Miracle-dz/UniFAR-FTUs huggingface dataset:
Suplatast Tosilate Alters DC1/DC2 Balance in Peripheral Blood in Bronchial Asthma

Suplatast tosilate is an antiallergic drug that selectively suppresses Th2-cytokine production and inhibits airway hyperresponsiveness and eosinophilic airway inflammation. This drug has been also shown to improve pulmonary function and symptoms in steroid-dependent asthma, resulting in a decrease in doses of inhaled corticosteroid. However, the precise mechanism by which suplatast tosilate exerts an antiasthmatic effect in vivo remains to be known. Our previous study showed the polarization of circulating type 1 dendritic cells (DC1)/type 2 dendritic cells (DC2) balance toward DC2 in asthma, which might be associated with its Th2-dominant immune response. In the present study, we attempted to clarify the effect of suplatast tosilate on DC1/DC2 balance in asthma. Using multicolor flow cytometry, we enumerated circulating DC1 and DC2 before and 8 weeks after treatment with suplatast tosilate in nine patients with asthma. Before the treatment, the patients with asthma had a significant higher percentage of DC2 together with a significant lower ratio of DC1/DC2 compared with normal subjects. Administration of suplatast tosilate significantly decreased the percentage of DC2, but not that of DC1, resulting in a significant raises of the ratio of DC1/DC2. Concomitantly, intracellular cytokine analysis showed that the percentage of IL-4 producing CD4+ T cells was significantly decreased after the treatment. These data suggest that suplatast tosilate normalizes the polarized DC1/DC2 balance toward DC2 in asthma, which may also alter its Th2-dominant Th1/Th2 balance toward Th1.
Deep Voice 3: 2000-Speaker Neural Text-to-Speech

We present Deep Voice 3, a fully-convolutional attention-based neural text-to-speech (TTS) system. Deep Voice 3 matches state-of-the-art neural speech synthesis systems in naturalness while training ten times faster. We scale Deep Voice 3 to data set sizes unprecedented for TTS, training on more than eight hundred hours of audio from over two thousand speakers. In addition, we identify common error modes of attention-based speech synthesis networks, demonstrate how to mitigate them, and compare several different waveform synthesis methods. We also describe how to scale inference to ten million queries per day on one single-GPU server.
Total colectomy for Crohn's disease.

BACKGROUND Total colectomy for Crohn's disease of the colon may be restorative with ileorectal anastomosis or with an ileostomy and rectal stump. The present paper retrospectively audits the results of total colectomy and in particular assesses the number of patients who had a permanent ileostomy and whether this was related to disease in the rectum at the time of the original operation. METHODS A retrospective case note review was undertaken of patients operated upon between 1968 and 1994. RESULTS Thirty-eight patients were identified (mean age 35 years; range 17-65 years). One patient died perioperatively from an anastomotic leak. Median follow-up for the remaining patients was 7 years (range 1-29 years). Ileorectal anastomosis was performed in 17 patients and total colectomy and ileostomy in 20 patients. Indications for surgery were failure of medical treatment (61%); toxic colitis (18%); abscess (8%); perforation (5%); large bowel obstruction (5%); and colovesical fistula (3%). Subsequent proctectomy (14 patients, 38%) was more likely with subtotal colectomy and ileostomy (nine patients, 45%) than ileorectal anastomosis (five patients, 29%). This was not statistically significant (P = 0.33). Additionally, seven patients had diversion of the rectum making 21 with an ileostomy (57%). Rectal involvement at the time of the original procedure significantly increased the likelihood of permanent ileostomy (P = 0.001). The presence of anal disease did not increase the prospect of ileostomy. One patient died with advanced adeno carcinoma in a defunctioned rectum. CONCLUSIONS A permanent ileostomy after total colectomy for Crohn's disease is common and significantly more likely with rectal involvement.
Failed Endoscopic Carpal Tunnel Release

From 1994 to 1997, 22 patients (24 wrists) underwent open revision carpal tunnel release for persistent carpal tunnel syndrome after a primary endoscopic release. The age range was from 21 to 77 years. At the time of revision surgery, 22 wrists had an incomplete release of the flexor retinaculum and two patients had median nerve transection (one partial and one complete). One patient had release of Guyon’s canal and not the carpal tunnel. After the open revision carpal tunnel release, 20 patients returned to work with five patients returning to jobs of lighter duty. In addition, these 20 patients had significant improvement in symptoms. The remaining two patients had sustained a median nerve injury and did not return to work. One of these patients developed a painful neuroma in continuity of the median nerve which required vein wrapping with a saphenous vein graft. This study indicates that endoscopic release of the flexor retinaculum holds the same risks and complications as open release. Based on our study we believe that patients with persistent carpal tunnel syndrome after failed endoscopic flexor retinaculum release can be successfully treated with open release.
Initial Base Deficit as Predictors for Mortality and Transfusion Requirement in the Severe Pediatric Trauma Except Brain Injury

Objective: The initial base deficit (BD) is an important indicator of shock in adult trauma patients, but its value is unclear in pediatric trauma patients. This study assessed the ability of the initial BD to predict mortality and blood transfusion requirements in children except severe brain injury patients. Methods: This study was a retrospective review of pediatric patients with severe trauma arriving at the emergency department of a university hospital from January 1998 to June 2005. Blood pressure, the initial BD, and the Injury Severity Score were assessed as independent predictors of mortality and the blood transfusion requirement using multiple regression analysis. Results: The study group constituted 102 patients. According to the multiple regression analysis results, the initial systolic blood pressure, Injury Severity Score, and blood transfusion requirement were not independent predictors of mortality (P = 0.104, 0.959, 0.386, respectively). By contrast, the initial BD was an independent predictor, with an odds ratio of 13.6 for BD of −8 mEq/L or less (confidence interval [CI], 3.51-35.23, P = 0.037), and systolic blood pressure and BD were independent predictors of blood transfusion requirement; the odds ratio for hypotension was 3.2 (CI, 0.51-8.32, P = 0.044), and the odds ratio was 15.3 for BD values of −8 or less (CI, 2.24-51.43, P = 0.003). Conclusion: The initial BD in pediatric trauma patients except severe brain injury was an independent predictor of mortality and blood transfusion requirement within 24 hours. Mortality and blood transfusion requirement were significantly high when initial BD was less than −8 mEq/L.
Expression of c-myc oncoprotein in laryngeal squamous cell carcinoma

Objective c-myc seems to play a pivotal role in normal growth and development as well in cellular transformation and carcinogenesis. Overexpression of the c-myc oncogene has been observed in many hematopoetic and solid tumors. The role of c-myc protein in squamous cell carcinoma of the head and neck in general and laryngeal squamous cell carcinomas (LSCCs) in particular is far from clear. The aim of this study was to evaluate the relations between the level of c-myc protein in LSCCs and the clinicopathological data of patients, DNA ploidy and the SG2M phase index (PI). Material and Methods The c-myc protein level was evaluated immunohistochemically in tumor specimens from 50 patients with LSCC. The DNA index and SG2M PI were determined by means of flow cytometry. Results We found c-myc protein in 34 (68%) tumors. Expression of c-myc protein was demonstrated to be frequent in non-metastatic cases (p=0.016). There was no association between c-myc protein level and age, primary tumor size, histological grading or type of cancer. In 13 (26%) cases we observed DNA aneuploid tumors. The mean value of the SG2M PI was 22.5%. Expression of c-myc protein was not related to SG2M PI or DNA ploidy. Conclusions We have shown that c-myc oncoprotein may be involved in the genesis of LSCC. Our findings suggest that the detectability of c-myc protein is associated with a lower metastatic potential. The c-myc oncogene is probably not as important in laryngeal cancers compared to other cancers. Further investigations must be performed to establish the value of predicting nodal metastases in LSCC.
Macrophage Receptors for Influenza A Virus: Role of the Macrophage Galactose-Type Lectin and Mannose Receptor in Viral Entry

ABSTRACT Although sialic acid has long been recognized as the primary receptor determinant for attachment of influenza virus to host cells, the specific receptor molecules that mediate viral entry are not known for any cell type. For the infection of murine macrophages by influenza virus, our earlier study indicated involvement of a C-type lectin, the macrophage mannose receptor (MMR), in this process. Here, we have used direct binding techniques to confirm and characterize the interaction of influenza virus with the MMR and to seek additional macrophage surface molecules that may have potential as receptors for viral entry. We identified the macrophage galactose-type lectin (MGL) as a second macrophage membrane C-type lectin that binds influenza virus and is known to be endocytic. Binding of influenza virus to MMR and MGL occurred independently of sialic acid through Ca2+-dependent recognition of viral glycans by the carbohydrate recognition domains of the two lectins; influenza virus also bound to the sialic acid on the MMR. Multivalent ligands of the MMR and MGL inhibited influenza virus infection of macrophages in a manner that correlated with expression of these receptors on different macrophage populations. Influenza virus strain A/PR/8/34, which is poorly glycosylated and infects macrophages poorly, was not recognized by the C-type lectin activity of either the MMR or the MGL. We conclude that lectin-mediated interactions of influenza virus with the MMR or the MGL are required for the endocytic uptake of the virus into macrophages, and these lectins can thus be considered secondary or coreceptors with sialic acid for infection of this cell type.
Inhibition of Phosphatidylinositol 3-Kinase Induces Nitric-oxide Synthase in Lipopolysaccharide- or Cytokine-stimulated C6 Glial Cells*

Nitric oxide (NO) produced by inducible nitric-oxide synthase (iNOS) in different cells including brain cells in response to proinflammatory cytokines plays an important role in the pathophysiology of demyelinating and neurodegenerative diseases. The present study underlines the importance of phosphatidylinositol 3-kinase (PI 3-kinase) in the expression of iNOS in C6 glial cells and rat primary astrocytes. Bacterial lipopolysaccharide (LPS) or interleukin-1β (IL-1β) was unable to induce the expression of iNOS and the production of NO in rat C6 glial cells. Similarly, wortmannin and LY294002, compounds that inhibit PI 3-kinase, were also unable to induce the expression of iNOS and the production of NO. However, a combination of wortmannin or LY294002 with LPS or IL-1β induced the expression of iNOS and the production of NO in C6 glial cells. Consistent with the induction of iNOS, wortmannin also induced iNOS promoter-derived chloramphenicol acetyltransferase activity in LPS- or IL-1β-treated C6 glial cells. The expression of iNOS by LPS in C6 glial cells expressing a dominant-negative mutant of p85α, the regulatory subunit of PI 3-kinase, further supports the conclusion that inhibition of PI 3-kinase provides a necessary signal for the induction of iNOS. Next we examined the effect of wortmannin on the activation of mitogen-activated protein (MAP) kinase and nuclear factor NF-κB in LPS- or IL-1β-stimulated C6 glial cells. In contrast to the inability of LPS and IL-1β alone to induce the expression of iNOS, both LPS and IL-1β individually stimulated MAP kinase activity and induced DNA binding and transcriptional activity of NF-κB. Wortmannin alone was unable to activate MAP kinase and NF-κB. Moreover, wortmannin had no effect on LPS- or IL-1β-mediated activation of MAP kinase and NF-κB, suggesting that wortmannin induced the expression of iNOS in LPS- or IL-1β-stimulated C6 glial cells without modulating the activation of MAP kinase and NF-κB. Similar to C6 glial cells, wortmannin also stimulated LPS-mediated expression of iNOS and production of NO in astrocytes without affecting the LPS-mediated activation of NF-κB. Taken together, the results from specific chemical inhibitors and dominant-negative mutant expression studies demonstrate that apart from the activation of NF-κB, inhibition of PI 3-kinase is also necessary for the expression of iNOS and production of NO.
Insulin-like growth factor-I induces reactive oxygen species production and cell migration through Nox4 and Rac1 in vascular smooth muscle cells.

AIMS We showed previously that insulin-like growth factor-I (IGF-I)-induced vascular smooth muscle cells (VSMCs) proliferation through the production of reactive oxygen species (ROS). However, how IGF-I-induced ROS was unknown. The aim of this study is to investigate the mechanisms by which IGF-I induces ROS production in VSMCs. Methods results Reverse transcription-PCR, real-time PCR, immunoblotting, and confocal microscopic image analysis were employed to determine protein expression, small Rho-GTPase Rac1 activation, and ROS production. Inhibition of NADPH oxidase 4 (Nox4) or Rac1 was performed by means of siRNA technology. Inhibition of Rac1 activity was accomplished using dominant-negative form of Rac1 (N17Rac1) plasmid. VSMCs from Sprague-Dawley rat thoracic aortas were used in this work.IGF-I enhanced ROS production in rat VSMCs. IGF-I increased the protein level of Nox4 but had little effect on its mRNA level. IGF-I induced the activation of Rac1. Either knockdown of Nox4 or inactivation of Rac1 impaired IGF-I-induced ROS. Over-expression of Nox4 increased NADPH oxidase activity, which was not influenced by inactivation of Rac1. Neither over-expression nor knockdown of Rac1 influenced Nox4 expression. Knockdown of Nox4 did not affect IGF-I-induced activation of Rac1. IGF-I increased matrix metalloproteinase (MMP)-2 and 9 activity and promoted VSMC migration, which was inhibited by knockdown of Nox4 and inactivation of Rac1. CONCLUSION Our results suggest that Nox4 and Rac1 mediate IGF-I-induced ROS production and cell migration in VSMCs and that Nox4 is not regulated by Rac1.
[Phacoemulsification in white cataract].

PURPOSE The study presents the technical difficulties of the capsulorhexis and phacoemulsification in the white, intumescent cataract and the incidences occurred during the foldable IOL implantation with the Monarch II injector. METHODS The clinical study comprises a number of 70 eyes with white intumescent cataract operated during 15 January-15 December 2003 by the same surgeon. The surgical intervention consisted of lens extraction by phacoemulsification with clear corneal incision, using the Monarch II injector for the foldable IOL implantation. In 56 eyes, the anterior capsule was stained with trypan blue. RESULTS The intraoperative complications include: failed capsulorexis in 4 cases (5.71%), rupture of posterior capsule in 1 case (1.43%) and the conversion to classical extracapsular extraction in 3 cases (4.29%). IOL implantation was made with the help of the Monarch II injector in 67 cases (95.71%). The foldable IOL implantation in the bag was realised a single time in 44 cases (62.9%). We had the following incidences in the other cases: the upside down turning of the IOL during unfolding in 2 cases, the second haptic capture in the tunnel of the cartridge in 2 cases, the second haptic stucks outside or in the anterior chamber in 18 cases, the first haptic stays in the sulcus and the second one stays outside in 1 case. CONCLUSIONS In eyes with 1 intumescent cataract we can perform the continuous curvilinear capsulorhexis using trypan blue, but also without staining the anterior capsule using mechanical or manual aspiration of the liquefied cortex and viscoelastic substances. The foldable intraocular lens implantation with the injector proves to be an easy and comfortable method after it has been practiced for a longer period of time if the right size of the cartridge is used.
Evidence of viscerally‐mediated cold‐defence thermoeffector responses in man

Visceral thermoreceptors that modify thermoregulatory responses are widely accepted in animal but not human thermoregulation models. Recently, we have provided evidence of viscerally‐mediated sweating alterations in humans during exercise brought about by warm and cool fluid ingestion. In the present study, we characterize the modification of shivering and whole‐body thermal sensation during cold stress following the administration of a graded thermal stimuli delivered to the stomach via fluid ingestion at 52, 37, 22 and 7°C. Despite no differences in core and skin temperature, fluid ingestion at 52°C rapidly decreased shivering and sensations of cold compared to 37°C, whereas fluid ingestion at 22 and 7°C led to equivalent increases in these responses. Warm and cold fluid ingestion independently modifies cold defence thermoeffector responses, supporting the presence of visceral thermoreceptors in humans. However, the cold‐defence thermoeffector response patterns differed from previously identified hot‐defence thermoeffectors.
Activation of proteinase‐activated receptor 1 stimulates epithelial chloride secretion through a unique MAP kinase‐and cyclo‐oxygenase‐dependent pathway

Proteinase‐activated receptor 1 (PAR‐1) is activated by thrombin and induces chloride secretion by intestinal epithelial cells. To elucidate further the mechanisms whereby PAR‐1 stimulates secretion, monolayers of SCBN intestinal epithelial cells were studied in modified Ussing chambers. Short circuit current responses were determined after basolateral application of thrombin and the PAR‐1‐activating pep‐tide, Ala‐parafluoro‐Phe‐Arg‐cyclohexyl‐Ala‐Citrulline‐Tyr (Cit‐NH2) in the presence or absence of a variety of signal transduction and cyclo‐oxygenase (COX) pathway inhibitors. Increased kinase activity was monitored by immunoprecipitation and Western blot analysis of target phosphoproteins. The PAR‐1‐induced chloride secretory response was significantly attenuated by inhibitors of the EGF receptor tyrosine kinase, Srckinase, MEK1/2, as well as by inhibitors of cytosolic phospholipase (cPL) A2, COX‐1 and COX‐2. PAR‐1induced activation of cPLA2, as shown by Western blot of phosphoserine residues, was blocked in cells treated with the MEK inhibitor U0126, indicating that the MEK‐ERK1/2 MAP kinase pathway mediated PAR‐1induced cPLA2 phosphorylation. Our data show that PAR‐1‐induced chloride secretion in SCBN cells involves Src, EGF receptor trans‐activation, activation of a MAPK pathway, phosphorylation of cPLA2, COX activity, but not PGF2a or PGE2. These findings may be of clinical importance in inflammatory diseases of the intestine where secretory dysfunction is evident and thrombin levels are elevated. —Buresi, M. C. , Buret, A. G. , Hollenberg, M. D. , MacNaughton, W. K. Activation of proteinase‐activated receptor 1 stimulates epithelial chloride secretion through a unique MAP kinase‐and cyclo‐oxygenase‐dependent pathway. FASEB J. 16, 1515–1525 (2002)
Nuclear Pnn/DRS Protein Binds to Spliced mRNPs and Participates in mRNA Processing and Export via Interaction with RNPS1

ABSTRACT Pnn/DRS protein is associated with desmosomes and colocalizes with splicing factors in nuclear speckled domains. The potential interaction of Pnn with RNPS1, a pre-mRNA splicing factor and a component of the exon-exon junction complex, prompted us to examine whether Pnn is involved in nuclear mRNA processing. By immunoprecipitation, we found that Pnn associates preferentially with mRNAs produced by splicing in vitro. Oligonucleotide-directed RNase H digestion revealed that Pnn binds to the spliced mRNAs at a position immediately upstream of the splice junction and that 5′ splice site utilization determines the location of Pnn in alternatively spliced mRNAs. Immunoprecipitation further showed that Pnn binds to mRNAs produced from a transiently expressed reporter in vivo. Although associated with mRNPs, Pnn is a nuclear-restricted protein as revealed by the heterokaryon assay. Overexpression of an amino-terminal fragment of Pnn that directly interacts with RNPS1 leads to blockage of pre-mRNA splicing. However, although suppression of Pnn expression shows no significant effect on splicing, it leads to some extent to nuclear accumulation of bulk poly(A)+ RNA. Therefore, Pnn may participate, via its interaction with RNPS1, in mRNA metabolism in the nucleus, including mRNA splicing and export.
Transcriptional Interaction of an Estrogen Receptor Splice Variant and ErbB4 Suggests Convergence in Gene Susceptibility Pathways in Schizophrenia*

Mounting evidence from clinical and basic research suggests that estrogen signaling may be altered in the brains of people with schizophrenia. Previously, we found that DNA sequence variation in the estrogen receptor (ER) α gene, lower ERα mRNA levels, and/or blunted ERα signaling is associated with schizophrenia. In this study, we asked whether the naturally occurring truncated ERα isoform, Δ7, which acts as a dominant negative, can attenuate gene expression induced by the wild-type (WT) receptor in an estrogen-dependent manner in neuronal (SHSY5Y) and non-neuronal (CHOK1 and HeLa) cells. In addition, we determined the extent to which ERα interacts with NRG1-ErbB4, a leading schizophrenia susceptibility pathway. Reductions in the transcriptionally active form of ErbB4 comprising the intracytoplasmic domain (ErbB4-ICD) have been found in schizophrenia, and we hypothesized that ERα and ErbB4 may converge to control gene expression. In the present study, we show that truncated Δ7-ERα attenuates WT-ERα-driven gene expression across a wide range of estrogen concentrations in cells that express functional ERα at base line or upon co-transfection of full-length ERα. Furthermore, we find that ErbB4-ICD can potentiate the transcriptional activity of WT-ERα at EREs in two cell lines and that this potentiation effect is abolished by the presence of Δ7-ERα. Immunofluorescence microscopy revealed nuclear co-localization of WT-ERα, Δ7-ERα, and ErbB4-ICD, whereas immunoprecipitation assays showed direct interaction. Our findings demonstrate convergence between ERα and ErbB4-ICD in the transcriptional control of ERα-target gene expression and suggest that this may represent a convergent pathway that may be disrupted in schizophrenia.