Miracle-dz/UniFAR-FTUs huggingface dataset:
Constitutive and induced expression of APO-1, a new member of the nerve growth factor/tumor necrosis factor receptor superfamily, in normal and neoplastic cells.

BACKGROUND APO-1 is a 48 kilodalton transmembrane, cysteine-rich glycoprotein identical with the Fas antigen which belongs to the nerve growth factor/tumor necrosis factor receptor superfamily. Cross-linking of APO-1 induces apoptotic cell death in sensitive cells. EXPERIMENTAL DESIGN As suggested by our preliminary results, APO-1 expression is not restricted to cells of the hematopoietic lineage. We therefore investigated APO-1 expression in normal human tissues and in various epithelial and nonepithelial tumors. RESULTS We show by immunohistochemistry that APO-1 is a non-lineage antigen constitutively expressed in a variety of epithelial cells. This includes the basal layers of various squamous epithelia, transitional epithelium and columnar epithelium of the biliary tract and intestine. Among the epithelial cell types of the reproductive system of both genders, APO-1 expression is complex. Except the satellite cells of autonomic ganglia, all cells of the nervous tissue are APO-1-negative. Among mesenchymal cells, constitutive APO-1 expression is rare but detectable in various kinds of activated cells, e.g. fibroblasts, osteoblasts, and subpopulations of endothelial cells. Within the immune system, APO-1 is broadly distributed among histiocytic cells but restricted to minor subpopulations of peripheral T and B cells. Immature T cells, i.e., thymocytes, do not express detectable APO-1-antigen. Expression of APO-1 was induced in phytohemagglutinin activated T cells and in a mammary carcinoma cell line by interferon-gamma alone and in combination with tumor necrosis factor alpha. Consistently, there was an in situ induction of APO-1 in several types of glandular epithelium in microtopographic association with lymphohistiocytic infiltrates. This inflammation-associated APO-1 induction went along with increased expression of this molecule within the lymphocytic compartment of the lesion. In tumors. APO-1 expression was heterogeneous. In comparison to their normal counterparts, some tumors showed abnormal hypo-expression or loss of APO-1. However, abnormal neo-expression was also found. CONCLUSIONS Tissue distribution, in vitro expression, and reaction upon cytokine-induced activation suggest that APO-1 might not only transmit apoptotic signals but might play a more general role in growth control.
Bioengineering and subjective approaches to the clinical evaluation of dry skin

Dry skin (also known as xerosis) is a cutaneous reaction pattern indicative of abnormal desquamation, which has not only cosmetic considerations, but can also lead to the penetration of irritants and allergens through the stratum corneum (SC). Over the last few decades, our understanding of the structure, composition, formation and function of the SC has advanced tremendously; however, despite these advancements, the occurrence of dry skin remains prevalent in the adult population. The clinical evaluation of dry skin is therefore of significant importance to the cosmetic industry not only for understanding the condition but also for measuring the effects of treatment. Traditionally, dry skin has been evaluated by visual inspection, however, recently a variety of bioengineering techniques have emerged enabling the investigator to objectively assess the extent of xerotic conditions. The most frequently employed methods for the evaluation of dry skin are discussed in this review, including regression testing, squametry, measurement of transepidermal water loss, epidermal hydration, profilometry, confocal Raman spectroscopy, optical coherence tomography, in vivo confocal microscopy and magnetic resonance imaging.
Liver transplantation for alveolar echinococcosis in an endemic region

Alveolar echinococcosis (AE) is a chronic disease caused by ingestion of the eggs of the parasitic cestode Echinococcosis multilocularis (EM). In severe cases, liver transplantation (LT) may represent the only possibility of survival and cure. Patients undergoing LT associated with hepatic AE at our institution between April 2011 and October 2014 were investigated retrospectively. The clinical findings of the 27 patients who participated in the study were noted. Kaplan‐Meier and chi‐square tests were used to investigate the effect of these characteristics on survival and mortality. Living donor LT was performed on 20 patients (74.1%), and deceased donor LT was performed on 7 patients (25.9%). Hilar invasion was the most common indication (14 patients, 51.9%) for transplantation. The patient follow‐up was 16.1 ± 11.4 months, and the overall survival rate was 77.8%. Primary nonfunction developed only in 2 patients in the posttransplantation period. Six patients died during monitoring, the most common cause of death being sepsis (3 patients). The relationship between the mortality rate of the patients and the invasion of the bile duct and/or portal vein by alveolar lesions was found to be statistically significant (P = 0.024 and P = 0.043, respectively). According to PNM staging, when the AE disease exceeds the resectability limits, the only alternative for the treatment of the disease is LT. However, different from LT due to cirrhosis, it is extremely difficult to perform a transplantation for AE disease because of the invasive characteristics of it. In order to decrease the difficulty of the operation and the postoperative mortality, the intracystic abscess and cholangitis which occur because of AE must be treated via medical and percutaneous methods before transplantation. Liver Transpl 21:1096‐1102, 2015. © 2015 AASLD.
Ovine fetal mesenchymal stem cell differentiation to cardiomyocytes, effects of co‐culture, role of small molecules; reversine and 5‐azacytidine

The aim of the present study was to investigate the effect of small molecules: Reversine and 5‐azacytidine (5‐AC), in an indirect co‐culture condition with the cardiac fibroblasts as well as non co‐culture condition, in order to explore the effect of such molecules in the process of differentiation of the ovine bone‐marrow mesenchymal stem cells (BM‐MSCs) towards cardiomyocytes. Surface antigens of the isolated cells were analysed using flow‐cytometry. In addition, following to three passages cells were examined for their differentiation capacity into osteocytes and adipose cells, in order to ensure the mesenchymal origin of the stem cells. Six types of treatments were carried out in the present investigation, such that, in the first treatment BM‐MSCs were cultured for 28 days as control group; the second treatment was composed of culturing ovine fetal cardiac fibroblasts on inserts, aiming to use these inserts for culturing plates which were seeded with BM‐MSCs (Chamber group). As the third treatment, BM‐MSCs were supplemented with 10‐μM 5‐AC and incubated for 48 h. The fourth treatment was composed of supplementing BM‐MSCs with the 600‐nM reversine, incubated for 48 h, and subsequently the incubation was further extended for another 48 h in the presence of 5‐AC. The fifth treatment was composed of supplementing the chamber group with 10‐μM 5‐AC and incubation for 48 h, and the last or the sixth treatment was such that chamber group was supplemented with 600‐nM reversine and an incubation period of 48 h. Following to the incubation, medium was replaced with 10‐μM 5‐AC and further incubated for another round of 48 h. In all treatments, following to addition of the small molecules incubations were carried out for 28 days; same as controls. Expression of cardiac alpha‐actinin was analysed by immunocytochemistry. BM‐MSCs have shown to express CD44 and CD166 along with a weak expression of the CD90, CD34, in addition to CD45. Multilineage differentiation has indicated that BM‐MSCs could differentiate into adipose and osteocytes cells as well. In the treatment 4 it was observed that FGF signalling involved genes and all cardiac‐related genes (ANP, MYH6 and Troponin I) were significantly expressed, except connexin 43 compared to other treatments. All treatments received small molecules, either alone or as a co‐culture were seen to express sarcomeric alpha‐actinin. This finding was partially supported by immunocytochemistry. These results validate that reversine and 5‐AC have an effect on ovine BM‐MSC differentiation into cardiomyocytes. Copyright © 2016 John Wiley & Sons, Ltd.
Effects of T-82, a new quinoline derivative, on cholinesterase activity and extracellular acetylcholine concentration in rat brain.

The effects of T-82 (2-[2-(1-benzylpiperidin-4-yl)ethyl]-2,3-dihydro-9-methoxy-1H-pyrrolo [3,4-b]quinolin-1-one hemifumarate), a new quinoline derivative, on acetylcholinesterase (AChE) activity and acetylcholine (ACh) release were compared with those of the well-known cholinesterase inhibitors tacrine and E2020. T-82, tacrine and E2020 all concentration-dependently inhibited AChE in rat brain homogenate (IC50 = 109.4, 84.2 and 11.8 nM, respectively). In addition, although tacrine strongly inhibited butyrylcholinesterase (BuChE), T-82 and E2020 showed only weak activity on BuChE in human plasma. In ex vivo experiments, intraperitoneal administration of T-82 at a dose of 30 mg/kg inhibited AChE activity in the hippocampus, frontal cortex and parietal cortex of rats. The effect of T-82 on the extracellular ACh concentration in rat brain was measured using in vivo microdialysis. T-82 at doses of 10 and 30 mg/kg, i.p. increased the extracellular ACh concentration in the hippocampus and striatum in a dose-dependent manner. These findings suggest that T-82 activates the central cholinergic system by selectively inhibiting AChE activity, while weakly affecting peripheral BuChE activity, and that T-82 increases the extracellular ACh concentration in the brain, which is followed by inhibited AChE activity.
Perceptual Characterization of Children with Auditory Neuropathy

Objective To characterize the perceptual abilities of a group of children with auditory neuropathy (AN)-type hearing loss, correlating results on a range of psychophysical tasks with open-set speech perception performance. Design Frequency resolution, temporal resolution and frequency discrimination ability was assessed in a group of 14 children with AN. Data also were obtained from a cohort of matched subjects with sensorineural hearing loss, and from a group of normally hearing children. Results Frequency resolution (notched noise masking) results for the AN subjects were equivalent to those of the normal-hearing subjects reflecting the “normal” outer hair cell function that characterizes the AN condition. Temporal resolution (TMTF) findings were, however, abnormal in many AN subjects and the degree of temporal disruption was correlated with speech discrimination (CNC) score. Frequency discrimination ability (for both fixed and frequency modulated stimuli) was also affected in those children with poor temporal resolution Conclusions The findings of this study indicate that the perceptual profiles of children with AN are quite different from those with sensorineural hearing loss. Where subjects in the latter group presented with impaired frequency resolution and normal temporal processing, the AN subjects typically showed normal frequency resolution and varying degrees of temporal disruption. The severity of this temporal abnormality, which appeared to affect both temporal resolution/amplitude modulation detection and the temporal aspects of frequency discrimination (such as phase locking), was strongly correlated to speech perception performance.
Ion‐concentration dependence of the reversal potential and the single channel conductance of ion channels at the frog neuromuscular junction.

1. The acetylcholine‐sensitive ionic channels at the neuromuscular junction were studied in voltage‐clamped single muscle fibres from a monolayer preparation of the cutaneous pectoris muscle from Rana pipiens. The experimental observations were of three types: (a) reversal potential as a function of external Na and Ca concentrations, (b) the single channel conductance (gamma) from noise analysis as a function of these same concentrations, and (c) gamma as a function of membrane potential. 2. The reversal potential in normal Na Ringer was ‐3.8 +/‐ 0.5 mV (+/‐ S.E. of mean, n = 22) and decreased approximately linearly as the logarithm of the outside Na activity as this activity decreased to 10% of normal. 3. The single channel conductance in normal Na Ringer was 27.5 +/‐ 0.7 pS (n = 28) and reached a limiting value close to 10 pS as Na was replaced with sucrose. 4. Increasing [Ca]o from 2 to 10 mM made the reversal potential more positive and decreased the single channel conductance. Mg caused similar effects. 5. Various theories that have been used to describe the mechanism of ion permeation through e.p.c. channels were tested. Constant field theory (eqns. (3), (4) and (5)), a modified Takeuchi approach (eqn. (6)), and a single barrier theory (eqns. (8), (9) and (10)) could not account for all of the experimental observations. 6. In particular, constant field theory, with no surface charge density, could account for the following: (a) the reversal potential measurements for solutions containing 2 mM‐Ca (with PK/PNa = 1.2 and PCa/PNa = 1.02), (b) the single channel conductance values for solutions containing 2 mM‐Ca and Na concentrations down to 20% of normal, (c) that gamma has little voltage dependence. 7. However, constant field theory, with no assumed surface charge density, could not account for the following: (a) the reversal potential observed for Ringer containing 80 mM‐Ca, (b) the gamma values observed for very low Na concentrations, (c) the observation that increasing Ca from 2 to 10 mM in a solution containing 75% normal Na results in a decrease in gamma. 8. From the failure of the Takeuchi approach (eqn. (6)), it is argued that ion interactions must occur at e.p.c. channels because ion flux independence is the only asumption in the derivation of eqn. (6) without experimental verification. 9. The ion interactions at e.p.c. channels probably include both surface charge effects and competition for a binding site.
The Long Form of FLIP Is an Activator of Caspase-8 at the Fas Death-inducing Signaling Complex*

Death receptors, such as Fas and tumor necrosis factor-related apoptosis-inducing ligand receptors, recruit Fas-associated death domain and pro-caspase-8 homodimers, which are then autoproteolytically activated. Active caspase-8 is released into the cytoplasm, where it cleaves various proteins including pro-caspase-3, resulting in apoptosis. The cellular Fas-associated death domain-like interleukin-1-β-converting enzyme-inhibitory protein long form (FLIPL), a structural homologue of caspase-8 lacking caspase activity because of several mutations in the active site, is a potent inhibitor of death receptor-induced apoptosis. FLIPL is proposed to block caspase-8 activity by forming a proteolytically inactive heterodimer with caspase-8. In contrast, we propose that FLIPL-bound caspase-8 is an active protease. Upon heterocomplex formation, a limited caspase-8 autoprocessing occurs resulting in the generation of the p43/41 and the p12 subunits. This partially processed form but also the non-cleaved FLIPL-caspase-8 heterocomplex are proteolytically active because they both bind synthetic substrates efficiently. Moreover, FLIPL expression favors receptor-interacting kinase (RIP) processing within the Fas-signaling complex. We propose that FLIPL inhibits caspase-8 release-dependent pro-apoptotic signals, whereas the single, membrane-restricted active site of the FLIPL-caspase-8 heterocomplex is proteolytically active and acts on local substrates such as RIP.
RHD sequencing: a new tool for decision making on transfusion therapy and provision of Rh prophylaxis

The serological differentiation of weak D from partial D, D‐negative and D‐positive is not always unequivocal. Therefore, sequencing of the RHD gene is required in some cases. Very recently, several new differences between RHD and RHCE have been identified which permitted us to design primers close to the exon/intron boundaries of the RHD‐exons. We evaluated these primers in 83 D‐positive and 18 D‐negative blood donors and applied the new method for the characterization of the RHD gene in six individuals with weak D phenotype. The amplification reactions were concordant with serological findings in 100 of 101 donors (99·0%). In one D‐positive donor the PCR for exons 2 and 5 gave a negative result, while the sequence of the remaining eight exons was unchanged. By sequencing samples with very weak D serological reactions, we identified weak D type 4.2. 2 and weak D type 15, both previously reported to be associated with anti‐D‐alloimmunization. Consequently, we recommended the selection of D‐negative blood in the weak D type 4.2. 2 patient, and the provision of Rh prophylaxis for pregnant women with weak D type 15. In summary, a new RHD sequencing method was developed which can be applied if serological reactions are inconclusive.
Flavonoids Suppress Androgen-Independent Human Prostate Tumor Proliferation

The present studies compared the effects of selected bioflavonoids on the proliferation of androgen-independent human prostatic tumor cells (PC-3). Complete growth retardation was observed in PC-3 cells treated with 100 μM quercetin, kaempferol, and luteolin, while isomolar genistein, apigenin, and myricetin suppressed PC-3 proliferation by 73%, 70%, and 59%, respectively (p < 0.05). Naringenin and rutin were not as effective and inhibited growth by <25%. Exposure to increasing concentrations of quercetin and kaempferol led to a dose-dependent decrease in proliferation. Refeeding kaempferol-treated cells (50 μM) complete medium without the flavonoid resulted in a return toward control growth rates. Similar growth recovery was not observed in quercetin-treated cells. The antiproliferative response of PC-3 cells to quercetin and kaempferol was additive when supplemented to the medium at 25 μM. A block in G2-to-M phase progression was observed after the addition of 25 μM kaempferol. When quercetin reached 100 μM, an increase in the proportion of cells in the S phase became apparent within 24 hours. Apoptosis was not evident, even when concentrations of quercetin or kaempferol were raised to 100 μM. The present studies suggest that alterations in cell cycle progression contribute significantly to the antiproliferative effects of quercetin and kaempferol in PC-3 cells.
Abnormal limb regeneration in the short-toes mutant of the axolotl, Ambystoma mexicanum: studies of age, level of amputation, and extracellular matrix.

Limb regeneration in the short-toes axolotl is impaired. Our goal was to characterize the regeneration process in this mutant by histological and immunocytochemical methods. Previous research indicates that age and a defective basement membrane may be instrumental factors in short-toes axolotl regeneration (Del Rio-Tsonis et al. [1992] Proc. Natl. Acad. Sci. U.S.A., 89:5502-5506). The present results show that limb regeneration can occur even in older (1-2-year-old) short-toes axolotls. The process was always significantly delayed, but the time required for complete regeneration varied. Even so, the basement membrane of short-toes regenerates showed no differences in thickness or shape compared with wild-type regenerates. Distally amputated short-toes limbs gave rise to more digits in the regenerate, indicating that regeneration may be somewhat dependent on the level of amputation. Since extracellular matrix (ECM) remodeling occurs extensively during regeneration, we compared the ECM of the short-toes and wild-type regenerates using monoclonal antibodies (mAbs) MT2 and ST1 (Tassava et al. [1996] Wound Rep. Reg., 4:75-81). The short-toes regenerates showed decreased reactivity to mAb MT2, which identifies type XII collagen, an ECM protein that is normally unregulated during regeneration, and increased reactivity to mAb ST1, which identifies a limb ECM component that typically undergoes breakdown in the distal stump. Thus, impaired regeneration in the short-toes axolotl is correlated with impaired ECM remodeling in the distal limb stump. This supports the view that ECM remodeling plays an important role in regeneration.
Sofosbuvir and ribavirin prevent recurrence of HCV infection after liver transplantation: an open-label study.

BACKGROUND & AIMS Patients with detectable hepatitis C virus (HCV) RNA at the time of liver transplantation universally experience recurrent HCV infection. Antiviral treatment before transplantation can prevent HCV recurrence, but existing interferon-based regimens are poorly tolerated and are either ineffective or contraindicated in most patients. We performed a trial to determine whether sofosbuvir and ribavirin treatment before liver transplantation could prevent HCV recurrence afterward. METHODS In a phase 2, open-label study, 61 patients with HCV of any genotype and cirrhosis (Child-Turcotte-Pugh score, ≤7) who were on waitlists for liver transplantation for hepatocellular carcinoma, received up to 48 weeks of sofosbuvir (400 mg) and ribavirin before liver transplantation. The primary end point was the proportion of patients with HCV-RNA levels less than 25 IU/mL at 12 weeks after transplantation among patients with this HCV-RNA level at their last measurement before transplantation. RESULTS Sixty-one patients received sofosbuvir and ribavirin, and 46 received transplanted livers. The per-protocol efficacy population consisted of 43 patients who had HCV-RNA level less than 25 IU/mL at the time of transplantation. Of these 43 patients, 30 (70%) had a post-transplantation virologic response at 12 weeks, 10 (23%) had recurrent infection, and 3 (7%) died (2 from nonfunction of the primary graft and 1 from complications of hepatic artery thrombosis). Of all 61 patients given sofosbuvir and ribavirin, 49% had a post-transplantation virologic response. Recurrence was related inversely to the number of consecutive days of undetectable HCV RNA before transplantation. The most frequently reported adverse events were fatigue (in 38% of patients), headache (23%), and anemia (21%). CONCLUSIONS Administration of sofosbuvir and ribavirin before liver transplantation can prevent post-transplant HCV recurrence. ClinicalTrials.gov: NCT01559844.
Subtle myelin defects in PLP‐null mice

This study explores subtle defects in the myelin of proteolipid protein (PLP)‐null mice that could potentially underlie the functional losses and axon damage known to occur in this mutant and in myelin diseases including multiple sclerosis. We have compared PLP‐null central nervous system (CNS) myelin with normal myelin using ultrastructural methods designed to emphasize fine differences. In the PLP‐null CNS, axons large enough to be myelinated often lack myelin entirely or are surrounded by abnormally thin sheaths. Short stretches of cytoplasm persist in many myelin lamellae. Most strikingly, compaction is incomplete in this mutant as shown by the widespread presence of patent interlamellar spaces of variable width that can be labeled with ferricyanide, acting as an aqueous extracellular tracer. In thinly myelinated fibers, interlamellar spaces are filled across the full width of the sheaths. In thick myelin sheaths, they appear filled irregularly but diffusely. These patent spaces constitute a spiral pathway through which ions and other extracellular agents may penetrate gradually, possibly contributing to the axon damage known to occur in this mutant, especially in thinly myelinated fibers, where the spiral path length is shortest and most consistently labeled. We show also that the “radial component” of myelin is distorted in the mutant (“diagonal component”), extending across the sheaths at 45° instead of 90°. These observations indicate a direct or indirect role for PLP in maintaining myelin compaction along the external surfaces of the lamellae and to a limited extent, along the cytoplasmic surfaces as well and also in maintaining the normal alignment of the radial component. © 2006 Wiley‐Liss, Inc.