title stringlengths 0 1.13k | abstract stringlengths 1 15.7k | PMID int64 22 36.5M |
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Infrequent and low expression of cancer-testis antigens located on the X chromosome in colorectal cancer: implications for immunotherapy in South African populations. | Cancer-testis (CT) antigens are a group of tumor antigens that are expressed in the testis and aberrantly in cancerous tissue but not in somatic tissues. The testis is an immune-privileged site because of the presence of a blood-testis barrier; as a result, CT antigens are considered to be essentially tumor specific and are attractive targets for immunotherapy. CT antigens are classified as the CT-X and the non-X CT antigens depending on the chromosomal location to which the genes are mapped. CT-X antigens are typically highly immunogenic and hence the first step towards tailored immunotherapy is to elucidate the expression profile of CT-X antigens in the respective tumors. In this study we investigated the expression profile of 16 CT-X antigen genes in 34 colorectal cancer (CRC) patients using reverse transcription-polymerase chain reaction. We observed that 12 of the 16 CT-X antigen genes studied did not show expression in any of the CRC samples analyzed. The other 4 CT-X antigen genes showed low frequency of expression and exhibited a highly variable expression profile when compared to other populations. Thus, our study forms the first report on the expression profile of CT-X antigen genes among CRC patients in the genetically diverse South African population. The results of our study suggest that genetic and ethnic variations in population might have a role in the expression of the CT-X antigen genes. Thus our results have significant implications for anti-CT antigen-based immunotherapy trials in this population. | 18,956,367 |
Determination of pharmaceuticals in drinking water by CD-modified MEKC: separation optimization using experimental design. | A suite of 12 widely used pharmaceuticals (ibuprofen, diclofenac, naproxen, bezafibrate, gemfibrozil, ofloxacin, norfloxacin, carbamazepine, primidone, sulphamethazine, sulphadimethoxine and sulphamethoxazole) commonly found in environmental waters were separated by highly sulphated CD-modified MEKC (CD-MEKC) with UV detection. An experimental design method, face-centred composite design, was employed to minimize run time without sacrificing resolution. Using an optimized BGE composed of 10 mM ammonium hydrogen phosphate, pH 11.5, 69 mM SDS, 6 mg/mL sulphated beta-CD and 8.5% v/v isopropanol, a separation voltage of 30 kV and a 48.5 cm x 50 microm id bare silica capillary at 30 degrees C allowed baseline separation of the 12 analytes in a total analysis time of 6.7 min. Instrument LODs in the low milligram per litre range were obtained, and when combined with offline preconcentration by SPE, LODs were between 4 and 30 microg/L. | 18,956,383 |
On the overestimation of early wall thickening at the carotid bulb by black blood MRI, with implications for coronary and vulnerable plaque imaging. | Black blood MRI is an attractive tool for monitoring normal and pathological wall thickening; however, limited spatial resolutions can conspire with complex vascular geometries to distort the appearance of the wall in ways hitherto unclear. To elucidate this, a thin-walled cylinder model was developed to predict the composite effects of obliqueness, in-plane resolution and voxel anisotropy on the accuracy of MRI-derived wall thickness measurements. These predictions were validated by means of imaging of a thin-walled carotid bifurcation phantom. Typical thick-slice axial acquisitions were found to result in artifactual wall thickening at the carotid bulb, owing to its obliqueness to the nominal imaging plane. Obliqueness was less problematic for near-isotropic resolutions; however, the obligatory reduction of in-plane resolution served to inflate wall thicknesses uniformly by up to 50%. Moreover, the nonlinear relationship between wall thickness and its overestimation served to mask genuine differences in wall thickness, an effect predicted to be worse for thinner coronary artery walls and plaque caps. Therefore, care must be taken when interpreting black blood MRI wall thickness measurements in the presence-or absence-of observed differences within or between individuals. | 18,956,420 |
Identification of rat urinary glycoproteome captured by three lectins using gel and LC-based proteomics. | Many different types of urine proteome studies have been done, but urine glycoprotein studies are insufficient. Therefore, we studied the glycoproteins from rat urine, which could be used to identify biomarkers in an animal model. First, urinary proteins were prepared by using the dialysis and lyophilizing methods from rat urine. Glycoproteins enriched with lectin affinity purification, concanavalin A, jacalin and wheat germ agglutinin from the urinary proteins were separated by means of reverse-phase fast protein LC (FPLC) or 1-D PAGE. Each FPLC fraction and 1-D PAGE gel band were trypsin-digested and analyzed by means of nanoLC-MS/MS. LC-MS/MS analyses were carried out by using linear ion trap MS. A total of 318 rat urinary glycoproteins were identified from the FPLC fractions and gel bands; approximately 90% of identified proteins were confirmed as glycoproteins in Swiss-Prot. Many glycoproteins, known as biomarkers, including C-reactive protein, uromodulin, amyloid beta A4 protein, alpha-1-inhibitor 3, vitamin D-binding protein, kallikrein 3 and fetuin-A were identified in this study. By studying urinary glycoproteins collected from rat, these results may help to assist in identifying urinary biomarkers regarding various types of disease models. | 18,956,432 |
Simultaneous determination of seven pesticides in waters using multi-walled carbon nanotube SPE and NACE. | In this work, NACE with UV detection is combined with SPE using multi-walled carbon nanotubes (MWCNT) as stationary phase to determine a group of seven pesticides (pirimicarb, pyrifenox, penconazol, carbendazim, cyromazine, pyrimethanil and cyprodinil) in mineral water samples using ametryn as internal standard. The optimized BGE, consisting of a mixture of MeOH and ACN (1:2 v/v) with 90 mM SDS and 20.5 mM HClO(4), was satisfactory to get a good resolution of the seven compounds in less than 13 min. On-line preconcentration was carried out by electrokinetic injection of the sample dissolved in 78:22 v/v MeOH/ACN, 1.11 mM HClO(4). Repeatability was studied for the same day (n=4), for nine different days (n=36) and for four different capillaries. RSD values were appropriate in all cases, i.e. in the range 4.3-9.4% between different capillaries. MWCNT of 10-15 nm od, 2-6 nm id and 0.1-10 mum length were used as SPE materials for the preconcentration of these pesticides from water samples. SPE parameters influencing the enrichment were optimized and the most favorable conditions were as follows: the amount of stationary phase, eluent, sample pH and sample volume were 40 mg MWCNT, 10 mL ACN and 10 mL dichloromethane containing 5% v/v formic acid, pH 8.0, and 750 mL, respectively. Mean recovery values ranged between 53 and 94% for Milli-Q water and between 47 and 93% for mineral waters (RSD values were in the range 2-16%). The method allowed the determination of these pesticides at concentrations below the maximum residue limits established by the European Union legislation (LOD in the range 27-58 ng/L). When the cost, amount and type of the carbon nanotubes used in this work are compared with those carbon nanotubes previously used in the literature it is clear that the proposed materials can be used as economical stationary phases, even cheaper than conventional SPE cartridges. | 18,956,435 |
SPE and large-volume sample stacking in MEKC for determination of doxycycline in biological fluids: comparison of direct injection to SPE-MEKC. | A novel and simple method has been developed for the determination of doxycycline (DOX) in biological fluids. The method is based on SPE, large-volume sample stacking (LVSS) and MEKC with UV-DAD detection. Six SPE cartridges have been used in investigation for sample clean up and pre-concentration (Supelco LC-8, LC-18, LC-SCX, and LC-WCX, as well as Strata-X and X-C). DOX was determined on a 56 cm (effective length 50 cm) x 50 microm id fused-silica capillary. The BGE was 20 mM borate buffer, pH 9.3, containing 80 mM SDS and 7.5% v/v of methanol (30 sx50 mbar), and the temperature and voltage were 25 degrees C and 30 kV, respectively. The analytical wavelength was set at 210 nm. Under optimized conditions it is possible to determine DOX in human serum, urine, semen, tears and saliva with recovery of 97.5% (RSD 2.5%). The method was shown to be sensitive (LOD is 1 microg/L) and precise (intra-day RSD 0.2 and 2.4%; inter-days 0.4 and 3.5% for migration time and peak area, respectively). Results for developed SPE-LVSS-MEKC were compared with LVSS-MEKC method with direct sample injection. The new LVSS-MEKC method is presented as a useful technique for rapid determination without extraction procedure of DOX in human urine and serum, using 80 mM of SDS, 10% v/v of methanol and 40 mM borate buffer (pH 9.3; 30 s x 50 mbar; 25 degrees C; 30 kV; 350 nm), but not for the other biological fluids, according to lower sensitivity of the method and because of the sample composition. | 18,956,436 |
Dizygotic monochorionic twin pregnancy conceived following intracytoplasmic sperm injection treatment and complicated by twin-twin transfusion syndrome and blood chimerism. | We report a case of a dizygotic monochorionic twin pregnancy preceded by intracytoplasmic sperm injection treatment including assisted hatching. On ultrasound examination at 25 weeks' gestation the twins, which had been assumed to be monochorionic, were found to be of different sexes. Karyotyping and zygocity determination were performed on amniotic fluid and showed the twins to be dizygotic with normal female and male karyotypes. There were clinical and sonographic signs of twin-twin transfusion syndrome (TTTS), and Cesarean delivery was performed at 32 weeks' gestation. At birth the twins were phenotypically a normal male and a normal female. Histology of the placenta showed it to be monochorionic diamniotic. Blood chimerism was found postnatally as both infants had the karyotypes 46,XX[13]/46,XY[17]. Chimerism was not found in cells from a buccal swab at 6 months of age. This is one of only a few reported cases of dizygotic monochorionic twins. Nearly all of these cases have been conceived after assisted reproductive technology procedures. It is of clinical importance to be aware of this rare phenomenon in relation to TTTS, prenatal screening and parental counseling. | 18,956,441 |
Main traumatic events in Europe: PTSD in the European study of the epidemiology of mental disorders survey. | A potentially traumatic event (PTE) contributes to trauma through its frequency, conditional probability of posttraumatic stress disorder (PTSD), and experience of other PTEs. A cross-sectional survey was conducted, enrolling 21,425 adults nationally representative of six European countries. Using the WHO-Composite International Diagnostic Interview, 8,797 were interviewed on 28 PTEs and PTSD. Prevalence of 12-month PTSD was 1.1%. When PTSD was present, the mean number of PTEs experienced was 3.2. In a multivariate analysis on PTEs and gender, six PTEs were found to be more traumatic, and to explain a large percentage of PTSD, as estimated by their attributable risk of PTSD: rape, undisclosed private event, having a child with serious illness, beaten by partner, stalked, beaten by caregiver. | 18,956,444 |
Characteristics and management of infectious industrial waste in Taiwan. | Infectious industrial waste management in Taiwan is based on the specific waste production unit. In other countries, management is based simply on whether the producer may lead to infectious disease. Thus, Taiwan has a more detailed classification of infectious waste. The advantage of this classification is that it is easy to identify the sources, while the disadvantage lies in the fact that it is not flexible and hence increases cost. This study presents an overview of current management practices for handling infectious industrial waste in Taiwan, and addresses the current waste disposal methods. The number of small clinics in Taiwan increased from 18,183 to 18,877 between 2003 and 2005. Analysis of the data between 2003 and 2005 showed that the majority of medical waste was general industrial waste, which accounted for 76.9%-79.4% of total medical waste. Infectious industrial waste accounted for 19.3%-21.9% of total medical waste. After the SARS event in Taiwan, the amount of infectious waste reached 19,350 tons in 2004, an increase over the previous year of 4000 tons. Waste minimization was a common consideration for all types of waste treatment. In this study, we summarize the percentage of plastic waste in flammable infectious industrial waste generated by medical units, which, in Taiwan was about 30%. The EPA and Taiwan Department of Health have actively promoted different recycling and waste reduction measures. However, the wide adoption of disposable materials made recycling and waste reduction difficult for some hospitals. It has been suggested that enhancing the education of and promoting communication between medical units and recycling industries must be implemented to prevent recyclable waste from entering the incinerator. | 18,956,484 |
Food labeling: health claims; soluble fiber from certain foods and risk of coronary heart disease. Final rule. | The Food and Drug Administration (FDA) is adopting as a final rule, without change, the provisions of the interim final rule (IFR) that amended the regulation authorizing a health claim on soluble fiber from certain foods and risk of coronary heart disease (CHD), to add barley betafiber as an additional eligible source of beta-glucan soluble fiber. FDA is taking this action to complete the rulemaking initiated with the IFR. | 18,956,498 |
Immunohistochemical detection of HIF-1alpha and CAIX in advanced head-and-neck cancer. Prognostic role and correlation with tumor markers and tumor oxygenation parameters. | Tumor hypoxia has an impact on the outcome of cancer patients treated with radiotherapy. The validity of endogenous markers such as hypoxia-inducible factor-1alpha (HIF-1alpha) and carbonic anhydrase isozyme IX (CAIX) to detect therapeutically relevant Levels of hypoxia within tumors is controversially discussed. Furthermore, the association of these hypoxia markers with tumor markers or tumor oxygenation parameters is of importance for understanding the relationship between the different factors. Tumortissue sections of 34 patients with advanced head-and-neck cancertreated with radio(chemo)therapy were assessed by immunohistochemistry for the expression of HIF-1alpha and CAIX. The relationships of both markers with tumor oxygenation parameters, molecular factors like P53, OPN, VEGF, VHL, survivin, and Ki67 levels, and clinical parameters were studied. Bivariate analysis showed a significant correlation of HIF-1alpha expression with high P53 and high OPN expression, high serum VEGF Levels, and low VHL and low Ki67 expression. The CAIX expression was inversely correlated with pH value and directly correlated with T-stage. However, no correlation was found between HIF-1alpha and CAIX expression. Neither in a univariate Cox proportional hazard regression nor in a Kaplan-Meier analysis did expression of HIF-1alpha or CAIX have a significant impact on clinical outcome. However, in a Kaplan-Meier analysis, the combination of both factors showed that patients with intratumoral overexpression of either HIF-1alpha or CAIX or both markers died on average 2 years earlier than patients whose tumors had low expression of both factors (p < 0.05). Expression of HIF-1alpha and CAIX was correlated with different tumor parameters. Only combined HIF-1alpha and CAIX expression was significantly predictive of patients' overall survival. | 18,956,515 |
United we stand. Power shifts marginalize physician practices--unless we act and integrate. | How three "seismic events" in Fort Wayne, Ind., pushed a multispecialty group administrator to embrace integration. | 18,956,545 |
Day-night fluctuation of pulse oximetry: an exploratory study in pediatric inpatients. | Pulse oximetry is a simple and non-invasive procedure widely used nowadays in the clinical practice. However, it is unclear if SpO2 values are constant throughout the 24 hours of the day or have periodic fluctuations. In the present study we evaluated if progressive day-night variations of SpO, values occur in children. Pulse oximetry (Nonin 2500) was carried out approximately every 2 hours during a 24-hours period in pediatric patients hospitalized due to different diseases but without acute or chronic respiratory diseases. Measurements were analyzed through the cosinor method (sinusoidal curve fitting). A total of 131 patients (23 days to 16 years old) were studied. A sinusoidal fitting of the SpO2 values was accomplished in 84.7% of children. According to these curves, maximal SpO2 values occurred in the late afternoon [4:53 PM (3:49-5:32 PM), median (quartile 1-quartile 3)], while minimal values appeared in the first hours of the day [3:06 AM (2:12-4:08 AM)]. This pattern was the same in sleeping or awake children. More than half of these sinusoidal curves had a period near to 24 hours (between 20 and 28 hours). An additional finding was that maximal and minimal SpO2 values diminished with age (approximately 0.15 and approximately 0.13% SpO2 per year, respectively). In children less than six years old 5th percentile of SpO2 values were 93.8% in the late afternoon and 89.8% in the early hours of the day, while corresponding figures for older children were 91.0% and 88.5%, respectively. Our results suggested that, regardless of the sleep influence, in most children the SpO2 follows a progressive fluctuation during a 24-hours cycle, a pattern which is suggestive of a circadian rhythm. A prospective study in healthy children is warranted. | 18,956,552 |
[Proof of transovarial transmission of Lymantria dispar nucleopolyhedrovirus (fam. Baculoviridae) with the RAPD-PCR method]. | Transovarial transmission of Lymantria dispar Nucleopolyhedrovirus is shown with the RAPD-PCR method. Genetic markers of virus DNA found with the primer OPA-08 are recommended for diagnostics of Lymantria dispar nucleopolyhedrosis, in particular at the egg stage. Genetic markers of virus DNA found with the use of OPA-08 primer are helpful for estimation of genetic diversity of virus, level of the virus presence among the eggs, and for a decision about forestry protective measures. | 18,956,576 |
Clinical review of 23 patients with tuberculous peritonitis: presenting features and diagnosis. | To better identify which clinical, laboratory, radiological and invasive procedures were most useful in diagnosing tuberculous peritonitis and to assess the methods in order to reach the diagnosis in future cases. Tuberculous peritonitis cases diagnosed between 2000 and 2006 were reviewed retrospectively. Their clinical presentation, physical examination, laboratory and diagnostic methods were evaluated. Twenty-three cases oftuberculous peritonitis were diagnosed. The mean age of the patients were 30 +/- 11 years and 16 were women. The mean duration of symptoms prior to diagnosis was 3.6 months. All patients presented with abdominal pain. Abdominal swelling (91.3%), loss of appetite (87%) and weight loss (82.6%) were the other commonest symptoms. The major physical findings were ascites (78.3%) and fever (60.9%). The serum ascites albumin gradient was < 1.1 g/dL in all. An ascites fast bacilli smear was positive in 12 (52.2%) patients. Skin tests with purified protein derivative, adenosine deaminase and polymerase chain reaction were performed in seven, four and five patients, respectively. The tuberculous culture was positive in only two. The most common radiological findings were ascites (100%) and omental involvement (65.2%). A laparoscopy was performed in nine of 23 patients. A total of 22 patients completed anti-tuberculous therapy successfully and were cured, except one with cirrhosis. Tuberculous peritonitis may be fatal but is medically cured if diagnosed in a timely fashion. Although both non-invasive and invasive tests have additional benefits, clinician suspicion is still the first step for the diagnosis of tuberculous peritonitis. | 18,956,596 |
[Safety and efficacy of modified radical lymph nodes dissection in patients with papillary thyroid cancer (PTC) and clinically manifested lymph metastasis]. | Papillary cancer of the thyroid gland is well known as lymphotropic type. In more than 50 percent of cases it metastized in regional lymph nodes. The extent of surgical exploration remains controversial. The aim of our retrospective study is to evaluate safety and efficacy of modified radical lymph node dissection (MRND) in patients with PTC and regional lymph nodes metastasis. A retrospective analysis of survival, local recurrences and quality of life on 19 patients operated in Department of General Surgery, Medical University, Plovdiv. All patients were with PTC and regional lymph nodes metastasis. The results were compared with these in patients with the same disease and "berry picking" (BP) lymph nodes dissection. The performed analysis and comparison of data revealed better survival rate and quality of life in patients with (total thyroidectomy) TT and MRND than this one with TT and BP. MRND is safe and effective procedure for the treatment of patients with PTC and regional lymph nodes metastasis. Exactly performed it assure better survival, quality of life as well as better control of distant metastasis. | 18,956,604 |
[Surgical treatment of patients with therapy-resistant obsessive-compulsive disorder. Review]. | In spite of adequate pharmaco- and psychotherapy, only 60-80 percent of the patients with obsessive compulsive disorder (OCD) respond to treatment and the symptoms of OCD will persist in 20-40 percent of the cases. These patients are considered therapy resistant. Neurosurgical procedures may bring a breakthrough for patients with OCD, especially in therapy resistant OCD and the burden of the illness can be reduced. The theoretical background of these procedures is based on the new biological theories of OCD. Here we summarise the loop theories and describe the four different types of irreversible neurosurgical techniques used in OCD (cingulotomy, subcaudate tractotomy, limbic leucotomy and anterior capsulotomy). We will review the reversible neurosurgical techniques (deep brain stimulation), as well. Two techniques, namely anterior capsulotomy and deep brain stimulation will be discussed in greater detail. Finally, we review the results of neuropsychological and personality changes associated with anterior capsulotomy. | 18,956,611 |
[Exercise addiction: a literature review]. | Exercise in appropriate quantity and of proper quality contributes significantly to the preserve our health. On the contrary, excessive exercise may be harmful to health. The term 'exercise addiction' has been gaining increasing recognition to describe the latter phenomenon. The exact definition of exercise addiction and its potential associations with other disorders is still under study, although according to the authors this phenomenon can be primarily described as a behavioral addiction. Accordingly, exercise addiction, among other behavioral and mental disorders, can be well describe within the obsessive-compulsive spectrum suggested by Hollander (1993). There are several tools used to assess exercise addiction. The authors here present the Hungarian version of the Exercise Dependence Scale (Hausenblas és Downs, 2002) and the Exercise Addiction Inventory (Terry, Szabo és Griffiths, 2004). Exercise addiction has many symptoms in common and also shows a high comorbidity with eating disorders and body image disorders. It may be more closely associated with certain sports but more data is needed to demonstrate this specificity with more certainty. Sel-evaluation problems seem to have a central role in the etiology from a psychological aspect. The relevance of neurohormonal mechanisms is less clear. The authors emphasize the importance of further research on exercise addiction. One important question to be answered is if this disorder is an independent entity to be classified as a distinct clinical disorder or is it rather a subgroup of another disorder. | 18,956,613 |
[Central and peripheral mechanisms in antinociception: current and future perspectives]. | As it is well known opioids are the most powerful drugs used for acute and chronic pain, although, their several serious side effects, such as respiratory depression, mental clouding, constipation, and tolerance dependence producing capacity, as well as large interpatient variability in responses limit their safe everyday use. Furthermore, the treatment of certain types of pain (e.g. neuropathic pain) is not very satisfactorily managed. Consequently, there is a continuous need to find analgesics efficient against chronic neuropathic pain and avoid these side actions and still retain opioid like potency. There are several possible way to find new targets for these purposes. Recently opioid receptors have been identified on peripheral processes of sensory neurons. These findings provide new insights into intrinsic mechanisms of pain control and suggest innovative strategies for developing drugs and alternative approaches to pain treatment. In the effort to discover better analgesic drugs for chronic pain, attention is being paid to specific ion channels at the periphery, include members of transient receptor potential family (TRPV1, capsaicin receptors), as well as P2x receptors, sensitive to purines released from tissue injury. A special tetradotoxin-resistant, voltage dependent type of sodium channel is associated with dorsal root ganglia neurons is blocked by mexiletine, used in chronic pain. A synthetic peptide analogue of marine snail toxin ziconitine blocks N-type calcium channels. GABA and NMDA receptors are also involved in the antinociceptive actions of gabapentin and ketamine, respectively. Furthermore nicotine and analogues (epibatidine) induce analgesia through nicotinic ACh receptors. We studied mostly the peripheral targets of hydrophilic heterocyclic opioids in antinociceptive processes. | 18,956,616 |
[Assessment of gestures and their psychiatric relevance]. | Analyzing and investigating non-verbal behavior and gestures has been receiving much attention since the last century. Thanks to the pioneer work of Ekman and Friesen we have a number of descriptive-analytic, categorizing and semantic content related scales and scoring systems. Generation of gestures, the integrative system with speech and the inter-cultural differences are in the focus of interest. Furthermore, analysis of the gestural changes caused by lesions of distinct neurological areas point toward to formation of new diagnostic approaches. The more widespread application of computerized methods resulted in an increasing number of experiments which study gesture generation, reproduction in mechanical and virtual reality. Increasing efforts are directed towards the understanding of human and computerized recognition of human gestures. In this review we describe the results emphasizing the relations of those results with psychiatric and neuropsychiatric disorders, specifically schizophrenia and affective spectrum. | 18,956,625 |
[Relationship between Helicobacter pylori infection and expression of connexin (Cx) 32 and Cx43 genes in gastric cancer and gastric precancerous lesions]. | To investigate the expression of connexin (Cx)32 and Cx43 genes in gastric cancer and precancerous lesion, and to investigate the relation between the changes of expression of Cx32 and Cx43 genes and Helicobacter pylori (Hp) infection. Gastroscopy and biopsy of gastric mucosa were conducted on 33 patients with chronic superficial gastritis (CSG), 88 with precancerous lesion, and 70 with gastric cancer. Hp was detected by rapid urease test, basic fuchsin staining, and 14C-urea breath test. The CagA gene of Hp was determined by PCR. SABC immunohistochemical method was used to detect the expression of Cx32 and Cx43 genes in gastric mucosa biopsy specimens. The positive expression rates of Cx32 and Cx43 genes were 15.7% and 32.9% respectively in the gastric cancer patients, 51.1% and 54.5% in the patients with precancerous lesion, and 100.0% and 93.9% in the CSG patients. The positive Cx32 and Cx43 expression rates of the gastric cancer and precancerous lesion patients were significantly lower than those of the CSG patients (all P < 0.05). The positive Cx32 expression rate of the gastric cancer patients with Hp infection was 16.7%, not significantly different from that of the gastric cancer patients without Hp infection (13.6%). The positive Cx43 expression rate of the gastric cancer patients with Hp infection was 25%, significantly lower than that of the gastric cancer patients without Hp infection (50%, P = 0.039). The positive Cx32 and Cx43 expression rates and expression intensity of the precancerous lesion patients with Hp infection were all significantly lower than those of the precancerous lesion patients without Hp infection (all P < 0.05). The positive Cx43 expression rate of the gastric cancer patients with CagA+ Hp infection was 17.9%, significantly lower than that of the CagA- Hp group (55.6%, P = 0.027), however, the positive Cx32 expression rate of the gastric cancer patients with CagA+ Hp infection was 12.8%, not significantly different from that of the gastric cancer patients with CagA- Hp infection (33.3%, P = 0.159). The positive Cx32 and Cx43 expression rates of the CSG patients with CagA+ Hp and CagA- Hp infection were all 100%, but the expression intensity of the CagA+ Hp group was significantly lower than that of the CagA- Hp group (P = 0.032). The positive Cx32 and Cx43 expression rates after Hp eradication of the precancerous lesion patients with Hp infection were 97.9% and 91.7% respectively, both significantly higher than those before eradication therapy (41.4% and 44.8% respectively, both P < 0.05). However, the positive Cx32 and Cx43 expression rates of the precancerous lesion patients with Hp infection without Hp eradication were still 40% and 50%, not significantly different from those before treatment. The expression levels of Cx32 and Cx43 in gastric cancer and precancerous lesion decrease. The change of expression of Cx43 was associated with Hp infection, especially CagA+ Hp infection. Hp eradication in patients with precancerous lesion up-regulates the expression of Cx32 and Cx43. | 18,956,631 |
[Expression and significance of glypican-3 in colorectal cancer]. | To investigate the expression and significance of Glypican-3 in colorectal cancer. Immunohistochemistry was used to detect the expression of Glypican-3 in 200 specimens of colorectal cancer and adjacent non-cancerous tissues resected during operation. Glypican-3 immunoreactivity was recognized in both the cytoplasm and cellular membrane. The Glypican-3 positive expression rate in the tumor samples was 66.0% (132/200), significantly higher than that in the adjacent nontumor tissues (24%, 48/200, P = 0.019). The Glypican-3 expression rate was significantly correlated with the carcinoma invasion (P = 0.023) and lymph node metastasis (P = 0.015), but not associated with gender, age, tumor size, and differentiation grade (all P > 0.05). Over-expression of Glypican-3 may play an important role in the genesis and development of colorectal cancer, and may be used as a new biological parameter in predicting invasion and metastasis of colorectal carcinoma. | 18,956,635 |
[Study on the comparison of high risk behaviors related to AIDS among different status of income in men who have had sex with men]. | To explore the risk sexual behaviors related to AIDS among different status of income among men who have had sex with men and to provide relevant interventions for AIDS control and prevention. Study objectives were recruited through target sampling and anonymous questionnaires were adopted. Men's sexual behaviors were reported under the categories as high, mid or low-income. The total number of same-gender partners with high and mid-income was 110.17 with an average of 71.97. Among high and mid-income men, the number of partners for oral sex was 62.45, with an average of 46.6 respectively. The number of partners having anal intercourse was 52.21, with an average of 32.3, obviously more than in the low-income group (P < 0.01). The rates of condom use among high-income and mid-income men were 79.03% and 77.29% respectively and were higher than that those among low-income men (P < 0.01). The percentage of high-income men who recently had had sex with male sex workers was 3.81%, higher than that of the mid-income and the low-income men (P < 0.01). The rates of high-income and mid-income men who had paid for sex from men were 24.27% and 14.7% respectively and were all higher than that of the low-income men with the highest in the high-income group (P < 0.01). The rates of high-income and mid-income men who were male sex workers were 6.72% and 11.05% respectively, which were all lower than that from the low-income group (P < 0.01). The characteristics of sexual behaviors related to AIDS were different in the three groups. In high-income group, risk sexual behaviors also existed, suggesting that different interventions for different people should be developed. | 18,956,671 |
[Study on the indeterminate results of characterization and verification of HIV antibody from Western blot test]. | To study the serological characterization of indeterminate Western blot (WB) results of HIV antibody and to find a new way to verify the HIV antibody indeterminate results and provide references for editing "National Guideline for Detection of HIV/AIDS". All of the 42 subjects who were confirmed as indeterminate HIV antibody in People' Liberation Army HIV Confirmation Laboratory from 2005 to 2006, were collected. Line immunoassay, HIV viral load test and HIV-1 p24 were tested and followed up for 3-6 months' to compare the changes of WB bands patterns. (1) For the 42 individuals with indeterminate HIV antibody, a total of 8 different patterns of bands were found in WB test including 45.2% of them were p24 mono band, 30.9% were gp160 mono band, 11.9% were gp160 with p24, 2.4% (only one case) were gp160gp120 +/-, gp41p24, p24p17, gp41 or gp120 respectively. It was noticed that the most patterns of common bands with indeterminate results were p24 mono band, gp160 mono band and gp160 with p24, which composed 88.0% of the whole indeterminate WB band patterns. (2) Twenty three cases had been followed up for more than 3 months with 22 giving no WB band image change and were confirmed as HIV sero-negative. The other one with case gp160 and p24 had developed to more bands in the period of 77 days follow-up with more bands, including gp160, gp120, p66, p31, p24 and p17,showed up and was confirmed as HIV primary infection. (3) Line immunoassay was applied to all of those 23 cases who had been followed up and the results showed that only one serological change was found and the case was confirmed to be HIV-positive. Among the other 22 cases without serological changes, 16 cases were proved to be HIV-negative, 6 cases were still indeterminate. The specificity was 72.7%. P24 antigen test showed negative in all the 23 cases, including the case which later was confirmed as HIV-positive. Of all the 23 originally indeterminate cases, viral loads were tested in 7 cases. Positive result was found in the case which was proved later to be HIV-positive. No viral loads were detected in the other 6 cases (< LDL). The most common band patterns of indeterminate HIV antibody were mainly p24 monoband, gp160 monoband or with p24. Most of them (95.6%) were not infected by HIV, the bands showed up in WB test and demonstrated as non-specific reactions. Line immunoassay could determine about 70% of the indeterminate reactions. Results from viral load test also suggested that it was an efficient method to discriminate indeterminate results. With these two techniques, HIV serology could be diagnosed without 3 months' follow-up in primary infection which gave indeterminate WB results. | 18,956,682 |
[Clinical characteristics and prognostic factors of synchronous gastric carcinoma associated with esophageal carcinoma]. | To investigate the clinical characteristics and prognostic factors of synchronous gastric adenocarcinoma associated with squamous carcinoma of esophagus (SGCEC). From June 1979 to April 2005, 44 patients with SGCEC were treated and the data were retrospectively reviewed. There were 34 male and 10 female. The median age was 65 years old (range from 41 to 77 years old). The clinical features including sex, age, history, T stages and N stages of gastric carcinoma and esophageal carcinoma, curative or palliative resection, chemotherapy or/and radiotherapy were analyzed. Of all patients, 22.7% (10/44) had family history of carcinoma. Before or in the operations, some gastric carcinomas could not be easily found out, but they were determined in the resected specimens. The cumulative 5-year overall survival rate was 27%, and median survival was 22 months. Univariate analysis and multivariate analysis of prognostic factors identified both lymph node status of gastric carcinoma and curative resection as the predominating independent predictors of long-term survival. The patients with SGCEC show distinct clinical characteristics. Receiving curative operation and completely resection of gastric lymph nodes may improve the outcomes. | 18,956,720 |
[Clinical research about balloon dilation before incision for patients with ureteric stricture]. | To study the use about balloon dilatation before incision for the patients with ureteric stricture. Sixteen patients with ureteric stricture were included in our study. The cases were reviewed retrospectively with regards to the etiological factor, the site of stricture, symptom and diagnosis. Six patients with ureteric stricture were dilated with balloon before incision using Ho YAG laser. Ten patients with ureteric stricture were dilated with rigid ureteroscope before incision using Ho YAG laser. The double "J" stent was kept for 4-6 weeks after operation. All the patients were followed up by ultrasound, BUN and creatinine. Complete success is defined as symptomatic improvement, resolution of hydronephrosis and absence of ureteric stricture 3 months after removal of the double "J" stent. If the hydronephrosis and ureteric stricture did not deteriorate, and symptom improved after stent removal, it was considered as improvement. Failure is defined as deterioration of hydronephrosis and symptoms upon removal of double "J" stent. The length of stenosis was from 0.8 to 1.4 cm. Three patients failed to improve after initial dilatation with rigid ureteroscope, but were later successfully dilated using balloon. All the patients who were treated using balloon dilatation were successful. The operative time of balloon dilatation was shorter than that of dilatation by rigid ureteroscope (P < 0.05). However, the cost of balloon dilatation was higher (P < 0.05). The period of follow-up was 3-28 months. None of the patients had any complications. There were 2 cases of recurrent stricture in patients who underwent ureteroscopic dilatation. Despite a higher cost, balloon dilatation followed by laser incision for ureteric stricture is safe and effective. This technique may be used for selected patients. | 18,956,723 |
[Effects on lymphangiogenesis and angiogenesis of lung cancer with antisense oligonucleotides of vascular endothelial growth factor C]. | To investigate the effects on lymphangiogenesis and angiogenesis of orthotopic implantation of lung cancer in nude mice with antisense oligonucleotides of VEGF-C. The model in nude mice was established with orthotopic implantation for the human lung cancer cell line A549. Thirty nude mice were randomized into three groups: PBS control group, sense oligonucleotides control group and antisense oligonucleotides group (AODN group). After treatments were completed, the expression of VEGF-C and lymphatic microvessel density (LMVD) and microvessel density (MVD) of lung cancer were detected by RT-PCR,Western Blot and immunohistochemistry. The expression of VEGF-C in AODN group was inhibit significantly (P < 0.05). The LMVD in AODN group was decreased significantly (P < 0.1). Though the MVD in AODN group was also decreased, but there were no significant differences compared with control groups (P > 0.05). The antisense oligonucleotides of VEGF-C can inhibit the expression of VEGF-C in nude mice of orthotopic implantation of lung cancer. It could inhibit the lymphangiogenesis. | 18,956,726 |
[The microclimate of an unoccupied wintering sett of the badger, Meles meles (Carnivora: Mustelidae), in the Darwin State Nature Reserve, Vologda Region]. | Data on the microclimate (air temperature and humidity) within an unoccupied badger sett in the Darwin Reserve (the Vologda Region) between September 2005 and May 2006 have been analyzed in relation to changes in the temperature and humidity of the ground air layer and soil. A positive correlation has been revealed between the temperature regime of the soil and air temperature within the sett. After the establishment of snow cover, air and soil temperatures within the sett vary slightly and barely depend on ambient air temperature. | 18,956,735 |
[Identification of antimicrobial susceptibility of foodborne Salmonella and related plasmid]. | We tested the antimicrobial susceptibility of 390 Salmonella isolates. We also studied the relationship between plasmids in some multidrug resistant Salmonella isolates and the antibiotic resistance profile of their hosts, as well as conjugation test of some multidrug resistant Salmonellas. Salmonella strains were isolated by using selective cultures, putative Salmonella was confirmed by PCR. Antimicrobial susceptibility was tested according to the National Committee for Clinical Laboratory Standards. Plasmid of some representative multidrug resistant strains was isolated by using QIAGEN Plasmid Mini Kit and digested with Hind III. The plasmid profiles were acquired by gel electrophoresis and analyzed by DPS. The conjugation test was done to illustrate the function of plasmid during the antibiotic resistance transfer. Of the Salmonella isolates, 58.2% were resistant to tetracycline, followed by resistance to streptomycin (42.8%), kanamycin (39%), ampicillin (38.2%), cefoxitin (27.2%), chloramphenicol (26.9%), gentamicin (21%), ceftriaxone (19%), amoxicillin-clavulanic (18.2%), trimethoprim-sulfamethoxazole (17.9%), ceftiofur (14.6%) and nalidixic acid (12.3%). There was no strict corresponding relationship between antibiotic resistance profile of the host Salmonella and its plasmid profile. The conjugation frequency of the plasmid was from 2.4 x 10(-4) to 5.6 x 10(-1). Antimicrobial resistance is common in foodborne Salmonella, direct relativity does not exist between the homology of plasmids and their hosts' antibiotic resistance phenotype, antibiotic resistant genes in the plasmid can transfer from donor to the recipient in interspecies and intraspecies with high frequency accompanying conjugation. | 18,956,747 |
[Construction of recombinant fowlpox virus coexpressing HA from subtype H5 of avian influenza virus and chicken interleukin-18]. | We developed recombinant fowlpox viruses (rFPV) coexpressing chicken IL-18 and H5 AIV HA. Recombinant expression plasmid pSYHA/IL-18 was constructed by cloning chicken IL-18 into transfer plasmid containing HA gene and transfected by lipofectamine on the chicken embryo fibroblasts cell (CEF) pre-infected with S-FPV-017. By selecting blue plaques on the CEF overlaid with agar containing X-gal, recombinants fowlpox virus rFPV-HA-IL-18 were obtained, and identified by PCR. The recombinant fowlpox viruses contained chicken IL-18 and HA gene and had stable genetic properties. The expression of HA was detected in the recombinant virus-infected CEF by indirect immunofluorescence using antibody against AIV. The expression of chicken IL-18 was detected by MTT in the recombinant virus-infected CEF fluid. The chickens vaccinated with recombinant fowlpox virus rFPV-HA-IL-18 and rFPV-HA had detectable hemagglutination inhibition (HI) antibody at 7 days post-vaccination, and HI antibody titers rose to peak at 14 days post-vaccination. No HI antibody was detected in the control or fowlpox virus immunized chickens before or after immunization. The chickens vaccinated with rFPV-HA-IL-18 had higher HI antibody titers than the chickens vaccinated with rFPV-HA. Development of recombinant fowlpox virus (rFPV-HA-IL-18) had strong biological activity. | 18,956,750 |
[Analysis and isolation of radical scavengers from metabolites of Hirsutella sp]. | During a screening for free radical scavengers from metabolites of entomogenous fungi, we fond a fermentation broth of the strain RCEF 0881 of Hirsutella sp. exhibited strong radical scavenging activity. To make clear of the constituents of the active compounds, and prepare some pure active compound for further structure identification we launched this study. We used organic solvent for active compounds extraction. DPPH-TLC and DPPH- Microplate assay were used for activity analysis. Components analysis was carried out on a HPLC-DAD-HRMS, and bioactive compound preparation on a preparative RP-HPLC. Our extraction tests showed that ethylacetate was the best solvent for the bioactive constituents extracting. HPLC-DAD-HRMS-DPPH assay revealed that the molecular formular of the radical scavengers existed in the extract were possibly C7H6O4, C8H8O3 and C12H14N2O. From the chromatographic and Uv properties, and the MS fragments, and database consulting, the compounds could be deduced as dihydroxybenzoic acid, methyl-hydroxyl benzoic acid, and an alkaloid, however, the structures are still needed to be confirmed. The pick area of HPLC and MS showed that the compound C12H14N2O was the main component of the extract. It was isolated via activity directed fractionation. The activity of the prepared compound was confirmed with DPPH-TLC assay and its purity was confirmed with HPLC-DAD-HR-ESIMS. The occurance of the three active compounds in entomogenous fungi was revealed for the first time. | 18,956,752 |
[Analysis of xanthones in gamboge by HPLC-PDA-ESI/MS]. | The MS and multi-MS spectra of gambogic acid and gambogenic acid in positive ion detection mode were analyzed by electrospray ion trap mass spectrometry (ESI-QITMS) and their cleavage patterns were summarized. Gamboge samples were separated by a Kromasil C18 column and analyzed by HPLC-PDA and MS. Sixteen xanthones could be separated and detected, A collision induced dissociation (CID) experiment was carried out. Molecular weight and UV spectra with of these compounds were obtained. Ten xanthone compounds in Gamboge were identified by online photodiode array detection-MS(n) and by comparing with data from literature. It is expected to develop a comprehensive quality control method for this kind of compounds in commonly used herbal preparation especially in structure analysis of trace substances. | 18,956,777 |
[Tuberculosis epidemiology in Mayotte Island]. | Mayotte is a French territory island, part of the Comoros Archipelago in the Indian Ocean with 200,000 inhabitants. The tuberculosis control program started in 1976, although available epidemiological data remains incomplete. We conducted a retrospective hospital-based survey in 202 outpatients and hospital medical records from the Hospital Centre of the main city to contribute to the epidemiological evaluation of tuberculosis patterns. The tuberculosis frequency remains unchanged since 2000. It affects a young population partly coming from the other neighbouring Comoro Islands (69%) with illegal immigrate status (53% in 2004). The systematic diagnostic screening efficiency of the condition appears marginal. Pulmonary involvement is the most frequent clinical manifestation (78%), although severe extrapulmonary manifestations are not exceptional. Co-infection with HIV and multi resistance to antituberculosis agents are not frequent. Up to 60% of cases have been proven to be bacteriologically linked. The notification rate remains critically low with an estimate of 39% of notifications to the local sanitary authorities in charge of secondary cases screening. The case coverage seems limited both by low socio-economical status and poor health facility accessibility The loss of follow up is dramatically high, 41% on the overall period, and up to 51% in 2004. Our results make mandatory the reinforcement of a tuberculosis survey and control involvement within the context of this French territory. Screening, care and follow up are to be implemented particularly for vulnerable and precarious groups and for patients. | 18,956,814 |
Alkane hydroxylation by peroxy acids: a comparison with the cytochrome P450 hydroxylation. | Alkane hydroxylation by peroxy acids proceeds by a synchronous nonconcerted peroxy oxygen insertion into the C-H bond according to density functional theory. A comparable reaction sequence, initiated by homolytic peroxy bond cleavage, can be formulated for the alkane hydroxylation by the cytochrome P450 hydroperoxo-heme Compound 0. This hydroxylation reaction proceeds by a two-step process because the formed reactive intermediate, Compound II, is significantly stabilized. | 18,956,858 |
Palladium-catalyzed formylation of aryl bromides: elucidation of the catalytic cycle of an industrially applied coupling reaction. | The first comprehensive study of the catalytic cycle of the palladium-catalyzed formylation of aryl bromides with synthesis gas (CO/H2, 1:1) is presented. The formylation in the presence of efficient (Pd/PR2(n)Bu, R = 1-Ad, (t)Bu) and nonefficient (Pd/P(t)Bu3) catalysts was investigated. The main organometallic complexes involved in the catalytic cycle were synthesized and characterized, and their solution chemistry was studied in detail. Comparison of stoichiometric and catalytic reactions using P(1-Ad)2(n)Bu, the most efficient ligand known for the formylation of aryl halides, led to two pivotal results: (1) The corresponding carbonylpalladium(0) complex [Pd(n)(CO)(m)L(n)] and the respective hydrobromide complex [Pd(Br)(H)L2] are resting states of the active catalyst, and they are not directly involved in the catalytic cycle. These complexes maintain the concentration of most active [PdL] species at a low level throughout the reaction, making oxidative addition the rate-determining step, and provide high catalyst longevity. (2) The product-forming step proceeds via base-mediated hydrogenolysis of the corresponding acyl complex, e.g., [Pd(Br)(p-CF3C6H4CO){P(1-Ad)2(n)Bu}]2 (8), under mild conditions (25-50 degrees C, 5 bar). Stoichiometric studies using the less efficient Pd/P(t)Bu3 catalyst resulted in the isolation and characterization of the first stable three-coordinated neutral acylpalladium complex, [Pd(Br)(p-CF3C6H4CO)(P(t)Bu3)] (10). Hydrogenolysis of 10 needed significantly more drastic conditions compared to that of dimeric 8. In the presence of amine base, complex 10 gave a catalytically inactive diamino acyl complex, which explains the low activity of the Pd/P(t)Bu3 catalyst formylation of aryl bromides. | 18,956,867 |
Dystrophic-like alterations characterize orbicularis oris and palatopharyngeal muscles in patients affected by cleft lip and palate. | This study analyzed histological and histochemical features of specimens of the orbicularis oris muscle, and palatal and pharyngeal muscles biopsied during surgery from 33 patients affected by cleft lip and palate. Three groups were studied: 20 patients affected by cleft palate with or without cleft lip (at the time of primary palatoplasty), seven by cleft lip with or without cleft palate (primary lip closure), and six by cleft lip with or without cleft palate (secondary cheiloplasty). Muscle sections were stained with hematoxylin-eosin, modified Gomori trichrome, ATPase reaction at pH 9.4, and NADH-TR. Analyzed parameters included organization, muscle fiber size and type, nuclear changes, presence of ragged-red fibers, degree of fibrosis, and presence of inflammatory infiltrate. In all patients who underwent primary palatoplasty and lip closure we noted dystrophic-like alterations of orbicularis oris and palatopharyngeal muscles, such as variability of fiber size, fiber disorganization, and increased fibrosis. The same alterations were found in adult patients submitted to secondary cheiloplasty, notwithstanding surgical repair. Furthermore, in all groups neither neurogenic atrophy nor ragged-red fibers or inflammatory infiltrate were detected. Muscle damage is a constant event in this deformity, and it could play an important role in its etiopathogenesis. Muscular biopsy during cheiloplasty and palatoplasty could offer useful information about muscle condition and possible functional recovery in cleft lip and palate patients. | 18,956,931 |
Cleft lip and/or palate: 10 years experience at a pediatric cleft center in Southern Thailand. | To study the clinical characteristics, demographic data, and associated congenital anomalies of pediatric patients with cleft lip and/or palate in Southern Thailand. Retrospective, hospital-based study. Cleft Clinic Center, Songklanagarind Hospital Children with cleft lip and/or palate who were born or seen at Songklanagarind Hospital between January 1997 and December 2006. Clinical features including demographic data, types of cleft, associated anomalies, family history of clefts, and physical growth. A total of 153 children were seen during the studied period, of whom 36 (23.5%) had isolated cleft lip, 32 (20.9%) had isolated cleft palate, and 85 (55.6%) had combined cleft lip and palate. Twenty-seven children (17.7%) had a family history of clefts. Congenital malformations (syndromic cleft) were found in 20 children (13%), and chromosomal abnormalities were found in four of these (20%). There were no significant differences among the three groups (isolated cleft lip, isolated cleft palate, and combined cleft lip and palate) in maternal and paternal ages, gestational age, birth weight, family history of cleft, or associated malformations. The physical growth parameters of children with nonsyndromic cleft were the same as in the general population. Children with syndromic cleft were significantly lighter at birth and had grown up significantly shorter and lighter, with smaller head circumference. Chromosomal abnormalities are commonly found in children with syndromic cleft. Children with nonsyndromic cleft have normal growth; whereas, those with syndromic cleft have some degree of prenatal and postnatal growth restriction. | 18,956,943 |
Evaluation of the Respimat Soft Mist Inhaler using a concurrent CFD and in vitro approach. | The Respimat Soft Mist Inhaler is reported to generate an aerosol with low spray momentum and a small droplet size. However, the transport characteristics of the Respimat aerosol are not well understood. The objective of this study was to characterize the transport and deposition of an aerosol emitted from the Respimat inhaler using a combination of computational fluid dynamics (CFD) modeling and in vitro experiments. Deposition of the Respimat aerosol was assessed in the inhaler mouthpiece (MP), a standard induction port (IP), and a more realistic mouth-throat (MT) geometry at an inhalation flow rate of 30 L/min. Aerosols were generated using an albuterol sulfate (0.6%) solution, and the drug deposition was quantified using both in vitro experiments and a CFD model of the Respimat inhaler. Laser diffraction experiments were used to determine the initial polydisperse aerosol size distribution. It was found that the aerosol generated from the highly complex process of jet collision and breakup could be approximated in the model using effective spray conditions. Computational predictions of deposition fractions agreed well with in vitro results for both the IP (within 20% error) and MT (within 10% error) geometries. The experimental results indicated that the deposition fraction of drug in the MP ranged from 27 to 29% and accounted for a majority of total drug loss. Based on the CFD solution, high MP deposition was due to a recirculating flow pattern that surrounded the aerosol spray and entrained a significant number of small droplets. In contrast, deposition of the Respimat aerosol in both the IP (4.2%) and MT (7.4%) geometries was relatively low. Results of this study indicate that modifications to the current Respimat MP and control of specific patient variables may significantly reduce deposition in the device and may decrease high oropharyngeal drug loss observed in vivo. | 18,956,950 |
HIV-related risk behaviors among female sex workers in Ho Chi Minh City, Vietnam. | This study quantitatively and qualitatively described HIV risk behaviors among Vietnamese female sex workers (FSWs) who work at three distinct venues in Ho Chi Minh City: street, massage parlors, and bars/clubs. Although 35% of the participants had never been tested for HIV, 18% of street and 7% of bar/club FSWs reported being positive. Almost all massage parlor FSWs had never used a condom for oral sex. Inconsistent condom use for vaginal sex with customers was more prevalent among bar/club FSWs (85%) than massage parlor (72%) and street FSWs (68%). Many participants reported difficulties in negotiating condom use with customers because of economic pressure, maintaining relationships, and lack of bargaining power. Bar/club FSWs revealed a difficult situation where drinking is part of their work. Thirty percent of street FSWs had injected drugs and reported addiction to heroin in relation to their helpless condition as FSWs. Street FSWs had the lowest levels of self-esteem and norms toward practicing safe sex and the highest levels of economic pressure. This study recommends future HIV prevention programs for FSWs in Vietnam that target their specific risk behaviors and work environments. | 18,956,984 |
[Post-transplant diabetes mellitus depending on the pre-transplant dialysis technique]. | Post-transplant diabetes mellitus (PTDM) is one of the most important complications in kidney transplant patients because it has a significant impact on graft and patient survival. Diagnosis of PTDM should be based on the American Diabetic Association criteria. Recent studies show the value of performing an oral glucose tolerance test in all patients. Multiple risk factors promote PTDM. PTDM incidence may be reduced by controlling modifiable factors (immunosuppression, obesity, infections...). According to RMRC data, patients on peritoneal dialysis are younger, but have a greater incidence rate of dyslipidemia and obesity. Recent data suggest that subclinical information, adiponectin, and ghrelin may be a significant pathogenetic factor in development of insulin resistance and diabetes mellitus. There is no clear evidence that the dialysis procedure influences the subclinical inflammatory state and adipocytokines. According to data from the Spanish group for the study of PTDM, a relationship exists between ghrelin levels and sex in patients on peritoneal dialysis. The most common metabolic complication in patients on peritoneal dialysis is hyperglycemia. Pre-transplant hyperglycemia promotes the occurrence of PTDM. There is no clear evidence in the literature showing that the dialysis procedure is a risk factor for the occurrence of PTDM. Additional multicenter studies are required to analyze the clinical and biological characteristics of renal patients and their relationship to PTDM. | 18,957,019 |
Development of a PCR-based strategy for CYP2D6 genotyping including gene multiplication of worldwide potential use. | There is growing consensus on the potential use of pharmacogenetics in clinical practice, and hopes have been expressed for application to the improvement of global health. However, two major challenges may lead to widening the "biotechnological gap" between the developing and the industrial world; first the unaffordability of some current technologies for poorer countries, and second the necessity of analyzing all described alleles for every clinical case due to the inability to predict the ethnic group of a given patient. Because of its role in the metabolism of a number of drugs, cytochrome P450 2D6 (CYP2D6) is an excellent candidate for use in the optimization of drug therapy. CYP2D6 is a highly polymorphic gene locus with more than 50 variant alleles, and subjects can be classified as poor metabolizers (PM), extensive metabolizers (EM), or ultrarapid metabolizers (UM) of a given CYP2D6 substrate. Several strategies and methods for CYP2D6 genotyping exist. Some, however, are expensive and laborious. The aim of this study was to design a PCR-based genotyping methodology to allow rapid, straightforward, and inexpensive identification of 90%-95% of CYP2D6 PM or UM genotypes for routine clinical use, independent of the individual's ethnic group. CYP2D6 is amplified in initial extra long PCRs (XL-PCRs), which subsequently undergo fragment-length polymorphism analysis for the determination of carriers of CYP2D6 allelic variants. The same XL-PCRs are also used for the determination of CYP2D6 multiplication and 2D6*5 allele (abolished activity). The application of this new strategy for the detection of CYP2D6 mutated alleles and multiplications to routine clinical analysis will enable the PM and UM phenotypes to be predicted and identified at a reasonable cost in a large number of individuals at most locations. | 18,957,039 |
Association of epidermal growth factor receptor (EGFR) gene mutations with EGFR amplification in advanced non-small cell lung cancer. | Somatic mutations in the epidermal growth factor receptor (EGFR) gene are associated with the response to EGFR tyrosine kinase inhibitors in patients with non-small cell lung cancer (NSCLC). Increased EGFR copy number has also been associated with sensitivity to these drugs. However, given that it is often difficult to obtain sufficient amounts of tumor tissue for genetic analysis from patients with advanced NSCLC, the relationship between these two types of EGFR alterations has remained unclear. We have now evaluated EGFR mutation status both by direct sequencing and with a high-sensitivity assay, the Scorpion-amplification-refractory mutation system, and have determined EGFR copy number by fluorescence in situ hybridization (FISH) analysis in paired tumor specimens obtained from 100 consecutive patients with advanced NSCLC treated with chemotherapy. EGFR mutations or FISH positivity (EGFR amplification or high polysomy) were apparent in 18% (18/100) and 32% (32/100) of patients, respectively. The Scorpion-amplification-refractory mutation system was more sensitive than direct sequencing for the detection of EGFR mutations. Furthermore, EGFR mutations were associated with EGFR amplification (P = 0.009) but not with FISH positivity (P = 0.266). Our results therefore suggest the existence of a significant association between EGFR mutation and EGFR amplification in patients with advanced NSCLC. | 18,957,054 |
Novel centrosome protein, TCC52, is a cancer-testis antigen. | A novel centrosome protein, TCC52, was identified as a cancer-testis (CT) antigen. The TCC52 gene was tissue-restricted in normal tissues but highly expressed in lung cancer tissues and some cancer cell lines. Immunoglobulin G antibody specific to TCC52 was detected in serum samples from patients with prostate cancer (59.4%, 69/116), cholangiocarcinoma (17.6%, 6/34), laryngeal cancer (8%, 8/100) and lung cancer (5.6%, 4/71) in patients, rather than from healthy donors. Based on its restricted expression pattern and immunogenicity in some types of tumor, TCC52, as a novel CT antigen, would be a promising candidate for cancer immunotherapy. | 18,957,058 |
Pre-hospital advanced airway management by anaesthesiologists: is there still room for improvement? | Endotracheal intubation is an important part of pre-hospital advanced life support that requires training and experience, and should only be performed by specially trained personnel. In Norway, anaesthesiologists serve as Helicopter Emergency Medical Service HEMS physicians. However, little is known about how they themselves evaluate the quality and safety of pre-hospital advanced airway management. Using a semi-structured questionnaire, we interviewed anaesthesiologists working in the three HEMS programs covering Western Norway. We compared answers from specialists and non-specialists as well as full- and part-time HEMS physicians. Of the 17 available respondents, most (88%) felt that their continuous exposure to intubations was not sufficient. Additional training was mainly acquired through other clinical practice and mannequin- or cadaver-based skills training. Of the respondents, 77% and 35% reported having experienced difficult and failed intubations, respectively. Further, 59% reported knowledge of airway management-related deaths in their HEMS program. Significantly more full- than part-time HEMS physicians had experienced these problems. All respondents had airway back-up equipment in their service, but 29% were not familiar with all the equipment. The majority of anaesthesiologists working as HEMS physicians view pre-hospital advanced airway management as a high-risk procedure. Relevant airway management competencies for HEMS physicians in Norway seem to be insufficiently trained and maintained. A better-defined level of competence with better training methods and systems seems warranted. | 18,957,064 |
Prognostication after out-of-hospital cardiac arrest, a clinical survey. | Numerous parameters and tests have been proposed for outcome prediction in comatose out-of-hospital cardiac arrest survivors. We conducted a survey of clinical practice of prognostication after therapeutic hypothermia (TH) became common practice in Norway. By telephone, we interviewed the consultants who were in charge of the 25 ICUs admitting cardiac patients using 6 structured questions regarding timing, tests used and medical specialties involved in prognostication, as well as the clinical importance of the different parameters used and the application of TH in these patients. Prognostication was conducted within 24-48 hours in the majority (72%) of the participating ICUs.The most commonly applied parameters and tests were a clinical neurological examination (100%), prehospital data (76%), CCT (56%) and EEG (52%). The parameters and tests considered to be of greatest importance for accurate prognostication were prehospital data (56%), neurological examination (52%), and EEG (20%).In 76% of the ICUs, a multidisciplinary approach to prognostication was applied, but only one ICU used a standardised protocol. Therapeutic hypothermia was in routine use in 80% of the surveyed ICUs. Despite the routine use of TH, outcome prediction was performed early and was mainly based on prehospital information, neurological examination and CCT and EEG evaluation. Somatosensory evoked potentials appear to be underused and underrated, while the importance of prehospital data, CCT and EEG to appear to be overrated as methods for making accurate predictions.More evidence-based protocols for prognostication in cardiac arrest survivors, as well as additional studies on the effect of TH on known prognostic parameters are needed. | 18,957,071 |
Neutralizing human monoclonal antibody against H5N1 influenza HA selected from a Fab-phage display library. | Identification of neutralizing antibodies with specificity away from the traditional mutation prone antigenic regions, against the conserved regions of hemagglutinin from H5N1 influenza virus has the potential to provide a therapeutic option which can be developed ahead of time in preparation for a possible pandemic due to H5N1 viruses. In this study, we used a combination of panning strategies against the hemagglutinin (HA) of several antigenic distinct H5N1 isolates to bias selection of Fab-phage from a naïve human library away from the antigenic regions of HA, toward the more conserved portions of the protein. All of the identified Fab clones which showed binding to multiple antigenically distinct HA were converted to fully human IgG, and tested for their ability to neutralize the uptake of H5N1-virus like particles (VLP) into MDCK cells. Five of the antibodies which showed binding to the relatively conserved HA2 subunit of HA, exhibited neutralization of H5N1-VLP uptake in a dose dependant manner. The inhibitory effects of these five antibodies were similar to those observed with a previously described neutralizing antibody specific for the 140s antigenic loop present within HA1 and highlight the exciting possibility that these antibodies may be efficacious against multiple H5N1 strains. | 18,957,074 |
Dual-hemisphere tDCS facilitates greater improvements for healthy subjects' non-dominant hand compared to uni-hemisphere stimulation. | Transcranial direct current stimulation (tDCS) is a non-invasive technique that has been found to modulate the excitability of neurons in the brain. The polarity of the current applied to the scalp determines the effects of tDCS on the underlying tissue: anodal tDCS increases excitability, whereas cathodal tDCS decreases excitability. Research has shown that applying anodal tDCS to the non-dominant motor cortex can improve motor performance for the non-dominant hand, presumably by means of changes in synaptic plasticity between neurons. Our previous studies also suggest that applying cathodal tDCS over the dominant motor cortex can improve performance for the non-dominant hand; this effect may result from modulating inhibitory projections (interhemispheric inhibition) between the motor cortices of the two hemispheres. We hypothesized that stimultaneously applying cathodal tDCS over the dominant motor cortex and anodal tDCS over the non-dominant motor cortex would have a greater effect on finger sequence performance for the non-dominant hand, compared to stimulating only the non-dominant motor cortex. Sixteen right-handed participants underwent three stimulation conditions: 1) dual-hemisphere - with anodal tDCS over the non-dominant motor cortex, and cathodal tDCS over the dominant motor cortex, 2) uni-hemisphere - with anodal tDCS over the non-dominant motor cortex, and 3) sham tDCS. Participants performed a finger-sequencing task with the non-dominant hand before and after each stimulation. The dependent variable was the percentage of change in performance, comparing pre- and post-tDCS scores. A repeated measures ANOVA yielded a significant effect of tDCS condition (F(2,30) = 4.468, p = .037). Post-hoc analyses revealed that dual-hemisphere stimulation improved performance significantly more than both uni-hemisphere (p = .021) and sham stimulation (p = .041). We propose that simultaneously applying cathodal tDCS over the dominant motor cortex and anodal tDCS over the non-dominant motor cortex produced an additive effect, which facilitated motor performance in the non-dominant hand. These findings are relevant to motor skill learning and to research studies of motor recovery after stroke. | 18,957,075 |
NG2 cells response to axonal alteration in the spinal cord white matter in mice with genetic disruption of neurofilament light subunit expression. | Chondroitin sulphate proteoglycan (NG2) expressing cells, morphologically characterized by multi-branched processes and small cell bodies, are the 4th commonest cell population of non-neuronal cell type in the central nervous system (CNS). They can interact with nodes of Ranvier, receive synaptic input, generate action potential and respond to some pathological stimuli, but the function of the cells is still unclear. We assumed the NG2 cells may play an active role in neuropathogenesis and aimed to determine if NG2 cells could sense and response to the alterations in the axonal contents caused by disruption of neurofilament light subunit (NFL) expression. In the early neuropathological development stage, our study showed that the diameter of axons of upper motor neurons of NFL-/- mice decreased significantly while the thickness of their myelin sheath increased remarkably. Although there was an obvious morphological distortion in axons with occasionally partial demyelination, no obvious changes in expression of myelin proteins was detected. Parallel to these changes in the axons and their myelination, the processes of NG2 cells were disconnected from the nodes of Ranvier and extended further, suggesting that these cells in the spinal cord white matter could sense the alteration in axonal contents caused by disruption of NFL expression before astrocytic and microglial activation. The structural configuration determined by the NFL gene may be important for maintenance of normal morphology of myelinated axons. The NG2 cells might serve as an early sensor for the delivery of information from impaired neurons to the local environment. | 18,957,081 |
Spectrum of heart diseases in a new cardiac service in Nigeria: an echocardiographic study of 1441 subjects in Abeokuta. | Echocardiography is a non-invasive, relatively cheap and useful imaging technique for the evaluation of cardiac diseases. The procedure has reliable levels of accuracy. Echocardiography commenced at the Federal medical centre Abeokuta on September 9, 2005.The aim of this study is to report our experience with the procedure, and to define the clinical cases seen in our setting. This is a retrospective analysis of a prospectively collected data. Echocardiography was performed using Aloka SSD 1,100 echocardiograph equipped with 2.5-5.0 MHz transducer During the period of 18 months under review (September 2005-February 2007), 1629 procedures were performed. The reports of 188 echocardiograms were excluded due to poor echo-window, repeated procedure or incomplete report. 1441 reports were reviewed for demographic parameter, indications for the procedure and the main echocardiographic diagnoses.The mean age of the 1441 individuals studied was 54 +/- 14.3 years (15-90). There were 744 men and 697 women. Eight hundred and seventeen subjects (56.7%) had hypertensive heart disease, 53 subjects (3.7%) had rheumatic heart disease while 44(3.0%) had dilated cardiomyopathy. Pericardial diseases, cor-pulmonale, ischaemic heart disease, congenital heart diseases, diabetic heart disease, thyroid heart disease, sickle cell cardiopathy were present in 26(1.8%), 23(1.6%), 9(0.6%), 6(0.4%), 6(0.4%), 6(0.4%), 1(0.1%), and 1(0.1%) respectively. Four hundred and forty nine (31.2%) subjects had normal study. Hypertensive heart disease was found to be the most prevalent cardiac condition in this study. The relatively frequent diagnoses of rheumatic heart disease, cardiomyopathies and pericardial diseases reflect the impact of infections and infestations on the cardiovascular health of adult Nigerians.We suggest that prevention and treatment of cardiac diseases in our setting should among other things focus on blood pressure control and early treatment of infections causing heart diseases. | 18,957,102 |
Severe maternal morbidity (near miss) as a sentinel event of maternal death. An attempt to use routine data for surveillance. | To identify all the records within the Brazilian Hospital Information System (HIS) that contained information suggestive of severe maternal morbidity (near miss); to describe the diagnoses and procedures used; to identify variables associated with maternal death. A descriptive population study with data from the HIS and Mortality Information System (MIS) files of records of women during pregnancy, delivery and in the postpartum period in all the capital cities of the Brazilian states in 2002. Initially, records of women between 10 and 49 years of age were selected; next, those records with at least one criterion suggestive of near miss were selected. For the linkage of HIS with MIS and HIS with itself, a blocking strategy consisting of three independent steps was established. In the data analysis, near miss ratios were calculated with corresponding 95% confidence interval and the diagnoses and procedures were described; a multiple logistic regression model was adjusted. Primary and secondary diagnoses and the requested and performed procedures during hospitalization were the main outcome measures. The overall maternal near miss ratio was 44.3/1,000 live births. Among the records indicating near miss, 154 maternal deaths were identified. The criteria of severity most frequently found were infection, preeclampsia and hemorrhage. Logistic regression analysis resulted in 12 variables, including four significant interactions. Although some limitations, the perspective of routinely using this information system for surveillance of near miss and implementing measures to avoid maternal death is promising. | 18,957,110 |
Giant fibrovascular polyp of the oesophagus: a case report and review of the literature. | We present a case of fibrovascular polyp, a rare submucosal tumour of the oesophagus that has been reported only sporadically in the literature. The biapproach for surgical removal of fibrovascular polyp has only been mentioned once in the literature. A 65-year-old Greek man presented with a 9-month history of gradually progressive intermittent dysphagia. Radiologic work-up with oesophagogram and computed tomography revealed a large, sausage-shaped intraluminal polyp extending from the level of the cervical oesophagus to the level of the upper body of the stomach. The diagnosis of giant fibrovascular polyp was made radiographically and confirmed by endoscopic biopsy. The polyp was removed using a biapproach surgical technique: pharyngotomy and subsequent gastrostomy. Fibrovascular polyp is a rare submucosal tumour. Proper treatment depends on accurate assessment of the origin, size, and vascularity of the pedicle and the size of the tumour. Choice of the appropriate surgical approach depends on the correct diagnosis, which can usually be indicated radiographically by the presence of a smooth, sausage-shaped defect with a discrete bulbous tip. | 18,957,112 |
Careers in ecstasy use: do ecstasy users cease of their own accord? Implications for intervention development. | Ecstasy (MDMA, 3, 4-methylenodioxymethamphetamine) use is widespread in the Netherlands, with a lifetime prevalence of 4.3%, and two-thirds of dance party visitors being ecstasy users. However, research into Dutch ecstasy use patterns is lacking. In addition, recent studies suggest that ecstasy users cease their use automatically, which implies that interventions would do better to better focus on the promotion of harm reduction strategies than on inducing cessation. The current study addresses this process of ecstasy cessation. 32 participants from the Dutch dance scene were interviewed, and the results were systematically analysed using NVivo. Most ecstasy users had started to use out of curiosity. During use, users applied a host of harm reduction strategies, albeit inconsistently and sometimes incorrectly. Most users appeared to cease ecstasy use automatically because of loss of interest or changing life circumstances (e.g. a new job or relationship). It appears that cessation of ecstasy use is largely determined by environmental variables and not by health concerns. This supports the idea that health promotion resources are better spent in trying to promote consistent and correct application of harm reduction practices than in trying to induce cessation. | 18,957,117 |
MetaMine--a tool to detect and analyse gene patterns in their environmental context. | Modern sequencing technologies allow rapid sequencing and bioinformatic analysis of genomes and metagenomes. With every new sequencing project a vast number of new proteins become available with many genes remaining functionally unclassified based on evidences from sequence similarities alone. Extending similarity searches with gene pattern approaches, defined as genes sharing a distinct genomic neighbourhood, have shown to significantly improve the number of functional assignments. Further functional evidences can be gained by correlating these gene patterns with prevailing environmental parameters. MetaMine was developed to approach the large pool of unclassified proteins by searching for recurrent gene patterns across habitats based on key genes. MetaMine is an interactive data mining tool which enables the detection of gene patterns in an environmental context. The gene pattern search starts with a user defined environmentally interesting key gene. With this gene a BLAST search is carried out against the Microbial Ecological Genomics DataBase (MEGDB) containing marine genomic and metagenomic sequences. This is followed by the determination of all neighbouring genes within a given distance and a search for functionally equivalent genes. In the final step a set of common genes present in a defined number of distinct genomes is determined. The gene patterns found are associated with their individual pattern instances describing gene order and directions. They are presented together with information about the sample and the habitat. MetaMine is implemented in Java and provided as a client/server application with a user-friendly graphical user interface. The system was evaluated with environmentally relevant genes related to the methane-cycle and carbon monoxide oxidation. MetaMine offers a targeted, semi-automatic search for gene patterns based on expert input. The graphical user interface of MetaMine provides a user-friendly overview of the computed gene patterns for further inspection in an ecological context. Prevailing biological processes associated with a key gene can be used to infer new annotations and shape hypotheses to guide further analyses. The use-cases demonstrate that meaningful gene patterns can be quickly detected using MetaMine.MetaMine is freely available for academic use from http://www.megx.net/metamine. | 18,957,118 |
Practice of noninvasive ventilation for cystic fibrosis: a nationwide survey in France. | No guidelines are available for noninvasive ventilation (NIV) for cystic fibrosis (CF). To survey and evaluate the use of NIV for CF in France. We surveyed the coordinator physicians of every accredited CF center in France. The respondents represented 36 centers (15 pediatric centers, 13 adult centers, and 8 centers that see both pediatric and adult patients), which had a total of 4,416 patients with CF at the time of the study, 168 (3.8%) of whom were using NIV. NIV was being used more often in the adults centers (7.6% of these patients) than in the pediatric centers (1.2% of these patients) or adult-and-pediatric centers (4.1% of these patients) (P= .01). All the respondent centers use NIV as first-line treatment for severe hypercapnic respiratory exacerbation and for stable diurnal hypercapnia, especially when associated with sleep disturbance. Bi-level pressure-targeted ventilation is the preferred ventilation mode. Settings are adjusted based on arterial blood gas values, noninvasive evaluation of patient-ventilator synchrony, patient comfort, and sometimes a sleep study. The surveyed centers reported a number of expected benefits from NIV, but few of those benefits have been proven. Problems with NIV are common and limit its use. We found a relative homogeneity in these French centers' stated indications for and use of NIV, which highlights their numerous expectations about the benefits of NIV, which contrasts with the few validated benefits. Studies of the benefits of NIV are needed. | 18,957,151 |
Effect of pH and water-soluble polymers on the aqueous solubility of nimesulide in the absence and presence of beta-cyclodextrin derivatives. | The aqueous solubility of nimesulide in the absence and presence of beta-cyclodextrin (beta-CD) and its alkyl derivatives hydroxypropyl-beta-CD and methyl-beta-CD was studied. We also investigated the effect of water-soluble polymers, hydroxypropylmethyl-cellulose, sodium-carboxymethyl-cellulose, polyvinylpyrrolidone and polyethyleneglycol on the solubilization efficacy and complexation ability of cyclodextrins with nimesulide. The solubility of nimesulide in the absence and presence of cyclodextrins and polymers was studied using a phase solubility technique combined with a spectrophotometric method. The study was carried out at 25 degrees C and pH values of 6.0 and 7.0. Conditions in terms of polymer concentration and polymer heating with and without sonication were optimized. Values of the solubility enhancement factor of nimesulide in the presence of each cyclodextrin and in the absence and presence of each polymer were determined and the formation constants, K, of the inclusion complexes formed calculated. beta-CDs increased the aqueous solubility of nimesulide in the following order: methyl-beta-CD > beta-CD > hydroxypropyl-beta-CD. Addition of hydroxypropylmethyl-cellulose at a concentration of 0.1% (w/v) had the greatest influence on complexation of all three beta-CDs with nimesulide, while preheating of the polymer at 70 degrees C under sonication resulted in an additional two-fold increase in the aqueous solubility of the drug. Sodium-carboxymethyl-cellulose, polyvinylpyrrolidone and polyethyleneglycol had minor effects on the aqueous solubility of nimesulide. Thus beta-CD, hydroxypropyl-beta-CD and methyl-beta-CD are proposed as good solubilizing agents for nimesulide in the presence and absence of hydroxypropylmethyl-cellulose in order to enhance its oral bioavailability. | 18,957,163 |
Pharmacological and local toxicity studies of a liposomal formulation for the novel local anaesthetic ropivacaine. | This study reports an investigation of the pharmacological activity, cytotoxicity and local effects of a liposomal formulation of the novel local anaesthetic ropivacaine (RVC) compared with its plain solution. RVC was encapsulated into large unilamellar vesicles (LUVs) composed of egg phosphatidylcholine, cholesterol and alpha-tocopherol (4:3:0.07, mole %). Particle size, partition coefficient determination and in-vitro release studies were used to characterize the encapsulation process. Cytotoxicity was evaluated by the tetrazolium reduction test using sciatic nerve Schwann cells in culture. Local anaesthetic activity was assessed by mouse sciatic and rat infraorbital nerve blockades. Histological analysis was performed to verify the myotoxic effects evoked by RVC formulations. Plain (RVC(PLAIN)) and liposomal RVC (RVC(LUV)) samples were tested at 0.125%, 0.25% and 0.5% concentrations. Vesicle size distribution showed liposomal populations of 370 and 130 nm (85 and 15%, respectively), without changes after RVC encapsulation. The partition coefficient value was 132 +/- 26 and in-vitro release assays revealed a decrease in RVC release rate (1.5 fold, P < 0.001) from liposomes. RVC(LUV) presented reduced cytotoxicity (P < 0.001) when compared with RVC(PLAIN). Treatment with RVC(LUV) increased the duration (P < 0.001) and intensity of the analgesic effects either on sciatic nerve blockade (1.4-1.6 fold) and infraorbital nerve blockade tests (1.5 fold), in relation to RVC(PLAIN). Regarding histological analysis, no morphological tissue changes were detected in the area of injection and sparse inflammatory cells were observed in only one of the animals treated with RVC(PLAIN) or RVC(luv) at 0.5%. Despite the differences between these preclinical studies and clinical conditions, we suggest RVC(LUV) as a potential new formulation, since RVC is a new and safe local anaesthetic agent. | 18,957,165 |
Design and synthesis of new symmetrical derivatives of dihydropyridine containing a pyridyl group on the 3, 5-positions and evaluation of their cytotoxic and multidrug resistance reversal activity. | Today, chemotherapy is an important part in the treatment of several kinds of cancer; however, the development of drug resistance remains one of the major obstacles in successful chemotherapy. Several types of agents have been recognized as multidrug resistance (MDR) inhibitors, among which the 1,4-dihydropyridines (DHPs) have been investigated the most. P-glycoprotein inhibition has been reported as the main MDR reversal mechanism of DHPs, whilst other mechanisms such as inhibition of topoisomerase II have received less attention. Therefore, in this study new derivatives of DHP have been synthesized. Their cytotoxic activity and their effects in reversing atypical MDR have been evaluated. The results confirmed the appropriate effect of these compounds on atypical MDR. Although it was observed that these compounds had a moderate cytotoxic effect, the cytotoxicity of one compound on the K562 cell line (IC50 = 6.61 microM) was comparable with that of doxorubicin (IC50 = 4.17 microM). Finally, the Ca(2+)-channel antagonistic activity, an undesired effect for these compounds, was evaluated. | 18,957,169 |
HIV-associated neurocognitive disorders and the impact of combination antiretroviral therapies. | HIV-associated neurocognitive disorders (HAND) are the most common preventable and treatable cause of dementia. While the incidence of the most severe form of HAND, HIV-associated dementia, has decreased since the introduction of combination antiretroviral therapy (cART), the prevalence of less severe forms of HAND has continued to rise. HAND leads to a subcortical dementia consisting of a triad of cognitive, behavior, and motor dysfunction. No single laboratory test can establish HAND, but ancillary studies including neuropsychological testing, neuroimaging studies, and cerebrospinal fluid (CSF) analysis are useful for supporting or refuting the diagnosis. More recent evidence has suggested that higher central nervous system-penetrating cART may lead to greater suppression of CSF HIV viral loads and improved cognition. Because viral control generally has been successful without eliminating cognitive dysfunction, further clinical studies that assess adjunctive neuroprotective drugs are likely to be required. | 18,957,181 |
Nuclear roadblocks for mRNA export. | The THO complex and Sub2 RNA helicase have been shown to function in both transcription and mRNA processing. Rougemaille et al. (2008) now uncover evidence that THO/Sub2 coordinates mRNA processing and nuclear export. | 18,957,194 |
Kinetochores and microtubules wed without a ring. | Proper chromosome segregation in mitosis requires tethering of spindle microtubules to the kinetochore. Using electron tomography of mammalian cells, McIntosh et al. (2008) now report the presence of fibrils that connect the inner kinetochore to the curved protofilaments at microtubule ends, suggesting a new model for force generation in chromosome movement. | 18,957,196 |
Nature, nurture, or chance: stochastic gene expression and its consequences. | Gene expression is a fundamentally stochastic process, with randomness in transcription and translation leading to cell-to-cell variations in mRNA and protein levels. This variation appears in organisms ranging from microbes to metazoans, and its characteristics depend both on the biophysical parameters governing gene expression and on gene network structure. Stochastic gene expression has important consequences for cellular function, being beneficial in some contexts and harmful in others. These situations include the stress response, metabolism, development, the cell cycle, circadian rhythms, and aging. | 18,957,198 |
The hippocampus and dopaminergic midbrain: old couple, new insights. | Humans have a natural ability to gain new insights by generalizing from previous experience. In this issue of Neuron, Shohamy and Wagner reveal how generalizations naturally emerge during associative learning through a partnership between putatively dopaminergic circuitry in the midbrain and the hippocampus. | 18,957,213 |
Interaction between Reelin and Notch signaling regulates neuronal migration in the cerebral cortex. | Neuronal migration is a fundamental component of brain development whose failure is associated with various neurological and psychiatric disorders. Reelin is essential for the stereotypical inside-out sequential lamination of the neocortex, but the molecular mechanisms of its action still remain unclear. Here we show that regulation of Notch activity plays an important part in Reelin-signal-dependent neuronal migration. We found that Reelin-deficient mice have reduced levels of the cleaved form of Notch intracellular domain (Notch ICD) and that loss of Notch signaling in migrating neurons results in migration and morphology defects. Further, overexpression of Notch ICD mitigates the laminar and morphological abnormalities of migrating neurons in Reeler. Finally, our in vitro biochemical studies show that Reelin signaling inhibits Notch ICD degradation via Dab1. Together, our results indicate that neuronal migration in the developing cerebral cortex requires a Reelin-Notch interaction. | 18,957,219 |
Human cortex: reflections of mirror neurons. | Claims to have identified mirror neurons in human cortex have been controversial. A recent study has applied an fMRI adaptation protocol to the problem and come up with novel evidence for the existence of movement-selective mirror neurons in human cortex. | 18,957,251 |
Association between individual differences in self-reported emotional resilience and the affective perception of neutral faces. | Resilience, i.e., the ability to cope with stress and adversity, relies heavily on judging adaptively complex situations. Judging facial emotions is a complex process of daily living that is important for evaluating the affective context of uncertain situations, which could be related to the individual's level of resilience. We used a novel experimental paradigm to test the hypothesis that highly resilient individuals show a judgment bias towards positive emotions. 65 non-treatment seeking subjects completed a forced emotional choice task when presented with neutral faces and faces morphed to display a range of emotional intensities across sadness, fear, and happiness. Overall, neutral faces were judged more often to be sad or fearful than happy. Furthermore, high compared to low resilient individuals showed a bias towards happiness, particularly when judging neutral faces. This is a cross-sectional study with a non-clinical sample. These results support the hypothesis that resilient individuals show a bias towards positive emotions when faced with uncertain emotional expressions. This capacity may contribute to their ability to better cope with certain types of difficult situations, especially those that are interpersonal in nature. | 18,957,273 |
Methyltransferase-inhibition interferes with neuronal differentiation of P19 embryonal carcinoma cells. | We have analyzed the importance of substrate methylation by S-adenosylmethionine-dependent methyltransferases for neuronal differentiation of P19 embryonal carcinoma cells. We show that treatment of cells with methyltransferase inhibitor adenosine dialdehyde (AdOx) interferes with neuronal differentiation. Retinoic acid (RA) and AdOx co-treated cells had a decreased number of neurites and a flattened morphology compared with cells differentiated by RA. Also, the amount of neuronal class III tubulin (Tuj1) decreased from 76% to 9.6% with AdOx-treatment. Gene expression levels of wnt-1, brn-2, neuroD, and mash-1 were also down-regulated by AdOx-treatment. But AdOx-treatment did not up-regulate BMP-4 and GFAP genes. Treatment of RA decreased E-cadherin expression during neuronal differentiation. However, in AdOx/RA co-treated cells, E-cadherin expression was restored to the control level. Also, mRNA expression of N-cadherin decreased with AdOx-treatment. Taken together, these data show that methylation reactions might influence the cell-fate decision and neuronal differentiation of P19 cells. | 18,957,285 |
Source of the elevation Ca2+ evoked by 15-HETE in pulmonary arterial myocytes. | We have previously reported that 15-hydroxyeicosatetraenoic acid (15-HETE), a metabolite of arachidonic acid by 15-lipoxygenase, causes pulmonary vasoconstriction via increasing the intracellular Ca(2+) concentration ([Ca(2+)]i). However, the multiple sources of Ca(2+) that contribute to Ca(2+) elevation during and after 15-HETE exposure have not been investigated. In the present study, pulmonary arterial ring technique and confocal laser scanning microscope were used to investigate the origin of Ca(2+). 15-HETE (1 microM) elicited an increase in [Ca(2+)]i in pulmonary artery smooth muscle cells in a time-dependent manner under both normal and hypoxic condition. The increases were composed of an initial rapid rise followed by a slow increase in the present of extracellular Ca(2+). The initial rapid phase was attenuated by inositol 1,4,5-triphosphate (IP(3)) receptor antagonist 2-aminoethoxydiphenyl borate (2-APB) and ryanodine receptor-operated Ca(2+) store depletion agent caffeine; the slow increasing phase and the constriction of pulmonary arterial ring were significantly inhibited by voltage-operated Ca(2+) channel blocker nifedipine or transient receptor potential canonical (TRPC) channel blocker La(3+), and almost completely diminished in Ca(2+)-free external solution, suggesting that the initial phase depends on intracellular Ca(2+) store and the second phase relies on extracellular Ca(2+). Interestingly, the effect of caffeine and La(3+) but not nifedipine were diminished in the present of 2-APB. Thus, these results suggest that 15-HETE mobilizes Ca(2+) signaling through: 1) Ca(2+) release immediately from Ca(2+) stores via activation of IP(3) receptor and, subsequently that of ryanodine receptor, 2) the depletion of Ca(2+) through CCE leading to the activation of TRPC, and 3) Ca(2+) entry through L-type Ca(2+) channels. | 18,957,290 |
Knockout of spinophilin, an endogenous antagonist of arrestin-dependent alpha2-adrenoceptor functions, enhances receptor-mediated antinociception yet does not eliminate sex-related differences. | We have previously shown gonadal steroid-dependent, gender specific modulation of nociception by alpha(2)-adrenoceptors. Agonist activation of the receptor enhances its association with spinophilin that antagonizes arrestin functions both by diminishing receptor phosphorylation by G-protein-coupled receptor kinase 2 (GRK2) and by competing for receptor interactions with arrestin. Since spinophilin is highly enriched in dendritic spines, we investigated whether alpha(2)-adrenoceptor-induced antinociception as well as sex-related differences are modified in spinophilin knockout mice. We evaluated alpha(2)-adrenoceptor antinociception in a heat-evoked tail flick test in spinophilin wild type (Sp(+/+)) and knockout (Sp(-/-)) mice. Baseline tail flick latencies (TFLs) did not change between any groups. Interestingly, the alpha(2)-adrenoceptor agonist, clonidine, increased TFL in male and diestrous (low estrogen) Sp(-/-) as well as Sp(+/+) mice; in fact, this increase in TFL was significantly higher in Sp(-/-) male and diestrous groups than in their Sp(+/+) counterparts. This unexpected finding is consistent with enhanced alpha(2)-adrenoceptor-mediated sedation observed previously in Sp(-/-) mice, presumably due to accelerated endocytosis of desensitized receptors and recycling of refreshed receptors when arrestin is not competed for by spinophilin in Sp(-/-) mice. Despite modulation of alpha(2)-adrenoceptor effects in Sp(-/-) mice, sex-related differences were retained; thus, clonidine was ineffective in proestrous females (highest estrogen levels), in both Sp(-/-) and Sp(+/+) mice, reaffirming that estrogen suppresses alpha(2)-adrenoceptor-evoked antinociception. These findings show that elimination of spinophilin enhances alpha(2)-adrenoceptor-evoked antinociception in estrogen-deprived physiological settings, suggesting a role for spinophilin to suppress these effects, and yet this enhanced response cannot overcome the absence of antinociception with elevated estrogen levels. | 18,957,308 |
Evaluation of candidate reference genes in Q-PCR studies of Atlantic cod (Gadus morhua) ontogeny, with emphasis on the gastrointestinal tract. | To obtain reliable relative qPCR data in developing fish larvae, stable reference genes have to be found. This study is focused on finding good candidates for normalization of qPCR data for ontogenetic studies of Atlantic cod. Ten commonly used reference genes; Acidic ribosomal protein, Actin-related protein 2, beta-actin, Elongation factor 1 A, Glyceraldehyde-3-phosphate dehydrogenase, Ribosomal protein 37, Ribosomal protein 4, Ribosomal protein S9, beta 2-Tubulin and Ubiquitin were analyzed in developing larvae from 3 to 97 day post hatch (DPH). Two different tools were used to evaluate the stabilities of these genes; the geNorm software ranks the most stable genes based on a pair-wise analysis whereas NormFinder uses a model-based approach. The same genes were also analyzed in GI tract homogenates and compared to whole larvae homogenates. During Atlantic cod larval development there are several strong candidates with Ubiquitin as the most stable. The ribosomal proteins RPL4 and RPS9 are also strong candidates. RPL37 may be used but only when normalizing qRT-PCR results from one type of tissue. We also suggest the use of multiple genes for normalization of qRT-PCR. Our study suggests that whole-larvae samples can be used to study relative expression of genes that are expressed only in certain tissues. | 18,957,329 |
First population study of the general public awareness and perception of epilepsy in Bosnia and Herzegovina. | Public knowledge of, perception of, and attitudes toward epilepsy in Bosnia and Herzegovina (BH) were studied for the first time. One thousand randomly selected adults were asked 12 questions about epilepsy. Ninety-one percent (91%) of respondents had heard about epilepsy, 41% knew someone with epilepsy, 32.5% had witnessed a seizure, and 33.1% did not know any of the symptoms of epilepsy. On average, interviewees were ready to accept a person with epilepsy. Approximately 15% would object if their child played with a child with epilepsy, and 39% believed that a child with epilepsy could not succeed as well as a child without epilepsy. Although 55.9% would approach a person experiencing a seizure and help, 25.9% would call "911." Positive attitudes correlated with knowing someone with epilepsy and/or witnessing a seizure. General awareness of and attitudes toward epilepsy in BH approach those of developed countries. These results are somewhat more favorable than expected and an encouraging foundation for a necessary public health awareness campaign. | 18,957,332 |
Unravelling the nuclear matrix proteome. | The nuclear matrix (NM) model posits the presence of a protein/RNA scaffold that spans the mammalian nucleus. The NM proteins are involved in basic nuclear function and are a promising source of protein biomarkers for cancer. Importantly, the NM proteome is operationally defined as the proteins from cells and tissue that are extracted following a specific biochemical protocol; in brief, the soluble proteins and lipids, cytoskeleton, and chromatin elements are removed in a sequential fashion, leaving behind the proteins that compose the NM. So far, the NM has not been sufficiently verified as a biological entity and only preliminary at the molecular level. Here, we argue for a combined effort of proteomics, immunodetection and microscopy to unravel the composition and structure of the NM. | 18,957,335 |
Crucial cytokine interactions in nitric oxide production induced by Mycoplasma arthritidis superantigen. | Mycoplasma arthritidis causes autoimmune arthritis in rodents. It produces a superantigen (MAM) that simultaneously activates antigen presenting cells and T cells inducing nitric oxide and cytokine release. Nitric oxide is a key inducer and regulator of the immune system activation. Here, we investigated nitric oxide and cytokine production and interactions of these molecules in MAM-stimulated co-cultures of macrophages (J774A.1 cell line) with spleen lymphocytes. We found that: a) MAM-induced nitric oxide, interferon-gamma, membrane-associated tumor necrosis factor and interleukin-2 production in co-cultures of macrophages with lymphocytes from BALB/c and C3H/HePas but not from C57Bl/6 mice; b) production of nitric oxide was dependent on interferon-gamma whereas that of interferon-gamma was dependent on interleukin-2 and membrane-associated tumor necrosis factor; c) these cytokines up regulated MAM-induced nitric oxide production. Unraveling the mechanisms of cell activation induced by MAM might be helpful to design strategies to prevent immune system activation by superantigens and therefore in seeking amelioration of associated immunopathologies. | 18,957,330 |
[Fruit of the emergence of an enterovirus: acute haemorrhagic conjunctivitis]. | First seen in Ghana and Indonesia in the early 70's, acute haemorrhagic conjunctivitis or "Apollo 11" disease is an eye infection caused by Enterovirus type 70 (EV70). The disease appeared to be a highly contagious conjunctivitis which spread rapidly all over the world. EV70 has been considered as an emerging virus and was classified as a new Enterovirus. No human or animal virus genetically similar to EV70 was known before the sudden outcome of the disease in Ghana, West Africa. EV70 appeared as a pretty demonstrative example of virus emergence and virus spreading. Studies of virus genetic mutations emphasized the variations of RNA virus within a short time period. The current review presents the EV70 infection and the genetic profile of the virus from its emergence to nowadays. | 18,957,336 |
[CSF: diagnosis of neurosyphilis in a patient hospitalized for an acute brain stroke]. | We report the case of a sixty-eight years old patient, who was admitted to the emergency for paresthesis associated with dysarthra and speech complaints. Neuroimaging revealed the presence of stenosis caused by arteritis. The notion of history of syphilis infection led to diagnosis of neurosyphilis. Diagnosis is difficult due to its clinical polymorphism and requires using several tests in the cerebrospinal fluid (CSF) because infection involving the central nervous system. Neurosyphilis is diagnosed by finding elevated cell count (80 leukocytes/mm3), high protein level (1.07 g/L) and positive IgG oligoclonal bands. In addition CSF and blood should be titrated with the VDRL and TPHA tests which are difficult to interpret. The diagnosis of active neuro-syphilis requires positive, non specific and specific inflammatory tests. | 18,957,346 |
[Meningoencephalitis due to community Klebsiella pneumoniae in an adult immunocompetent: a case report]. | We report the first Moroccan case of community-acquired meningoencephalitis due to Klebsiella pneumoniae in an adult immunocompetent without medical history, complicated of cerebral vasculitis and right endophthalmitis. K. pneumoniae is exceptionally responsible for meningitis community in the world excepted in some countries of Southeast Asia. It usually occurs on fragile field and is associated with high mortality. The early management of the patient, the immunocompetent field and the wild phenotype of the isolated strain probably allowed to get a medical cure with some sequelae. | 18,957,347 |
Testing the island rule: primates as a case study. | The island rule states that after island colonization, larger animals tend to evolve reduced body sizes and smaller animals increased sizes. Recently, there has been disagreement about how often, if ever, this rule applies in nature, and much of this disagreement stems from differences in the statistical tests employed. This study shows, how different tests of the island rule assume different null hypotheses, and that these rely on quite different biological assumptions. Analysis and simulation are then used to quantify the biases in the tests. Many widely used tests are shown to yield false support for the island rule when island and mainland evolution are indistinguishable, and so a Monte Carlo permutation test is introduced that avoids this problem. It is further shown that tests based on independent contrasts lack power to detect the island rule under certain conditions. Finally, a complete reanalysis is presented of recent data from primates. When head-body length is used as the measure of body size, reports of the island rule are shown to stem from methodological artefacts. But when skull length or body mass are used, all tests agree that the island rule does hold in primates. | 18,957,368 |
The structure of the Na+,K+-ATPase and mapping of isoform differences and disease-related mutations. | The Na+,K+-ATPase transforms the energy of ATP to the maintenance of steep electrochemical gradients for sodium and potassium across the plasma membrane. This activity is tissue specific, in particular due to variations in the expressions of the alpha subunit isoforms one through four. Several mutations in alpha2 and 3 have been identified that link the specific function of the Na+,K+-ATPase to the pathophysiology of neurological diseases such as rapid-onset dystonia parkinsonism and familial hemiplegic migraine type 2. We show a mapping of the isoform differences and the disease-related mutations on the recently determined crystal structure of the pig renal Na+,K+-ATPase and a structural comparison to Ca2+-ATPase. Furthermore, we present new experimental data that address the role of a stretch of three conserved arginines near the C-terminus of the alpha subunit (Arg1003-Arg1005). | 18,957,371 |
Review. ATP hydrolysis-driven gating in cystic fibrosis transmembrane conductance regulator. | Proteins belonging to the ATP-binding cassette superfamily couple ATP binding and hydrolysis at conserved nucleotide-binding domains (NBDs) to diverse cellular functions. Most superfamily members are transporters, while cystic fibrosis transmembrane conductance regulator (CFTR), alone, is an ion channel. Despite this functional difference, recent results have suggested that CFTR shares a common molecular mechanism with other members. ATP binds to partial binding sites on the surface of the two NBDs, which then associate to form a NBD dimer, with complete composite catalytic sites now buried at the interface. ATP hydrolysis and gamma-phosphate dissociation, with the loss of molecular contacts linking the two sides of the composite site, trigger dimer dissociation. The conformational signals generated by NBD dimer formation and dissociation are transmitted to the transmembrane domains where, in transporters, they drive the cycle of conformational changes that translocate the substrate across the membrane; in CFTR, they result in opening and closing (gating) of the ion-permeation pathway. | 18,957,373 |
Review. The mammalian proton-coupled peptide cotransporter PepT1: sitting on the transporter-channel fence? | The proton-coupled di- and tripeptide transporter PepT1 (SLC15a1) is the major route by which dietary nitrogen is taken up from the small intestine, as well as being the route of entry for important therapeutic (pro)drugs such as the beta-lactam antibiotics, angiotensin-converting enzyme inhibitors and antiviral and anti-cancer agents. PepT1 is a member of the major facilitator superfamily of 12 transmembrane domain transporter proteins. Expression studies in Xenopus laevis on rabbit PepT1 that had undergone site-directed mutagenesis of a conserved arginine residue (arginine282 in transmembrane domain 7) to a glutamate revealed that this residue played a role in the coupling of proton and peptide transport and prevented the movement of non-coupled ions during the transporter cycle. Mutations of arginine282 to other non-positive residues did not uncouple proton-peptide cotransport, but did allow additional ion movements when substrate was added. By contrast, mutations to positive residues appeared to function the same as wild-type. These findings are discussed in relation to the functional role that arginine282 may play in the way PepT1 operates, together with structural information from the homology model of PepT1 based on the Escherichia coli lactose permease crystal structure. | 18,957,377 |
Early expression of monocyte chemoattractant protein-1 correlates with the onset of isoproterenol-induced cardiac fibrosis in rats with distinct angiotensin-converting enzyme polymorphism. | Isoproterenol treatment of Brown Norway and Lewis rats (high and low plasma angiotensin-I-converting enzyme activity, respectively) results in similar cardiac hypertrophy but higher cardiac fibrosis in Brown Norway rats. Rats were infused in vivo with isoproterenol for two or 10 days. Cardiac fibrosis and inflammation were evaluated histochemically. We measured the mRNAs of pro-fibrotic factors (transforming growth factor beta(1), endothelin-1) and pro-inflammatory factors (monocyte chemoattractant protein-1). In studies with cardiac fibroblasts incubated with isoproterenol in vitro , we measured cell proliferation, angiotensin-I-converting enzyme and matrix metalloprotease 2 activities and deposition of collagen type I and fibronectin. After treatment with isoproterenol for two days, there were large areas of myocardial injury and numerous inflammatory foci in the left ventricle, these being greater in Brown-Norway than in Lewis rats. After treatment with isoproterenol for 10 days, there were large areas of damage with extensive collagen deposition only in the left ventricle; both strains exhibited this damage which was, however, more severe in Brown-Norway than in Lewis rats. After treatment with isoproterenol for two, but not 10, days, greater amounts of monocyte chemoattractant protein-1 mRNA were found in Brown Norway than in Lewis rats. Cell proliferation, activities of angiotensin-I-converting enzyme and matrix metalloprotease 2, amounts of collagen type I and fibronectin were similar in cardiac fibroblasts from both strains; changes after isoproterenol (10 microM) were also similar in both strains. We conclude that the greater cardiac fibrosis in Brown Norway rats treated with isoproterenol correlates with the early and higher expression of proinflammatory factors. | 18,957,386 |
Rexinoid-induced expression of IGFBP-6 requires RARbeta-dependent permissive cooperation of retinoid receptors and AP-1. | The synthetic rexinoid bexarotene (Targretin, LGD1069) inhibits the formation of both estrogen receptor-negative and estrogen receptor-positive breast cancer in preclinical models and controls the expression of growth-regulatory biomarkers, such as IGFBP-6 (insulin-like growth factor-binding protein 6), RARbeta, or cyclin D1. In this study, we identified a classical retinoic acid-responsive element in the first intron in the IGFBP-6 gene adjacent to a consensus AP-1 binding site, both elements essential for rexinoid-induced expression of IGFBP-6. In chromatin binding experiments, bexarotene increased the occupancy of the identified enhancer element by RXRalpha, RARbeta, cJun, cFos, and p300. In normal mammary epithelial cells and T47D breast cancer cells, small interfering RNA-mediated knockdown of all RXR isoforms or RARbeta, but not RARalpha or RARgamma alone, blocked the induction of IGFBP-6 by bexarotene. Simultaneous knockdown of RARalpha and RARgamma abrogated both the induction of RARbeta and the up-regulation and secretion of IGFBP-6. The suppression of either RARbeta or cJun by small interfering RNA blocked the recruitment of RXRalpha and cJun to the enhancer. These results demonstrate a novel cooperative interaction between retinoid receptors and AP-1 orchestrated by RARbeta and highlight a novel mechanism by which RARbeta can mediate the cancer-preventive effects of rexinoids. | 18,957,410 |
The essential cytosolic iron-sulfur protein Nbp35 acts without Cfd1 partner in the green lineage. | In photosynthetic eukaryotes assembly components of iron-sulfur (Fe-S) cofactors have been studied in plastids and mitochondria, but how cytosolic and nuclear Fe-S cluster proteins are assembled is not known. We have characterized a plant P loop NTPase with sequence similarity to Nbp35 of yeast and mammals, a protein of the cytosolic Cfd1-Nbp35 complex mediating Fe-S cluster assembly. Genome analysis revealed that NBP35 is conserved in the green lineage but that CFD1 is absent. Moreover, plant and algal NBP35 proteins lack the characteristic CXXC motif in the C terminus, thought to be required for Fe-S cluster binding. Nevertheless, chemical reconstitution and spectroscopy showed that Arabidopsis (At) NBP35 bound a [4Fe-4S] cluster in the C terminus as well as a stable [4Fe-4S] cluster in the N terminus. Holo-AtNBP35 was able to transfer an Fe-S cluster to an apoprotein in vitro. When expressed in yeast, AtNBP35 bound 55Fe dependent on the cysteine desulfurase Nfs1 and was able to partially rescue the growth of a cfd1 mutant but not of an nbp35 mutant. The AtNBP35 gene is constitutively expressed in planta, and its disruption was associated with an arrest of embryo development. These results show that despite considerable divergence from the yeast Cfd1-Nbp35 Fe-S scaffold complex, AtNBP35 has retained similar Fe-S cluster binding and transfer properties and performs an essential function. | 18,957,412 |
tRNAdb 2009: compilation of tRNA sequences and tRNA genes. | One of the first specialized collections of nucleic acid sequences in life sciences was the 'compilation of tRNA sequences and sequences of tRNA genes' (http://www.trna.uni-bayreuth.de). Here, an updated and completely restructured version of this compilation is presented (http://trnadb.bioinf.uni-leipzig.de). The new database, tRNAdb, is hosted and maintained in cooperation between the universities of Leipzig, Marburg, and Strasbourg. Reimplemented as a relational database, tRNAdb will be updated periodically and is searchable in a highly flexible and user-friendly way. Currently, it contains more than 12 000 tRNA genes, classified into families according to amino acid specificity. Furthermore, the implementation of the NCBI taxonomy tree facilitates phylogeny-related queries. The database provides various services including graphical representations of tRNA secondary structures, a customizable output of aligned or un-aligned sequences with a variety of individual and combinable search criteria, as well as the construction of consensus sequences for any selected set of tRNAs. | 18,957,446 |
Increased prevalence of white matter hyperintensities in patients with panic disorder. | The aim of the current study is to compare the prevalence, severity and location of cerebral white matter hyperintensities (WMH) between patients with panic disorder (PD) and healthy control subjects. Patients with PD (n = 24) and matched healthy control subjects (n = 24) were scanned using a 3.0 Tesla whole-body magnetic resonance scanner. Axial T2-weighted and fluid-attenuated inversion recovery images were acquired and evaluated for the prevalence, severity and location of WMH using the modified composite scale of Fazekas and Coffey and coded separately for deep and periventricular WMH. Logistic regression analyses were used to assess the association between WMH and the diagnosis of PD. A greater severity of total WMH was associated with a diagnosis of PD in a dose-dependent pattern (odds ratio [OR] = 8.8, P = 0.005 for mild WMH; OR = 27.7, P = 0.007 for moderate to severe WMH). Deep WMH, where most group differences originated, were predominantly located in the frontal region of the brain (n = 16 in PD, n = 1 in control). The current report is the first study to report an increased prevalence of WMH in patients with PD. | 18,957,476 |
Annotation of tertiary interactions in RNA structures reveals variations and correlations. | RNA tertiary motifs play an important role in RNA folding and biochemical functions. To help interpret the complex organization of RNA tertiary interactions, we comprehensively analyze a data set of 54 high-resolution RNA crystal structures for motif occurrence and correlations. Specifically, we search seven recognized categories of RNA tertiary motifs (coaxial helix, A-minor, ribose zipper, pseudoknot, kissing hairpin, tRNA D-loop/T-loop, and tetraloop-tetraloop receptor) by various computer programs. For the nonredundant RNA data set, we find 613 RNA tertiary interactions, most of which occur in the 16S and 23S rRNAs. An analysis of these motifs reveals the diversity and variety of A-minor motif interactions and the various possible loop-loop receptor interactions that expand upon the tetraloop-tetraloop receptor. Correlations between motifs, such as pseudoknot or coaxial helix with A-minor, reveal higher-order patterns. These findings may ultimately help define tertiary structure restraints for RNA tertiary structure prediction. A complete annotation of the RNA diagrams for our data set is available at http://www.biomath.nyu.edu/motifs/. | 18,957,492 |
Dissecting the involvement of formins in Bud6p-mediated cortical capture of microtubules in S. cerevisiae. | In S. cerevisiae, spindle orientation is linked to the inheritance of the ;old' spindle pole by the bud. A player in this asymmetric commitment, Bud6p, promotes cortical capture of astral microtubules. Additionally, Bud6p stimulates actin cable formation though the formin Bni1p. A relationship with the second formin, Bnr1p, is unclear. Another player is Kar9p, a protein that guides microtubules along actin cables organised by formins. Here, we ask whether formins mediate Bud6p-dependent microtubule capture beyond any links to Kar9p and actin. We found that both formins control Bud6p localisation. bni1 mutations advanced recruitment of Bud6p at the bud neck, ahead of spindle assembly, whereas bnr1Delta reduced Bud6p association with the bud neck. Accordingly, bni1 or bnr1 mutations redirected microtubule capture to or away from the bud neck, respectively. Furthermore, a Bni1p truncation that can form actin cables independently of Bud6p could not bypass a bud6Delta for microtubule capture. Conversely, Bud6(1-565)p, a truncation insufficient for correct actin organisation via formins, supported microtubule capture. Finally, Bud6p or Bud6(1-565)p associated with microtubules in vitro. Thus, surprisingly, Bud6p may promote microtubule capture independently of its links to actin organisation, whereas formins would contribute to the program of Bud6p-dependent microtubule-cortex interactions by controlling Bud6p localisation. | 18,957,510 |
Altered gene expression profiles define pathways in colorectal cancer cell lines affected by celecoxib. | It is well established that celecoxib, a selective inhibitor of cyclooxygenase-2 (COX-2) and a tested chemopreventive agent, has several COX-2-independent activities. In an attempt to better understand COX-2-independent molecular mechanisms underlying the chemopreventive activity of celecoxib, we did global transcription profiling of celecoxib-treated COX-2-positive and COX-2-deficient colorectal cancer cell lines. Celecoxib treatment resulted in significantly altered expression levels of over 1,000 to 3,000 transcripts in these cell lines, respectively. A pathway/functional analysis of celecoxib-affected transcripts, using Gene Ontology and Biocarta Pathways and exploring biological association networks, revealed that celecoxib modulates expression of numerous genes involved in a variety of cellular processes, including metabolism, cell proliferation, apoptotic signaling, cell cycle check points, lymphocyte activation, and signaling pathways. Among these processes, cell proliferation and apoptotic signaling consistently ranked as the highest-scoring Gene Ontology terms and Biocarta Pathways in both COX-2 expresser and nonexpresser cell lines. Altered expression of many of the genes by celecoxib was confirmed by quantitative PCR and at the protein level by Western blotting. Many novel genes emerged from our analysis of global transcription patterns that were not previously reported to be affected by celecoxib. In the future, in-depth work on selected genes will determine if these genes may serve as potential molecular targets for more effective chemopreventive strategies. | 18,957,522 |
Association between alcohol intake and serum sex hormones and peptides differs by tamoxifen use in breast cancer survivors. | To measure the association between alcohol intake and 11 hormones and peptides in postmenopausal breast cancer survivors and to evaluate whether this association differs by tamoxifen use. Self-reported alcohol intake was assessed via food frequency questionnaire on average 30 months post-breast cancer diagnosis in 490 postmenopausal women from three western states. Concurrently, a fasting blood sample was obtained for assay of estrone, estradiol, free estradiol, testosterone, free testosterone, dehydroepiandrosterone sulfate (DHEAS), sex hormone-binding globulin (SHBG), leptin, C-peptide, insulin-like growth factor-I (IGF-I), and IGF-binding protein-3. Adjusted means of these hormones and peptides were calculated for categories of alcohol intake, overall and stratified by tamoxifen use. The association between alcohol intake and serum hormone and peptide levels differed by tamoxifen use. We found statistically significant inverse associations between alcohol intake and both leptin and SHBG values but only among tamoxifen users. In women not using tamoxifen, we found a positive association between alcohol intake and DHEAS but no association in tamoxifen users. Tamoxifen may modify the association between alcohol intake and serum hormones and peptides. The significant associations found for DHEAS and SHBG are in a direction considered unfavorable for breast cancer prognosis. Postmenopausal breast cancer survivors may benefit from decreasing their alcohol intake. | 18,957,523 |
Wnt-mediated self-renewal of neural stem/progenitor cells. | In this work we have uncovered a role for Wnt signaling as an important regulator of stem cell self-renewal in the developing brain. We identified Wnt-responsive cells in the subventricular zone of the developing E14.5 mouse brain. Responding cell populations were enriched for self-renewing stem cells in primary culture, suggesting that Wnt signaling is a hallmark of self-renewing activity in vivo. We also tested whether Wnt signals directly influence neural stem cells. Using inhibitors of the Wnt pathway, we found that Wnt signaling is required for the efficient cloning and expansion of single-cell derived populations that are able to generate new stem cells as well as neurons, astrocytes, and oligodendrocytes. The addition of exogenous Wnt3a protein enhances clonal outgrowth, demonstrating not only a critical role for the Wnt pathway for the regulation of neurogenesis but also its use for the expansion of neural stem cells in cell culture and in tissue engineering. | 18,957,545 |
A model of efficiency: stress tolerance by Streptococcus mutans. | The complete genome sequence of Streptococcus mutans, a bacterial pathogen commonly associated with human dental caries, was published in 2002. The streamlined genome (2.03 Mb) revealed an organism that is well adapted to its obligately host-associated existence in multispecies biofilms on tooth surfaces: a dynamic environment that undergoes rapid and substantial fluctuations. However, S. mutans lacks many of the sensing systems and alternative sigma factors that bacteria often use to coordinate gene expression in response to stress and changes in their environment. Over the past 7 years, functional genomics and proteomics have enhanced our understanding of how S. mutans has integrated the stress regulon and global transcriptional regulators to coordinate responses to environmental fluctuations with modulation of virulence in a way that ensures persistence in the oral cavity and capitalizes on conditions that are favourable for the development of dental caries. Here, we highlight advances in dissection of the stress regulon of S. mutans and its intimate interrelationship with pathogenesis. | 18,957,579 |
Additive attenuation of virulence and cariogenic potential of Streptococcus mutans by simultaneous inactivation of the ComCDE quorum-sensing system and HK/RR11 two-component regulatory system. | The genome of Streptococcus mutans harbours 13 two-component signal transduction systems (TCSTSs). Of these, a peptide-mediated quorum-sensing system, ComCDE, and the HK/RR11 two-component system are well known to regulate several virulence-associated traits in in vitro experiments, including genetic competence, bacteriocin production, biofilm formation and stress responses. In this study, we investigated the hypothesis that inactivation of ComCDE, HK/RR11 or both systems would attenuate the virulence and cariogenicity of S. mutans. The results showed that simultaneous inactivation of both signal transduction systems additively attenuated S. mutans virulence and cariogenicity, since inactivation of either of these systems alone did not result in the same degree of effect. The double deletion mutant SMcde-hk11 was defective in genetic competence, had a reduced acid production, was unable to grow at pH 5.0 and formed an abnormal biofilm with reduced biomass. Animal studies showed that this mutant had reduced capabilities for oral colonization, succession and initiation of dental caries. A competitive index (CI) analysis using a mixed-infection animal model revealed that all the mutants, particularly SMcde-hk11, had reduced fitness in their ecological niches and were unable to compete with the wild-type strain for persistence in dental biofilms. The evidence from this study suggests that the ComCDE and HK/RR11 signal transduction systems can be considered to be novel targets for the development of strategies in the prevention and treatment of S. mutans infections. | 18,957,580 |
L-Cysteine is required for induced antibiotic resistance in actively swarming Salmonella enterica serovar Typhimurium. | Swarm-cell differentiation in Salmonella enterica serovar Typhimurium (S. typhimurium) results in a biosynthetic mode of growth, despite growing on a rich medium, and cells that have elevated antibiotic resistance. These phenotypes are not a prerequisite for swarm motility. By blocking the switch to anabolic growth using amino acid auxotrophs and screening for the presence of elevated antibiotic resistance in the swarm state, we found that cysteine biosynthesis is crucial for complete swarm-cell differentiation. Mutants were made in each cys biosynthetic operon and all had decreased antibiotic resistance in the swarm state, while swim-cell resistance remained the same as that of wild-type cells. This swarm-state-specific decreased resistance in Deltacys strains could be restored to wild-type levels by the addition of cysteine to swarm medium. Two regulatory mutants, DeltacysB and DeltacysE, failed to swarm unless cysteine was supplemented to the medium. We show that all CysB-responsive operons involved in cysteine biosynthesis are upregulated in the swarm state, even though swarm cells are cultivated on a medium that represses cysteine biosynthesis in the swim state. While swarm medium has sufficient cysteine for growth of S. typhimurium, it does not contain enough for swarm-cell differentiation. We hypothesize that in these cells, the additional cysteine requirement is for use in pathways not directly related to cell growth. | 18,957,594 |
A comparative study of host response to three Mycobacterium tuberculosis PE_PGRS proteins. | Three Mycobacterium tuberculosis proteins, PE_PGRS 16 (Rv0977), PE_PGRS 26 (Rv1441c) and PE_PGRS 33 (Rv1818c), were expressed in Mycobacterium smegmatis and used to investigate the host response to members of this unique protein family. Following infection of macrophages with the recombinant M. smegmatis (Ms) strains, Ms-PE_PGRS 33 and Ms-PE_PGRS 26 were significantly more persistent (4.4 and 4.2 log c.f.u.) compared with Ms-PE_PGRS 16 (3.4 log c.f.u.) at day 6. Similarly, after infection of mice, Ms-PE_PGRS 33 and Ms-PE_PGRS 26 persisted at significantly higher levels in the spleen (3.5 and 3.2 log c.f.u.) and liver (3 and 2.6 log c.f.u.) compared with Ms-PE_PGRS 16 in the spleen (2 log c.f.u.) and in the liver (1 log c.f.u.) at day 10. Increased persistence of Ms-PE_PGRS 33 and Ms-PE_PGRS 26 was associated with cell death and increased release of lactate dehydrogenase in macrophage cultures as well as increased levels of IL-10 and, in contrast, lower levels of IL-12 and NO both in vitro and in mouse splenocytes. Conversely, poor survival of Ms-PE_PGRS 16 was associated both in macrophage cultures and in vivo with higher levels of NO and IL-12. All three PE_PGRS proteins were found to be cell-surface antigens, but immunization of mice with these PE_PGRS antigens as DNA vaccines showed no protection in a TB aerosol challenge model. In general, the results suggest that variable expression of different PE_PGRS proteins within host cells can affect either the fate of the mycobacterial pathogen or that of the host during infection and point to the importance of studying the expression and function of individual members of the PE_PGRS gene family of M. tuberculosis. | 18,957,600 |
AMPA receptors promote perivascular glioma invasion via beta1 integrin-dependent adhesion to the extracellular matrix. | High-grade gliomas release excitotoxic concentrations of glutamate, which has been shown to enhance tumor proliferation and migration. alpha-Amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) glutamate receptors are abundantly expressed at the invading edge of glioblastoma specimens, suggesting they may play an important biologic role in tumor invasion. In this study, we examined potential mechanisms by which AMPA receptor (AMPAR) expression and stimulation promote glioma cell migration and invasion. Overexpression of GluR1, the most abundant AMPAR subunit in gliomas, positively correlated with glioma cell adhesion to type I and type IV collagen, which was decreased in cells with knockdown of GluR1 and with blocking antibodies to beta1 integrin. Furthermore, stimulation of the AMPAR led to detachment of cells from the extracellular matrix (ECM). Immunoprecipitation studies showed that GluR1 associated with the actin cytoskeleton-linked protein band 4.1B (brain type), which may serve as a link between GluR1 and integrins. Overexpression of GluR1 correlated with increased cell-surface expression of beta1 integrin, increased phosphorylation of focal adhesion kinase (FAK-Y397), and enhanced numbers of focal adhesion (FA) complexes. Cells overexpressing GluR1 had increased colocalization of actin and paxillin at FAs and, in several glioma cell lines, significantly increased invasion in an in vitro Matrigel transwell assay. Likewise, in an intracranial xenograft model, overexpression of GluR1 led to perivascular and subependymal glioma cell invasion similar to patterns of tumor dissemination described in human glioblastoma. Together, these results suggest that AMPARs may link signals from the ECM to sites of FA, where signal integration promotes tumor invasion. | 18,957,620 |
Addition of thiazolidinedione or exenatide to oral agents in type 2 diabetes: a meta-analysis. | The introduction of several new therapeutic agents for the treatment of type 2 diabetes mellitus has led to significant challenges for providers in deciding which agent to select during the disease course. To provide a relative comparison of the efficacy and safety of adding thiazolidinediones (TZDs) or exenatide to oral agents for the management of type 2 diabetes mellitus by performing meta-analyses of relevant published studies. We systematically searched PubMed, MEDLINE, CINHAL, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, EMBASE (inception to March 2008 for all databases), and abstracts presented at the 2006 and 2007 American Diabetes Association conferences to identify all relevant publications. Studies were included in the analysis if they (1) were published in English, (2) were prospective, randomized, and controlled with placebo or comparator, (3) were at least 24 weeks' duration, (4) included nonpregnant adults with type 2 diabetes, (5) were full-text, peer-reviewed articles examining the efficacy of either TZDs (rosiglitazone or pioglitazone) or exenatide in combination with other oral drugs, and (6) included hemoglobin A(1C) (AIC) outcomes in a manner that allowed data analysis. We evaluated mean change in A1C levels, proportion of subjects reaching A1C goals of less than 7%, mean change in fasting plasma glucose (FPG) and body weight, and the occurrence of nonsevere hypoglycemia and gastrointestinal adverse events. A total of 5212 TZD and 3582 exenatide publications were identified. After critical evaluation, 22 publications met all of the inclusion criteria for the meta-analysis. A1C was reduced from baseline for TZDs (weighted mean difference -0.80%; 95% CI -1.10 to -0.50) and exenatide (weighted mean difference -0.60%; 95% CI -1.04 to -0.16). Compared with controls, TZD- and exenatide-based therapies had odds ratios greater than 1 for reaching A1C targets of less than 7% (TZD OR 2.27; 95% CI 1.22 to 4.24 and exenatide OR 2.90; 95% CI 1.28 to 6.55). FPG concentrations were reduced significantly from baseline in the TZD-based regimens (weighted mean difference -29.58 mg/dL; 95% CI -39.27 to -19.89), but did not achieve significance in the exenatide trials (weighted mean difference -8.77 mg/dL; 95% CI -28.85 to 11.31). Body weight was reduced with exenatide (weighted mean difference -2.74 kg; 95% CI -4.85 to -0.64) and increased in subgroup analyses for TZDs (weighted mean difference 2.19 kg; 95% CI 1.24 to 3.14). There was no significant association between TZD or exenatide therapy and the risk of nonsevere hypoglycemia. The odds ratios for nausea, vomiting, and diarrhea with exenatide relative to controls were 9.02 (95% CI 3.66 to 22.23), 4.56 (95% CI 3.13 to 6.65), and 2.96 (95% CI 2.05 to 4.26), respectively. TZDs and exenatide have modest but beneficial effects on glycemic control and are relatively safe in regard to the adverse events studied. TZDs produce greater improvement in glycemic control, while exenatide is associated with reduction in body weight. | 18,957,626 |
Occurrence of mycoplasmas in free-ranging birds of prey in Germany. | Mycoplasmas are well-known avian pathogens of poultry and some passerines. Although reported in birds of prey, their role as pathogens is still unclear. Healthy, free-ranging raptor nestlings sampled during a routine ringing (banding) program, and birds of prey from rehabilitation centers, tested positive for Mycoplasma spp. by culture and a genus-specific polymerase chain reaction (PCR). Given the lack of clinical signs and disease, we suggest that mycoplasmas in raptors may be commensal rather than pathogenic. Using immunobinding assay and species-specific PCR tests, Mycoplasma buteonis, M. falconis, and M. gypis were identified; M. falconis was only detected in falcons. Additionally, some isolates could not be identified. This is the first report of Mycoplasma spp. isolations from Western Marsh Harriers (Circus aeroginosus), a Eurasian Hobby (Falco subbuteo), and a Barn Owl (Tyto alba). | 18,957,640 |
Ranavirus infection of free-ranging and captive box turtles and tortoises in the United States. | Iridoviruses of the genus Ranavirus are well known for causing mass mortality events of fish and amphibians with sporadic reports of infection in reptiles. This article describes five instances of Ranavirus infection in chelonians between 2003 and 2005 in Georgia, Florida, New York, and Pennsylvania, USA. Affected species included captive Burmese star tortoises (Geochelone platynota), a free-ranging gopher tortoise (Gopherus polyphemus), free-ranging eastern box turtles (Terrapene carolina carolina), and a Florida box turtle (Terrepene carolina bauri). Evidence for Ranavirus infection was also found in archived material from previously unexplained mass mortality events of eastern box turtles from Georgia in 1991 and from Texas in 1998. Consistent lesions in affected animals included necrotizing stomatitis and/or esophagitis, fibrinous and necrotizing splenitis, and multicentric fibrinoid vasculitis. Intracytoplasmic inclusion bodies were rarely observed in affected tissues. A portion of the major capsid protein (MCP) gene was sequenced from each case in 2003-2005 and found to be identical to each other and to Frog virus 3 (FV3) across 420 base pairs. Ranavirus infections were also documented in sympatric species of amphibians at two locations with infected chelonians. The fragment profiles of HindIII-digested whole genomic DNA of Ranavirus, isolated from a dead Burmese star tortoise and a southern leopard frog (Rana utricularia) found nearby, were similar. The box turtle isolate had a low molecular weight fragment that was not seen in the digestion profiles for the other isolates. These results suggest that certain amphibians and chelonians are infected with a similar virus and that different viruses exist among different chelonians. Amphibians may serve as a reservoir host for susceptible chelonians. This report also demonstrated that significant disease associated with Ranavirus infections are likely more widespread in chelonians than previously suspected. | 18,957,641 |
Prevalence of tetracycline and rabies virus antibody in raccoons, skunks, and foxes following aerial distribution of V-RG baits to control raccoon rabies in Ontario, Canada. | More than 3.6 million baits containing a recombinant vaccinia virus-rabies glycoprotein (V-RG) oral rabies vaccine were aerially or hand-distributed during 1999-2006 in an approximate 4,000-9,000 km(2) area of eastern Ontario, Canada, as part of a multitactic approach to control the raccoon variant of rabies. The efficacy of the program was assessed through the collection and testing of > 6,900 animals for bait acceptance and rabies virus-specific antibodies. Raccoon acceptance of rabies vaccine baits was significantly greater (71-83% ) in areas baited at a density of 150 baits/km(2) compared to areas baited at 75 baits/km(2) (26-58% ), and more raccoons consumed vaccine baits in areas baited with a flight line spacing of 0.75 km (45.3% [321/708]) than with a spacing of 1.5 km (33.8% [108/320]). In addition, greater numbers of raccoons consumed vaccine baits during a drop in September (52.7% [213/404]) as opposed to a June bait drop (34.6% [216/624]). Seropositivity rates for raccoons ranged between 7% and 28% in areas baited at 75/km(2) and 10% to 27% in areas baited at 150/km(2) with statistical differences varying among years and treatments. The last case of raccoon-variant rabies reported in Ontario was in September 2005. The control of raccoon rabies in Ontario has resulted in an estimated $6M to $10 M Cdn annual savings in rabies-associated costs. | 18,957,651 |
The HIF-1 alpha-C/EBP alpha axis. | The hypoxia inducible factors (HIFs) and CCAAT/enhancer binding protein alpha (C/EBP alpha) are transcription factors that mediate adaptive responses to hypoxia and control aspects of energy metabolism, respectively. New evidence suggests that when HIF-1 alpha and C/EBP alpha interact, they bring about reciprocal functional changes, so that the activity of HIF-1 alpha is decreased and that of C/EBP alpha is restricted or increased in a tissue-specific manner. This Journal Club article highlights research depicting interactions between HIF-1 alpha and C/EBP alpha and discusses conditions and tissues in which this interaction might occur. | 18,957,690 |
Positron-emission tomography in imaging and staging prostate cancer. | With increasing application of positron-emission tomography (PET) imaging, familiarity with the applications of PET in genitourinary oncology, especially prostate-cancer (PCa) imaging, becomes important. PET studies provide functional information using radiolabeled tracers, with fluoro-dexoxy-glucose (FDG) being the most commonly used. Nevertheless FDG has limitations for evaluation of PCa patients and therefore alternative tracers are being investigated. To date, the best results have been obtained with 11C-choline and 11C-acetate PET, which seem to demonstrate similar values in this field. We review the current role of PET in PCa patients based on data published in the literature as well as our own experience. Most studies of PET imaging of PCa address three goals: a) detecting primary PCa; b) staging PCa; and c) assessing PCa recurrence. From available results, routine clinical use of 11C-choline PET cannot be recommended for detecting and staging primary PCa. At present, the only clinical indication for imaging PCa with 11C-choline-PET is evaluation of suspected recurrence after treatment. | 18,957,716 |
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