A PTHrP Gradient Drives Mandibular Condylar Chondrogenesis via Runx2.

The mandibular condylar cartilage (MCC) is an essential component of the temporomandibular joint, which orchestrates the vertical growth of the mandibular ramus through endochondral ossification with distinctive modes of cell differentiation. Parathyroid hormone-related protein (PTHrP) is a master regulator of chondrogenesis; in the long bone epiphyseal growth plate, PTHrP expressed by resting zone chondrocytes promotes chondrocyte proliferation in the adjacent layer. However, how PTHrP regulates chondrogenesis in the MCC remains largely unclear.

Hedgehog activation promotes osteogenic fates of growth plate resting zone chondrocytes through transient clonal competency.

The resting zone of the postnatal growth plate is organized by slow-cycling chondrocytes expressing parathyroid hormone-related protein (PTHrP), which include a subgroup of skeletal stem cells that contribute to the formation of columnar chondrocytes. The PTHrP-Indian hedgehog feedback regulation is essential for sustaining growth plate activities; however, molecular mechanisms regulating cell fates of PTHrP+ resting chondrocytes and their eventual transformation into osteoblasts remain largely undefined. Here, in a mouse model, we specifically activated Hedgehog signaling in PTHrP+ resting chondrocytes and traced the fate of their descendants using a tamoxifen-inducible Pthrp-creER line with patched-1-floxed and tdTomato reporter alleles.

Growth plate resting zone chondrocytes acquire transient clonal competency upon Hedgehog activation and efficiently transform into trabecular bone osteoblasts.

The resting zone of the postnatal growth plate is organized by slow-cycling chondrocytes expressing parathyroid hormone-related protein (PTHrP), which include a subgroup of skeletal stem cells that contribute to the formation of columnar chondrocytes. The PTHrP-indian hedgehog (Ihh) feedback regulation is essential for sustaining growth plate activities; however, molecular mechanisms regulating cell fates of PTHrP resting chondrocytes and their eventual transformation into osteoblasts remain largely undefined. Here, in a mouse model, we utilized a tamoxifen-inducible line with ( ) floxed and tdTomato reporter alleles to specifically activate Hedgehog signaling in PTHrP resting chondrocytes and trace the fate of their descendants.

The fate of early perichondrial cells in developing bones.

In endochondral bone development, bone-forming osteoblasts and bone marrow stromal cells have dual origins in the fetal cartilage and its surrounding perichondrium. However, how early perichondrial cells distinctively contribute to developing bones remain unidentified. Here we show using in vivo cell-lineage analyses that Dlx5 fetal perichondrial cells marked by Dlx5-creER do not generate cartilage but sustainably contribute to cortical bone and marrow stromal compartments in a manner complementary to fetal chondrocyte derivatives under the regulation of Hedgehog signaling.

Risk factors for short-term re-bleeding in patients with colonic diverticular bleeding: a multicenter retrospective study.

Background And Aim: Few studies have evaluated risk factors for short-term re-bleeding in patients with colonic diverticular bleeding (CDB). We aimed to reveal risk factors for re-bleeding within a month in patients with CDB.

Methods: We retrospectively analyzed clinical course of patients with CDB diagnosed at 10 institutions between 2015 and 2019.

Hypoxia-inducible factor 1α induces osteo/odontoblast differentiation of human dental pulp stem cells via Wnt/β-catenin transcriptional cofactor BCL9.

Accelerated dental pulp mineralization is a common complication in avulsed/luxated teeth, although the mechanisms underlying this remain unclear. We hypothesized that hypoxia due to vascular severance may induce osteo/odontoblast differentiation of dental pulp stem cells (DPSCs). This study examined the role of B-cell CLL/lymphoma 9 (BCL9), which is downstream of hypoxia-inducible factor 1α (HIF1α) and a Wnt/β-catenin transcriptional cofactor, in the osteo/odontoblastic differentiation of human DPSCs (hDPSCs) under hypoxic conditions.

HIF1α inhibits LPS-mediated induction of IL-6 synthesis via SOCS3-dependent CEBPβ suppression in human dental pulp cells.

Hypoxia-inducible factor 1 alpha (HIF1α) is a transcriptional factor that plays a key role in the regulation of various molecules expressed in hypoxic conditions. Ischemic/hypoxic conditions are regarded as a distinct characteristic of dental pulp inflammation due to the encasement of pulp tissue within the rigid tooth structure. This study was performed to examine the role of HIF1α in the regulation of interleukin (IL)-6, a proinflammatory cytokine expressed in inflamed dental pulp, in lipopolysaccharide (LPS)-stimulated human dental pulp cells (hDPCs).

Methotrexate-associated lymphoproliferative disorder with hypopituitarism and central diabetes insipidus.

Summary: Patients treated with immunosuppressive drugs, especially methotrexate (MTX), rarely develop lymphoproliferative disorders (LPDs), known as MTX-related LPD (MTX-LPD). The primary site of MTX-LPD is often extranodal. This is the first reported case of MTX-LPD in the pituitary.

Self-study of the non-extension sign in an e-learning program improves diagnostic accuracy of invasion depth of early gastric cancer.

 We developed an e-learning program for endoscopic diagnosis of invasion depth of early gastric cancer (EGC) using a simple diagnostic criterion called non-extension sign, and the contribution of self-study quizzes to improvement of diagnostic accuracy was evaluated.  We conducted a prospective randomized controlled study that recruited endoscopists throughout Japan. After completing a pretest, the participants watched video lectures and undertook post-test 1.

Effect of repeated oral administration of Bifidobacterium longum BB536 on apomorphine-induced rearing behavior in mice.

Schizophrenia is a chronic psychiatric illness. Disruption of the dopaminergic system has been suggested to be the pathogenic cause of this disease. The effect of Bifidobacterium longum BB536 (BB536) on schizophrenic behavior was investigated in an animal model.

Dabigatran-induced esophagitis: The prevalence and endoscopic characteristics.

Background And Aim: There have been some descriptions of dabigatran-induced esophagitis in the literature. The aim of this study was to examine the prevalence and endoscopic characteristics of the disease.

Methods: We reviewed the endoscopic database and medical records of 91 patients with dabigatran internal use who underwent upper gastrointestinal endoscopy.

Lipoma of the small intestine treated with endoscopic resection.

We report a case of lipoma of the small intestine that was treated by endoscopic resection. A 79-year-old man who complained of tarry stool was diagnosed as having jejunal tumor at a neighboring clinic. Computed tomography (CT) and enteroscopy demonstrated an ulcerating jejunal mass.

The effect of granulocyte and monocyte adsorptive apheresis on serum cytokine levels in patients with ulcerative colitis.

Granulocyte and monocyte adsorptive apheresis (GMA) with an Adacolumn has been reported to be effective as induction therapy in ulcerative colitis (UC). However, the effects of GMA on serial changes in cytokine levels have not been well characterized. We therefore, investigated cytokine levels in UC patients before and after treatment with GMA.

Suprapubic versus transurethral bladder drainage after radical prostatectomy: impact on patient discomfort.

We evaluated the feasibility and the benefits of total prostatectomy with suprapubic cystostomy drainage instead of a urethral Foley catheter. Of 65 consecutive total retropubic prostatectomies, 42 were carried out with the suprapubic cystostomy, and 23 with the urethral Foley catheter. Patients were asked postoperatively to complete a 5-cm visual analog scale on pain intensity related to the catheter and to urination after catheter removal.

Peripheral Blood CD64 Levels Decrease in Crohn's Disease following Granulocyte and Monocyte Adsorptive Apheresis.

Granulocyte and monocyte adsorptive apheresis (GMA) is reportedly useful as induction therapy for Crohn's disease (CD). However, the effects of GMA on CD64 have not been well characterized. We report here our assessment of CD64 expression on neutrophils before and after treatment with GMA in two patients with CD.

Synthesis and structure-activity relationship study of antimicrotubule agents phenylahistin derivatives with a didehydropiperazine-2,5-dione structure.

Plinabulin (11, NPI-2358) is a potent microtubule-targeting agent derived from the natural diketopiperazine "phenylahistin" (1) with a colchicine-like tubulin depolymerization activity. Compound 11 was recently developed as VDA and is now under phase II clinical trials as an anticancer drug. To develop more potent antimicrotubule and cytotoxic derivatives based on the didehydro-DKP skeleton, we performed further modification on the tert-butyl or phenyl groups of 11, and evaluated their cytotoxic and tubulin-binding activities.

[Long-term prognosis of incidental renal cell carcinoma--clinical analysis of renal cell carcinoma detected by our health checkup].

Purpose: We retrospectively evaluated the characteristics and long-term prognosis of incidentally detected renal cell carcinoma by health checkup.

Materials And Methods: From January 1987 to December 2005, 556 patients were treated for renal cell carcinoma in our department. Among them, 56 patients were detected by abdominal ultrasonography in health checkup of our health care center.

A randomized comparative study of endocrine monotherapy and a combination of estramustine phosphate with the endocrine therapy in patients with untreated stage D prostate cancer.

Background: We investigated the clinical efficacy and the prolongation of survival with combination therapy of estramustine phosphate (EMP) and endocrine therapy in untreated patients with progressive prostate cancer.

Methods: We randomly divided 57 patients with untreated stage D prostate cancer into two groups, an endocrine monotherapy group and a group receiving combination treatment, consisting of endocrine therapy plus EMP. Treatment was continued until deterioration.

Midline extraperitoneal approach to upper urinary tract surgery: anatomical basis of surgical technique.

To overcome the disadvantages inherent in the standard surgical approach to the kidney, we introduced a novel surgical technique via a midline extraperitoneal approach. The surgical technique is not substantially different from that of the standard midline transperitoneal approach, except no entry is made into the peritoneal cavity. Although the peritoneum itself is extremely thin and fragile, the peritoneum together with underlying subperitoneal fascia can be dissected readily as a substantial layer, if the proper plane is dissected.

[Pathophysiology and clinical implication of obstructive nephropathy].

Obstructive nephropathy refers to the mechanical or functional changes in the urinary tract that interfere with normal urinary flow. Once obstruction is set, it leads to progressive renal damage that is mainly characterized with tubulointerstitial fibrosis. Here we reviewed the pathophysiology of urinary tract obstruction and indicated future therapeutic options.

Gamma-knife radiosurgery for brain metastasis of renal cell carcinoma: results in 42 patients.

Background: The present study provides data from clinical experience with gamma-knife radiosurgery (GK) in patients with brain metastasis from renal cell carcinoma (RCC) and shows the value of this less invasive treatment modality.

Methods: Forty-two patients received GK. Twenty of the 42 cases had multiple brain metastases.

Upregulated expression of transforming growth factor-beta, type IV collagen, and plasminogen activator inhibitor-1 mRNA are decreased after release of unilateral ureteral obstruction.

Tubulointerstitial fibrosis is a major cause of irreversible renal damage in the obstructed kidney. The effects of release of obstruction on the obstructed kidney are not clearly understood. We investigated the effects of the release of ureteral obstruction on renal fibrosis and the expression of fibrogenic factors.

Monoclonal antibody (5F3) defining renal cell carcinoma-associated antigen disialosyl globopentaosylceramide (V3NeuAcIV6NeuAcGb5), and distribution pattern of the antigen in tumor and normal tissues.

Renal cell carcinoma (RCC) has been characterized by high expression of three types of disialogangliosides: two based on lacto-series type 1 structure (disialosyl Lc(4), GalNAc disialosyl Lc(4)), the other based on globo-series structure (disialosyl globopentaosylceramide; disialosyl Gb5). The present study established a mAb, 5F3, directed to disialosyl Gb5. 5F3 was established after immunization with RCC cell line ACHN.