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Antxr1, Which is a Target of Runx2, Regulates Chondrocyte Proliferation and Apoptosis
Get PDFAntxr1/Tem8 is highly expressed in tumor endothelial cells and is a receptor for anthrax toxin.
Mutation of Antxr1 causes GAPO syndrome, which is characterized by growth retardation, alopecia,
pseudo-anodontia, and optic atrophy. However, the mechanism underlying the growth retardation
remains to be clarified. Runx2 is essential for osteoblast di erentiation and chondrocyte maturation and regulates chondrocyte proliferation through Ihh induction. In the search of Runx2 target genes in chondrocytes, we found that Antxr1 expression is upregulated by Runx2. Antxr1 was highly expressed in cartilaginous tissues and was directly regulated by Runx2. In skeletal development, the process of endochondral ossification proceeded similarly in wild-type and Antxr1–/– mice. However,the limbs of Antxr1–/– mice were shorter than those of wild-type mice from embryonic day 16.5 due to the reduced chondrocyte proliferation. Chondrocyte-specific Antxr1 transgenic mice exhibited shortened limbs, although the process of endochondral ossification proceeded as in wild-type mice.BrdU-uptake and apoptosis were both increased in chondrocytes, and the apoptosis-high regions were mineralized. These findings indicated that Antxr1, of which the expression is regulated by Runx2, plays an important role in chondrocyte proliferation and that overexpression of Antxr1 causes chondrocyte apoptosis accompanied by matrix mineralization
Detection of viral RNA in diverse body fluids in an SFTS patient with encephalopathy, gastrointestinal bleeding and pneumonia: a case report and literature review
Get PDFBACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that commonly has a lethal course caused by the tick-borne Huaiyangshan banyang virus [former SFTS virus (SFTSV)]. The viral load in various body fluids in SFTS patients and the best infection control measure for SFTS patients have not been fully established. CASE PRESENTATION: A 79-year-old man was bitten by a tick while working in the bamboo grove in Nagasaki Prefecture in the southwest part of Japan. Due to the occurrence of impaired consciousness, he was referred to Nagasaki University Hospital for treatment. The serum sample tested positive for SFTSV-RNA in the genome amplification assay, and he was diagnosed with SFTS. Furthermore, SFTSV-RNA was detected from the tick that had bitten the patient. He was treated with multimodal therapy, including platelet transfusion, antimicrobials, antifungals, steroids, and continuous hemodiafiltration. His respiration was assisted with mechanical ventilation. On day 5, taking the day on which he was hospitalized as day 0, serum SFTSV-RNA levels reached a peak and then decreased. However, the cerebrospinal fluid collected on day 13 was positive for SFTSV-RNA. In addition, although serum SFTSV-RNA levels decreased below the detectable level on day 16, he was diagnosed with pneumonia with computed tomography. SFTSV-RNA was detected in the bronchoalveolar lavage fluid on day 21. By day 31, he recovered consciousness completely. The pneumonia improved by day 51, but SFTSV-RNA in the sputum remained positive for approximately 4 months after disease onset. Strict countermeasures against droplet/contact infection were continuously conducted. CONCLUSIONS: Even when SFTSV genome levels become undetectable in the serum of SFTS patients in the convalescent phase, the virus genome remains in body fluids and tissues. It may be possible that body fluids such as respiratory excretions become a source of infection to others; thus, careful infection control management is needed
Development of HPLC method for estimation of glyoxylic acid after pre-column fluorescence derivatization approach based on thiazine derivative formation: A new application in healthy and cardiovascular patients’ sera
No full textGlyoxylic acid (GA) is the intermediate metabolite in various mammalian metabolic pathways. GA showed high reactivity towards formation of advanced glycation end-products (AGEs); the main cause of pathogenesis and complications of many diseases. The presented study aimed to detect GA in healthy and cardiovascular patients’ (CV) sera; however analysis of GA in biological fluid is a challenge and requires chemical derivatization. Hence, a new, highly sensitive, time saving and reproducible pre-column fluorescence derivatization procedure coupled with high performance liquid chromatography (HPLC) method was developed. The derivatization method was based on reaction of 2-aminobenzenthiol (2-ABT), a fluorogenic reagent, with GA in acidic medium to form highly fluorescent thiazine derivative (290 and 390 nm for excitation and emission wavelengths respectively). The fluorescent derivative was separated within 6 min on a reversed-phase ODS column using an isocratic elution with a mixture of methanol–water (70:30, v/v%). The proposed method parameters were optimized and the method was validated. A good linearity in the concentration range (0.05–5.0 µM) was obtained with detection limit (LOD) of 10 nM (200 fmol/injection), which is more sensitive than several previous methods. Moreover, the recovery results were within the range of 85.0–95.5 % and the intra- and inter-day precision results were ≤3.5%. It should be emphasized that this method is the first one for monitoring of GA in CV patients; to investigate its role for diagnosis and monitoring the severity and complications of this disease in clinical laboratory
Behçet's Disease with Severe Autonomic Disorders Developing after Herpes Zoster
Get PDFA 58-year-old Japanese woman with herpes zoster developed Behçet's disease (BD) with symptoms including orthostatic intolerance as an autonomic disorder. Multiple immune-suppressive therapies and a β-blocker successfully controlled both the disease activity of BD and the autonomic disorders. A cytokine multiplex analysis of her serum revealed the elevation of proinflammatory cytokines [interleukin (IL)-1, IL-6, IL-12, tumor necrosis factor alfa (TNFα), and interferon gamma (IFN-γ)] and a low IL-10 concentration. IL-10 production is reported to be important for defense against herpes zoster virus (VZV). Insufficient IL-10 production is reported in BD. The reactivation of VZV with this cytokine profile suggests that BD will develop with various symptoms, including severe autonomic disorders
Efficacy and Safety of Modified FOLFOXIRI+α in the Treatment of Advanced and Recurrent Colorectal Cancer: A Single-center Experience
Get PDFObjective: In the treatment of advanced and recurrent colorectal cancer (ARCC), FOLFOXIRI regimens have been proven to be significantly superior to FOLFIRI in terms of the progression-free survival (PFS), response rate (RR), and overall survival (OS). Furthermore, the Tribe trial showed that the RR and PFS rates in patients who received bevacizumab (Bmab)+FOLFOXIRI were superior to those in patients treated with Bmab+FOLFIRI. A phase III trial of panitumumab (Pmab)+FOLFOXIRI is currently ongoing. A modified FOLFOXIRI regimen is also widely used to reduce adverse events. In our department, we introduced modified FOLFOXIRI+a (mFOLFOXIRI+a) in 2015. The present study reviewed the efficacy and safety of mFOLFOXIRI+a. Methods: Eligible patients were retrospectively reviewed, and their results were compared to those of patients treated with other regimens (OTHERS) (n=134) to demonstrate the efficacy of this treatment. Patients: Between February 2015 and November 2018, 12 patients with ARCC (male/female=6/6; average age, 60.7 years old) received mFOLFOXIRI+a (Bmab: 10, Pmab: 1, alone: 1). Results: The median PFS in the mFOLFOXIRI+a and OTHERS groups was 565 and 322 days, respectively (p=0.0544). The RR in the mFOLFOXIRI+a and OTHERS groups was 66.7% and 31.3%, respectively (p= 0.0135). The conversion rate (Conv R) in the mFOLFOXIRI+a and OTHERS groups was 50.0% and 12.7%, respectively (p=0.0007). While 58% of patients treated with FOLFOXIRI+a developed grade >3 leukopenia, the incidence of febrile neutropenia (FN) was only 17%. In all patients with symptoms due to the tumor burden, the symptoms subsided with mFOLFOXIRI+a treatment. Conclusion: Based on the RR, Conv R, and symptom palliation ability, mFOLFOXIRI+a was suggested to be a viable candidate for first-line treatment for patients with ARCC, especially those with a high tumor burden
Impact of heat modification conditions on the removal of N-nitrosodimethylamine by polyamide reverse osmosis membranes
No full textAdvanced wastewater treatment using a reverse osmosis (RO) membrane is a key separation process for ensuring the removal of chemical hazards so that treated wastewater can be used for potable purposes. This study systematically assesses the effects of heat modification conditions of three commercial RO membranes on the removal of a challenging chemical of emerging concern–N-nitrosodimethylamine (NDMA). The RO membranes were modified in pure water at the heat treatment temperature between 70 and 100 °C; 90–100 °C achieved the highest NDMA rejection during separation tests. A lower pH during heat treatment generally resulted in higher NDMA rejection, however a solution pH lower than four can reduce NDMA rejection depending on the presence of a protective layer on the RO membrane surface. Overall, a linear tradeoff between NDMA rejection and water permeance was commonly observed among the heat-treated RO membranes. The stability of a heat-modified membrane in water permeance and NDMA rejection was demonstrated over a week-long test using treated wastewater. The enhanced removal of NDMA by heat-treated RO membranes was speculated to occur due to the shrinking of the passage of solutes–free-volume holes. This study demonstrates the importance of heat modification conditions on RO membranes to achieve a high NDMA rejection