Miracle-dz/UniFAR-FTUs huggingface dataset:
Stimulatory and inhibitory regulation of calcium-activated potassium channels by guanine nucleotide-binding proteins.

The regulation of membrane ion channels by guanine nucleotide-binding proteins (G proteins) has been described in numerous tissues. This regulation has been shown to involve the membrane-delimited stimulatory action of G proteins on ion channels. We now show that single calcium-activated potassium channels (KCa channels) in airway smooth muscle cells are both stimulated and inhibited by G proteins in membrane patches. We demonstrate that the beta-adrenergic agonist isoproterenol stimulates channel activity via the alpha subunit of the stimulatory G protein of adenylyl cyclase, Gs, and that channel opening is inhibited by the action of the muscarinic agonist methacholine, acting via a pertussis toxin-sensitive G protein. Isoproterenol stimulated and methacholine inhibited channel activity in the same outside-out patches when GTP was present at the cytosolic surface of the patch. In inside-out patches, addition of GTP and guanosine 5'-[gamma-thio]triphosphate (GTP[gamma S]) augmented channel activity when isoproterenol was included in the patch pipette, and inhibited channel activity when methacholine was included in the pipette. Consistent with these results, in the presence of GTP[gamma S], the alpha subunit of Gs (alpha s.GTP[gamma S] complex) opened KCa channels in a dose-dependent manner, whereas in the presence of guanosine 5'-[beta-thio]diphosphate, alpha s had no effect. By contrast, application of activated alpha i or alpha o proteins did not inhibit channel activity in inside-out patches, indicating that channel inhibition is more complex than a simple alpha subunit/channel interaction, similar to the complex inhibitory regulation of adenylyl cyclase. These results suggest that hormonal regulation of KCa channels shares substantial features with the regulation of adenylyl cyclase and demonstrate that a single ion channel may serve as the regulatory target for the membrane-delimited action of stimulatory and inhibitory G proteins. Moreover, they demonstrate a potentially important functional pathway by which beta-adrenergic and other Gs-linked receptors stimulate relaxation of smooth muscle, independent of cAMP-dependent protein phosphorylation.
Percutaneous nephrolithotomy success rate and complications in patients with previous open stone surgery.

PURPOSE To determine the effect of previous single or multiple open stone surgeries on percutaneous nephrolithotomy (PCNL) results and complications. MATERIALS AND METHODS We reviewed medical records of 1422 patients who had been undergone PCNL in our institute between 1998 and 2011 by the same surgeon. Patients were divided into 3 groups. The first group included patients with no history of previous ipsilateral open stone surgery (n = 711). Patients in second group had been undergone only one open stone surgery before PCNL (n = 405) and patients with more than one previous open stone surgery were placed in third group (n = 306). We compared operation duration, stone free rate (SFR), number of attempts to access the collecting system and intraoperative and postoperative complications between 3 groups. RESULTS There were no differences in sex, body mass index, stone burden and laterality between 3 groups. Operation time was significantly shorter in the first group (P = .000) while there was no statistically significant differences in operation duration between second and third groups (P > .973). The number of attempts to enter the collecting system was significantly lower in the first group in comparison to other two groups (P = .00). We didn’t find significant differences between 3 groups in hospital stay, SFR, intraoperative and postoperative complications. CONCLUSION Our findings demonstrated that PCNL can be performed in patients with one or more open stone surgery history successfully without further complications.
Effect of chronic cocaine administration on the hemodynamic response to acute hemorrhage in awake and anesthetized sheep.

BACKGROUND Although Cocaine use is common in trauma victims, little is known about how cocaine affects the cardiovascular response to trauma and associated blood loss. This study determined the effect of chronic cocaine use on the cardiovascular response to hemorrhage in awake and anesthetized sheep. METHODS The hemodynamic and acid-base responses to graded hemorrhage were determined in awake and anesthetized sheep at baseline and after 15 and 18 days of chronic cocaine exposure. RESULTS Chronic cocaine exposure resulted in a moderate paradoxical bradycardic response to hemorrhage in awake sheep, but did not otherwise alter the hemodynamic response to hemorrhage. In anesthetized animals, cocaine exposure impaired the ability to maintain mean arterial pressure and cardiac output during hemorrhage, and resulted in a marked paradoxical bradycardic response to hemorrhage. CONCLUSIONS Chronic cocaine exposure did not have an important effect on the cardiovascular response to hemorrhage in awake sheep. However, in anesthetized sheep, chronic cocaine exposure diminished the compensatory cardiovascular response to graded hemorrhage.
Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam

Objectives: To study the prevalence of drug resistance and genotype testing for HIV drug resistance on HIV/AIDS patients with first-line antiretroviral treatment failure at Dong Da Hospital, Hanoi, Vietnam. Patients and methods: Forty-seven patients in Dong Da Hospital, Hanoi, with confirmation of first-line antiretroviral therapy (ART) failure were enrolled in this study from June 2006 to December 2016. Both the protease and reverse transcriptase genes were amplified and sequenced using Trugene® HIV-1 Genotyping Kit and OpenGene® DNA system at the biomolecular laboratory of the National Institute of Hygiene and Epidemiology, Vietnam. The Stanford HIV database algorithm was used for interpretation of resistance data and genotyping. Results: Drug resistance mutations were 90.7% in patients with first-line treatment failure. Amongst patients with drug resistance mutation, 97.7% resisted to non-nucleoside reverse transcriptase inhibitors (NNRTIs), followed by nucleoside reverse transcriptase inhibitors (NRTIs, 95.3%) and protease inhibitors (PIs, 11.6%). Amongst the genetic mutations resistant to NNRTIs, G190S mutation was the highest (51.2%), K101HQ mutation was 39.5% and Y181I mutation was 34.9%. In genetic mutations to NRTIs, M184V mutation was 88.4%. In thymidine analogue mutations, K70R mutation was the most common (37.2%), followed by D67N, T215F and T69N mutations (27.9%, 27.9% and 25.6%, respectively). In genetic mutations in PIs, M36I and K20R mutations made up 9.3%. In NNRTIs, the prevalence of nevirapine resistance was 55.8%, and that of efavirenz resistance was 4.7%. In NRTIs, the ratio of lamivudine resistance was 93.0%, and that of zidovudine resistance was 9.3%. No lopinavir/ritonavir resistance was recorded. Conclusions: Drug resistance mutations in patients with first-line ART failure had a high prevalence of NNRTI and NRTI resistance but still susceptible to PIs.
Chronic graft-versus-host disease following allogeneic peripheral blood and bone marrow stem cell transplants: a single center experience.

We examined the influence of graft-versus-host disease (GVHD) on outcome in patients with hematologic malignancies undergoing allogeneic bone marrow transplantation (allo-BMT) and peripheral blood stem cell transplantation (allo-PBSCT). Our data confirm that allo-PBSCT patients experience more chronic GVHD than allo-BMT patients, translating into a more potent graft-versus-leukemia (GVL) effect.
The binocular input to cells in the feline dorsal lateral geniculate nucleus (dLGN).

1. Cells in the A laminae of the dorsal lateral geniculate nucleus receive their primary innervation from either the contralateral (A) or ipsilateral (A1) eye. This paper provides evidence concerning the responses they give to visual stimulation of what is commonly regarded as the ineffective or non‐dominant eye. It also examines the contribution of the corticofugal input to these responses. 2. Cells were identified and classified according to their responses to stimulation of the dominant eye receptive field. This was then occluded and the corresponding location in the non‐dominant eye field stimulated by a moving bar. Out of fifty‐seven cells examined forty‐three (75%) gave a response to stimulation of the non‐dominant eye. There was no obvious difference between the effects on X and Y cells in these experiments. 3. In most cases (thirty‐seven) the response involved an inhibition of the resting discharge level, but three cells gave a mixed excitatory and inhibitory response and three a pure excitatory response. All the responses were weak and only revealed by prolonged periods of averaging (20‐100 trials). 4. Ionophoretic application of the GABA antagonist N‐methyl‐bicuculline (NMB) blocked the visually elicited inhibitory effects and in most cases (twenty‐seven out of thirty‐two tested) revealed an excitatory response. Out of a further eight cells previously unresponsive to the non‐dominant eye, NMB application revealed excitatory responses in three. 5. Increasing background discharge levels and cell excitability by ionophoretic application of either acetylcholine or the excitatory amino acid, quisqualate, did not eliminate inhibitory responses and did not reveal excitatory responses. We suggest that the visually driven non‐dominant eye suppression of the background discharge involves a GABA‐mediated inhibitory input which masks an underlying excitatory input. 6. An excitatory non‐dominant eye response could potentially derive from the influence of the corticofugal projection. However, removal of the corticofugal input by aspiration of areas 17 and 18 did not reduce either the excitatory or the inhibitory components of the response. 7. In the absence of corticofugal input all cells tested (fourteen) exhibited a non‐dominant eye response and all studied during NMB application (eleven) gave an excitatory response. The primary effect of removing the corticofugal input appeared to involve the loss of a ‘damping’ influence on the excitatory and inhibitory responses, such that they were more easily revealed. The significance of these findings is discussed.
A general framework for minimizing translation effort: towards a principled combination of translation technologies in computer-aided translation

This paper motivates the need for an homogeneous way of measuring and estimating translation effort (quality) in computer-aided translation. It then deﬁnes a general framework for the measurement and estimation of translation effort so that translation technologies can be both optimized and combined in a principled manner. In this way, professional translators will bene-ﬁt from the seamless integration of all the technologies at their disposal when working on a translation job
Studies on " Dipetalonema viteae " ( Filarioidea ) . Teil I , Microfilaraemia in hamsters inrelation to worm burden and humoral immune response

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Wollastonite toxicity: an update

Abstract This review updates earlier work addressing the epidemiology and toxicity of wollastonite. Earlier chronic animal bioassay and human mortality data were inadequate (IARC term) or negative and no new studies of these types have been published. Wollastonite has been determined to have low biopersistence in both in vivo and in vitro studies, which probably accounts for its relative lack of toxicity. Earlier morbidity studies of mining/mineral processing facilities in Finland and New York State indicated that exposure to wollastonite might result in pleural plaques (Finland) or decrements in certain measures of lung function (New York). More recent analysis of data from an ongoing health surveillance program at one facility (New York) indicates that there are no pleural plaques or interstitial lung disease or decrements in lung function among never smokers or former smokers occupationally exposed to wollastonite. This result probably reflects continued reduction in exposures as part of an ongoing product stewardship program at this facility and suggests that wollastonite has relatively low toxicity as currently managed.
Novel treatments for cancer cachexia

Cancer cachexia is a debilitating and life-threatening syndrome characterised by anorexia, body weight loss, loss of adipose tissue and skeletal muscle, and accounts for ≥ 20% of deaths in neoplastic patients. Cancer cachexia significantly impairs quality of life and response to antineoplastic therapies, increasing the morbidity and mortality of cancer patients. Muscle wasting is the most important phenotypic feature of cancer cachexia and the principle cause of function impairment, fatigue and respiratory complications, and is mainly related to a hyperactivation of muscle proteolytic pathways. Existing therapeutic strategies have proven to be only partially effective. In the last decade, the correction of anorexia, the inhibition of catabolic processes and the stimulation of anabolic pathways in muscle has been attempted pharmacologically, giving encouraging results in animal models and through preliminary clinical trials.
Clinical significance of microvessel density and vascular endothelial growth factor expression in hepatocellular carcinoma and surrounding liver: Possible involvement of vascular endothelial growth factor in the angiogenesis of cirrhotic liver

As in other tumors, the assessment of microvessel density (MVD) in hepatocellular carcinoma (HCC) may be essential to perform an effective anti‐angiogenic therapy for this tumor. The relationship between vascular endothelial growth factor (VEGF) and MVD of HCC as well as the surrounding liver remains to be elucidated. In 71 patients who had undergone curative hepatic resection for HCC, MVD and VEGF expressions were evaluated for HCC and the liver by quantitative reverse‐transcription polymerase chain reaction (RT‐PCR) and/or immunostaining. The intensity and extent of VEGF immunoreactivity were evaluated using a computer image analyzer–cell analysis system (CAS). Angiographic data were re‐evaluated and compared with MVD in 50 tumors. Tumoral MVD was significantly correlated with tumor capsule formation (t test, P = .0016). Small HCCs (≤2 cm) had a significantly lower MVD compared with moderate‐sized HCCs (2‐5 cm) (t test, P = .016), and the MVD of large HCCs was relatively lower than that of moderate tumors. Tumor vascularity on angiography was not correlated with the MVD. Neither VEGF mRNA levels nor protein expression in HCC were correlated with the tumoral MVD or any histopathological features of the tumor. However, cirrhotic livers had significantly higher MVD and VEGF expressions compared with noncirrhotic livers (t test, P = .0015 and P = .047, respectively). Only the MVD of tumor was significantly correlated with intrahepatic recurrence (t test, P = .0048) and disease‐free survival (DFS) rates (log rank test, P = .0035). Moreover, the MVD was an independent predictor for DFS by multivariate analysis (χ2 test, P = .03). In conclusion, the MVD in HCC may be involved in the dismal prognosis of this tumor, and VEGF may be associated with the angiogenic process of the cirrhotic liver, but not with the angiogenesis of HCC.
OCCURRENCE OF PASTEURELLACEAE BACTERIA IN THE ORAL CAVITY OF SELECTED MARINE MAMMAL SPECIES

Abstract: The occurrence of bacteria belonging to Pasteurellaceae in the oral cavity of captive marine mammals was investigated using culture and subsequent geno- and phenotypic characterization and phylogenetic analyses. A total of 89 bacterial isolates from pinnipeds tentatively classified with the family Pasteurellaceae were further characterized by phylogenetic analysis of rpoB gene sequences, which showed that the isolates investigated formed five distinct groups. Four strains from California sea lions (Zalophus californianus) made up group I, which was classified with Pasteurella canis. Group II comprised four strains from harbor seals (Phoca vitulina) and grey seals (Halichoerus grypus) classified with Pasteurella stomatis. Group III consisted of 28 strains, isolated from harbor and gray seals and represented Bisgaardia genomospecies 1. Two strains from a harbor and a grey seal, group IV, were classified with Bisgaardia hudsonensis. Fifty-two strains from northern fur seals (Callorhinus ursinus), walruses (Odobenus rosmarus), and California and Steller sea lions (Eumetopias jubatus) formed group V and represented Otariodibacter oris. No Pasteurellaceae isolates were obtained from cetaceans, but Pasteurellaceae were isolated from all sampled pinnipeds. On the basis of these results, it is very likely that Pasteurellaceae bacteria represent a part of the normal oral flora in pinnipeds.
Comparison of primary and secondary esophageal peristalsis in humans: effect of atropine.

To determine whether physiological differences exist between primary (swallow-induced) and secondary (distension-induced) peristalsis in humans, 10 healthy male volunteers underwent esophageal manometry on 2 consecutive days using a perfused intraluminal catheter system that incorporated a latex balloon. Initially the catheter was positioned so that the balloon was centered 16 cm above the lower esophageal sphincter (LES), and intraluminal pressures were recorded 21, 11, 6, and 1 cm above the LES. After a series of wet swallows, dry swallows, and balloon distensions, the catheter was repositioned so that the balloon was 6 cm above the LES and pressures were recorded 1 and 11 cm above the LES. A series of balloon distensions were repeated in this position, and the subject was then given either atropine (10 micrograms/kg iv) or placebo in a double-blind randomized fashion (on consecutive days). The protocol was then repeated in reverse order. Distension-induced responses aboral to the balloon with the balloon located 16 cm above the LES were 1) of lower amplitude, 2) more often nonperistaltic, and 3) less atropine sensitive than swallow-induced contractions at comparable sites. With the balloon located distally (6 cm above LES) contractions induced at the 11-cm site (i.e., orad to the balloon) were much more atropine sensitive than contractions induced at the same site when the balloon was located proximally (i.e., 16 cm above LES). These data suggest that, contrary to previous reports, secondary peristalsis differs significantly from primary peristalsis. Furthermore, atropine differentially effects these two types of peristalsis, suggesting that the neural pathways involved are dissimilar.
Leukotriene D4 receptor-mediated synthesis and release of arachidonic acid metabolites in guinea pig lung: induction of thromboxane and prostacyclin biosynthesis by leukotriene D4.

The effects of the peptidoleukotrienes C4 (LTC4), D4 (LTD4), E4 (LTE4) and a series agonists and antagonists on arachidonic acid metabolism were characterized in minced guinea pig lung. In response to LTD4, guinea pig lung utilized and converted the endogenous arachidonic acid into a variety of cyclooxygenase metabolites [prostaglandins (PGs) E2, F2 alpha, 6-keto-F1 alpha and thromboxane (Tx) B2] and lipoxygenase metabolites (5,12-dihydroxy-6,8,11,14-eicosatetraneoic acid and 5,15-dihydroxy-5,9,11,13-eicosatetraneoic acid). Using radioimmunoassays, the stable, pharmacologically important metabolites of the cyclooxygenase pathway, 6-keto-PGF1 alpha and TxB2, were quantitated. LTD4, LTE4 and several synthetic agonists induced dose-dependent synthesis and release of TxB2 and 6-keto-PGF1 alpha. Agonist-induced synthesis and release of 6-keto-PGF1 alpha and TxB2 was time-dependent and was maximal after 10 to 12 min of incubation. The slow-reacting substance of anaphylaxis antagonist, FPL 55712, and the newly reported dithioacetal LTD4 receptor antagonists (SKF 102922 and SKF 102081) did not induce synthesis and release of TxB2 and 6-keto-PGF1 alpha in concentrations that blocked the agonist-induced smooth muscle contraction. Preincubation with these antagonists inhibited the synthesis and release of prostanoids induced by LTD4 in the guinea pig lung. Islet activating protein, which inactivates the inhibitory guanine nucleotide binding protein (Gi protein), partially inhibited the agonist-induced synthesis and release of prostanoids. Furthermore, the receptor binding affinities and/or the myotonic activities of the LTD4 agonists correlated linearly with the agonist-induced prostanoid synthesis and release effect. (ABSTRACT TRUNCATED AT 250 WORDS)
Mortality attributable to smoking among HIV-1-infected individuals: a nationwide, population-based cohort study.

BACKGROUND We assessed mortality attributable to smoking among patients with human immunodeficiency virus (HIV). METHODS We estimated mortality rates (MRs), mortality rate ratios (MRRs), life expectancies, life-years lost, and population-attributable risk of death associated with smoking and with HIV among current and nonsmoking individuals from a population-based, nationwide HIV cohort and a cohort of matched HIV-negative individuals. RESULTS A total of 2921 HIV patients and 10 642 controls were followed for 14 281 and 45 122 person-years, respectively. All-cause and non-AIDS-related mortality was substantially increased among smoking compared to nonsmoking HIV patients (MRR, 4.4 [95% confidence interval {CI}, 3.0-6.7] and 5.3 [95% CI, 3.2-8.8], respectively). Excess MR per 1000 person-years among current vs nonsmokers was 17.6 (95% CI, 13.3-21.9) for HIV patients and 4.8 (95% CI, 3.2-6.4) for controls. A 35-year-old HIV patient had a median life expectancy of 62.6 years (95% CI, 59.9-64.6) for smokers and 78.4 years (95% CI, 70.8-84.0) for nonsmokers; the numbers of life-years lost in association with smoking and HIV were 12.3 (95% CI, 8.1-16.4) and 5.1 (95% CI, 1.6-8.5). The population-attributable risk of death associated with smoking was 61.5% among HIV patients and 34.2% among controls. CONCLUSIONS In a setting where HIV care is well organized and antiretroviral therapy is free of charge, HIV-infected smokers lose more life-years to smoking than to HIV. The excess mortality of smokers is tripled and the population-attributable risk of death associated with smoking is doubled among HIV patients compared to the background population.
Locus Coeruleus Lesions Suppress the Seizure‐Attenuating Effects of Vagus Nerve Stimulation

Summary: Purpose: Although vagus nerve stimulation (VNS) is now marketed throughout most of the world as a treatment for drug‐resistant epilepsy, the therapeutic mechanism of action of VNS‐induced seizure suppression has not yet been established. Elucidation of this mechanism is an important first step in the development of strategies to improve VNS efficacy. Because the locus coeruleus (LC) has been implicated in the antinociceptive effects of VNS, we chemically lesioned the LC in the present study to determine if it is a critical structure involved in the anticonvulsant mechanisms of VNS.