Part of the book: Biochemistry
Part of the book: Immune Response Activation
Living-donor liver transplant is a life-saving procedure for people with end-stage liver disease that has increased the number of organs available for people on the liver transplant waiting list. Patients often receive grafts from their relatives in living-donor liver transplantation. Maintenance of long-term graft function is important in liver transplant recipients. Livers from older donors have worse graft survival rates in human liver transplantation, and therefore, accurate evaluation of graft aging and senescence is expected to provide critical data for therapeutic intervention in long-term grafts. Many insults, including rejection, can contribute to post-transplant damage. Late post-transplant biopsies frequently show chronic hepatitis of unknown cause, and this can cause late graft dysfunction leading to cirrhosis. Telomere length in chronic hepatitis or cirrhosis is significantly lower than that in normal livers of the same age. Sustained cellular turnover in chronic liver disease accelerates cellular senescence or a crisis because of telomere shortening. Here, we review the mechanisms involved in post-transplant complications including acute cellular rejection, chronic rejection, and chronic hepatitis of unknown cause by ageing and senescence due to telomere shortening.
Part of the book: Telomere
Stat5, c-myc, Hipk2, Fiz1, and ZFP521 to lymphomagenesis precursor B-cell lymphoblastic lymphoma/leukemia have been previously identified as a putative gene involved in the induction of B-cell lymphomagenesis. In this review, we summarize the role of ZFP521 in B-cell lymphomagenesis. Zinc finger protein 521 (Zfp521) is a novel identified gene that is responsible for pre–B-lymphoblastic lymphomagenesis through activation of pre–B-cell receptor (pre-BCR)-signaling by upregulation of adaptor genes and related kinases in the signaling downstream. The pre-BCR-signaling molecules, FLT3, CD43, and IL-7 receptor (IL-7R) were positively regulated by these genes. Stimulation of pre-BCR and/or IL-7R signaling caused aberrant upregulation of other oncogene sets such as cyclin genes, thereby inducing the growth of pre–B cells. IL-7R/Janus kinase (JAK)/STAT signaling cascade is one of the key signaling pathways that are activated in precursor B-cell lymphoblastic lymphoma/leukemia. FLT3, CD43, and pre-BCR cascades crosstalk with JAK/STAT cascade. FLT3 and CD43 cascades have the potential to enhance JAK/STAT cascade effect on pre-B cell growth. On the other hand, pre-BCR and interleukin (IL)-7 receptor exerted competitive effects on pre–B-cell growth; thus, precursor B-cell lymphoblastic lymphomagenesis is a consequence through interaction with these cascades.
Part of the book: Lymphocyte Updates
This review introduces a novel mathematical description of protein assembly. Protein assembly occurs in a substantially open non-equilibrium and non-linear kinetic system. The goal of systems biology is to make predictions about such complicated systems, but few have conducted stability analysis for given systems. Particularly, simulated dynamic behaviors have not been sufficiently verified by kinetic analysis in predicting macromolecular protein interactions and assembly. The non-linearity of protein assembly kinetics is complex, and it is very difficult to determine a model of multi-protein interactions based on numerical calculation. We studied the non-linear kinetics involved in the diffusion process of proteins consisting of two or three species of macromolecules and set a novel model in which non-linearity is given by the diffusion coefficient that depends on the protein concentration. By making the diffusion coefficient concentration-dependent, non-linearity leads to a simple system model. Protein assembly is initiated by monomeric protein interactions and regulated by cofactors such as guanidine triphosphate (GTP) or adenosine triphosphate (ATP) binding to the monomer. This cofactor concentration promotes the dynamic behavior of protein assembly and can be treated as an order parameter. Further, kinetic stability analysis in the center manifold theory (CMT) is introduced for analyzing the behavior of the system around the critical state. Although CMT has not been sufficiently applied for stability analysis of protein assembly systems, this theory predicts the dynamic behavior of the assembly system around the critical point using concentration as a cofactor. Protein assembly theory will provide a novel framework for nonlinear multi-parametric analysis.
Part of the book: Kinetic Theory
Bone marrow (BM) clots are routinely sampled in aspiration tests, and their sections are prepared for histological observation by hematoxylin and eosin (H&E) staining. However, H&E-stained sections are considered less informative than those stained by the May-Grünwald Giemsa (M-G) stain; thus, diagnosis using H&E-stained clot samples is challenging for pathologists. In fact, the diagnostic evaluation is limited to the observation of cellular morphology and the myeloid-erythroid cell ratio. Pathologists leave cellular observation to laboratory hematologists, who generally use M-G staining. In this chapter, the utility of bone marrow clot specimens for diagnosis by H&E staining is reviewed. Specifically, the review provides a descriptive and illustrative explanation of the diagnosis of acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and myelodysplastic syndrome/myelocytic proliferative neoplasm (MDS/MPN) and demonstrates the possibility of diagnosis on the basis of the characteristic features of blast cells. Clot specimens appear to be useful for the diagnosis of hematopoietic dysplasia by pathologists, and this approach can provide more informative findings for hematologists.
Part of the book: Myeloid Leukemia
Pre-B cells represent the immature stage of the B cell lineage and express genes for the pre-B cell receptor (preBCR). PreBCR consists of lambda 5 and VpreB and its expression elicits a rearrangement of the immunoglobulin heavy chain prior to rearrangement of the immunoglobulin light chain. The lambda 5 and VpreB form a surrogate light chain, which is a premature type of light chain immunoglobulin. PreBCR may cooperate or interact with the IL-7 receptor, which contributes to pre-B cell development. The preBCR distal signaling pathway recruits several adaptor proteins and protein kinases. This review aims to illustrate the framework of the signaling pathway that contributes to B cell lineage development and reconsiders the relationship between the preBCR and IL-7 receptors.
Part of the book: Lymphocytes
Intracellular signal transduction is the most important research topic in cell biology, and for many years, model research by system biology based on network theory has long been in progress. This article reviews cell signaling from the viewpoint of information thermodynamics and describes a method for quantitatively describing signaling. In particular, a theoretical basis for evaluating the efficiency of intracellular signal transduction is presented in which information transmission in intracellular signal transduction is maximized by using entropy coding and the fluctuation theorem. An important conclusion is obtained: the average entropy production rate is constant through the signal cascade.
Part of the book: Cell Signalling
Application of mass spectrometry (MS) has recently been developed for the identification of biomarkers using pathologic samples, whereas its application using formaldehyde-fixed paraffin-embedded (FFPE) tissues remains limited. In this review, we introduce MS imaging (MSI) using FFPE tissue. This method is still challenging for peptide ionization, and various pretreatment techniques have been conducted for enhancing the ionization signal of peptides. A simple chemical pretreatment method involving heating in acetonitrile-containing buffer under pressurized conditions is introduced. Further, two-dimensional MSI data are summarized in a DM for region of interest (ROI) and hierarchical cluster analyses. These techniques enable MALDI-MSI analysis of archived pathological FFPE samples to identify new biomarkers.
Part of the book: Histology