Miracle-dz/UniFAR-FTUs huggingface dataset:
Disruption of c-Fos leads to increased expression of NAD(P)H:quinone oxidoreductase1 and glutathione S-transferase.

Regulation of the basal and induced expression of detoxifying enzymes such as NAD(P)H:quinone oxidoreductasel (NQO1) and glutathione S-transferase (GST) by the antioxidant response element (ARE) is important for cellular protection against oxidative stress. The ARE contains AP1 and AP1-like elements and is known to bind to several leucine zipper proteins including c-Fos. Previous studies (Venugopal, R., and Jaiswal, A.K. (1996) Proc. NatL Acad. Sci. USA 93, 14960-14965) have shown that overexpression of c-Fos in transfected cells leads to repression of ARE-mediated gene expression. In the present report, we used c-Fos-/- mice and investigated the physiological (in vivo) role of c-Fos in repression of the NQO1 and GST genes expression. The analysis of enzyme activity levels showed significant increases in NQO1 and GST activities in several tissues of c-Fos-/- mice, as compared with wild type (c-Fos+/+) mice. The increases in enzyme activities were supported by Wetern analysis of respective proteins. Western analyses showed significant increases in the expression of NQO1 in kidney, liver and skin tissues of c-Fos-/- mice, as compared with wild type (c-Fos+/+) controls. Western analyses also demonstrated an increased expression of the GST Ya gene in kidney and liver tissues of the c-Fos-/-mice. These results confirm a negative (repressive) role for c-Fos in the expression of NQO1, GST Ya, and other detoxifying enzyme genes.
4,4‐Dimethyl‐ and Diastereomeric 4‐Hydroxy‐4‐methyl‐ (2S)‐Glutamate Analogues Display Distinct Pharmacological Profiles at Ionotropic Glutamate Receptors and Excitatory Amino Acid Transporters

Subtype‐selective ligands are of great interest to the scientific community, as they provide a tool for investigating the function of one receptor or transporter subtype when functioning in its native environment. Several 4‐substituted (S)‐glutamate (Glu) analogues were synthesized, and altogether this approach has provided important insight into the structure–activity relationships (SAR) for ionotropic and metabotropic glutamate receptors (iGluRs and mGluRs), as well as the excitatory amino acid transporters (EAATs). In this work, three 4,4‐disubstituted Glu analogues 1–3, which are hybrid structures of important 4‐substituted Glu analogues 4–8, were investigated at iGluRs and EAATs. Collectively, their pharmacological profiles add new and valuable information to the SAR for the iGluRs and EAAT1–3.
Specific binding, internalization, and degradation of human recombinant interleukin‐3 by cells of the acute myelogenous, leukemia line, KG‐1

We have studied the interaction of 35S‐labeled recombinant IL‐3 with the acute myelogenous leukemia cell line, KG‐1. 35S‐IL‐3 bound to these cells in a time dependent, saturable, and specific manner at 4°C. Scatchard transformation of binding isotherms demonstrated the existence of a small number (200) of binding sites, with an apparent dissociation constant of 70‐105 pM. After a temperature shift from 4°C to 37°C, surface‐bound 35S‐IL‐3 was rapidly internalized and processed into a trichloroacetic acid soluble form that was released into the medium. Experiments to address the specificity of the IL‐3 binding site revealed that neither human IL‐2, M‐CSF, erythropoietin, transferrin, bovine insulin, nor murine nerve growth factor compete with IL‐3 for binding to KG‐1 cells. Both human and gibbon recombinant IL‐3 and, surprisingly, human recombinant GM‐CSF effectively competed the binding of the labeled IL‐3 to these cells at 4°C. The competition by GM‐CSF was found to be concentration dependent, but much higher concentrations were required to achieve the levels obtained with IL‐3. These results suggest that GM‐CSF may also interact with the high‐affinity IL‐3 binding site on KG‐1 cells or, alternatively, that GM‐CSF binding to its own receptor may decrease the affinity of the IL‐3 receptor for its ligand.
Cisatracurium vs. Rocuronium: A prospective, comparative, randomized study in adult patients under total intravenous anaesthesia.

AIMS To compare the pharmacodynamics of cisatracurium and rocuronium-induced neuromuscular block following single dose, allowing either spontaneous or neostigmine-accelerated complete recovery. METHODS Following the ethics committee approval and informed consent, 120 patients scheduled for elective surgery under TIVA with tracheal intubation were randomized into 4 groups with different cisatracurium (CIS, 0.10 or 0.15 mg.kg(-1)) or rocuronium (ROC, 0.60 or 0.90 mg.kg(-1)) doses administered. For each patient, the onset time for 95 % depression of T1, clinical duration until 25 % recovery, recovery index (T1 from 25 to 75 %) and time from T1 25 % to TOF-ratio 0.9 were determined allowing either spontaneous or induced recovery. RESULTS The onset times were 277 (SD 58), 220 (46), 91 (16) and 77 (16) s for the CIS 0.10, CIS 0.15, ROC 0.60 and ROC 0.90 groups (p < 0.05), respectively, with lower variability in both ROC groups (p < 0.05). The clinical durations were 42 (7), 52 (7), 35 (11) and 52 (12) min, respectively (p < 0.05 for lower doses). Recovery index was identical in all groups allowing either spontaneous recovery - 15.9 (1.8), 15.5 (1.7), 16.1 (3.7) and 16.1 (4.0) min, or following neostigmine administration - 4.4 (0.9), 4.5 (0.8), 4.3 (0.8) and 4.7 (0.7) min for respective groups. During spontaneous recovery, the variability of DUR25-TOF90 was twice as great for ROC than CIS groups (p < 0.05), while after neostigmine administration it was uniform in all groups. CONCLUSIONS For equipotent doses, the onset times for CIS were approximately three times longer than for ROC. The average clinical duration for both relaxants ranged from 35 to 52 min with acceptable variability. Neostigmine administration accelerated the recovery and reduced its variability. When allowing for spontaneous recovery, less scatter was demonstrated for both CIS groups than for ROC ones.
Effects of amiloride on active sodium transport by the isolated frog skin: evidence concerning site of action

1 Amiloride reduces short‐circuit current and potential difference across the isolated frog skin. 2 Isotopically measured sodium influx and efflux are diminished. 3 Total electrical conductance and partial sodium conductance are diminished, the reduction in total conductance being entirely accounted for by the reduction in partial sodium conductance. 4 The effect of antidiuretic hormone (ADH), cyclic 3′5′‐adenosine monophosphate (cyclic AMP) and theophylline can be antagonized by pretreatment with amiloride but the antagonism can be abolished by increasing the concentration of these compounds. 5 Amiloride has no effect on oxygen consumption in concentrations which inhibit sodium transport. However, it prevents the stimulatory effect of ADH on oxygen consumption. 6 The results are consistent with an action of amiloride at the passive outside membrane of the transporting cells of isolated frog skin.
Bayes Prediction in Exponential Life-Testing When Sample Size is a Random Variable

This paper deals with the problem of predicting the range in a future sample, based on ranges in the earlier samples. Samples are drawn from an exponential population. Sample sizes are taken as random variables and the prediction process is performed on the lines of Lingappalah (1978). First, for two samples, prediction intervals for two cases (sample sizes fixed, and random variables) are compared. Similarly, variances of predictive distributions for the two cases are compared. As an extension, prediction in k-th sample is made, based on earlier (k-1) samples. Finally, the case when all the parameters are equal is compared to the case when at least one is not the same.
Urodynamic findings in adults with primary nocturnal enuresis.

PURPOSE We evaluate bladder function in adults with primary nocturnal enuresis (PNE) since childhood. MATERIALS AND METHODS We recruited all patients older than 16 years who presented to our PNE clinic with persistent enuretic symptoms. All patients were assessed by a detailed voiding diary, uroflowmetry and ultrasonography of the urinary tract. Urodynamic studies were performed for those with moderate or severe PNE (more than 3 wet nights a week). RESULTS The study included 18 males and 29 females with a mean age of 20 years (range 16 to 43). Of these patients 37 (79%) had moderate or severe symptoms and 17 (38%) also had daytime urinary symptoms. Urodynamic studies were conducted in 30 patients, including 12 males and 16 females (93%) with detrusor overactivity. In addition, 73% of patients had urodynamic evidence of functional bladder outflow obstruction, including dysfunctional voiding and detrusor sphincter or detrusor pelvic discoordination. Two male patients (6.7%) had an obstructive pattern on urodynamics and subsequent cystoscopic examination confirmed the presence of congenital obstructive urethral lesions. Sixteen patients (53%) had significantly reduced bladder capacity of less than 300 ml. CONCLUSIONS Unlike in early childhood, the majority (79%) of enuretic adults had significant symptoms, and more than a third also had daytime urinary symptoms. We believe that PNE in adults is not only a psychologically disturbing condition, but also a urological disorder with significant underlying bladder dysfunction that warrants special attention to management.
Digenetic trematodes of marine fishes from the Arabian Gulf off the coast of Kuwait. Family Bucephalidae Poche, 1907, and the description of a new species

SummarySix species of Bucephalidae are reported: Subfamily Bucephalinae: Bucephalus sphyraenae Yamaguti, 1952 from Sphyraena obtusata and S. chrysotaenia (Sphyraenidae) (new host records); Bucephalus margaritae Ozaki and Ishibashi, 1934 from Atropus atropos, Scomberoides commersonianus, Carangoides malabaricus (Carangidae), Gerres filamentosus (Gerreidae) (new host record) and Sphyraena jello (new host record); Rhipidocotyle pseudorhombi n. sp. from Pseudorhombus arsius is characterized by and differs from its congeners by several characteristics including an elongate body, a rhynchus with 7 thin papillae, a long tuular caecum extending posteriorly to the ovarian level, goads in the posterior half of the body, and contiguous testes not separated by uterine coils. More specifically it differs from R. heptathelata and R. septapapillata by having a long cirrus sac relative to body length, tandem and more anterior testes. Subfamily Prosorhynchinae: Prosorhynchus pacificus Manter, 1940 from Epinephelus tauvina (Serranidae) and Gnathonodon speciosus (Carangidae) (new host record); P. epinepheli Yamaguti, 1939 from Epinephelus areolatus; P. manteri Srivastava, 1938 from Trichiurus lepturus (Trichiuridae). All species, except Prosorhynchus epinepheli represent new records from the Arabian Gulf.
Synthesis of Research on School-Based Management

D adc County, Florida, has made front-page headlines with its pilot School-Based Manage ment/Shared Decision Making Pro gram The Montgomery County School Board in Maryland has approved a similar plan for spring 1989 In Baton Rouge, Louisiana, school-based man agement is coupled with parental choice as pan of an unusual desegre gation strategy Santa Fe. New Mexico, is implementing school-based man agement with teacher-led school im provement teams. The list goes on 'School-based management" is rap idly becoming the centerpiece of the current wave of reform The growing number of districts "restructuring" their sch<x)ls, as well as commentary from the National Governors' Associa tion, both national teachers' unions, and corporate leaders—all make ref erence to some form of increased school autonomy Yet there is surprisingly little empir ical research on the topic. Searches of education indexes yield numerous ref erences for school-based manage ment, but virtually all are conceptual arguments, how-to guides, and testi monials from practitioners. There is, nevertheless, an abundance of rele vant research Topics ranging from school improvement to corporate in novation bear directly on schoolbased management. v.ieir relevance can be seen when We look at why districts are turning to school-based management today
The Evolution of Titan's Mid-Latitude Clouds

Spectra from Cassini's Visual and Infrared Mapping Spectrometer reveal that the horizontal structure, height, and optical depth of Titan's clouds are highly dynamic. Vigorous cloud centers are seen to rise from the middle to the upper troposphere within 30 minutes and dissipate within the next hour. Their development indicates that Titan's clouds evolve convectively; dissipate through rain; and, over the next several hours, waft downwind to achieve their great longitude extents. These and other characteristics suggest that temperate clouds originate from circulation-induced convergence, in addition to a forcing at the surface associated with Saturn's tides, geology, and/or surface composition.
The Microtubule-Associated Protein Lis1 Regulates T Lymphocyte Homeostasis and Differentiation

The microtubule-associated protein lissencephaly 1 (Lis1) is a key regulator of cell division during stem cell renewal and differentiation. In this study, we examined the role of Lis1 in T lymphocyte homeostasis and fate diversification in response to microbial infection. T cell–specific deletion of Lis1 resulted in depletion of the peripheral CD4+ and CD8+ T lymphocyte pool owing to a loss of homeostatic, cytokine-induced proliferation. In contrast, cognate Ag-triggered proliferation was much less affected, enabling Lis1-deficient CD8+ T cells to differentiate into terminal effector cells in response to microbial infection. Strikingly, however, the specification of Lis1-deficient long-lived memory CD8+ T lymphocytes was impaired due, in part, to an apparent failure to differentiate appropriately to IL-15. Taken together, these findings suggest that Lis1 plays an important role in T cell homeostasis and the generation of memory T lymphocytes.
Direct measurement of viraemia in patients infected with HIV‐1 and its relationship to disease progression and zidovudine therapy

Cell‐free human immunodeficiency virus type‐I (HIV‐1) was precipitated from archival serum with polyethylene glycol (PEG), and HIV‐1 RNA was detected and quantified by reverse transcription and amplification in a nested polymerase chain reaction (PCR). The assay of endpoint dilutions cDNA in nested PCRs allowed an estimation of the minimum RNA copies per unit volume of serum. RNA titres correlated with the classification of HIV‐1 infection by CDC disease groups (30 patients). The geometric mean titres of HIV‐1 serum RNA from patients grouped by disease stage gave minimum estimates of 340 and 400 virions per millilitre of serum in CDC groups II and Ill (n = 6 and 10, respectively) and 4,240 virions per millilitre in CDC group IV (n = 14). An overall fall in viral titre measured in this way was observed in 3 patients during zidovudine treatment. HIV‐1 titres increased in a further 4 patients when therapy was interrupted, stopped, or complicated by secondary infection.
Overproduction of the xylS gene product and activation of the xylDLEGF operon on the TOL plasmid

The effect of high-level expression of the regulatory gene xylS of the Pseudomonas putida TOL plasmid on the activation of the xylDLEGF operon was investigated in Escherichia coli. The xylS gene was placed downstream from the tac promoter, and the resultant fusion was cloned in cis to the xylDLEGF operon. The expression of the operon was monitored by the level of catechol 2,3-dioxygenase, whose structural gene xylE was placed directly after the operator-promoter region of xylDLEGF. xylS transcription was also determined by reverse transcriptase mapping of mRNA. Overproduction of the xylS gene product elicited constitutive high expression of the xylDLEGF operon even in the absence of the inducer for the operon. The results were consistent with a cascade model for the positive control of the xylDLEGF operon by the xylR and xylS genes (S. Inouye, A. Nakazawa, and T. Nakazawa, Proc. Natl. Acad. Sci. USA, in press): m-xylene, a substrate of the degradative pathway, binds to the xylR gene product; the m-xylene-xylR product complex activates the xylS gene; and the xylS product thus synthesized de novo activates the xylDLEGF operon.
Process parameter shifting: Part II. Biphasic cultivation—A tool for enhancing the volumetric productivity of batch processes using Epo‐Fc expressing CHO cells

Regulation of cell growth and protein expression potentially results in a sustainable enhancement of the volumetric productivity in a fermentation process. Following a biphasic cultivation strategy the process initially passes through a cell proliferation phase to generate a sufficiently high viable cell mass. In the subsequent production phase cells are maintained viable and productive without significant cell proliferation leading to increased viable cell days and product yields. In a previous work we have shown that the well directed alteration of the process environment based on process parameter shifting is a promising tool to regulate cell growth and protein expression. In continuation of this work we investigated process parameters which have been identified to affect cell proliferation in favor of an increased specific productivity and total product yield in a series of biphasic batch cultivation experiments. In most of these processes the integral of viable cells and the specific productivity were increased leading to a significant improvement of both final product concentration and volumetric productivity. In addition, combined parameter shifts (pH 6.90/30°C and pH 6.90/33°C) exerted a synergistic effect on product quality. The loss of product sialylation which occurred at reduced temperatures was prevented by simultaneously reducing the external pH. In conclusion, biphasic cultivation based on combined shifting of process parameters is a suitable tool for controlling cell proliferation and protein expression of mammalian cells in a batch bioreactor leading to enhanced volumetric productivities and therefore offers an enormous potential for bioprocess optimization. © 2006 Wiley Periodicals, Inc.
Inhibition of ATP‐sensitive potassium channels causes reversible cell‐cycle arrest of human breast cancer cells in tissue culture

The purpose of this study was to determine if potassium channel activity is required for the proliferation of MCF‐7 human mammary carcinoma cells. We examined the sensitivities of proliferation and progress through the cell cycle to each of nine potassium channel antagonists. Five of the potassium channel antagonists produced a concentration‐dependent inhibition of cell proliferation with no evidence of cytotoxicity following a 3‐day or 5‐day exposure to drug. The IC50 values for these five drugs, quinidine (25 μM), glibenclamide (50 μM), linogliride (770 μM), 4‐aminopyridine (1.6 mM), and tetraethylammmonium (5.8 mM) were estimated from their respective concentration‐response curves. Four other potassium channel blockers were tested at supra‐maximal channel blocking concentrations, including charybdotoxin (200 nM), iberiotoxin (100 nM), margatoxin (10 nM), and apamin (500 nM), and they had no effect on MCF‐7 cell proliferation, viability, or cell cycle distribution. Of the five drugs that inhibited proliferation, only quinidine, glibenclamide, and linogliride also affected the cell cycle distribution. Cell populations exposed to each of these drugs for 3 days showed a statistically significant accumulation in GO/G1 phase and a significant proportional reduction in S phase and G2/M phase cells. The inhibition of cell proliferation correlated significantly with the extent of cell accumulation in GO/G1 phase, and the threshold concentrations for inhibition of growth and GO/G1 arrest were similar. The GO/G1 arrest produced by quinidine and glibenclamide was reversed by removing the drug, and cells released from arrest entered S phase synchronously with a lag period of ∼24 hours. Based on the differential sensitivity of cell proliferation and cell cycle progression to the nine potassium channel antagonists, we conclude that inhibition of ATP‐sensitive potassium channels in these human mammary carcinoma cells reversibly arrests the cells in the GO/G1 phase of the cell cycle, resulting in an inhibition of cell proliferation. © 1995 Wiley‐Liss, Inc.
Resistance to HER2-directed antibodies and tyrosine kinase inhibitors

The antibody trastuzumab and the tyrosine kinase inhibitor lapatinib are approved by the FDA for the treatment of HER2-overexpressing breast cancer. These anti-HER2 drugs are changing the natural history of HER2-overexpressing breast cancer. However, therapeutic resistance to trastuzumab or lapatinib, as either single-agents or in combination with chemotherapy in the metastatic setting, typically occurs within months of starting therapy. Several mechanisms of trastuzumab-resistance have been reported that include signaling from other HER receptors, signaling from receptor tyrosine kinases (RTKs) outside of the HER (ErbB) family, increased phosphatidylinositol 3-kinase signaling, and the presence of truncated forms of HER2. Mechanisms of resistance to lapatinib also point to increased phosphatidylinositol 3-kinase signaling as well as derepression/activation of compensatory survival pathways. In this review, we discuss how these models and mechanisms enhance our understanding of the clinical resistance to HER2-directed therapies.
Management of Internal Root Resorption: A Review

Internal root resorption (IRR) is a particular category of pulp disease considered as the loss of dentine as a result of the action of clastic cells stimulated by pulpal inflammation. This review article explains the etiology, the prevalence of internal root resorption, and, in addition to the clinical data, the contribution of the 3D imaging (cone beam computed tomography) to the diagnosis, the clinical decision, and the therapeutic management of internal root resorption. The authors reviewed the different therapeutic possibilities including the orthograde or retrograde fillings of the root canal resorption areas. Root canal treatment stays the treatment of choice of internal root resorption as it eliminates the granulation tissue and blood supply of the clastic cells. The authors describe with different clinical cases the modern endodontic techniques including optical aids, ultrasonic enhancement of chemical debridement, and the usage of alternative materials like calcium silicate combined with thermoplastic filling (warm gutta-percha). In these conditions, the prognosis of the conservative management of internal resorptions, even if root walls are perforated, is good. Mineral trioxide aggregate is being progressively used as a root canal filling material, preferably in cases of perforation.
Juvenile Idiopathic Arthritis-related Uveitis

IntroductionJuvenile idiopathic arthritis (JIA), formerly known as juvenile rheumatoid arthritis (JRA) in the United States and referred to as juvenile chronic arthritis (JCA) in Europe, is a group of idiopathic arthritides with an onset before 16 years of age that persists for at least 6 weeks.1,2