Miracle-dz/UniFAR-FTUs huggingface dataset:
Oxidation of glutathione and superoxide generation by inorganic and organic selenium compounds

The carcinostatic activities of selenium (Se) compounds have been shown to be composition and concentration dependent. Several studies have indicated that the ratios between glutathione (GSH) and Se may play an important role in Se catalysis and toxicity. The present study examined the catalytic effect of three selenium compounds on GSH oxidation using lucigenin‐dependent chemiluminescence (CL) as an indirect measure of superoxide generation. Various GSH:Se ratios were assayed for the glutathione oxidase activity of selenite, selenocystamine and diselenodipropionic acid. CL emitted from the reaction of selenite with GSH increased more rapidly and was greater than those from the diselenides, but the diselenide CL reactions were sustainable. Both selenite‐ and diselenide‐induced CL were markedly suppressed by superoxide dismutase (SOD). Iodoacetic acid (IAc) effectively inhibited CL generated from selenite‐, selenocystamine‐ and diselenodipropionic acidcatalyzed GSH oxidation. These results suggest that GSH oxidation catalyzed by selenite, and the diselenides selenocystamine and diselenodipropionic acid, generated the superoxide radical in which the CL was inhibited by SOD. Furthermore, CL inhibition by IAc suggests that the catalytic species producing superoxide were the GSSe− or RSe− anion. This redox chemistry may be responsible for selenite and organoselenium toxicity and apoptosis, making possible the design and synthesis of organoselenium‐containing pharmaceuticals.
Molecular, Cellular, and Antigen Requirements for Development of Age-Associated T Cell Clonal Expansions In Vivo1

T cell aging manifests itself both at the cellular (cell-autonomous defects in signaling) and at the population (age-related dysregulation of T cell homeostasis) levels. A prominent contributor to the latter is the appearance of T cell clonal expansions (TCE), with a potential to impair immune defense. In this study, we investigated molecular, cellular, and Ag requirements for TCE development. Of the mutant mice tested, old animals lacking MHC class I exhibited 7-fold fewer TCE than controls, with a 7-fold reduction in TCE. By contrast, animals lacking only one of the MHC class I molecules (Kb or Db), or IL-7R, or devoid of T cell renewal via adult thymectomy, all exhibited significant increases in TCE incidence. This increase directly correlated to lymphopenia, increased CD8 T cell turnover and an accumulation of memory-phenotype T cells. These data suggested that homeostatic cell division in the CD8 compartment enhances the formation of TCE. Repeated immunization with peptide/adjuvant did not result in an increase in Ag-specific TCE; however, adjuvant alone increased TCE incidence. In these experiments, therefore, nonspecific and/or homeostatic proliferation was more efficient in generating TCE in mice than repeated Ag-driven stimulation, suggesting that many, if not most, TCE in specific pathogen-free laboratory mice may be Ag-independent.
Serum creatine kinase levels are associated with extremity compartment syndrome

BACKGROUND Limb compartment syndrome (CS) is a difficult diagnosis. Accurate measurement of compartment pressure is user dependent, and there is no consensus on values to define CS. Given the prevalence of extremity CS, difficulty in timely diagnosis, and ramifications of a delay in diagnosis, a precise and reliable means for early diagnosis is needed. The purpose of our study was to determine if a threshold serum creatinine kinase (CK) level is associated with the development of CS. METHODS All patients with isolated tibial/fibula fractures or extremity CS admitted to a three-hospital consortium from July 1, 2001, to June 30, 2011, were identified retrospectively using coded data. Age, basic metabolic panel, lactic acid, CK, and troponin I levels were abstracted. Univariate and multivariate regression analysis was undertaken using maximum and minimum values for each laboratory test to evaluate the association between the test and CS versus tibia/fibula fracture. RESULTS Of the 97 patients in the study, 39 had CS. Tests most strongly associated with CS were maximum CK, minimum calcium, minimum blood urea nitrogen (BUN), maximum chloride, maximum lactate, and minimum HCO3. On univariate analysis, only maximum CK had adequate correlation with CS. Optimal cut points were maximum CK of greater than 4,000 U/L. Using the model CK level of greater than 4,000 U/L, chloride level of greater than 104 mg/dL, and BUN level of less than 10 mg/dL, 0 of 6 patients had CS when all three variables were absent. When one, two, or three variables were present, the percentage of patients with CS was 36%, 80%, and 100%, respectively. Using a cut point of two or more of these three variables being positive produced sensitivity, specificity, positive and negative prediction values, and total accuracy of 0.85, 0.87, 0.76, 0.92, and 0.86, respectively. CONCLUSION CK level greater than 4,000 U/L is associated with CS. A model combining maximal CK level greater than 4,000 U/L, maximal chloride level greater than 104 mg/dL, and minimal BUN level less than 10 mg/dL has a 100% association with CS. LEVEL OF EVIDENCE Diagnostic study, level III.
Fine‐needle aspiration cytology of salivary gland: A review of 341 cases

Three hundred and forty‐one salivary gland fine‐needle aspiration (FNA) cytology specimens taken over a 6‐yr period were reviewed and correlated with clinical and/or histological findings. The aspirates were derived from parotid gland (212 cases), submandibular gland (124 cases), and minor salivary gland (5 cases). The major diagnostic categories were unsatisfactory (10 cases), normal (100 cases), sialadenitis (74 cases), cyst (34 cases), lipoma (5 cases), pleomorphic adenoma (55 cases), Warthin's tumor (36 cases), and malignancy (27 cases). The latter included 14 primary salivary neoplasms (4 lymphomas of mucosa‐associated lymphoid tissue (MALT) type, 3 adenocarcinomas, 2 squamous carcinomas, 2 adenoid cystic cacinomas, and one case each of carcinoma ex pleomorphic adenoma, undifferentiated carcinoma, and high‐grade mucoepidermoid carcinoma), and 13 metastases, 9 of which were derived from squamous carcinomas of head and neck origin. Clinicopathological review showed that 88 of 91 (97%) benign epithelial tumors and 27 of 31 (87%) malignant neoplasms with adequate FNA sampling were accurately diagnosed cytologically. False‐negative results were caused by sampling error (7 cases), most notably in cystic tumors, or were due to misinterpretation of uncommon neoplasms (3 cases). The overall sensitivity, specificity, and accuracy were 92%, 100%, and 98%, respectively. FNA cytology provides accurate diagnosis of most salivary gland lesions and contributes to conservative management in many patients with nonneoplastic conditions. Diagn. Cytopathol. 2000;22:139–146. © 2000 Wiley‐Liss, Inc.
Anti-CD14 Antibody-treated Neutrophils Respond to LPS: Possible Involvement of CD14 Upregulated by Anti-CD14 Antibody Binding

ABSTRACT CD14 and Toll-like receptor 4/MD2 (TLR4/MD2) mediate the action of LPS on neutrophils. The anti-CD14 antibody and the TLR4/MD2-antagonist, synthetic lipid IVa (LA-14-PP), are known to inhibit the response of neutrophils to LPS. We studied the role of CD14 in LPS-induced priming of neutrophils for enhanced release of the superoxide anion. The anti-CD14 antibody at much higher concentrations than required to saturate CD14 was required to inhibit priming by LPS. The inhibitory effect of the anti-CD14 antibody was overcome by LPS. After washing, anti-CD14-treated neutrophils showed upregulated CD14 upon incubation at 37°C and responded to LPS with a delayed time-course. Thus, CD14-blocked neutrophils gained responsiveness to LPS through newly upregulated CD14. These results suggested that the unbound/free anti-CD14 antibody was essential to inhibit LPS-induced priming by blocking CD14 that were newly expressed during incubation at 37°C. LA-14-PP inhibited the response of neutrophils to LPS in an anti-CD14 antibody sensitive manner. When neutrophils were treated with LA-14-PP followed by treatment with the anti-CD14 antibody, CD14 was upregulated upon warming, but priming was blocked, suggesting that TLR4/MD2 was not newly expressed by warming in association with CD14 molecules. Thus, in addition to blocking CD14, the anti-CD14 antibody was found to induce the expression of new CD14.
Long-term follow-up of unilateral pallidotomy in advanced Parkinson's disease.

BACKGROUND Although the short-term benefits of posteroventral pallidotomy for patients with advanced Parkinson's disease have been well documented, little is known about the long-term outcome of the procedure. METHODS We conducted a long-term follow-up study of a cohort of 40 patients who had undergone unilateral posteroventral medial pallidotomy between 1993 and 1996. Twenty patients were not evaluated because they had undergone a second surgical procedure (11 patients) or had died (2) or because they had dementia or another debilitating illness (4), lived too far away (1), or had been lost to follow-up (2). We conducted serial postoperative assessments of parkinsonism in the remaining 20 patients while they were taking medications ("on" period) and after overnight withdrawal of the drugs ("off" period). The mean follow-up time was 52 months (range, 41 to 64). RESULTS The combined off-period score for activities of daily living and motor function on the Unified Parkinson's Disease Rating Scale was 18.0 percent better at the last evaluation than at base line (95 percent confidence interval, 4.9 to 31.0 percent; P=0.01). Significant improvements were also evident in the off-period scores for contralateral tremor (65.4 percent improvement, P=0.007), rigidity (43.2 percent, P=0.03), and bradykinesia (18.2 percent, P=0.04) and in the on-period score for contralateral dyskinesia (70.6 percent, P<0.001). Changes in medication did not contribute to the sustained improvement. The 20 patients who could not be included in the long-term analysis had similar base-line characteristics but a worse response to surgery at six months. CONCLUSIONS In the group of patients with advanced Parkinson's disease who could be enrolled in our long-term follow-up study of unilateral posteroventral medial pallidotomy (20 patients from the original cohort of 40), significant early improvements in off-period contralateral signs of parkinsonism were sustained for up to five and a half years. There was a sustained significant improvement in on-period contralateral dyskinesia but not in other on-period signs of parkinsonism.
Reported early family environment covaries with menarcheal age as a function of polymorphic variation in estrogen receptor-α

Abstract Age at menarche, a sentinel index of pubertal maturation, was examined in relation to early family relationships (conflict, cohesion) and polymorphic variation in the gene encoding estrogen receptor-α (ESR1) in a midlife sample of 455 European American women. Consistent with prior literature, women who reported being raised in families characterized by close interpersonal relationships and little conflict tended to reach menarche at a later age than participants reared in families lacking cohesion and prone to discord. Moreover, this association was moderated by ESR1 variation, such that quality of the family environment covaried positively with menarcheal age among participants homozygous for minor alleles of the two ESR1 polymorphisms studied here (rs9304799, rs2234693), but not among women of other ESR1 genotypes. In addition, (a) family relationship variables were unrelated to ESR1 variation, and (b) genotype-dependent effects of childhood environment on age at menarche could not be accounted for by personality traits elsewhere shown to explain heritable variation in reported family conflict and cohesion. These findings are consistent with theories of differential susceptibility to environmental influence, as well as the more specific hypothesis (by Belsky) that girls differ genetically in their sensitivity to rearing effects on pubertal maturation.
An Articulatory-Perceptual Account of Vocalization and Elision of Dark /l/ in the Romance Languages

This investigation seeks to understand the factors causing vocalization and elision of dark /l/ in the Romance languages. Contrary to articulatory-and perceptual-based arguments in the literature it is claimed that preconsonantal vocalization conveys the phonemic categorization of the /w/-like formant transitions generated by the tongue dorsum retraction gesture (in a similar fashion to other processes such as /Vji/ > /Vjn/). The evolution /VwlC/ > /VwC/ may be explained using articulatory and perceptual arguments. A dissimilatory perceptual mechanism is required in order to account for a much higher frequency of vocalizations before dentals and alveolars than before labials and velars in the Romance languages. Through this process listeners assign the gravity property of dark /l/ to a following grave labial or velar consonant but not so to a following acute dental or alveolar consonant in spite of the alveolar lateral being equally dark (i.e., grave) in the three consonantal environments. Other articulatory facts appear to play a role in the vocalization of final /l/ (i.e., the occurrence of closure after voicing has ceased) and of geminate /ll/ (i.e., its being darker than non-geminate /l/). The elision of dark /l/ may occur preconsonantally and word finally either after vocalization has applied or not. This study illustrates the multiple causal factors and the articulatory-perceptual nature of sound change processes.
The cyclin-dependent kinase inhibitors olomoucine and roscovitine arrest human fibroblasts in G1 phase by specific inhibition of CDK2 kinase activity.

The specificity and the temporal location of cell cycle arrest induced by the cyclin-dependent kinase (CDK) inhibitors olomoucine and roscovitine were investigated in normal human fibroblasts. Effects on the cell cycle were compared with those induced by the kinase inhibitor staurosporine, which arrests normal cells in early G1 phase by acting upstream of CDK2. Consistent with their in vitro activity, olomoucine and roscovitine, but not the related compound iso-olomoucine, induced a dose-dependent arrest in G1 phase. Following removal of CDK inhibitors, cells resumed cycle progression entering S phase with a kinetics faster than staurosporine-treated samples. Cellular levels of PCNA, cyclin D1, and cyclin E were not affected by the CDK inhibitors. In contrast, staurosporine significantly reduced the levels of these proteins, as determined by immunocytometry and Western blot analysis. Cyclin A was detectable only in some cells remaining in the G2 + M compartment of samples treated with CDK inhibitors, but not in samples treated with staurosporine. Significant reduction in the hyperphosphorylated forms of retinoblastoma protein was found in samples treated with CDK inhibitors, while only hypophosphorylated forms were observed in staurosporine-treated samples. Concomitantly, CDK2, but not CDK4, activity immunoprecipitated from cells treated with olomoucine or roscovitine was markedly inhibited. These results suggest that in normal cells, CDK2 kinase activity is the specific target of olomoucine and roscovitine.
The Leopoldina international symposium on parasitism, commensalism and symbiosis – common themes, different outcome

The development of new methods, including genomics, which can even be applied to unculturable microorganisms, has significantly increased our knowledge about bacterial pathogenesis and symbiosis and, in consequence, is profoundly modifying our views on the evolution and the genetic and physiological basis of bacteria–host interactions. The presentations at this symposium revealed conceptual links between bacterial pathogenesis and symbiosis. The close co‐operation of experts in both fields will result in significant synergy and new insights into basic mechanisms of bacteria–host interactions and their evolution. The meeting provided fascinating news about the genetic and metabolic consequences that the change in their lifestyle had for bacteria that developed from free‐living to permanent host‐associated organisms exemplified by intracellular pathogens or symbionts. In addition, surprising similarities but also striking differences between the strategies involved in the establishment of a symbiotic versus a parasitic lifestyle can be noted. In the long run, the characterization of such differences might lead to lifestyle prediction or to an evaluation of the pathogenic potential of newly isolated bacteria via the definition of genetic and/or metabolic signatures characteristic for pathogenic or symbiotic organisms. Moreover, it is expected that these investigations will lead to new strategies for the treatment or prevention of bacterial infections, or the avoidance of pathogen transmission.
Strategic planning of future products with product scenarios

Manufacturing based corporations often find themselves confronted with complexities of increased pressures to innovate in order to ensure their comparative market positions. In order to react to various exogenous changes corporations need to develop strategies that match their manufacturing resources as well as products with the markets requirements. Product scenarios represent a holistic approach for managing innovation processes and technologies efficiently. The analysis through evolutionary algorithms for compatibility between and amongst the product structure segments provides the necessary information about their suitability. The resulting scenarios, roadmaps and a regular monitoring processes are prerequisite for the managerial decision making process and the implementation of product and technology strategies.
Staphylococcus aureus Capsular Polysaccharide Types 5 and 8 Reduce Killing by Bovine Neutrophils In Vitro

ABSTRACT Isogenic variants of Staphylococcus aureus strain Reynolds expressing either no capsule or capsular polysaccharide (CP) type 5 (CP5) or type 8 (CP8) were used to assess the effect of CP on bacterial killing and the respiratory burst of bovine neutrophils. The effects of antisera specific for CP5 and CP8 were also evaluated. The killing of live bacteria by isolated neutrophils was quantified in a bactericidal assay, while the respiratory burst after stimulation with live bacteria in whole blood was measured by flow cytometry. The expression of a CP5 or CP8 capsule protected the bacteria from being killed by bovine neutrophils in vitro (P < 0.001), and the capsule-expressing variants did not stimulate respiratory burst activity in calf whole blood. The addition of serotype-specific antisera increased the killing of the capsule-expressing bacteria and enhanced their stimulating effect in the respiratory burst assay (P < 0.01). When the S. aureus variants were grown under conditions known not to promote capsule expression, there were no significant differences between them. The present study demonstrates that the expression of S. aureus CP5 or CP8 confers resistance to opsonophagocytic killing and prevents the bacteria from inducing respiratory burst of bovine neutrophils in vitro and that these effects can be reversed by the addition of serotype-specific antisera.
Exercise on prescription: a randomized study on the effect of counseling vs counseling and supervised exercise

The aim of this study was to compare short‐ (0–4 months) and long‐term (0–10 months) effects of high‐intensive Exercise on Prescription (EoP) intervention (counseling and supervised exercise) implemented in primary healthcare in a number of Danish counties with a low‐intensive intervention (counseling) using maximal oxygen uptake (VO2max) as the primary outcome. The study was conducted as a randomized trial in 2005–2006 with a high and a low‐intensive group. All the patients referred to the EoP scheme by their GP in the counties of Vejle and Ribe, Denmark, were eligible for the trial. The high‐intensive EoP group received 4 months of group‐based supervised training and attended five motivational counseling sessions. The low‐intensive group only attended four motivational counseling sessions. Three hundred and twenty‐seven patients entered the EoP scheme, and 52 (16%) volunteered for the randomized trial. No short‐ or long‐term differences were found between the high and the low‐intensive groups for VO2max (short‐term 95% CI −1.1; 4.4 mL O2/(kg min), long‐term 95% CI −1.6 to 2.1). The present study did not demonstrate any significant clinical outcome for the high‐intensive EoP intervention as opposed to the low‐intensive intervention.
Review: Systemic inflammation and Alzheimer's disease

There is a great deal of evidence suggesting an important role for systemic inflammation in the pathogenesis of Alzheimer's disease. The role of systemic inflammation, and indeed inflammation in general, is still largely considered to be as a contributor to the disease process rather than of aetiological importance although there is emerging evidence to suggest that its role may predate the deposition of amyloid. Therapies aimed at reducing inflammation in individuals with mild cognitive impairment and Alzheimer's disease have been disappointing and have largely focused on the need to ameliorate central inflammation with little attention to the importance of dampening down systemic inflammation. Novel approaches in this area require a greater understanding of the effects of systemic inflammation on the development and progression of Alzheimer's disease and of the communicating pathways between the systemic and central innate immune systems.
Membrane Estrogen Receptors Stimulate Intracellular Calcium Release and Progesterone Synthesis in Hypothalamic Astrocytes

In hypothalamic astrocytes obtained from adult female rats, estradiol rapidly increased free cytoplasmic calcium concentrations ([Ca2+]i) that facilitate progesterone synthesis. The present study demonstrated that estradiol (1 nm) significantly and maximally stimulated progesterone synthesis within 5 min, supporting a rapid, nongenomic mechanism. The group I metabotropic glutamate receptor (mGluR1a) antagonist LY 367385 [(S)-(+)-a-amino-4-carboxy-2-methylbenzeneacetic acid] attenuated both the estradiol-induced [Ca2+]i release and progesterone synthesis. To investigate membrane-associated estrogen receptors (mERs), agonists for ERα, ERβ, STX-activated protein, and GPR30 were compared. The selective ERα agonist propylpyrazole triole (PPT) and STX most closely mimicked the estradiol-induced [Ca2+]i responses, where PPT was more potent but less efficacious than STX. Only high doses (100 nm) of selective ERβ agonist diarylpropionitrile (DPN) and GPR30 agonist G-1 induced estradiol-like [Ca2+]i responses. With the exception of DPN (even at 100 nm), all agonists stimulated progesterone synthesis. The PPT- and STX-induced [Ca2+]i release and progesterone synthesis were blocked by LY 367385. While the G-1-stimulated [Ca2+]i release was blocked by LY 367385, progesterone synthesis was not. Since GPR30 was detected intracellularly but not in the membrane, we interpreted these results to suggest that G-1 could activate mGluR1a on the membrane and GPR30 on the smooth endoplasmic reticulum to release intracellular calcium. Although STX and G-1 maximally stimulated [Ca2+]i release in astrocytes from estrogen receptor-α knock-out (ERKO) mice, estradiol in vivo did not stimulate progesterone synthesis in the ERKO mice. Together, these results indicate that mERα is mainly responsible for the rapid, membrane-initiated estradiol-signaling that leads to progesterone synthesis in hypothalamic astrocytes.
Intrathecal chloroprocaine vs. lidocaine in day‐case surgery: recovery, discharge and effect of pre‐hydration on micturition

This randomised, double blind prospective study compares intrathecal lidocaine with chloroprocaine in day‐case surgery and the influence of a 500 ml pre‐load intravenously. We tested the hypothesis that chloroprocaine provides faster recovery and discharge in day‐case surgery. Secondary we studied the influence of a preload compared with fluid restriction on discharge time and micturition problems.