Establishment of Dental Epithelial Cell Line (HAT-7) and the Cell Differentiation Dependent on Notch Signaling Pathway

Rat incisors grow continuously throughout life. Producing a variety of dental epithelial cells is performed by stem cells located in the cervical loop of the incisor apex. To study the mechanisms for cell differentiation, we established a dental epithelial cell line (HAT-7) originating from a cervical loop epithelium of a rat incisor. Immunochemical studies showed that HAT-7 produced the cells expressing amelogenin, ameloblastin, or alkaline phosphatase (ALP). To illustrate a role of Notch signaling in the determinant of the cell fate, we examined expression patterns of Notch1 and Jagged1 in HAT-7 density dependently. At lower cell density, Notch1- or Jagged1-expressing cells were not seen. However, when they were fully confluent, cells began to express Notch1 or Jagged1 strongly. Some ALP-positive cells were almost consistent with Notch1-expressing cells but not Jagged1-expressing cells. These results suggested that the determinant of direction of differentiation was associated with Notch signaling pathway.     

IL-17A/F Modulates Fibrocyte Functions in Cooperation with CD40-Mediated Signaling

T helper 17 (Th17) cells that produce interleukin (IL)-17A and IL-17F have been found to participate in the development of bronchial asthma and bleomycin-induced pulmonary fibrosis. However, whether they play a causative role in the airway remodeling observed in these respiratory diseases remains unclear. Because fibrocytes are involved in tissue repair and fibrosis and are presumably precursors of lung fibroblasts and myofibroblasts, we examined the effects of IL-17A/F on fibrocyte functions. Both IL-17A and IL-17F enhanced fibrocytes’ α-smooth muscle actin expression. Priming fibrocytes with IL-17A enhanced their CD40-mediated IL-6 production, whereas IL-17F-priming increased the CD40-mediated mRNA expression of collagen I, vascular endothelial growth factor, and angiogenin. CD4⁺ T cells co-cultured with fibrocytes produced IL-17A, which was inhibited by blocking CD40 and CD40 ligand interactions. These findings suggest that cooperative interactions between fibrocytes and Th17 cells play an important role via CD40- and IL-17A/F-mediated signaling for collagen and proangiogenic factor production, which may lead to the extracellular matrix deposition and neovascularization seen in airway remodeling.     

Difference in the distribution of tumor-infiltrating CD8+ T cells and FOXP3+ T cells between micronodular thymoma with lymphoid stroma and micronodular thymic carcinoma with lymphoid stroma

Micronodular thymoma with lymphoid stroma (MNT) is a rare thymic epithelial neoplasm subtype characterized by a micronodular tumor cell growth pattern and abundant lymphoid stroma. Micronodular thymic carcinoma with lymphoid stroma (MNCA) is considered as a malignant counterpart of MNT and exhibits a growth pattern similar to that of MNT but has histologic features reminiscent of thymic squamous cell carcinoma, such as cytologic atypia and CD5 and CD117 immunoexpression. Although both MNT and MNCA are characterized by abundant lymphoid stroma, it remains unknown whether there are differences in infiltrating lymphocytes between MNT and MNCA. We analyzed the immune microenvironment profile in eight MNT and three MNCA cases. The cell density of CD8-positive T cells was significantly higher in MNT than in MNCA, whereas that of FOXP3-positive T cells was significantly higher in MNCA than in MNT. There was no significant difference in the cell density of programmed death protein 1-positive T cells and programmed death ligand 1 expression between the MNT and MNCA cases. Our findings indicated that the immune microenvironment of MNCA differed from that of MNT and, compared with the T-cell profile of MNT, that of MNCA was more suppressive to patients′ antitumor immune response.     

Clinical potential of hemodynamic ramp test by simultaneous echocardiography and right heart catheterization for aortic insufficiency in a patient with continuous-flow left ventricular assist device

Journal of Artificial Organs - Aortic insufficiency (AI) is an important adverse event in patients with continuous-flow (CF) left ventricular assist device (LVAD) support. AI is often progressive,...     

Usefulness of albumin–globulin ratio as a clinical prognostic factor in patients with thyroid cancer treated with radioiodine

Annals of Nuclear Medicine - Albumin–globulin ratio (AGR), which is calculated by dividing serum albumin by serum globulin, is considered as a cancer-related inflammation biomarker. Although...     

Numerical analysis of blood flow distribution in 4- and 3-branch vascular grafts

Trifurcated arch grafts (3-branch grafts) are now being used to repair the thoracic aorta in addition to conventional arch grafts (4-branch grafts). The anatomical shape of the 3-branch graft is different from the original vessel, so it is necessary for clinical application to evaluate blood flow distribution in the graft to assess whether there is adequate blood flow to the target organs. To achieve this, we developed a computational fluid dynamics (CFD) method to evaluate blood flow distribution in the grafts. Aortic blood flow was measured by phase-contrast magnetic resonance imaging (PC-MRI), and flow distribution into the branched vessels was obtained. The MRI image was used to create a patient-specific image model that represents the geometry of the aortic arch. The CFD analysis method was employed to determine a boundary condition of the blood flow analysis in the aorta using a patient-specific image model. We also created simplified models of 4-branch and 3-branch grafts and used our CFD analysis method to compare blood flow distribution among simplified models. It was found that blood flow distribution in the descending aorta was 71.3 % for the 4-branch graft and 67.7 % for the 3-branch graft, indicating that a sum of branching flow in the 3-branch graft was almost the same as the one in the 4-branch graft. Therefore, there is no major concern about implanting a new 3-branch graft. Our CFD analysis method may be applied to estimate blood flow distribution of a newly developed vascular graft prior to its clinical use and provide useful information for safe use of the graft.     

Fecoflowmetric Analysis of Anorectal Motor Function in Postoperative Anal-Preserving Surgery Patients With Low Rectal Cancer Comparison With the Wexner Score and Anorectal Manometry

The aim of this study was to elucidate whether fecoflowmetry (FFM) could evaluate more detailed evacuative function than anorectal manometry by comparing between FFM or anorectal manometric findings and the clinical questionnaires and the types of surgical procedure in the patients who received anal-preserving surgery. Fifty-three patients who underwent anal-preserving surgery for low rectal cancer were enrolled. The relationships between FFM or the manometric findings and the clinical questionnaires and the types of procedure of anal-preserving surgery were evaluated. There were significant differences between FFM markers and the clinical questionnaire and the types of the surgical procedure, whereas no significant relationship was observed between the manometric findings and the clinical questionnaire and the types of the surgical procedure. FFM might be feasible and useful for the objective assessment of evacuative function and may be superior to manometry for patients undergoing anal-preserving surgery.Key words: Anorectal manometry, Anal-preserving surgery, Fecoflowmetry, Incontinence, Rectal cancerSphincter preservation has been one of the key issues of rectal cancer surgery. Low anterior resection (LAR)¹ and internal and external sphincter resection (ISR and ESR) are anal-preserving surgeries.^2,3 The aim of these procedures is to restore the normal process of defecation, along with its function, and to improve the quality of life of patients by avoiding permanent colostomy. However, anal-preserving surgery is often associated with evacuative dysfunction and various degrees of incontinence.^4–7Most studies that have assessed the evacuation function have used clinical questionnaires, which are subjective and may vary according to the patient perception.⁷ There are many factors that can affect the evacuative function, such as the stool consistency, rectal capacity, anal sphincters, pelvic floor muscles, and intra-abdominal pressure. Although manometry with or without the clinical score has also commonly been used, fecoflowmetry (FFM) has been reported to be more accurate and useful for assessing the postoperative anorectal motor function.^8–13 FFM was first introduced by Shafik and is a dynamic method for examining the anorectal motor activity that simulates the natural act of defecation.¹⁴ Some studies have shown its usefulness in postoperative patients with anorectal disease,^8–11 but only a few studies have been performed to examine the evacuative function following anal-preserving surgery.^12,13 The aim of this study was to evaluate the evacuative function in the postoperative period following anal-preserving surgery in patients with low rectal cancer using FFM, and to compare the results with the Wexner score and anorectal manometry.¹⁵     

Effects of a low dose of indapamide, a diuretic, given daily or every-other-day on blood pressure and metabolic parameters.

To investigate the effects of the diuretic, indapamide, on blood pressure (BP) and metabolic parameters, thirty hypertensive patients were treated with 1 mg of indapamide either every day or every other day. BP, fasting plasma glucose, lipids, serum potassium and uric acid were determined at baseline and after 3 months of a stable regimen of the drug. At the termination of the study, 48-h ambulatory blood pressure monitoring (ABPM) was performed. Three patients received only indapamide, while other patients were treated in combination with additional antihypertensive medications. Patients treated with daily indapamide showed a BP reduction from 162 +/- 2.9/85 +/- 2.4 mmHg to 134 +/- 2.4/71 +/-2.6 mmHg (p < 0.001). The BP reduction was similar in those patients receiving the drug every other day (137 +/- 3.4/71 +/- 3.6 mmHg). While plasma lipids and serum potassium did not differ significantly with the intervention, uric acid increased significantly with daily treatment and normalized with every-other-day treatment. Glycosylated hemoglobin A1c (HbA1c) was not altered (5.6 +/- 0.1% vs. 5.4 +/- 0.2%), and did not differ between patients with and without diabetes mellitus. ABPM revealed an average 24-h BP of 134 +/- 3.3/75 +/- 1.7 mmHg on days in which patients received the medication and 139 +/- 4.9/78 +/- 2.6 mmHg on the intervening day without indapamide (no significant difference). These results suggest that a low dose of indapamide given every day or every other day is effective in lowering BP and does not result in metabolic derangements.     

Effects of Inducers and Epoxide Hydrase on the Metabolism of Benzo[a]pyrene by Liver Microsomes and a Reconstituted System: Analysis by High Pressure Liquid Chromatography

The mobilities of 24 potential metabolites of benzo[a]pyrene were examined with high pressure liquid chromatography. Twelve phenols, five quinones, four dihydrodiols, and three oxides were studied. The chromatographic procedure employed allowed the separation and quantitation of benzopyrene metabolites into three major groups consisting of phenols, quinones, and dihydrodiols. Two of the benzopyrene oxides were unstable during chromatography, whereas the third oxide was more stable and chromatographed in the quinone fraction.Treatment of rats with phenobarbital or 3-methylcholanthrene enhanced the metabolism of benzopyrene by liver microsomes and altered the relative amounts of the various metabolites formed. In the absence of epoxide hydrase (EC 4.2.1.63), benzopyrene was metabolized primarily to phenols and quinones but was not appreciably metabolized to dihydrodiols by a solubilized, reconstituted cytochrome P-448 monooxygenase system. Addition of partially purified epoxide hydrase resulted in the formation of benzopyrene dihydrodiols with a concomitant decrease in the formation of phenolic metabolites, indicating that benzopyrene undergoes metabolism via arene oxides that are precursors for dihydrodiols and phenols.