Aggressive inflammatory myofibroblastic tumor of the tongue (clinical case)

The study objective is to present a rare clinical case of an aggressive myofibroblastic tumor of the tongue.Clinical case. A 24-year-old patient was revealed a 44 × 25 × 50 mm volumetric formation of the left side of the tongue spreading to the contralateral side and bottom of the oral cavity. The patient denied injuries or chronic autoimmune diseases. Additional studies did not reveal failure of other organs or systems. Histological conclusion: malignant spindle-polymorphic cell neoplasm with myxomatosis, perineal growth, muscle fiber infiltration and their death. An immunohistochemistry revealed expression of vimentin, CD34, S100; Ki-67 – 30 % in tumor cells. He was diagnosed with T3N0M0 fibrosarcoma of the tongue. Subtotal resection of the tongue with simultaneous microsurgical plasty via re-activated radiation autograft was performed. According to morphological study of the removed tissues, he was finally diagnosed with an aggressive inflammatory myofibroblastic tumor of the tongue. Observation period at the time of writing was 15 months. The patient eats solid food, sound pronunciation is restored in full. There are no signs of relapse or metastasis.Conclusion. Diagnostics of an inflammatory myofibroblastic tumor of the oral cavity is complex and depends on clinical and morphological features of a particular tumor. We need reliable criteria to differentiate aggressive forms of inflammatory myofibroblastic tumor of the tongue from non-aggressive ones to choose treatment. The main difficulties arise in determining the resection volume and predicting relapse or metastasis.

Self-identity barcodes encoded by six expansive polymorphic toxin families discriminate kin in myxobacteria

Myxobacteria are an example of how single-cell individuals can transition into multicellular life by an aggregation strategy. For these and all organisms that consist of social groups of cells, discrimination against, and exclusion of, nonself is critical. In myxobacteria, TraA is a polymorphic cell surface receptor that identifies kin by homotypic binding, and in so doing exchanges outer membrane (OM) proteins and lipids between cells with compatible receptors. However, TraA variability alone is not sufficient to discriminate against all cells, as traA allele diversity is not necessarily high among local strains. To increase discrimination ability, myxobacteria include polymorphic OM lipoprotein toxins called SitA in their delivered cargo, which poison recipient cells that lack the cognate, allele-specific SitI immunity protein. We previously characterized 3 SitAI toxin/immunity pairs that belong to 2 families. Here, we discover 4 additional SitA families. Each family is unique in sequence, but share the characteristic features of SitA: OM-associated toxins delivered by TraA. We demonstrate that, within a SitA family, C-terminal nuclease domains are polymorphic and often modular. Remarkably, sitA loci are strikingly numerous and diverse, with most genomes possessing >30 and up to 83 distinct sitAI loci. Interestingly, all SitA protein families are serially transferred between cells, allowing a SitA inhibitor cell to poison multiple targets, including cells that never made direct contact. The expansive suites of sitAI loci thus serve as identify barcodes to exquisitely discriminate against nonself to ensure populations are genetically homogenous to conduct cooperative behaviors.

Short-Stalked Prosthecomicrobium hirschii Cells Have a Caulobacter-Like Cell Cycle

ABSTRACTThe dimorphic alphaproteobacteriumProsthecomicrobium hirschiihas both short-stalked and long-stalked morphotypes. Notably, these morphologies do not arise from transitions in a cell cycle. Instead, the maternal cell morphology is typically reproduced in daughter cells, which results in microcolonies of a single cell type. In this work, we further characterized the short-stalked cells and found that these cells have aCaulobacter-like life cycle in which cell division leads to the generation of two morphologically distinct daughter cells. Using a microfluidic device and total internal reflection fluorescence (TIRF) microscopy, we observed that motile short-stalked cells attach to a surface by means of a polar adhesin. Cells attached at their poles elongate and ultimately release motile daughter cells. Robust biofilm growth occurs in the microfluidic device, enabling the collection of synchronous motile cells and downstream analysis of cell growth and attachment. Analysis of a draftP. hirschiigenome sequence indicates the presence of CtrA-dependent cell cycle regulation. This characterization ofP. hirschiiwill enable future studies on the mechanisms underlying complex morphologies and polymorphic cell cycles.IMPORTANCEBacterial cell shape plays a critical role in regulating important behaviors, such as attachment to surfaces, motility, predation, and cellular differentiation; however, most studies on these behaviors focus on bacteria with relatively simple morphologies, such as rods and spheres. Notably, complex morphologies abound throughout the bacteria, with striking examples, such asP. hirschii, found within the stalkedAlphaproteobacteria.P. hirschiiis an outstanding candidate for studies of complex morphology generation and polymorphic cell cycles. Here, the cell cycle and genome ofP. hirschiiare characterized. This work sets the stage for future studies of the impact of complex cell shapes on bacterial behaviors.

An Immunohistochemistry Study of Sox9, Runx2, and Osterix Expression in the Mandibular Cartilages of Newborn Mouse

The purpose of this study is to investigate the spacial expression pattern and functional significance of three key transcription factors related to bone and cartilage formation, namely, Sox9, Runx2, and Osterix in cartilages during the late development of mouse mandible. Immunohistochemical examinations of Sox9, Runx2, and Osterix were conducted in the mandibular cartilages of the 15 neonatal C57BL/6N mice. In secondary cartilages, both Sox9 and Runx2 were weakly expressed in the polymorphic cell zone, strongly expressed in the flattened cell zone and throughout the entire hypertrophic cell zone. Similarly, both transcriptional factors were weakly expressed in the uncalcified Meckel’s cartilage while strongly expressed in the rostral cartilage. Meanwhile, Osterix was at an extremely low level in cells of the flattened cell zone and the upper hypertrophic cell zone in secondary cartilages. Surprisingly, Osterix was intensely expressed in hypertrophic chondrocytes in the center of the uncalcified Meckel’s cartilage while moderately expressed in part of hypertrophic chondrocytes in the rostral process. Consequently, it is suggested that Sox9 is a main and unique positive regulator in the hypertrophic differentiation process of mandibular secondary cartilages, in addition to Runx2. Furthermore, Osterix is likely responsible for phenotypic conversion of Meckel’s chondrocytes during its degeneration.

Indian Hedgehog Roles in Post-natal TMJ Development and Organization

Indian hedgehog (Ihh) is essential for embryonic mandibular condylar growth and disc primordium formation. To determine whether it regulates those processes during post-natal life, we ablated Ihh in cartilage of neonatal mice and assessed the consequences on temporomandibular joint (TMJ) growth and organization over age. Ihh deficiency caused condylar disorganization and growth retardation and reduced polymorphic cell layer proliferation. Expression of Sox9, Runx2, and Osterix was low, as was that of collagen II, collagen I, and aggrecan, thus altering the fibrocartilaginous nature of the condyle. Though a disc formed, it exhibited morphological defects, partial fusion with the glenoid bone surface, reduced synovial cavity space, and, unexpectedly, higher lubricin expression. Analysis of the data shows, for the first time, that continuous Ihh action is required for completion of post-natal TMJ growth and organization. Lubricin overexpression in mutants may represent a compensatory response to sustain TMJ movement and function.

Pathogenesis of Human Reactive-Appearing «Non-Monomorphous» Malignant Lymphoproliferative Disorders: A Hypothesis

Human reactive-appearing « non-monomorphous » malignant disorders, such as Hodgkin's disease, T-cell-rich B-cell lymphomas and angioimmunoblastic lymphadenopathy display a peculiar and unifying characteristic, which biologically differentiates them from « monomorphous » non-Hodgkin's lymphomas. It consists in the coexistence within the pathologic tissue of a polyclonal, normal-appearing, presumed reactive cellular component, mainly composed of T-lymphocytes together with a clonal cell component constituting a minority of the pathologic mass. To explain the long-lasting coexistence of such polymorphic cell populations in the pathologic tissue of synchronous and metachronous localizations of the disease, it is hypothesized that they are interconnected by « biological interactions » which determine and sustain the pathologic process. Based on the biological characteristics of an experimental model (the follicular center cell « lymphoma » of the SJL murine strain), it is suggested that these human « non-monomorphous » malignant diseases should be regarded as a continuous spectrum of lymphoproliferative disorders sustained by a biological loop which interconnects different cell populations able to stimulate each other for growth.

Mls is not a single gene, allelic system. Different stimulatory Mls determinants are the products of at least two nonallelic, unlinked genes.

Mls determinants share with MHC products the unique property of stimulating T cells at extraordinarily high precursor frequencies. The Mls system was originally described as a single locus on chromosome 1, with four alleles, Mlsa, Mlsb, Mlsc, and Mlsd, that encode polymorphic cell surface structures. However, the fundamental issues of polymorphism and allelism in the Mls system remain controversial. To clarify these questions, a formal segregation analysis of the genes encoding Mlsa and Mlsc determinants was carried out by testing the capacity of spleen cells from progeny of (Mlsa X Mlsc)F1 X Mlsb breedings to stimulate responses by unprimed T cells and by Mlsa- and Mlsc-specific cloned T cells. The results of this analysis indicated that the gene encoding Mlsa determinants is neither allelic to nor linked to the gene encoding Mlsc determinants. Together with previous findings, these results also suggest that another strongly stimulatory type, Mlsd, in fact results from the independent expression of unlinked Mlsa and Mlsc gene products. Based on these observations, it is concluded that, contrary to conventional concepts, the stimulatory phenotypes designated as Mlsa, Mlsc, and Mlsd can be accounted for by the independent expression of the products of at least two unlinked gene loci.