Linear B Mycenaean Greek and medical nomenclature.

This brief report is intended to call attention to the fact that we use some very old terms in our daily medical speaking that were in use about 3500 years ago and were probably uttered as early as the late Bronze Age by Achilles, Agamennon and the other Homeric heroes outside the walls of Troy.

Surface markers: An identity card of endothelial cells.

All endothelial cells have the common characteristic that they line the vessels of the blood circulatory system. However, endothelial cells display a large degree of heterogeneity in the function of their location in the vascular tree. In this article, we have summarized the expression patterns of a number of well-accepted endothelial surface markers present in normal microvascular endothelial cells, arterial and venous endothelial cells, lymphatic endothelial cells, tumor endothelial cells, and endothelial precursor cells.

Cross talk between natural killer cells and mast cells in tumor angiogenesis.

Natural killer (NK) cells are large granular lymphocytes of the innate immune system, responsible for direct targeting and killing of both virally infected and transformed cells. Under pathological conditions and during inflammation, NK cells extravasate into the lymph nodes and accumulate at inflammatory or tumor sites. The activation of NK cells depends on an intricate balance between activating and inhibitory signals that determines if a target will be susceptible to NK-mediated lysis. Many experimental evidences indicate that NK cells are also involved in several immunoregulatory processes and have the ability to modulate the adaptive immune responses. Many other important aspects about NK cell biology are emerging in these last years. The aim of this review is to elucidate the role of NK cells in tumor angiogenesis and their interaction with mast cells. In fact, it has been observed that NK cells produce pro-angiogenic factors and participate alone or in cooperation with mast cells to the regulation of angiogenesis in both physiological and pathological conditions including tumors.

Mast cells and primary systemic vasculitides.

Vasculitides are characterized by inflammation and necrosis of blood vessels leading to vessel occlusion and ischemic damages of tissues. Among the inflammatory cells involved in vasculitides, neutrophils, T cells, and macrophages have been identified as the predominant cell type. This review article is focused on the role of mast cells in these chronic inflammatory processes. Mast cells are characterized by their complex plasticity. Increasing evidences document that mast cells exert both pro- and anti-inflammatory functions depending on the cell types and the microenvironment they reside in. In this context, mast cell mediators able to modulate progression of vasculitides at different levels and the anatomic localization of mast cells in different vasculitides will be described. Finally, therapeutic approach including inhibition of recruitment of mast cells to the inflammatory infiltrate and blockade of their proinflammatory effects and proangiogenic functions as potential new targets for the treatment of these diseases will be discussed.

The role of mast cell in tissue morphogenesis. Thymus, duodenum, and mammary gland as examples.

Mast cells (MCs) are strategically located at host/environment interfaces like skin, airways, and gastro-intestinal and uro-genital tracts. MCs also populate connective tissues in association with blood and lymphatic vessels and nerves. MCs are absent in avascular tissues, such as mineralized bone, cartilage, and cornea. MCs have various functions and different functional subsets of MCs are encountered in different tissues. However, we do not' know exactly what is the physiological function of MC. Most of these functions are not essential for life, as various MC-deficient strains of mice and rats seems to have normal life spans. In this review article, we have reported and discussed the literature data concerning the role of MCs in tissue morphogenesis, and in particular their role in the development of thymus, duodenum, and mammary gland.

"Sprouting angiogenesis", a reappraisal.

Angiogenesis is defined as a new blood vessel sprouting from pre-existing vessels. This highly regulated process take place through two non-exclusive events, the so-called endothelial sprouting or non-sprouting (intussusceptive) microvascular growth. This review article will provide a brief overview of some relevant topics defining sprouting angiogenesis and including: (i) The concept of functional specialization of endothelial cells during different phases of this process, involving the specification of endothelial cells into tip cells, stalk cells, and phalanx cells bearing different morphologies and functional properties; (ii) The interplay between numerous signaling pathways, including Notch and Notch ligands, VEGF and VEGFRs, semaphorins, and netrins, in the regulation and modulation of the phenotypic characteristics of these cells; (iii) Some fundamental and consecutive morphological processes, including lumen formation and perfusion, network formation, remodeling, pruning, leading to the final vessel maturation and stabilization.

Mast cells, angiogenesis, and tumour growth.

Accumulation of mast cells (MCs) in tumours was described by Ehrlich in his doctoral thesis. Since this early account, ample evidence has been provided highlighting participation of MCs to the inflammatory reaction that occurs in many clinical and experimental tumour settings. MCs are bone marrow-derived tissue-homing leukocytes that are endowed with a panoply of releasable mediators and surface receptors. These cells actively take part to innate and acquired immune reactions as well as to a series of fundamental functions such as angiogenesis, tissue repair, and tissue remodelling. The involvement of MCs in tumour development is debated. Although some evidence suggests that MCs can promote tumourigenesis and tumour progression, there are some clinical sets as well as experimental tumour models in which MCs seem to have functions that favour the host. One of the major issues linking MCs to cancer is the ability of these cells to release potent pro-angiogenic factors. This review will focus on the most recent acquisitions about this intriguing field of research. This article is part of a Special Issue entitled: Mast cells in inflammation.

Effects of prednisolone on the dystrophin-associated proteins in the blood-brain barrier and skeletal muscle of dystrophic mdx mice.

The mdx mouse, the most widely used animal model of Duchenne muscular dystrophy (DMD), develops a seriously impaired blood-brain barrier (BBB). As glucocorticoids are used clinically to delay the progression of DMD, we evaluated the effects of chronic treatment with α-methyl-prednisolone (PDN) on the expression of structural proteins and markers in the brain and skeletal muscle of the mdx mouse. We analyzed the immunocytochemical and biochemical expression of four BBB markers, including endothelial ZO-1 and occludin, desmin in pericytes, and glial fibrillary acidic protein (GFAP) in glial cells, and the expression of the short dystrophin isoform Dp 71, the dystrophin-associated proteins (DAPs), and aquaporin-4 (AQP4) and α-ß dystroglycan (DG) in the brain. We evaluated the BBB integrity of mdx and PDN-treated mdx mice by means of intravascular injection of horseradish peroxidase (HRP). The expression of DAPs was also assessed in gastrocnemius muscles and correlated with utrophin expression, and laminin content was measured in the muscle and brain. PDN treatment induced a significant increase in the mRNA and protein content of the BBB markers; a reduction in the phosphorylation of occludin in the brain and of AQP4/ß DG in both tissues; an increase of Dp71 protein content; and an increase of both mRNA and protein levels of the AQP4/α-ß DG complex. The latter was associated with enhanced laminin and utrophin in the muscle. The HRP assay demonstrated functional restoration of the BBB in the PDN-treated mdx mice. Specifically, mdx mice showed extensive perivascular labeling due to escape of the marker, while HRP was exclusively intravascular in the PDN-treated mice and the controls. These data illustrate for the first time that PDN reverses the BBB alterations in the mdx mouse and re-establishes the proper expression and phosphorylation of ß-DG in both the BBB and skeletal muscle. Further, PDN partially protects against muscle damage. The reduction in AQP4 and occludin phosphorylation, coupled with their anchoring to glial and endothelial membranes in PDN-treated mice, suggests that the drug may target the glial and endothelial cells. Our results suggest a novel mechanism for PDN action on cerebral and muscular function, restoring the link between DAPs and the extracellular matrix, most likely through protein kinase inactivation.

Congenital axis dysmorphism in a medieval skeleton : secunda a vertendo epistropheus .

PURPOSE: We describe here the axis dysmorphism that we observed in the skeletal remains of a human child dug up from a fifteenth century cemetery located in north-eastern Italy. This bone defect is discussed in the light of pertinent literature. METHODS: We performed macroscopical examination and CT scan analysis of the axis. RESULTS: Axis structure was remarkably asymmetric. Whilst the left half exhibited normal morphology, the right one was smaller than normal, and its lateral articular surface showed horizontal orientation. In addition, the odontoid process appeared leftward deviated and displayed a supplementary articular-like facet situated on the right side of its surface. CONCLUSIONS: These findings suggest a diagnosis of unilateral irregular segmentation of atlas and axis, a rare dysmorphism dependent upon disturbances of notochordal development in early embryonic life. Likewise other malformations of the craniovertebral junction, this axis defect may alter the delicate mechanisms of upper neck movements and cause a complex series of clinical symptoms. This is an emblematic case whereby human skeletal remains may provide valuable information on the anatomical defects of craniovertebral junction.

The "self-similarity logic" applied to the development of the vascular system.

From a structural standpoint, living systems exhibit a hierarchical pattern of organization in which structures are nested within one another. From a temporal point of view, this type of organization is the outcome of a 'history' resulting from a set of developmental steps. Recently, it has been suggested that some auto similarity prevails at each nested level or time step and a principle of "self-similarity logic" has been proposed to convey the concept of a multi-level organization in which very similar rules (logic) apply at each level. In this study, the hypothesis is put forward that such a principle is particularly apparent in many morphological and developmental aspects of the vascular system. In fact, not only the morphology of the vascular system exhibits a high degree of geometrical self-similarity, but its remodelling processes also seem to be characterized by the application of almost the same rules, from the macroscopic to the endothelial cell to the sub-cellular levels, potentially allowing a unitary description of features such as sprouting and intussusceptive angiogenesis, and phenotypic differences of endothelial cells. The influence of the "self-similarity logic" shaping the vascular system on the organogenesis has been also discussed.

Single-cell dynamics of mast cell-CD4+ CD25+ regulatory T cell interactions.

The biological behavior of immune cells is determined by their intrinsic properties and interactions with other cell populations within their microenvironment. Several studies have confirmed the existence of tight spatial interactions between mast cells (MCs) and Tregs in different settings. For instance, we have recently identified the functional cross-talk between MCs and Tregs, through the OX40L-OX40 axis, as a new mechanism of reciprocal influence. However, there is scant information regarding the single-cell dynamics of this process. In this study, time-lapse video microscopy revealed direct interactions between Tregs and MCs in both murine and human cell co-cultures, resulting in the inhibition of the MC degranulation response. MCs incubated with WT, but not OX40-deficient, Tregs mediated numerous and long-lasting interactions and displayed different morphological features lacking the classical signs of exocytosis. MC degranulation and Ca2+ mobilization upon activation were inhibited by Tregs on a single-cell basis, without affecting overall cytokine secretion. Transmission electron microscopy showed ultrastructural evidence of vesicle-mediated secretion reconcilable with the morphological pattern of piecemeal degranulation. Our results suggest that MC morphological and functional changes following MC-Treg interactions can be ascribed to cell-cell contact and represent a transversal, non-species-specific mechanism of immune response regulation. Further research, looking at the molecular composition of this interaction will broaden our understanding of its contribution to immunity.

The Cerebral Cortex and the Songs of Homer: When Neuroscience Meets History and Literature.

In this article we reconsider Homer's poetry in the light of modern achievements in neuroscience. This perspective offers some clues for examining specific patterns of brain functioning. Homer's epics, for instance, painted a synthetic picture of the human body, emphasizing some parts and neglecting others. This led to the formation of a body schema reminiscent of a homunculus, which we call the "Homeric homunculus." Both poems were largely the product of centuries of oral tradition, in which the prodigious memory of courtly rhapsodists was essential to the performance of the epics. The underlying cognitive functions required a close interplay of memory and language skills, supported by the musical and rhythmic cadence of Homeric verse.

Epo is involved in angiogenesis in human glioma.

In this study, the extent of angiogenesis, evaluated as microvascular density, and the immunoreactivity of tumor cells to erythropoietin (Epo) and of endothelial cells to Epo receptor (EpoR) have been correlated in human glioma specimens, and the effect of anti-Epo antibody on glioma-induced angiogenesis in vivo in the chick embryo chorioallantoic membrane (CAM) has been investigated. Results show that: (1) Epo/EpoR expression correlates with angiogenesis, (2) in the CAM assay, tumor bioptic specimens induce a strong angiogenic response, comparable to that induced by VEGF, and (3) an anti-Epo antibody co-administered with tumor bioptic specimens significantly inhibits the angiogenic response. These findings suggest the presence of a loop in the Epo/EpoR system, i.e. Epo is secreted by glioma tumor cells and it affects glioma vascular endothelial cells via its receptor and promotes angiogenesis in a paracrine manner. Moreover, as demonstrated by in vivo experiments, Epo is responsible for the strong angiogenic response induced by human glioma bioptic specimens, because an anti-Epo antibody is able to significantly inhibit this response.

Tryptase-positive mast cells and CD8-positive T cells in human endometrial cancer.

In this study, we correlated the number of tryptase-reactive mast cells with the number of CD8-positive T cells in human endometrial adenocarcinoma biopsy specimens by means of immunohistochemical techniques. Results have shown that CD8-positive T cell counts correlate to tryptase-positive mast cell counts and that these parameters increase in accordance with the tumor progression of human endometrial carcinoma. These data suggest that inhibition of inflammation or manipulation of inflammatory resolution pathways may be a new therapeutic approach for the treatment of endometrial adenocarcinoma.

Mast cells, angiogenesis and cancer.

Mast cells (MCs) were first described by Paul Ehrlich 1 in his doctoral thesis. MCs have long been implicated in the pathogenesis of allergic reactions and certain protective responses to parasites. As most tumors contain inflammatory cell infiltrates, which often include plentiful MCs, the question as to the possible contribution of MCs to tumor development has progressively been emerging. In this chapter, the specific involvement of MCs in tumor biology and tumor fate will be considered, with particular emphasis on the capacity of these cells to stimulate tumor growth by promoting angiogenesis and lymphangiogenesis. Data from experimental carcinogenesis and from different tumor settings in human pathology will be summarized. Information to be presented will suggest that MCs may serve as a novel therapeutic target for cancer treatment.

Bilateral arcuate foramen associated with partial defect of the posterior arch of the atlas in a medieval skeleton: case report and review of the literature. Looking backward to go forward.

PURPOSE: We observed a complex atlas (C1) dysmorphism in a human medieval skeleton dug up from the sixth to the seventh century necropolis located in the north-eastern Italy. We analyzed such a dysmorphism in the light of pertinent literature and discussed the functional and clinical implications related to this type of C1 structural malformation. METHODS: Macroscopical and CT-SCAN examinations of the atlas were carried out. RESULTS: Bone findings consisted of partial aplasia of the posterior arch of the C1 accompanied by a bilateral arcuate foramen. In addition, the spinous processes of C7 and T1 were found to be bifid. CONCLUSIONS: Although such abnormalities are supposed to be clinically inconspicuous, yet they may become challenging or even dangerous in the context of trauma. They may even complicate specific diagnostic or surgical procedures. In addition, they may cause a great number of symptoms, ranging from headache and neck pain to loss of postural muscle tone and consciousness, due to the close and complex relationship of bone structures with nerves, blood vessels, muscles, and ligaments. As a result, radiologists, clinicians, surgeons, and chiropractors should consider in their clinical reasoning the possibility that atlas dysmorphisms may occur.

The role of mast cells in human skin cancers.

Mast cells (MCs) are immune cells derived from myeloid lineage present in all classes of vertebrates and have emerged preceding much time the development of adaptive immunity. MCs are involved in inflammatory processes, allergic reactions, and host responses to parasites and bacteria infectious diseases. MCs are located at the host-environment interface, at many sites of initial antigen entry, including skin, lung and gastrointestinal tract, and have part of a protective mechanism. Skin has an important role in protecting the host from invasion both as physical barriers and by employing an intricate network of resident immune and non-immune cells include macrophages, T and B lymphocytes, MCs, neutrophils, eosinophils, and Langerhans cells. In this review we discussed the role of MCs in human skin cancers.

The Italian law on body donation: A position paper of the Italian College of Anatomists.

In Italy, recent legislation (Law No. 10/2020) has tuned regulations concerning the donation of one's postmortem body and tissues for study, training, and scientific research purposes. This study discusses several specific issues to optimise the applicability and effectiveness of such an important, novel regulatory setting. Critical issues arise concerning the learners, the type of training and teaching activities that can be planned, the position of academic anatomy institutes, the role of family members in the donation process, the time frame of the donation process, the eligibility of partial donation, or the simultaneous donation of organs and tissues to patients awaiting transplantation. In particular, a universal time limit for donations (i.e., one year) makes it impossible to plan the long-term use of specific body parts, which could be effectively preserved for the advanced teaching and training of medical students and surgeons. The abovementioned conditions lead to the limited use of corpses, thus resulting in the inefficiency of the whole system of body donation. Overall, the donors' scope for the donation of their body could be best honoured by a more flexible and tuneable approach that can be used on a case-by-case basis. Furthermore, it is deemed necessary to closely monitor the events scheduled for corpses in public nonacademic institutions or private enterprises. This paper presents useful insights from Italian anatomists with the hope of providing inspiration for drafting the regulations. In conclusion, this paper focuses on the critical issues derived from the recently introduced Italian law on the donation and use of the body after death and provides suggestions to lawmakers for future implementations.

Glial dystrophin-associated proteins, laminin and agrin, are downregulated in the brain of mdx mouse.

In this study, we investigated the involvement of dystrophin-associated proteins (DAPs) and their relationship with the perivascular basement membrane in the brains of mdx mice and controls at the age of 2 months. We analyzed (1) the expression of glial DAPs α-ß-dystroglycan (DG), α-syntrophin, aquaporin-4 (AQP4) water channel, Kir 4.1 and dystrophin isoform (Dp71) by immunocytochemistry, laser confocal microscopy, immunogold electron microscopy, immunoblotting and RT-PCR; (2) the ultrastructure of the basement membrane and expression of laminin and agrin; and (3) the dual immunofluorescence colocalization of AQP4/α-ß-DG, and of Kir 4.1/agrin. The following results were observed in mdx brain as compared with controls: (1) a significant reduction in protein content and mRNA expression of DAPs; (2) ultrastructurally, a thickened and discontinuous appearance of the basement membrane and a significant reduction in laminin and agrin; and (3) a molecular rearrangment of α-ß-DG, coupled with a parallel loss of agrin and Kir 4.1 on basement membrane and glial endfeet. These data indicate that in mdx brain the deficiency in dystrophin and dystrophin isoform (Dp71) is coupled with a reduction of DAP components, coupled with an altered anchoring to the basement membrane.

The fundamental contribution of William Bate Hardy to shape the concept of mast cell heterogeneity.

This review article acknowledges the pioneering contribution of William Bate Hardy in shaping the concept of mast cell heterogeneity. In two outstanding papers, published in 1894 and 1895, he focussed on the 'wandering cells' (the modern leucocytes) in different mammalian species and distinguished two types of granular basophil cells, i.e., the coarsely granular basophil cells and the splanchnic basophil cells. These corresponded to the populations of connective tissue-type and mucosal mast cells, respectively, described 70 years later by Enerbäck in rodents. Among the coarsely granular basophil cells, he also differentiated those cells which populated the serosal cavities - the so-called coelomic coarsely granular basophil cells - from the common coarsely granular basophil cells, which were localized in the connective tissues. He stated that the granular basophil cells presented with different morphological and histochemical characteristics in diverse animal species as well as at different anatomical sites. Remarkably, he performed a series of functional experiments on the basophil cells as well as the other wandering cells, and suggested the view that different granular basophil cells might express functional specializations.