seizures were associated with known antiepileptic and epileptic drugs. These findings provide predictive biomarkers of epilepsy, insights into the cellular connections and causal changes associated with TLE, and a drug discovery method focusing on these events.

scholarly journals Water contaminated with Didymosphenia geminata alters fish cell line viability

2018 ◽  
Author(s):  
Pamela Olivares ◽  
Matias Peredo-Parada ◽  
Viviana Chavez ◽  
Erico Carmona ◽  
Allison Astuya ◽  
...  
Keyword(s):  
River System ◽  
Cell Types ◽  
Complex Problem ◽  
Cellular Level ◽  
Lower Sensitivity ◽  
Fish Cell ◽  
Fish Cell Lines ◽  
Didymosphenia Geminata ◽  
Chronic Effects ◽  
The Moment

Didymosphenia geminata (D. geminata) in Chilean rivers is a complex problem. Its biology and effects on ecosystems is still being studied, at the moment not research has focused on its D. geminata effects at the cellular level. We developed an artificial river system to maintain D. geminata study material and evaluate effects of water contaminated with this diatom on the viability of two fish cell lines. Results indicate that CHSE-214 cells are sensitive to increasing D. geminata extract concentrations, reducing crop viability by 50% when exposed for 24 hours at a 0.01V/V dilution and reducing proliferative capacity by 70% on a 5 day temporal curve. SHK-1 cells showed lower sensitivity, presenting a decrease of 20% in viability at 24 hours, and a lower cell proliferation rate by day 5, but higher than of the CHSE-214 cells. Both lines were affected by exposure to D. geminata extracts, but CHSE-214 lines were more sensitive to polyphenols extracted from the microalgae. We conclude that certain cell types are sensitive to D. geminata in rivers, meaning that chronic effects on aquatic species contaminated with this diatom should be observed. Effects of this plague at a cellular level can be further studied to understand its full impact on river ecosystems.

scholarly journals Monitoring Tacrolimus Concentrations in Whole Blood and Peripheral Blood Mononuclear Cells: Inter- and Intra-Patient Variability in a Cohort of Pediatric Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Amedeo De Nicolò ◽  
Michele Pinon ◽  
Alice Palermiti ◽  
Antonello Nonnato ◽  
Alessandra Manca ◽  
...  
Keyword(s):  
Peripheral Blood Mononuclear Cells ◽  
Whole Blood ◽  
Peripheral Blood ◽  
Pediatric Patients ◽  
Mononuclear Cells ◽  
Individual Variability ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Intracellular Concentrations ◽  
The One

Tacrolimus (TAC) is a first-choice immunosuppressant for solid organ transplantation, characterized by high potential for drug-drug interactions, significant inter- and intra-patient variability, and narrow therapeutic index. Therapeutic drug monitoring (TDM) of TAC concentrations in whole blood (WB) is capable of reducing the incidence of adverse events. Since TAC acts within lymphocytes, its monitoring in peripheral blood mononuclear cells (PBMC) may represent a valid future alternative for TDM. Nevertheless, TAC intracellular concentrations and their variability are poorly described, particularly in the pediatric context. Therefore, our aim was describing TAC concentrations in WB and PBMC and their variability in a cohort of pediatric patients undergoing constant immunosuppressive maintenance therapy, after liver transplantation. TAC intra-PBMCs quantification was performed through a validated UHPLC–MS/MS assay over a period of 2–3 months. There were 27 patients included in this study. No significant TAC changes in intracellular concentrations were observed (p = 0.710), with a median percent change of −0.1% (IQR −22.4%–+46.9%) between timings: this intra-individual variability was similar to the one in WB, −2.9% (IQR −29.4–+42.1; p = 0.902). Among different patients, TAC weight-adjusted dose and age appeared to be significant predictors of TAC concentrations in WB and PBMC. Intra-individual seasonal variation of TAC concentrations in WB, but not in PBMC, have been observed. These data show that the intra-individual variability in TAC intracellular exposure is comparable to the one observed in WB. This opens the way for further studies aiming at the identification of therapeutic ranges for TAC intra-PBMC concentrations.

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