1,162 research outputs found
Investigation of the SH3BP2 Gene Mutation in Cherubism
Cherubism is a rare developmental lesion of the jaw that is generally inherited as an autosomal dominant trait. Recent studies have revealed point mutations in the SH3BP2 gene in cherubism patients. In this study, we examined a 6-year-old Korean boy and his family. We found a Pro418Arg mutation in the SH3BP2 gene of the patient and his mother. A father and his 30-month-old younger brother had no mutations. Immunohistochemically, the multinucleated giant cells proved positive for CD68 and tartrate-resistant acid phosphatase (TRAP). Numerous spindle-shaped stromal cells expressed a ligand for receptor activator of nuclear factor kB (RANKL), but not in multinucleated giant cells. These results provide evidence that RANKL plays a critical role in the differentiation of osteoclast precursor cells to multinucleated giant cells in cherubism. Additionally, genetic analysis may be a useful method for differentiation of cherubism.</p
Anaphylaxis Caused by Benzalkonium in a Nebulizer Solution
Benzalkonium chloride (BAC) is commonly used as a bactericidal preservative in nebulizer solutions, and can cause paradoxical onchoconstriction following nebulizing therapy in some asthmatics. We describe a case of anaphylactic shock in a 23-yr-old asthmatic woman following an intradermal skin test with a salbutamol solution containing BAC. Since she complained of cough and dyspnea after inhalation therapy with a nebulizer solution, we conducted an intradermal skin test using the same solution, which contained BAC. About 10 min later, the patient reported dizziness, palpitations, and dyspnea. On examination, tachycardia, tachypnea, and hypotension were found. She was resuscitated with a subcutaneous injection of epinephrine and an infusion of saline. One month later, we conducted a bronchial provocation test with BAC, and she showed a positive response
Treatment of Chronic Hepatitis C Using Newly Developed Oral Antiviral Agents
Standard care for chronic hepatitis C has been a combination of pegylated interferon-alpha and ribavirin, although this treatment has suboptimal antiviral efficacy and significant adverse events. The hepatitis C virus treatment landscape has been transformed recently by the development of direct-acting antiviral agents (DAAs) that target NS3 protease, NS5A protein, and NS5B polymerase. Several DAAs showed potent antiviral activity leading to increased rates of sustained virological response (SVR), even in difficult-to-treat patients such as older patients and those with advanced liver disease and prior failed peg-interferon/ribavirin treatment. Use of multiple DAAs without pegylated interferon has shown dramatically high SVR rates (up to nearly 100%) with negligible side effects. Interferon-free regimens are close to becoming the new standard of care for patients with chronic hepatitis C in USA and Europe. Similarly, several DAAs are near clinical use in Korea. This review discusses DAAs that have been approved or are under investigation for approval in Koreaope
Optical pulse differentiation based on a resonant slow & fast light system
We experimentally demonstrate that temporal differentiation of optical pulses can be realized in a slow & fast light system based on a resonance. The waveform of a 13 ns Gaussian pulse was experimentally first-order differentiated
Tenofovir alafenamide and tenofovir disoproxil fumarate reduce incidence of hepatocellular carcinoma in patients with chronic hepatitis B
Antiviral therapy; IncidenceTerapia antiviral; IncidenciaTerร pia antiviral; IncidรจnciaBackground & Aims
Antiviral therapy may attenuate the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). We aimed to explore how tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF) affect HCC risk in patients with CHB.
Methods
The REACH-B, aMAP, and mPAGE-B models were utilized to assess HCC risk in patients with CHB from two global randomized-controlled trials evaluating the impact of TAF vs. TDF treatment. Standard incidence ratios (SIRs) were calculated using data from the REACH-B model as a ratio of observed HCC cases in the TAF- or TDF-treated patients vs. predicted HCC cases for untreated historical controls. Proportions of treated patients shifting aMAP and mPAGE-B risk categories between baseline and Week 240 were calculated.
Results
Of the 1,632 patients (TAF, n = 1,093; TDF, n = 539) followed for up to 300 weeks, 22 HCC cases developed. Those receiving TAF had an SIR that was lower compared to the SIR of individuals receiving TDF: 0.32 (p <0.001) vs. 0.56 (p = 0.06). In the general study population, individuals without cirrhosis at baseline had an SIR that was lower compared to the SIR of individuals with cirrhosis at baseline: 0.37 (p <0.001) vs. 0.58 (p = 0.15). Of the patients at low risk of HCC at baseline, the majority (97%) remained low risk by mPAGE-B and aMAP scoring at Week 240. Among those at medium or high risk at baseline, substantial portions shifted to a lower risk category by Week 240 (mPAGE-B: 22% and 42%; aMAP: 39% and 63%, respectively).
Conclusions
This evaluation provides evidence that treatment with TAF or TDF can reduce HCC risk in patients with CHB, particularly in patients without cirrhosis.
Impact and implications
Despite the substantial impact of HCC on long-term outcomes of patients with CHB, the differential risk of HCC development among those receiving treatment with TAF vs. TDF has not been well elucidated. Using three validated risk prediction models, we found that TAF is at least as effective as TDF in reducing HCC risk in patients with CHB. While TDF is well-studied in the context of HCC risk reduction, our novel findings underscore the effectiveness of TAF as a treatment option for patients with CHB.
Clinical trial numbers
NCT01940341; NCT02836249; NCT01940471; NCT02836236.This study was sponsored by Gilead Sciences. This article was based on the original studies GS-US-320-0108 and GS-US-320-0110 sponsored by Gilead Sciences. Support for third-party writing assistance for this article, provided by Julianna Catania, MPH, and Isabel Haber, BS, Costello Medical, US, was funded by Gilead in accordance with Good Publication Practice (GPP3) guidelines (http://www.ismpp.org/gpp3)
An Unusual Odontogenic Cyst with Diverse Histologic Features
An unusual odontogenic cyst, which was originally believed to be a clinical dentigerous cyst associated with an impacted mandibular third molar, was found histologically to demonstrate the characteristics of a glandular odontogenic cyst with para- and orthokeratinization. These histologic diversities were interpreted as a reflection of the pluripotentiality of the epithelial remnants of the mandibular third molars or dentigerous cyst epithelium. It is possible that it has the capacity to induce the formation of cysts in both squamous and glandular epithelium
Suppression of STAT3 and HIF-1 Alpha Mediates Anti-Angiogenic Activity of Betulinic Acid in Hypoxic PC-3 Prostate Cancer Cells
Background: Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that regulates various cellular processes such as cell survival, angiogenesis and proliferation. In the present study, we examined that betulinic acid (BA), a triterpene from the bark of white birch, had the inhibitory effects on hypoxia-mediated activation of STAT3 in androgen independent human prostate cancer PC-3 cells. Methodology/Principal Findings: BA inhibited the protein expression and the transcriptional activities of hypoxia-inducible factor-1a (HIF-1a) under hypoxic condition. Consistently, BA blocked hypoxia-induced phosphorylation, DNA binding activity and nuclear accumulation of STAT3. In addition, BA significantly reduced cellular and secreted levels of vascular endothelial growth factor (VEGF), a critical angiogenic factor and a target gene of STAT3 induced under hypoxia. Furthermore, BA prevented in vitro capillary tube formation in human umbilical vein endothelial cells (HUVECs) maintained in conditioned medium of hypoxic PC-3 cells, implying anti-angiogenic activity of BA under hypoxic condition. Of note, chromatin immunoprecipitation (ChiP) assay revealed that BA inhibited binding of HIF-1a and STAT3 to VEGF promoter. Furthermore, silencing STAT3 using siRNA transfection effectively enhanced the reduced VEGF production induced by BA treatment under hypoxia. Conclusions/Significance: Taken together, our results suggest that BA has anti-angiogenic activity by disturbing th
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