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Carboplatin and paclitaxel plus ASA404 as first-line chemotherapy for extensive-stage small-cell lung cancer: a multicenter single arm phase II trial (SAKK 15/08). Small-cell lung cancer (SCLC) is a highly vascularized tumor. ASA404 is a tumor vascular disrupting agent. This is the first trial to report the effects of combining chemotherapy with ASA404 in SCLC. Patients with untreated metastatic SCLC were treated with carboplatin (area under curve, 6) plus paclitaxel (175 mg/m(2)) plus ASA404 (1800 mg/m(2)) on day 1 every 21 days for up to 6 cycles. The primary endpoint was the progression-free survival (PFS) rate at 24 weeks. Median age was 61 years; 53% were women, 41% had weight loss; and 96% had a performance status of 0-1. Twelve patients completed all 6 cycles, and most adverse events were related to chemotherapy. Median PFS and time to progression were 7.0 months (95% CI, 5.7-9.4 months) and 7.5 months (95% CI, 5.7-9.4 months), respectively. The progression-free survival (PFS) rate at 24 weeks was 41% (95% CI, 18%-65%). The overall response rate was 94%. The median overall survival time was 14.2 months (95% CI, 8.2-16.0 months) and 1-year survival was 57%. The median follow-up time was 17.7 months. Due to negative results with ASA404 in non-small-cell lung cancer trials, the trial was stopped prematurely after 17 of 56 planned patients were being accrued. This is the first report of a clinical trial with a vascular disrupting agent in SCLC. No unexpected toxicity was observed. PFS was not prolonged with carboplatin and paclitaxel plus ASA404.
{ "pile_set_name": "PubMed Abstracts" }
Calibration, information, and control strategies for braking to avoid a collision. This study explored visual control strategies for braking to avoid collision by manipulating information about speed of self-motion. Participants watched computer-generated displays and used a brake to stop at an object in the path of motion. Global optic flow rate and edge rate were manipulated by adjusting eye-height and ground-texture size. Stopping distance, initiation of braking, and the magnitude of brake adjustments were influenced by both optical variables, but global optic flow rate had a stronger effect. A new model is introduced according to which braking is controlled by keeping the perceived ideal deceleration, based in part on global optic flow rate, within a "safe" region between 0 and the maximum deceleration of the brake.
{ "pile_set_name": "PubMed Abstracts" }
Diversity of glutathione s-transferase omega 1 (a140d) and 2 (n142d) gene polymorphisms in worldwide populations. 1. Glutathione S-transferase class omega (GSTO) 1 and 2 are members of the glutathione-S-transferase family, which uses glutathione in the process of the biotransformation of drugs, xenobiotics and oxidative stress. Associations with the age-at-onset of Alzheimer's and Parkinson's diseases have been shown in the genetic polymorphism of GSTO1 and GSTO2. 2. In the present study, the frequencies of GSTO1*A140D and GSTO2*N142D in Ovambos (n = 163), Turks (n = 194), Mongolians (n = 243) and Japanese (n = 102) were investigated and compared with findings from other studies. Detection of these single nucleotide polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism analysis. 3. The allele frequencies of these polymorphisms in Ovambos, Turks, Mongolians and Japanese were 0.040, 0.085, 0.128 and 0.108, respectively, for GSTO1*A140D and 0.583, 0.219, 0.173 and 0.216, respectively, for GSTO2*N142D. Ovambos showed the lowest allele frequency of GSTO1*A140D. Conversely, Africans, including Ovambos, showed higher allele frequencies of GSTO2*N142D than Caucasians and Asians. 4. The existence of a certain genetic heterogeneity in the worldwide distribution of these two polymorphisms is revealed in the present study.
{ "pile_set_name": "PubMed Abstracts" }
Randomized clinical trial of splenic radiofrequency ablation versus splenectomy for severe hypersplenism. Radiofrequency ablation (RFA) is a relatively new treatment for hypersplenism. The results of a randomized clinical trial comparing RFA and splenectomy with 5 years of follow-up are reported. Fifty-seven patients with hypersplenism due to liver cirrhosis were assigned randomly (in a 1 : 2 ratio) to splenectomy (19 patients) or RFA (38). The RFA group was subdivided according to the percentage of the spleen ablated: less than 50 per cent (9 patients), 50-70 per cent (18) or over 70 per cent (11). Routine blood tests were performed before and after operation, and total spleen volume and ablated volume were measured by contrast-enhanced computed tomography. The primary endpoint of the trial was recurrence of hypersplenism, assessed as platelet and white cell counts, at 5 years after surgery. White cell and platelet counts increased rapidly after intervention in both groups. By 36 months after operation peripheral platelet and white cell counts had decreased significantly in the RFA group compared with the splenectomy group, and declined to baseline levels by 48 months. Hypersplenism recurred after 6 months in patients with less than 50 per cent of the spleen ablated. Blood cell count in the splenectomy group and in patients with more than 50 per cent of the spleen ablated decreased with time after operation, but to levels that remained significantly higher than those before operation (P < 0·050). Splenic volume reached its nadir 12 months after RFA and then increased with time. Splenic RFA represents an attractive alternative treatment for hypersplenism induced by liver cirrhosis, particularly when more than 50 per cent of the spleen is ablated.
{ "pile_set_name": "PubMed Abstracts" }
[Primary culturing and effects of insulin glargine on proliferation, differentiation of human preadipocytes from subcutaneous and omental adipose tissue]. To compare the morphological and functional differences of human primary preadipocytes from different fat depots and explore the effects of insulin glargine on their proliferation and differentiation. Primary preadipocytes isolated from human subcutaneous and omental adipose tissue by collagenase I were passaged in vitro.Inverted phase contrast microscope was used to observe the morphological differences of two kinds of preadipocytes. Then two kinds of preadipocytes were cultured or induced to differentiation with different doses of insulin glargine. The methyl thiazolyl tetrazolium (MTT) assay was used to detect their proliferative differences.Reverse transcription-polymerase chain reaction (RT-PCR) was used to observe the effects of insulin on adipogenic gene expression. (1) Both preadipocytes could be successfully cultured from adipose tissue and amplified in vitro.Subcutaneous preadipocytes were more slender and proliferated more quickly while omental preadipocytes were polygonal and aged easily.(2) MTT results showed that insulin glargine could inhibit the proliferation of omental preadipocytes in a dose-dependent fashion. After 72 h incubation, compared with negative control, the absorbance (A) value of 1000 nmol/L insulin glargine group decreased greatly (0.144 ± 0.021 vs 0.267 ± 0.040, P < 0.01). But it had no effect on subcutaneous preadipocytes (0.305 ± 0.045 vs 0.350 ± 0.037, P > 0.05). (3) Insulin at 500 nmol/L was a suitable concentration for inducing differentiation.RT-PCR analysis showed that, for subcutaneous adipocytes, adipogenic genes such as peroxisome proliferator-activated receptor gamma (PPARγ) (F = 31.31, P < 0.01) and CCAAT enhancer binding protein α (C/EBPα) (F = 9.86, P < 0.05) had the highest mRNA expression while preadipocytes gene Pref-1 had the lowest expression at this concentration. But insulin dose had no obvious effect on PPARγ or C/EBPα mRNA (P > 0.05) for omental adipocytes. Insulin glargine could inhibit the proliferation of omental preadipocytes, and enhance the differentiation of subcutaneous and omental preadipocytes.
{ "pile_set_name": "PubMed Abstracts" }
Representation of auditory-filter phase characteristics in the cortex of human listeners. Harmonic tone complexes with component phases, adjusted using a variant of a method proposed by Schroeder, can produce pure-tone masked thresholds differing by >20 dB. This phenomenon has been qualitatively explained by the phase characteristics of the auditory filters on the basilar membrane, which differently affect the flat envelopes of the Schroeder-phase maskers. We examined the influence of auditory-filter phase characteristics on the neural representation in the auditory cortex by investigating cortical auditory evoked fields (AEFs). We found that the P1m component exhibited larger amplitudes when a long-duration tone was presented in a repeating linearly downward sweeping (Schroeder positive, or m(+)) masker than in a repeating linearly upward sweeping (Schroeder negative, or m(-)) masker. We also examined the neural representation of short-duration tone pulses presented at different temporal positions within a single period of three maskers differing in their component phases (m(+), m(-), and sine phase m(0)). The P1m amplitude varied with the position of the tone pulse in the masker and depended strongly on the masker waveform. The neuromagnetic results in all cases were consistent with the perceptual data obtained with the same stimuli and with results from simulations of neural activity at the output of cochlear preprocessing. These findings demonstrate that phase effects in peripheral auditory processing are accurately reflected up to the level of the auditory cortex.
{ "pile_set_name": "PubMed Abstracts" }
Sofosbuvir/ledipasvir fixed-dose combination for treatment of chronic hepatitis C virus infection in children. The United States Food and Drug Administration recently approved sofosbuvir and the fixed-dose combination of ledipasvir/sofosbuvir for the treatment of hepatitis C virus (HCV) infection in children ages 12 to 17. These are the first direct-acting antiviral treatments approved for children and adolescents with HCV. Pharmacokinetic data confirm equivalent drug exposure in this population as that found in adults during clinical trials. The efficacy and safety of these drugs has been shown in clinical trials.
{ "pile_set_name": "PubMed Abstracts" }
The Moral Lives of Laboratory Monkeys: Television and the Ethics of Care. Why do lab monkeys watch TV? This essay examines the preponderance of televisions in primate housing units based in academic research laboratories. Within such labs, television and related visual media are glossed as part-and-parcel of welfare or species-specific enrichment practices intended for research monkeys, a logic that is simultaneously historically- and ontologically-based. In many research centers, television figures prominently in the two inseparable domains of a lab monkey's life: as a research tool employed during experiments, and in housing units where captive monkeys are said to enjoy watching TV during "down time." My purpose is not to determine whether monkeys do indeed enjoy, or need, television; rather, I employ visual media as a means to uncover, and decipher, the moral logic of an ethics of care directed specifically at highly sentient creatures who serve as human proxies in a range of experimental contexts. I suggest that this specialized ethics of animal care materializes Mattingly's notion of "moral laboratories" (Mattingly in Moral laboratories: family peril and the struggle for a good life, University of California Press, Berkeley, 2014), where television mediates the troublesome boundary of species difference among the simian and human subjects who cohabit laboratory worlds.
{ "pile_set_name": "PubMed Abstracts" }
A Rett syndrome patient with a ring X chromosome: further evidence for skewing of X inactivation and heterogeneity in the aetiology of the disease. Rett syndrome (RTT) is an X-linked neurodevelopmental disorder, characterised by regression of development in young females. Recently, mutations in the MECP2 gene were found to be present in 80% of sporadic cases, but in much lower frequency (< 30%) among familial cases. Several reports claim that the pattern of X chromosome inactivation (XCI) relates to the penetrance of RTT; in some cases skewed XCI is seen in Rett patients, and in others it is observed among normal carriers. We present here a case of RTT with a 46,X,r(X) in which complete skewed inactivation of the ring was demonstrated. Further, no mutations were found in the MECP2 gene present on the intact X. Our data, in conjunction with two previously published cases of X chromosome abnormalities in RTT, indicate that X chromosome rearrangements are sporadically associated with RTT in conjunction with extreme skewing of X inactivation. Based on our case and reported data, we discuss the evidence for a second X-linked locus for RTT associated with lower penetrance, and a different pattern of XCI, than for MECP2. This would result in a larger proportion of phenotypically normal carrier women transmitting the mutation for this putative second locus, and account for the minority of sporadic and majority of familial cases that are negative for MECP2 mutations.
{ "pile_set_name": "PubMed Abstracts" }
Preliminary study of the anaerobic bacteria isolated from subgingival plaque from sheep. A preliminary study was made to determine the genera of cultivable anaerobic bacteria which could be isolated from subgingival plaque of sheep. Samples were taken from 10 sheep on farms with a known record of broken mouth periodontitis. For assessment of the sampling technique, samples were also taken from freshly exposed tooth roots in killed sheep. The bacteria isolated on several selective and non-selective media were identified to genus level by a combination of Gram reaction, colony morphology and gas chromatographic analysis of volatile and non-volatile fatty acid metabolic end products. At least 10 different genera were isolated and these findings are discussed in relation to the bacteriology of human periodontitis and recent studies of sheep broken mouth periodontitis.
{ "pile_set_name": "PubMed Abstracts" }
Purification and characterisation of MHC class I antigen from rat liver with monoclonal antibody. We have described three monoclonal antibodies (HAM1, HAM2, and HAM3) to rat liver cell membrane glycoproteins. Recently also we reported another monoclonal antibody (HAM4) to rat hepato-renal membrane antigen. Using these monoclonal antibodies, it is possible to purify membrane antigens. This paper describes the details of the purification and the nature of the antigen purified with one of the monoclonal antibodies (HAM2) to rat liver cell membrane glycoproteins. Antigen was purified with immunoaffinity column. The amino acid composition was determined and compared with those of mice MHC class I antigen (H-2) and with the rat lymphocyte membrane antigens which were purified with monoclonal antibodies and of which amino acids compositions were determined.
{ "pile_set_name": "PubMed Abstracts" }
Polymorphisms in the apoptotic pathway gene BCL-2 and survival in small cell lung cancer. We investigated the single-nucleotide polymorphism C-938A in the apoptotic gene BCL-2 to assess the potential impact as a genetic marker for response to chemotherapy and outcome prediction in small cell lung cancer (SCLC) patients. Such a marker might help optimize lung cancer treatment in a tailored approach. DNA derived from peripheral blood lymphocytes of 188 Caucasian SCLC patients treated at the Thoraxklinik Heidelberg was genotyped. Chemotherapy response, time to progression (TTP), and overall survival (OS) were evaluated using multivariable regression (unconditional logistic for response and Cox proportional hazard for TTP and OS) with odds ratios and hazard ratios (HRs) and their 95% confidence intervals (CIs) as quantitative outcome measures, respectively. Small cell lung cancer patients carrying the BCL-2 -938CC genotype showed significantly worse TTP than patients carrying the BCL-2 -938AA genotype (HR = 1.86; 95% CI = 1.10-3.13, p = 0.021). The same adverse effect was shown for OS (HR = 2.38; 95% CI = 1.38-4.12, p = 0.002). Also, patients with limited disease (HR = 2.57; 95% CI = 1.18-5.60, p = 0.017) showed worse OS with the BCL-2 -938CC genotype. BCL-2 -938CC genotype shows significantly worse outcome in small cell lung cancer patients. This genetic marker might particularly impact on treatment strategies using BCL-2 antisense approaches.
{ "pile_set_name": "PubMed Abstracts" }
Pretherapeutic 124I dosimetry reliably predicts intratherapeutic blood kinetics of 131I in patients with differentiated thyroid carcinoma receiving high therapeutic activities. The aim of this study was to assess the agreement between predicted blood uptake values using I and actually measured I blood uptake values (reference) in patients with differentiated thyroid carcinoma receiving largely high therapeutic activities. Fourteen patients were analyzed retrospectively, who underwent a series of both pretherapeutic and intratherapeutic blood sampling using median I activities of 23 MBq and median therapy I activities of 10 GBq. Data of five blood samples from each patient were analyzed. Lin's concordance correlation coefficient analysis was carried out to assess the kinetic agreement. The time-integrated I activity coefficient (TIAC) for the blood compartment and the effective I clearance time (ECT), expressed as effective I half-life on the basis of a monoexponential model, were ascertained. For each patient, the (intrapatient) percentage differences between pretherapeutic and intratherapeutic TIACs and ECTs were calculated. The (interpatient) difference in TIACs and ECTs between pretherapy and intratherapy groups was evaluated using the Mann-Whitney U-test. Lin's concordance correlation coefficient was at least 0.97, indicating substantial kinetic agreement between pretherapeutic and intratherapeutic radioiodine kinetics. The mean (median)±SD (range) of the absolute percentage difference was 9% (11%)±7% (0.33-20%) for the TIAC and 11% (10%)±10% (0-23%) for the ECT. A slightly higher median TIAC was observed in intratherapy (2.8 vs. 3.3 h), but this was not statistically significant (P=0.15), whereas no remarkable ECT difference (P=0.62) was found. The pretherapeutic blood kinetics derived from diagnostic I activities provides a reliable estimation of the intratherapeutic I blood kinetics in patients receiving largely high therapy activities, showing its potential for radioiodine treatment planning.
{ "pile_set_name": "PubMed Abstracts" }
A systematic review of the diagnosis and treatment of patients with neurogenic hyperactivity of the detrusor muscle. Neurogenic detrusor hyperactivity (NDH) is a urodynamic observation characterised by involuntary detrusor contractions during the filling phase that are caused by an underlying neurological disease. The common and severe complications that can result from NDH warrant the preparation of healthcare protocols for the proper management of patients with NDH. The aim of this study is to standardise the criteria for the decision-making process in the management of patients with diagnosed or suspected NDH, providing personalised medical care. We performed a systematic noncomprehensive literature review on the aspects of the diagnosis and treatment of NDH. Based on the review, recommendations were issued by nominal consensus of a group of urology specialists. In general, the diagnosis of NDH is arrived at by a proper review of the medical history, physical examination and voiding diary before performing any diagnostic study. The main treatment objectives are to protect the upper urinary tract, restore function of the lower tract and improve these patients' continence and quality of life. The treatment consists of several steps aimed at obtaining proper bladder storage that allows for sufficiently spaced voidings. The follow-up should be personalised based on each patient's needs. The identification and management of NDH is important for positively redirecting the function of the lower urinary tract, in terms of filling and voiding, thereby improving the patients' quality of life.
{ "pile_set_name": "PubMed Abstracts" }
Regional alterations in blood-to-brain transfer of alpha-aminoisobutyric acid and sucrose, after chronic administration and withdrawal of dexamethasone. The effect of dexamethasone administration and withdrawal was studied with respect to blood-brain barrier function. The tracers alpha-[3H]aminoisobutyric acid (AIB) (MW 104) and [14C]sucrose (MW 342), which have a low permeability across the intact endothelium, were simultaneously injected intravenously in rats treated with dexamethasone and placebo-treated control animals or in rats in which dexamethasone treatment was discontinued 3 days before the experiment. Unidirectional transfer constants (Ki) were determined in discrete brain regions. Steroid administration reduced the rate of influx of AIB and sucrose, whereas discontinuation of drug resulted in an increased permeability. These findings suggest that when exposure to glucocorticoids is prolonged, the efficiency of medical treatment of CNS diseases may decrease due to reduction of drug delivery to CNS. Thus, these experimental findings may have particular importance in the clinical setting of drug administration when considering the combination of steroids with other drugs, and may aid in understanding better the pathogenesis of some types of brain edema seen in patients from whom corticosteroid therapy has been withdrawn.
{ "pile_set_name": "PubMed Abstracts" }
Role of NF-kappaB and PPAR-gamma in lung inflammation induced by monocyte-derived microparticles. Microparticles (MP) are phospholipid vesicles shed by cells upon activation or apoptosis. Monocyte-derived MP upregulate the synthesis of proinflammatory mediators by lung epithelial cells; the molecular bases of such activity are unknown. Peroxisome proliferator-activated receptors (PPAR) have been demonstrated to be involved in the modulation of nuclear factor (NF)-κB transcriptional activity and inflammation. We investigated whether the upregulation of the synthesis of proinflammatory cytokines by human lung epithelial cells induced by monocyte/macrophage-derived MP involves NF-κB activation and is modulated by PPAR-γ. MP were generated by stimulation of human monocytes/macrophages with the calcium ionophore, A23187. MP were incubated with human lung epithelial cells. NF-κB translocation was assessed by electrophoretic mobility shift assay. Interleukin (IL)-8 and monocyte chemotactic protein (MCP)-1 synthesis was assessed by ELISA and RT-PCR. Stimulation of A549 alveolar cells with monocyte/macrophage-derived MP caused an increase in NF-κB activation and IL-8 and MCP-1 synthesis that was inhibited by pre-incubation with the PPAR-γ agonists, rosiglitazone and 15-deoxy-Δ12,14-prostaglandin-J2. Parallel experiments with normal human bronchial epithelial cells largely confirmed the results. The effects of PPAR-γ agonists were reversed by the specific antagonist, GW9662. Upregulation of the synthesis of proinflammatory mediators by human lung epithelial cells induced by monocyte/macrophage-derived MP is mediated by NF-κB activation through a PPAR-γ dependent pathway.
{ "pile_set_name": "PubMed Abstracts" }
Metabolic activation and nucleic acid binding of acetaminophen and related arylamine substrates by the respiratory burst of human granulocytes. Following stimulation with phorbol myristate acetate, human granulocytes were found to incorporate acetaminophen, p-phenetidine, p-aminophenol, and p-chloroaniline into cellular DNA and RNA. Phenacetin was not incorporated into nucleic acid or metabolized by such activated granulocytes. None of the substrates gave nucleic acid binding if the granulocyte cultures were not induced to undergo the respiratory burst. Additional studies on the binding of acetaminophen to DNA and RNA were made by use of both ring-14C-labeled and carbonyl-14C-labeled forms of this substrate. The finding that equivalent amounts of these two labeled acetaminophen substrates were bound to cellular DNA demonstrated that the intact acetaminophen molecule was incorporated into DNA. On the other hand, the finding that excess ring-14C-labeled acetaminophen was incorporated into cellular RNA implies partial hydrolysis of the acetaminophen substrate prior to RNA binding. Evidence was presented which strongly indicates that the nucleic acid binding of the substrates was covalent in nature. The inability of the respiratory burst to result in the binding of phenacetin to nucleic acid suggests that arylamides are not normally activated or metabolized by activated granulocytes. Acetaminophen is an exception to the recalcitrance of arylamides to such bioactivation processes because it also possesses the phenolic functional group, which, like the arylamine group, is oxidized by certain reactive oxygen species. Myeloperoxidase appears to be much more important in the binding of acetaminophen to DNA than it is in the DNA binding of arylamines in general. The role of the respiratory burst in causing the bioactivation of certain arylamines, which are not normally genotoxic via the more usual microsomal activation pathways, was extended to include certain amide substrates such as acetaminophen.
{ "pile_set_name": "PubMed Abstracts" }
Hormonal changes and mood in the puerperium. This investigation is an attempt to test the common supposition that postpartum emotional disturbance is related to hormone changes. A group of 27 normal pregnant women were assessed three times before delivery and sixteen times in the six weeks following delivery. During the first two interviews baseline data on personality and other personal variables were obtained. On each occasion blood was taken and three measures of clinical status and mood were completed. Plasma LH, FSH, total oestrogen and progesterone results are presented in detail and the results of prolactin assays mentioned more briefly. An attempt to correlate hormone findings and clinical findings is described. This failed to produce any strong evidence that hormones are related to mood at this time, although hormone changes were correlated weakly with a few specific symptoms. Some of the unexpected clinical findings and technical difficulties of the study are discussed, with special reference to possible further research in this area.
{ "pile_set_name": "PubMed Abstracts" }
Fasciola hepatica: immunoprecipitation analysis of biosynthetically labelled antigens using sera from infected sheep. The antigenicity of the biosynthetically labelled somatic and excretory/secretory proteins of adult Fasciola hepatica was investigated over 20 weeks of an infection with F. hepatica in sheep. The antibody response was initially detected by ELISA 2 weeks after infection, and was sustained at this level for the remainder of the infection. Immunoprecipitation analysis indicated that a large number of proteins were recognized by the sheep, with several dominant antigens occurring in the 29-31 kilodalton molecular weight range. No differences were found between the antigens recognized by sheep in the early or late stages of infection suggesting that there are similarities between the antigens of the immature and mature forms of the parasite.
{ "pile_set_name": "PubMed Abstracts" }
[Multicenter prospective epidemiological studies on Haemophilus influenzae infection among hospitalized children with lower respiratory tract infections]. To understand epidemiological characteristics of Haemophilus influenzae (Hi) infection in hospitalized children with lower respiratory tract infection (LRTI) in west Sichuan China. The multicenter prospective cross-sectional design was used; four hospitals in west Sichuan China were chosen as research field, sputum bacterial culture was done and biological typing, PCR identification and drug sensitivity test of Hi epidemic strains were carried out among 0-17y hospitalized patients with LRTI in four hospitals located in west Sichuan China. Totally 5 748 cases with LRTI in four hospitals were investigated in west Sichuan from Nov. 2013 to April 2014 and the rate of sputum culture was 46.96% (2,699/5 748). The total pathogenic bacteria positive rate of sputum culture was 43.53% (1,175/2 699), and 279 Haemophilus influenzae (Hi) strain in 272 cases were isolated, the Hi positive rate was 10.08% (272/2 699). All the strains (100%) were non-typeable Haemophilus influenzae (NTHi ) indentified by PCR. The main biotype of 279 strains was type Ⅰ with 39.07% (109/279) and type Ⅳ with 50.90% (142/279) ; 272 cases were enrolled in this survey, 12.50% (34/272) had broncheolitis, the rest of lower respiratory infection was 87.50 % (238/272), and 2.57% (7/272) was neonatal pneumonia, 2.21%(6/272)was pneumonia complicated with sepsis; in four hospitals the overall positive rate of Hi in inpatients with lower respiratory infection was 10.21%, 28.96%, 4.80%, 10.21% (χ(2) = 112.561, P = 0.000) and the positive rate of Hi inpatients with broncheolitis was 11.92%, 20.93%, 4.76%, and 66.67% (Fisher exact probability P = 0.001), with the rest lower respiratory infection was 9.96%, 30.90%, 4.81%, 9.85% (χ(2) =108.876, P = 0.000); 2.87% (8/279) bacterial strains of β-lactamase-nonproducing-ampicillin-intermediary (BLNAI) distributed in four hospitals, and 1.79% (5/279) bacterial strains of β-lactamase-nonproducing-ampicillin-resistant (BLNAR), 0.72% (2/279) bacterial strains of β-lactamase-positive amoxicillin-clavulanate-resistance (BLPACR) were found in two hospitals respectively. All the Hi isolated from sputum were non-typeable among 0-17y inpatients with LRTI and the main biotype were type Ⅰ and type Ⅳ in west Sichuan China. Much attention should be paid to BLNAR and BLPACR strains found in the west Sichuan region.
{ "pile_set_name": "PubMed Abstracts" }
Synthesis, colon-targeted studies and pharmacological evaluation of an anti-ulcerative colitis drug 4-Aminosalicylic acid-β-O-glucoside. A glycoside prodrug of 4-aminosalicylic acid (4-ASA) with d-glucose was synthesized for targeted drug delivery to inflammatory bowel. The in vitro assessment of 4-aminosalicylic acid-β-O-glucoside (4-ASA-Glu) as a colon-specific prodrug was studied using colitis rat with the healthy one as control. The stability studies in aqueous buffers (pH 1.2, 6.8 and 7.4) indicated that 4-ASA-Glu was stable over a period of 12 h. The incubation of 4-ASA-Glu with cecal or colonic contents of healthy rats at 37 °C released 4-ASA in 77 or 80% of the dose in 12 h, respectively. The amount of 4-ASA liberated from the incubation of 4-ASA-Glu in cecal or colonic contents of colitis rats at 37 °C was 69 or 79% in 12 h respectively, while less than 9% 4-ASA was detected from the incubation of 4-ASA-Glu with the homogenates of stomach or small intestine. The curative effect of 4-ASA-Glu was evaluated in 2, 4, 6-trinitrobenzenesulfonic acid (TNBS) induced experimental colitis model in male Sprague-Dawley (SD) rats. It was found that 4-ASA-Glu possess significantly ameliorate effect than sulfasalazine, oral 4- and 5-aminosalicylic acid.
{ "pile_set_name": "PubMed Abstracts" }
Frontal functions in juvenile myoclonic epilepsy. The authors investigated cognition in juvenile myoclonic epilepsy (JME), focusing on frontal functions as suggested by maximal spatial distribution of epileptiform activity seen over frontocentral regions. Fifteen patients with JME (mean age, 34.3 years; mean estimated IQ 101) were administered a battery of tests sensitive to frontal dysfunction. The number of patients with impaired test performance and the frequency of impairment per test were calculated. Performance on selected tests was compared with that of 15 patients with temporal lobe epilepsy (TLE) who were matched for estimated IQ using paired t-tests. Although the performance of the group with JME was not uniform--some patients showed marked impairment whereas others showed little or no deficit--a high frequency of impairment was found on tests of concept formation-abstract reasoning and mental flexibility, cognitive speed, and planning and organization. Significant differences were found between the group with JME and the group with TLE on tests requiring mental flexibility and concept formation-abstract reasoning. In conjunction with studies demonstrating intractable seizures in approximately 20% of patients, the results from this study suggest that JME is not a uniformly benign condition. Frontal deficits may have maladaptive behavioral consequences suggestive of personality dysfunction, as described anecdotally by previous investigators.
{ "pile_set_name": "PubMed Abstracts" }
Tackling dementia. DISCHARGE PLANNING for patients with dementia can be difficult enough when arranging local services, so imagine trying to organise a care package for a patient being discharged to the US. This is exactly what leading dementia nurse Jeni Bell did when the daughter of a patient came to one of the cafés she runs to support the carers of patients with dementia at University Hospital Southampton NHS Foundation Trust.
{ "pile_set_name": "PubMed Abstracts" }
[Inflammatory abdominal aortic aneurysm]. The reported incidence of inflammatory abdominal aortic aneurysm (IAAA) is from 2% to 14% of patients with abdominal aortic aneurysm and the etiology of this disease is still discussed--according to the literature several pathogenic theories have been proposed. From 1992 to 1997 32 patients with IAAA were operated on. The patients were mostly symptomatic--abdominal pain was present in 68.75% cases, back pain in 31.25%, fever in 12.5% and weight loss in 6.25% of the operated patients. In all the patients ultrasound examination was performed, in 4 patients CT and in 3 cases urography. All the patients were operated on and characteristic signs of inflammatory abdominal aortic aneurysm like: thickened aortic wall, perianeurysmal infiltration or retroperitoneal fibrosis with involvement of retroperitoneal structures were found. In all cases surgery was performed using transperitoneal approach; in three cases intraoperatively contiguous abdominal organs were injured, which was connected with their involvement into periaortic inflammation. In 4 cases clamping of the aorta was done at the level of the diaphragmatic hiatus. 3 patients (9.37%) died (one patient with ruptured abdominal aortic aneurysm). Authors present diagnostic procedures and the differences in the surgical tactic, emphasizing the necessity of the surgical therapy in patients with inflammatory abdominal aortic aneurysm.
{ "pile_set_name": "PubMed Abstracts" }
[Surgical discovery of parathyroid glands and the recurrent laryngeal nerve. Application of well known embryological concepts in the operating room]. Surgery for thyroid or parathyroid glands has to be logical. It is based upon a precise knowledge of the development of the 3rd and 4th pharyngeal pouches and aortic arches. Pharyngeal pouches are endodermal derivatives of the lateral walls of the early foregut. Parathyroid glands have an ectodermal origin in concert with inductive forces of cells derived from the neural crest (which also creates parafollicular cells secreting calcitonin). From the third pouch thymus and parathyroid III move down together because of the cervical flexure and heart's "descent" (stages 14 to 20 mm). The fourth pouch gives rise to the so called "caudal pharyngeal complex" constituted by parathyroid IV dorsally, a "lateral thyroid" ventrally and an ultimo-branchial body derived from the fifth pouch. The thyroid gland first appears at the 4th week as a thickening of the endoderm of the floor of the pharynx which evaginates as a diverticulum in front of the trachea below. This medial component of the thyroid joins both lateral thyroids derived from the caudal pharyngeal complexes to form a bi-lobed structure with an isthmus. The lateral edge of the adult thyroid lobe has a thickening which is called Zuckerkandl's tuberculum because of the fusion of the ultimobranchial body into the principal médial thyroid process. This tuberculum lies in front of the caudal thyroid artery born from the 4th aortic arch. The recurrent laryngeal nerve courses round the 4th aortic arch: therefore parathyroids IV have to be above and behind the nerve and parathyroids III below and in front of the nerve.(ABSTRACT TRUNCATED AT 250 WORDS)
{ "pile_set_name": "PubMed Abstracts" }
Gangrene in the diabetic foot: its implications and consequences. Diabetic problems of the feet are not uncommon. Occasionally, these difficulties progress to the point where surgical intervention is required. A case was presented which involved a deep abscess of the foot that compromised the circulation to the toe. Ultimately, open toe amputation was necessary. The etiologic factors causing diabetic complications were presented and the importance of each was stressed. The preoperative considerations for surgical amputation and debridement were defined, as well as the possibility for successful healing.
{ "pile_set_name": "PubMed Abstracts" }
Monocyte lipid rafts contain proteins implicated in vesicular trafficking and phagosome formation. Lipid rafts are membrane microdomains of unique lipid composition that segregate proteins with poorly understood consequences for membrane organization. Identification of raft associated proteins could therefore provide novel insight into raft-dependent functions. Monocytes process antigens for presentation to T cells by ingesting pathogens into calcium-dependent plasma membrane invaginations called "phagosomes" which develop by sequential fusion with the endoplasmic reticulum, early and late endosomes. We investigated the protein composition of Triton X-100 insoluble low density membranes of the monocyte cell-line THP-1 by matrix-assisted laser desorption/ionization-time of flight and tandem mass spectrometry. The ganglioside GM1 colocalized on the plasma membrane with the raft markers flotillin 1 and 2, which were enriched in low buoyant density fractions containing 52 identifiable proteins, 28 of which have not been reported in rafts, and nine of which are associated with the endoplasmic reticulum (ER). Remarkably, 27 of the 52 proteins are components of phagosomes, including the ER protein calnexin which we demonstrate is phosphorylated on serine 562, a switch controlling calcium homeostasis. The presence of the early and late endosome trafficking proteins Rab-1, and Rab-7 together with the late endosome protein LIMPII, indicate lipid rafts are present throughout endosome maturation. Identification of vacuolar ATP synthase, and synaptosomal-associated protein-23, proteins implicated in membrane fusion, together with the cytoskeletal proteins actin, alpha-actinin, and vimentin, and Rac 1, 2, and 3, regulators of cytoskeletal assembly, indicate monocyte lipid rafts contain the machinery to direct vesicular fusion and actin based vesicular migration throughout phagosome development.
{ "pile_set_name": "PubMed Abstracts" }
Laparoscopic cholecystectomy by ultrasonic dissection without cystic duct and artery ligature. Laparoscopic cholecystectomy (LC) is the gold standard treatment of gallstones. Nevertheless, there are some pitfalls due to the limits of current technology and the use of inappropriate ligature material, with a relevant risk of injuries and postoperative, mainly biliary, complications. Ultrasonically activated scissors may divide both vessels and cystic duct, with no need of further ligature, and possibly reduce the risk of thermal injuries. A prospective nonrandomized clinical trial was started in 1999 to test harmonic shears (Ultracision, Ethicon Endo-Surgery, Cincinnati, OH, USA) in 461 consecutive patients undergoing LC in order to evaluate the theoretical benefits of ultrasonic dissection and the possible reduction in intraoperative bile duct injuries (BDIs) and postoperative complications. Patients were divided in two groups: in group 1 (HS; 331 patients) the operation was performed by Ultracision (including coagulation-division of cystic duct and artery); in group 2 (LOOP; 130 patients) the cystic duct, after coagulation-division by harmonic scissors, was further secured with an endo-loop. Both groups were further divided into two subgroups: expert and surgeon-in-training. The following categories of data were collected and analyzed: individual patient data, indication for laparoscopic cholecystectomy, surgical procedure data (associated procedures, intraoperative cholangiography, intraoperative complications, length of surgery, and conversion to open), and postoperative course data (postoperative morbidity, postoperative mortality, reinterventions, and postoperative hospital stay). Furthermore, biliary complications were analyzed as a single parameter comparing the incidence within groups and subgroups. Cumulative complications (intraoperative and postoperative) were also analyzed as a single parameter comparing their incidence in the series of each surgeon within the surgeon-in-training subgroup to the average results of the expert subgroup. Finally, length of surgery, postoperative complication rate, and length of postoperative hospital stay within subgroups were analyzed to evaluate the learning curve. Overall conversion rate was 0.87%. The mean operating time was 76.8 min (median, 70 min) in group 1 and 97.5 min (median 90 min) in group 2. BDI occurred in 1 case (0.32%) in the surgeon-in-training subgroup. Overall BDI rate was 0.22% (1/461). The overall incidence of postoperative bile leak was 2.7% (9 patients of subgroup 1 and 1 patient of subgroup 2). Clinical observation with spontaneous resolution occurred in 4 patients, and in 1 case the management consisted in an endoscopic biliary drainage; surgery was requested in the remaining cases. A laparoscopic approach was successfully attempted in all cases. Overall morbidity rate was 8.76% in group 1 and 13.84% in group 2. Rates of major complications, overall biliary complication, and postoperative bile leaks within the expert and surgeon-in-training subgroup differ significantly (p = 0.026, p = 0.03, and p = 0.049, respectively). There was 1 death (0.22%) due to sepsis that resulted from a small bowel injury by trocar insertion. Mean postoperative stay was 4.28 days for group 1 and 5.05 days for group 2. No significant difference was found in both patient groups regarding postoperative mortality and complications, biliary complications, and especially cystic duct leaks. A retrospective comparison of literature data showed that use of ultrasonic dissection during LC seems to reduce the risk of BDI. Nevertheless, a learning curve in the use of ultrasonic-activated devices is required: a significant differences in postoperative major complications and biliary complications between the expert and the surgeon-in-training subgroups was shown. Furthermore, ultrasonic scissors misuse may cause bowel injuries in patients with severe adhesions, and this could represent a possible limitation for surgical safety.
{ "pile_set_name": "PubMed Abstracts" }
Potassium channels: gene family, therapeutic relevance, high-throughput screening technologies and drug discovery. Existing drugs that modulate ion channels represent a key class of pharmaceutical agents across many therapeutic areas and there is considerable further potential for potassium channel drug discovery. Potassium channels represent the largest and most diverse sub-group of ion channels and they play a central role in regulating the membrane potential of cells. Recent advances in genomics have greatly added to the number of these potential drug targets, but selecting a suitable potassium channel for drug discovery research is a key step. In particular, the potential therapeutic relevance of a potassium channel should be taken into account when selecting a target for screening. Potassium channel drug discovery is being driven by a need to identify lead compounds that can provide tractable starting points for medicinal chemistry. Furthermore, advances in laboratory automation have brought significant opportunities to increase screening throughput for potassium channel assays, but careful assay configuration to model drug-target interactions in a physiological manner is an essential consideration. Several potassium channel screening platforms are described in this review in order to provide some insight into the variety of formats available for screening, together with some of their inherent advantages and limitations. Particular emphasis is placed on the mechanistic basis of drug-target interaction and those aspects of structure/function that are of prime importance in potassium channel drug discovery.
{ "pile_set_name": "PubMed Abstracts" }
Comparison of nuchal translucency measurement and second-trimester triple serum screening in twin versus singleton pregnancies. Maternal serum screening for Down syndrome (DS) in twin pregnancies poses difficulties due to a lack of precise biochemical information about each co-twin. The current study attempts, for the first time, to compare two screening methods: nuchal translucency (NT) measurement and serum screening for DS, in twin pregnancies. 60 women with twin pregnancies (study group) underwent both first-trimester NT scanning and mid-trimester triple-marker serum screening, and were followed throughout their gestation. Nuchal translucency measurements were compared with a matched control of 120 singleton pregnancies with a similar (+/-2 years) maternal age and fetal crown-rump length (CRL) (+/-3 mm). In both analyses, a risk of 1:380, or higher, of having a DS newborn was considered screen positive. Both mean maternal age (31+/-3 years) and CRL (62+/-11 mm) were similar in the study and control groups. The median NT measurement expressed as multiples of the median (MOM) for CRL was similar in the study and control groups (0.85 and 0.88, respectively). Based on NT measurements, 5 per cent of the pregnancies in the study group and 2.5 per cent in the control group were defined as screen positive (p =N. S). Mid-gestation serum screening was associated with 15 per cent and 6 per cent screen-positive rate in study and control groups, respectively (p<0. 05). There was a ratio of 1:3 screen-positive rate between first and second-trimester screening tests within the study group. This high false-positive rate results led to 18.3 per cent amniocentesis rate in the study group compared with 7.5 per cent of the control group (p<0.03). Only one co-twin which was picked up by the NT screen was further diagnosed as trisomy 21, and one co-twin with cardiac and neural tube defect was missed by the two screening tests and was later picked up in an anomaly scan. Although the current series is too small to provoke any changes in screening practice, when twin pregnancies are diagnosed, it seems very reasonable to offer them NT measurement. A larger group may be needed to clarify which approach is the most beneficial screening policy for this highly selected group of pregnant women.
{ "pile_set_name": "PubMed Abstracts" }
Character congruence of multiple data partitions and the origin of the Hawaiian Drosophilidae. We address two systematic questions, the origin and monophyly of the Hawaiian Drosophilidae and the question of how to analyze multiple data partitions containing disparate kinds of information, in this study. New evidence, from analysis of characters from morphology, mitochondrial DNA, and nuclear DNA suggests that the Hawaiian Drosophilidae are a monophyletic assemblage. Although we are not able to suggest a single species group which may represent the continental sister taxon to the Hawaiian Drosophilidae, the candidates suggested by our analysis, the melanicarobusta lineage and the virilis-repleta lineage, have been suggested by other investigators as probable sister taxa. Through analyses of our data partitions separately and in a variety of combinations, we conclude that the best phylogenetic hypothesis to be generated from multiple data partitions will be obtained if the data from these partitions are combined and analyzed simultaneously. We advocate performing tests for congruence between and among data partitions not to justify keeping them apart, but for understanding the interactions among the signals included in the analysis and how they affect the topology of, and support for, the total evidence tree.
{ "pile_set_name": "PubMed Abstracts" }
The tip-of-the-tongue phenomenon: do experimenter-presented interlopers have any effect? When a person is in a tip-of-the-tongue (TOT) state, they will sometimes recall a word that is similar in sound to the word they are attempting to retrieve. Woodworth (1929) argued that these interloper words both cause and sustain TOT states, whereas Brown and McNeill (1966) suggested that they are part of the process that leads to TOT resolution. Jones and Langford (1987) and Jones (1989) explicitly presented interloper words along with definitions of words that subjects were asked to recall. They reported that interlopers that were phonologically related to the target word increased the incidence of TOTs and concluded that this supported Woodworth's position. In three experiments, we adopted the interloper paradigm, but also included a control group who heard the definitions without interloper words. In Experiment 1, the definitions that Jones used with phonological interlopers created more TOTs even when no interlopers were presented. In Experiments 2a and 2b, we matched definitions for the number of TOTs they produced in the absence of interlopers. Under these circumstances we found no effect of interloper words at all. We conclude that there is no evidence from this paradigm to support the idea that interloper words are involved in either the causation or resolution of TOTs.
{ "pile_set_name": "PubMed Abstracts" }
Elemental-tagged immunoassay combined with inductively coupled plasma mass spectrometry for the detection of tumor cells using a lead sulfide nanoparticle label. This work reports an efficient, specific and sensitive immunoassay protocol for detection of tumor cells by using inductively coupled plasma mass spectrometry (ICP-MS) with lead sulfide nanoparticles (PbS NPs) as the elemental tags. PbS NPs conjugated with anti-EpCAM target the HepG2 cells with high affinity and specificity. The conditions of the ICP-MS based immunoassay for the detection of HepG2 cells were carefully optimized, including the incubation time, the concentration of the labeling probe, and the elution conditions. Under the optimized conditions, the limit of detection of 282 HepG2 cells and the linear range of 800-40,000 were obtained, and the relative standard deviation for seven replicate determinations of 3000 HepG2 cells was 5.0%. The proposed method has numerous advantages, including ease of preparation, high sensitivity and selectivity. Importantly, this methodology could be extended to the detection of other cells based on their cellular biomarkers.
{ "pile_set_name": "PubMed Abstracts" }
Identification of degradation products of ionic liquids in an ultrasound assisted zero-valent iron activated carbon micro-electrolysis system and their degradation mechanism. Ionic liquids (ILs) have potential applications in many areas of chemical industry because of their unique properties. However, it has been shown that the ILs commonly used to date are toxic and not biodegradable in nature, thus development of efficient chemical methods for the degradation of ILs is imperative. In this work, degradation of imidazolium, piperidinium, pyrrolidinium and morpholinium based ILs in an ultrasound and zero-valent iron activated carbon (ZVI/AC) micro-electrolysis system was investigated, and some intermediates generated during the degradation were identified. It was found that more than 90% of 1-alkyl-3-methylimidazolium bromide ([Cnmim]Br, n = 2, 4, 6, 8, 10) could be degraded within 110 min, and three intermediates 1-alkyl-3-methyl-2,4,5-trioxoimidazolidine, 1-alkyl-3-methylurea and N-alkylformamide were detected. On the other hand, 1-butyl-1-methylpiperidinium bromide ([C4mpip]Br), 1-butyl-1-methylpyrrolidinium bromide ([C4mpyr]Br) and N-butyl-N-methylmorpholinium bromide ([C4mmor]Br) were also effectively degraded through the sequential oxidization into hydroxyl, carbonyl and carboxyl groups in different positions of the butyl side chain, and then the N-butyl side chain was broken to form the final products of N-methylpiperidinium, N-methylpyrrolidinium and N-methylmorpholinium, respectively. Based on these intermediate products, degradation pathways of these ILs were suggested. These findings may provide fundamental information on the assessment of the factors related to the environmental fate and environmental behavior of these commonly used ILs.
{ "pile_set_name": "PubMed Abstracts" }
Isoelectric focusing in cyclic olefin copolymer microfluidic channels coated by polyacrylamide using a UV photografting method. As an alternative material to glass or silicon, microfluidic devices made from a cyclic olefin copolymer (COC) were fabricated. This material is of interest because of the relative ease of fabrication, low costs, and solvent resistance. However, as a result of the strong hydrophobic interactions normally present, COC surfaces are not suitable for protein separations. To reduce the protein adsorption and make COC suitable for protein separations, UV-initiated grafting of polyacrylamide was used to coat the surface of COC devices. The change in surface properties caused by different graft times was studied. The surface hydrophilicity and electroosmotic mobility were characterized by contact angle and electroosmosis measurements. Isoelectric focusing was performed to test protein separations in polyacrylamide-coated COC microchannels. A single protein, carbonic anhydrase, was used to analyze the focusing effects and peak capacities in uncoated and polyacrylamide-coated COC devices. Peak capacities ranging from 75 to 190 were achieved with a polyacrylamide-coated surface. A mixture of two proteins, conalbumin labeled with Alexa Fluor 488 and beta-lactoglobulin A labeled with Alexa Fluor 546, was used to test protein separations. Linear and rapid separation of proteins was achieved in the polyacrylamide-coated COC microfluidic device.
{ "pile_set_name": "PubMed Abstracts" }
Abnormalities in periodontal and salivary tissues in conditional presenilin 1 and presenilin 2 double knockout mice. We used forebrain-specific conditional presenilin 1 (PS1) and presenilin 2 (PS2) double knockout mice (dKO mice), which exhibit neurodegenerative disease-like symptoms, including inflammation of the brain and periphery, to investigate whether periodontal and salivary tissues display alterations. Mandibles were dissected for alveolar bone height analysis. Maxillae were fixed and decalcified for histological observation and osteoclast detection. Submandibular glands were fixed for histological observation. The submandibular gland and the gingiva of the mandibular incisor teeth were used to assay inflammatory mediators. At 9 months, the number of osteoclasts had significantly increased in the periodontal ligament and the periodontal tissues exhibited obvious histomorphological abnormalities in the dKO mice compared to the control mice at the same age. Alveolar bone loss in dKO mice increased with age. The salivary tissues in dKO mice exhibited obvious age-dependent histomorphological abnormalities. The levels of the inflammatory mediators IL-1β, TNF-α, and GM-CSF in the submandibular gland and gingiva also increased in an age-dependent manner. These findings suggest that inflammation in the dKO brain could expand to the periphery, including the oral tissue, which could ultimately induce abnormalities in the periodontal and salivary tissues.
{ "pile_set_name": "PubMed Abstracts" }
Long-term cryopreservation of non-spore-forming fungi in Microbank™ beads for plant pathological investigations. Long-term preservation of experimental fungi without genetic, morphological, and pathogenic changes is of paramount importance in mycological and plant pathological investigations. Several cryogenic and non-cryogenic methods are available for the preservation of fungi, but the methods can be cumbersome, hazardous, expensive, and often not suitable for long-term storage of non-spore-forming (sterile) fungi. A method of preservation of spore-forming fungi in commercially available porous beads (Micrbank™) under cryogenic condition was successfully tested for three non-spore-forming basidiomycetes genera: Rhizoctonia solani (teleomorph: Thanatephorus cucumeris) (n = 19), Ceratobasidium species (n = 1), and Waitea circinata (n = 3), and a non-spore forming ascomycetes, Sclerotinia sclerotiorum (n = 1). For comparison, spore-forming ascomycetous fungi, Alternaria alternata (n = 1), Bauveria basiana (n = 2), Botrytis cinerea (n = 1), Fusarium oxysporum f.sp. gladiolii (n = 1), Trichoderma spp. (n = 3), and Thielaviopsis basicola (n = 2) were also cryopreserved in Microbank beads. Viable fungal isolates of all test species were retrieved after five years of storage at -80 °C, which was longer than the viabilities of the corresponding isolates cryopreserved in agar plugs or colonized wheat seeds. Fungi revived from the Microbank beads maintained identical morphology and cultural characteristics of the parent isolates. Randomly selected Rhizoctonia isolates revived from the Microbank beads maintained respective pathological properties of the parent isolates; also, no mutation was detected in the internal transcribed spacer (ITS) ribosomal DNA when compared with respective cultures maintained at ambient temperature. This finding demonstrated the utility of cryopreservation in Microbank beads as a convenient alternative to conventional long-term preservation of a wide group of fungal cultures for plant pathological investigations and serves as the first report of using porous beads under cryogenic conditions for long-term storage of sterile fungi.
{ "pile_set_name": "PubMed Abstracts" }
CHANGING INFUSION PRACTICE GENERATES SIGNIFICANT EFFICIENCIES IN NURSING TIME AND RESOURCE USAGE IN PAEDIATRIC INTENSIVE CARE. Infusion preparation in British PICUs uses the Rule of Six (ROS) which was developed for administration without infusion devices. This method is inaccurate.1 Regulators recommend standardised approaches to IV infusions to improve patient safety and quality of care.2 Administration set changes also have an association with resource use and central line infections.3 We report the impact of fixed concentration infusions and reduced administration set changes on nursing time and infusion equipment cost. Morphine and midazolam infusions were standardised in September 2014. Direct observation of infusion preparation was carried out beforeand after the introduction of fixed-concentration (FC) infusions to quantify the nursing time required to prepare infusions. Administration was prospectively documented using purposive sampling until a population-representative sample for age and weight was obtained (1 month). This data was then scaled up to predict activity over one year. Syringe use and administration set use was calculated. Reducing frequency of administration set changes to 72 hrs in accordance with infection control policy was then calculated retrospectively. It takes 40 minutes (2 nurses×20 minutes) to prepare ROS syringes and 30 minutes (2 nurses×15 minutes) for FC syringes.In total ROS infusions required 2433 hrs of nursing time to prepare. FC infusions reduced this time by 25% (608 hrs) releasing 0.5 WTE nursing time back to patient care.Mean duration of IV sedation in these patients was 100 hrs. The cost associated with replacing administration sets with each syringe was £16,060. By changing every 72 hrs, this cost is reduced to £4,400 - a cost saving of £11,660. FC syringes are more efficient than ROS. FC preparations have released 0.5 WTE nurses back to patient care. Changing administration sets 72 hrly realises significant cost efficiencies.
{ "pile_set_name": "PubMed Abstracts" }
Metabolomics reveals novel biomarkers of illegal 5-nitromimidazole treatment in pigs. Further evidence of drug toxicity uncovered. The aim of the study was to investigate the potential of a metabolomics platform to distinguish between pigs treated with ronidazole, dimetridazole and metronidazole and non-medicated animals (controls), at two withdrawal periods (day 0 and 5). Livers from each animal were biochemically profiled using UHPLC-QTof-MS in ESI+ mode of acquisition. Several Orthogonal Partial Least Squares-Discriminant Analysis models were generated from the acquired mass spectrometry data. The models classified the two groups control and treated animals. A total of 42 ions of interest explained the variation in ESI+. It was possible to find the identity of 3 of the ions and to positively classify 4 of the ionic features, which can be used as potential biomarkers of illicit 5-nitroimidazole abuse. Further evidence of the toxic mechanisms of 5-nitroimidazole drugs has been revealed, which may be of substantial importance as metronidazole is widely used in human medicine.
{ "pile_set_name": "PubMed Abstracts" }
Vanadate is a potent (Na,K)-ATPase inhibitor found in ATP derived from muscle. A potent (Na,K)-ATPase inhibitor purified from "Sigma Grade* ATP has been identified as vanadium using electron probe microanalysis and confirmed by microwave-induced emission spectroscopy and electron paramagnetic resonance spectroscopy. Sodium orthovanadate (Na3 VO4) is identical with the purified inhibitor with respect to ultraviolet absorbance, migration on thin layer chromatography, and inhibition of (Na,K)-ATPase. The (Na,K)-ATPase is in-inhibited 50% by 40 nM Na3 VO4 under optimal conditions (28 mM Mg2+) and the inhibition is 100% reversible by millimolar concentrations of norepinephrine. The physiological significance of this inhibition is discussed in relation to vanadium concentrations in vivo.
{ "pile_set_name": "PubMed Abstracts" }
The active species of "CO2" utilized in ferredoxin-linked carboxylation reactions. The active species of "CO2", i.e. CO2 or HCO-3(H2CO3) utilized by enzymes catalyzing ferredoxin-linked carboxylation reactions was determined. The enzyme investigated was pyruvate synthase from Clostridium pasteurianum (EC 1.2.7.1; Pyruvate: ferredoxin oxidoreductase). Data were obtained which were compatible with those expected if CO2 is the active species. The dissociation constant (Ks) of the enzyme-CO2 complex was measured. At pH 7.2 Ks for CO2 of pyruvate synthase was found to be approximately 5 mM.
{ "pile_set_name": "PubMed Abstracts" }
[Cefotiam passage into the maxillary sinus tissues]. Clinical study was made on cefotiam (CTM) and the following results were obtained. Tissue concentrations of CTM were determined 1 hour after intravenous injection (CTM 1 g) in chronic sinusitis and maxillary cyst. Concentrations of CTM were 16.53 micrograms/g, 13.26 micrograms/g in mucosa of the maxillary sinus, maxillary cyst, respectively. Antibacterial activity of CTM was measured on Escherichia coli, Staphylococcus epidermidis, Aerococcus, Acidaminococcus fermentans, Peptostreptococcus anaerobius; that were isolated from pus of maxillary sinus. The highest MIC on them was 3.13 micrograms/ml.
{ "pile_set_name": "PubMed Abstracts" }
Triterpenoid saponins from Acacia victoriae (Bentham) decrease tumor cell proliferation and induce apoptosis. This report describes the isolation and partial purification of novel triterpenoid saponins [Fraction 35 (F035)] and two pure biologically active derivatives (termed avicins D and G) from Acacia victoriae, an Australian desert tree of the Leguminosae family. F035 and the avicins markedly inhibited the growth of several tumor cell lines with minimum growth inhibition in human foreskin fibroblasts, mouse fibroblasts, and immortalized breast epithelial cells at similar concentrations. F035 and the avicins induced cell cycle (G1) arrest of the human MDA-MB-453 breast cancer cell line and apoptosis of the Jurkat (T-cell leukemia) and the MDA-MB-435 breast cancer cell line. The triterpenoid saponins also partially inhibited phosphatidylinositol 3-kinase activity in Jurkat T cells in a time-dependent manner and phosphorylation in the downstream protein Akt, whereas no affect was seen on the Ras/mitogen-activated protein kinase cascade. These observations as well as other work from our laboratory demonstrating mitochondrial perturbation, chemoprevention, and inhibition of nuclear factor kappaB suggest that triterpenoid saponins from A. victoriae have potential as novel anticancer agents. Recent work linking Akt signaling with glucose metabolism, stress resistance, and longevity suggests other potential applications of these compounds.
{ "pile_set_name": "PubMed Abstracts" }
[Rapid identification of clinical yeast species by single-strand conformation polymorphism analysis of 26S rDNA D1/D2 domain]. To investigate the reliability of single-strand conformation polymorphism (SSCP) analysis of 26S rDNA D1/D2 domain for rapid identification of clinical yeast species and to examine the distribution of the yeast species in clinical strains from Beijing. Type and authentic strains of five common pathogenic yeast species were used as references. Approximately 260 yeast strains with diversified clinical origins were collected from four hospitals located in Beijing. The 26S rDNA D1/D2 domain of each strain was amplified by PCR and subjected to SSCP or sequence analysis. SSCP analysis showed that the Candida strains with slight sequence differences in the D1/D2 domain could be effectively detected. The common pathogenic Candida species, including C. albicans, C. parapsilosis, C. tropicalis, C. glabrata and C. krusei, were clearly distinguished from each other by their SSCP patterns of PCR amplified D1/D2 domain products. Twenty species belonging to 10 genera were identified from the approximately 260 clinical yeast strains based on SSCP pattern comparison for the common species and D1/D2 sequence analysis for the uncommon species. The dominant species and their frequencies were: C. albicans (57.7%), C. parapsilosis (10.0%), C. tropicalis (9.2%), C. glabrata (6.7%) and C. krusei (5.8%). The results indicated that PCR-SSCP analysis of D1/D2 is a powerful approach for rapid species identification of clinical yeast strains. The most common clinical yeast species was C. albicans in Beijing but the increasing trend of non-albicans Candida species was observed.
{ "pile_set_name": "PubMed Abstracts" }
Diffusion in curved fluid membranes. We analyze theoretically the effects of curvature on the diffusion in a fluid membrane, within the Saffman-Delbrück hydrodynamic model. We calculate the effect of curvature on the intrinsic fluidity of a membrane through changes in its thickness, for both static or fluctuating curvature. We treat both thermal curvature fluctuations, and fluctuations due to active processes. Such curvature fluctuations increase the average membrane thickness and diminish the projected area, thereby decreasing the diffusion coefficient. This calculation allows us to predict the effect of shear flow on the membrane diffusion, and to compare to observations on living cells.
{ "pile_set_name": "PubMed Abstracts" }
Exposure to a specific time-varying electromagnetic field inhibits cell proliferation via cAMP and ERK signaling in cancer cells. Exposure to specific electromagnetic field (EMF) patterns can affect a variety of biological systems. We have shown that exposure to Thomas-EMF, a low-intensity, frequency-modulated (25-6 Hz) EMF pattern, inhibited growth and altered cell signaling in malignant cells. Exposure to Thomas-EMF for 1 h/day inhibited the growth of malignant cells including B16-BL6 mouse melanoma cells, MDA-MB-231, MDA-MB-468, BT-20, and MCF-7 human breast cancer and HeLa cervical cancer cells but did not affect non-malignant cells. The Thomas-EMF-dependent changes in cell proliferation were mediated by adenosine 3',5'-cyclic monophosphate (cAMP) and extracellular-signal-regulated kinase (ERK) signaling pathways. Exposure of malignant cells to Thomas-EMF transiently changed the level of cellular cAMP and promoted ERK phosphorylation. Pharmacologic inhibitors (SQ22536) and activators (forskolin) of cAMP production both blocked the ability of Thomas-EMF to inhibit cell proliferation, and an inhibitor of the MAP kinase pathway (PD98059) was able to partially block Thomas-EMF-dependent inhibition of cell proliferation. Genetic modulation of protein kinase A (PKA) in B16-BL6 cells also altered the effect of Thomas-EMF on cell proliferation. Cells transfected with the constitutively active form of PKA (PKA-CA), which interfered with ERK phosphorylation, also interfered with the Thomas-EMF effect on cell proliferation. The non-malignant cells did not show any EMF-dependent changes in cAMP levels, ERK phosphorylation, or cell growth. These data indicate that exposure to the specific Thomas-EMF pattern can inhibit the growth of malignant cells in a manner dependent on contributions from the cAMP and MAP kinase pathways. Bioelectromagnetics. 39;217-230, 2018. © 2017 Wiley Periodicals, Inc.
{ "pile_set_name": "PubMed Abstracts" }
Modelling transmission dynamics of paratuberculosis of red deer under pastoral farming conditions. This study aimed to develop a mathematical model describing the dynamics of paratuberculosis (PTB) in red deer (Cervus elaphus) under pastoral farming conditions in New Zealand. The model examined infectivity differences between ovine and bovine strains of Mycobacterium avium subspecies paratuberculosis (MAP) and seasonality of MAP survival. We also evaluate variable use of pasture and the effect of management interventions on the infection prevalence and annual clinical incidence of PTB. A state-transition model was developed and calibrated to observed data on both prevalence of infection and incidence of clinical PTB. To accommodate specific PTB features for deer, the model included a fast and a slow track for progression of infection to disease. MAP on pasture was the source for horizontal transmission and infected dams for vertical transmission. In the presence of a single strain, an infectivity reduction of up to 80% allowed MAP to persist in the herd (R(0)>1). For mixed infection by two strains however, a 30% reduction in infectivity of one strain was sufficient to outcompete a strain with lower infectivity, suggesting that mixed infection of MAP strains with different infectivity may not be common in deer. The model showed that seasonal variation of MAP survival on pasture had little impact on transmission dynamics, and that rotational grazing with pasture spelling vs. permanent grazing of the same paddock reduced both infection prevalence and clinical PTB by about 50%. Based on model outputs, early detection of young deer in a high-shedding state was the most effective means of controlling PTB among the tested scenarios.
{ "pile_set_name": "PubMed Abstracts" }
A Single-Wing Removal Method to Assess Correspondence Between Gene Expression and Phenotype in Butterflies: The Case of Distal-less. It is often desirable but difficult to retrieve information on the mature phenotype of an immature tissue sample that has been subjected to gene expression analysis. This problem cannot be ignored when individual variation within a species is large. To circumvent this problem in the butterfly wing system, we developed a new surgical method for removing a single forewing from a pupa using Junonia orithya; the operated pupa was left to develop to an adult without eclosion. The removed right forewing was subjected to gene expression analysis, whereas the non-removed left forewing was examined for color patterns. As a test case, we focused on Distal-less (Dll), which likely plays an active role in inducing elemental patterns, including eyespots. The Dll expression level in forewings was paired with eyespot size data from the same individual. One third of the operated pupae survived and developed wing color patterns. Dll expression levels were significantly higher in males than in females, although male eyespots were smaller in size than female eyespots. Eyespot size data showed weak but significant correlations with the Dll expression level in females. These results demonstrate that a single-wing removal method was successfully applied to the butterfly wing system and suggest the weak and non-exclusive contribution of Dll to eyespot size determination in this butterfly. Our novel methodology for establishing correspondence between gene expression and phenotype can be applied to other candidate genes for color pattern development in butterflies. Conceptually similar methods may also be applicable in other developmental systems.
{ "pile_set_name": "PubMed Abstracts" }
Aerobic blood cardioplegia for revascularization of acute infarct: effects of delivery temperature. The effects of different cardioplegia temperatures on myocardial protection with continuous aerobic blood cardioplegia were studied in a canine model of acute regional injury after left anterior descending coronary artery occlusion and subsequent revascularization. Twenty-five animals underwent 90 minutes of occlusion followed by revascularization during 60 minutes of electromechanical arrest with continuous retrograde blood cardioplegia delivered at one of three temperatures: 18 degrees C (n = 8), 28 degrees C (n = 8), and 37 degrees C (n = 9). Left ventricular protection was assessed in a right heart bypass model in terms of the left ventricular pressure-volume relationships, myocardial oxygen consumption, regional myocardial blood flow, adenosine trisphosphate concentration, and water content. The preload recruitable stroke work relationship at 90 minutes after reperfusion was better in the 18 degrees C and 28 degrees C groups than that in the 37 degrees C group (18 degrees C, 85 +/- 14 erg x 10(3)/mL; 28 degrees C, 77 +/- 17 erg x 10(3)/mL; 37 degrees C, 58 +/- 13 erg x 10(3)/mL; p < 0.05). The maximum elastance and stress-strain relationships showed there were no significant differences between the groups at 90 minutes. The myocardial oxygen consumption was greatest in the 37 degrees C group during the first hour after reperfusion (18 degrees C, 5.4 +/- 1.4 mL O2.min-1.100 g-1; 28 degrees C, 4.7 +/- 1.1 mL O2.min-1.100 g-1; 37 degrees C, 6.3 +/- 1.6 mL O2.min-1.100 g-1; p < 0.05). The regional myocardial blood flow, adenosine triphosphate concentration, and myocardial water content were similar in the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)
{ "pile_set_name": "PubMed Abstracts" }
Rationale and design of the RT-AF study: Combination of rivaroxaban and ticagrelor in patients with atrial fibrillation and coronary artery disease undergoing percutaneous coronary intervention. Optimal antithrombotic strategy for patients with concomitant coronary artery disease and atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) is still controversial, and the role of novel antithrombotic agents has nerve been tested. Therefore, the aim of this study is to evaluate and overall safety and efficacy profile of the combination of rivaroxaban and ticagrelor in this particular population. The RT-AF study is an open-label, randomized, active-controlled, multicenter clinical trial with up to 420 subjects enrolled in 5 centers. Eligible patients, who have a history or new onset paroxysmal, persistent, or permanent non-valvular AF, referred to the study centers with indications for PCI will be randomly assigned to receive triple therapy (including warfarin, clopidogrel and aspirin) or dual therapy (rivaroxaban and ticagrelor). All subjects will have clinical follow-up at discharge, at 30 days, 6 months and 12 months. The primary end point is major or clinically relevant non-major bleeding events at 12 months. The major secondary end point is the composite efficacy outcome of death, myocardial infarction, stent thrombosis and ischemic stroke. The study will be sufficiently powered to provide data primarily regarding the safety of dual therapy with rivaroxaban and ticagrelor over the traditional triple therapy in patients with AF undergoing PCI at 12 months. It will also provide important information regarding the efficacy of the two different antithrombotic regimens. (ClinicalTrials.gov identifier: NCT02334254).
{ "pile_set_name": "PubMed Abstracts" }
[Fournier's gangrene. Case report and review of the literature]. Fournier's gangrene is a rare condition, far from being 'idiopathic', which must be taken seriously and which is, although at first manifesting itself only locally, a generalized condition with high mortality and--unless recognized--taking a rapid course with lethal outcome. Many risk factors have been recognized which favor an often lethal outcome. Although oftentimes not recognized, a port of entry is always present and haemolytic streptococci are as a rule involved. Since Fournier the age limit has moved to the 5th and 6th decades. Early recognition, prompt and aggressive surgical treatment and antibiotic coverage are mandatory to offer patients a chance to survive.
{ "pile_set_name": "PubMed Abstracts" }
Neuropathological Assessment as an Endpoint in Clinical Trial Design. Different neurodegenerative conditions can have complex, overlapping clinical presentations that make accurate diagnosis during life very challenging. For this reason, confirmation of the clinical diagnosis still requires postmortem verification. This is particularly relevant for clinical trials of novel therapeutics where it is important to ascertain what disease and/or pathology modifying effects the therapeutics have had. Furthermore, it is important to confirm that patients in the trial actually had the correct clinical diagnosis as this will have a major bearing on the interpretation of trial results. Here we present a simple protocol for pathological assessment of neurodegenerative changes.
{ "pile_set_name": "PubMed Abstracts" }
Optimizing cell preparation technique to enhance adsorption capacity of pseudomonas putida 5-x to heavy metal ions. A heavy metal accumulation bacterium Pseudomonas putida 5-x isolated from electroplating effluent was used as biosorbent for heavy metal removal from wastewater. In order to compete with physical adsorbent, the optimization of the cell preparation technique for further improving its heavy metal adsorption capacity was conducted. Experimental results showed that the variation of medium compositions and cell growth age, and different cell pre-treating technique would result in the variation of the cell surface components and structural, hence the variation of adsorption capacity of the cell to heavy metal ions. With optimum cell culture conditions and pretreatment technique, the Cu2+ adsorption capacity of the cell was obviously increased from 51.2 mg g-1 to 89.6 mg g-1. The optimised P. putida 5-x cell could be reused at least five cycles to remove heavy metal ions from electroplating effluent with about 95% removal efficiency.
{ "pile_set_name": "PubMed Abstracts" }
The influence of anxiety on student nurse performance in a simulated clinical setting: A mixed methods design. Anxiety has a powerful impact on learning due to activation of anxiety hormones, which target related receptors in the working memory. Experiential learning requires some degree of challenge and anxiety. Patient simulation, as a form of experiential learning, has been an integrated component of health professional education internationally over the last two decades, especially in undergraduate nursing education. Little information is available to determine if and how anxiety impacts nursing students' clinical performance during simulation. To investigate physiological and psychological anxiety during emergency scenarios in high-fidelity simulation and understand the effect of anxiety on clinical performance. First2Act was the model for the simulation intervention. Second and third year undergraduate nursing students attended a two-hour simulation session and completed a demographic questionnaire plus pre-simulation self-reported psychological anxiety scale. A heart rate variability monitor was attached to each student's chest to measure heart rate variability (as a sign of anxiety) before engaging in two video-recorded simulated emergency scenarios (cardiac and respiratory) with a professional actor playing the patient. Performance was rated by a clinician followed by video-assisted debriefing. Finally, heart monitors were removed and students repeated self-reports of psychological anxiety. Students' psychological anxiety was high pre-simulation and remained high post-simulation. With regard to physiological anxiety, students were anxious at the start of the simulation but became more relaxed toward the end as they gained familiarly with the simulation environment (p < .007). Clinical performance increased significantly in the second scenario (p < .001). Factors found to positively affect clinical performance were length of enrolment in the nursing degree (p = .001), current employment in a nursing or allied healthcare field (p = .030), and previous emergency experience (p = .047). The relationship between physiological anxiety and clinical performance was statistically not significant, although there was an indication that low level anxiety led to optimal performance. High-fidelity patient simulation has the capacity to arouse novice nurses psychologically and physiologically while managing emergency situations. Indicative outcomes suggest that optimal performance was apparent when anxiety levels were low, indicating that they had received insufficient training to deal with situations that induced moderate to high anxiety levels.
{ "pile_set_name": "PubMed Abstracts" }
[Occupational risk factors in the biotechnology industry and workers' health status]. The mechanisms of the pathogenic effect of microbial cultures used in biotechnological industry and the products of their vital activity on the workers were investigated. A unique classification of the components of the disease incidence with temporary disability is described. The necessity of detecting prepathological conditions and initial occupational affections in the workers for preventing severe consequences of occupational diseases is indicated. On the basis of complex investigations of disease incidence in the workers, revision of the present sanitary and hygienic regulations may be of need.
{ "pile_set_name": "PubMed Abstracts" }
Net degradation of methyl mercury in alder swamps. Wetlands are generally considered to be sources of methyl mercury (MeHg) in northern temperate landscapes. However, a recent input-output mass balance study during 2007-2010 revealed a black alder (Alnus glutinosa) swamp in southern Sweden to be a consistent and significant MeHg sink, with a 30-60% loss of MeHg. The soil pool of MeHg varied substantially between years, but it always decreased with distance from the stream inlet to the swamp. The soil MeHg pool was significantly lower in the downstream as compared to the upstream half of the swamp (0.66 and 1.34 ng MeHg g⁻¹ SOC⁻¹ annual average⁻¹, respectively, one-way ANOVA, p = 0.0006). In 2008 a significant decrease of %MeHg in soil was paralleled by a significant increase in potential demethylation rate constant (k(d), p < 0.02 and p < 0.004, respectively). In contrast, the potential methylation rate constant (k(m)) was unrelated to distance (p = 0.3). Our results suggest that MeHg was net degraded in the Alnus swamp, and that it had a rapid and dynamic internal turnover of MeHg. Snapshot stream input-output measurements at eight additional Alnus glutinosa swamps in southern Sweden indicate that Alnus swamps in general are sinks for MeHg. Our findings have implications for forestry practices and landscape planning, and suggest that restored or preserved Alnus swamps may be used to mitigate MeHg produced in northern temperate landscapes.
{ "pile_set_name": "PubMed Abstracts" }
Characterization of oligosaccharide structures on a chimeric respiratory syncytial virus protein expressed in insect cell line Sf9. The oligosaccharide structures added to a chimeric protein (FG) composed of the extracellular domains of respiratory syncytial virus F and G proteins, expressed in the insect cell line Sf9, were investigated. Cells were labeled in vivo with [3H]glucosamine and infected with a recombinant baculovirus containing the FG gene. The secreted chimeric protein was isolated by immunoprecipitation and subjected to oligosaccharide analysis. The FG protein contains two types of O-linked oligosaccharides: GalNAc and Gal beta 1-3GalNAc constituting 17 and 66% of the total number of structures, respectively. Only one type of N-linked oligosaccharide, constituting the remaining 17% of the structures on FG, was detected: a trimannosyl core structure with a fucose residue linked alpha 1-6 to the asparagine-linked N-acetylglucosamine.
{ "pile_set_name": "PubMed Abstracts" }
[Complexity in general practice]. In general practice, we see complexity in the patient ('case complexity'), in the treatment ('care complexity'), and, to an important degree, in the context in which patient characteristics and environmental factors together lead to disease ('complexity thinking'). This context makes linear medical thinking, i.e. in which a symptom of a disease has one direct biological cause, problematic and the outcomes of interventions based on this thinking are uncertain. Complex patients make much greater demands on a practice than average. Complex interventions occur mainly in the context of coordination of collaboration with other professionals. Complex systems thinking has taken root in general practice, certainly in the scientific field. General practice is often complex, and the only good way to practice is to provide personal care with a focus on the context in which the health problems occur.
{ "pile_set_name": "PubMed Abstracts" }
Inhibition of the epidermal growth factor receptor preserves podocytes and attenuates albuminuria in experimental diabetic nephropathy. Early renal enlargement may predict the future development of nephropathy in patients with diabetes. The epidermal growth factor (EGF)-EGF receptor (EGFR) system plays a pivotal role in mediating renal hypertrophy, where it may act to regulate cell growth and proliferation and also to mediate the actions of angiotensin II through transactivation of the EGFR. In the present study we sought to investigate the effects of long-term inhibition of the EGFR tyrosine kinase in an experimental model of diabetes that is characterized by angiotensin II dependent hypertension. Female heterozygous streptozotocin-diabetic TGR(mRen-2)27 rats were treated with the EGFR inhibitor PKI 166 by daily oral dosing for 16 weeks. Treatment of TGR(mRen-2)27 rats with PKI 166 attenuated the increase in kidney size, glomerular hypertrophy and albuminuria that occurred with diabetes. The reduction in albuminuria, with EGFR inhibition in diabetic TGR(mRen-2)27 rats, was associated with preservation of the number of glomerular cells staining positively for the podocyte nuclear marker, WT1. Immunostaining for WT1 inversely correlated with glomerular volume in diabetic rats. In contrast to agents that block the renin-angiotensin system (RAS), EGFR inhibition had no effect on either the quantity of mesangial matrix or the magnitude of tubular injury in diabetic animals. These observations indicate that inhibition of the tyrosine kinase activity of the EGFR attenuates kidney and glomerular enlargement in association with podocyte preservation and reduction in albuminuria in diabetes. Accordingly, targeting the EGF-EGFR pathway may represent a therapeutic strategy for patients who continue to progress despite RAS-blockade.
{ "pile_set_name": "PubMed Abstracts" }
Anatomy and ultrastructure of the sporophyte of Takakia ceratophylla (Bryophyta). In this study, morphogenesis and structure of the sporophyte of Takakia ceratophylla are characterized beginning with the late embryo and culminating in the fully dehisced capsule. Information is presented on the development, ultrastructure, and anatomy of the three organographic regions of the sporophyte, namely capsule, seta, and foot. Diagnostic features that identify Takakia as a moss include the gradual elongation of seta, persistence of an apical calyptra, expansion of the capsule after cessation of seta elongation, existence of a columella, monoplastidic meiosis, spore ultrastructure (including a perine layer deposited late in spore wall (development), and the structure of the foot. Commonalities with the capsule of the Andreaeopsida include sporogenous tissue that overarchs a central columella, absence of stomata, and lack of a peristome and operculum. Peculiarities of the genus are seen in the internal structure of the capsule, the disintegration of the columella with spore maturation, and the dehiscence of the capsule along a single, spiralled, longitudinal suture line. Passive spore dispersal through longitudinal splitting of the capsule occurs in andreaeopsid mosses, liverworts, hornworts, and seedless vascular plants. The precise mechanism of dehiscence along a spiralled suture is unparalleled in extant archegoniates but finds counterparts in ancestral land plants such as the pteridophyte Tortilicaulis.
{ "pile_set_name": "PubMed Abstracts" }
Mean maternal second-trimester hemoglobin concentration and outcome of pregnancy: a population-based study. Both anemia and the lack of physiological maternal plasma volume expansion during the second trimester are associated with higher maternal morbidity and poor fetal outcome. Mean hemoglobin levels between the 14th and 30th gestational weeks were calculated in 4985 consecutive pregnant women and were correlated with outcome data of pregnancy. It was found that 9.4% of participants (n=3959) had normal pregnancy outcome. Mean maternal hemoglobin levels were significantly lower in women with a normal pregnancy (11.96+/-0.94 g/dL) compared with women who had adverse outcome events (preeclampsia, n=423, 12.5 +/- 1.0 g/dL, P< .0001; early birth, n=464, 12.2+/-1.01 g/dL, P< .0001; low birth weight newborn, n=473, 12.2+/-1.10 g/dL, P< .0001; intrauterine growth retardation, n=250, 12.2+/-1.0 g/dL, P< .0001). The risk for any adverse outcome event was lowest with a mean hemoglobin between 11.0 and 12.0 g/dL (odds ratio, 0.625; 95% confidence interval, 0.43-0.89) and highest between 13.0 and 15.0 g/dL (odds ratio, 2.24; 95% confidence interval, 1.54-3.31). In this population-based study from a community in Western Germany, impaired plasma volume expansion was an independent risk factor for the development of an adverse outcome of pregnancy.
{ "pile_set_name": "PubMed Abstracts" }
The shape of high fertility in a traditional Mennonite population. The Wenger Mennonites, a traditional horse-and-buggy group, are one of at least 30 embedded Anabaptist religious groups in the USA. This first study of Wenger fertility documents, explains, and compares Wenger fertility to three other Anabaptist groups: the Amish, the Hutterites, and the Old Colony Mennonites. The 1997 Wenger church directory provides household and fertility data for 14530 individuals. This directory was transformed into an SPSS database so that age-specific birth rates could be analysed. From 1966 to 1996, total fertility ranged from 10.68 to 8.31 for married women, and age-specific fertility rates for 20-24-year-old women never dropped below 0.500. For similar time periods, no higher rates were found in any of the comparison groups. Even so, fertility has dropped over 22% in the last 30 years, suggesting increasing regulation of fertility. Wenger fertility has been very high, at least since the 1960s, and continues to be higher than the comparison groups, even though there is some evidence of fertility decline, especially in older women. This high fertility is powered by high economic and social capital, and a farming community with a strong pro-natalist ideology.
{ "pile_set_name": "PubMed Abstracts" }
Kinetics and consequences of binding of nona- and dodecapeptides to the oligopeptide binding protein (OppA) of Lactococcus lactis. The oligopeptide transport system (Opp) of Lactococcus lactis belongs to the class of binding protein-dependent ABC-transporters. This system has the unique capacity to mediate the uptake of peptides from 4 up to at least 18 residues. Kinetic analysis of peptide binding to the binding protein, OppA, revealed a relationship between the peptide dissociation constants and the length of the ligand. The dissociation constants varied from submicromolar for dodecapeptides to millimolar for pentapeptides. This implies that the residues 6-12 of the peptide contribute to the binding affinity, and, in contrast to the current views on peptide binding by homologous proteins, these residues must interact with OppA. Analysis of pre-steady-state kinetics of binding showed that the observed differences in the -values result primarily from variations in the dissociation rate constants. These results are discussed in relation to the affinity constant for transport of these substrates. Overall, the data suggest that the slow dissociation rate constants for the larger peptides are rate determining in the translocation of peptides across the membrane.
{ "pile_set_name": "PubMed Abstracts" }
Sloping alveolar plateaus of CO2, O2, and intravenously infused C2H2 and CHClF2 in the dog. To investigate the role of the various mechanisms assumed to contribute to the slope of the alveolar plateau, two test gases exhibiting identical solubility but two-fold differing diffusivity, acetylene (C2H2) and chlorodifluoromethane (Freon 22, CHClF2), dissolved in saline were intravenously infused in 10 anesthetized, paralyzed, artificially ventilated dogs (mean body mass, 18 kg). The partial pressures of C2H2, CHClF2, CO2 and O2 during a constant-flow single-breath washout maneuver were recorded by mass spectrometry and analyzed in terms of slope of the alveolar plateau (phase III) and series (Fowler) dead space. The slope of the alveolar plateau (S) was determined as the relative alveolar slope normalized to mixed-expired partial pressure and referred to expired volume (VE), S(V) = delta PE/(PE - PI)/delta VE or expiration time (tE), S(t) = delta PE/(PE - PI)/delta tE (subscripts I, E, and E refer to inspired, instantaneous expired and mixed-expired gas, respectively). The effects of expiratory flow rate (VE), and time of breath-hold (BH) were studied with reference to control conditions (VI = 0.5 L.sec-1, VE = 0.1 L.sec-1, VI = 50% and VE = 75% of volume at FRC, BH = 0 sec). In control conditions, the following significantly different S(V) values (units: L-1), grouped in ascending order, were obtained (means +/- SD): CO2, 0.83 +/- 0.26; C2H2, 0.93 +/- 0.18; CHClF2, 1.00 +/- 0.20; O2, 1.07 +/- 0.29. The mean C2H2/CHClF2 ratio for S(V), 0.94 (SD +/- 0.03), was statistically different from unity. In line with model calculations, the experimental findings suggest that three mechanisms contribute to the sloping alveolar plateaus: 1, continuing gas exchange during expiration; 2, ventilation-perfusion inequality combined with sequential emptying; 3, intrapulmonary diffusion limitation.
{ "pile_set_name": "PubMed Abstracts" }
Dopamine sulphate: an enigma resolved. 1. The source and physiological significance of dopamine (DA) sulphate, which exists in plasma at much higher concentrations than free DA, have long been a puzzle. The present article reviews how the convergence of modern molecular and traditional clinical approaches is shedding new light on the origins and meaning of DA sulphate. 2. The sulphotransferase isoenzyme responsible for production of DA sulphate in humans (SULT1A3) has been cloned and shown to be expressed in large quantities in the gastro-intestinal tract, but not in liver. No orthologue of SULT1A3 has yet been identified in other species, consistent with the greater importance of sulphate conjugation of DA in humans than in most animals. 3. Diet has a major impact on plasma DA sulphate, with dramatic increases after ingestion of meals and foods rich in biogenic amines; however, substantial amounts of DA sulphate remaining after prolonged fasting indicate the presence of a mainly endogenous source. The lack of influence of acute or chronic changes in sympathetic outflow or of sympathoneural degeneration on plasma DA sulphate indicates that DA sulphate does not derive from sympathetic nerve. Relatively low rates of production from intravenously infused DA indicate that very little DA sulphate (< 2%) derives from metabolism of circulating DA, such as in red cells or platelets. 4. Consistent increments in DA sulphate from arterial to the outflowing venous plasma draining mesenteric organs, without increments across other organs or tissues (e.g., heart, lungs, liver), indicate that the gastrointestinal tract is a major source of more than 75% of DA sulphate produced in the body. The gastro-intestinal tract is also the site of a novel DA autocrine/paracrine system that produces nearly 50% of the DA in the body. Therefore, production of DA sulphate appears to reflect an enzymatic 'gut-blood' barrier for detoxifying dietary biogenic amines and delimiting autocrine/paracrine effects of endogenous DA generated in a novel 'third catecholamine system'.
{ "pile_set_name": "PubMed Abstracts" }
Insulin resistance in non-diabetic subjects is associated with increased incidence of myocardial infarction and death. To compare the incidence of myocardial infarction and death in non-diabetic subjects with and without insulin resistance. Population-based prospective cohort study, in Malmö, Sweden, of 4748 non-diabetic subjects (60% women), aged 46-68 years, with no history of myocardial infarction or stroke. The prevalence of insulin resistance was established by the homeostasis model assessment (HOMA) and defined as values above the sex-specific 75th percentile (1.80 for women and 2.12 for men). Incidence of myocardial infarction and death is based on record linkage with local and national registers. Cox's proportional hazards model was used to assess the influence of insulin resistance after adjustment for age, sex, hyperglycaemia, raised arterial blood pressure, dyslipidaemia, central obesity, smoking and leisure-time physical activity. Sixty-two subjects suffered a coronary event, and 93 subjects died during the 6-year follow-up period. Insulin resistance was after adjustment for other factors included in the insulin resistance syndrome and other potential confounders, associated with an increased incidence of coronary events (relative risk (RR) 2.18; 95% confidence interval (CI) 1.22-3.87; P = 0.008) and deaths (RR 1.62; 1.03-2.55; P = 0.038). Insulin resistance, as assessed by the HOMA method, was in this cohort of middle-aged non-diabetic subjects associated with an increased incidence of myocardial infarction and death. This risk remained when smoking, low physical activity and factors included in the insulin resistance syndrome were taken into account in a stepwise regression model.
{ "pile_set_name": "PubMed Abstracts" }
Role of nitric oxide and endothelium in rat pial vessel dilation response to isoflurane. Isoflurane induces cerebral hyperemia. We sought to assess whether isoflurane induces cerebral microvessel dilation in vivo, and if so, to determine whether nitric oxide (NO) and endothelium are involved. By using a rat closed cranial window model, pial arterioles and venules of 30-70 microns in diameter were measured using intravital microscopy. The cerebral microvascular dilatory response was recorded as percent change of diameter from baseline. The pial vessels were suffused with sodium nitroprusside (SNP) or S-nitroso-acetyl-penicillamine (SNAP) to verify intact vascular smooth muscle relaxation function, and with adenosine diphosphate (ADP) and/or acetylcholine (ACh) to verify endothelial NO-generating capability. To isolate NO's role in the cerebral microvascular effects of isoflurane (Protocol I), microvessels were studied with and without nitric oxide synthase (NOS) inhibition by topically applied nitro-L-arginine methyl ester (L-NAME). In controls, L-NAME was replaced by its inactive enantiomer, nitro-D-arginine methyl ester (D-NAME). Mercury light plus fluorescein dye (LD) endothelial injury (Protocol II) was used to delineate an endothelium-mediated mechanism. Subsequently, vasodilator applications were repeated to verify the desired effects of the interventions and followed by suffusion of isoflurane 1%, 2%, and 3% (Protocol I) or isoflurane 3% (Protocol II). Suffusions of SNP, ADP, and ACh induced diameter increases of 15%-30%. NOS inhibition with L-NAME greatly attenuated ADP and ACh responses, but did not alter the SNP response, confirming that NO generation was blocked, but not NO action. These responses were unaffected in D-NAME-suffused rats. Isoflurane dilated arterioles 17% and venules 6% in the presence of D-NAME suffusion.(ABSTRACT TRUNCATED AT 250 WORDS)
{ "pile_set_name": "PubMed Abstracts" }
Putative myosin heavy and light chains in Tetrahymena: co-localization to the basal body-cage complex and association of the heavy chain with skeletal muscle actin filaments in vitro. The basal body cage is a fibrillar chamber which surrounds each basal body in the ciliate cytoskeleton. The function of this chamber is unknown. In Tetrahymena, the cage contains actin filaments which connect the cage to triplet microtubules. In this study, we have examined the cage for the presence of myosin. Skeletal muscle myosin-II heavy and light chains were used to affinity-purify anti-MHC and anti-MLC antibodies, respectively, from an antiserum raised against Tetrahymena oral apparatus proteins. On western immunoblots of ATP-solubilized Tetrahymena proteins, the anti-MHC antibody detected a putative myosin heavy (180 kDa) chain, and the anti-MLC antibody detected a putative myosin light (18 kDa) chain. The anti-MHC antibody specifically labeled the AI zone of sarcomeres. In cosedimentation assays with an ATP-solubilized protein fraction, the 180 kDa polypeptide associated with skeletal muscle actin filaments in an ATP-dependent manner. The sedimented actin filaments appeared to be organized into bundles. Immunodepletion of the 180 kDa rendered the ATP-solubilized protein fraction ineffective in bundling actin filaments in a cosedimentation assay. ATP-solubilized Tetrahymena proteins, which included the 180 kDa polypeptide, exhibited F-actin-stimulated, Mg2+ ATPase activity and K+, EDTA ATPase activity which are characteristic of myosin ATPases. Immunodepletion of the 180 kDa polypeptide reduced the F-actin, Mg2+ ATPase activity of the ATP-solubilized protein fraction by more than 80%. Based on these various observations, we conclude that the 180 kDa polypeptide is a putative myosin heavy chain, probably a myosin-II and that the 18 kDa polypeptide is probably a myosin-II light chain. We have used the affinity-purified, anti-myosin antibodies with immunofluorescence microscopy and immunogold electron microscopy to map the location of the putative myosin heavy and light chains in Tetrahymena. Immunofluorescence microscopy showed that the anti-myosin antibodies localized to Tetrahymena somatic and oral region basal bodies. At the ultrastructural level, the anti-myosin antibodies localized to filaments in the basal body-cage complex. The labeling patterns with both anti-myosin antibodies were identical to the labeling pattern observed with an anti-actin antibody reported in a previous study. The co-localization of myosin and actin argue for a motility system within the basal body-cage complex.
{ "pile_set_name": "PubMed Abstracts" }
Reproductive endocrinology and weight change in relation to reproductive success in the magellanic penguin (Spheniscus magellanicus). The Magellanic penguin is a colonial monogamous species that lays only a single clutch of two eggs per year. However, failed breeders remain at the colony and engage in nest building, fights, and copulations without relaying. The seasonal changes in reproductive hormones and body weight through the nesting cycle were studied, with respect to the reproductive success or failure of individuals. Body weight changed dramatically in both sexes through the season, in response to fasting during incubation, and high body weight in males at the onset of incubation was a strong predictor of eventual reproductive success. Circulating steroid hormones had a biphasic seasonal pattern, with elevated levels during the sexual phase of breeding (prior to egg laying), declining to low, stable levels during the parental phase after eggs were laid. Luteinizing hormone levels were elevated in females, but not in males, prior to egg laying. Both sexes responded to reproductive failure by increasing the secretion of testosterone, and females also increased the secretion of estradiol, a response that would be expected of a species that can renest following failure. However, renesting is extremely rare, and this hormonal response to failure may instead serve to promote maintenance of pair bonds and also territory ownership across years.
{ "pile_set_name": "PubMed Abstracts" }
Important considerations for designing and reporting epidemiologic and clinical studies in dental traumatology. The purpose of this article is to suggest important considerations for epidemiologic and clinical studies in the field of dental traumatology. The article is based on the authors' experiences from research in this field and editorial board work for the scientific journal Dental Traumatology. Examples are given of issues where development is important. The importance of planning ahead of the study and consulting with experts in other fields is emphasized.
{ "pile_set_name": "PubMed Abstracts" }
Restoration of transforming growth factor-beta signaling enhances radiosensitivity by altering the Bcl-2/Bax ratio in the p53 mutant pancreatic cancer cell line MIA PaCa-2. In this study, we investigated whether lack of transforming growth factor beta (TGF-beta) type II receptor (RII) expression and loss of TGF-beta signaling played a role in radiation resistance of pancreatic cancer cells MIA PaCa-2 that possess a mutated p53 gene. Transfection of this cell line with a RII cDNA led to a stimulation of the transcriptional activity of p3TP-Lux, a TGF-beta-responsive reporter construct. The RII transfectants (MIA PaCa-2/RII) showed a significant increase in sensitivity to radiation when compared with MIA PaCa-2/vector cells. The increase in sensitivity to radiation was reversed by neutralizing antibodies to TGF-beta, indicating that these changes were dependent on TGF-beta signaling. Compared with MIA PaCa-2/vector cells, MIA PaCa-2/RII cells showed a greater than 3-fold increase in apoptosis after radiation. Enhanced radiation sensitivity of MIA PaCa-2/RII cells was associated with an induction of Bax mRNA and protein that was followed by a release of cytochrome c and activation of caspase-3 and poly(ADP-ribose) polymerase cleavage after radiation exposure. Overexpression of Bcl-x(L) or treatment with antisense oligodeoxynucleotides targeted against Bax significantly inhibited radiation-induced apoptosis in MIA PaCa-2/RII but not in MIA PaCa-2/Vector cells, suggesting that Bax induction is necessary for radiation-induced TGF-beta signaling-mediated apoptosis. Thus, restoration of TGF-beta signaling sensitized these cells to ionizing radiation, although these cells possess a mutated p53 gene. In addition, disruption of RII function by dominant negative mutant of RII inhibited the radiation-induced TGF-beta signaling and apoptosis in primary cultures of mouse embryonic fibroblasts. Together, these observations imply that RII is an important component of radiation-induced TGF-beta signaling, and loss of function of RII may enhance resistance to radiation-induced apoptosis.
{ "pile_set_name": "PubMed Abstracts" }
Lower threshold for referral for psychiatric treatment for adopted adolescents. Epidemiological data on a national sample of 3,698 adolescents, of whom 145 were adopted, indicate that adoption significantly increases the likelihood of referral for psychiatric treatment even after controlling for the fact that adoptees display more behavior problems and come from more educated families. This is accounted for by the fact that adoptees are significantly more likely to be referred when they display few problems. Thus, contrary to popular myth and clinical lore, the overrepresentation of young adoptees in clinical settings is not attributable solely to the fact that adoptees are more troubled. Rather, adoptees do display more problems but they are also referred more readily even after controlling for extent of problems.
{ "pile_set_name": "PubMed Abstracts" }
Fluorescence resonance energy transfer between green fluorescent protein and doxorubicin enabled by DNA nanotechnology. DNA nanotechnology is a rapidly growing research area, where DNA may be used for wide range of applications such as construction of nanodevices serving for large scale of diverse purposes. Likewise a panel of various purified fluorescent proteins is investigated for their ability to emit their typical fluorescence spectra under influence of particular excitation. Hence these proteins may form ideal donor molecules for assembly of fluorescence resonance emission transfer (FRET) constructions. To extend the application possibilities of fluorescent proteins, while using DNA nanotechnology, we developed nanoconstruction comprising green fluorescent protein (GFP) bound onto surface of surface active nanomaghemite and functionalized with gold nanoparticles. We took advantage of natural affinity between gold and thiol moieties, which were modified to bind DNA fragment. Finally we enclosed doxorubicin into fullerene cages. Doxorubicin intercalated in DNA fragment bound on the particles and thus we were able to connect these parts together. Because GFP behaved as a donor and doxorubicin as an acceptor using excitation wavelength for GFP (395 nm) in emission wavelength of doxorubicin (590 nm) FRET was observed. This nanoconstruction may serve as a double-labeled transporter of doxorubicin guided by force of external magnetic force owing to the presence of nanomaghemite. Further nanomaghemite offers the possibility of using this technology for thermotherapy.
{ "pile_set_name": "PubMed Abstracts" }
Arthroscopic double-row cuff repair with suture-bridging: a structural and functional comparison of two techniques. The aim of this study was to compare the functional and structural outcomes of 2 techniques for double-row, suture-bridging cuff repair. A consecutive series of 73 patients who underwent arthroscopic, double-row, suture-bridge primary rotator cuff repair of full-thickness supraspinatus tear were evaluated. Thirty-eight shoulders were repaired by the arthroscopic, tied, suture-bridging technique (group A), and 35 shoulders by knot-less bridging with suture tape material (group B). Constant scores, pain, range of motion, strength, and complications were measured after a minimum follow-up period of 12 months post-operatively. Structural integrity of the repairs was evaluated systematically by either magnetic resonance imaging or computed tomography arthrography. Median follow-up after surgery was 29 (23-32) months in group A, and 21 (12-23) months in group B. Mean pain relief, range of motion, strength, and constant score improved significantly in both groups. No statistical differences were found between groups in the post-operative period. According to control imaging, the re-tear rate trended to be higher in group A (23.4 %) than in group B (17.1 %), although not significantly. Both bridging repair techniques achieved successful functional outcomes. In terms of structural outcome, the knot-less tape-bridging construct showed a lower but not significant re-tear rate. Longer follow-up is needed to confirm these results and to evaluate potential differences between the two techniques. A prospective, non-randomized, comparative study, Level III.
{ "pile_set_name": "PubMed Abstracts" }
Pharmacological modulations of cardiac ultra-rapid and slowly activating delayed rectifier currents: potential antiarrhythmic approaches. Despite the emerging new insights into our understandings of the cellular mechanisms underlying cardiac arrhythmia, medical therapy for this disease remains unsatisfactory. Atrial fibrillation (AF), the most prevalent arrhythmia, is responsible for significant morbidity and mortality. On the other hand, ventricular fibrillation results in sudden cardiac deaths in many instances. Prolongation of cardiac action potential (AP) is a proven principle of antiarrhythmic therapy. Class III antiarrhythmic agents prolong AP and QT interval by blocking rapidly activating delayed rectifier current (I(Kr)). However, I(Kr) blocking drugs carry the risk of life-threatening proarrhythmia. Recently, modulation of atrial-selective ultra-rapid delayed rectifier current (I(Kur)), has emerged as a novel therapeutic approach to treat AF. A number of I(Kur) blockers are being evaluated for the treatment of AF. The inhibition of slowly activating delayed rectifier current (I(Ks)) has also been proposed as an effective and safer antiarrhythmic approach because of its distinguishing characteristics that differ in remarkable ways from other selective class III agents. Selective I(Ks) block may prolong AP duration (APD) at rapid rates without leading to proarrhythmia. This article reviews the pathophysiological roles of I(Kur) and I(Ks) in cardiac repolarization and the implications of newly developed I(Kur) and I(Ks) blocking agents as promising antiarrhythmic approaches. Several recent patents pertinent to antiarrhythmic drug development have been discussed. Further research will be required to evaluate the efficacy and safety of these agents in the clinical setting.
{ "pile_set_name": "PubMed Abstracts" }
Transcranial Magnetic Stimulation-Electroencephalography Measures of Cortical Neuroplasticity Are Altered after Mild Traumatic Brain Injury. While the potential long-term side effects of mild traumatic brain injury (mTBI) are becoming increasingly recognized, the associated neurophysiological mechanisms remain poorly understood. However, changes in cortical inhibitory function and neuroplasticity have been suggested as possible contributing factors. The current study applied transcranial magnetic stimulation (TMS) in conjunction with electroencephalography (combined TMS-EEG) to investigate further the effects of mTBI on these processes. In 17 patients with a history of mTBI and 15 healthy control subjects with no mTBI history, paired-pulse TMS-EEG measures of short- (SICI) and long-interval intracortical inhibition (LICI) were used to assess intracortical inhibitory function. Single-pulse TMS-EEG was used to assess neuroplastic changes in cortical excitability after application of continuous theta burst stimulation (cTBS, a plasticity inducing TMS paradigm). Inhibition of the TMS-evoked EEG potential after application of SICI and LICI was not different between groups. In contrast, the inhibitory effects of cTBS on both P30 (p < 0.05) and N45 (p = 0.04) TEP components was significantly increased in patients, with the modulation of N45 in patients significantly related to the time since injury (p = 0.04). While these results provide further evidence that inhibitory circuits involving γ-aminobutyric acid (GABA) are modified after mTBI, they place greater emphasis on the plasticity of inhibitory networks involving the GABAA receptor subtype.
{ "pile_set_name": "PubMed Abstracts" }
Chemotherapy-induced parkinsonism responsive to levodopa: an underrecognized entity. Parkinsonism is a rare neurological complication of cancer treatment. Although individual case reports of this syndrome have been reported, the clinical features and prevalence of this syndrome are unknown. We present 3 patients, encountered over 6 months at one institution, who developed parkinsonism after treatment with various chemotherapeutic agents. Parkinsonism was severe in 2 patients, affecting postural reflexes, speech, and swallowing. All 3 patients responded dramatically to treatment with levodopa, and parkinsonism spontaneously improved or remitted over months. This unusual complication of cancer therapy is treatable and may be underappreciated.
{ "pile_set_name": "PubMed Abstracts" }
"Pierce and inhale" design in capsule based dry powder inhalers: Effect of capsule piercing and motion on aerodynamic performance of drugs. In this work three capsule-based dry powder inhalers, available for generics product development, were compared. Two technologically different dry powder formulations were used in order to relate the capsule piercing position and motion in the device to their aerodynamic performance. A "pierce and inhale" design, in which the capsules pierced with RS01, HandiHaler or Turbospin devices were aerosolized in the same device or transferred and aerosolized with another device, was constructed and carried out. The results obtained showed that two dry powder formulations, i.e., a drug/lactose blend or a carrier-free powder, aerosolized using capsule based inhalers, performed differently. The aerosolization of drug carrier mixture in terms of drug dispersion and emitted dose, was more sensible to the piercing and device combination than the carrier free powder. The motion of the capsule during the aerosolization boosted the powder emission, whereas the powder disaggregation was more influenced by the airflow pattern around the capsule and inside the inhaler turbulence chamber.
{ "pile_set_name": "PubMed Abstracts" }
Contrast-Enhanced Ultrasound for the Characterization of Malignant versus Benign Focal Liver Lesions in a Prospective Multicenter Experience - The SRUMB Study. This study evaluated the accuracy of contrast-enhanced ultrasound (CEUS) for the differential diagnosis of benign vs. malignant focal liver lesions (FLL) in a real-life, multicenter experience. This prospective study, including 14 Romanian centers, was performed over a 6 year period (February 2011- April 2017) and included 2062 FLLs assessed by CEUS. Inclusion criteria were: newly diagnosed FLL on B-mode ultrasound, less than three lesions/patient, all FLLs evaluated by CEUS and by a second-line imaging technique (contrast enhanced CT or contrast enhanced MRI) or histology, considered as reference. The trial was registered in clinicaltrials.gov (Identifier NCT01329458). From the 2062 FLLs included in the study, 57.2% (1179) were malignant and 42.8% (883) were benign. CEUS had 83.9% sensitivity (Se), 97.8% specificity (Sp), 98.1% positive predictive value (PPV), 82.2% negative predictive value (NPV) and a diagnostic accuracy (Ac) of 89.9% for the positive diagnosis of malignant lesions. For the benign lesions, CEUS had 97.8% Se, 83.9% Sp, 82.2% PPV, 98.1% NPV 89.9% Ac. The diagnostic performance of CEUS for hepatocellular carcinoma was 76.6% Se, 98.4% Sp, and 91.2% Ac; for hemangioma: 89.2% Se, 99% Sp, and 96.9% Ac and for metastases: 90.9% Se, 98.4% Sp, and 96.9% Ac. CEUS proved a high accuracy in differentiating the malignant vs. benign character of a FLL. It can be confidently used as a first line imaging method in daily practice.
{ "pile_set_name": "PubMed Abstracts" }
Cyclestheria hislopi (Crustacea: Branchiopoda): a group of morphologically cryptic species with origins in the Cretaceous. Cyclestheria hislopi is thought to be the only extant species of Cyclestherida. It is the sister taxon of all Cladocera and displays morphological characteristics intermediate of Spinicaudata and Cladocera. Using one mitochondrial (COI) and two nuclear (EF1α and 28S rRNA) markers, we tested the hypothesis that C. hislopi represents a single circumtropic species. South American (French Guiana), Asian (India, Indonesia, Singapore) and several Australian populations were included in our investigation. Phylogenetic and genetic distance analyses revealed remarkable intercontinental genetic differentiation (uncorrected p-distances COI>13%, EF1α>3% and 28S>4%). Each continent was found to have at least one distinct Cyclestheria species, with Australia boasting four distinct main lineages which may be attributed to two to three species. The divergence of these species (constituting crown group Cyclestherida) was, on the basis of phylogenetic analyses of COI and EF1α combined with molecular clock estimates using several fossil branchiopod calibration points or a COI substitution rate of 1.4% per million years, dated to the Cretaceous. This was when the South American lineage split from the Asian-Australian lineage, with the latter diverging further in the Paleogene. Today's circumtropic distribution of Cyclestheria may be best explained by a combination of Gondwana vicariance and later dispersal across Asia and Australia when the tectonic plates of the two continents drew closer in the early Miocene. The lack of morphological differentiation that has taken place in this taxon over such a long evolutionary period contrasts with the high level of differentiation and diversification observed in its sister taxon the Cladocera. Further insights into the evolution of Cyclestheria may help us to understand the evolutionary success of the Cladocera.
{ "pile_set_name": "PubMed Abstracts" }
Health-seeking patterns among participants of population-based morbidity surveillance in rural western Kenya: implications for calculating disease rates. Calculation of disease rates in developing countries using facility-based surveillance is affected by patterns of health utilization. We describe temporal patterns in health care seeking by syndrome as part of population-based morbidity surveillance in rural western Kenya. From July 2006 to June 2008, health utilization data were collected from 27 171 participants at biweekly home visits and at Lwak Hospital, the designated referral clinic where free care provided by dedicated study clinical staff was available. Ill persons were asked if and where they sought care. Proportions seeking care for children and adults with fever, acute respiratory infection (ARI), acute lower respiratory infection (ALRI), and diarrhea were compared by Chi-square test. Care-seeking by distance was evaluated by logistic regression. While care-seeking outside the home was common for all syndromes (>50%), only 18-38% of care-seeking was to health facilities. Children were more likely than adults to visit health facilities for all syndromes. Of ill persons visiting Lwak Hospital, 45-54% had previously sought care elsewhere, mostly from informal drug sellers, and 11-24% with fever, ARI, or ALRI had already taken an antimalarial or antibiotic. The distance from the participant's home to Lwak Hospital was the most common reason (71%) for ill participants not seeking care there. The likelihood of visiting Lwak decreased with increasing distance of residence (p<0.001) and fluctuated significantly over the study period. Even in a study setting where free and reliable care is offered, health utilization is affected by other factors, such as distance. Health utilization data in population-based surveillance are important in adjusting disease rates.
{ "pile_set_name": "PubMed Abstracts" }
Elective Cardioversion in the Era of Novel Oral Anticoagulants - Does a Nurse Administered Verbal Questionnaire for Compliance Negate the Need for Routine Transoesophageal Echocardiography? Anticoagulation prior to elective external direct current cardioversion (EDCCV) is mandatory. The inability to monitor compliance with novel oral anticoagulants (NOACs) raises a potential safety issue. We aimed to evaluate whether a structured, nurse-led assessment of compliance prior to EDCCV ensures safety without the need for routine transoesophageal echocardiography (TOE). Data was prospectively collected on consecutive patients undergoing EDCCV during 2014-2015. All procedures were supervised by an electrophysiology clinical nurse consultant (EPCNC). Drug compliance was verbally assessed using a standardised questionnaire by the EPCNC. Novel oral anticoagulants compliance was required for a continuous period of 3 weeks prior to EDCCV; otherwise a TOE-guided EDDCV was performed. All patients had follow-up 30 days post-procedure. Three hundred and eleven cardioversions were performed on 256 patients in whom 154 (49.5%) were prescribed a NOAC (rivaroxaban (n=105; 68.2%), dabigatran (n=38; 24.7%), apixaban (n=11; 7.1%)). Median age was 63 years (24-94 yrs), mean CHADS2-Vasc score was 2.0±1.5 and 138 (89.6%) were outpatients. One hundred and twenty-nine (83.8%) EDCCV were for atrial fibrillation and 25 (16.2%) for atrial flutter. Sinus rhythm was achieved in 90.3% of cases. Fourteen patients (9%) assessed as non-compliant underwent TOE. 129 (83.8%) EDCCV were performed without prior TOE. No stroke or systemic embolism was identified in any patient treated with either warfarin or a NOAC. A standardised, verbal questionnaire can be administered to detect NOAC non-compliance in patients undergoing EDCCV. With appropriate compliance assessment a nurse-led EDCCV without routine TOE did not significantly compromise safety in this study group.
{ "pile_set_name": "PubMed Abstracts" }
Callus induction and high frequency plant regeneration in Italian millet (Setaria italica). Callus was induced from mature seeds of two cultivars of Setaria italica (L.) on Murashige and Skoog's medium (1962) supplemented with 2mg/l 2,4-D and 0.5 mg/l KN. Regenerating ability of the callus was better in the cultivar 315 compared to 212. Organogenesis was influenced not only by cytokinin, but also by the sucrose concentration in the medium. High frequency (80%) plant regeneration was achieved and quantified on the basis of callus fresh weight. The ability of the callus (cultivar 212) to regenerate whole plants was retained until the 5th passage, but during the 6th passage it declined considerably.
{ "pile_set_name": "PubMed Abstracts" }
Three-dimensional magnetic resonance cholangiopancreatography with respiratory triggering in the diagnosis of primary sclerosing cholangitis: comparison with endoscopic retrograde cholangiography. The purpose of this study was to evaluate the accuracy of respiratory-triggered three-dimensional magnetic resonance cholangiopancreatography (3D-MRCP) for the detection of primary sclerosing cholangitis (PSC) and to compare the specific findings of magnetic resonance cholangiography and endoscopic retrograde cholangiography in patients with PSC. The MRCP findings were evaluated in 150 patients with clinical symptoms (progressive fatigue, pruritus followed by icterus) and/or elevated values for alkaline phosphatase and serum aspartate transaminase, and occasionally an elevated serum concentration of bilirubin as a sign of cholestasis, who were consecutively referred for magnetic resonance imaging. Two observers independently classified bile duct abnormalities and established the MRCP diagnosis in a consensus reading. The results of MRCP were compared with the definitive diagnosis, which was based on the clinical history and laboratory and histological data, as well as on endoscopic retrograde cholangio-pancreatography (ERCP) findings. In a second step, the observers compared the delineation of the biliary system and morphological findings using MRCP and ERCP in patients with confirmed PSC. Diagnostic examinations were obtained in 146 of the 150 MRCPs (97 %). The diagnosis of PSC was confirmed by clinical data and ERCP in 34 of these 150 patients (23 %). The sensitivity and specificity of MRCP for diagnosing PSC were 88 % (29 of 33) and 99 % (108 of 109), respectively. MRCP and ERCP yielded similar scores for the delineation of the biliary system (P = 0.2) in patients with PSC. However, different bile duct abnormalities leading to the diagnosis of PSC were depicted by MRCP and ERCP; more bile duct stenoses and pruning were seen with ERCP and more skip dilatation with MRCP (P < 10(-4)). In patients with PSC, MRCP is a highly sensitive method and its diagnostic accuracy is comparable to that of ERCP.
{ "pile_set_name": "PubMed Abstracts" }
Recurrent malignant Leydig cell tumor of testis: a case report with review of literature. Malignant Testicular Leydig Cell tumors (leydigomas) are extremely rare to occur and mostly carry a bad prognosis. Here we describe the disease course of a middle aged patient with recurrent / metastatic Leydig cell tumor of testes, who needed repeated oncosurgical intervention and chemotherapy.
{ "pile_set_name": "PubMed Abstracts" }
[Effect of surface-active substances on bioluminescence intensity of bacteria]. The study of sensitivity of luminous bacteria isolated from the Black and Azov seas to surfactants from various classes was carried out. It was shown that cationic surfactants had a strong inhibition effect on bacterial luminescence in contrast to anionic and in particular nonionic surfactants. To increase the luminous bacteria sensitivity to the action of OP-10 (nonionic surfactant) and ABS (anionic surfactant), which are widely used in industry, several approaches have been developed. They include modulation of bacterial sensitivity by the additives of cationic substances, use of luminous bacteria at a logarithmic stage of growth, realization of biotesting at low pH = 5.5. The use of these approaches allows to lower effective concentrations of OP-10 and ABS, which caused a decrease of bioluminescence by 50%, 3-200 times and opens perspectives for the use of the bioluminescent method to study these surfactants toxicity on the principle of biosensorics.
{ "pile_set_name": "PubMed Abstracts" }
[Ecological and biological characteristics of Drosophila melanogaster features depending on the dose of electromagnetic radiation of various types]. Biological effects of exposure to red light (lambda = 660 +/- 10 nm) on the viability and morphophysiological characteristics of Drosophila melanogaster have been studied. The ability of this physical agent to modify these features is shown. The degree of expression and impact of biological effects depend on the dose, functional and genetic status of the organism. The study of the life expectancy of the exposed to EHF and white light D. melanogaster has revealed that expression of the features depends on the radiation doses, genotype, sex, the nature of the position of wings and lighting conditions. It has been found that the dark mode (24 h-night) is more favorable than the artificial lighting. Individuals with the left wing at the top are more sensitive to the external factors.
{ "pile_set_name": "PubMed Abstracts" }
Migration of an abandoned pacemaker generator into the pouch of Douglas in a child with complex congenital heart disease. A young girl with complex congenital heart disease underwent Fontan procedure and multiple pacemaker revisions, including abandonment of an intraabdominal pacemaker generator at age eight. She presented two years later with constipation and abdominal twitching. Radiographs, pacemaker interrogation, and laparoscopy confirmed dislocation of the abandoned generator and intraperitoneal migration into the pouch of Douglas. The device was removed surgically without incident.
{ "pile_set_name": "PubMed Abstracts" }
The Sines industrial complex monitoring programme: A preliminary report. It is anticipated that the establishment of the industrial complex at Sines, Alentejo, Portugal, will have some impact on the environment. Details of the methods used in the monitoring programme are provided. Records of the epiphytic lichen vegetation in permanent quadrats have been made and changes shown in selected sites over a three year period are discussed. Material has been collected for analysis for heavy metals and the results discussed. There is considerable variation in replicates and in interspecies values. The problem of age and bio-accumulation is mentioned. Scanning electron microscopy has shown the accumulation of particulates, as yet unidentified, the quantity varying with increase in age and surface texture. A broadly based study of the local epiphytic flora is being carried out to record the present day diversity. There appears, as yet, to be no detectable influence of the industrial complex on the epiphytic flora of the permanent quadrats.
{ "pile_set_name": "PubMed Abstracts" }
Schistosomiasis may contribute to goblet cell carcinoid of the appendix. Abstract : To investigate whether schistosomiasis can contribute to appendiceal goblet cell carcinoid, appendix samples were obtained from 3 patients with combined appendiceal schistosomiasis and goblet cell carcinoid (CSG), 6 patients with goblet cell carcinoid only (GCC), 12 patients with appendiceal schistosomiasis only (ASO), and 12 cases with normal appendix (NA), all of similar gender ratio and age distributions. Hematoxylin and eosin-(H&E) stained sections were studied in 3 CSGs and 12 ASOs to diagnose schistosomiasis by detecting schistosome eggs. H&E and alcian blue/PAS-stained sections and immunohistochemistry of CgA and CEA were employed to establish the diagnosis of GCC in the 3 CSGs and 6 GCCs. Then, to determine whether schistosomiasis can contribute to GCC, immunostaining patterns of CgA and Ki67 in mucosal crypt epithelia were investigated and compared among all 33 cases. Our results revealed typical histological and immunohistochemical phenotypes of GCC in the 3 CSGs and 6 GCCs and schistosome egg deposits in 3 CSGs and 12 ASOs. We found that the expression levels of both CgA and Ki67 in mucosal crypt epithelia were significantly higher in CSG than in GCC (P < 0.05 = 0.013 and P = 0.004, respectively). Moreover, high expression levels of both CgA and Ki67 in mucosal crypt epithelia favor ASO as compared to NA (P < 0.001 = 3.4 × 10(-6) and 3.1 × 10(-5), respectively). Our findings suggest that appendiceal schistosomiasis was associated with increased proliferation and neuroendocrine differentiation of mucosal pluripotent crypt cells and that it may contribute to GCC, which is documented to originate from mucosal pluripotent crypt cells in mucosal crypt epithelia.
{ "pile_set_name": "PubMed Abstracts" }
Oral leukoplakia associated with amalgam restorations. The World Health Organization has defined oral leukoplakia (OL) as "a white patch or plaque of the oral mucosa that cannot be characterized clinically or pathologically as any other disease". A 21-year-old male with OL presented with a bilateral burning sensation in the buccal mucosa. The patient had amalgam restorations, and an epicutaneous patch test indicated a positive response to amalgam. The amalgam restorations were therefore removed and the cavities were refilled with a composite resin restorative material. During 5 years of follow-up, there was no recurrence of the oral lesions. This case illustrates that amalgam fillings may cause OL lesions. (J Oral Sci 58, 445-448, 2016).
{ "pile_set_name": "PubMed Abstracts" }
Analyzing protein function on a genomic scale: the importance of gold-standard positives and negatives for network prediction. The concept of 'protein function' is rather 'fuzzy' because it is often based on whimsical terms or contradictory nomenclature. This currently presents a challenge for functional genomics because precise definitions are essential for most computational approaches. Addressing this challenge, the notion of networks between biological entities (including molecular and genetic interaction networks as well as transcriptional regulatory relationships) potentially provides a unifying language suitable for the systematic description of protein function. Predicting the edges in protein networks requires reference sets of examples with known outcome (that is, 'gold standards'). Such reference sets should ideally include positive examples - as is now widely appreciated - but also, equally importantly, negative ones. Moreover, it is necessary to consider the expected relative occurrence of positives and negatives because this affects the misclassification rates of experiments and computational predictions. For instance, a reason why genome-wide, experimental protein-protein interaction networks have high inaccuracies is that the prior probability of finding interactions (positives) rather than non-interacting protein pairs (negatives) in unbiased screens is very small. These problems can be addressed by constructing well-defined sets of non-interacting proteins from subcellular localization data, which allows computing the probability of interactions based on evidence from multiple datasets.
{ "pile_set_name": "PubMed Abstracts" }
Erythrocyte oxidative damage in chronic fatigue syndrome. It has been hypothesized that a link exists between erythrocyte metabolism (particularly redox metabolism) and erythrocyte shape and that both are related to erythrocyte deformability. The aim of this research is to confirm the results of earlier studies and to investigate a correlation between erythrocyte morphology and erythrocyte oxidative damage in chronic fatigue syndrome (CFS). Reduced glutathione (GSH), malondialdehyde (MDA), methemoglobin (metHb) and 2,3-diphosphoglyceric acid (2,3-DPG) were measured in 31 patients suffering from CFS and 41 healthy control subjects. Scanning electron microscopic studies of the erythrocytes from both groups were also carried out. There was evidence of oxidative damage in CFS with statistically significant increases in 2,3-DPG (p < 0.05), metHb (p < 0.005) and MDA (p < 0.01). The CFS patients in this study also had significantly more stomatocytes in their blood than the normal subjects (p < 0.005). There is a strong likelihood that the increase in erythrocyte antioxidant activity is associated with the presence of stomatocytes. The results of this study provide further evidence for the role of free radicals in the pathogenesis of CFS and a link between erythrocyte metabolism and erythrocyte shape.
{ "pile_set_name": "PubMed Abstracts" }
Cutaneous localization in multiple myeloma in the context of bortezomib-based treatment: how do myeloma cells escape from the bone marrow to the skin? The skin is a possible site of extramedullary localization in multiple myeloma (MM) patients; however, the mechanisms involved in this process are poorly understood. We describe the case of a refractory MM patient who developed a cutaneous localization under bortezomib treatment and we further expanded observations in other eight MM patients. We focused on the expression of genes involved in plasma cell skin homing, including CCR10, which was highly expressed. Moreover, we observed a lack of CXCR4 surface expression and the down-regulation of ICAM1/CD54 throughout the progression of the disease, suggesting a possible mechanism driving the escape of MM cells from the bone marrow into the skin.
{ "pile_set_name": "PubMed Abstracts" }
High-grade transitional cell carcinoma of the bladder in a 5-year-old boy successfully treated with partial cystectomy and intravesical bacillus Calmette-Guerin. Pediatric transitional cell carcinomas of the bladder are typically characterized by low-grade histology, adolescent and young adult age, and cure with surgical resection. Here, we report a high-grade transitional cell carcinoma of the bladder in a 5-year-old boy treated with a partial cystectomy and adjuvant intravesical Bacillus Calmette-Guerin.
{ "pile_set_name": "PubMed Abstracts" }
Achieving remission and recovery in bipolar disorder. Pharmacotherapy is the primary treatment for bipolar disorder, and several medications have proven efficacy for treating patients with the disorder. However, an efficacy/effectiveness gap exists in preventing recurrence of mood episodes and in returning patients to full functional recovery. A lack of treatment adherence is a major factor in treatment refractoriness in patients with bipolar disorder. Evidence suggests that psychoeducation can be a helpful tool in improving treatment adherence and in addressing other factors that complicate the treatment of bipolar disorder, such as comorbidity, substance use, and cognitive impairment.
{ "pile_set_name": "PubMed Abstracts" }
Pneumococcal conjugate vaccine: review of cost-effectiveness studies in Australia, North America and Europe. The pneumococcal conjugate vaccine (PCV) is the first vaccine proven to be effective in reducing the incidence of invasive pneumococcal disease, pneumonia and acute otitis media in children, and has been recommended for universal use in children in a number of high-income countries. The high cost of the vaccine relative to previous vaccines has generated interest in assessing its cost-effectiveness and numerous cost-effectiveness analyses of PCV have been performed in Australia, North America and Europe. The primary objectives of this review are to enhance the ability to make direct comparisons between these analyses, to aid in the identification and interpretation of methodological differences and to summarize the findings. Although these studies varied greatly in terms of methodology and assumptions, if and when indirect effects and quality-of-life improvements are taken into account, the cost-effectiveness ratios of PCV in these countries are likely to be within the ranges generally considered favorable vis-à-vis other health interventions.
{ "pile_set_name": "PubMed Abstracts" }
The minimum quantity of nitrite required to stain sliced and homogenised cooked pork. The levels of nitrite used in curing pork are in excess of those required to produce an adequate cured colour, but the minimum level for pink coloration to be visible has not been established experimentally. This paper demonstrates the effect of low nitrite levels from local surface application to pork muscle, simulating inadvertent contamination from work surfaces. An homogenate is used for comparison in which the nitrite was evenly distributed throughout the product. The results indicate that surface contact with nitrite produces essentially the same pattern of colour change as in the homogenate. Visible pink coloration was evident from 1-2 mg kg(-1) sodium nitrite absorbed.
{ "pile_set_name": "PubMed Abstracts" }
Circulating soluble CR1 (CD35). Serum levels in diseases and evidence for its release by human leukocytes. C receptor type 1 (CR1, CD35) is present in a soluble form in plasma (sCR1). Soluble CR1 was measured with a specific ELISA assay in normal individuals and in patients with different diseases. The mean serum concentration of sCR1 in 31 normal donors was 31.4 +/- 7.8 ng/ml, and was identical in plasma. An increase in sCR1 was observed in 36 patients with end-stage renal failure on dialysis (54.8 +/- 11.7 ng/ml, p < 0.0001), and in 22 patients with liver cirrhosis (158.3 +/- 49.9 ng/ml, p < 0.0001). The mean sCR1 levels dropped from 181 +/- 62.7 to 52.1 +/- 24.0 ng/ml (p < 0.001) in nine patients who underwent liver transplantation, and was 33.5 +/- 7.3 in 10 patients with functioning renal grafts, indicating that the increase in sCR1 was reversible. Soluble CR1 was elevated in some hematologic malignancies (> 47 ng/ml), which included B cell lymphoma (12/19 patients), Hodgkin's lymphoma (4/4), and chronic myeloproliferative syndromes (4/5). By contrast, no increase was observed in acute myeloid or lymphoblastic leukemia (10) or myeloma (5). In two patients with chronic myeloproliferative syndromes, sCR1 decreased rapidly after chemotherapy. The mean concentration of sCR1 was not significantly modified in 181 HIV-infected patients at various stages of the disease (34.8 +/- 14.4 ng/ml), and in 13 patients with active SLE (38.3 +/- 19.6 ng/ml), although in both groups the number of CR1 was diminished on E. There was a weak but significant correlation between sCR1 and CR1 per E in HIV infection and SLE (r = 0.39, p < 0.0001, and r = 0.60, p < 0.03 respectively). In vitro, monocytes, lymphocytes, and neutrophils were found to release sCR1 into culture supernatants. In vivo, sCR1 was detected in the serum of SCID mice populated with human peripheral blood leukocytes. The sCR1 levels correlated with those of human IgG (r = 0.97, p < 0.0001), suggesting synthesis of sCR1 by the transferred lymphocytes. The mechanisms underlining the increased levels of sCR1 and its biologic consequences remain to be defined.
{ "pile_set_name": "PubMed Abstracts" }
Detection of the cyanobacterial hepatotoxins microcystins. Concern regarding the presence of microcystins in drinking water and their possible contamination in food (e.g., salad vegetables, fish, shellfish) has resulted in the need for reliable methods for the detection and accurate quantification of this class of toxins. Currently, routine analysis of microcystins is most commonly carried out using high-performance liquid chromatography with photodiode array detection (HPLC-PDA), although more sensitive biological assays such as antibody-based ELISAs and protein phosphatase inhibition assays have also proven useful. However, many of these methods have been hindered by the availability of a wide range of purified microcystins. Although over 60 variants have now been reported, only a very small number are commercially available and calibrated standards are not yet obtainable. This has led to the common practice of reporting microcystin-LR equivalence regardless of which variant is present. The increased availability of HPLC with online mass spectral analysis (HPLC-MS) may facilitate more accurate detection of toxin variants but as several microcystins share the same molecular mass, definitive identification can be difficult. A further difficulty in analyzing microcystins is the requirement for sample processing before analysis. Solid phase extraction (SPE) is typically used to enrich environmental concentrations of microcystins, or to eliminate contaminants from complex samples such as animal and plant tissues. Recently, new technologies employing recombinant antibodies and molecularly imprinted polymers have been exploited to develop assays and biosensors for microcystins. These novel detection systems are highly sensitive, often do not require sample processing, and offer a simpler, less expensive alternative to analytical techniques. They have also been successfully employed in solid phase extraction formats for the concentration and clean up of environmental samples before HPLC analysis.
{ "pile_set_name": "PubMed Abstracts" }