title stringlengths 0 1.13k | abstract stringlengths 1 15.7k | PMID int64 22 36.5M |
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Intrinsic severity as a determinant of antiepileptic drug refractoriness. | For the most part, resistance to medications in epilepsy is independent of the choice of antiepileptic drug. This simple clinical observation constrains the possible biological mechanisms for drug refractory epilepsy by imposing a requirement to explain resistance for a diverse set of chemical structures that act on an even more varied group of molecular targets. To date, research on antiepileptic drug refractoriness has been guided by the "drug transporter overexpression" and the "reduced drug-target sensitivity" hypotheses. These concepts posit that drug refractoriness is a condition separate from the underlying epilepsy. Inadequacies in both hypotheses mandate a fresh approach to the problem. In this article, we propose a novel approach that considers epilepsy pharmacoresistance in terms of intrinsic disease severity. We suggest that neurobiological factors that confer increased disease severity lead to drug intractability. The occurrence of frequent seizures at disease onset is an important factor that signals increased severity. | 18,852,835 |
The Severely-Distressed African American Family in the Crack Era: Empowerment is not Enough. | Numerous African American families have struggled for generations with persistent poverty, especially in the inner city. These conditions were further strained during the 1980s and 1990s by the widespread use of crack cocaine. For many, crack use became an obsession, dominated their lives, and superseded family responsibilities. This behavior placed additional pressure on already stressed kin support networks. This paper explores the processes prevailing in two households during this period. In the 2000s, children born to members of the Crack Generation are avoiding use of crack but face major deficits from their difficult childhoods. This presents both challenges and opportunities. The discussion considers initiatives from both a social problems and a strengths perspective that could help these families and help these families help themselves to advance their economic circumstances. | 18,852,841 |
An integrated approach for the analysis of biological pathways using mixed models. | Gene class, ontology, or pathway testing analysis has become increasingly popular in microarray data analysis. Such approaches allow the integration of gene annotation databases, such as Gene Ontology and KEGG Pathway, to formally test for subtle but coordinated changes at a system level. Higher power in gene class testing is gained by combining weak signals from a number of individual genes in each pathway. We propose an alternative approach for gene-class testing based on mixed models, a class of statistical models that: a) provides the ability to model and borrow strength across genes that are both up and down in a pathway, b) operates within a well-established statistical framework amenable to direct control of false positive or false discovery rates, c) exhibits improved power over widely used methods under normal location-based alternative hypotheses, and d) handles complex experimental designs for which permutation resampling is difficult. We compare the properties of this mixed models approach with nonparametric method GSEA and parametric method PAGE using a simulation study, and illustrate its application with a diabetes data set and a dose-response data set. | 18,852,846 |
Evaluating assay precision. | * When evaluating the precision of a method it is necessary to assess the repeatability (within-run) and the total or within-laboratory precision. * It is insufficient to assess repeatability in a single run. * Clinical and Laboratory Standards Institute (CLSI) document EP05-A2 describes the protocols for determining the precision of a method. The precision of a method should be tested at at-least two levels; each run in duplicate, with two runs per day over 20 days. CLSI document EP15-A2 describes the protocols that should be undertaken by the user to verify precision claims by a manufacturer. Precision claims by a manufacturer should be tested at at-least two levels, by running three replicates over five days. * A spreadsheet for assisting with the calculations described in this article is available from the AACB web-site. | 18,852,851 |
A new antigen retrieval technique for human brain tissue. | Immunohistochemical staining of tissues is a powerful tool used to delineate the presence or absence of an antigen. During the last 30 years, antigen visualization in human brain tissue has been significantly limited by the masking effect of fixatives. In the present study, we have used a new method for antigen retrieval in formalin-fixed human brain tissue and examined the effectiveness of this protocol to reveal masked antigens in tissues with both short and long formalin fixation times. This new method, which is based on the use of citraconic acid, has not been previously utilized in brain tissue although it has been employed in various other tissues such as tonsil, ovary, skin, lymph node, stomach, breast, colon, lung and thymus. Thus, we reported here a novel method to carry out immunohistochemical studies in free-floating human brain sections. Since fixation of brain tissue specimens in formaldehyde is a commonly method used in brain banks, this new antigen retrieval method could facilitate immunohistochemical studies of brains with prolonged formalin fixation times. | 18,852,880 |
Underutilization of social insurance among the poor: evidence from the Philippines. | Many developing countries promote social health insurance as a means to eliminate unmet health needs. However, this strategy may be ineffective if there are barriers to fully utilizing insurance. We analyzed the utilization of social health insurance in 30 hospital districts in the central regions of the Philippines between 2003 and 2007. Data for the study came from the Quality Improvement Demonstration Study (QIDS) and included detailed patient information from exit interviews of children under 5 years of age conducted in seven waves among public hospital districts located in the four central regions of the Philippines. These data were used to estimate and identify predictors of underutilization of insurance benefits--defined as the likelihood of not filing claims despite having legitimate insurance coverage--using logistic regression. Multivariate analyses using QIDS data from 2004 to 2007 reveal that underutilization averaged about 15% throughout the study period. Underutilization, however, declined over time. Among insured hospitalized children, increasing length of stay in the hospital and mother's education, were associated with less underutilization. Being in a QIDS intervention site was also associated with less underutilization and partially accounts for the downward trend in underutilization over time. The surprisingly high level of insurance underutilization by insured patients in the QIDS sites undermines the potentially positive impact of social health insurance on the health of the marginalized. In the Philippines, where the largest burden of health care spending falls on households, underutilization suggests ineffective distribution of public funds, failing to reach a significant proportion of households which are by and large poor. Interventions that improve benefit awareness may combat the problem of underutilization and should be the focus of further research in this area. | 18,852,881 |
Worm grunting, fiddling, and charming--humans unknowingly mimic a predator to harvest bait. | For generations many families in and around Florida's Apalachicola National Forest have supported themselves by collecting the large endemic earthworms (Diplocardia mississippiensis). This is accomplished by vibrating a wooden stake driven into the soil, a practice called "worm grunting". In response to the vibrations, worms emerge to the surface where thousands can be gathered in a few hours. Why do these earthworms suddenly exit their burrows in response to vibrations, exposing themselves to predation? Here it is shown that a population of eastern American moles (Scalopus aquaticus) inhabits the area where worms are collected and that earthworms have a pronounced escape response from moles consisting of rapidly exiting their burrows to flee across the soil surface. Recordings of vibrations generated by bait collectors and moles suggest that "worm grunters" unknowingly mimic digging moles. An alternative possibility, that worms interpret vibrations as rain and surface to avoid drowning is not supported. Previous investigations have revealed that both wood turtles and herring gulls vibrate the ground to elicit earthworm escapes, indicating that a range of predators may exploit the predator-prey relationship between earthworms and moles. In addition to revealing a novel escape response that may be widespread among soil fauna, the results show that humans have played the role of "rare predators" in exploiting the consequences of a sensory arms race. | 18,852,902 |
Fibromyalgia syndrome: definition and diagnostic aspects. | Ever since it was first defined, fibromyalgia (FM) has been considered one of the most controversial diagnoses in the field of rheumatology, to the point that not everybody accepts its existence as an independent entity. The sensitivity and specificity of the proposed diagnostic criteria are still debated by various specialists (not only rheumatologists), whose main criticism of the 1990 American College of Rheumatology criteria is that they identify subsets of particular patients that do not reflect everyday clinical reality. Furthermore, the symptoms characterising FM overlap with those of many other conditions classified in a different manner. Over the last few years, this has led to FM being considered less as a clinical entity and more as a possible manifestation of alterations in the psychoneuroendocrine system (the spectrum of affective disorders) or the stress reaction system (dysfunctional symptoms). More recently, doubts have been raised about even these classifications; and it now seems more appropriate to include FM among the central sensitisation syndromes, which identify the main pathogenetic mechanism as the cause of skeletal and extra-skeletal symptoms of FM and other previously defined "dysfunctional" syndromes. | 18,852,904 |
Model-based assessment of data availability in health information systems. | To introduce a formal definition of data availability as a contribution to trustworthiness of health information systems and to automatically detect respective weaknesses and propose solutions. Specifying an ontology, based on enterprise functions and application systems of (health) information systems and closely linked to the Three-Layer Graph-Based Meta Model (3LGM2). Deriving appropriate measures and algorithms. A formal definition for data availability is introduced and elucidated by an example. This concept is used e.g. to disclose missing communication links and to suggest solutions. Data availability is a necessary but not sufficient condition for trustworthiness of health information systems. If information management has a thorough description of the information system at its disposal, e.g. by using 3LGM2, the calculation of data availability does not need further efforts. | 18,852,915 |
Thyroid sonomorphology, thyroid peroxidase antibodies and thyroid function: new epidemiological data in unselected German employees. | Employees of Sanofi-Aventis Deutschland GmbH underwent thyroid screening in 2006 to assess new data about the prevalence of irregular sonomorphological pattern, elevated thyroid peroxidase antibodies (TPO AB) and thyroid function in an unselected adult German population. The examination included 700 unselected employees. Blood samples were analyzed for serum TSH and TPO AB, and ultrasound of the thyroid was performed. In 40.7% of the participants (n = 285) an irregular sonomorphological pattern was detected: goiter in 13.7%, nodules in 35.6%, nodular goiter in 8.6% and a hypoechogenic pattern of the thyroid gland in 20.4%. Serum TSH was increased in 3.9% and decreased in 0.6%. Elevated TPO AB values were observed in 13%. Only 1.4% (n = 10) showed elevated TPO AB combined with a TSH increase. Sonomorphological abnormalities were associated with increased TPO AB in 7.1%. Elevated TPO AB was observed significantly more often in combination with sonomorphological pathology (54.9%) than without (45.1%) (p = 0.003). Sonomorphological disorders are still very common in Germany and our results are comparable with previous screening examinations. Elevated TPO AB correlated significantly with the sonomorphological pattern of nodules and goiter. This may reflect an improved iodine supply or a hypertrophic stage of autoimmune thyroiditis in some cases. | 18,852,925 |
Human papillomavirus infection in men residing in Brazil, Mexico, and the USA. | To assess Human Papillomavirus (HPV) type distribution among men ages 18 years and older recruited from three different countries utilizing a common protocol for sampling HPV detection, and to evaluate whether HPV detection differs by age and country. MATERIAL AD METHODS: The study protocol includes a pre-enrollment run-in visit, a baseline (enrollment) visit, and nine additional visits after enrollment scheduled six months apart. For this analysis, the first 1160 men who completed both the run-in and baseline visit were included. To maximize sampling and prevent fraying of applicators, three different applicators were utilized to sample the external genitalia of participants among different anatomic sites. These samples were later combined to form a single sample for the detection of HPV using polymerase chain reaction (PCR) for amplification of a fragment of the HPV L1 gene. Among 1160 men from Brazil, Mexico, and the United States (U.S.), overall HPV prevalence was 65.2%; with 12.0% oncogenic types only, 20.7% non-oncogenic types only, 17.8% both oncogenic and non-oncogenic, and 14.7% unclassified infections. Multiple HPV types were detected in 25.7% of study participants. HPV prevalence was higher in Brazil (72.3%) than in the U.S. (61.3%) and Mexico (61.9%). HPV 16 (6.5%), 51 (6.5%), and 59 (5.3%) were the most commonly detected oncogenic infections, and HPV 84 (7.7%), 62 (7.3%), and 6 (6.6%) were the most commonly detected non-oncogenic infections. Overall HPV prevalence was not associated with age. However, significant associations with age were observed when specific categories of oncogenic, non-oncogenic, and unclassified HPV infections were considered. Studies of HPV type distribution among a broad age range of men from multiple countries is needed to fill the information gap internationally with respect to our knowledge of HPV infection in men. | 18,852,938 |
[Endoscopic placement of a "plug" made of acellular biomaterial: a new technique for the repair of gastric leak after Roux-en-Y gastric bypass]. | Roux-en-Y gastric bypass is one of the most commonly performed bariatric surgeries in Brazil. Gastric leaks are relatively uncommon and potentially dangerous complications. The initial management of gastric leaks consists in adequate drainage, nutritional support, antibiotics and acid suppression. In almost 30% of the cases the fistula will become chronic. A novel peroral endoscopic treatment of gastric leaks in Roux-en-Y gastric bypassed patients is presented. An acellular biomaterial was endoscopically placed in the fistulous orifice in order to promote healing and avoid surgery in 25 patients. The time between fistula diagnosis and endoscopic treatment varied from 4 to 25 weeks (median: 7 weeks). Endoscopic treatment was successful in 20 (80%) patients. Fistula closure was obtained after one, two and three sessions in 6 (30%), 11 (55%) and 3 (15%) patients, respectively. No procedure related complications were observed. Endoscopic repair of gastric leak after Roux-en-Y gastric bypass by using an acellular biomaterial is safe and effective. However two or three endoscopic sessions are usually needed. | 18,852,948 |
The small bowel flora in individuals with cecoileal reflux. | The observation of cecoileal reflux to barium enema is not rare; however, its causes and consequences have not been widely investigated. Considering that ileocecal junction exerts a function as barrier to invasion of bacteria from colon to small bowel, it seems interesting to study the intestinal microflora in subjects carrying cecoileal reflux. This study aims at evaluating the ileal flora in individuals with cecoileal reflux. A group of 36 subjects comprising 30 females and 6 males with a mean age of 54 years was assessed. Twenty-five individuals with cecoileal reflux and 11 without cecoileal reflux were submitted to small intestine contamination evaluation through the breath test with lactulose-H2 and measurement of the orocecal transit time by means of alternate current biosusceptometry. Small intestine bacterial overgrowth was characterized by orocecal transit time-H2 shortening. Comparison of basal H2, orocecal transit time-H2 and orocecal transit time-alternate current biosusceptometry measurements did not statistically differ between the groups with and without cecoileal reflux. Orocecal transit time-H2 was significantly smaller than orocecal transit time-alternate current biosusceptometry, particularly in individuals with cecoileal reflux. A significant correlation between the two methods was observed only in relation to control, not existing in relation to cecoileal reflux group. Smaller orocecal transit time-H2 and the loss of correlation with orocecal transit time-alternate current biosusceptometry observed in the individuals with cecoileal reflux suggest a differentiated behavior for such group relative to control, which could be associated with small intestine bacterial overgrowth. | 18,852,949 |
Detection of hepatitis B virus DNA in sera from 18 alcoholic carriers of "anti-HBc alone" and response to a single dose of hepatitis B vaccine. | To evaluate the possibility of occult hepatitis B virus (HBV) infection in alcoholics carriers of "anti-HBc alone", and to verify the behavior of this serological pattern after a single dose of hepatitis B vaccine, 18 alcoholics who had this serological profile were evaluated by the polymerase chain reaction method, and 17 of them were vaccined. All were negative for HBV DNA. Nine (52.9%) of those vaccined had anamnestic response, mainly those with positive anti-HBe (8/10; 80%). "Anti-HBc alone" was compatible with low levels of anti-HBs in half of the patients, and probably with false positive results for anti-HBc in the others. | 18,852,957 |
Liver transplantation for acute liver failure: a 5 years experience. | Fulminant hepatic failure carries a high morbidity and mortality. Liver transplantation has markedly improved the prognosis of patients with fulminant hepatic failure. To evaluate the outcome of 20 patients with acute liver failure and indication for liver transplantation. A retrospective review of 20 patients with acute liver failure and indication for liver transplantation was performed. Patients were divided into two groups: group A with 12 patients who underwent liver transplantation and group B with 8 patients who did not receive liver transplantation. Both groups were analyzed according to age, sex, ABO blood type, etiology of acute liver failure, time on list until transplantation or death, and survival rates. Group A patients were additionally analyzed according to preoperative INR, AST, and ALT peak values and MELD (Model for End-stage Liver Disease) scores; intraoperative red blood cells and plasma transfusion and cold ischemia time; postoperative lenght of intensive care unit and hospital stay, and needed for dialysis. Group A: there were four men and eight women with an average age of 24.6 years. The average liver waiting time period was 3.4 days and MELD score 36. Seven patients are alive with good hepatic function at a medium follow-up of 26.2 months. The actuarial survival rate was 65.2% at 1 year. Group B: There were two men and six women with an average age of 30.9 years. The mean waiting time on list until death was 7.4 days. All patients died while waiting for a liver donor. Despite the improvements in intensive care management, most patients with acute liver failure and indication for liver transplantation ca not survive long without transplant. Liver transplantation is potentially the only curative modality and has markedly improved the prognosis of those patients. | 18,852,944 |
Actions in vocal health: a proposal for improving the vocal profile of teachers. | several authors have pointed to the urgent need of researches and actions involving teachers, in the school environment, that have a preventive and vocal health promotion character with the purpose of improving work conditions. to analyze the vocal complaints, laryngeal symptoms, vocal habits and vocal profile of teachers of a public school before and after their participation in voice workshops. the study was divided in different steps: 1st step - closed interview, larynx and perceptive-auditory assessment in which 42 teachers were evaluated; 2nd step - voice workshops; 3rd step - perceptive-auditory reassessment in which 13 teachers were evaluated. 73% of the subjects presented vocal complaints; 57.14% presented mild to moderate hoarseness, 78.57% presented breathiness and 52.38% vocal tension. Evaluation of the larynx indicated that 75.86% of the subjects presented glottal gaps and 34.48% mucous thickening. After the voice workshops a significant difference was observed in the level of vocal tension, both in the analysis of the /e/ vowel and in the analysis of Spontaneous Speech (p = 0.0277 for p > 0.05 for both). Improvement was observed in vocal care and in the understanding of intervening and determinant factors for vocal alterations, which are present in the teaching environment. health actions, such as voice workshops, are important to trigger changes in the work environment as well as in the health of teachers. | 18,852,965 |
Transient evoked otoacustic emissions and distortion product in school children. | Past five years of age, the main complaint of children who are hard of hearing is that they have difficulty in learning. Compare these results to suspected hearing loss, through triage with the exams of evoked otoacoustic emissions (EOAE) transients (TEOAE) and by distortion product (DPEOAE), using data from audiometric exams; observe which of the procedures of EOAE better respond to school children triage. To evaluate 451 school children, grade one students, from the public schools in São Luís. At school, otoscopic exams with the removal of wax and the TEOAE and DPEOAE exams were also carried on all school children. Audiometry and acoustic impedance were performed on the children who presented alterations at any point during the TEOAE and/or DPEOAE exams. Transversal-Prospective. 18.6% had ear wax. As for the TEOAE and DPEOAE triage, no significant statistic difference was found when comparing the results of the exams which failed only in the TEOAE and DOEOAE with audiometric exam data, nonetheless, when comparing this failure data to both of these exams there was a significant difference (p<0.05). Both EOAE procedures responded well to the hearing triage in school children. | 18,852,974 |
[Strongyloides stercoralis hyperinfection: autopsy case report]. | Asymptomatic infection due to Strongyloides stercoralis may result in potentially fatal disease in immunodepressed patients. A case of Strongyloides stercoralis hyperinfection discovered at autopsy in a 55-year-old man who had been undergoing treatment for multiple myeloma is reported, emphasizing the clinical and pathological findings. One day earlier, he presented severe headache, abdominal pain and oliguria, from which he developed acute respiratory failure and septic shock. Because of difficulty in reaching this diagnosis, empirical treatment before starting immunosuppressive therapy may be the best strategy for preventing hyperinfection by this worm. | 18,853,018 |
[New selective indicator medium for detection of Aeromonas and Plesiomonas: UNISC agar]. | We evaluated a new selective indicator medium (UNISC Agar) for isolation of classical enteropathogens, Aeromonas spp and Plesiomonas shigelloides. The xylose fermentation capacity is indicated by a yellow color (fermenting agents) or blue (no fermenting agent). This, together with the oxidase test, establishes it as an indicator for detecting Aeromonas and Plesiomonas shigelloides. Its productivity and selectivity, as assessed using the absolute count index and relative count index, indicate it as an alternative to the classical feces culturing media. This is because, in a single medium, it enables isolation of Escherichia coli, Shigella spp and Salmonella spp, in addition to Aeromonas and Plesiomonas shigelloides, thereby favoring the laboratory diagnosis of gastroenteritis. | 18,853,024 |
Epigastric pain relating to menses can be a symptom of bowel endometriosis. | Endometriosis is a common affliction that may affect the intestinal tract. The objective of this case report was to describe an unusual clinical presentation of this form of the disease. The patient was a 35-year-old woman with epigastric pain that only occurred during menstruation, who had a history of bladder endometriosis. Endoscopy of the upper digestive tract showed normal results. Transvaginal ultrasound and nuclear magnetic resonance of the pelvis showed a lesion involving the ileocecal junction and appendix, measuring 30 x 22/x/13/mm, that was suggestive of endometriosis. The patient underwent laparoscopic resection of the bowel segment affected by the disease, followed by anastomosis of the ileum and ascending colon for immediate restoration of intestinal transit. Histological analysis confirmed the diagnosis of endometriosis. In young women, recurrent epigastric pain should be evaluated with regard to its relationship to menstruation, particularly if there is a history of endometriosis, since this may be a clinical sign that the disease is affecting the intestinal transit. | 18,853,038 |
What is the angiography error when defining myocardial ischemia during percutaneous coronary interventions? | The angiography has been used as a reference standard to define coronary artery disease (CAD), although its limitations are well-known. The significance of the myocardial fractional flow reserve (FFR) in the assessment of CAD is well established. The aim of this study was to evaluate the accuracy of angiography when defining ischemic lesions and its correlation with FFR. Two hundred and fifty consecutive patients (471 arteries) were included in this study. All stenoses >or= 50% at the angiography visual estimate (AVE) were assessed by FFR measurements. When FFR was < 0.75, stenting was performed; when FFR was >or= 0.75, no interventional treatment was carried out. Offline quantitative coronary angiography (QCA) was performed in all stenoses, which were divided in intermediate (< 70% - 327) and severe (125). The correlation coefficients between the diameter of the stenosis (%DS) and FFR and the accuracy of VA of the angiography when assessing ischemia were determined. FFR could be obtained in 452 lesions (96%). Mean %DS and FFR were 56 +/- 8% and 0.74 and 76 +/- 6% and 0.48 for moderate and severe stenoses, respectively. Concordance between QCA and FFR was poor, especially in intermediate stenoses (Spearman's rho = - 0.33, p<0.0001). Visual assessment resulted in an accuracy of 57% and 96% in intermediate and severe lesions, respectively. Neither the visual assessment of an angiogram nor QCA can accurately predict the significance of most intermediate coronary stenoses, which emphasizes the importance of associating it to a functional evaluation of the coronary circulation, resulting in an adequate treatment of these stenoses. | 18,853,058 |
Athlete's heart or hypertrophic cardiomyopathy? | Intensive endurance training is able to cause a distinct pattern of functional and structural changes of the cardiovascular system. In an unknown proportion of athletes a so called "athlete's heart" develops. There is an overlap between this type of physiologic cardiac hypertrophy and mild forms of hypertrophic cardiomyopathy (HCM), the most common genetic disorder of the cardiovascular system with a prevalence of 0.2%. HCM is caused by mutations in 14 genes coding for sarcomere proteins. In the literature up to 50% of cases of sudden cardiac death (SCD) in younger sportsmen were connected to hypertrophic cardiomyopathy. It is therefore the most common cause of SCD in highly trained young athletes. Because of this data a great interest in distinguishing these two diagnoses exists. Apart from clinical examination and some non-specific ECG-changes, Echocardiography is the method of choice. The athlete's heart shows an eccentric biventricular hypertrophy with wall thicknesses under 15 mm and a moderately dilated left ventricle (LVEDD up to 58 mm). HCM is commonly characterized by asymmetric left ventricular hypertrophy with a reduced LV-diameter. In up to 70% of cases left ventricular outflow tract obstruction is evident during stress echocardiography. Systolic function is normal in highly trained athletes and the majority of HCM patients as well. There are important differences regarding diastolic filling patterns. Physiological hypertrophy is consistent with a normal diastolic function with even increased early diastolic filling. In case of HCM diastolic dysfunction (mostly relaxation disturbances) occurs in the majority of patients and is therefore inconsistent with an athlete's heart. If the diagnosis could not be stated using echocardiography, methods like cardiac-MRI, metabolic exercise testing, histological studies of endomyocardial biopsies and genetic testing can provide further information. A correct diagnosis may on the one hand prevent some athletes from sudden cardiac death. On the other hand sportsmen with an athlete's heart are reassured and able to continue as competitors. New insights into electrophysiological changes during physiological hypertrophy could probably change this view. | 18,853,091 |
How to manage patients with need for antiplatelet therapy in the setting of (un-)planned surgery. | The growing incidence of cardiovascular diseases leads to an increase in patients who require treatment with antiplatelet drugs. About 5% of patients who underwent a percutaneous coronary intervention will have to undergo surgery within the first year. In these patients the problem evolves how to handle the antiplatelet therapy in the perioperative period. A continuation of these drugs in order to reduce cardiovascular events is associated with increased perioperative bleeding. Withdrawing antiplatelet agents in order to reduce surgical hemorrhage leads to a significant increase of cardiovascular morbidity and mortality, especially in patients who have been treated with implantation of drug eluting stents. This review balances the specific risks of either approach and offers an algorithm how to manage patients in need for antiplatelet therapy in the setting of (un-)planned surgery. | 18,853,094 |
Chemopreventive potential of Epoxy clerodane diterpene from Tinospora cordifolia against diethylnitrosamine-induced hepatocellular carcinoma. | Medicinal plants are a promising source for identification of lead molecules for cancer therapy. In our continuous search to discover bioactive compounds from natural products, we isolated (5R, 10R)-4R, 8R-dihydroxy-2S, 3R:15, 16-diepoxycleroda-13(16), 17, 12S:18,1S-dilactone (ECD), a diterpenoid from Tinospora cordifolia and studied its chemopreventive potential in diethylnitrosamine (DEN) induced hepatocellular carcinoma (HCC) rats. Fifty male Wistar rats were divided into five groups. Group I served as normal control. Group II-IV were given DEN (0.01% in drinking water) for twenty weeks. In addition, Group III (preventive treatment) received ECD (10 mg/kg body weight) throughout the study. Group IV (curative treatment) received ECD (10 mg/kg body weight) for the last 8 weeks. Group V received ECD alone (10 mg/kg body weight) throughout the experimental period. At the end of the experimental period all the animals were sacrificed and analyzed for biochemical end points to assess the effect of ECD treatment in DEN induced HCC. The animals treated with DEN showed a decrease in the activities of antioxidant (SOD, CAT) and detoxification enzymes (GSH, GPx) with increase in the activities of the hepatic markers (SGOT, SGPT, LDH). Treatment of ECD in both preventive and curative DEN induced animals increased the level of antioxidants and detoxification enzymes, and decreased serum transaminase level and hepatic marker enzymes to near normal. Histopathological and nodular incidence also confirmed that ECD remarkably reduced tumor incidence and reversed damaged hepatocytes to normal. Our findings confirm that ECD exhibits preventive effect against chemically induced HCC in rats. ECD can be a potent chemopreventive drug for HCC. | 18,853,103 |
VZV retinal vasculitis without systemic infection: diagnosis and monitoring with quantitative Polymerase Chain Reaction. | To report a case of unilateral varicella zoster virus (VZV) retinal vasculitis aspect in an immunocompetent child without systemic infection. Clinically, no signs of retinal necrosis or frosted branch vasculitis were present. This is an observational case report. Quantitative PCR was performed on the aqueous humor (AH) using primers specific for herpes virus (cytomegalovirus, Epstein-Barr virus, herpes simplex virus 1-2, and VZV). The patient was treated with intravenous acyclovir, intravitreous ganciclovir, and oral valacyclovir. A positive quantitative PCR result was found for VZV DNA (1.72 x 10(6) viral copies/ml) in the AH. After 6 months, PCR of the AH was negative. Herpes viruses are involved in the pathogenesis of isolated retinal vasculitis. This case demonstrates that quantitative PCR is useful to detect viral DNA in AH and to monitor the viral activity and the therapeutic response. | 18,853,105 |
Comparison of peristaltic and Venturi pumps in bimanual microincisional cataract surgery. | Comparison of peristaltic and Venturi pumps in bimanual microincision phacoemulsification on the success of the cataract surgery by using sleeveless phaco tip. Bimanual microincision phacoemulsification was done in 49 eyes using a 1.4-mm temporal clear corneal incision. A peristaltic pump was used in 23 eyes, and a Venturi pump was used in 26 eyes for phacoemulsification. Intraoperative complications, anterior chamber stability, and mean duration of surgery were recorded. Duration of surgery was shorter in the Venturi pump group. Anterior chamber stability could not be established in 17 eyes in the peristaltic pump group; it was established in all eyes in the Venturi pump group. Corneal burns were observed in two eyes in the peristaltic pump group and no eyes in the Venturi pump group. Use of a Venturi pump system and a vented gas-forced infusion system can significantly shorten surgery time and reduce risk of thermal burns. | 18,853,107 |
Effect of Jinguo Weikang Capsule on proto-oncogene expression of gastric mucosa in rats with gastric precancerous lesions. | To study the effect of Jinguo Weikang Capsule [see text] on the gene expression of H-ras, epidermal growth factor receptor (EGFR), P53 and C-myc of the gastric mucosa in rats with gastric precancerous lesions, and to investigate the action mechanism of JWC on gastric precancerous lesions. A rat model with paratypical proliferation of the gastric epithelium mucosa was established by using 60Co irradiation. Rats were divided into the normal group, model group, high-, medium-, low-dose JWC treatment groups, and the vitacoenzyme control group, and were treated for 30 days. The expression of H-ras, EGFR, P53 and C-myc genes of the gastric mucosa was detected by using immunohistochemical methods. The expression and over-expression rates of H-ras, EGFR, P53 and C-myc gene in the high-and medium-dose JWC treatment groups were significantly lower (P<0.05) as compared with those of the model group. JWC can inhibit the expression of the H-ras, EGFR, P53 and C-myc genes expression of the gastric mucosa in rats, which may be one of mechanisms involved in suppressing or reversing gastric carcinogenesis. | 18,853,119 |
Observation on the effect of Salvia miltiorrhiza injection in treating traumatic hyphema and the opportune time for its application. | To observe the effect of Salvia miltiorrhiza Injection (SMI) in treating traumatic hyphema (TH) and the opportune time for its application. A retrospective study was conducted in 174 patients with TH (all with a single eye wounded), of whom 92 patients were treated with dicynone and 82 with SMI, and their status of recurrent or aggravated hemorrhage within 5 days after trauma were analyzed. Further, a prospective study was conducted in 76 TH patients (all with a single eye wounded), who were treated with dicynone though they had hyphema 5 days after treatment. After the dicynone medication was discontinued, 39 of them were treated with SI, but 37 were not. The status of hyphema absorption was observed. The retrospective study showed that the number of cases with recurrent or aggravated bleeding in the SMI-treatment group was much more than that in the dicynonetreated group (Z=-2.531, P=0.011). On the other hand, the prospective study showed that the status of hyphema absorption among the SMI-treated patients was significantly better than in those untreated with SMI (Z=-2.642, P=0.008). SMI shows an effect of promoting the absorption of TH, and SMI treatment is worthy of being spread in clinical practice. For safety considerations, it is suitable to apply the treatment 5 days after trauma. | 18,853,121 |
QTL mapping for grain filling rate and yield-related traits in RILs of the Chinese winter wheat population Heshangmai x Yu8679. | A set of 142 winter wheat recombinant inbred lines (RILs) deriving from the cross Heshangmai x Yu8679 were tried in four ecological environments during the seasons 2006 and 2007. Nine agronomic traits comprising mean grain filling rate (GFR(mean)), maximum grain filling rate (GFR(max)), grain filling duration (GFD), grain number per ear (GNE), grain weight per ear (GWE), flowering time (FT), maturation time (MT), plant height (PHT) and thousand grain weight (TGW) were evaluated in Beijing (2006 and 2007), Chengdu (2007) and Hefei (2007). A genetic map comprising 173 SSR markers and two EST markers was generated. Based on the genetic map and phenotypic data, quantitative trait loci (QTL) were mapped for these agronomic traits. A total of 99 putative QTLs were identified for the nine traits over four environments except GFD, PHT and MT, measured in two environments (BJ07 and CD07), respectively. Of the QTL detected, 17 for GFR(mean), 16 for GFR(max), 21 for TGW and 10 for GWE involving the chromosomes 1A, 1B, 2A, 2D, 3A, 3B, 3D, 4A, 4D, 5A, 5B, 6D and 7D were identified. Moreover, 13 genomic regions showing pleiotropic effects were detected in chromosomes 1A, 1B, 1D, 2A, 2B, 2D, 3A, 3B, 4B, 4D, 5B, 6D and 7D; these QTL revealing pleiotropic effects may be informative for a better understanding of the genetic basis of grain filling rate and other yield-related traits, and represent potential targets for multi-trait marker aided selection in wheat. | 18,853,131 |
Noninvasive ventilation for acute respiratory failure after lung resection: an observational study. | A single prospective randomized study found that, in selected patients with acute respiratory failure (ARF) following lung resection, noninvasive ventilation (NIV) decreases the need for endotracheal mechanical ventilation and improves clinical outcome. We prospectively evaluated early NIV use for ARF after lung resection during a 4-year period in the setting of a medical and a surgical ICU of a university hospital. We documented demographics, initial clinical characteristics and clinical outcomes. NIV failure was defined as the need for tracheal intubation. Among 690 patients at risk of severe complications following lung resection, 113 (16.3%) experienced ARF, which was initially supported by NIV in 89 (78.7%), including 59 with hypoxemic ARF (66.3%) and 30 with hypercapnic ARF (33.7%). The overall success rate of NIV was 85.3% (76/89). In-ICU mortality was 6.7% (6/89). The mortality rate following NIV failure was 46.1%. Predictive factors of NIV failure in univariate analysis were age (P = 0.046), previous cardiac comorbidities (P = 0.0075), postoperative pneumonia (P = 0.0016), admission in the surgical ICU (P = 0.034), no initial response to NIV (P < 0.0001) and occurrence of noninfectious complications (P = 0.037). Only two independent factors were significantly associated with NIV failure in multivariate analysis: cardiac comorbidities (odds ratio, 11.5; 95% confidence interval, 1.9-68.3; P = 0.007) and no initial response to NIV (odds ratio, 117.6; 95% confidence interval, 10.6-1305.8; P = 0.0001). This prospective survey confirms the feasibility and efficacy of NIV in ARF following lung resection. | 18,853,141 |
Reinfusion of unwashed salvaged blood after total knee arthroplasty in patients with rheumatoid arthritis. | Autotransfusion with unwashed salvaged blood (USB) is effective for avoiding allogeneic blood transfusion (ABT) in patients undergoing total knee arthroplasty (TKA). We performed a retrospective study to determine the percentage of patients receiving ABT and the volume of postoperative blood drainage after introduction of autotransfusion with USB for patients with rheumatoid arthritis (RA) undergoing TKA. In 100 patients without autotransfusion (group 1) and 100 patients receiving autotransfusion of USB (group 2), we compared the number of patients who required ABT, as well as the postoperative drainage volume, ABT volume, and autotransfusion volume. In group 1, 83% of the patients received ABT, while only 47% received ABT in group 2, and there was a significant decrease (p < 0.001). However, the postoperative drainage volume was significantly increased in group 2 (p < 0.001). | 18,853,156 |
Cellular glutathione peroxidase in human brain: cellular distribution, and its potential role in the degradation of Lewy bodies in Parkinson's disease and dementia with Lewy bodies. | Glutathione peroxidase (GPx-1) is regarded as one of the mammalian cell's main antioxidant enzymes inactivating hydrogen peroxide and protecting against oxidative stress. Using control, Parkinson's disease (PD), and dementia with Lewy bodies tissue (DLB) we have shown that GPx-1 is a 21-kD protein under reducing conditions in all tissues examined but is not in high abundance in human brain. Using immunohistochemistry we have mapped the cellular distribution of GPx-1 and have shown it to be in highest levels in microglia and with lower levels in neurons. Only a trace amount was detectable in astrocytes using immunofluorescence and GPx-1 was not detectable in oligodendrocytes. GPx-1 positive microglia were hypertrophied and more abundant in PD and DLB tissues and were seen to be making multiple contacts with neurons. In some cases neurons containing Lewy bodies were surrounded by microglia. Unstructured Lewy bodies were enveloped with a layer of GPx-1 that was partially colocalized with alpha-synuclein whereas concentric Lewy bodies had discrete deposits of GPx-1 around the periphery which appeared to be involved in the degradation of the Lewy bodies. These results suggest that abnormal alpha-synuclein as found in Lewy bodies produce hydrogen peroxide and these neurons are capable of directing antioxidant enzymes to regions of oxidative stress. These results also suggest that GPx-1 positive microglia are involved in neuroprotection in PD and DLB and that GPx-1 is an important antioxidant enzyme in neuronal defences. | 18,853,169 |
Typing keystroke duration changed after submaximal isometric finger exercises. | A repeated-measures laboratory experiment tested whether keystroke duration during touch-typing changes after a finger performs submaximal isometric flexion exercises. Fourteen right-handed touch-typists used right ring finger to perform three 15-min exercise conditions, two isometric exercises and a no-force condition, each on a separate day. Before and after each exercise condition, typing keystroke duration and isometric force elicited by electrical stimulation were measured for right ring finger. Keystroke duration of right ring finger decreased by 5% (6 ms, P < 0.05) immediately after the exercises but not after the no-force condition. Peak isometric finger force elicited by electrical stimulation decreased by 17-26% (P < 0.05) for the flexor digitorum superficialis and decreased by 4-8% for the extensor digitorum communis after the isometric exercises. After the finger was exposed to isometric exercises, changes in typing keystroke duration coincided with changes in the physiological state of the finger flexor and extensor muscles. | 18,853,179 |
Field evaluation of G10, a celery (Apium graveolens)-based topical repellent, against mosquitoes (Diptera: Culicidae) in Chiang Mai province, northern Thailand. | The potential of G10, a celery (Apium graveolens)-based topical product, as a repellent against natural mosquito populations was evaluated in comparison to commercial (Insect Block 28) and standard (25% DEET) repellents in Chiang Mai province, northern Thailand. These repellent products afforded encouragingly excellent personal protection against a broad range of mosquito species belonging to various genera, including Aedes, Anopheles, Armigeres, Culex, and Mansonia. No mosquito bite was observed on the volunteers treated with G10 and Insect Block 28 throughout the field study, whereas two species, i.e., six A. barbirostris and two A. subalbatus, came to bite or land on 25% DEET-treated volunteers. Thus, it can be concluded that while G10 and Insect Block 28 exhibited similarly powerful repellent activities with complete (100%) protection, 25% DEET was effective in minimizing bites with 99.68% protection. G10 formula was also studied for physical properties and biological stability after being kept under two conditions; a heating and cooling cycle, and varying temperature and time storage. Most samples of stored G10 not only demonstrated a similarity in appearance and physical properties, but also provided comparable repellency to that of the fresh preparation. These findings encourage commercial development of G10 formula as an alternative to conventional synthetic repellents. | 18,853,188 |
Kinetic study of mannitol production using cashew apple juice as substrate. | The use of agriculture excess as substrate in industrial fermentations became an interesting alternative to reduce production costs and to reduce negative environmental impact caused by the disposal of these products. In this work, a kinetic study of mannitol production using cashew apple juice as substrate was studied. The carbohydrates of cashew apple juice are glucose and fructose. Sucrose addition favored the yield of mannitol (85%) at the expense of lower productivity. The best results were obtained applying only cashew apple juice as substrate, containing 50 g L(-1) of total reducing sugar (28 g L(-1) of fructose), yielding 18 g L(-1) of mannitol with 67% of fructose conversion into mannitol and productivity of 1.8 g L(-1) h(-1). | 18,853,193 |
Studies on the activity and stability of immobilized horseradish peroxidase on poly(ethylene terephthalate) grafted acrylamide fiber. | Having been activated with glutaraldehyde, modified poly(ethylene terephthalate) grafted acrylamide fiber was used for the immobilization of horseradish peroxidase (HRP). Both the free HRP and the immobilized HRP were characterized by determining the activity profile as a function of pH, temperature, thermal stability, effect of organic solvent and storage stability. The optimum pH values of the enzyme activity were found as 8 and 7 for the free HRP and the immobilized HRP respectively. The temperature profile of the free HRP and the immobilized HRP revealed a similar behaviour, although the immobilized HRP exhibited higher relative activity in the range from 50 to 60 degrees C. The immobilized HRP showed higher storage stability than the free HRP. | 18,853,194 |
Pilot-scale process development and scale up for antifungal production. | A pilot-scale fermentation was developed for an antifungal compound produced by a filamentous fungus. Replacement of galactose with lactose (20-fold cost savings) and a threefold phosphate reduction (15 to 5 g/L) improved productivity 2.5-fold. Addition of supplements--glycine, cobalt chloride, and trace elements--resulted in a further twofold productivity increase, greater process robustness, and less foaming which reduced antifoam addition tenfold (30 to <3 mL/L). Mid-cycle lactose limitations were addressed by raising initial lactose levels (40 to 120 g/L) resulting in another twofold productivity increase. Overall, peak titers increased tenfold from 45 +/- 9 to 448 +/- 39 mg/L, and productivities improved from 3 to 25 mg/L day. Despite its high productivity, process scale up was challenged by high broth viscosity (5,000-6,000 cP at 16.8 s(-1)). Gassed power requirements at the 600 L scale (4.7 kW/1,000 L) exceeded available power at the 15,000 L scale (3.0 kW/1,000 L), and broth transfer to the downstream isolation facility was hindered. Mid-cycle broth dilution with up to five 10 vol% additions of 12 wt% lactose solution or whole medium-reduced viscosity three- to fivefold (1,000-1,500 cP at 16.8 s(-1)), gassed power within scale-up limits (2.5 kW/1,000 L), and peak titer by up to 45%. The process was scaled up to the 15,000 L working volume based on constant aeration rate (vvm) and peak impeller tip speed, raising superficial velocities at similar shear. This strategy maximized mass transfer rates at target gassed power per unit volume levels, and along with controlled broth viscosity, precluded multiple dilution additions. A final titer of 333 mg/L with one dilution addition was achieved, somewhat lower than expected, likely owing to inhibition from some unmeasured volatile compound (not believed to be carbon dioxide) during an extended period of high back-pressure in the early production phase. | 18,853,195 |
Characterization of sulfate-reducing bacteria dominated surface communities during start-up of a down-flow fluidized bed reactor. | An anaerobic down-flow fluidized bed reactor was inoculated with granular sludge and started-up with sulfate containing synthetic wastewater to promote the formation of a biofilm enriched in sulfate-reducing bacteria (SRB), to produce biogenic sulfide. The start-up was done in two stages operating the reactor in batch for 45 days followed by 85 days of continuous operation. Low-density polyethylene was used as support. The biofilm formation was followed up by biochemical and electron microscopy analyses and the composition of the community was examined by 16S rDNA sequence analysis. Maximum immobilized volatile solids (1.2 g IVS/L(support)) were obtained after 14 days in batch regime. During the 85 days of continuous operation, the reactor removed up to 80% of chemical oxygen demand (COD), up to 28% of the supplied sulfate and acetate was present in the effluent. Sulfate-reducing activity determined in the biofilm with ethanol or lactate as substrate was 11.7 and 15.3 g COD/g IVS per day, respectively. These results suggested the immobilization of sulfate reducers that incompletely oxidize the substrate to acetate; the phylogenetic analysis of the cloned 16S rDNA gene sequences showed high identity to the genus Desulfovibrio that oxidizes the substrates incompletely. In contrast, in the granular sludge used as inoculum a considerable number of clones showed homology to Methanobacterium and just few clones were close to SRB. The starting-up approach allowed the enrichment of SRB within the diverse community developed over the polyethylene support. | 18,853,208 |
Analysis of N-glycans in embryonated chicken egg chorioallantoic and amniotic cells responsible for binding and adaptation of human and avian influenza viruses. | The initial step essential in influenza virus infection is specific binding of viral hemagglutinin to host cell-surface glycan receptors. Influenza A virus specificity for the host is mediated by viral envelope hemagglutinin, that binds to receptors containing glycans with terminal sialic acids. Human viruses preferentially bind to alpha2-->6 linked sialic acids on receptors of host cells, whereas avian viruses are specific for the alpha2-->3 linkage on the target cells. Human influenza virus isolates more efficiently infect amniotic membrane (AM) cells than chorioallantoic membrane (CAM) cells. N-glycans were isolated from AM and CAM cells of 10-day-old chicken embryonated eggs and their structures were analyzed by multi-dimensional HPLC mapping and MALDI-TOF-MS techniques. Terminal N-acetylneuraminic acid contents in the two cell types were similar. However, molar percents of alpha2-->3 linkage preferentially bound by avian influenza virus were 27.2 in CAM cells and 15.4 in AM cells, whereas those of alpha2-->6 linkage favored by human influenza virus were 8.3 (CAM) and 14.2 (AM). Molar percents of sulfated glycans, recognized by human influenza virus, in CAM and AM cells were 3.8 and 12.7, respectively. These results have revealed structures and molar percents of N-glycans in CAM and AM cells important in determining human and avian influenza virus infection and viral adaptation. | 18,853,253 |
Inhibition of apoptosis by Heliothis virescens ascovirus (HvAV-3e): characterization of orf28 with structural similarity to inhibitor of apoptosis proteins. | Ascoviruses (AVs) induce a unique pathology in their insect host cells causing cleavage of the cells into virion-containing vesicles. The mechanism by which AVs induce vesicle formation is poorly understood. It is postulated that the virus initially induces apoptosis leading to cell fragmentation. The apoptotic bodies are however, rescued by the virus to form the vesicles. Here we show that Heliothis virescens AV (HvAV-3e) is able to inhibit chemically induced apoptosis from around 16 h after infection. Analysis of the genome of the virus indicated the presence of a putative inhibitor of apoptosis (orf28) gene that encodes a protein with an imperfect baculovirus inhibitor of apoptosis repeat (BIR) and a RING domain. Transiently expressed orf28 did not inhibit chemically induced apoptosis suggesting that the protein may not serve as an inhibitor of apoptosis. Nevertheless, RNA interference studies revealed that the gene is probably essential for virus pathology and replication. | 18,853,258 |
Estimation of chlorophyll-a concentration using field spectral data: a case study in inland Case-II waters, North China. | In the remote sensing of chlorophyll-a (Chla) in inland Case-II waters, the assumption that the optical parameter of Chla specific absorption coefficient a*ph remains constant usually restrains application of many models. In this paper, we presented a newly developed model [Rrs(-1)(lambda1) - Rrs(-1)(lambda2)] x Rrs(lambda3) x a*ph(-1)(lambda1) which was improved on a previous three-band model to isolate interferences from a*ph. In terms of the importance of water optical properties in the model development, spectral and absorption characteristics were analyzed for Shitoukoumen Reservoir and Songhua Lake in Northeast China, as typical examples of inland Case-II waters. Both waters showed overwhelming absorption sum of tripton and chromophoric dissolved organic matter (CDOM) owing to their relatively low Chla contents (1.53 to 19.35 microgl(-1)). According to the optical characteristics of waters studied, optimal positions for lambda (1), lambda (2) and lambda (3) were spectrally tuned to be at 664, 684 and 705 nm, respectively. The model allowed accurate Chla estimation with a determination coefficient (R (2)) close to 0.98 and a root mean square error (RMSE) of 0.87 microgl(-1). Comparison of different models further showed the stability of the improved model, implying its potential use in water color remote sensing. Although the findings underline the rationale behind the improved model, an extensive database containing data in different water conditions and water types is required to generalize its application. | 18,853,267 |
A novel transgenic mice model for venous malformation. | Vascular anomalies are most commonly seen in the head and neck region, and there is no animal model available of this disease until now. The purpose of this study was to construct a conditional murine polyomavirus middle T antigen gene (PyMT) transgenic mice model, in order to provide a basis for the treatment of vascular anomalies in vivo, as well as the study of PyMT's molecular function. A new conditional transgenic vector based on Tet-On system was constructed successfully. After the experiment in vitro, pronuclear microinjection method was used to introduce the purified transgene into the chromosomes of fertilized mice eggs, and five transgenic positive mice were obtained. The transgenic positive animals went down to future generation by hybridization. After induction of PyMT's expression in the F1 generation, three transgenic mice developed venous malformation which was confirmed histopathologically. The mice model generated could be used as a tool to study venous malformation, as well as the function of PyMT gene. | 18,853,270 |
Pupillometric assessment of autonomic nervous system in children with functional enuresis. | Functional enuresis is defined as repeated voiding of urine into bed or clothes in children after 5 years of age following the exclusion of major somatic diseases. Autonomic nervous system dysregulation has been proposed as a pathophysiologic mechanism in the etiopathogenesis. The objective of this study was to evaluate autonomic nervous system functions with pupil diameter measurement in enuretic children. The study group consisted of 17 children with functional enuresis (ten boys, seven girls), and the control group consisted of 34 healthy children (20 boys, 14 girls). Pupil diameter measurements were performed under photopic and mesopic lighting conditions by using a pupillometer. Mean photopic pupil diameter was found to be larger in the enuretic children than in the healthy controls (4.47 +/- 0.52 mm vs. 4.03 +/- 0.75 mm; P = 0.03). Autonomic nervous system imbalance of the ocular system is considered to be part of the autonomic nervous system dysregulation in functional enuretic children. | 18,853,271 |
Cloning of the Rhizomucor miehei 3-hydroxy-3-methylglutaryl-coenzyme A reductase gene and its heterologous expression in Mucor circinelloides. | In this study, the gene hmgR encoding the 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase) was cloned and characterized in the zygomycete fungus Rhizomucor miehei. The hmgR gene comprises a total of 3,585 bp including the coding sequence of a 1,058 amino acids length putative protein and five introns (137, 83, 59, 60 and 69 bp in length) dispersed in the whole coding region. Southern hybridization analysis revealed that the gene is present only in one copy in the R. miehei genome. The isolated Rhizomucor gene was expressed in the related fungus, Mucor circinelloides. Transformants harbouring the Rhizomucor hmgR gene in an autoreplicative plasmid proved to be more tolerant to statins (e.g. lovastatin, simvastatin, and fluvastatin), the competitive inhibitors of the HMG-CoA reductase, than the original M. circinelloides strain. At the same time, heterologous expression of the Rhizomucor hmgR did not affect the carotenoid production of M. circinelloides. | 18,853,273 |
A joint coordinate system proposal for the study of the trapeziometacarpal joint kinematics. | The International Society of Biomechanics (ISB) has recommended a standardisation for the motion reporting of almost all human joints. This study proposes an adaptation for the trapeziometacarpal joint. The definition of the segment coordinate system of both trapezium and first metacarpal is based on functional anatomy. The definition of the joint coordinate system (JCS) is guided by the two degrees of freedom of the joint, i.e. flexion-extension about a trapezium axis and abduction-adduction about a first metacarpal axis. The rotations obtained using three methods are compared on the same data: the fixed axes sequence proposed by Cooney et al., the mobile axes sequence proposed by the ISB and our alternative mobile axes sequence. The rotation amplitudes show a difference of 9 degrees in flexion-extension, 2 degrees in abduction-adduction and 13 degrees in internal-external rotation. This study emphasizes the importance of adapting the JCS to the functional anatomy of each particular joint. | 18,853,290 |
Prediction of atmospheric degradation data for POPs by gene expression programming. | Quantitative structure-activity relationship models for the prediction of the mean and the maximum atmospheric degradation half-life values of persistent organic pollutants were developed based on the linear heuristic method (HM) and non-linear gene expression programming (GEP). Molecular descriptors, calculated from the structures alone, were used to represent the characteristics of the compounds. HM was used both to pre-select the whole descriptor sets and to build the linear model. GEP yielded satisfactory prediction results: the square of the correlation coefficient r(2) was 0.80 and 0.81 for the mean and maximum half-life values of the test set, and the root mean square errors were 0.448 and 0.426, respectively. The results of this work indicate that the GEP is a very promising tool for non-linear approximations. | 18,853,297 |
Postoperative lomefloxacin 0.3% prophylaxis in strabismus surgery. | To evaluate the efficacy of topical lomefloxacin 0.3% versus chloramphenicol 0.2% with polymyxin B 2500 U/ml in the treatment of patients after strabismus surgery. Seventy-nine consecutive patients who underwent strabismus surgery from April through October 2006 were randomized to receive topical lomefloxacin 0.3% (n = 45, 58 eyes) or chloramphenicol 0.2% with polymyxin B 2500 U/ml (n = 34, 40 eyes) postoperatively, in addition to topical dexamethasone 0.1% and diclophenac 0.1%. The groups were compared for clinical signs of local cellulitis and findings on conjunctival cultures. From postoperative day 1 to day 28, rates of chemosis decreased from 96% to 9.5% in the lomefloxacin group and from 94% to zero in the chloramphenicol group; rates of hyperemia decreased from 100% to zero in both groups. Accordingly, rates of a cumulative clinical sign score (CCSS) decreased from 60% to zero in the lomefloxacin group and 50% to zero in the chloramphenicol group. Rates of positive bacterial cultures dropped from 59.6% preoperatively to 48.3% on day 14 in the lomefloxacin group and from 63% to 47% in the chloramphenicol group. Topical lomefloxacin is a potent alternative to topical chloramphenicol eye drops after strabismus surgery for the control of pain, infection and discharge, chemosis, hyperemia, and conjunctival hemorrhage. | 18,853,315 |
Relationship between body mass index and brain volume in healthy adults. | There is a growing evidence that elevated body mass index (BMI) is associated with adverse neurocognitive outcome, though no study has examined whether morphometric differences are found in persons across the adult life span. We compared 201 healthy individuals in normal weight, overweight, and obese groups (aged 17-79). After correcting for demographic differences, obese individuals showed smaller whole brain and total gray matter volume than normal weight and overweight individuals. These findings support an independent relationship between BMI and brain structure and demonstrate that these differences are not limited to older adults. | 18,853,335 |
Targeting NF-kappaB: a promising molecular therapy in inflammatory arthritis. | The nuclear factor-kappa B family of transcription factors is intimately involved in the regulation of the inflammatory responses that play a fundamental role in the damage of articular tissues. Thus, many studies have examined the important contributions of components of the NF-kappaB signaling pathways to the pathogenesis of various rheumatic diseases and their pharmacologic modulation. Currently available therapeutic agents including nonsteroidal anti-inflammatory drugs, corticosteroids, nutraceuticals, and disease-modifying antirheumatic drugs, as well as novel specific small-molecule inhibitors have been employed. In addition, promising nucleic acid-based strategies have shown encouraging results. However, further research will be needed before NF-kappaB-aimed strategies become an effective therapy for inflammatory arthritis. | 18,853,343 |
Mass spectrometry for the characterization of unsulfated chondroitin oligosaccharides from 2-mers to 16-mers. Comparison with hyaluronic acid oligomers. | This study reports for the first time the complete liquid chromatography/electrospray ionization mass spectrometry (LC/ESI-MS) and tandem mass spectrometry (MS/MS) analyses performed in negative ion mode of saturated unsulfated chondroitin oligosaccharides up to 16-mers and comparison with hyaluronic acid (HA) oligomers differing only in the nature of the hexosamine residue. MS/MS of the chondroitin disaccharide on the singly charged precursor at m/z 396.1 afforded a glycosidic cleavage C1 product ion at m/z 192.9. In the tetrasaccharide, C2 (m/z 396.0) and C3 (m/z 572.0) product anions were generated by glycosidic cleavage. A C5 [M-2H]2- product ion at m/z 475.1 was generated by the glycosidic cleavage of the hexasaccharide, and a C7 ion (m/z 664.6, charge state of -2) was produced from the octasaccharide. The same fragmentation pattern of deprotonated oligomers was observed for the largest oligosaccharides, from 10- to 16-mers. There has been no previous report of MS/MS spectra for unsulfated chondroitin oligomers of these sizes. Unsulfated saturated chondroitin oligosaccharides with x-mer units and larger than a tetrasaccharide dissociate to almost exclusively form CX-1-type ions. Saturated HA oligomers also afforded the same fragmentation pattern as deprotonated oligomers by ESI-MS and MS/MS analyses. Thus, under the experimental conditions used in the current study, we were unable to distinguish between unsulfated chondroitin and HA. | 18,853,395 |
Mandibular osteotomies for access to select parapharyngeal space neoplasms. | Tumors involving the parapharyngeal space present a challenge of surgical access. We reviewed all parapharyngeal space tumors resected at the University of California, San Francisco, between 2003 and 2006 and identified 14 patients who had a mandibular osteotomy to enhance surgical access to the parapharyngeal space. The surgical approach for the 14 patients who had a mandibulotomy was accomplished via either 1 or 2 mandibular osteotomies. A single paramedian osteotomy between the canine and the first premolar was used in 4 cases, whereas a combination of a horizontal osteotomy above the lingula and a paramedian osteotomy between the canine and first premolar was employed in 8 cases. A lingual dental splint and rigid fixation were used to achieve mandibular stabilization and fixation. We found that the single and double mandibular osteotomies provided excellent surgical access allowing for total tumor removal with few sequelae. | 18,853,448 |
Angiosarcoma developing after curative induction chemotherapy and radiotherapy for locally advanced squamous cell carcinoma of the larynx. | Angiosarcoma arising after radiation is described in breast cancer but occurs elsewhere. Here, we present an angiosarcoma of the neck occurring after curative chemoradiation. This is a case of angiosarcoma developing 5 years after curative therapy for T3N0 squamous cell carcinoma of the supraglottic larynx. Therapy consisted of 3 cycles of induction cisplatin/5-fluorouracil chemotherapy followed by radiotherapy. The patient did well until developing a rapidly progressive lesion of the left neck. Examination showed a 7-cm mass and biopsy revealed angiosarcoma. CT scans assessed the local extent of the tumor and ruled out metastatic disease prior to initiating therapy. Therapy consisted of 4 cycles of paclitaxel chemotherapy. At completion, examination revealed mild induration of the neck with near-complete resolution of the mass. Imaging confirmed this excellent response. This rare therapy-related second malignancy developed after curative larynx-preserving treatment. Paclitaxel was an effective therapy in this setting. | 18,853,452 |
Incidence and risk factors of bisphosphonate-associated osteonecrosis of the jaws. | Intravenous bisphosphonate therapy has been used for treatment of benign and malignant bone diseases and has been linked to osteonecrosis of the jaws. Records of 638 patients treated with intravenous bisphosphonates were reviewed. Drug used, number of infusions, dosing interval, dosage, duration, and occasion of osteonecrosis, diagnosed by history and physical examination, were analyzed. The overall incidence of osteonecrosis was 0.94% (6/638). No significant relationship was observed between the incidence of osteonecrosis and demographic parameters, primary tumor, cumulative drug dose, or dosing interval. However, patients who developed osteonecrosis had a significantly greater mean number of infusions (p = .016) and significantly greater mean hours of infusion time (p = .0036). The findings suggest positive correlation between the development of osteonecrosis and drug exposure as measured by number of infusions and total infusion hours. However, the relatively low incidence of osteonecrosis precluded definition of a direct dose-response relationship. | 18,853,454 |
Structural characterization of in vitro rat liver microsomal metabolites of antihistamine desloratadine using LTQ-Orbitrap hybrid mass spectrometer in combination with online hydrogen/deuterium exchange HR-LC/MS. | In vitro drug metabolism study is an integral part of drug discovery process. In this report, we have described the application of LTQ-Orbitrap hybrid mass spectrometer in conjunction with online hydrogen (H)/deuterium (D) exchange high resolution (HR)-LC/MS for structural characterization of in vitro rat liver microsomal metabolites of antihistamine desloratadine. Five metabolites M1--M5 have been identified, including three hydroxylated metabolites M1--M3, one N-oxide M4 and one uncommon aromatized N-oxide M5. Accurate mass data have been obtained in both full scan and MSn mode support assignments of metabolite structures with reported mass errors less than 3 ppm. Online H/D exchange HR-LC/MS experiments provide additional evidence in differentiating hydroxylated metabolites from N-oxides. This study demonstrates the effectiveness of this approach in structural characterization of drug metabolites. | 18,853,472 |
ESI+ MS/MS confirmation of canine ivermectin toxicity. | Ivermectin is a semisynthetic macrocyclic lactone anthelmintic of the avermectin family derived from Streptomyces fermentation products. Avermectins are used as antiparasitic agents in domestic animals; although considered relatively safe, one must consider animal species, breed, weight, and age in dosage determinations.In January 2006, two canines were presented to the UK Livestock Disease Diagnostic Center after dying from suspected ivermectin overdoses [30-50 mg/kg body weight]. To confirm this clinical diagnosis we developed a rapid, sensitive semiquantitative ElectroSpray Ionization-Mass Spectrometry (ESI/MS) method for ivermectin in canine tissue samples. Pharmaceutical ivermectin contains two ivermectins differing by a single methyl group, and each compound forms interpretation-confounding adducts with tissue Na(+) and K(+) ions. We now report that ivermectin administration was clearly confirmed by comparison with standard and dosage forms of ivermectin, and simple proportionalities based on mass spectral intensity of respective molecular ions allowed semiquantitative estimates of injection site tissue concentrations of 20 and 40 microg/g tissue (wet weight) in these animals, consistent with the history of ivermectin administration and the clinical signs observed.There is a distinct need for both rapid detection and confirmation of toxic exposures in veterinary diagnostics, whether for interpretation of clinical cases antemortem or for forensic reasons postmortem. It is vital that interpreters of analytical results have appropriate guidance in the scientific literature and elsewhere so as to enable clear-cut answers. The method presented here is suitable for routine diagnostic work in that it allows rapid extraction of ivermectin from tissue samples, avoids the need for high-performance liquid chromatography and allows ready interpretation of the multiple ivermectin species seen by ESI(+) MS/MS in samples originating from veterinary dosage forms. | 18,853,478 |
Pulmonary Mycobacterium tuberculosis (Beijing strain) infection in a stray dog. | Mycobacterium tuberculosis infection in dogs is rarely reported and has not previously been documented in South Africa. A case of a stray Maltese crossbreed dog with extensive multifocal pulmonary tuberculosis due to M. tuberculosis is described. Pulmonary granulomas in this case were poorly encapsulated and contained large numbers of acid-fast bacteria, highlighting the potential for infected companion animals to excrete the pathogen. Treatment of canine tuberculosis is generally not advised, and for this reason, euthanasia of diseased animals must be advocated in most instances. Physicians and veterinarians must be aware that companion animals with active disease caused by M. tuberculosis could act as a potential source of infection. | 18,853,521 |
Physician workforce: the special case of health centers and the National Health Service Corps. | Federally funded health centers and the National Health Service Corps (NHSC) depend on family physicians (FPs) and general practitioners (GPs) to meet the needs of millions of medically underserved people. Policy makers and workforce planners should consider how changes in the production of FPs would affect these programs. | 18,853,530 |
Observing object motion induces increased generalization and sensitivity. | Learning to recognize a new object requires binding together dissimilar images of that object into a common representation. Temporal proximity is a useful computational cue for learning invariant representations. We report experiments that demonstrate two distinct psychophysical effects of temporal association via observed object motion on object perception. First, we use an implicit priming criterion to demonstrate that observation of a dynamic object induces generalization over close temporal neighbors. Second, in contrast to predictions from previous work, we find that shape discrimination between images actually improves following the same training procedure. We suggest that these apparently conflicting sets of results, one demonstrating blurring and the other demonstrating sharpening of the perceived distinction between temporally proximate frames, are consistent with a highly redundant code for object appearance. | 18,853,553 |
The monocular-boundary-contour mechanism in binocular surface representation and suppression. | Boundary contours are important for representing binocular surfaces, including those in binocular rivalry. Ooi and He (2006, Perception 35 581-603) showed that a half-image with a boundary contour defined by abutting gratings predominates in binocular rivalry. We investigated the monocular-boundary-contour mechanism using Kanizsa square-like rivalry displays. In experiment 1, the left half-image had a vertical illusory contour on the right edge while the right half-image had a vertical illusory contour on the left edge. The Kanizsa elements (discs and pacmen) were filled with a 135 degree grating and placed on a 45 degree-grating background. When fused, observers experienced a strong predominance for perceiving an illusory rectangle in front of four discs. But this percept was replaced by robust rivalry alternations when the stimulus was manipulated by (i) switching the half-images between eyes, (ii)relocating the pacmen in each half-image to form horizontal illusory contours, or (iii) placing the pacmen diagonally (thus eliminating each monocular illusory contour). Such robust rivalry alternations were similar to those experienced when a 135 degree-grating disc was in rivalry with a 135 degree-grating pacman alone on the 45 degree-grating background (experiment 2). Experiment 3 showed that the relatively stable illusory-rectangle percept in experiment 1 is affected by the alignment of the images in the two eyes, in a manner consistent with adherence to the occlusion constraint in binocular surface formation. | 18,853,556 |
Highlighting human form and motion information enhances the conspicuity of pedestrians at night. | Exploring how biological motion can make pedestrians more conspicuous to drivers at night, one-hundred-and-twenty participants were driven along an open-road route at night and pressed a button whenever they recognized that a pedestrian was present. A test pedestrian wearing black clothing alone or with 302 cm2 of retroreflective markings in one of four configurations either stood still or walked in place on an unilluminated sidewalk. Participants' response distances were maximal for the full biological-motion configuration and remained surprisingly long when convenient subsets of reflective markers were positioned on the pedestrian's ankles and wrists. When the pedestrian wore a reflective vest, the responses were no better than when he wore no reflective markings. The biological-motion advantage actually results from interacting form-perception and motion-perception mechanisms. These results confirm that basic perceptual phenomena-observers' sensitivity to human form and motion can be harnessed to reduce an important problem of traffic safety. | 18,853,562 |
Non-invasive cardiac output measurement using a fast mixing box to measure carbon dioxide elimination. | This study investigated the accuracy of a new technique for measuring cardiac output using the derivative Fick principle based on the ratio of change in the partial pressures of end-tidal and mixed expired carbon dioxide produced by short periods of partial rebreathing. A prospective clinical study involving 24 patients following cardiopulmonary bypass for coronary artery bypass grafting or valvular surgery was undertaken in the intensive care unit of a university-affiliated hospital. Haemodynamic measurements were performed after admission to the intensive care unit. Cardiac output was measured simultaneously by bolus pulmonary artery thermodilution and by a non-invasive carbon dioxide partial rebreathing technique. Cardiac output measurement using the new technique demonstrated a significant but consistent underestimate, with a bias of -0.60 +/- 0.87 l/min. This new adaptation of the partial rebreathing technique is reliable in measuring cardiac output in postoperative patients. Reasons for the consistent discrepancy between thermodilution and partial rebreathing techniques are discussed. | 18,853,584 |
An audit of perioperative cardiac arrests in a Southeast Asian university teaching hospital over 15 years. | An audit of the incidence, causes and outcome of perioperative cardiac arrest was conducted in a university hospital in Pakistan. All perioperative cardiac arrests from induction of anaesthesia to post anaesthesia care unit discharge or intensive care unit admission during noncardiac surgery, from January 1992 to December 2006 were included. Patients' demographic information, physical status and type of surgery and anaesthesia were noted. Outcome variables were noted as immediate survival and survival to discharge. Anaesthesia-related cardiac arrests were identified and their causes analysed. Forty-two cardiac arrests occurred among 140,384 patients. Overall frequency was 2.99 per 10,000 (95% confidence interval: 2.90 to 3.08). Twenty-four (3.77/10,000) were females. Thirty-four (13.59/10,000) patients were ASA physical status III to V, 10 (4.95/10,000) were children and 14 (4.28/10,000) above 60 years. Sixteen patients (6.48/10,000) were undergoing emergency surgery. Anaesthesia was deemed primarily responsible in nine cases (0.64/10,000). The causes of anaesthesia-related arrests were medication related (4), airway related (3), massive air embolism (1) and under-replacement of fluids (1). The event was considered to be avoidable in 26 cases. Seventeen patients died during the arrest, 15 survived more than one hour and 10 were discharged home. The number of perioperative cardiac arrests and their mortality was higher in patients with poor physical status and in emergency surgery. The number was also higher in infants, patients above 60 and females. The majority of the cases were considered avoidable, indicating the importance of prevention strategies. | 18,853,592 |
Anemia, interleukin-10, tumor necrosis factor alpha, and erythropoietin levels in children with acute, complicated and uncomplicated malignant malaria in Jazan, Saudi Arabia. | To gain insight into potential relationships between tumor necrosis factor alpha (TNF-alpha), interleukin 10 (IL-10), erythropoietin (EPO), and anemia in acute malaria, 90 children 3 to 11 years with acute malaria were studied. According to parasitemia and hemoglobin levels, they were divided into 3 groups: G1 (mild): asexual low-density Plasmodium falciparum parasitemia <8000 parasites/ul and hemoglobin levels >8g/dl. G2 (high-density uncomplicated): asexual high-density parasitemia (>8000 parasites/ul, with hemoglobin levels >8 g/dl. G3 (anemia): with severe malaria symptoms and parasitemia with anemia (hemoglobin levels <8 g/dl). Hospital controls included 10 children with matching age group who required inpatient management but had no malaria parasitemia. Good marrow response was in G1 & G2 showed by elevation of serum EPO and soluble transferring receptors (sTfR) and increased red cell distribution width (RDW). In G3, bone marrow suppression was in spite of increased EPO level in response to anemia. TNF-alpha level was significantly higher G2 and G3 (P.05). IL-10 levels in G1 were significantly higher than in hospital control group (P<0.05). The highest level of IL-10 was in G2. The mean IL-10 to TNF-alpha ratio in G2 (4.64) was significantly higher (P<.005) than in G3 (mean ratio, 1.77). | 18,853,611 |
Detection of molecular markers of toxoplasmosis among Egyptian patients with miscarriage using avidity IgG-ELISA and Western blotting. | A total of 54 miscarriage patients were divided into 3 groups. GI: 10 toxoplasmosis patients with +ve IgM-ELISA; GII: 24 toxoplasmosis patients with +ve IgG-ELISA, and GIII: 20 non-toxoplasmosis cross-matched females as a control. All groups were subjected to IgG-avidity ELISA & IgG-avidity immunoblotting. Avidity Indices (AI) by ELISA ranged from 22.6% to 73.3% in GI and from 9.6%-75.6% in GII. AI were high (>40%) in 3 (30%) patients in G I and in 8 (33.3%) patients in G II. Sera of GI recognized the 20, 28, 32, 60, 93 & 100 Kda bands with 55% reduction in the 38 and 60 Kda bands after treatment with 6 M urea solutions. Sera of GII recognized the 20, 28, 32, 38, 45, 95-97 & 106 Kda bands. There was 12.5%, 16.6% & 16.7% reduction in the 20, 32, & 106 Kda bands, respectively, after urea. The 38 & 60 Kda bands were identified as good diagnostic markers for the recent toxoplasmosis infection (GI). The 20, 32 & 106 Kda bands were good markers of high avidity antibodies during the chronic toxoplasmosis (GII). | 18,853,626 |
Cystic hydatidosis: a zoonotic silent health problem. | Examination of five hundred pet dogs revealed Echinococcus granulosus in nine dogs, Dipylidium caninum in twenty dogs, and Toxocara canis in thirty dogs. The risky role played by pet dogs in the transmission and spreading of zoonotic cystic hydatidosis was discussed. | 18,853,634 |
Multilocus genetic analysis of Cryptosporidium isolates from Saudi Arabia. | A total of 35 Cryptosporidium positive samples were collected from children in Jeddah city. The samples were microscopically examined with Ziehl Neelsen (ZN) and Auramin phenol (AP) staining methods. Cryptosporidium antigen was detected in the faecal samples by using the Cryptosporidium ELISA kit. Cryptosporidium sp. were identified by targeting an 840 bp of the hyper-variable region of the 18S rRNA gene and about 550 of the first domain (N terminal) of the COWP gene. The sub-genotypic identification of C. parvum and C. hominis isolates was done by targeting the sporozoite antigen gp15/45/60 gene. Four sp. were identified; C. hominis 13/35 (37%), C. parvum 15/35 (42.9%), C. meleagridis 1/35(2.9 %), & C. muris 1/35 (2.9 %). One isolate was a mixed infection of C. parvum & C. hominis. | 18,853,635 |
Domestic violence, contraceptive use, and unwanted pregnancy in rural India. | This study examines the relationship between male-to-female physical domestic violence and unwanted pregnancy among women in three economically and culturally diverse areas of India. A central methodological focus of the study is the examination of retrospective and prospective measures of pregnancy unwantedness, contrasting their usefulness for specifying levels of unwanted pregnancy and its relationship with domestic violence. Data from India's 1998-99 National Family Health Survey and a 2002-03 follow-up survey for which women in four states were reinterviewed are analyzed, and the factors associated with the intersurvey adoption of contraception and the experience of an unwanted pregnancy are examined. Women who experience physical violence from their husbands are significantly less likely to adopt contraception and more likely to experience an unwanted pregnancy. A prospectively measured indicator of unwanted pregnancy identifies a higher prevalence of unwanted pregnancies than do the traditionally employed retrospective measures and is more successful in establishing a relationship between unwanted pregnancies and domestic violence. The results demonstrate a clear relationship between a woman's experience of physical violence from her husband and her ability to achieve her fertility intentions. The need to improve the measurement of pregnancy intendedness is clear, and a move toward using prospective measures as the standard is necessary. | 18,853,639 |
[Time dependent effect of melatonin administration on lipid peroxidation, superoxide dismutase activity and melatonin concentration in the elderly patients with essential arterial hypertension]. | Oxidative stress and melatonin (the pineal hormone) are involved in the pathogenesis of aging and aging-related diseases, including essential arterial hypertension. The aim of study was determination of time dependent effect of melatonin administration on malondialdehyde (MDA) concentration, Cu, Zn-superoxide dismutase (SOD-1) activity and melatonin concentration in the elderly patients with essential arterial hypertension. The study was carried out on 11 patients with essential arterial hypertension (NT group, average 76.7 +/- 10 years), who were treated with thiazide diuretic. The reference group (K) was constituted 13 people without the chronic diseases (average 76.9 +/- 8 years). In the groups NT and K melatonin (Melatonin 5mg, LEKAM) one hour before sleep was administrated. MDA concentration and SOD-1 activity was performed before beginning of experiment and after 15 and after 30 days of the melatonin administration. Melatonin concentration was determined before beginning of experiment and after 30 days of the melatonin administration. Venous blood was taken from the cubital vein at 08.00 am. Melatonin concentration was determined in serum, and MDA content and SOD-1 acitivity were determined in erythrocytes. In NT group in comparison to K group non-significant higher MDA concentration (0.293 +/- 0.03 and 0.286 +/- 0.03 micromol/g Hb, respectively), lower SOD-1 activity (2591 +/- 304.1 and 2630 +/- 301 U/g Hb, respectively) and lower melatonin concentration (7.65 +/- 4.6 and 8.36 +/- 4.7 pg/ml, respectively) were observed. After 15 days of melatonin administration lower MDA concentration and higher SOD-1 activity: in NT group (0.250 +/- 0.03, p < 0.01 and 2757 +/- 299, NS, respectively) and in K group (0.264 +/- 0.03, NS and 3065 +/- 529, p < 0.02, respectively) were measured. After 30 days of supplementation MDA concentration further decreased in NT group (0.247 +/- 0.03, NS) and in K group (0.240 +/- 0.03, p < 0.002). However, after 30 days of melatonin administration in comparison to the results of 15 days the statistically non-significant differences of SOD-1 activity, either in NT group (2680 +/- 332 U/g Hb) and in K group (3012 +/- 417 U/g Hb) were observed. After 30 days of supplementation melatonin concentration increased in NT group (19.57 +/- 11.7 pg/ml, p < 0.01) and in K group (19.33 +/- 17.8 pg/ml, p < 0.05). The results may indicate on the intensification of oxidative stress in elderly patients with essential arterial hypertension and on the beneficial antioxidant effect of melatonin, already after 15 days of supplementation. This results may have indicates on the therapeutic implications. | 18,853,657 |
[Premedication with intraoperative clonidine and low-dose ketamine in outpatient laparoscopic cholecystectomy]. | To determine the efficacy of premedication with intraoperative clonidine in association with low-dose ketamine to reduce the need for postoperative opiate analgesia in outpatient laparoscopic cholecystectomy. We performed a prospective study of patients undergoing outpatient laparoscopic cholecystectomy between November 2005 and November 2006. The patients were distributed randomly in 2 groups: patients in the clonidine-ketamine group received clonidine (0.15 mg orally 60 minutes before surgery) and ketamine (20-mg intravenous bolus followed by intraoperative perfusion of 20 mg h(-1)); patients in the control group did not receive this medication. Pain assessed on a verbal numerical scale, number of times rescue analgesia was required to achieve a value below 3, and adverse effects of the medication were recorded in the postoperative period. Thirty-one patients (16 in the clonidine-ketamine group and 15 in the control group) were enrolled. Rescue analgesia was required on 2 occasions by 25% of patients in the clonidine-ketamine group and on 2 or 3 occasions by 533% of patients in the control group. Adverse effects were reported by 87.5% of patients in the clonidine-ketamine group (mainly visual disturbances, sedation, and nausea) and by 46.7% in the control group. This difference was significant during the patients' stay in the postanesthesia recovery unit. Patients receiving clonidine and ketamine required less additional opiate analgesia to achieve mild pain values (<3 on the numerical verbal scale) but suffered more adverse effects during their stay in the postanesthesia recovery unit. Discharge was not delayed, however. | 18,853,679 |
Incidence of lymphocytic esophagitis in baboons. | We previously reported a novel histological phenotype of chronic esophagitis, lymphocytic esophagitis, in patients without gastroesophageal reflux. The aim of the present study was to explore the possible occurrence of lymphocytic esophagitis in baboons. Filed hematoxylin and eosin (H&E)-stained sections from the esophagi of 103 consecutive baboons were reviewed. Lymphocytic esophagitis is characterized by high numbers of intraepithelial lymphocytes (IELs) gathered mainly around papillary areas and by none to occasional CD15+ intraepithelial granulocytes. Forty-five of the 103 baboons (43.7%) had lymphocytic esophagitis. A mean of 52 IELs/high-power field were found around the papillae. Immunostains showed that the IEL population in lymphocytic esophagitis was composed of T-cells, a subset of natural killer cells and of helper and inflammatory T-cells. Since lymphocytic esophagitis is by far much more frequent in baboons than in humans, the baboon emerges as a good animal model to study the etiology of this inflammatory disease in humans. | 18,853,756 |
H-ras and c-fos exhibit similar expression patterns during most stages of oral oncogenesis. | H-ras and c-fos oncogenes interact in signalling pathways but their level and time course of expression during oral cancer development are unclear. The present study used an animal model for the simultaneous investigation of H-Ras and c-Fos expression in sequential stages of oral oncogenesis. Three experimental groups of Syrian golden hamsters (A, B and C; 10 animals each) and one control group (7 animals) were used. The buccal pouches of hamsters in groups A, B and C were treated with 0.5% of the carcinogen 9,10-dimethyl-1,2-benzanthracene and were excised at 10, 14 and 19 weeks, respectively. The biopsies, which included tissue stages ranging from normal oral mucosa to moderately differentiated carcinoma, were studied immunohistochemically. A reduction in both H-Ras and c-Fos expression was observed from group A to B and from hyperplasias to early tumour stages, while a simultaneous increase was noted from group B to C and from well-differentiated to moderately-differentiated carcinomas. The H-ras/c-fos expression ratio had a value of approximately (1.09 +/- 0.21) in five out of seven studied tissue stages. H-Ras and c-Fos exhibit a similar expression pattern throughout most stages of oral carcinogenesis, an observation supported by the known molecular pathway connecting H-ras signalling with subsequent c-fos gene transcription. | 18,853,758 |
Clay minerals affect the stability of surfactant-facilitated carbon nanotube suspensions. | Carbon nanotubes (CNTs), because of their wide application, will inevitably enter aquatic systems, but the fate and transport of their suspensions in the environment are largely unknown. Clay minerals are expected to interact with CNT suspensions, affecting their fate and bioavailability. This study investigated the influence of clay minerals (kaolinite and montmorillonite) on the stability of surfactant (SDBS, CTAB, and TX100) facilitated multiwalled CNT (MWCNT) suspensions. Adsorption of the surfactants by MWCNTs and clay minerals was also examined. This is a first study on the interaction between clay minerals and surfactant-CNT suspensions. Sorption of SDBS by clay minerals and MWCNTs followed the order MWCNTs >> montmorillonite approximately kaolinite; but sorption of CTAB and TX100 followed the order montmorillonite > MWCNTs > kaolinite. For SDBS suspended MWCNTs, introduction of montmorillonite and kaolinite could not change their stability; for CTAB suspended MWCNTs, both montmorillonite and kaolinite greatly deposited the suspended MWCNTs; for TX100 suspended MWCNTs, montmorillonite could partially deposit the suspended MWCNTs, whereas kaolinite showed minimal effect. Two mechanisms of clay minerals affecting MWCNT suspensions are (1) removal of surfactants by clay minerals from solution and MWCNT surface and (2) bridging between clay mineral and MWCNTs by surfactant. | 18,853,802 |
Whole body diffusion weighted imaging: a new era of oncological radiology. | Cancer has become the leading cause of mortality in the urban area of China. Whole body diffusion weighted imaging (WB-DWI), also known as virtual positron emission tomography, has gradually become accepted as an image tool in tumor localization, characterization, staging and monitoring response to therapy or tumor recurrence. Our article aimed to summarize the limited initial clinical use of WB-DWI in the referred area, and to analyze the most potential advantage of WB-DWI in therapeutic monitoring and tumor staging. WB-DWI as a highly sensitive, completely non-invasive, well-tolerated and low price technique has a promising furture in tumor assessment. Profound clinical study is necessary for its further application improvement. | 18,853,845 |
Experimental study of inflammatory and metastatic lymph nodes with diffusion weighted imaging on animal model: comparison with conventional methods. | To investigate the feasibility of magnetic resonance (MR) diffusion weighted imaging (DWI) in discriminating inflammatory from VX2 carcinoma metastatic lymph nodes in rabbit model. Twenty New Zealand white rabbits were randomly divided into 2 groups. Complete Freund's adjuvant was injected into the bilateral dorsal footpads to set up ipsilateral lymphadenitis model (n = 10), and the other 10 rabbits received a subcutaneous implantation of VX2 tumor cell suspension (1.5 x 10(7) cells/mL) in both thighs to set up metastatic lymph node model. MR imaging scan covering the popliteal fossa and iliac fossa including short time inversion recovery echo-planar imaging DWI (STIR-EPI-DWI), T1-weighted imaging (T1WI) and T2-weighted imaging (T2WI) was performed 2 weeks after injection. T2WI signal intensity (SI), DWI SI, long/short axial ratio (LSR) and apparent diffusion coefficient (ADC) values of the lymph nodes were evaluated in all cases. Right after MR imaging scan, popliteal and iliac fossa lymph nodes were collected for hematoxylin-eosin staining. Totally 33 lymph nodes larger than 5 mm, including 22 inflammatory and 11 metastatic ones, were successfully isolated and taken into pathological analysis. LSR showed no significant difference between the inflammatory and malignant lymph nodes (P > 0.05). Both benign and malignant lymph nodes appeared iso-intense on T1WI and hyperintense on both T2WI and DWI images with an even lower T1WI and higher T2WI SI core at the hilum. Both T2WI and DWI SI showed no significant difference between two pathological groups (P > 0.01) in popliteal fossa. The mean ADC value of inflammatory nodes [(1.199 +/- 0.281) x 10(-3) mm2/s] was significantly higher than that of metastatic nodes [(0.858 +/- 0.090) x 10(-3) mm2/s, P < 0.01]. On ADC map, a high ADC value central area could be seen in most of the lymph nodes no matter benign or malignant. ADC value gave out the largest area under curve (AUC(ADC) = 0.955) compared with other three indexes (AUC(LSR) = 0.488; AUC(T2WI SI)= 0.727; AUC(DWI SI) = 0.822) and gave the best sensitivity and specificity in lymph node differential diagnosis compared with the other three indexes. High quality DWI image can be obtained using STIR-EPI-DWI sequence in rabbit model. DWI is a new promising technique for differentiating inflammatory from metastatic lymph nodes. Compared with routine MR sequence, DWI could provide more useful physiological and functional information for diagnosis. | 18,853,852 |
Neurogenic inflammation of the upper airway mucosa. | Chronic inflammation of the upper airway mucosa is most likely caused by multiple factors, but is frequently associated with local neurogenic inflammation. This phenomenon can be induced by the inhalation of exogenous particles and chemicals present in our environment, as well as irritants produced endogenously. These irritants, i.e. histamine, H+ or bradykinin, can stimulate the abundant afferent sensory nerves endings, epithelial and neuroendocrine cells present in the upper airways mucosa. These structures can interact with our immune and neural cells by producing pro-inflammatory neuropeptides, cytokines, chemokines and neurotrophins. This short review summarizes some of our current knowledge with regard to the role of airborne chemical stimuli and their possible implications in the development of chronic inflammation of the upper airways mucosa. | 18,853,864 |
The relationship between allergy and rhinosinusitis. | IgE-mediated hypersensitivity is considered by some to be a predisposing factor for developing rhinosinusitis, although the theory is still controversial. The purpose of this study was to evaluate the relationship between allergy and rhinosinusitis. A cross-sectional study. 198 rhinitis patients were enrolled. An allergy skin prick test was done and the subjects categorized as allergic or nonallergic. Nasal endoscopy and sinus radiography were performed. The criteria for diagnosis of rhinosinusitis were rhinitis symptoms and positive nasal endoscopy (discharge from middle and/or superior meatus) and/or abnormal sinus radiography. Allergic patients were significantly more likely to have abnormal findings on sinus radiography than non-allergic patients (p < 0.001) and would therefore fulfill the criteria on which rhinosinusitis may be diagnosed, but the two groups were not significantly different in positive nasal endoscopy results (p = 0.553). Among the patients with abnormal sinus radiography, the allergic patients were significantly less likely to have a positive nasal endoscopy compared to the nonallergic patients (p = 0.006). Allergic rhinitis subjects were significantly more likely to have abnormal findings on sinus radiography compared with nonallergic subjects potentially leading to a diagnosis of rhinosinusitis. However, they were also significantly more likely to have abnormal sinus radiography with negative nasal endoscopy than the nonallergic subject. These findings could suggest an association between allergic rhinitis and rhinosinusitis via IgE mediated hypersensitivity. | 18,853,872 |
Tissue-specific immunoglobulin E in maxillary sinus mucosa of allergic fungal sinusitis. | The objectives of this prospective study were to analyze the specific immunoglobulin E (sIgE) in maxillary sinus mucosa and to determine the importance of local tissue sIgE in the patients with allergic fungal sinusitis (AFS). We investigated tissue-specific IgE in the maxillary sinus mucosa. Thirty-four patients with rhinosinusitis and nasal polyposis were included in the study. The patients were divided into three groups--AFS, fungal sinusitis and chronic rhinosinusitis (CRS). The sIgE profile of the maxillary sinus mucosa was studied by the CAP method. Other parameters, such as allergic symptoms, presence of fungi hyphae and eosinophilic mucin in the sinus cavities as well as computed tomography (CT) scanning findings were also evaluated in all groups. All patients in the AFS group had allergic symptoms, and the serum IgE test was positive to mites or house dust, but none had a positive serum IgE response to Aspergillus. However, 85.7% of this group had tissue sIgE to Aspergillus. The local tissue sIgE profile is more specific than the systemic sIgE profile in determining the allergic status of AFS patients. Tissue sIgE for fungi may be considered as a part of AFS diagnostic criteria. | 18,853,876 |
A feasibility study of methodology for recruitment and for comparative testing of ciliary function in Hawaiians and Caucasians. | Native Hawaiians have higher lung cancer incidence and mortality than other ethnic groups, even after controlling for smoking. Could reduced mucociliary clearance, suspected in Polynesians, play a role? In this pilot study of 9 Hawaiian and 8 Caucasian men, mean velocities were faster although not statistically significant in Caucasians. This pilot also generated recommendations on subject recruitment, measures, and data analysis for future studies. | 18,853,892 |
Zolpidem extended-release 12.5 mg associated with improvements in work performance in a 6-month randomized, placebo-controlled trial. | Although most research on pharmacotherapy for chronic insomnia focuses on changes in sleep outcomes, the functional impact of treatment is also of great importance to patients, families, physicians, and employers. To analyze changes in functioning at work (or work performance) among a subset of employed subjects (N = 752) from a 24-week, randomized, double-blind, placebo-controlled trial of zolpidem extended-release 12.5 mg taken nightly, at least 3 nights per week, by healthy adults with chronic insomnia. Using 2 scales (Time Management and Work Output) from the Work Limitations Questionnaire (WLQ), subjects' health-related work limitations were evaluated at baseline, week 4, week 12, and week 24 (end of study) or premature discontinuation. To compare zolpidem extended-release 12.5 mg with placebo, within-group and between-group differences were analyzed and effect sizes were computed. The relationship of WLQ scores to scores on the Patient Global Impression, Item 1 (PGI-1), scale, the primary outcome measure for benefit to sleep, was also analyzed. Data were obtained from August 31, 2004 through January 6, 2006. Scores on both WLQ scales were substantially elevated at baseline in this population, reflecting impairment relative to healthy controls. The zolpidem extended-release 12.5 mg group had significantly greater improvement at all time points on the WLQ Time Management (P < 0.0001) and Work Output (P < 0.01) scales. Effect size analysis confirmed the clinical relevance of these improvements. Subjects rating their sleep as improved on the PGI-1 had significantly greater improvement on both WLQ scales at week 12 than did those who reported no benefit or worsening (P < 0.01). Employed adults with chronic insomnia treated with zolpidem extended-release 12.5 mg experienced significantly improved work performance over 24 weeks. | 18,853,934 |
Lack of effects of pramipexole on REM sleep behavior disorder in Parkinson disease. | REM sleep behavior disorder (RBD) is a common manifestation of Parkinson disease (PD) which is characterized by dream-enacting behaviors, unpleasant dreams, and loss of muscle atonia during REM sleep. Dopaminergic mechanisms are thought to play a role in RBD pathogenesis. To further asses such a role, we have evaluated the effect of pramipexole, a dopamine receptor agonist, on RBD features in PD patients. University hospital sleep disorder center. Eleven PD patients with untreated RBD. interventions: Not applicable. In a prospective study, 11 consecutive PD patients with untreated RBD on levodopa monotherapy were placed on pramipexole to further ameliorate their parkinsonism. The effects on RBD were evaluated before and 3 months after stable pramipexole therapy through patient and bed partner interviews and blind assessment of video-polysomnographic measures. Pramipexole improved parkinsonism in all patients. Patients and bed partners reported no significant changes in frequency and severity of the abnormal RBD related motor and vocal sleep behaviors or the frequency of unpleasant dreams. Video-polysomnography analyses showed no differences in RBD related sleep measures including tonic submental electromyographic activity, phasic submental electromyographic activity, percentage of REM sleep time spent with abnormal behaviors, and severity of the abnormal behaviors detected on the videotapes. In PD, pramipexole improved parkinsonism but did not modify RBD related symptoms and objective video-polysomnographic abnormalities. This observation suggests that in PD, dopamine mechanisms do not play a central role in the pathogenesis of RBD. | 18,853,939 |
CD8+ T-Cell depletion and rapamycin synergize with combined coreceptor/stimulation blockade to induce robust limb allograft tolerance in mice. | The growing development of composite tissue allografts (CTA) highlights the need for tolerance induction protocols. Herein, we developed a mouse model of heterotopic limb allograft in a stringent strain combination in which potentially tolerogenic strategies were tested taking advantage of donor stem cells in the grafted limb. BALB/c allografts were transplanted into C57BL/6 mice treated with anti-CD154 mAb, nondepleting anti-CD4 combined to either depleting or nondepleting anti-CD8 mAbs. Some groups received additional rapamycin. Both depleting and nondepleting mAb combinations without rapamycin only delayed limb allograft rejection, whereas the addition of rapamycin induced long-term allograft survival in both combinations. Nevertheless, robust donor-specific tolerance, defined by the acceptance of a fresh donor-type skin allograft and simultaneous rejection of third-party grafts, required initial CD8(+) T-cell depletion. Mixed donor-recipient chimerism was observed in lymphoid organs and recipient bone marrow of tolerant but not rejecting animals. Tolerance specificity was confirmed by the inability to produce IL-2, IFN-gamma and TNF-alpha in MLC with donor antigen while significant alloreactivity persisted against third- party alloantigens. Collectively, these results show that robust CTA tolerance and mixed donor-recipient chimerism can be achieved in response to the synergizing combination of rapamycin, transient CD8(+) T-cell depletion and costimulation/coreceptor blockade. | 18,853,957 |
Iron intake and body iron stores as risk factors for Barrett's esophagus: a community-based study. | High iron stores are a proposed modifiable risk factor for esophageal adenocarcinoma, but minimal human data exist. We evaluated whether iron intake and iron stores were associated with Barrett's esophagus, a metaplastic change that is a strong risk factor for esophageal adenocarcinoma. We conducted a case-control study within the Kaiser Permanente Northern California population. We identified all persons with a new diagnosis of Barrett's esophagus (cases); they were matched to persons with GERD (without Barrett's esophagus) and to population controls. Subjects completed examinations, dietary questionnaires, and testing for serum iron stores (ferritin and transferrin saturation). Analyses used unconditional logistic regression. We evaluated 319 cases, 312 GERD patients, and 313 population controls. Compared with population controls, Barrett's esophagus patients had lower dietary iron intakes (4th vs 1st quartiles, odds ratio [OR]= 0.37, 95% confidence interval [CI] 0.17-0.80), similar total iron intakes (including supplement use), and lower iron stores (4th vs 1st quartiles, ferritin OR = 0.24, 95% CI 0.14-0.40;% transferrin saturation OR = 0.66, 95% CI 0.41-1.04; P value trend <0.01 and 0.03, respectively). Similar associations were observed in comparisons with GERD controls and among subjects without clear sources of blood loss on endoscopy. Patients with Barrett's esophagus had lower dietary iron intakes and lower serum iron stores than controls in our population. These findings do not provide support for the current hypothesis that high iron stores or a high iron intake are risk factors for Barrett's esophagus, a potential early event in the carcinogenic sequence for esophageal adenocarcinoma. | 18,853,987 |
Molecular mechanisms of pancreatitis: current opinion. | Pancreatitis (necroinflammation of the pancreas) has both acute and chronic manifestations. Gallstones are the major cause of acute pancreatitis, whereas alcohol is associated with acute as well as chronic forms of the disease. Cases of true idiopathic pancreatitis are steadily diminishing as more genetic causes of the disease are discovered. The pathogenesis of acute pancreatitis has been extensively investigated over the past four decades; the general current consensus is that the injury is initiated within pancreatic acinar cells subsequent to premature intracellular activation of digestive enzymes. Repeated attacks of acute pancreatitis have the potential to evolve into chronic disease characterized by fibrosis and loss of pancreatic function. Our knowledge of the process of scarring has advanced considerably with the isolation and study of pancreatic stellate cells, now established as the key cells in pancreatic fibrogenesis. The present review summarizes recent developments in the field particularly with respect to the progress made in unraveling the molecular mechanisms of acute and chronic pancreatic injury secondary to gallstones, alcohol and genetic factors. It is anticipated that continued research in the area will lead to the identification and characterization of molecular pathways that may be therapeutically targeted to prevent/inhibit the initiation and progression of the disease. | 18,853,993 |
Transgenic rice expressing Allium sativum leaf agglutinin (ASAL) exhibits high-level resistance against major sap-sucking pests. | Rice (Oryza sativa) productivity is adversely impacted by numerous biotic and abiotic factors. An approximate 52% of the global production of rice is lost annually owing to the damage caused by biotic factors, of which approximately 21% is attributed to the attack of insect pests. In this paper we report the isolation, cloning and characterization of Allium sativum leaf agglutinin (asal) gene, and its expression in elite indica rice cultivars using Agrobacterium-mediated genetic transformation method. The stable transgenic lines, expressing ASAL, showed explicit resistance against major sap-sucking pests. Allium sativum leaf lectin gene (asal), coding for mannose binding homodimeric protein (ASAL) from garlic plants, has been isolated and introduced into elite indica rice cultivars susceptible to sap-sucking insects, viz., brown planthopper (BPH), green leafhopper (GLH) and whitebacked planthopper (WBPH). Embryogenic calli of rice were co-cultivated with Agrobacterium harbouring pSB111 super-binary vector comprising garlic lectin gene asal along with the herbicide resistance gene bar, both under the control of CaMV35S promoter. PCR and Southern blot analyses confirmed stable integration of transgenes into the genomes of rice plants. Northern and western blot analyses revealed expression of ASAL in different transgenic rice lines. In primary transformants, the level of ASAL protein, as estimated by enzyme-linked immunosorbent assay, varied between 0.74% and 1.45% of the total soluble proteins. In planta insect bioassays on transgenic rice lines revealed potent entomotoxic effects of ASAL on BPH, GLH and WBPH insects, as evidenced by significant decreases in the survival, development and fecundity of the insects. In planta insect bioassays were carried out on asal transgenic rice lines employing standard screening techniques followed in conventional breeding for selection of insect resistant plants. The ASAL expressing rice plants, bestowed with high entomotoxic effects, imparted appreciable resistance against three major sap-sucking insects. Our results amply demonstrate that transgenic indica rice harbouring asal exhibit surpassing resistance against BPH, GLH and WBPH insects. The prototypic asal transgenic rice lines appear promising for direct commercial cultivation besides serving as a potential genetic resource in recombination breeding. | 18,854,007 |
The dual transcriptional regulator CysR in Corynebacterium glutamicum ATCC 13032 controls a subset of genes of the McbR regulon in response to the availability of sulphide acceptor molecules. | Regulation of sulphur metabolism in Corynebacterium glutamicum ATCC 13032 has been studied intensively in the last few years, due to its industrial as well as scientific importance. Previously, the gene cg0156 was shown to belong to the regulon of McbR, a global transcriptional repressor of sulphur metabolism in C. glutamicum. This gene encodes a putative ROK-type regulator, a paralogue of the activator of sulphonate utilisation, SsuR. Therefore, it is an interesting candidate for study to further the understanding of the regulation of sulphur metabolism in C. glutamicum. Deletion of cg0156, now designated cysR, results in the inability of the mutant to utilise sulphate and aliphatic sulphonates. DNA microarray hybridisations revealed 49 genes with significantly increased and 48 with decreased transcript levels in presence of the native CysR compared to a cysR deletion mutant. Among the genes positively controlled by CysR were the gene cluster involved in sulphate reduction, fpr2 cysIXHDNYZ, and ssuR. Gel retardation experiments demonstrated that binding of CysR to DNA depends in vitro on the presence of either O-acetyl-L-serine or O-acetyl-L-homoserine. Mapping of the transcription start points of five transcription units helped to identify a 10 bp inverted repeat as the possible CysR binding site. Subsequent in vivo tests proved this motif to be necessary for CysR-dependent transcriptional regulation. CysR acts as the functional analogue of the unrelated LysR-type regulator CysB from Escherichia coli, controlling sulphide production in response to acceptor availability. In both bacteria, gene duplication events seem to have taken place which resulted in the evolution of dedicated regulators for the control of sulphonate utilisation. The striking convergent evolution of network topology indicates the strong selective pressure to control the metabolism of the essential but often toxic sulphur-containing (bio-)molecules. | 18,854,009 |
A role for SNX5 in the regulation of macropinocytosis. | The mechanisms and components that regulate macropinocytosis are poorly understood. Here we have investigated the role of sorting nexin 5 (SNX5) in the regulation of macropinocytic activity. SNX5 is abundantly expressed in macrophages, cells very active in macropinocytosis, and is recruited onto newly-formed macropinosomes. LPS treatment of bone marrow-derived macrophages resulted in a 2.5 fold decrease in macropinosome formation that correlates with a reduction in the levels of SNX5. To investigate the relationship between SNX5 levels and macropinocytic activity we examined the formation of macropinosomes in HEK-FlpIn cells stably expressing GFP-SNX5. Constitutive macropinocytosis was increased approximately 2 fold in HEK-GFP-SNX5 cells compared with parental HEK-FlpIn cells. Furthermore, EGF stimulation resulted in a significant increase in macropinocytosis and there was also a 2.0 fold increase in the generation of macropinosomes in HEK-GFP-SNX5 cells compared with parental HEK-FlpIn cells. SNX5, which interacts specifically with PtdIns(3)P and PtdIns(3,4)P2 through its PX domain, was recruited to regions on the plasma membrane containing EGF receptor or positive for PtdIns(3,4)P2 as detected with the PH domain of TAPP1. Treatment with AG1478, an EGF receptor specific tyrosine kinase inhibitor, prevented the recruitment of SNX5 to the cytosolic face of the plasma membrane and inhibited the formation of macropinosomes in response to EGF treatment. Based on these data, we propose that SNX5 requires the generation of phosphoinositides for recruitment to the plasma membrane and, moreover, influences the level of macropinocytic activity. | 18,854,019 |
Lifestyle counseling in hypertension-related visits--analysis of video-taped general practice visits. | The general practitioner (GP) can play an important role in promoting a healthy lifestyle, which is especially relevant in people with an elevated risk of cardiovascular diseases due to hypertension. Therefore, the aim of this study was to determine the frequency and content of lifestyle counseling about weight loss, nutrition, physical activity, and smoking by GPs in hypertension-related visits. A distinction was made between the assessment of lifestyle (gathering information or measuring weight or waist circumference) and giving lifestyle advice (giving a specific advice to change the patient's behavior or referring the patient to other sources of information or other health professionals). For this study, we observed 212 video recordings of hypertension-related visits collected within the Second Dutch National Survey of General Practice in 2000/2001. The mean duration of visits was 9.8 minutes (range 2.5 to 30 minutes). In 40% of the visits lifestyle was discussed (n = 84), but in 81% of these visits this discussion lasted shorter than a quarter of the visit. An assessment of lifestyle was made in 77 visits (36%), most commonly regarding body weight and nutrition. In most cases the patient initiated the discussion about nutrition and physical activity, whereas the assessment of weight and smoking status was mostly initiated by the GP. In 35 visits (17%) the GP gave lifestyle advice, but in only one fifth of these visits the patient's motivation or perceived barriers for changing behavior were assessed. Supporting factors were not discussed at all. In 40% of the hypertension-related visits lifestyle topics were discussed. However, both the frequency and quality of lifestyle advice can be improved. | 18,854,020 |
Complete genome sequence of a highly divergent astrovirus isolated from a child with acute diarrhea. | Astroviruses infect a variety of mammals and birds and are causative agents of diarrhea in humans and other animal hosts. We have previously described the identification of several sequence fragments with limited sequence identity to known astroviruses in a stool specimen obtained from a child with acute diarrhea, suggesting that a novel virus was present. In this study, the complete genome of this novel virus isolate was sequenced and analyzed. The overall genome organization of this virus paralleled that of known astroviruses, with 3 open reading frames identified. Phylogenetic analysis of the ORFs indicated that this virus is highly divergent from all previously described animal and human astroviruses. Molecular features that are highly conserved in human serotypes 1-8, such as a 3'NTR stem-loop structure and conserved nucleotide motifs present in the 5'NTR and ORF1b/2 junction, were either absent or only partially conserved in this novel virus. Based on the analyses described herein, we propose that this newly discovered virus represents a novel species in the family Astroviridae. It has tentatively been named Astrovirus MLB1. | 18,854,035 |
Transcriptional regulation of subclass 5b fimbriae. | Enterotoxigenic Escherichia coli (ETEC) is a major cause of infant and child mortality in developing countries. This enteric pathogen causes profuse watery diarrhea by elaborating one or more enterotoxins that intoxicate eukaryotic cells and ultimately leads to a loss of water to the intestinal lumen. Virulence is also dependent upon fimbrial adhesins that facilitate colonization of the small intestine. The expression of CS1 fimbriae is positively regulated by Rns, a member of the AraC/XylS superfamily of transcriptional regulators. Based on fimbrial protein homology, CS1 fimbriae have been categorized as subclass 5b along with CS17, CS19, and PCFO71 fimbriae. In this study we show that Rns positively regulates the expression of these other subclass 5b members. DNase I footprinting revealed a Rns binding site adjacent to the -35 hexamer of each fimbrial promoter. The CS17 and PCFO71 fimbrial promoters carry a second Rns binding site centered at -109.5, relative to the Rns-dependent transcription start site. This second binding site is centered at -108.5 for the CS19 promoter. Mutagenesis of either site reduced Rns-dependent transcription from each promoter indicating that the molecules bound to these sites apparently function independently of one another, with each having an additive effect upon fimbrial promoter activation. This study demonstrates that the ETEC virulence regulator Rns is required for the expression of all known 5b fimbriae. Since Rns is also known to control the expression of additional ETEC fimbriae, including those within subclasses 5a and 5c, the inactivation or inhibition of Rns could be an effective strategy to prevent ETEC infections. | 18,854,044 |
Sickness behaviour pushed too far--the basis of the syndrome seen in severe protozoal, bacterial and viral diseases and post-trauma. | Certain distinctive components of the severe systemic inflammatory syndrome are now well-recognized to be common to malaria, sepsis, viral infections, and post-trauma illness. While their connection with cytokines has been appreciated for some time, the constellation of changes that comprise the syndrome has simply been accepted as an empirical observation, with no theory to explain why they should coexist. New data on the effects of the main pro-inflammatory cytokines on the genetic control of sickness behaviour can be extended to provide a rationale for why this syndrome contains many of its accustomed components, such as reversible encephalopathy, gene silencing, dyserythropoiesis, seizures, coagulopathy, hypoalbuminaemia and hypertriglyceridaemia. It is thus proposed that the pattern of pathology that comprises much of the systemic inflammatory syndrome occurs when one of the usually advantageous roles of pro-inflammatory cytokines--generating sickness behaviour by moderately repressing genes (Dbp, Tef, Hlf, Per1, Per2 and Per3, and the nuclear receptor Rev-erbalpha) that control circadian rhythm--becomes excessive. Although reversible encephalopathy and gene silencing are severe events with potentially fatal consequences, they can be viewed as having survival advantages through lowering energy demand. In contrast, dyserythropoiesis, seizures, coagulopathy, hypoalbuminaemia and hypertriglyceridaemia may best be viewed as unfortunate consequences of extreme repression of these same genetic controls when the pro-inflammatory cytokines that cause sickness behaviour are produced excessively. As well as casting a new light on the previously unrationalized coexistence of these aspects of systemic inflammatory diseases, this concept is consistent with the case for a primary role for inflammatory cytokines in their pathogenesis across this range of diseases. | 18,854,046 |
Tracheopathia chondro-osteoplastica--an unusual cause of stridor. | A case of tracheopathia chondro-osteoplastica causing sub-glottic stenosis is described. Case report and literature review. A 37-year-old man presented with a 15-year history of gradually worsening dyspnoea and stridor due to sub-glottic stenosis. His medical and radiographic records were reviewed. This patient's presentation, histopathological findings and radiology images are presented and discussed. Histopathological evaluation of microlaryngoscopy biopsy specimens, taken during laser debulking of the stenosis, confirmed the presence of tracheopathia chondro-osteoplastica. This is the first reported case of sub-glottic stenosis caused by tracheopathia chondro-osteoplastica which required an urgent tracheostomy. | 18,854,058 |
Successful treatment of secondary hemophagocytic lymphohistiocytosis in a patient with disseminated histoplasmosis. | Hemophagocytic lymphohistiocytosis (HLH) is an overwhelming inflammatory response, associated with an outpouring of cytokines and inappropriate activation of the macrophage system, causing severe morbidity and possible death. HLH has inherited and acquired forms. Secondary HLH can be related to any number of underlying conditions including infections, malignancy and autoimmune diseases. There are similarities between "cytokine storm" seen in HLH and the clinical findings of avian influenza. We report a patient with a history of sarcoidosis on chronic steroid treatment, who developed HLH secondary to an infection with Histoplasma capsulatum. | 18,854,090 |
Symposium: innovative techniques in human embryo viability assessment. Assessing embryo viability by measurement of amino acid turnover. | This review assesses the ability of non-invasive 'amino acid profiling' to predict early embryo viability. The history of amino acid supplementation of embryo culture media and the role of amino acids in early embryo development are first considered and these are followed by a review of methods to quantify amino acid depletion and production by single embryos. Data on amino acid profiling of embryos from a number of species are then discussed. It is concluded that this technology has excellent potential to improve the selection of single embryos for transfer in clinical IVF. | 18,854,101 |
Growth differentiation factor-9 and anti-Müllerian hormone expression in cultured human follicles from frozen-thawed ovarian tissue. | In-vitro growth of frozen-thawed human follicles is perceived as a potential option for restoring women's fertility. The aims of this study were: (i) to test the usefulness of a defined serum-free medium for growth of frozen-thawed human follicles; and (ii) to evaluate the expression of growth differentiation factor-9 (GDF-9) and anti-Müllerian hormone (AMH) in cultured follicles. Frozen-thawed ovarian cortical pieces from 7-, 12-, 25- and 27-year-old women were cultured for 0, 7, 14, 21 and 28 days. Follicle developmental quality was evaluated and expression of proliferating cell nuclear antigen (PCNA) (day 21), GDF-9 (days 14 and 28) and AMH (day 21) was assessed by immunohistochemistry. Primary follicles and enclosed oocytes underwent significant growth at the end of culture (P < 0.05). Cultured follicles from all patients studied reached the early secondary stage and a few follicles from two patients developed up to the secondary stage. The rate of atresia was variable throughout the culture periods. PCNA was expressed in the granulosa cells at all the different follicular stages. AMH and GDF-9 immunostaining were found respectively in the granulosa cells and oocytes after several weeks of culture. The transition from resting to growing follicles leading to the development of secondary follicles showed the normal expression patterns of GDF-9 and AMH. | 18,854,109 |
The endoderm of the mouse embryo arises by dynamic widespread intercalation of embryonic and extraembryonic lineages. | The cell movements underlying the morphogenesis of the embryonic endoderm, the tissue that will give rise to the respiratory and digestive tracts, are complex and not well understood. Using live imaging combined with genetic labeling, we investigated the cell behaviors and fate of the visceral endoderm during gut endoderm formation in the mouse gastrula. Contrary to the prevailing view, our data reveal no mass displacement of visceral endoderm to extraembryonic regions concomitant with the emergence of epiblast-derived definitive endoderm. Instead, we observed dispersal of the visceral endoderm epithelium and extensive mixing between cells of visceral endoderm and epiblast origin. Visceral endoderm cells remained associated with the epiblast and were incorporated into the early gut tube. Our findings suggest that the segregation of extraembryonic and embryonic tissues within the mammalian embryo is not as strict as believed and that a lineage previously defined as exclusively extraembryonic contributes cells to the embryo. | 18,854,136 |
An Elmo-like protein associated with myosin II restricts spurious F-actin events to coordinate phagocytosis and chemotaxis. | Elmo proteins positively regulate actin polymerization during cell migration and phagocytosis through activation of the small G protein Rac. We identified an Elmo-like protein, ElmoA, in Dictyostelium discoideum that unexpectedly functions as a negative regulator of actin polymerization. Cells lacking ElmoA display an elevated rate of phagocytosis, increased pseudopod formation, and excessive F-actin localization within pseudopods. ElmoA associates with cortical actin and myosin II. TIRF microscopic observations of functional ElmoA-GFP reveal that a fraction of ElmoA localizes near the presumptive actin/myosin II cortex and the levels of ElmoA and myosin II negatively correlate with that of polymerizing F-actin. F-actin-regulated dynamic dispersions of ElmoA and myosin II are interdependent. Taken together, our data suggest that ElmoA modulates actin/myosin II at the cortex to prevent excessive F-actin polymerization around the cell periphery, thereby maintaining proper cell shape during phagocytosis and chemotaxis. | 18,854,143 |
An Afg2/Spaf-related Cdc48-like AAA ATPase regulates the stability and activity of the C. elegans Aurora B kinase AIR-2. | The Aurora B kinase is the enzymatic core of the chromosomal passenger complex, which is a critical regulator of mitosis. To identify novel regulators of Aurora B, we performed a genome-wide screen for suppressors of a temperature-sensitive lethal allele of the C. elegans Aurora B kinase AIR-2. This screen uncovered a member of the Afg2/Spaf subfamily of Cdc48-like AAA ATPases as an essential inhibitor of AIR-2 stability and activity. Depletion of CDC-48.3 restores viability to air-2 mutant embryos and leads to abnormally high AIR-2 levels at the late telophase/G1 transition. Furthermore, CDC-48.3 binds directly to AIR-2 and inhibits its kinase activity from metaphase through telophase. While canonical p97/Cdc48 proteins have been assigned contradictory roles in the regulation of Aurora B, our results identify a member of the Afg2/Spaf AAA ATPases as a critical in vivo inhibitor of this kinase during embryonic development. | 18,854,144 |
Global transcriptional repression in C. elegans germline precursors by regulated sequestration of TAF-4. | In C. elegans, four asymmetric divisions, beginning with the zygote (P0), generate transcriptionally repressed germline blastomeres (P1-P4) and somatic sisters that become transcriptionally active. The protein PIE-1 represses transcription in the later germline blastomeres but not in the earlier germline blastomeres P0 and P1. We show here that OMA-1 and OMA-2, previously shown to regulate oocyte maturation, repress transcription in P0 and P1 by binding to and sequestering in the cytoplasm TAF-4, a component critical for assembly of TFIID and the pol II preinitiation complex. OMA-1/2 binding to TAF-4 is developmentally regulated, requiring phosphorylation by the DYRK kinase MBK-2, which is activated at meiosis II after fertilization. OMA-1/2 are normally degraded after the first mitosis, but ectopic expression of wild-type OMA-1 is sufficient to repress transcription in both somatic and later germline blastomeres. We propose that phosphorylation by MBK-2 serves as a developmental switch, converting OMA-1/2 from oocyte to embryo regulators. | 18,854,162 |
Sulforaphane induces DNA double strand breaks predominantly repaired by homologous recombination pathway in human cancer cells. | Cytotoxicity and DNA double strand breaks (DSBs) were studied in HeLa cells treated with sulforaphane (SFN), a well-known chemo-preventive agent. Cell survival was impaired by SFN in a concentration and treatment time-dependent manner. Both constant field gel electrophoresis (CFGE) and gamma-H2AX assay unambiguously indicated formation of DSBs by SFN, reflecting the cell survival data. These DSBs were predominantly processed by homologous recombination repair (HRR), judging from the SFN concentration-dependent manner of Rad51 foci formation. On the other hand, the phosphorylation of DNA-PKcs, a key non-homologous end joining (NHEJ) protein, was not observed by SFN treatment, suggesting that NHEJ may not be involved in DSBs induced by this chemical. G2/M arrest by SFN, a typical response for cells exposed to ionizing radiation was also observed. Our new data indicate the clear induction of DSBs by SFN and a useful anti-tumor aspect of SFN through the induction of DNA DSBs. | 18,854,174 |
Integrin alphavbeta3-mediated transcriptional regulation of TIMP-1 in a human ovarian cancer cell line. | We have previously reported that a disintegrin inhibits solid tumor growth and metastasis in mouse model [I.C. Kang, Y.D. Lee, D.S. Kim, A novel disintegrin salmosin inhibits tumor angiogenesis, Cancer Res. 59 (1999) 3754-3760; S.I. Kim, K.S. Kim, H.S. Kim, D.S. Kim, Y. Jang, K.H. Chung, Y.S. Park, Inhibitory effect of the salmosin gene transferred by cationic liposomes on the progression of B16BL6 tumors, Cancer Res. 63 (2003) 6458-462]. In this study, we have investigated the modulatory effect of a disintegrin, saxatilin, on the balance between MMP-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1) in human ovarian cancer cell line MDAH 2774. Functional mechanism of the disintegrin-mediated transcriptional regulation of MMP-9 and TIMP-1 was examined in the ovarian cancer cell line. Saxatilin strongly induced TIMP-1 expression in dose- and time-dependent manners, while the disintegrin suppressed MMP-9 expression. Further analyses clearly indicated that interaction of the disintegrin and integrin alphavbeta3 results in the TIMP-1 promoter activation via c-fos to suppress TNF-alpha-induced cancer cell invasion. These results demonstrate that integrin alphavbeta3-mediated transcriptional regulation of MMP-9 and TIMP-1 is critical for suppressing the ovarian cancer cell invasion. | 18,854,176 |
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