The Microscope as a Tool for Disease Discovery—A Personal Voyage

Abstract

This review reflects the trajectory of my career in hematopathology, and my personal reflections on scientific advances in the field. During the course of more than 40 years, the approach to classification of hematological malignancies has evolved from descriptive approaches, based on either cytological or clinical features, to a modern approach, which incorporates cutting-edge technologies. My philosophy has focused on defining individual diseases, an approach that can best lead to an understanding of molecular pathogenesis. To quote Carolus Linnaeus (1, p. 19), the father of taxonomy, "The first step in wisdom is to know the things themselves; this notion consists in having a true idea of the objects; objects are distinguished and known by classifying them methodically and giving them appropriate names. Therefore, classification and name-giving will be the foundation of our science."

Classification of Tumors of the Hematopoietic and Lymphoid Tissues. Discovering Diseases—Defining Their Features

“…It seems appropriate to describe the understanding of the disease model applied in the WHO Classification of Tumours as applicable to research. This model, extrapolated from consideration of Dr. Jaffe, starts from clinical observation, and throughout the pathogenetic study, has clear effects in terms of diagnosis, prognosis, and treatment [5]. Disease discovery and disease definition using the microscope as a tool on tumor tissue sections are critical first steps in elucidating the pathogenesis of lymphomas.…”

“…To quote Dr. Jaffe, "The discovery of the disease nearly always precedes the discovery of gene. However, the process is iterative such that knowledge of the genetic pathogenesis provides new diagnostic tools, which help define the disease and its borderlands" (Figure 1) [5]. This model has been applied in understanding, for example, mantle cell lymphoma and peripheral T-cell lymphoma, not otherwise specified.…”

HSP70 promotes MLKL polymerization and necroptosis

“…The lytic cell death pathway, necroptosis, has emerged as a critically important mode of regulated cell death over the past two decades. 1 Phenotypically, necroptosis is indistinguishable from necrosis, identified by organelle swelling, loss of plasma membrane integrity, and release of cytoplasmic contents including pro-inflammatory mediators or damage associated molecular patterns (DAMPs), which magnify the innate inflammatory response. Necroptosis also stimulates a cell-autonomous increase in cytokine production that contributes to the inflammatory milieu and paracellular signaling.…”

“…The canonical necroptosis pathway relies on a multimillion Dalton complex called the necrosome, which includes two kinases, receptor interacting protein kinase 1 and 3 (RIPK1, RIPK3), and a pseudokinase, mixed lineage kinase domain-like protein (MLKL) ( Figure 1 ). 1 Upstream signal promotes RIPK1 interaction with RIPK3 through RIP homotypic interaction motif (RHIM), leading to RIPK3 auto-phosphorylation and homo-oligomerization. RIPK3 homo-oligomer then recruits the casein kinase 1 (CK1) family proteins, CK1α, CK1δ and CK1ε, which phosphorylate serine 227 of human RIPK3, enabling RIPK3 to recruit and phosphorylate MLKL.…”

Incomplete Ischemia-reperfusion on Skin Pressure Sores in Rats and Its Mechanism

“…(1) Microscope medical cell image processing Microscope cell image processing is an important research topic in the field of image recognition, involving image processing, pattern recognition, computer vision and other disciplines, and has wide application value. Previously, charge-coupled device imaging has been used to study certain animal tissue cells [5][6]. One of the optical fiber bundles was used to directly contact live experimental animals with voltage-sensitive dyes to image cortical activity.…”