Preparation and In Vitro Release Property of PLA Microspheres Enclosing Antitumor Agent

Recently, many antitumor agents developed. Irinotecan hycrochloride (CPT) has a great side effect even though it is well effective against the cancer. Drug delivery system (DDS) medicine indicates that the release rate of medicine is constant for a long time. Therefore, in order to materialize the general idea of DDS, we applied microencapsulation technique to prepare biodegradable polymer microspheres (MS) enclosing antitumor drug having no side effect. Polylactide microparticles enclosing antitumor agent were prepared by solvent evaporation method under various operation conditions. The effects of operation parameter on release rate of drug and morphology of microparticles were studied

Cell-Surface Protein Profiling Identifies Distinctive Markers of Progenitor Cells in Human Skeletal Muscle

SummarySkeletal muscle contains two distinct stem/progenitor populations. One is the satellite cell, which acts as a muscle stem cell, and the other is the mesenchymal progenitor, which contributes to muscle pathogeneses such as fat infiltration and fibrosis. Detailed and accurate characterization of these progenitors in humans remains elusive. Here, we performed comprehensive cell-surface protein profiling of the two progenitor populations residing in human skeletal muscle and identified three previously unrecognized markers: CD82 and CD318 for satellite cells and CD201 for mesenchymal progenitors. These markers distinguish myogenic and mesenchymal progenitors, and enable efficient isolation of the two types of progenitors. Functional study revealed that CD82 ensures expansion and preservation of myogenic progenitors by suppressing excessive differentiation, and CD201 signaling favors adipogenesis of mesenchymal progenitors. Thus, cell-surface proteins identified here are not only useful markers but also functionally important molecules, and provide valuable insight into human muscle biology and diseases

Mutations in the J domain of DNAJB6 cause dominant distal myopathy

Eight patients from five families with undiagnosed dominant distal myopathy underwent clinical, neurophysiological and muscle biopsy examinations. Molecular genetic studies were performed using targeted sequencing of all known myopathy genes followed by segregation of the identified mutations in the affected families using Sanger sequencing. Two novel mutations in DNAJB6 J domain, c.149C>T (p.A50V) and c.161A>C (p.E54A), were identified as the cause of disease. The muscle involvement with p.A50V was distal calf-predominant, and the p.E54A was more proximo-distal. Histological findings were similar to those previously reported in DNAJB6 myopathy. In line with reported pathogenic mutations in the glycine/phenylalanine (G/F) domain of DNAJB6, both the novel mutations showed reduced anti-aggregation capacity by filter trap assay and TDP-43 disaggregation assays. Modeling of the protein showed close proximity of the mutated residues with the G/F domain. Myopathy-causing mutations in DNAJB6 are not only located in the G/F domain, but also in the J domain. The identified mutations in the J domain cause dominant distal and proximo-distal myopathy, confirming that mutations in DNAJB6 should be considered in distal myopathy cases.Peer reviewe

Optimal Intravascular Ultrasound-Guided Percutaneous Coronary Intervention in Patients With Multivessel Disease

BACKGROUND: Intravascular ultrasound (IVUS) was only rarely used in landmark trials comparing percutaneous coronary intervention (PCI) with coronary artery bypass grafting (CABG) in patients with multivessel disease. OBJECTIVES: The authors aimed to evaluate clinical outcomes after optimal IVUS-guided PCI in patients undergoing multivessel PCI. METHODS: The OPTIVUS (OPTimal IntraVascular UltraSound)-Complex PCI study multivessel cohort was a prospective multicenter single-arm study enrolling 1, 021 patients undergoing multivessel PCI, including left anterior descending coronary artery using IVUS, aiming to meet the prespecified criteria (OPTIVUS criteria: minimum stent area > distal reference lumen area [stent length ≥28mm], and minimum stent area >0.8 × average reference lumen area [stent length <28mm]) for optimal stent expansion. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE) (death/myocardial infarction/stroke/any coronary revascularization). The predefined performance goals were derived from the CREDO-Kyoto (Coronary REvascularization Demonstrating Outcome study in Kyoto) PCI/CABG registry cohort-2 fulfilling the inclusion criteria in this study. RESULTS: In this study, 40.1% of the patients met OPTIVUS criteria in all stented lesions. The cumulative 1-year incidence of the primary endpoint was 10.3% (95% CI: 8.4%-12.2%), which was significantly lower than the predefined PCI performance goal of 27.5% (P < 0.001), and which was numerically lower than the predefined CABG performance goal of 13.8%. The cumulative 1-year incidence of the primary endpoint was not significantly different regardless of meeting or not meeting OPTIVUS criteria. CONCLUSIONS: Contemporary PCI practice conducted in the OPTIVUS-Complex PCI study multivessel cohort was associated with a significantly lower MACCE rate than the predefined PCI performance goal, and with a numerically lower MACCE rate than the predefined CABG performance goal at 1 year

Conversion to complete resection with mFOLFOX6 with bevacizumab or cetuximab based on K‐RAS status for unresectable colorectal liver metastasis (BECK study): Long‐term results of survival

[Background/Purpose]To investigate the long‐term outcome and entire treatment course of patients with technically unresectable CRLM who underwent conversion hepatectomy and to examine factors associated with conversion to hepatectomy. [Methods]Recurrence and survival data with long‐term follow‐up were analyzed in the cohort of a multi‐institutional phase II trial for technically unresectable colorectal liver metastases (the BECK study). [Results]A total of 22/12 patients with K‐RAS wild‐type/mutant tumors were treated with mFOLFOX6 + cetuximab/bevacizumab. The conversion R0/1 hepatectomy rate was significantly higher in left‐sided primary tumors than in right‐sided tumors (75.0% vs 30.0%, P = .022). The median follow‐up was 72.6 months. The 5‐year overall survival (OS) rate in the entire cohort was 48.1%. In patients who underwent R0/1 hepatectomy (n = 21), the 5‐year RFS rate and OS rate were 19.1% and 66.3%, respectively. At the final follow‐up, seven patients had no evidence of disease, five were alive with disease, and 20 had died from their original cancer. All 16 patients who achieved 5‐year survival underwent conversion hepatectomy, and 11 of them underwent further resection for other recurrences (median: 2, range: 1‐4). [Conclusions]Conversion hepatectomy achieved a similar long‐term survival to the results of previous studies in initially resectable patients, although many of them experienced several post‐hepatectomy recurrences. Left‐sided primary was found to be the predictor for conversion hepatectomy

Transgenic Monkey Model of the Polyglutamine Diseases Recapitulating Progressive Neurological Symptoms

Age-associated neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and the polyglutamine (polyQ) diseases, are becoming prevalent as a consequence of elongation of the human lifespan. Although various rodent models have been developed to study and overcome these diseases, they have limitations in their translational research utility owing to differences from humans in brain structure and function and in drug metabolism. Here, we generated a transgenic marmoset model of the polyQ diseases, showing progressive neurological symptoms including motor impairment. Seven transgenic marmosets were produced by lentiviral introduction of the human ataxin 3 gene with 120 CAG repeats encoding an expanded polyQ stretch. Although all offspring showed no neurological symptoms at birth, three marmosets with higher transgene expression developed neurological symptoms of varying degrees at 3–4 months after birth, followed by gradual decreases in body weight gain, spontaneous activity, and grip strength, indicating time-dependent disease progression. Pathological examinations revealed neurodegeneration and intranuclear polyQ protein inclusions accompanied by gliosis, which recapitulate the neuropathological features of polyQ disease patients. Consistent with neuronal loss in the cerebellum, brain MRI analyses in one living symptomatic marmoset detected enlargement of the fourth ventricle, which suggests cerebellar atrophy. Notably, successful germline transgene transmission was confirmed in the second-generation offspring derived from the symptomatic transgenic marmoset gamete. Because the accumulation of abnormal proteins is a shared pathomechanism among various neurodegenerative diseases, we suggest that this new marmoset model will contribute toward elucidating the pathomechanisms of and developing clinically applicable therapies for neurodegenerative diseases.ArticleeNeuro.4(2):e0250(2017)journal articl

Spontaneous bladder rupture diagnosis based on urinary appearance of mesothelial cells: a case report

Introduction. Spontaneous bladder rupture is an extremely rare clinical event that is associated with urinary ascites and apparent acute renal failure. This event is difficult to diagnose clinically, even with advanced techniques such as computed tomography; however, the timely diagnosis of this condition is critical. Here, we report a case of a patient who experienced a spontaneous intraperitoneal bladder rupture 10 years after postoperative pelvic irradiation for the treatment of uterine cancer. In this report of a rare case, we describe the contribution of the appearance of mesothelial cells in the urine to the diagnosis of this condition. Case presentation. Our patient was a 71-year-old Asian woman who experienced lower abdominal pain and vomiting of two days duration. On admission, abdominal computed tomography showed intraperitoneal fluid collection and her blood tests revealed acute renal failure and hyperkalemia. She underwent hemodialysis and a transurethral catheter was inserted. The transurethral catheter was removed three days after her admission. Four days after the catheter removal, her symptoms recurred and her serum creatinine and blood urea nitrogen levels were elevated. We noted the presence of mesothelial cells in her urine, which led to a diagnosis of intraperitoneal bladder rupture. She underwent surgical repair of her bladder and hyperbaric oxygen therapy, and was discharged after her renal function returned to normal. Conclusion: Urine analysis is a simple and non-invasive test and we believe that a thorough urine analysis may contribute to the early diagnosis of an intraperitoneal bladder rupture. We think that the findings presented in this case report will significantly enhance our understanding of the etiology of bladder rupture. Moreover, these case findings may help nephrologists and urologists to rapidly diagnose this condition

Constraints on axion-like polarization oscillations in the cosmic microwave background with POLARBEAR

Very light pseudoscalar fields, often referred to as axions, are compelling dark matter candidates and can potentially be detected through their coupling to the electromagnetic field. Recently a novel detection technique using the cosmic microwave background (CMB) was proposed, which relies on the fact that the axion field oscillates at a frequency equal to its mass in appropriate units, leading to a time-dependent birefringence. For appropriate oscillation periods this allows the axion field at the telescope to be detected via the induced sinusoidal oscillation of the CMB linear polarization. We search for this effect in two years of POLARBEAR data. We do not detect a signal, and place a median $95 \%$ upper limit of $0.65 ^\circ$ on the sinusoid amplitude for oscillation frequencies between $0.02\,\text{days}^{-1}$ and $0.45\,\text{days}^{-1}$, which corresponds to axion masses between $9.6 \times 10^{-22} \, \text{eV}$ and $2.2\times 10^{-20} \,\text{eV}$. Under the assumptions that 1) the axion constitutes all the dark matter and 2) the axion field amplitude is a Rayleigh-distributed stochastic variable, this translates to a limit on the axion-photon coupling $g_{\phi \gamma} < 2.4 \times 10^{-11} \,\text{GeV}^{-1} \times ({m_\phi}/{10^{-21} \, \text{eV}})$.Comment: 17 pages, 5 figures, 2 tables. Published in Physical Review