Plap-1 lineage tracing and single-cell transcriptomics reveal cellular dynamics in the periodontal ligament.

Periodontal tissue supports teeth in the alveolar bone socket via fibrous attachment of the periodontal ligament (PDL). The PDL contains periodontal fibroblasts and stem/progenitor cells, collectively known as PDL cells (PDLCs), on top of osteoblasts and cementoblasts on the surface of alveolar bone and cementum, respectively. However, the characteristics and lineage hierarchy of each cell type remain poorly defined.

Temporal control of PDGFRα regulates the fibroblast-to-myofibroblast transition in wound healing.

Fibroblasts differentiate into myofibroblasts by acquiring new contractile function. This is important for tissue repair, but it also contributes to organ fibrosis. Platelet-derived growth factor (PDGF) promotes tissue repair and fibrosis, but the relationship between PDGF and myofibroblasts is unclear.

Periodontal tissue stem cells and mesenchymal stem cells in the periodontal ligament.

Periodontal tissue stem cells, which play a crucial role in maintaining the homeostasis of periodontal tissues, are found in the periodontal ligament (PDL). These cells have long been referred to as mesenchymal stem/stromal cells (MSCs), and their clinical applications have been extensively studied. However, tissue stem cells in the PDL have not been thoroughly investigated, and they may be different from MSCs.

Mouse Model of Loeys-Dietz Syndrome Shows Elevated Susceptibility to Periodontitis via Alterations in Transforming Growth Factor-Beta Signaling.

Loeys-Dietz syndrome (LDS) is a syndromic connective tissue disorder caused by a heterozygous missense mutation in genes that encode transforming growth factor (TGF)-β receptor () and . We encountered a patient with LDS, who had severe periodontal tissue destruction indicative of aggressive periodontitis. The patient had a missense mutation in the glycine and serine-rich domain of exon 3.

Zbp1-positive cells are osteogenic progenitors in periodontal ligament.

Periodontal ligament (PDL) possesses a stem/progenitor population to maintain the homeostasis of periodontal tissue. However, transcription factors that regulate this population have not yet been identified. Thus, we aimed to identify a molecule related to the osteogenic differentiation of PDL progenitors using a single cell-based strategy in this study.

Mice lacking PLAP-1/asporin counteracts high fat diet-induced metabolic disorder and alveolar bone loss by controlling adipose tissue expansion.

Adipose tissue fibrosis with chronic inflammation is a hallmark of obesity-related metabolic disorders, and the role of proteoglycans in developing adipose tissue fibrosis is of interest. Periodontal disease is associated with obesity; however, the underlying molecular mechanisms remain unclear. Here we investigated the roles of periodontal ligament associated protein-1 (PLAP-1)/asporin, a proteoglycan preferentially and highly expressed in the periodontal ligament, in obesity-related adipose tissue dysfunction and adipocyte differentiation.

Mosaic Mutant Analysis Identifies PDGFRα/PDGFRβ as Negative Regulators of Adipogenesis.

Adipocyte progenitors (APs) express platelet-derived growth factor receptors (PDGFRs), PDGFRα and PDGFRβ. Elevated PDGFRα signaling inhibits adipogenesis and promotes fibrosis; however, the function of PDGFRs in APs remains unclear. We combined lineage tracing and functional analyses in a sequential dual-recombinase approach that creates mosaic Pdgfr mutant cells by Cre/lox recombination with a linked Flp/frt reporter to track individual cell fates.

STAT1 modulates tissue wasting or overgrowth downstream from PDGFRβ.

Platelet-derived growth factor (PDGF) acts through two conserved receptor tyrosine kinases: PDGFRα and PDGFRβ. Gain-of-function mutations in human have been linked recently to genetic diseases characterized by connective tissue wasting (Penttinen syndrome) or overgrowth (Kosaki overgrowth syndrome), but it is unclear whether mutations alone are responsible. Mice with constitutive PDGFRβ signaling caused by a kinase domain mutation (D849V) develop lethal autoinflammation.

Pseudodysplastic regenerative mucosa associated with congenital ileal atresia.

A male neonate was clinically diagnosed with congenital intestinal atresia. Surgical operation was performed and the ileum including the atretic portion was resected. Grossly, there was a plaque-like elevation of mucosa at the proximal side of the ileal atresia.

Apparent diffusion coefficient as an MR imaging biomarker of low-risk ductal carcinoma in situ: a pilot study.

Purpose: To evaluate the potential of apparent diffusion coefficients (ADCs) obtained at quantitative diffusion-weighted magnetic resonance (MR) imaging of the breast as a biomarker of low-grade ductal carcinoma in situ (DCIS).

Materials And Methods: This retrospective study was approved by an institutional review board, and the requirement to obtain informed consent was waived. Twenty-two women (age range, 36-75 years; mean age, 56.

Suppression of colonic polyposis by homeoprotein CDX2 through its nontranscriptional function that stabilizes p27Kip1.

Caudal-related homeoprotein CDX2 is expressed in intestinal epithelial cells, in which it is essential for their development and differentiation. A tumor suppressor function is suggested by evidence that CDX2 levels are decreased in human colon cancer specimens and that an inactivating mutation of Cdx2 in Apc(Δ716) mice markedly increases the incidence of colonic polyps. In this study, we investigated roles for transcriptional and nontranscriptional functions of CDX2 in suppression of colonic tumorigenesis.

Acute Epstein-Barr virus infection presenting as severe gastroenteritis without infectious mononucleosis-like manifestations.

Primary Epstein-Barr virus (EBV) infection is usually a self-limiting disease. Although it is sometimes accompanied by severe complications such as thrombocytopenia, hemolytic anemia, and splenic rupture, predominantly gastrointestinal complications are rarely reported. We studied an unusual case of primary EBV infection associated with severe hemorrhagic gastroenteritis.

Requirement of protocol biopsy before and after complete cessation of immunosuppression after liver transplantation.

Background: Operational tolerance is defined as long-term acceptance of a transplanted organ after complete cessation of immunosuppression (IS), but may not always protect against antigen-dependent changes in graft morphology.

Method: IS free patients after living-donor liver transplantation (LDLT) underwent protocol biopsy (tolerance group [Gr-Tol]) and were evaluated for rejection and fibrosis. The degree of fibrosis was compared with those in the patients on maintenance IS group (Gr-IS) and the base line normal liver group (Gr-BS).

FasL expression in hepatic antigen-presenting cells and phagocytosis of apoptotic T cells by FasL+ Kupffer cells are indicators of rejection activity in human liver allografts.

Fas-Fas ligand (FasL) interaction and apoptosis are important in the mechanism of allograft rejection. However, the interaction between donor and recipient cells, specifically focusing on antigen-presenting cells (APCs), under various conditions is poorly understood in human liver allografts. FasL expression on APCs, its association with apoptosis, and the origin of apoptotic lymphocytes in human liver allografts were assessed by immunohistochemistry and in situ hybridization.

Significance of C4d staining in ABO-identical/compatible liver transplantation.

Complement degradation product C4d has become an important marker of humoral or antibody-mediated rejection in renal and heart allograft biopsies. Although there have been several reports on the detection of C4d in liver allografts, the significance of C4d in liver transplantation and its relationship with humoral rejection are still not clear. We investigated the frequency and pattern of C4d staining in liver allograft biopsies with reference to preoperative lymphocyte crossmatch tests, which detect donor-reactive lymphocyte antibody.

Antidonor antibody in patients receiving ABO-identical and HLA-mismatched living donor liver transplants: effect on survival.

We retrospectively determined the correlation of results of lymphocyte crossmatch tests by direct complement-dependent cytotoxicity, to the outcomes of 585 consecutive ABO-identical and human leukocyte antigen (HLA)-mismatched living donor liver transplants (LDLTs) (male:female=276:309; median age, 18 years). Crossmatch test results were positive in 14 recipients (2.4%).

Gastric foveolar metaplasia with dysplastic changes in Brunner gland hyperplasia: possible precursor lesions for Brunner gland adenocarcinoma.

Cases of adenocarcinomas developed in Brunner gland hyperplasia (BGH) have been sporadically reported. Herein, we report the morphologic spectrum of hyperplastic changes culminating into dysplasia and carcinoma in 722 cases of BGH listed in our files. Fifteen of these cases showed dysplastic changes, with 8 graded as low-grade dysplasia, 5 as high-grade dysplasia, 11 as atypical hyperplasia, and 2 as invasive carcinoma, although each frequently coexisted in the same tumor.

Pivotal role of CXCR3 in melanoma cell metastasis to lymph nodes.

Chemokines and their receptors play key roles in leukocyte trafficking and are also implicated in cancer metastasis to specific organs. Here we show that mouse B16F10 melanoma cells constitutively express chemokine receptor CXCR3, and that its ligands CXCL9/Mig, CXCL10/IP-10, and CXCL11/I-TAC induce cellular responses in vitro, such as actin polymerization, migration, invasion, and cell survival. To determine whether CXCR3 could play a role in metastasis to lymph nodes (LNs), we constructed B16F10 cells with reduced CXCR3 expression by antisense RNA and investigated their metastatic activities after s.

Hexokinase II and VEGF expression in liver tumors: correlation with hypoxia-inducible factor 1 alpha and its significance.

Background/aims: We analyzed the expressions of hexokinase II (HK II), a key enzyme in glycolysis, and VEGF in hepatocellular carcinoma (HCC) and metastatic liver cancer in relation to tumor vascularity, and the participation of hypoxia-inducible factor-1 (HIF-1) was studied.

Methods: A real-time quantitative reverse transcription-polymerase chain reaction was performed to examine the HK II and VEGF mRNA expression. Expression of HIF-1 alpha and HK II protein, and microvessel density (MVD) were examined immunohistochemically.