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Molecular basis for the interaction of four different classes of substrates and inhibitors with human aromatase.
Aromatase cytochrome P450 (CYP19) converts androgen to estrogen. In this study, the interactions of four classes of compounds, 17beta-estradiol (the product of aromatase), 17-methyltestosterone (a synthetic androgen), dibenzylfluorescein (a synthetic substrate of aromatase), and coumestrol (a phytoestrogen), with aromatase were investigated through spectral analysis using purified human recombinant aromatase and site-directed mutagenesis studies using CHO cells expressing wild-type human aromatase or five aromatase mutants, E302D, D309A, T310S, S478T and H480Q. Spectral analysis showed that a type I binding spectrum was produced by the binding of 17-methyltestosterone to aromatase and a novel binding spectrum of aromatase was induced by dibenzylfluorescein. Mutagenesis experiments demonstrated that residues S478 and H480 in the beta-4 sheet play an important role in the binding of all four compounds. Computer-assisted docking of these compounds into the three-dimensional model of aromatase revealed that: (1) weak interaction between 17beta-estradiol and the beta-4 sheet of aromatase facilitates the release of 17beta-estradiol from the active site of aromatase; (2) 17-methyl group of 17-methyltestosterone affects its binding to aromatase; (3) dibenzylfluorescein binds to the active site of aromatase with its O-dealkylation site near the heme iron and residue T310; and (4) coumestrol binds to aromatase in a manner such that rings A and C of coumestrol mimic rings A and B of steroid. These structure-function studies help us to evaluate the structural model of aromatase, and to accelerate the structure-based design for new aromatase inhibitors. | {
"pile_set_name": "PubMed Abstracts"
} |
Ginterferon (human leukocyte interferon) efficiency in the treatment of viral diseases. 1. Efficiency in viral keratoconjunctivitis.
Ginterferon is a human leukocyte interferon (IFN) produced in the "V. Babes" Institute by in vitro culture of leukocytes separated from neonatal cord blood. Ginterferon (50,000 IU/ml) was administered to 40 patients who suffered for at least two weeks of a hepatic keratoconjunctivitis resistant to treatment with conventional regimens of human immunoglobulins, Iduviran or topical antiinflammatory drugs. In 35 cases (87%) complete recovery (total epithelialization and disappearance of all symptoms) occurred in a significantly shorter time (10-14 days) as compared to similar cases which recovered after 30-40 days by conventional treatment. Local or general untoward effects were not observed in any of the patients. Recovery in the remaining 5 cases was slower, 28-30 days. This slow response may have been due to unusual weakness of the general immunobiological condition in these patients (myocardial infarction or repeated stress) which might have favoured repeated waves of virus spreads from foci of viral latency which are not attained by the topically administered IFN. | {
"pile_set_name": "PubMed Abstracts"
} |
[Usefulness of home visits in the control and evaluation of the appropriate use of home continuous oxygen therapy].
The aim of this study was to determine the usefulness of home visits to monitor and evaluate the appropriate use of domiciliary oxygen therapy (DOT). Appropriateness was based on the coincidence of circumstances needed to predict benefit from DOT: appropriate indications correct hypoxemia and patient compliance. All patients receiving DOT residing in the town of L'Hospitalet (Barcelona) in June 1994 were enrolled. During a home visit to each patient a questionnaire was administered and spirometric variables, CO in exhaled air and pulse oximetry were recorded. If DOT was not considered appropriate, the patient was referred to the hospital clinic for reevaluation of the prescription. One hundred twenty-eight patients (74% men) were visited. Mean age was 68 years. Use of DOT was seen to be appropriate in only 26% of patients. The prescription of DOT was considered strictly correct in 73 patients (49%); 13 of them were seen to have continued smoking. Of the 60 remaining patients, hypoxemia was correct with oxygen therapy in 46, and of these only 33 complied with DOT. The home visit combined with hospital monitoring allowed us to withdraw DOT from 20 patients, for whom the indications had been incorrect, and to introduce changes in oxygen supply sources for 16 patients who carried pumps. Fourteen started using a concentrator and 2 began using liquid oxygen. Periodic review is necessary for optimal treatment of DOT. The home visit is a good tool for improving DOT follow-up, as it allows the patient to be assessed in the setting where DOT is really applied. It is a monitoring method that is well accepted by the patient. | {
"pile_set_name": "PubMed Abstracts"
} |
Satisfactory results at 8 years mean follow-up after ADVANCE® medial-pivot total knee arthroplasty.
Although good overall results have been reported with TKA, certain problems and limitations remain, primarily due to postoperative differences in joint kinematics, when compared with the normal knee. ADVANCE® Medial-Pivot TKA involves replicating the medial pivoting behavior observed in normal knees. Here, we aimed to investigate the clinical and radiological results and complications of TKA using this implant, at mid-term follow-up. From January 2001 to March 2012, we retrospectively selected 76 patients (85 knees; mean age at operation, 70.2±8.1 years; range, 51-88 years) with a mean follow-up period of 93.1±14.3 months (range, 72-132 months). Indications for TKA included primary degenerative osteoarthritis (60 knees), rheumatoid arthritis (22 knees), osteonecrosis (two knees), and osteoarthritis following high tibial osteotomy (one knee). The clinical and radiographic results were evaluated. Kaplan-Meier survivorship analysis indicated a success rate of 98.3% (95% confidence interval, 96.6-99.9%). Comparison of pre- and postoperative knee extension angles and ranges of motion showed significant improvement postoperatively, in both the Knee Society Scores (KSS) and Knee Society Functional Scores (KSFS) (p<0.05). In one case, radiographic assessment indicated implant loosening due to infection; however, despite this complication, significant improvement of postoperative varus or valgus deformity angles were noted in all cases (p<0.05). Patients undergoing ADVANCE® Medial-Pivot TKA achieved excellent clinical and radiographic results without any implant-related failures at mid-term follow-up. Level IV. | {
"pile_set_name": "PubMed Abstracts"
} |
A comparison of two approaches to training visual analysis of AB graphs.
Visual analysis is the primary method of evaluating data in single-subject research. Few studies have evaluated interventions to teach visual analys is skills. The purpose of this study was to evaluate systematic instruction, delivered using computer-based intervention or a recorded lecture, on identifying changes in slope and level in AB graphs. Results indicated that both approaches were significantly more effective than a no-treatment control condition but were not different from each other. We discuss the implications of these results for training and directions for future research. | {
"pile_set_name": "PubMed Abstracts"
} |
Spatial distribution of motor units recruited during electrical stimulation of the quadriceps muscle versus the femoral nerve.
In this study we investigated differences in the spatial recruitment of motor units (MUs) in the quadriceps when electrical stimulation is applied over the quadriceps belly versus the femoral nerve. M-waves and mechanical twitches were evoked using over-the-quadriceps and femoral nerve stimulation of gradually increasing intensity from 22 young, healthy subjects. Spatial recruitment was investigated using recruitment curves of M-waves recorded from the vastus medialis (VM) and vastus lateralis (VL) and of twitches recorded from the quadriceps. At maximal stimulation intensity (Imax), no differences were found between nerve and over-the-quadriceps stimulation. At submaximal intensities, VL M-wave amplitude was higher for over-the-quadriceps stimulation at 40% Imax, and peak twitch force was greater for nerve stimulation at 60% and 80% Imax. For the VM, MU spatial recruitment during nerve and over-the-quadriceps stimulation of increasing intensity occurred in a similar manner, whereas significant differences were observed for the VL. | {
"pile_set_name": "PubMed Abstracts"
} |
Detailed bacteriologic tests to identify the origin of transvenous pacing system infections indicate a high prevalence of multiple organisms.
The reported incidence of pacing system-related infections (PSIs) varies widely, and the roles of leads and blood cultures remain poorly defined. Leads and blood cultures were obtained prospectively in 224 patients with suspected PSIs, and the results of cultures of blood and extravascular and intravascular lead fragments were compared. In 12.3% of the patients, no microorganism was found on the leads. Lead cultures with > or =1 microorganism cultured on the extravascular and intravascular fragments of the leads were found in 88.5% of the positive lead cultures. Infection was caused by Staphylococcus epidermidis and coagulase-negative staphylococci in 66.0% and 29.5%, respectively. Only 33 patients had positive blood cultures according to the Duke criteria with the same microorganism found by lead cultures in 30 cases. Infection was caused by multiple organisms in 39 (25%) patients. (1) Regardless of the clinical presentation, the extravascular and intravascular body of the lead is infected, even when the infection is local. More than one microorganism may be implicated. (2) Bacteriologic analyses must be performed on several segments of each implanted lead. (3) More than 2 positive blood cultures are a reliable clinical criterion for the diagnosis of pacemaker lead-related infection, but blood cultures alone are an insensitive method to identify the cause of infection. (4) Up to 50% of microorganisms isolated in a single blood culture are also recovered in lead cultures. | {
"pile_set_name": "PubMed Abstracts"
} |
Occlusal force after partial mandibular resection.
Surgical resection of a segment or loss of mandibular continuity can adversely affect most of the structures essential for maximum occlusal force. Five subjects who had partial mandibular resections for treatment of squamous cell carcinoma were studied. Occlusal force was recorded before and after cancer treatment and following prosthetic rehabilitation. A gnathodynamometer was used to record anterior occlusal force. Five edentulous and five dentate cancer-free subjects matched for age were studied to establish comparable normative data. The null hypothesis that partial mandibular resection would not affect maximum occlusal force was rejected (p = 0.0101). Mandibular resection did alter maximum occlusal force. The impact of the decrease in maximum occlusal force on masticatory function is yet to be determined. | {
"pile_set_name": "PubMed Abstracts"
} |
Learning game for training child bicyclists' situation awareness.
Encouraging more children to bicycle would produce both environmental and health benefits, but bicycling accidents are a major source of injuries and fatalities among children. One reason for this may be children's less developed hazard perception skills. We assume that children's situation awareness could be trained with a computer based learning game, which should also improve their hazard perception skills. In this paper, we present a prototype for such a game and pilot it with 8-9year old children. The game consisted of videos filmed from a bicyclist's perspective. Using a touchscreen, the player's task was to point out targets early enough to gain points. The targets were either overt (other visible road users on a potentially conflicting course) or covert (occlusions, i.e. locations where other road users could suddenly emerge). If a target was missed or identified too late, the video was paused and feedback was given. The game was tested with 49 children from the 2nd grade of primary school (aged 8-9). 31 young adults (aged 22-34) played the game for comparison. The effect of the game on situation awareness was assessed with situation awareness tests in a crossover design. Similar videos were used in the tests as in the game, but instead of pointing out the targets while watching, the video was suddenly masked and participants were asked to locate all targets which had been present just before the masking, choosing among several possible locations. Their performance was analyzed using Signal Detection Theory and answer latencies. The game decreased answer latency and marginally changed response bias in a less conservative direction for both children and adults, but it did not significantly increase sensitivity for targets. Adults performed better in the tests and in the game, and it was possible to satisfactorily predict group membership based on the scores. Children found it especially difficult to find covert targets. Overall, the described version of the learning game cannot be regarded as an effective tool for situation awareness/hazard perception training, but ways to improve the game are discussed. | {
"pile_set_name": "PubMed Abstracts"
} |
A research program in medical physics for remote students.
The University of Adelaide in co-operation with the Royal Adelaide Hospital offers a degree of Master of Science (Medical Physics) which is available both to students resident in Adelaide and to remote students employed in hospitals in Australia or New Zealand. The program comprises research carried out in the work place, and courses delivered from Adelaide. The courses Radiation Biology, Protection and Epidemiology and Radiotherapy Physics are currently delivered on-line. A project has commenced to modify the presentation of all courses so that remote students can interact with their fellow students in weekly tutorials and engage in informal discussions through a discussion forum. | {
"pile_set_name": "PubMed Abstracts"
} |
Time trends in reported prevalence of kidney stones in the United States: 1976-1994.
A body of evidence establishes that the occurrence of kidney stone disease has increased in some communities of industrialized countries. Information on recent temporal trends in the United States is lacking and population-based data on epidemiologic patterns are limited. Study objective was to determine whether kidney stone disease prevalence increased in the United States over a 20-year period and the influence of region, race/ethnicity, and gender on stone disease risk. We measured the prevalence of kidney stone disease history from the United States National Health and Nutrition Examination Survey (II and III), population-based, cross-sectional studies, involving 15,364 adult United States residents in 1976 to 1980 and 16,115 adult United States residents in 1988 to 1994. Disease prevalence among 20- to 74-year-old United States residents was greater in 1988 to 1994 than in 1976 to 1980 (5.2% vs. 3.8%, P < 0.05), greater in males than females, and increased with age in each time period. Among 1988 to 1994 adults, non-Hispanic African Americans had reduced risk of disease compared to non-Hispanic Caucasians (1.7% vs. 5.9%, P < 0.05), and Mexican Americans (1.7% vs. 2.6%, P < 0.05). Also, age-adjusted prevalence was highest in the South (6.6%) and lowest in the West (3.3%). Findings were consistent across gender and multivariate adjusted odds ratios for stone disease history, including all demographic variables, as well as diuretic use, tea or coffee consumption, and dietary intake of calcium, protein, and fat did not materially change the results. Prevalence of kidney stone disease history in the United States population increased between 1980 and 1994. A history of stone disease was strongly associated with race/ethnicity and region of residence. | {
"pile_set_name": "PubMed Abstracts"
} |
[Prevalence of antibodies against the hepatitis C virus among the staff of a general hospital].
The prevalence of antibodies against hepatitis C virus (HCV) in 413 hospital staff (57% total staff) was 1.7%. There were no significant differences in the sanitary workers (physicians, nurses and assistants of clinic and laboratory) versus cleaners, office and other non-sanitary workers of hospital staff. The seropositivity to HCV was not related to sex, age, years in occupation and the prevalence of hepatitis B virus serological markers. This relatively low prevalence let suppose than the hospital staff is not a high risk group for HCV infection. | {
"pile_set_name": "PubMed Abstracts"
} |
Measurement of social learning and its relationship to cognitive, behavioral, demographic, and diagnostic variables.
A curriculum-based paper and pencil group-administered test was developed to assess the objectives of the Self Level of the Social Learning Curriculum. The major objective of the study was to determine the extent to which performance on this measure was related to cognitive skills and adaptive behavior. A total of 242 primary level EMR subjects were tested. The results indicated that a reliable assessment procedure which taps cognitive skills and behavioral dimentions is feasible. Both of these factors related to the major assumptions underlying the Social learning curriculum. | {
"pile_set_name": "PubMed Abstracts"
} |
Prehospital electrocardiogram shortens ischaemic time in patients with ST-segment elevation myocardial infarction.
Total ischaemic time should be shortened as much as possible in patients with ST-segment elevation myocardial infarction (STEMI). This study evaluated whether prehospital 12-lead electrocardiogram (ECG) could shorten system delay in STEMI management. From November 2015 to November 2017, 15 ambulances equipped with X Series Monitor/ Defibrillator (Zoll Medical Corporation) were used in the catchment area of Queen Mary Hospital, Hong Kong. Prehospital ECG was performed for patients with chest pain; the data were tele-transmitted to attending emergency physicians at the Accident and Emergency Department (AED) for rapid assessment. Data from patients with STEMI who were transported by these 15 ambulances were compared with data from patients with STEMI who were transported by ambulances without prehospital ECG or who used self-arranged transport. Data were analysed from 197 patients with STEMI. The median patient delay for activation of the emergency response system was 90 minutes; 12% of patients experienced a delay of >12 hours. There was a significant difference in delay between patients transported by ambulance and those who used self-arranged transport (P<0.001). For system delay, the use of prehospital ECG shortened the median time from ambulance on scene to first ECG (P<0.001). When performed upon ambulance on scene, prehospital ECG was available 5 minutes earlier than if performed in ambulance compartment before departure. Use of prehospital ECG significantly shortened AED door-to-triage time, AED door-to-first AED ECG time, AED door-to-physician consultation time, and length of stay in the AED (P<0.001 for all comparisons). Prehospital ECG shortened ischaemic time prior to hospital admission. | {
"pile_set_name": "PubMed Abstracts"
} |
Purification and characterization of Ca2+/calmodulin-dependent actin-binding proteins from squid retina.
Ca2+/calmodulin (CaM)-dependent actin-binding proteins (CABPs) of 92, 105, 120 and 135 kDa were purified from squid retina. These proteins were eluted from the CaM affinity column in a Ca2+-dependent manner, and binding of the CABPs to F-actin was regulated by Ca2+/CaM. Electron microscopic observations employing the low-angle rotary shadowing technique showed the CABP molecules to have granular shapes similar to the granular proteins associated with actin filaments in squid rhabdomeral microvilli. We have previously reported that these actin filaments are fragmented upon exposure to light [(1988) J. Cell Biol. 106, 1151-1160]. Since the intracellular Ca2+ concentrations of the invertebrate retina are elevated during the light illumination, these results indicate that the CABPs are directly associated with the actin filament in the microvilli of the squid photoreceptors. We therefore suggest that the CABPs may regulate the light-induced structural changes of the microvillar cytoskeleton. | {
"pile_set_name": "PubMed Abstracts"
} |
Increased expression of cytosolic glutathione S-transferases in drug-resistant L5178Y murine lymphoblasts: chemical selectivity and molecular mechanisms.
The level of induction of three cytosolic glutathione-S-transferase (GST) classes has been compared in L5178Y murine lymphoblasts resistant to either the quinone-containing compound, hydrolyzed benzoquinone mustard (HBM), or the aromatic alkylating agent aniline mustard (AM). Three established cell lines, L5178Y/HBM2, L5178Y/HBM10, and the partial revertant, L5178Y/HBMR, were 2.5-, 6-, and 2.9-fold resistant to HBM and showed 3-, 11-, and 9-fold increases in GST activity, respectively, relative to the sensitive L5178Y cell line. Western blot analysis of cytosolic proteins showed overexpression of all three cytosolic GST classes pi, alpha, and mu, with predominance of the pi class. Northern blot analysis demonstrated corresponding elevations in the steady-state mRNA levels of each GST class. The level of GST-mu and -alpha isoforms correlated more closely with HBM resistance, whereas GST-pi, the predominant isoform in these cells, paralleled enzyme activity. These findings suggested that other factors such as quinone reductase may contribute to resistance. The AM-resistant cell line L5178Y/AM was 10-fold resistant to the alkylating agent AM, and GST activity was elevated 3.6-fold relative to the parental L5178Y cell line. Western blot analysis and Northern blot analysis provided evidence of overexpression of all three cytosolic GST classes but with marked predominance of the alpha class. These studies provide evidence that induction of GST isoforms in drug-resistant cells may have both a nonspecific as well as a selective component. The difference in isozyme profile between HBM- and AM-resistant cell lines emphasizes how structural differences, in particular, the nature of the electrophilic signal, may influence the pattern of induction of GST isozymes. | {
"pile_set_name": "PubMed Abstracts"
} |
Advances in thermochemical conversion of woody biomass to energy, fuels and chemicals.
Biomass has been recognised as a promising resource for future energy and fuels. The biomass, originated from plants, is renewable and application of its derived energy and fuels is close to carbon-neutral by considering that the growing plants absorb CO2 for photosynthesis. However, the complex physical structure and chemical composition of the biomass significantly hinder its conversion to gaseous and liquid fuels. This paper reviews recent advances in biomass thermochemical conversion technologies for energy, liquid fuels and chemicals. Combustion process produces heat or heat and power from the biomass through oxidation reactions; however, this is a mature technology and has been successfully applied in industry. Therefore, this review will focus on the remaining three thermochemical processes, namely biomass pyrolysis, biomass thermal liquefaction and biomass gasification. For biomass pyrolysis, biomass pretreatment and application of catalysts can simplify the bio-oil composition and retain high yield. In biomass liquefaction, application of appropriate solvents and catalysts improves the liquid product quality and yield. Gaseous product from biomass gasification is relatively simple and can be further processed for useful products. Dual fluidised bed (DFB) gasification technology using steam as gasification agent provides an opportunity for achieving high hydrogen content and CO2 capture with application of appropriate catalytic bed materials. In addition, multi-staged gasification technology, and integrated biomass pyrolysis and gasification as well as gasification for poly-generation have attracted increasing attention. | {
"pile_set_name": "PubMed Abstracts"
} |
Responses of mouse liver to dechlorane plus exposure by integrative transcriptomic and metabonomic studies.
Dechlorane plus (DP), a chlorinated flame retardant, has been widely detected in different environmental matrices and biota. However, toxicity data for DP have seldom been reported. In the present study, we investigated hepatic oxidative stress, DNA damage, and transcriptomic and metabonomic responses of male mice administered 500 mg/kg, 2000 mg/kg, and 5000 mg/kg of DP by gavage for 10 days. The results showed that DP exposure increased the level of superoxide dismutase (SOD) and 8-hydroxy-2-deoxyguanosine (8-OHdG). The microarray-based transcriptomic results demonstrated that DP exposure led to significant alteration of gene expression involved in carbohydrate, lipid, nucleotide, and energy metabolism, as well as signal transduction processes. The NMR-based metabonomic analyses corroborated these results showing changes of metabolites associated with the above altered mechanisms. Our results demonstrate that an oral exposure to DP can induce hepatic oxidative damage and perturbations of metabolism and signal transduction. These observations provide novel insight into toxicological effects and mechanisms of action of DP at the transcriptomic and metabonomic levels. | {
"pile_set_name": "PubMed Abstracts"
} |
Physical function and perceived quality of life in older persons.
Physical function and quality of life represent two major components of multidimensional evaluation in older people. The aim of the study was to verify which specific physical function measure is a more important predictor of quality of life in these individuals. Data are from 73 community-dwelling older persons attending a geriatric cardiovascular clinic. Linear regressions and analyses of covariance were performed to explore the relationships between physical function measures (4-meter walking test [4mWS], Short Physical Performance Battery [SPPB], Activities of Daily Living [ADL], and Instrumental ADL [IADL]) and quality of life (assessed using the European Quality of Life [EuroQoL] instrument). To provide fair comparisons across all the physical function measures, results were provided according to their increase in standard deviation (SD). The mean age of the sample population (women 52%) was 77.6 (SD=8.3) years old. Given significant gender interactions between physical function and quality of life, separate analyses were conducted for men and women. In women, all physical function measures were significantly associated with quality of life measures in unadjusted models (p-values<0.05). The EuroQoL visual analogic scale maintained its significant associations with SPPB, ADL and IADL, even after adjustment for potential confounders. In men, no physical function measure was consistently associated with quality of life in the fully-adjusted models. Gender-specific differences in the perception of quality of life were reported for disabilities in specific IADL tasks. Physical function is associated with quality of life in older persons. In particular, disabilities in some specific IADL tasks seem to be especially perceived by women as undermining their quality of life. The use of the IADL scale in men may not be as reliable as in women. | {
"pile_set_name": "PubMed Abstracts"
} |
Zeatin and Thidiazuron Induced Embryogenic Calli From In Vitro Leaf and Stem of Jojoba (Simmondsia chinensis).
Jojoba is a promising industrial plant, which recommended with pharmaceutical benefits. The present study was conducted to stimulate embryogenic calli formation from jojoba using zeatin and thidiazuron (TDZ), as well as determination of the antioxidant activity of proliferated calli. For callus induction, leaf and stem explants derived from in vitro grown shootlets, were cultured on Murashige and Skoog (MS) medium with different combinations of 0.5 mg L-1 benzyl adenine (BA) or kinetin with 2,4-Dichlorophenoxyacetic acid (2,4-D), Naphthalene acetic acid (NAA) and picloram at 0.5 or 1mg L-1. To stimulate embryogenic calli, friable callus were transferred to woody plant medium (WPM) supplemented with different concentrations of zeatin or TDZ. Antioxidant activity of different treatments was determined using hexane or petroleum ether extraction. Data was analyzed as mean±standard deviation (SD). The MS medium supplemented with 0.5 mg L-1 BA+0.5 or 1 mg L-1 picloram was the best treatment to obtain friable calli from both explants types. WPM medium supplemented with 2 mg L-1 zeatin gave the highest percentage of embryogenic calli derived from leaf explants. While the highest percentage of embryogenic calli derived from stem explants was registered using 1 or 4 mg L-1 TDZ containing medium. Embryogenic calli originated from leaves explants on 1.5 mg L-1 zeatin showed promising activity of antioxidant with hexane extraction. However, embryogenic calli originated from stem explants on 1 mg L-1 TDZ showed the highest antioxidant activity with petroleum ether extraction. TDZ has promising effect on embryogenic callus induction from stem explants. While, zeatin has promising effect on embryogenic callus induction from leaf explants. | {
"pile_set_name": "PubMed Abstracts"
} |
Electrophysiological characterization of the human Na(+)/nucleoside cotransporter 1 (hCNT1) and role of adenosine on hCNT1 function.
We previously reported that the human Na(+)/nucleoside transporter pyrimidine-preferring 1 (hCNT1) is electrogenic and transports gemcitabine and 5'-deoxy-5-fluorouridine, a precursor of the active drug 5-fluorouracil. Nevertheless, a complete electrophysiological characterization of the basic properties of hCNT1-mediated translocation has not been performed yet, and the exact role of adenosine in hCNT1 function has not been addressed either. In the present work we have used the two-electrode voltage clamp technique to investigate hCNT1 transport mechanism and study the kinetic properties of adenosine as an inhibitor of hCNT1. We show that hCNT1 exhibits presteady-state currents that disappear upon the addition of adenosine or uridine. Adenosine, a purine nucleoside described as a substrate of the pyrimidine-preferring transporters, is not a substrate of hCNT1 but a high affinity blocker able to inhibit uridine-induced inward currents, the Na(+)-leak currents, and the presteady-state currents, with a K(i) of 6.5 microM. The kinetic parameters for uridine, gemcitabine, and 5'-deoxy-5-fluorouridine were studied as a function of membrane potential; at -50 mV, K(0.5) was 37, 18, and 245 microM, respectively, and remained voltage-independent. I(max) for gemcitabine was voltage-independent and accounts for approximately 40% that for uridine at -50 mV. Maximal current for 5'-DFUR was voltage-dependent and was approximately 150% that for uridine at all membrane potentials. K(0.5)(Na(+)) for Na(+) was voltage-independent at hyperpolarized membrane potentials (1.2 mM at -50 mV), whereas I(max)(Na(+)) was voltage-dependent, increasing 2-fold from -50 to -150 mV. Direct measurements of (3)H-nucleoside or (22)Na fluxes with the charge-associated revealed a ratio of two positive inward charges per nucleoside and one Na(+) per positive inward charge, suggesting a stoichiometry of two Na(+)/nucleoside. | {
"pile_set_name": "PubMed Abstracts"
} |
Responding to a diagnosis of localized prostate cancer: men's experiences of normal distress during the first 3 postdiagnostic months.
Men experience localized prostate cancer (PCa) as aversive and distressing. Little research has studied the distress men experience as a normal response to PCa, or how they manage this distress during the early stages of the illness. The objective of this study was to explore the experience of men diagnosed with localized PCa during their first postdiagnostic year. This constructivist qualitative study interviewed 8 men between the ages of 44 and 77 years, in their homes, on 2 occasions during the first 3 postdiagnostic months. Individual, in-depth semistructured interviews were used to collect the data. After an initial feeling of shock, the men in this study worked diligently to camouflage their experience of distress through hiding and attenuating their feelings and minimizing the severity of PCa. Men silenced distress because they believed it was expected of them. Maintaining silence allowed men to protect their strong and stoic self-image. This stereotype, of the strong and stoic man, prevented men from expressing their feelings of distress and from seeking support from family and friends and health professionals. It is important for nurses to acknowledge and recognize the normal distress experienced by men as a result of a PCa diagnosis. Hence, nurses must learn to identify the ways in which men avoid expressing their distress and develop early supportive relationships that encourage them to express and subsequently manage it. | {
"pile_set_name": "PubMed Abstracts"
} |
Catharanthus roseus tissue culture: the effects of medium modifications on growth and alkaloid production.
A number of nutritional factors as well as the growth factors 2,4-D and IAA were studied to determine their influence on growth and alkaloid formation in Catharanthus roseus suspension cultures. The optimal 2,4-D concentration for growth and alkaloid production was 1 mg/liter. With IAA, both 0.5 and 2.0 mg/liter in media produced tissue growth comparable to tissue receiving 1 mg/liter 2,4-D; however, qualitative and quantitative differences in alkaloid production were observed. Media formulations containing 2,4 and 6% sucrose showed proportionate increases in cell yield with increased sucrose, but concomitant decreases in alkaloid production. Suspension cultures in media containing 2, 5, and 10 times the normal level of phosphate exhibited little change in growth or alkaloid production. When thiamin HCl, yridoxine nicotinic acid and inositol were deleted from the medium, the tissue continued to grow well through the 24 month duration of the experiment; however, alkaloid production was altered quantitatively and qualitatively. | {
"pile_set_name": "PubMed Abstracts"
} |
Synthesis and biological studies of pyrazolyl-diamine Pt(II) complexes containing polyaromatic DNA-binding groups.
New [PtCl(pz*NN)](n+) complexes anchored by pyrazolyl-diamine (pz*NN) ligands incorporating anthracenyl or acridine orange DNA-binding groups have been synthesized so as to obtain compounds that would display synergistic effects between platination and intercalation of DNA. Study of their interaction with supercoiled DNA indicated that the anthracenyl-containing complex L(2) Pt displays a covalent type of binding, whereas the acridine orange counterpart L(3) Pt shows a combination of intercalative and covalent binding modes with a strong contribution from the former. L(2) Pt showed a very strong cytotoxic effect on ovarian carcinoma cell lines A2780 and A2780cisR, which are, respectively, sensitive to and resistant to cisplatin. In these cell lines, L(2) Pt is nine to 27 times more cytotoxic than cisplatin. In the sensitive cell line, L(3) Pt showed a cytotoxic activity similar to that of cisplatin, but like L(2) Pt was able significantly to overcome cisplatin cross-resistance. Cell-uptake studies showed that L(2) Pt accumulates preferentially in the cytoplasm, whereas L(3) Pt reaches the cell nucleus more easily, as clearly visualized by time-lapse confocal imaging of live A2870 cells. Altogether, these findings seem to indicate that interaction with biological targets other than DNA might be involved in the mechanism of action of L(2) Pt because this compound, despite having a weaker ability to target the cell nucleus than L(3) Pt, as well as an inferior DNA affinity, is nevertheless more cytotoxic. Furthermore, ultrastructural studies of A2870 cells exposed to L(2) Pt and L(3) Pt revealed that these complexes induce different alterations in cell morphology, thus indicating the involvement of different modes of action in cell death. | {
"pile_set_name": "PubMed Abstracts"
} |
Cavernous hemangioma of the retina. Immunohistochemical and ultrastructural observations.
A 6-month old girl had unilateral leukokoria. Because retinoblastoma could not be excluded, the blind left eye was enucleated. Histopathologically, a total retinal detachment associated with a widespread cavernous hemangioma of the retina and a preretinal membrane were found. The specimen was further examined by immunohistochemistry and electron microscopy to determine the origin of the preretinal membrane and to study the anatomy of the telangiectatic retinal vessels. The preretinal membrane was mostly composed of spindle-shaped cells that demonstrated immunohistochemically the presence of glial fibrillary-acidic protein and showed, ultrastructurally, numerous glial filaments in their cytoplasm. These findings support the view that this membrane was of glial origin. By electron microscopy, the telangiectatic retinal vessels displayed the anatomic features normally encountered in retinal vessels, which accounts for the absence of exudates observed clinically and angiographically in cases of cavernous hemangioma of the retina. | {
"pile_set_name": "PubMed Abstracts"
} |
In silico evaluation, molecular docking and QSAR analysis of quinazoline-based EGFR-T790M inhibitors.
Mutated epidermal growth factor receptor (EGFR-T790M) inhibitors hold promise as new agents against cancer. Molecular docking and QSAR analysis were performed based on a series of fifty-three quinazoline derivatives to elucidate key structural and physicochemical properties affecting inhibitory activity. Molecular docking analysis identified the true conformations of ligands in the receptor's active pocket. The structural features of the ligands, expressed as molecular descriptors, were derived from the obtained docked conformations. Non-linear and spline QSAR models were developed through novel genetic algorithm and artificial neural network (GA-ANN) and multivariate adaptive regression spline techniques, respectively. The former technique was employed to consider non-linear relation between molecular descriptors and inhibitory activity of quinazoline derivatives. The later technique was also used to describe the non-linearity using basis functions and sub-region equations for each descriptor. Our QSAR model gave a high predictive performance [Formula: see text] and [Formula: see text]) using diverse validation techniques. Eight new compounds were designed using our QSAR model as potent EGFR-T790M inhibitors. Overall, the proposed in silico strategy based on docked derived descriptor and non-linear descriptor subset selection may help design novel quinazoline derivatives with improved EGFR-T790M inhibitory activity. | {
"pile_set_name": "PubMed Abstracts"
} |
Alcohol intoxication induces greater reductions in brain metabolism in male than in female subjects.
The mechanisms underlying the gender differences in alcohol drinking behavior and alcohol's effects are poorly understood and may reflect gender differences in brain neurochemistry. Alcohol decreases glucose metabolism in the human brain in a pattern that is consistent with its facilitation of GABAergic neurotransmission. We compared the regional changes in brain glucose metabolism during alcohol intoxication between female and male subjects. Ten female and 10 male healthy controls were scanned with positron emission tomography and 2-deoxy-2[18F]fluoro-D-glucose twice: 40 min after placebo (diet soda) or alcohol (0.75 g/kg mixed with diet soda). Alcohol significantly and consistently decreased whole-brain metabolism. The magnitude of these changes was significantly larger in male (-25 +/- 6%) than in female (-14 +/- 11%; p < 0.005) subjects. Half of the female subjects had reductions in metabolism during intoxication that were significantly lower than those in male subjects. This blunted response in the female subjects was not due to differences in alcohol concentration in plasma, because these did not differ between the genders. In contrast, the self-reports for the perception of intoxication were significantly greater in female than in male subjects. The cognitive deterioration during alcohol intoxication, although not significant, tended to be worse in female subjects. This study shows a markedly blunted sensitivity to the effects of acute alcohol on brain glucose metabolism in female subjects that may reflect gender differences in alcohol's modulation of GABAergic neurotransmission. The greater behavioral effects of alcohol in female subjects despite the blunted metabolic responses could reflect other effects of alcohol, for which the regional metabolic signal may be hidden within the large decrements in metabolism that occur during alcohol intoxication. | {
"pile_set_name": "PubMed Abstracts"
} |
Detection of tumor-associated antigen in human melanoma cell line supernatants.
Spent tissue culture medium (CDM-S) removed from a single cell line of human malignant melanoma grown in serum-free CDM, contained tumor-associated antigenic activity. Antibodies to CDM-S measured by complement fixation were detected in 44% (31/70) melanoma, 55% (15/27) sarcoma, 63% (24/38) carcinoma and 15% (11/72) normal sera. Delayed cutaneous hypersensitivity reactions (DCHR) were demonstrated in 4/5 melanoma patients at a 500 mug dose, 3/5 at a 100 mug dose and in 1/7 carcinoma patients at the 500 mug dose. One ml of CDM-S was shown to contain antigen equivalent to that obtained from the membranes of 2.9 X 10(7) tissue-cultured melanoma cells. After purification, 84% (16/19) sera from melanoma patients, 66% (12/18) from sarcoma and carcinoma patients and 8% (2/26) from normal controls were positive to the antigen by complement fixation. | {
"pile_set_name": "PubMed Abstracts"
} |
Intestinal stenosis following successful medical management of necrotizing enterocolitis.
In the past decade, increased clinical awareness and better medical and surgical management of necrotizing enterocolitis (NEC) has resulted in improved survival. With an increase in the number of infants surviving the acute stages of NEC the sequelae, including intestinal stenosis, have become more apparent. In the past 5.5 yr, 62 patients with NEC have been treated at our institution. Of the 28 survivors of medical management for NEC seven patients developed intestinal stenosis. An average of 23 days elapsed between the recovery from NEC and the diagnosis of colonic stenosis. Only three patients manifested symptoms of intestinal obstruction. Two patients had blood in their stools and two patients were asymptomatic. Five infants were managed by primary or staged resection of the intestinal stenosis. The remaining two patients were treated nonoperatively. Our data suggests a high incidence of intestinal stenosis (25%) following medical management of NEC. There is a marked preference for the stenosis to occur on the left side of the colon. Colon stenoses can exist without symptoms and radiographically proven areas of stenosis can resolve. We recommend that all infants following medical management of NEC have a barium enema prior to hospital discharge. In selected cases asymptomatic patients with colonic stenosis may not require operative intervention. | {
"pile_set_name": "PubMed Abstracts"
} |
Possibilities of column coupling electrophoresis provided with a fiber-based diode array detection in enantioselective analysis of drugs in pharmaceutical and clinical samples.
The present work illustrated possibilities of column coupling electrophoresis combined with ionizable chiral selector and diode array detection (DAD) for the enantioselective analysis of trace drugs (pheniramine and its analogs) in pharmaceutical and clinical samples. Isotachophoresis (ITP), on-line coupled with capillary zone electrophoresis (CZE), served as an ideal injection technique (high sample load capacity, narrow and sharp drugs zones) of on-line pretreated samples (preseparation, purification and preconcentration of drugs) for the CZE stage. Enhanced (enantio)separation selectivity of CZE with ionizable chiral selector (carboxyethyl-beta-cyclodextrin recognized between drugs enantiomers on one hand as well as between drugs and sample matrix constituents on the other hand) enabled to obtain pure zones of the drugs enantiomers, suitable for their detection and quantitation. DAD in comparison with single wavelength UV detection enhanced value of analytical information verifying purity of drugs enantiomers zones (indicating interferents with different spectra to those of drugs). Obtained results indicated pure zones of interest confirming effective ITP-CZE (enantio)separation process. Distinguishing the trace analytes signals superposed on the baseline noise was provided with sufficient reliability (for this purpose the background correction and smoothing procedure had to be applied to the raw DAD spectra). The proposed ITP-CZE-DAD methods were characterized by favorable performance parameters (sensitivity, linearity, precision, recovery, accuracy, robustness, selectivity) and successfully applied for (i) enantiomeric purity testing of dexbrompheniramine in commercial pharmaceutical tablets and (ii) enantioselective metabolic study of pheniramine in human urine. | {
"pile_set_name": "PubMed Abstracts"
} |
Poly(lactic-co-glycolic) acid loaded nano-insulin has greater potentials of combating arsenic induced hyperglycemia in mice: some novel findings.
Diabetes is a menacing problem, particularly to inhabitants of groundwater arsenic contaminated areas needing new medical approaches. This study examines if PLGA loaded nano-insulin (NIn), administered either intraperitoneally (i.p.) or through oral route, has a greater cost-effective anti-hyperglycemic potential than that of insulin in chronically arsenite-fed hyperglycemic mice. The particle size, morphology and zeta potential of nano-insulin were determined using dynamic light scattering method, scanning electronic and atomic force microscopies. The ability of the nano-insulin (NIn) to cross the blood-brain barrier (BBB) was also checked. Circular dichroic spectroscopic (CD) data of insulin and nano-insulin in presence or absence of arsenic were compared. Several diabetic markers in different groups of experimental and control mice were assessed. The mitochondrial functioning through indices like cytochrome c, pyruvate-kinase, glucokinase, ATP/ADP ratio, mitochondrial membrane potential, cell membrane potential and calcium-ion level was also evaluated. Expressions of the relevant marker proteins and mRNAs like insulin, GLUT2, GLUT4, IRS1, IRS2, UCP2, PI3, PPARγ, CYP1A1, Bcl2, caspase3 and p38 for tracking-down the signaling cascade were also analyzed. Results revealed that i.p.-injected nano-encapsulated-insulin showed better results; NIn, due to its smaller size, faster mobility, site-specific release, could cross BBB and showed positive modulation in mitochondrial signaling cascades and other downstream signaling molecules in reducing arsenic-induced-hyperglycemia. CD data indicated that nano-insulin had less distorted secondary structure as compared with that of insulin in presence of arsenic. Thus, overall analyses revealed that PLGA nano-insulin showed better efficacy in combating arsenite-induced-hyperglycemia than that of insulin and therefore, has greater potentials for use in nano-encapsulated form. | {
"pile_set_name": "PubMed Abstracts"
} |
A factorial experimental analysis of using wood fly ash as an alkaline activator along with coal fly ash for production of geopolymer-cementitious hybrids.
Alkaline activated materials such as geopolymers and cementitious materials derived from pozzolanic reactions offer several advantages over the currently widely used Portland cement, especially in terms of environmental sustainability and physiochemical properties. However due to the need of an alkaline activator, such as NaOH or KOH, which result in high production cost and requires skilled personnel, they have not been deeply explored and put to use. Here in this study, wood fly ash, a by product of wood combustion is used as an alternative source of alkaline activator for producing such alkaline activated materials along with coal fly ash, where the resulting geopolymer-cementitious hybrid (GCH) was characterized physico-chemically through electron microscopy, BET, FTIR, XRF & XRD. However, the leaching of heavy metals from the wood fly ash could potentially pose an environmental concern. Therefore, the focus of this study is to reduce the leachability factor of wood fly ash involved in the alkaline activated process and to understand the effects of various factors (i.e. water-to-ash ratio (w/a), method of curing, type of alkaline activator and ash sieving) on the leaching process, through factorial experimental analysis. The leaching patterns of various elements such as Pb, Zn, Cr, As. Hg, Se were studied along with the contributing factors and results showed that the dominant factor was the type of alkaline activator (i.e. Wood Fly Ash versus Na2SiO3). By comparing the leaching data to Denmark's leaching criteria, the best performing GCH sample was found to be 0.3DI_p_s (0.3 represents the w/a ratio, "p" denotes that samples were precured and "s" denotes sieving). | {
"pile_set_name": "PubMed Abstracts"
} |
Implantation of inflatable penile prosthesis in patients with severe corporeal fibrosis: introduction of a new penile cavernotome.
Implantation of penile prosthetic cylinders into scarred corpora remains a challenge in the field of prosthetic urology. We describe a new penile cavernotome, which allows for easier dilation of fibrotic corpora cavernosa and facilitates inflatable penile prosthesis cylinder insertion. A set of 5 cavernotomes between 6 and 13 mm. in diameter are used to drill a space in fibrotic corpora with controlled 1 mm. cuts. The cavernotomes are advanced in an oscillating fashion and also allow shaving of severely stenotic areas for easier cavity development. They were used in 16 patients with fibrotic corpora secondary to different etiologies. A high transverse scrotal incision was used in all cases. Of the 16 patients 14 received downsized cylinders. Implantation of both cylinders of an inflatable 3-piece device was successful in all cases. Proximal crural perforation occurred intraoperatively in 5 patients and was corrected by attaching the rear tip extender to the tunica with nonabsorbable suture. Postoperatively, distal tunical perforation of the corpora in 4 patients was repaired with natural tissue. Operative time was reduced compared to our previous experience with implantation in cases of corporeal fibrosis using extensive corporotomies or the Carrion-Rossello cavernotomes. In no case was the procedure terminated for urethral laceration or inadequate dilation for cylinder insertion. No grafting materials were necessary to close the corporotomy. The new cavernotomes along with the high transverse scrotal incision and downsized prostheses resulted in successful implantation in all of our cases. Dilation of fibrotic corpora was easier and quicker with the new cavernotomes because extensive corporeal resection was not necessary. Complications were acceptable for these difficult cases and prosthesis survival is 100% to date. | {
"pile_set_name": "PubMed Abstracts"
} |
Long-term persistence of metabolic abnormalities in absorptive or renal hypercalciuria.
Seven patients with absorptive hypercalciuria and seven with renal hypercalciuria were re-evaluated 1.67-7.33 years after the original diagnosis. When treatment was temporarily stopped, all showed the same metabolic abnormalities as before: those with absorptive hypercalciuria continued to show increased intestinal absorption of calcium and normal or suppressed parathyroid function, and those with renal hypercalciuria had persistent "renal leak" of calcium and parathyroid stimulation. In view of the persistence of metabolic abnormalities, medical therapy should be regarded as a long-term commitment. | {
"pile_set_name": "PubMed Abstracts"
} |
An autopsy study of sudden cardiac death.
To determine the cause of sudden cardiac death and observe the morphological changes in the heart after death. A cross sectional survey of 66 cases was carried out at Armed Forces Institute of Pathology (AFIP) Rawalpindi from 1992 to 1994. A detailed autopsy including external and internal postmortem examination was done. Representative sections were taken for histopathological examination and some viscera were sent to Chemical Examiner at Lahore for chemical analysis. All the cases were male with age range from 21 to 58 years. These cases died within 60 minutes with or without onset of symptoms. Fifty two cases revealed mild to severe atherosclerosis. Coronary occlusion with thrombosis was seen in 37 cases whereas 9 cases showed critical narrowing without evidence of thrombosis. Five showed both symmetric and asymmetric hypertrophy. Changes in conduction system of the heart were seen in 4 individuals. Myocarditis was noted in 2 cases only. The cause of death could not be determined in 3 cases. Majority of the cases died of coronary atherosclerosis whereas 17% cases revealed hypertrophic cardiomyopathy, changes in conduction system and myocarditis and 4% cases were undetermined. A detailed and thorough postmortem examination is mandatory to ascertain the cause of sudden cardiac death. | {
"pile_set_name": "PubMed Abstracts"
} |
Management practices of Australian surgeons in the treatment of venous ulcers.
Venous ulcers will affect 2% of the general population during the course of their lives causing significant morbidity. The aim of the present paper was to review assessment and treatment regimes used by surgeons throughout Australia and compare these with published guidelines. A structured questionnaire was sent to all general and vascular surgeons in Australia. Questions detailing practice demographics, initial treatment, investigation and surgical intervention were asked. Responses were analysed using Fisher's exact test. A response rate of 36% was obtained from 1390 surgeons. This included 30% of the general surgeons and 67% of the vascular surgeons surveyed. Three hundred and seventy-one of these surgeons managed patients with venous ulcers. Vascular surgeons recorded ankle-brachial pressures (88%vs 55%; P < 0.0001) more frequently and used compression therapy more often than general surgeons (99%vs 61%; P < 0.0001). Superficial vein ablation was performed by 95% in the presence of superficial vein reflux and a normal deep system, 46% also performed this procedure in the setting of an incompetent deep system. Antibiotics were prescribed by 15% of surgeons with no evidence of infection. Initially venous ulcers are well managed in Australia; however, antibiotics are overprescribed in their treatment. The current rate of compression therapy use is low for some groups of surgeons and should be improved. The failure to use compression in all cases of venous ulcers and the overprescription of antibiotics in the absence of cellulitis suggests that significant improvements can be made in the management of venous ulcers in Australia. | {
"pile_set_name": "PubMed Abstracts"
} |
Mechanisms of transcriptional activation of lipopolysaccharide binding protein (LBP).
The Lipopolysaccharide Binding Protein (LBP) is of high importance for endotoxin recognition, presentation and subsequent cytokine induction in immune cells. LBP, which is a member of a growing family of structurally and functionally related proteins, is synthesized in hepatocytes and secreted into the blood stream constitutively. During the acute phase response, however, LBP levels rise substantially and here the mechanisms of induction of LBP protein synthesis were reviewed. The induction of LBP in hepatocytes is due to transcriptional and posttranscriptional mechanisms as we have shown by nuclear run-on and RNA half-life experiments. Cloning of the 5'-flanking region of the LBP gene, furthermore revealed a typical acute phase protein promoter. Reporter gene assays employing the luciferase gene and mutation variants of the LBP promoter revealed that integrity of a common acute phase promoter motif, named APRE/STAT-3 is essential for activation of the LBP promoter. Elucidation of the transcriptional activation mechanism could point the way to a therapeutically lowering of LBP levels in high risk patients for reducing their susceptibility to Gram-negative septic shock. | {
"pile_set_name": "PubMed Abstracts"
} |
Pharmaceutical development of a parenteral lyophilized formulation of the investigational polymer-conjugated platinum anticancer agent AP 5280.
AP 5280 is a novel polymer-conjugated platinum anticancer agent showing promising in vitro and in vivo activity against solid tumors. The aim of this study was to develop a parenteral pharmaceutical dosage form for phase I clinical trials. AP 5280 drug substance was characterized by using a wide range of analytical techniques and showed excellent solubility in water. However, as aqueous solutions of AP 5280 proved to be labile upon sterilization by moist heat, it was decided to develop a lyophilized dosage form. Initially, glass vials were used as primary packaging, but this led to a high breakage rate, which could be completely prevented by the use of CZ resin vials. Stability studies to date show that the lyophilized product in glass vials is stable for at least 12 months when stored at 2-8 degrees C in the dark and the lyophilized product in CZ resin vials is stable for at least 6 months under these conditions. Photostability testing revealed photolability of AP 5280 drug substance and lyophilized product in both types of primary container, necessitating storage in the dark. The first clinical experiences indicate that the proposed formulation is fully applicable for use in the clinical setting. | {
"pile_set_name": "PubMed Abstracts"
} |
Mental Health Needs of the Elderly Vary by Setting.
To learn more about elderly patients who use outpatient mental health services, we retrospectively reviewed the charts of 75 patients overage 60 treated in an inner-city community mental health center during a 1-year period and compared them with 34 patients in a hospital-based psychogeriatric clinic and 26 patients in a suburban geriatric outreach program. The patients in the three settings differed with regard to age of onset and type of psychopathology, use of psychotropic medication, and mental health needs. | {
"pile_set_name": "PubMed Abstracts"
} |
Enriching membrane cholesterol improves stability and cryosurvival of buffalo spermatozoa.
Buffalo spermatozoa are comparatively more susceptible to freezing hazards than cattle spermatozoa. In recent times incubation of spermatozoa with cholesterol-loaded-cyclodextrins (CLC) has shown improvements in semen quality in several species. Therefore, this study was undertaken to evaluate the incubation level of CLC at which maximum benefit is derived for the buffalo spermatozoa. For the study, 120 million spermatozoa were incubated in 2, 3 and 4 mg/mL of CLC (Gr II, III and IV, respectively) and cholesterol and phospholipids content, their ratio, flow cytometric evaluation of plasma membrane integrity (PMI), plasma membrane fluidity and extent of cryoinjury (Chlortetracycline, CTC assay) were compared with an untreated control (Gr I). Additionally the ability of cholesterol-loaded-spermatozoa to undergo induced acrosome reaction (IAR) using ionophore calcium (A23187) was evaluated in frozen-thaw samples. Data show a significant and linear increase (CV=0.88) in cholesterol content of spermatozoa in Gr II, III and IV and a significant decrease in phospholipids content at frozen-thaw stage in Gr IV than Gr III spermatozoa. The study revealed a significant improvement in PMI and significant reduction in plasma membrane fluidity and cryoinjury of CLC treated spermatozoa at progressive stages in three groups compared to control. Nevertheless, spermatozoa of Gr II, III and IV were significantly less responsive to ionophore calcium (A23187) than Gr I. This study shows for the first time that incubation of buffalo bull spermatozoa with CLC (3mg/120×10(6)) prior to processing permits greater numbers of sperm to survive cryopreservation while allowing spermatozoa to capacitate and the acrosome to react to AR inducer ionophore calcium (A23187). | {
"pile_set_name": "PubMed Abstracts"
} |
Redo living-donor lobar lung transplantation for bronchiolitis obliterans associated with antibody-mediated rejection.
Living-donor lobar lung transplantation (LDLLT) is an established therapy for patients with end-stage lung disease, but living-donor lobar lung retransplantation (re-LDLLT) is rarely reported. We previously reported a case of unilateral antibody-mediated rejection after LDLLT in the presence of newly formed donor-specific antibodies against a right-lobe donor. The same patient developed contralateral bronchiolitis obliterans, resulting in bilateral bronchiolitis obliterans, but re-LDLLT was successful. Pathological findings of the explanted lungs were consistent with the clinical course of the patient. One year after re-LDLLT, the patient is doing well without any anti-human leukocyte antigen antibodies. Four lobes from four different donors were transplanted in this patient. The first two lobes were rejected eventually, but the two lobes implanted later presented no signs of rejection at least for 1 year after the transplant. Herein, we report this rare case and compare the clinical course and pathological findings. | {
"pile_set_name": "PubMed Abstracts"
} |
Exacerbation of Lambert-Eaton myasthenic syndrome caused by an L-type Ca2+ channel antagonist.
A 74 year-old Japanese woman, who had suffered from Lambert-Eaton myasthenic syndrome (LEMS), Sjoegren's syndrome, and discoid lupus erythematosus for 10 years and had been successfully controlled by 3,4-diaminopyridine and prednisolone, began to suffer from chest discomfort at night. Stress-induced myocardial ischemia in the left ventricular anterior septum was detected by thallium-201 scintigraphy. After diltiazem was prescribed, she began to feel systemic malaise and weakness in both thighs. She stopped taking diltiazem and the symptoms improved. Coronary angiography revealed 75% stenosis with calcification in the middle of the left anterior descending artery. After atherectomy with a lotablator and coronary stenting, diltiazem was prescribed. She felt malaise again, but continued taking diltiazem. After three months a follow-up coronary angiography showed no restenosis in the lesion and diltiazem was stopped. The weakness and malaise disappeared and her muscle strength recovered. LEMS is an autoimmune disorder of peripheral cholinergic transmission in which autoantibodies to the presynaptic P/Q-type voltage-gated calcium channels (VGCC) decrease the release of acetylcholine at the neuromuscular junction resulting in muscle weakness. P/Q-type VGCC regulates most of the neurotransmitter release and L-type VGCC regulates the remainder. L-type VGCC blockers are thought to have little effect on the neuromuscular junction. but they should be used very carefully. even in the remission stage of LEMS, because of preexisting neuromuscular blocking in transmission. | {
"pile_set_name": "PubMed Abstracts"
} |
[Effect of vitamins A and E on various indices of lipid and protein metabolism in children with perinatal pathology of the central nervous system].
In children with perinatal pathology of central nervous system content of vitamins A and E was decreased in blood serum. At the same time, some patterns of lipid and protein metabolism were altered. These alterations were especially distinct in pathological conditions accompanied by inflammatory reaction due to infections. Parenteral administration of a complex of vitamins A and E (drug "Aevit") within 2 weeks led to normalization of the content of these vitamins in blood serum. At the same time, the altered patterns of lipid and protein metabolism were normalized. | {
"pile_set_name": "PubMed Abstracts"
} |
Activation of human dendritic cells following infection with Mycobacterium tuberculosis.
Dendritic cells (DC) play an essential role in the initiation of primary T cell responses to foreign Ag. It is likely that these potent APC are critical in the initiation of immune responses to pathogens, such as bacteria or parasites. However, little is known about the interaction of these important APC with pathogens. To address this issue, the interaction of the bacterium Mycobacterium tuberculosis with human DC was studied. DC generated from human peripheral blood by short term culture in medium containing recombinant human cytokines granulocyte-macrophage-CSF and IL-4 were capable of phagocytosing M. tuberculosis. Infection of DC with live M. tuberculosis bacilli resulted in increased APC surface expression of the costimulatory molecules CD54, CD40, and B7.1, as well as MHC class I molecules. In addition, infected DC secreted elevated levels of inflammatory cytokines, including TNF-alpha, IL-1, and IL-12. M. tuberculosis-infected human monocytes also secreted inflammatory cytokines, but exhibited no enhancement of costimulatory or MHC class I molecule expression. These data indicate that infection with M. tuberculosis results in the direct activation and maturation of these DC. In vivo, such activation may facilitate migration to the lymph nodes, and enhance presentation of Ag to T cells, thereby facilitating the induction of the immune response against this pathogen. | {
"pile_set_name": "PubMed Abstracts"
} |
Patient-Side Appraisal of Late Radiation-Induced Oral Microvascular Changes.
To determine the clinical feasibility of examining and measuring late irradiation changes in the oral microcirculation of head and neck (HN) cancer patients using the novel CytoCam video microscope system. In 30 HN cancer patients and 30 age-matched controls, bilateral video images were recorded noninvasively of the oral microcirculation of the buccal mucosa and mandibular gingiva. Tissue perfusion parameters, such as functional capillary density (FCD), buccal blood vessel diameter, and microcirculatory flow index, were analyzed. No difference was observed for mean buccal mucosa FCD in irradiated versus healthy tissue, whereas a lower mean gingival FCD in irradiated versus healthy tissue was observed (34 ± 17 capillaries per millimeter squared [cpll/mm2] vs 68 ± 19 cpll/mm2; P < .001). A significant difference in mean buccal blood vessel diameter of 16 ± 3 μm was measured, compared with 14 ± 1 μm in control buccal mucosa (P < .001). No significant difference in microcirculatory flow index was observed between the 2 groups. Quantifying oral microcirculatory injury associated with late irradiation effects using the CytoCam was feasible in HN cancer patients. Results indicate that marked differences in tissue-specific microcirculatory measurements of angioarchitecture, diminished capillary density, and extensively dilated blood vessel diameters are associated with late irradiation effects in HN cancer patients. | {
"pile_set_name": "PubMed Abstracts"
} |
Asymmetric alpha-alkylation of phenylacetates using 2-alkylamino-2'-hydroxy-1,1'-binaphthyls as chiral auxiliaries.
alpha-Alkylation of 2-phenylacetate ester of 2-alkylamino-2'-hydroxy-1,1'-binaphthyls with various alkyl iodides proceeded with good stereoselectivities. An intramolecular hydrogen bonding between N-H group and the carbonyl oxygen seemed to play an important role for asymmetric induction. The auxiliary was also applicable to Diels-Alder reaction of an acrylate. | {
"pile_set_name": "PubMed Abstracts"
} |
Photoreactive TiO2/carbon nanotube composites: synthesis and reactivity.
Electron-hole recombination limits the efficiency of TiO2 photocatalysis. We have investigated the efficacy with which anatase/carbon nanotube (CNT) composite materials reduce charge recombination and enhance reactivity. We synthesized nanostructured assemblies composed of different proportions of anatase (5 or 100 nm) and either single-or multi-walled CNTs. The composites were prepared using a simple low temperature process in which CNTs and anatase nanoparticles were dispersed in water, dehydrated at 80 degrees C, and dried at 104 degrees C. The structures of the various TiO2/CNT composites were characterized by scanning electron microscopy (SEM) and their function was tested by phenol oxidation. Charge recombination was compared by measuring the photoluminescence spectra of select composites. We found that a nanostructured composite assembled from the 100 nm anatase and single-walled CNTs (SWCNTs) exhibited enhanced and selective photocatalytic oxidation of phenol in comparison to both pure anatase and Degussa P25. A mechanism for the enhanced reactivity is proposed in which electrons are shuttled from TiO2 particles to the SWCNTs as a result of an optimal TiO2/ CNT arrangement that stabilizes charge separation and reduces charge recombination. In addition, the SWCNT assembly provides better catalyst-support (dispersal and connection) than multi-walled CNTs. | {
"pile_set_name": "PubMed Abstracts"
} |
[Inpatient dialectical behaviour therapy for borderline personality disorder: effect on symptoms, coping, attachment and quality of life].
Dialectical behaviour therapy (dbt) is an effective treatment for patients suffering from borderline personality disorder (bpd). When outpatient treatment is ineffective, patients are often referred to inpatient (group) treatment. As of yet, little is known about the effectiveness of inpatient (group) dbt. An altered style of attachment is one of the presumed components of inpatient (group) treatment. At present, this supposition has not yet been examined in inpatient dbt programs. To examine the treatment outcome of an inpatient group dbt program for patients suffering from bpd, evaluating symptoms, coping, attachment style and quality of life. Whether an improvement in attachment style during treatment is a predictor of psychological wellbeing at the end of treatment will also be examined. An inpatient group dbt population, comprising of 64 patients diagnosed with bpd, was evaluated. Self-report questionnaires assessed symptoms, coping, attachment style and quality of life at the start of treatment, after 19 weeks and at the end of treatment. The mentioned variables significantly improved in the inpatients of the group dbt program (treatment lasting on average 7.2 months). Furthermore, positive changes in secure and preoccupied attachment style were a significant predictor of psychological wellbeing at the end of the treatment. We conclude that patients diagnosed with bpd may benefit from an inpatient dbt (group) program. Improvements in attachment style during inpatient treatment may contribute to this benefit. | {
"pile_set_name": "PubMed Abstracts"
} |
[Patients suffering dilated chagasic cardiopathy or non chagasic cardiopathy show an increased levels of tumor necrosis factor alpha].
Chagas' disease is a public health problem in Venezuela, affecting people living in rural areas. 30% of the patients evolve to a Chronic Chagasic Myocardiopathy (CCM) characterized by heart failure, arrhythmias, incapacity to work and sudden death. There are not predictive factors to determine the evolution from the indeterminate form of the disease (asymptomatic form) to CCM. In the present paper we have studied 115 patients enrolled in the Cardiology unit at the Baudilio Lara Hospital in Quibor (Lara State, Venezuela) and 12 healthy patients coming from the same area. Patients were evaluated by means of clinical history; echocardiography, electrocardiography and radiology. The presence of anti-T. cruzi antibodies and levels of Tumor Necrosis Factor alpha (TNFalpha) were determined in serum samples. Chagas' disease patients were classified in 3 groups: I (asymptomatic), II (asymptomatic with normal left ventricular ejection fraction (LVEF) and electrocardiographic alterations) and and III (symptomatic, electrocardiographic alterations and LVEF < 70%). The results showed that 33.04% of the patients had anti-T. cruzi antibodies in their serum; we also observed a significant increase in the serum levels of TNFalpha in groups I and III of Chagas' disease patients as compared with the control healthy group. Chagas' disease patients belonging to Group II displayed similar TNFalpha levels as controls. We observed a statistically significant (p < 0.05) negative correlation between serum TNFalpha values and LVEF. Patients suffering of non-chagasic myocardiopathy had a significant increase of TNFalpha as compared with control patients and similar levels to those observed in Chagas' disease group III patients. These results confirm that the elevation of TNFalpha serum levels could be a immunopathogenic mechanism in the evolution of myocardiopathies. | {
"pile_set_name": "PubMed Abstracts"
} |
[Prevention of nosocomial infections: surveillance based on microbiological data].
In the C. Poma Hospital of Mantua we have been using a system of continuous surveillance of nosocomial infections based on microbiological data for the past 4 years. This monitoring estimates the incidence of the microorganisms found in cultures, especially those at risk of causing nosocomial infections. Since June 2001 microbiological data have been registered using the Mercurio-Dianoema software and elaborated by means of Microsoft Excel in order to obtain information about isolated bacteria, especially those resistant to antibiotics. Surveillance in "critical" wards revealed the presence of Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans in the intensive care unit in the period 2003-2005. The most frequent bacteria in hemodialysis have been coagulase-negative Staphylococci and Staphylococcus aureus, with variable methicillin resistance. The analysis of microbiological data has promoted effective measures to reduce the incidence of these bacteria (increased rules of good practice, hand washing, etc.). If nosocomial infections or high-risk microorganisms occur, assessments are carried out; monitoring of the antibiotic resistance of the bacteria is very important. | {
"pile_set_name": "PubMed Abstracts"
} |
Reversible cerebral vasoconstriction syndrome.
Reversible cerebral vasoconstriction syndrome (RCVS) is a cerebrovascular disorder with a clinical picture that continues to be refined. It has presented to multiple subspecialties over the past several decades, bringing with it many questions regarding risk factors, diagnosis, and management. Answers have been forthcoming but many questions remain. RCVS presents with recurrent, secondary thunderclap headaches and predominantly affects young women. The mechanism of vasoconstriction is unclear, but there has been speculation regarding a hyperadrenergic state. Diagnosis requires physician awareness, vascular imaging, and knowledge of the differential. The hallmark of its diagnosis is reversibility. Management is empiric, usually with calcium-channel blockers, as there are no controlled treatment trials for RCVS. Randomized controlled trials are needed. | {
"pile_set_name": "PubMed Abstracts"
} |
Morphogenesis of the adrenal gland of Triturus cristatus carnifex during larval development and metamorphosis.
During the morphogenesis of the adrenal gland of Triturus cristatus, a cranio-caudal differentiation is observed together with a migration of the two cell types composing the adrenal gland: the steroidogenic cells and the chromaffin cells. During the cranio-caudal differentiation the two cell type gradually occupy an increasingly posterior position on the mesonephros until they are distributed, in the adult, along the whole kidney. The migration brings the cells from dorsal or dorso-lateral position, with respect to the venous vessels, to the ventral surface of the kidney, an arrangement typical of the adult. | {
"pile_set_name": "PubMed Abstracts"
} |
Determination of total procyanidins in selected chocolate and confectionery products using DMAC.
A simple, specific, high-throughput colorimetric method based on the reaction of 4-dimethylaminocinnamaldehyde (DMAC) with flavan-3-ols was developed to determine total procyanidins in selected cacao-based products. Extracts of defatted samples were dispensed into a 96-well plate and reacted with DMAC. The absorbance of the reaction products was measured at 640 nm and compared to commercially available procyanidin B2 as a standard. The use of the 96-well plates and a plate reader dramatically improved sample throughput. A standard protocol was established and used for further studies. The calibration was found to be linear from 1-100 ppm. The DMAC reagent reacted relatively specifically to (-)-epicatechin, (+)-catechin, epigallocatechin, gallocatechin, the gallates of catechin, epicatechin, gallocatechin, and epigallocatechin, oligomeric procyanidins of cocoa up to n=4, and A-type procyanidins. Little or no reaction occurred with cyanidins and representative compounds of phenolic acids, flavones, flavanones, flavonols, anthocyanidins, isoflavones, and stilbenes. Sample precision studies were carried out on 10 different test materials over several weeks, and yielded RSD values of 4.0 to 9.5%. The method was ring-tested in three laboratories using blinded test materials including cocoa beans, cocoa powder, chocolate liquor, dark chocolate, and milk chocolate. There was excellent agreement of the results between laboratories. | {
"pile_set_name": "PubMed Abstracts"
} |
On the Coupling between the Collective Dynamics of Proteins and Their Hydration Water.
Picosecond time scale dynamics of hydrated proteins has been connected with the onset of biological activity as it coincides with solvent-solute hydrogen bond rearrangements and amino acid rotational relaxation time scales. The presence and fluctuations of protein hydration water (PHW) largely influence protein motions that are believed to be slaved to those of the solvent, yet to date, how protein and hydration water dynamics are coupled remains unclear. Here, we provide a significant advance in characterizing this coupling; we present the first full study of both the longitudinal and transverse coherent collective motions in a protein-solvent system. The data show unexpectedly the presence in the water dynamics of collective modes belonging to the protein. The properties of these modes, in particular, their propagation velocities and amplitudes, indicate a strengthening of the interactions and a higher rigidity of the network of solvent molecules close to the protein surface. Accordingly, the present study presents the most compelling and clear evidence of a very strong dynamical coupling between a protein and its hydration water, previously suggested by studies using various experimental techniques. | {
"pile_set_name": "PubMed Abstracts"
} |
[Anesthesia management may alter long-term outcome-review of recent reports].
Perioperative management including anesthesia may alter long-term outcome of surgical patients. We have reviewed abstracts for meeting and articles published recently concerning effects of anesthetic depth, volatile anesthetic preconditioning, beta-blockers, alpha-agonists, statins, and glucose control on long-term outcome. Although research in this area has just been started, we, anesthesiologists should recognize its importance. | {
"pile_set_name": "PubMed Abstracts"
} |
HLA-B*08 Carry a Risk for Type 1 Diabetes among Cow's Milk Exposed Egyptian Infants and Unmarked Linkage Disequilibrium with DR3-DQA1*05-DQB1*02 Haplotype.
Type 1 diabetes (T1D) is an autoimmune disease associated with multiple genetics and environmental factors. The aim of the study is to determine the frequency of HLA-B*08 and HLA-B*39 and its linkage disequilibrium with common risk haplotypes DR3-DQA1*05-DQB1*02, and DR4-DQA1-03-DQB1*0302 among T1D Egyptian infants. And assess different environmental factors as early exposure to cow's milk, exclusive breast feeding, mode of delivery and low birth weight. Sixty eight diabetic infants and 120 healthy controls were studied. HLA-DQB1, and DQA1 alleles were identified using homogeneous PCR and oligonucleotide hybridization assays. HLA-B*08 and HLA-B*39 genes were identified using multiplex PCR. The results showed that early exposure to cow's milk before 6 months carry a significant risk for T1D (16% in patients versus 6.6%in control group, P value=0.03). HLA-B*08 frequency was significantly higher among T1D infants than in control group (14.5% in diabetic infants versus 5%in control group, P value=0.024). DR3-DQA1*05-DQB1*02, and DR4-DQA1-03-DQB1*0302 were significantly higher in diabetic infants than controls (P value < 0.001 and 0.004 respectively). HLA-B*08 gene was found in (15.5%) of DR3-DQA1*05-DQB1*02 positive cases while in control group it was found in (13.5%) (P value=0.8). In conclusion, HLA-B*08 gene carry a risk for T1D in Egyptian infants, while DR3-DQA1*05-DQB1*02 haplotype lacks linkage disequilibrium with HLA-B*08 among T1D infants. Further studies are needed to determine which HLA-B gene is strongly linked to DR3-DQA1*05-DQB1*02 haplotype in T1D infants other than HLA-B*08 and HLA-B*18. | {
"pile_set_name": "PubMed Abstracts"
} |
Expiratory volumetric MDCT evaluation of air trapping in pediatric patients with and without tracheomalacia.
The purpose of this study was to use paired inspiratory-expiratory volumetric MDCT to compare the frequency, severity, and pattern of air trapping in pediatric patients with tracheomalacia with the findings in children without tracheomalacia. The study group consisted of 15 consecutively registered pediatric patients (younger than 18 years) who had tracheomalacia, defined as 50% or greater reduction in tracheal cross-sectional luminal area between end inspiration and end expiration, diagnosed with MDCT and confirmed with bronchoscopy. The comparison group consisted of 15 consecutively registered pediatric patients without evidence of tracheomalacia at MDCT and bronchoscopy. Two blinded pediatric radiologists working in consensus interpreted the randomly viewed end-expiratory thin-section CT images of both groups of children for the presence, severity, and pattern of air trapping at three anatomic levels (upper, middle, and lower lung zones). The severity of air trapping was graded visually on a 5-point scale. The total air trapping scores, obtained by summing the values for the three anatomic levels for the study and comparison groups, were compared by Wilcoxon's rank sum test. The pattern of air trapping was categorized as lobular, segmental, lobar, diffuse, or mixed, and the patterns in the two study groups were compared by Pearson's chi-square test. The study cohort with tracheomalacia consisted of 15 patients (10 boys, five girls; mean age, 2.4 +/- 2.8 years; range, 1 month-11.8 years). The comparison group without tracheomalacia consisted of 15 patients (nine boys, six girls; mean age, 2.7 +/- 2.4 years; range, 1 month-8.1 years). Air trapping was identified in all 15 patients with tracheomalacia (median score, 5.0; range, 3-11) and in 10 of 15 children (67%) in the comparison group (median score, 3.0; range, 1-4). The median total air trapping score was significantly higher in the study cohort than in the comparison group (p = 0.002), but there were no significant differences in the air trapping patterns between the study groups (p = 0.53). Pediatric patients with tracheomalacia have a higher frequency and greater severity of air trapping than do children without tracheomalacia. | {
"pile_set_name": "PubMed Abstracts"
} |
Enteroatmospheric fistula: from soup to nuts.
Enteroatmospheric fistula (EAF), a special subset of enterocutaneous fistula (ECF), is defined as a communication between the gastrointestinal (GI) tract and the atmosphere. It is one of the most devastating complications of "damage control" laparotomy (DCL) and results in significant morbidity and mortality. The published incidence of EAF ranges from 5%-19% of patients who have undergone DCL and survived long enough to develop complications. Their etiology is complex and ranges from persistent abdominal infection, anastomotic leakage, adhesions of the bowel to itself or fascia, and repeated bowel manipulation during return trips to the operating room or dressing changes. Prevention is clearly the best treatment strategy but may be difficult to achieve. Once an EAF occurs, immediate management consists of treatment of sepsis if present; nutrition, fluid, and electrolyte support in the form of parenteral nutrition (PN); and wound/effluent control and protection of surrounding tissues and exposed bowel. It should be noted that EAF almost never close spontaneously, and definitive repair usually requires major surgical intervention and abdominal wall reconstruction 6 to 12 months after the original insult. Enteral feeding should be attempted once the anatomy of the EAF is defined and reliable enteral access is obtained. Most patients can tolerate some amount of enteral and even oral feeding and do not need to be maintained on PN alone. Professional judgment, experience, and teamwork are key to successfully managing the patient with EAF. | {
"pile_set_name": "PubMed Abstracts"
} |
Active targeting behaviors of biotinylated pluronic/poly(lactic acid) nanoparticles in vitro through three-step biotin-avidin interaction.
In order to prepare targeted drug carriers, previously a biotin group has been attached by our group to the end of Pluronic F87/poly(lactic acid) and Pluronic P85/poly(lactic acid) block co-polymers to obtain B-F87-PLA and B-P85-PLA, respectively. In this paper, the active targeting properties of B-F87-PLA and B-P85-PLA nanoparticles in vitro were investigated through a three-step biotin-avidin interaction by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) tests and fluorescence microscopy (FM). Two kinds of human ovarian cancer cells (OVCAR-3 and SKOV-3) and paclitaxel were chosen for the cytotoxicity tests. CA-125 antigen is over-expressed on OVCAR-3 cells but not on SKOV-3 cells. The loading and release behavior of paclitaxel loaded in B-Pluronic-PLA nanoparticles were also studied. Paclitaxel loaded in both B-F87-PLA and B-P85-PLA nanoparticles shows an initial rapid release followed by a slow release period. Compared with SKOV-3 cells, the cytotoxicity results implied that paclitaxel-loaded B-Pluronic-PLA nanoparticles were delivered more effectively to OVCAR-3 cells due to the specific interaction between the biotin groups on the surface of B-Pluronic-PLA nanoparticles and the avidin/biotinylated MAb X306/CA-125 antigen complexes on the surface of OVCAR-3 cells. The active targeting properties of B-F87-PLA nanoparticles were further confirmed by FM. | {
"pile_set_name": "PubMed Abstracts"
} |
Scattering robust 3D reconstruction via polarized transient imaging.
Reconstructing 3D structure of scenes in the scattering medium is a challenging task with great research value. Existing techniques often impose strong assumptions on the scattering behaviors and are of limited performance. Recently, a low-cost transient imaging system has provided a feasible way to resolve the scene depth, by detecting the reflection instant on the time profile of a surface point. However, in cases with scattering medium, the rays are both reflected and scattered during transmission, and the depth calculated from the time profile largely deviates from the true value. To handle this problem, we used the different polarization behaviors of the reflection and scattering components, and introduced active polarization to separate the reflection component to estimate the scattering robust depth. Our experiments have demonstrated that our approach can accurately reconstruct the 3D structure underlying the scattering medium. | {
"pile_set_name": "PubMed Abstracts"
} |
Proliferating cell nuclear antigen: more than a clamp for DNA polymerases.
DNA metabolic events such as replication, repair and recombination require the concerted action of several enzymes and cofactors. Nature has provided a set of proteins that support DNA polymerases in performing processive, accurate and rapid DNA synthesis. Two of them, the proliferating cell nuclear antigen and its adapter protein replication factor C, cooperate to form a moving platform that was initially thought of only as an anchor point for DNA polymerases delta and epsilon. It now appears that proliferating cell nuclear antigen is also a communication point between a variety of important cellular processes including cell cycle control, DNA replication, nucleotide excision repair, post-replication mismatch repair, base excision repair and at least one apoptotic pathway. The dynamic movement of proliferating cell nuclear antigen on and off the DNA renders this protein an ideal communicator for a variety of proteins that are essential for DNA metabolic events in eukaryotic cells. | {
"pile_set_name": "PubMed Abstracts"
} |
Allograft interference screw fixation in meniscus transplantation.
Allograft meniscus transplantation is indicated to restore proper knee biomechanics and prevent subsequent articular degeneration in patients with a meniscus-deficient knee. A variety of techniques for fixation of meniscal transplants exist, with some techniques using soft-tissue fixation of the meniscal horns and others using bony fixation. The authors present a technique of meniscus transplantation using a tibial slot with allograft interference screw fixation. We have had excellent early results with this technique and believe that a cortical allograft interference screw reliably maintains the anatomic position of the meniscal attachments that are critical to the biomechanics and functional outcome of meniscus transplantation. | {
"pile_set_name": "PubMed Abstracts"
} |
Investigation of the performance of PEG-PEI/ROCK-II-siRNA complexes for Alzheimer's disease in vitro.
Recent studies have showed inhibiting ROCK promoted axonal regeneration and suppressing ROCK-II decreased Aβ formation, suggesting ROCK is a potential target for the treatment of Alzheimer's disease. Because ROCK-II mRNA is abundantly expressed in brain, we targeted ROCK-II mRNA using a siRNA approach. To suppress ROCK-II mRNA expression, we synthesized PEG-PEI/ROCK-II-siRNA complexes and transfected C17.2 neural stem cells in vitro. The characteristics of the complexes were tested using a gel retardation assay. Particle size and zeta potential were examined using dynamic light scattering and the morphology of the complexes were observed by transmission electron microscopy. The toxicity was detected by an MTT assay and transfection efficiency was determined by flow cytometry. Laser confocal microscopy was employed to investigate the cell uptake of the complexes. RT-PCR and western blotting were used to verify the effect of gene silencing. Our results indicated that the characteristics of the complexes depended on the N/P ratios. At a high N/P ratio, PEG-PEI could completely condense the siRNA into small-sized uniform particles. However, high N/P ratios are accompanied with high cytotoxicity. Because of high transfection efficiency and low cytotoxicity, N/P=50 was chosen to transfect C17.2 cells in vitro. Laser confocal microscopy showed that ROCK-II-siRNA with green fluorescence was mainly distributed in the cytoplasm and synapses. Moreover, ROCK-II-siRNA was successfully released from the lysosome. RT-PCR and western blotting demonstrated effective gene silencing. These results indicated that PEG-PEI/ROCK-II-siRNA complexes effectively suppressed ROCK-II mRNA expression, providing the basis for future research in vivo. | {
"pile_set_name": "PubMed Abstracts"
} |
Phase I Study of DSTP3086S, an Antibody-Drug Conjugate Targeting Six-Transmembrane Epithelial Antigen of Prostate 1, in Metastatic Castration-Resistant Prostate Cancer.
Six-transmembrane epithelial antigen of the prostate 1 (STEAP1) is highly expressed in prostate cancers. DSTP3086S is a humanized immunoglobulin G1 anti-STEAP1 monoclonal antibody linked to the potent antimitotic agent monomethyl auristatin E. This study evaluated the safety and activity of DSTP3086S in patients with metastatic castration-resistant prostate cancer. Patients were enrolled in a 3 + 3 dose escalation study to evaluate DSTP3086S (0.3 to 2.8 mg/kg intravenously) given once every 3 weeks followed by cohort expansion at the recommended phase II dose or weekly (0.8 to 1.0 mg/kg). Seventy-seven patients were given DSTP3086S once every 3 weeks, and seven were treated weekly. Two patients in the once-every-3-weeks dose escalation had dose-limiting grade 3 transaminitis. Grade 3 hyperglycemia and grade 4 hypophosphatemia were dose-limiting toxicities in one patient treated at 1.0 mg/kg weekly. Initial cohort expansion evaluated dosing at 2.8 mg/kg once every 3 weeks (n = 10), but frequent dose reductions led to testing of 2.4 mg/kg (n = 39) in the expansion phase. Common related adverse events (> 20%) across doses (once every 3 weeks) were fatigue, peripheral neuropathy, nausea, constipation, anorexia, diarrhea, and vomiting. DSTP3086S pharmacokinetics were linear. Among 62 patients who received > 2 mg/kg DSTP3086S once every 3 weeks, 11 (18%) demonstrated a ≥ 50% decline in prostate-specific antigen; two (6%) of 36 with measurable disease at baseline achieved a radiographic partial response; and of 27 patients with informative unfavorable baseline circulating tumor cells ≥ 5/7.5 mL of blood, 16 (59%) showed conversions to favorable circulating tumor cells < 5. No prostate-specific antigen or RECIST responses were seen with weekly dosing. DSTP3086S has acceptable safety at the recommended phase II dose level of 2.4 mg/kg once every 3 weeks. Antitumor activity at doses between 2.25 and 2.8 mg/kg once every 3 weeks supports the potential benefit of treating STEAP1-expressing metastatic castration-resistant prostate cancer with an STEAP1-targeting antibody-drug conjugate. | {
"pile_set_name": "PubMed Abstracts"
} |
Population-level changes to promote cardiovascular health.
Cardiovascular diseases (CVD) cause 1.8 million premature (<75 years) death annually in Europe. The majority of these deaths are preventable with the most efficient and cost-effective approach being on the population level. The aim of this position paper is to assist authorities in selecting the most adequate management strategies to prevent CVD. Experts reviewed and summarized the published evidence on the major modifiable CVD risk factors: food, physical inactivity, smoking, and alcohol. Population-based preventive strategies focus on fiscal measures (e.g. taxation), national and regional policies (e.g. smoke-free legislation), and environmental changes (e.g. availability of alcohol). Food is a complex area, but several strategies can be effective in increasing fruit and vegetables and lowering intake of salt, saturated fat, trans-fats, and free sugars. Tobacco and alcohol can be regulated mainly by fiscal measures and national policies, but local availability also plays a role. Changes in national policies and the built environment will integrate physical activity into daily life. Societal changes and commercial influences have led to the present unhealthy environment, in which default option in life style increases CVD risk. A challenge for both central and local authorities is, therefore, to ensure healthier defaults. This position paper summarizes the evidence and recommends a number of structural strategies at international, national, and regional levels that in combination can substantially reduce CVD. | {
"pile_set_name": "PubMed Abstracts"
} |
Lipid target achievement among patients with very high and high cardiovascular risk in a lipid clinic.
This was a retrospective study that assessed achievement of lipid-lowering treatment targets in the setting of a University Hospital Lipid Clinic. Low-density lipoprotein cholesterol (LDL-C) goal attainment according to National Cholesterol Education Program-Adult Treatment Panel III (NCEP ATP III) and European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines was recorded in 1000 consecutive adult patients followed for ≥3 years (mean 8 years). The LDL-C targets according to the NCEP ATP III were attained by 66% and 86% of patients with "very high" (n = 477) and "high" (n = 408) cardiovascular risk, respectively. Fewer patients were within LDL-C goals according to the ESC/EAS guidelines: 25% and 42%. Overall, 92% of the patients were on statins: 67% were on statin monotherapy, while 33% were on combinations with ezetimibe (25%), ω-3 fatty acids (5%), fibrates (4%), or colesevelam (2%). Even in a specialist lipid clinic, a large proportion of patients are not at goal according to the recent ESC/EAS guidelines. | {
"pile_set_name": "PubMed Abstracts"
} |
Bias in proportion judgments: the cyclical power model.
When participants make part-whole proportion judgments, systematic bias is commonly observed. In some studies, small proportions are overestimated and large proportions underestimated; in other studies, the reverse pattern occurs. Sometimes the bias pattern repeats cyclically with a higher frequency (e.g., overestimation of proportions less than .25 and between .5 and .75; underestimation otherwise). To account for the various bias patterns, a cyclical power model was derived from Stevens' power law. The model proposes that the amplitude of the bias pattern is determined by the Stevens exponent, beta (i.e., the stimulus continuum being judged), and that the frequency of the pattern is determined by a choice of intermediate reference points in the stimulus. When beta < 1, an over-then-under pattern is predicted; when beta > 1, the under-then-over pattern is predicted. Two experiments confirming the model's assumptions are described. A mixed-cycle version of the model is also proposed that predicts observed asymmetries in bias patterns when the set of reference points varies across trials. | {
"pile_set_name": "PubMed Abstracts"
} |
Effects of glucose concentration on fetal breathing movements and electrocortical activity in fetal lambs.
Tracheal pressure and electrocortical activity were recorded in 10 unanesthetized fetal lambs in utero to determine the effect on fetal breathing movements (FBMs) of fasting and a subsequent infusion of glucose. The incidence of FBMs decreased significantly from 37.9% +/- 4.3% during fed control studies to 23.6% +/- 3.6% (P less than 0.05) after 24 to 36 hours of maternal fasting, with a related fall in fetal blood glucose. A 2-hour infusion of glucose to the fetuses of fasted animals resulted in a significant increase in FBMs to 39.5% +/- 4.9%, but only to a level similar to that in the fed control studies despite a twofold increase in the fetal concentration of glucose above fed control values. Changes in the incidence of FBMs paralleled the changes in fetal low-voltage electrocortical activity with alterations in glucose. In conclusion, FBM, although correlated with the concentration of glucose, may be influenced more by fetal hypoglycemia than hyperglycemia. Glucose appears to affect the incidence of FBM by altering the incidence of low-voltage electrocortical activity. | {
"pile_set_name": "PubMed Abstracts"
} |
The literature analysis has shown the risk of victimization in nursing professions. To date, very few studies have focused on the behavioral differences characterizing the stalking campaign, the consequences (physical and emotive), and the coping strategies adopted by victims (male and female nurses). The aim of this work was to compare the victimization experience of men and women working as nurses in public hospitals. 2.154 nurses were asked to fill a self-administered questionnaire and 765 (35.5%) filled it. Victims were 221 (29.8%), 172 (77.8%) female and 49 (22.2%) male. Findings show that the stalker is generally a man in the case of a female victim (76.2%) and a woman in the case of a male victim (71.4%). For both, the stalker is in most cases an acquaintance (for female victims=37.8%; for male victims=36.7%) who stalked for about one year. Stalking behavior causes in male nurses more physical symptoms (sleep and weakness disorders, respectively χ2=4.62, p=.024 and χ2=4.14, p=.043) than in female nurses. Female nurses (who cope by increasing social contact with friends and relatives and by talking to a psychologist) experienced more sadness (χ2=15.67, p=.000) and paranoia (χ2=10.07, p=.002) than male nurses. Possible strategies for preventing the phenomenon are discussed, highlighting the percentage (8.2% among female victims, 5.8% among male victims) of those who have reported to the police. | {
"pile_set_name": "PubMed Abstracts"
} |
Quantitative and qualitative lipoprotein abnormalities in diabetes mellitus.
In people with diabetes, the concentration of an individual lipoprotein or apolipoprotein can be highly variable and is totally different in the two major forms of the disease. Alterations in the concentrations of major lipids and lipoproteins are well characterized in both IDDM and NIDDM. In general, the lipoprotein pattern is antiatherogenic in individuals with IDDM who are treated and have optimal glycemic control. In contrast, NIDDM is associated with atherogenic changes of serum lipids and lipoproteins regardless of the mode of treatment. In people with both types of diabetes, the distribution of apoE phenotype seems to be similar to that in nondiabetic populations. IDDM patients with microalbuminuria show atherogenic changes of lipoproteins and have elevated levels of Lp(a), which is a risk factor of coronary artery disease. Whether glycemic control influences the concentration of Lp(a) is still an open question. An important issue is that the concentration of a lipoprotein can be normal without excluding compositional abnormalities that are potentially atherogenic. Such alterations are present in people with both IDDM and NIDDM. Consequently, it has been questioned whether the target values to start treatment should be lower in diabetic than in nondiabetic populations. | {
"pile_set_name": "PubMed Abstracts"
} |
Synergism between Phyllobacterium sp. (N(2)-fixer) and Bacillus licheniformis (P-solubilizer), both from a semiarid mangrove rhizosphere.
Mangrove seedlings were treated with a mixture of two bacterial species, the slow-growing, N(2)-fixing bacterium Phyllobacterium sp. and the fast-growing, phosphate-solubilizing bacterium Bacillus licheniformis, both isolated from the rhizosphere from black, white, and red mangroves of a semiarid zone. Nitrogen fixation and phosphate solubilization increased when the mixture was used compared to the effects observed when adding individual cultures, notwithstanding that there was no increase in bacterial multiplication under these conditions. Inoculation of black mangrove seedlings in artificial seawater showed the mixture performed somewhat better than inoculation of the individual bacterium; more leaves were developed and higher levels of (15)N were incorporated into the leaves, although the total nitrogen level decreased. This study demonstrates that interactions between individual components of the rhizosphere of mangroves should be considered when evaluating these bacteria as plant growth promoters. | {
"pile_set_name": "PubMed Abstracts"
} |
Interhemispheric and quadrigeminal cysts.
Interhemispheric and quadrigeminal cysts are rare lesions, similar in their propensity to present in young babies and to be associated with other central nervous system malformations, such as corpus callosum agenesia, holoprosencephaly, encephalocele, and neuronal heterotopias. Recently endoscopy has become increasingly popular in the treatment of arachnoid cysts, but experience with cysts located in the interhemispheric fissure and in the quadrigeminal cistern is limited. This study reviews the specific anatomy of interhemispheric and quadrigeminal cysts and their relationship with the ventricular system and subarachnoid cisterns to select the most appropriated treatment. It also reviews the literature on endoscopic treatment of interhemispheric and quadrigeminal cysts. Interhemispheric and quadrigeminal cysts are not homogeneous, they have different extensions toward surrounding regions. In most cases it is presented as an area of contiguity between the cyst and ventricular system and/or subarachnoid cisterns, making endoscopic treatment feasible. The success rate for endoscopic treatment is not different from that reported in large series of arachnoid cysts elsewhere. Endoscopic treatment should be considered the first-line option in the treatment of such lesions, even if some complications, such as subdural collections due to thinness of the cerebral mantle or subcutaneous CSF collections due to multifactorial associated hydrocephalus, must be expected. | {
"pile_set_name": "PubMed Abstracts"
} |
Affinity chromatography with nucleic acid polymers.
Column chromatography utilizing polynucleotides immobilized on solid support is reviewed. This form of affinity chromatography is used for the isolation of polynucleotides and polynucleotide binding proteins, and to a lesser extent for analysis. Several specific applications within these categories have been widely used in the biomedical sciences. Poly(A) mRNA is routinely isolated using oligo(dT) or oligo(dU) supports. Many DNA binding proteins, including transcription factors, restriction endonucleases, and proteins involved in DNA repair, replication, recombination, and transposition have been purified using DNA affinity chromatography. Recently, DNA supports suitable for use in high-performance liquid chromatography have been described and utilized. The current usage of DNA affinity chromatography is reviewed and potential future uses for this technology are speculated upon. | {
"pile_set_name": "PubMed Abstracts"
} |
A deleterious founder mutation in the BMPER gene causes diaphanospondylodysostosis (DSD).
Diaphonospondylodysostosis (DSD) is a rare, recessively inherited, lethal skeletal dysplasia, characterized by severe spinal ossification, segmentation defects, and renal cystic dysplasia with nephrogenic rests. We hereby present three affected individuals: two children and a fetus from two unrelated East Jerusalem Arab-Muslim families. Whereas most fetuses die in utero or perinatally, one of the children survived to 15 months. Homozygosity mapping in the two families demonstrated a single common 3.87 Mb region on chromosome 7, ruling out previously known spondylocostal/spondylothoracic dysostosis loci. The 15 protein coding genes in the region were prioritized, and some were sequenced. A single, novel deleterious mutation, Q104X, was detected in the bone morphogenetic protein-binding endothelial regulator protein (BMPER) gene, recently reported to be mutated in other DSD patients [Funari et al., 2010]. The novel mutation we identified is an ancestral founder allele, as evidenced by a shared 440 SNP haplotype, and its frequency in the general Arab population is estimated to be <1:123. Our findings confirm loss of BMPER function as a cause of axial versus appendicular skeletal defects, and suggest that less deleterious mutations may be involved in milder axial skeleton abnormalities. | {
"pile_set_name": "PubMed Abstracts"
} |
[Recombinant expression and antibacterial activity of i-type lysozyme from sea cucumber Stichopus japonicus].
The cDNA of an i type lysozyme was cloned from Stichopus japonicus (named as SjLys). The DNA fragment of the mature SjLys was subcloned into expression vector of pET-32a (+) to construct the recombinant plasmid of pET32a (+)-SjLys. The recombinant plasmid was then transformed into Escherichia coli BL21 (DE3) pLysS and induced by isopropylthio-beta-D-galactoside (IPTG). The recombinant protein expressed as inclusion bodies was denatured, partially purified and refolded to be an active form. The bacteriolytic activity of recombinant protein purified by the metal-chelating was 19.2 U/mg. The antibacterial activity of the purified recombinant SjLys (rSjLys) was analyzed. The rSjLys protein displayed inhibitive effect on the growth of the tested Gram-positive and Gram-negative bacteria. In particular, rSjLys had a strong inhibitive activity on Vibrio parahaemolyticus and Pseudomonas aeruginosa, both the most common pathogenic bacteria in the marine animals. The heat-treated rSjLys exhibited more potent activities against all tested bacteria. These results indicated that the S. japonicus lysozyme was the enzyme with combined enzymatic (glycosidase) and non-enzymatic antibacterial action, and it had a wide antibacterial spectrum. Therefore, it is suggested that the S. japonicus lysozyme should be one of the important molecules against pathogens in the innate immunity of sea cucumbers. | {
"pile_set_name": "PubMed Abstracts"
} |
Thyroid cancer in HCV-related mixed cryoglobulinemia patients.
The prevalence of thyroid cancer in a series of unselected HCV-related mixed cryoglobulinemic patients was investigated in comparison with a control group. Among 107 consecutive patients with mixed cryoglobulinemia (MC), 94 were eligible for the study. A control group was obtained from a sample of the general population (2,401 subjects), age > 50 years, who had undergone thyroid ultrasonography (582 subjects); 5 sex-matched controls were randomly assigned to each MC patients (470 individuals). The mean age was similar in the MC patients and controls (64.2 +/- 10.0 vs. 63.4 +/- 7.0). The prevalence of thyroid nodules was higher, although not significantly so, in control subjects than in MC patients (65.3 vs. 54.8%). Two patients with papillary thyroid cancer were found in the MC series, while no case was observed among controls (p = 0.001, chi-square P value; p = 0.02, Fisher's exact test). In both MC patients with papillary thyroid cancer lymphocytic infiltration was observed in the thyroid tissue. The possible association between HCV-related MC and thyroid cancer indicates that a careful monitoring of the thyroid would be opportune during the clinical follow-up of HCV-associated MC patients, especially in those with signs of thyroid autoimmune disorders. | {
"pile_set_name": "PubMed Abstracts"
} |
Monocyte-derived cytokine--IL-12, TGF-beta 1 and TNF-alpha in patients with tuberculosis.
Pulmonary tuberculosis is an infectious disease caused by Mycobacterium tuberculosis (MTB). This microorganism is capable of inducing a delayed hypersensitivity in the lung, with subsequent expression of the disease. This reaction depends on the presence of different cytokines that exert specific functions. To study the variability of different cytokine responses after MTB antigenic challenge, we used antigens derived from MTB to stimulate the monocytes from both normal healthy contact and the patients with active tuberculosis. We found in the resting state monocytes from healthy contact secreted higher amounts of IL-12 than those from patients. After stimulation with MTB antigen, the secretion of IL-12 did not increase in normal healthy contact, but in patients with tuberculosis the secretion increased. After MTB antigen stimulation, monocytes from patients with active tuberculosis secreted a higher amount of TNF-alpha. In summary, the patterns of monocyte-derived cytokine secretion upon mycobacterial antigen challenge were different in these two groups. | {
"pile_set_name": "PubMed Abstracts"
} |
Making all routes into nursing attractive.
Sam Foster, Chief Nurse, Oxford University Hospitals, discusses recent developments in technical qualifications and how to encourage more young people to consider a career in nursing. | {
"pile_set_name": "PubMed Abstracts"
} |
Radiation exposure in patients undergoing endoscopic retrograde cholangiopancreatography and endoscopic papillotomy.
Radiation exposure was studied in 327 patients undergoing endoscopic retrograde cholangiopancreatography, or endoscopic papillotomy taking into account fluoroscopy time and incident area exposure. The mean fluoroscopy time was 238 +/- 152 seconds and the incident area exposure 3,730 +/- 2,790 R X cm2. These results were compared with standard exposures in upper GI series and colon examinations as found in the literature. | {
"pile_set_name": "PubMed Abstracts"
} |
Effects of long-term storage at different temperatures on conidia of Botrytis cinerea Pers.: Fr.
Survival of Botrytis cinerea conidia was studied after storage without pretreatments at different temperatures (-80 degrees C, -20 degrees C, 4 degrees C and 21 degrees C). Germination tests performed during 3 years showed that viability at 21 degrees C was completely lost after 1 month. Conidia stored for 30 months at -80 degrees C, -20 degrees C and 4 degrees C were able to germinate, respectively, at 79%, 8% and 0.2%. Changes in adenylate level, energy charge and respiration (O(2) consumption) made on each set of conidia were correlated to the germination rate. The 30-month-old stored conidia showed differences in pathogenicity tests on apples. While the pathogenic aggressiveness of conidia stored at -80 degrees C was almost the same as for fresh conidia, it decreased with increasing temperature of storage. An ultrastructural study made on conidia stored for 30 months at -80 degrees C has shown the emergence of a new wall layer in a retraction zone of the cytoplasm by comparison to fresh conidia. However, the integrity of the cytoplasmic content was maintained. The effects of low temperature storage, maintenance of cell integrity and pathogenicity of conidia of B. cinerea are discussed. | {
"pile_set_name": "PubMed Abstracts"
} |
Promoting smoking cessation in adults.
There is a wealth of opportunities for nurses to facilitate smoking cessation with their patients. Nurses have shown to have a modest but positive effect on cessation rates when they deliver brief or intensive counseling. Because nurses work in a multitude of clinical settings, they can impact both prevention and treatment of nicotine addiction associated with cigarette use. More nurses need to be educated about their role in reducing the morbidity and mortality of tobacco-related diseases. | {
"pile_set_name": "PubMed Abstracts"
} |
The effect of a rapid kit for detection of streptococcal pharyngitis on the accuracy of the physicians' diagnoses.
In the last decade, the accuracy of rapid tests for detection of group A streptococcal antigen was evaluated in laboratory and clinical settings, and the tests were suggested as an alternative to the traditional throat culture. We evaluated 19 patients with a preliminary diagnosis of nonstreptococcal pharyngitis and 13 patients with a preliminary diagnosis of streptococcal pharyngitis. The physician performed a rapid latex agglutination test (Detect A Strep), took throat culture from all of the patients, reconsidered the preliminary diagnosis, and made a working diagnosis. A clinical score was calculated for each patient during data analysis. The accuracy of the physicians' preliminary diagnoses was compared with the accuracy of the scoring system, with the accuracy of the latex agglutination test, and with the accuracy of the physicians' working diagnoses. The scoring system, the physicians' preliminary diagnoses, the latex agglutination test, and the physicians' working diagnoses correlated significantly with throat culture results (p < or = 0.05). The efficiency of the physicians' preliminary diagnoses was 75% compared with an efficiency of 69% of the clinical scoring system, an efficiency of 66% of the latex agglutination test, and an efficiency of 69% of the physicians' working diagnoses. The physician changed the preliminary diagnosis only for two patients as a result of the latex agglutination test results; ironically, however, the preliminary diagnosis was correct in both of these cases. The use of a rapid test for the diagnosis of group A streptococcal antigen under normal working conditions did not improve the accuracy of the physician's diagnosis, so the use of the latex agglutination test in this study was not cost-effective. | {
"pile_set_name": "PubMed Abstracts"
} |
TLR-4 signaling promotes tumor growth and paclitaxel chemoresistance in ovarian cancer.
Evidence suggests that an inflammatory profile of cytokines and chemokines persisting at a particular site would lead to the development of a chronic disease. Recent studies implicate bacterial infection as one possible link between inflammation and carcinogenesis; however, the crucial molecular pathways involved remain unknown. We hypothesized that one possible upstream signaling pathway leading to inflammation in carcinogenesis may be mediated by Toll-like receptors (TLR). We describe for the first time an adaptive mechanism acquired by ovarian cancer cells that allows them to promote a proinflammatory environment and develop chemoresistance. We propose that the TLR-4-MyD88 signaling pathway may be a risk factor for developing cancer and may represent a novel target for the development of biomodulators. Our work explains how bacterial products, such as lipopolysaccharide, can promote, directly from the tumor, the production of proinflammatory cytokines and the enhancement of tumor survival. In addition, we provide new evidence that links TLR-4 signaling, inflammation, and chemoresistance in ovarian cancer cells. | {
"pile_set_name": "PubMed Abstracts"
} |
Erratum.
Lambert PR, Silverstein H, LeBel C, Bishop K. OTO-104 in Ménière's disease patients: phase 3 results. Otolaryngol Head Neck Surg. 2017;157:P122-P123. (Original doi: 10.1177/0194599817717251f) This Oral Presentation abstract should have included a note indicating that it was withdrawn during production of the issue. The online version has been updated to include this note. | {
"pile_set_name": "PubMed Abstracts"
} |
Type testing of a locally made LiF:Mg,Ti + PTFE TLD for its use as a personal dosimeter.
Our research group has developed a thermoluminescence dosimeter (TLD) based on pellets of LiF:Mg,Ti mixed with polytetrafluoroethylene (LiF:Mg,Ti +PTFE). This TLD can be used as a personal dosimeter. Extensive type testing, carried out with reference to the International Electrotechnical Commission (IEC) Standard, were performed for the purpose of accepting the LiF:Mg,Ti+PTFE as a personal TL dosimeter. Tests performed include repeatability, batch homogeneity, linearity, detection threshold, and light sensitivity. Results showed that locally made LiF:Mg,Ti+PTFE TLDs met all the standard requirements. | {
"pile_set_name": "PubMed Abstracts"
} |
Personal resources and the social distribution of depression.
This paper addresses the hypothesis that gender, age, marital status, and SES matter for depression partly because of associated differences in the availability and/or impact of the personal resources of mastery and self-esteem. It is argued that findings indicating that the social distributions of these resources complement those for depression would provide preliminary support for this hypothesis. Based on a large urban community sample (n = 1,390), our findings fail to support the availability hypothesis in relation to marital status, provide only modest support in reference to age and gender, but yield compelling support in relation to socioeconomic status (SES). Indeed, variations in the availability of these resources, especially mastery, provide a largely, if not entirely, adequate explanation for the SES-depressive symptoms relationship and accounts for nearly half of the SES-Major Depressive Disorder relationship. Although the significance of mastery was more pronounced among women and unmarried persons, such differences did not contribute to understanding observed gender or marital status variations in depression. | {
"pile_set_name": "PubMed Abstracts"
} |
Spatial correlation as an early warning signal of regime shifts in a multiplex disease-behaviour network.
Early warning signals of sudden regime shifts are a widely studied phenomenon for their ability to quantify a system's proximity to a tipping point to a new and contrasting dynamical regime. However, this effect has been little studied in the context of the complex interactions between disease dynamics and vaccinating behaviour. Our objective was to determine whether critical slowing down (CSD) occurs in a multiplex network that captures opinion propagation on one network layer and disease spread on a second network layer. We parameterized a network simulation model to represent a hypothetical self-limiting, acute, vaccine-preventable infection with short-lived natural immunity. We tested five different network types: random, lattice, small-world, scale-free, and an empirically derived network. For the first four network types, the model exhibits a regime shift as perceived vaccine risk moves beyond a tipping point from full vaccine acceptance and disease elimination to full vaccine refusal and disease endemicity. This regime shift is preceded by an increase in the spatial correlation in non-vaccinator opinions beginning well before the bifurcation point, indicating CSD. The early warning signals occur across a wide range of parameter values. However, the more gradual transition exhibited in the empirically-derived network underscores the need for further research before it can be determined whether trends in spatial correlation in real-world social networks represent critical slowing down. The potential upside of having this monitoring ability suggests that this is a worthwhile area for further research. | {
"pile_set_name": "PubMed Abstracts"
} |
Trapping efficacy of Duddingtonia flagrans against Haemonchus contortus at temperatures existing at lambing in Australia.
The aim of this study was to determine the trapping efficacy of Duddingtonia flagrans against Haemonchus contortus at the temperature ranges experienced around lambing in the major sheep producing regions of Australia. Faeces were collected from Merino wethers, maintained in an animal house and which had received either D. flagrans chlamydospores for a 6-day period (DF) or not (NIL). Faeces were incubated at one of four daily temperature regimens which were composed of hourly steps to provide 6-19 degrees C, 9-25 degrees C, 14-34 degrees C and 14-39 degrees C to mimic normal diurnal air temperature variation. Enumeration of the number of preinfective and infective larvae that had migrated from or remained in faecal pellets was used to calculate percentage recovery and trapping efficacy of D. flagrans. Recovery of H. contortus larvae of both stages was significantly lower in DF faeces but the magnitude of the effect was considerably greater for infective larvae. Mean recovery of infective larvae from NIL and DF faeces was 10.6 and 0.4%, respectively, indicating a mean trapping efficacy of 96.4%. The lowest trapping efficacy (80.7%) was observed at 6-19 degrees C but total recovery of infective larvae, from DF faeces, was greatest at the two highest temperature regimens, although still less than 0.9%. The results of this study indicate that typical Australian lambing temperatures should not be a barrier to the use of D. flagrans as an effective biocontrol of H. contortus in Australia. | {
"pile_set_name": "PubMed Abstracts"
} |
Estradiol levels in girls with Turner's syndrome compared to normal prepubertal girls as determined by an ultrasensitive assay.
Based on growing evidence that estradiol is produced in small amounts even in the prepubertal ovary, we hypothesized that estradiol levels in girls with Turner's syndrome (TS) are lower than in normal prepubertal girls secondary to the lack of normally functioning ovaries. Estradiol levels in untreated girls with TS have not been previously well defined because of the lack of adequate sensitivity of previously available estradiol assays. We utilized an ultrasensitive assay to study estradiol levels in 34 girls with TS and 34 normal age-matched prepubertal girls between the ages of 5 and 12 years. The average estradiol level in the girls with TS (6.4 +/- 4.9 pmol/l estradiol equivalents) was significantly lower than in the normal prepubertal girls (12.7 +/- 10.8 pmol/l estradiol equivalents; p < 0.01). Girls with TS were significantly shorter, and weighed less than the normal prepubertal girls, as expected. The estradiol level was not significantly correlated with height, bone age, or degree of bone age delay. In conclusion, girls with TS have significantly lower estradiol levels than normal age-matched prepubertal girls. This report is consistent with the hypothesis that the lack of normal ovarian function in girls with TS is evident even before puberty. | {
"pile_set_name": "PubMed Abstracts"
} |
Psoriatic arthritis: clinical improvement and correlation with hormone axes in etanercept-treated patients.
In a chronic inflammatory disease, such as rheumatoid arthritis (RA), the hypothalamic-pituitary-adrenal axis is altered in three ways: (1) the inflammation-related spontaneous and stimulated secretion of cortisol is inadequate; (2) the inflammation-related secretion of adrenocorticotropic hormone (ACTH) is low; and (3) the levels of adrenal androgens decrease. In patients with RA, long-term therapy with anti-TNF therapy sensitizes the pituitary gland and improves adrenal androgen secretion. We have recently found that the mean serum levels of ACTH, cortisol, 17-hydroxyprogesterone (17OHP), and androstenedione (ASD) in 11 prednisolone-naïve patients with psoriatic arthritis did not markedly change during 12 weeks of etanercept treatment, nor did the serum cortisol/ACTH ratio. However, the greater increase in serum cortisol in comparison with serum 17OHP or ASD was related to clinical improvement, which indicates that the improvement was more related to the higher cortisol levels. | {
"pile_set_name": "PubMed Abstracts"
} |
Evaluation of intensity and energy interaction parameters for the complexation of Pr(III) with selected nucleoside and nucleotide through absorption spectral studies.
The interactions of Pr(III) with nucleosides and nucleotides have been studied in different organic solvents employing absorption difference and comparative absorption spectrophotometry. The magnitudes of the variations in both energy and intensity interaction parameters were used to explore the degree of outer and inner sphere co-ordination, incidence of covalency and the extent of metal 4f-orbital involvement in chemical bonding. Various electronic spectral parameters like Slater-Condon (F(k)), Racah (E(k)), Lande parameter (ξ(4f)), Nephelauxatic ratio (β), bonding (b(1/2)), percentage covalency (δ) and intensity parameters like oscillator strength (P) and Judd Ofelt electronic dipole intensity parameter (T(λ), λ=2,4,6) have been evaluated. The variation of these evaluated parameters were employed to interpret the nature of binding of Pr(III) with different ligands i.e. Adenosine/ATP in presence and absence of Ca(2+). | {
"pile_set_name": "PubMed Abstracts"
} |
Pituitary adenomas in acromegaly: Comparison of different adenoma types with clinical data.
Adenoma tissues from 309 patients with active acromegaly was examined by routine light microscopy and immunohistochemistry, and selectively by electron microscopy. All adenomas were immunoreactive for growth hormone. Eighty-seven adenomas were monohormonal (28%), 58 were bihormonal (immunoreactive for growth hormone and prolactin) (19%), and 157 adenomas were plurihormonal (51%), with positivity for glyco-proteins and/or their α-subunit as well. The mean tumor size was significantly greater in monohormonal adenomas than in other adenoma types. There was no difference in invasiveness among the various adenoma types. Younger patients showed invasive tumor growth more often. Patients with densely granulated GH cell adenomas had a significantly longer duration of symptoms compared to patients with other adenoma types. More than half of the patients with sparsely granulated GH cell adenomas had a duration of less than 5 yr. There was no correlation between duration of symptoms and tumor size. The preoperative mean GH level was significantly higher in patients with sparsely granulated GH cell adenomas than in those with mixed GH/PRL cell adenomas. The preoperative mean PRL level was significantly higher in patients with bihormonal adenomas than in those with plurihormonal adenomas. There was an inverse correlation between age and preoperative GH and PRL levels. No linear correlation was found between preoperative basal GH and PRL levels. Monohormonal adenomas presented more often with suprasellar and/or parasellar extension than other adenoma types. Our data suggest a positive correlation between tumor extension and preoperative GH and PRL levels. Patients with plurihormonal adenomas were significantly older than patients with sparsely granulated GH cell adenomas and mixed GH/PRL cell adenomas. No significant difference was found between the various adenoma types and the extent of surgical removal, which depends on the degree of invasiveness, tumor size, and extrasellar tumor extension. | {
"pile_set_name": "PubMed Abstracts"
} |
MUC5B mucin production is upregulated by fibronectin and laminin in human lung epithelial cells via the integrin and ERK dependent pathway.
MUC5B mucin is a principal component of airway mucus and plays a key role in biodefense. We investigated the regulation of MUC5B production using the signals from extracellular matrix (ECM) components in NCI-H292 human lung epithelial cells. We found that MUC5B production in NCI-H292 cells cultured on fibronectin or laminin increased by 4-5-fold, with the increase occurring in a dose- and time-dependent manner. In contrast, MUC5B production was unchanged on type-IV collagen. Inhibition of integrin β1 induced upregulation of MUC5B and MUC5AC; however, inhibition of p38 MAPK did not show any remarkable change in overproduced MUC5B. Inhibition of extracellular signal-regulated kinase (ERK) pathway or the transcription factor NF-κB induced the recovery of overproduced MUC5B on fibronectin and laminin. These results suggest that MUC5B production can be regulated by ECM components and that MUC5B is upregulated by fibronectin and laminin via the integrin, ERK, and NF-κB dependent pathway. | {
"pile_set_name": "PubMed Abstracts"
} |
[Animal model of rat-to-mouse xenogeneic bone marrow transplantation with graft-versus-host disease].
To observe the graft-versus-host disease (GVHD) in rat-to-mouse model of bone marrow transplantation to build a GVHD model, BALB/c mice were conditioned with 8.5 Gy lethal total body irradiation and divided into two groups. One group of mice was infused with 4 x 10(7) bone marrow cells (BMC) from SD rats. The other group of mice was infused with 4 x 10(7) bone marrow cell and 2 x 10(7) spleen cells from SD rats. GVHD in mice of two groups were observed for 60 days. The results showed that mice in the group infused with only BMC mostly (80%) survived more than 60 days, but in the other group infused with mixed BMC and spleen cells, all mice died within 14 days and showed GVHD with pathologic evidence. In conclusion, to induce GVHD in rat-to-mouse bone marrow transplantation needs additional rat spleen cells. | {
"pile_set_name": "PubMed Abstracts"
} |
The risk of developing food allergy in premature or low-birth-weight children.
Premature or low-birth-weight children have increased gut permeability compared with term or normal-birth-weight children. To determine whether premature or low-birth-weight children have an increased risk of developing food allergy compared with term or normal-birth-weight children. The 1995 Manitoba Birth Cohort was studied using the Manitoba Health Services Insurance Plan (MHSIP) database. This database is a population-based, health care administrative and prescription database. It has records of every child born and subsequent utilization of the provincial health care system. The diagnosis of food allergy (ICD-9-CM code of 693 in hospital/medical claims or a prescription of injectable epinephrine excluding a sole diagnosis of venom allergy) was obtained up until the year 2002. The relative risks of food allergy in premature or low-birth-weight children compared with term or normal-birth-weight children were determined. A total of 13,980 children were born in 1995 and continue to live in the province of Manitoba. Of these, 592 children (4.23%) were found to have food allergy and epinephrine was prescribed in 316 (2.26%) children. No gestational age or birth weight group had a statistically significant increased risk for food allergy. Prematurity and low birth weight are not associated with a change in risk for development of food allergy in childhood. Immaturity of the gastrointestinal tract or immune response does not seem to change the risk for development of food allergies. We ask whether early exposure to food antigens may protect premature children by increasing immune tolerance to those antigens. | {
"pile_set_name": "PubMed Abstracts"
} |
Using national microbiological data to set meaningful performance criteria for slaughter and dressing of animals at Australian export abattoirs.
Slaughter establishments in Australia that export meat to the USA are required by the controlling authority, the Australian Quarantine and Inspection Service (AQIS), to test carcases under the Escherichia coli and Salmonella monitoring (ESAM) program and to use statistical process control techniques to ensure meat is produced hygienically. However, analysing the ESAM database for E. coli using standard statistical techniques proved difficult because of inter-plant variability and because the vast majority of results were below the limits of detection. As well, it is likely that, in slaughter and dressing, higher than normal microbiological counts can often be random events, for which there is neither logical explanation nor obvious management reaction. One approach to statistical process control is to set performance criteria so that a high proportion of establishments are likely to pass, while prompting individual plants to improve the process if they cannot meet the criteria. A spreadsheet-based tool was developed in Visual Basic in order to interrogate the ESAM database and to identify those plants with microbiological performance significantly different from the norm. The present paper describes how performance criteria for cattle, sheep, pigs and goats and for sub-categories within a species (e.g. sheep/lambs, cows/bulls) were established. | {
"pile_set_name": "PubMed Abstracts"
} |
Combinational immunotherapy for established tumors with engineered tumor vaccines and adenovirus-mediated gene transfer.
There are currently extensive studies relating to cancer vaccines using tumor cells engineered to express immunogenes and cancer gene therapy using adenovirus (AdV)-mediated gene transfer. In this study, a mouse tumor cell line, VKCK, was cotransfected with genes coding for tumor necrosis factor-alpha (TNF-alpha) and costimulatory B7-1 molecule to enhance immunogenicity. The transfectant cell line VKCK-TNF-alpha/B7-1 showed reduced tumorigenicity and tumor regression. Its inoculation further induced protective immunity; both CD4+ and CD8+ T cells were involved in the induction phase, whereas only CD8+ T cells mediated the effector phase. Susceptible mice bearing VKCK tumors developed a T helper type 2-dominant response, whereas resistant mice with VKCK-TNF-alpha/B7-1 tumor regression developed a T helper type 1-dominant response to VKCK, indicating that the tumor regression was related to a shift in the cytokine profile of the host from type 2 to type 1. Vaccination of VKCK-TNF-alpha/B7-1 cells inhibited tumor formation derived from a single dose of 3 x 10(6) VKCK cells and eradicated 3-day tumors but not 10-day tumors. AdV-mediated TNF-alpha gene transfer by intratumoral injection of AdV-TNF-alpha significantly inhibited tumor growth but failed to eradicate any well-established tumors. However, combinational immunotherapy with vaccination of VKCK-TNF-alpha/B7-1 cells and AdV-mediated TNF-alpha gene transfer not only significantly inhibited tumor growth but also eradicated 10-day VKCK tumors in three of eight mice. Therefore, the present study may be useful not only in understanding the mechanisms responsible for an efficient antitumoral immunity, but also in establishing a more effective immunotherapeutic approach for cancer patients. | {
"pile_set_name": "PubMed Abstracts"
} |
The stimulatory effect of platelet homogenate on prolyl hydroxylase activity in L-929 cells.
We have found that the addition of platelet homogenate to confluent cultures of L-929 cells increases 2-3 times the activity of prolyl hydroxylase in these cells. Furthermore, it was found that the platelet homogenate potentiates the effect of ferrous ions and ascorbic acid, which are known activators of prolyl hydroxylase. The effect of the platelet homogenate is diminished by cycloheximide. It seems probable that some products present in the platelet homogenate may promote biosynthesis of the enzyme or they stimulate glycolysis and accumulation of lactic acid, an activator of the hydroxylase. | {
"pile_set_name": "PubMed Abstracts"
} |
Yttrium-90 ibritumomab tiuxetan followed by rituximab maintenance as treatment for patients with diffuse large B-cell lymphoma are not candidates for autologous stem cell transplant.
Not all patients with diffuse large B-cell lymphoma (DLBCL) are candidates for aggressive regimens. (90)Y ibritumomab tiuxetan ((90)Y-IT), an anti-CD20 radionuclide-conjugated antibody, has demonstrated clinical efficacy in DLBCL with a favorable toxicity profile. This phase II trial investigated the overall response rate (ORR), event-free survival (EFS), overall survival (OS) and toxicity of treatment with (90)Y-IT (0.4 or 0.3 mCi (90)Y/kg based on platelets) followed by rituximab maintenance therapy in patients with DLBCL not candidates for transplant. 25 patients were enrolled. At best response 8 patients obtained a complete response (CR) and 1 a partial response (ORR 36%). Median EFS was 2.5 months and OS 8.1 months. No patient who obtained CR later relapsed systemically. Two patients were free of disease at the 61- and 100-month follow-ups; 65% had grade 3/4 thrombocytopenia, but no significant bleeding was observed. Grade 3 nonhematologic toxicity occurred in 36%. Patients who had progressed through a rituximab-containing regimen responded poorly. The ORR of 36% with (90)Y-IT as salvage therapy for DLBCL while inferior to more aggressive regimens is significant with acceptable toxicity. For a subset of patients not candidates for salvage with autologous transplant, this treatment strategy can produce a durable, long-lasting remission. | {
"pile_set_name": "PubMed Abstracts"
} |
Analytical aspects of smart (phone) fluorometric measurements.
Facing the problem of a growing number of analyses, the need for using simple equipment appears. Smartphone-based optical detection is one of the most widely applied ideas nowadays. A personal device such as a smartphone equipped with a camera is affordable even in the source-limited places. After a simple modification, providing the light source of both defined properties and orientation, a smartphone may become an efficient analytical device. In this work we present a uniform methodology of such a modification, offering a complete hand-held device for fluorometric measurements. Inducing the fluorescence of the tested analytes was done by ordinary light-emitting diodes, and phone camera was used as a detector. Then the obtained images were analyzed using the RGB colour model to get proper calibration curves. The demonstration of the system performing with the use of fluorescein preceded the examples of determination of quinine, rhodamine B, riboflavin and calcein in real-life circumstances. Example determinations of the calcium ions in mineral water and riboflavin in alcoholic beverages are provided. The results obtained with the designed device are fully comparable to the ones obtained with the conventional fluorometric equipment. The presented systems allow determination of all the investigated analytes with satisfactory detection limits, in some cases down to ppb levels. Thanks to the use of LEDs, the system could be adapted for both measuring and inducing fluorescence in different analytes, characterized by various excitation wavelengths. | {
"pile_set_name": "PubMed Abstracts"
} |
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