title stringlengths 0 1.13k | abstract stringlengths 1 15.7k | PMID int64 22 36.5M |
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A genetic model for cloacal exstrophy, the extreme cloacal malformation. | Cloacal exstrophy (CE) or vesicointestinal fissure is an uncommon but well known anomaly that represents the extreme cloacal malformation. It is most often seen as an isolated anomaly, or as part of the OEIS complex (omphalocele, exstrophy, imperforate anus, spinal defects). Limb anomalies are also seen with CE. Unlike the OEIS complex, limb anomalies occur as independent malformations. Here, we present two cases of CE with limb anomalies that are consistent with the phenotype seen in Disorganization (Ds), an unusual human malformation syndrome. From reviewing the mouse model, it may be that the Ds gene is a candidate for isolated CE as well. | 18,947,738 |
Neo-modified Koyanagi technique for the single-stage repair of proximal hypospadias. | To retrospectively analyze the results of a modification of the Koyanagi hypospadias repair developed to reduce complications. Twelve boys underwent a modified Koyanagi repair over the past 3 years. The technique included the preservation of a wide vascular pedicle for each parameatal flap. The distal urethral plate was left intact and attached on each lateral side to the medial side of each distal Koyanagi pedicle flap. One boy (8%) developed a urethral fistula. There was no instance of meatal stenosis, sacculation or urethral stricture. Modifying the Koyanagi repair by preserving a wide vascular pedicle for the distal skin flaps and utilizing the distal urethral plate as the base for the distal neourethra has lowered the incidence of complications. This technique is a suitable alternative to a two-stage approach for the correction of proximal hypospadias. | 18,947,743 |
Ossifying renal tumor of infancy. | A renal ossifying tumor of infancy is a rare event with few cases having been published, and the etiology has not yet been established. We report on two new cases of this unusual neoplasm. A 2-year-old boy presented with intermittent painless gross hematuria. After several diagnostic procedures, an open pyelolithotomy was performed and the histological diagnosis of renal tumor of infancy was finally made. The history of the second case is very similar. An 8-week-old infant presented with gross hematuria. As in the first case, an open pyelolithotomy was performed and a tumor entirely covered with blood clots was found in the renal pelvis and completely removed. A histological diagnosis of renal ossifying tumor of infancy was made. Using the literature available, the histological criteria and biological behavior are discussed, together with the diagnostic and therapeutic algorithm for this tumor. In infants with gross hematuria and a calcified (non-)invasive mass in the pelvi-calceal system, renal ossifying tumor should be considered in the differential diagnosis. MRI or CT scan offers a good diagnostic guide. | 18,947,750 |
Tissue-preserving feminizing clitoroplasty: a preliminary report. | To describe a tissue-preserving feminizing clitoroplasty that potentially allows for future total reversal to male and report on its initial result. A potentially reversible operation for feminizing clitoroplasty that preserves all available tissue was performed in three patients: two girls with congenital adrenal hyperplasia and a '46XY male' with androgen insensitivity. The phallus was disassembled into its individual components of the phallic skin, left and right corpus cavernosum, dorsal neurovascular bundle with the dorsal portion of the glans, and 'urethral plate-corpus spongiosum complex' with the ventral portion of the glans attached. Each corpus cavernosum was folded upon itself and then hidden in the subcutaneous fat to increase the size of the labia majora. The partially divided urethral plate was used to form the inner part of the labia minora and the clitoral hood. The phallic skin was partially divided and used to form the outer part of the labia minora. This operation allowed feminizing clitoroplasty to be completed without significant excision of any tissue, including the corpora cavernosa. The operation was completed successfully in all three patients, two with concomitant inverted 'V' flap vaginoplasty. One patient had postoperative haematoma. All three have a cosmetically acceptable 'female look' to the satisfaction of themselves and their parents. This preliminary result suggests that a cosmetically acceptable feminizing clitoroplasty can be performed with preservation of all phallic tissue, in particular the corpora cavernosa. This potentially reversible operation may be advantageous when feminizing genitoplasty has to be performed in a young child with disorders of sex development. | 18,947,794 |
Predictive modelling of cervical disc implant wear. | This study presents a chain of simulations aimed at estimating the wear in a cervical disc implant and providing insight into the in vivo biomechanical performance of the implant. The simulation chain can start with determining a representative maximum range of motion (ROM) of a person's head. The ROM is used as motion input to a kinematic simulation of the cervical spine containing a disc implant. The cervical spine geometry is obtained from computed tomography (CT) scans and converted to STL format using reverse engineering software. The time histories of the loads imposed by the adjacent vertebrae on the implant, as well as the vertebral relative rotations can be extracted from the kinematic simulation. Alternatively, force and motion profiles prescribed by wear test protocols (e.g. ISO 18192-1 and ASTM F2423-05) can be used. The force and motion profiles are applied as boundary conditions to a non-linear finite element model (FEM) of the implant to determine the time-varying contact stress and slip velocity distributions at the interface between the two halves of the implant. The stresses and slip velocities are used in a linear wear model to estimate the wear rate distribution at the FEM's nodal points where contact occurs. Reverse engineering software is used to triangulate the contact surface so that the total wear volume can be calculated. The simulation chain's predicted wear rate shows good agreement with in vitro results in the literature. The simulation chain is thereby demonstrated to be suitable for comparative pre-experimental studies of spinal implant designs. | 18,947,829 |
Formation of liquid menisci in flexible nanochannels. | In this paper we analyze the characteristic shape of the liquid meniscus at the fluid air interface in nanochannels of less than 80 nm height capped by a flexible membrane. Because of the induced negative pressure difference between the liquid pressure and the pressure outside, the 0.18 microm thin membrane on top of the channels bends downward. This elastocapillary equilibrium between the surface tension of the wetting liquid and the mechanical forces in the capillary results in a very peculiar shape of the interfacial meniscus, visible from the top through the transparent membrane. For increasing deflection of the membrane, the meniscus is seen to protrude along the channel and its curvature changes from concave to convex in the center. We present an analytical model to describe the meniscus shape in the deformed channel for small membrane deflections. We also show that the protrusion length of the meniscus, which can be measured easily, is an accurate and useful indicator for the membrane deflection. Experimental results on nanochannels filled with ethanol and water are presented and the observed menisci are seen to be in good agreement with the proposed model. | 18,947,834 |
Total laparoscopic hysterectomy versus abdominal hysterectomy with lymphadenectomy for early-stage endometrial cancer: a prospective randomized study. | The aim of this study was to compare, in a series of 159 women the feasibility, safety and morbidity of total laparoscopic hysterectomy (LPS) and abdominal hysterectomy with lymphadenectomy (LPT) for early-stage endometrial cancer and to assess disease-free survival and recurrence rate. 159 patients with clinical stage I endometrial cancer were enrolled in a prospective randomized trial and treated with LPS or LPT approach. The para-aortic lymphadenectomy was performed in all cases with positive pelvic lymph nodes discovered at frozen section evaluation, in patients with poorly differentiated tumors with myometrial invasion greater than 50% (ICG3), and non-endometrioid carcinomas. The mean operative time was 136 min+/-31 (95% CI 118-181) in the LPS group and 123 min+/-29 (95% CI 111-198) in the LPT group (P<0.01). The mean blood loss was 50 ml+/-12 in the LPS group (95% CI 20-90) and 145 ml+/-35 in the LPT group (95% CI 60-255) (P<0.01). The mean length of hospital stay was 5.1+/-1.2 in the LPT group (95% CI 1-7) and 2.1+/-0.5 in the LPS group (95% CI 1-5) (P<0.01). Laparoscopy is a suitable procedure for the treatment of patients with early endometrial cancer and may offer the potential benefits of decreased discomfort with decreased convalescence time without compromising the degree of oncological radicality required; however, it does not seem to modify the disease-free survival and the overall survival, although multicenter randomized trials and long-term follow-up are required to evaluate the overall oncologic outcomes of this procedure. | 18,947,861 |
The role of oxidation and enzymatic hydrolysis on the in vivo degradation of trimethylene carbonate based photocrosslinkable elastomers. | The in vivo degradation of trimethylene carbonate (TMC) containing elastomers was investigated, and the mechanism of degradation explored through in vitro degradation under enzymatic and oxidative conditions. The elastomers were prepared via UV initiated crosslinking of prepolymers of TMC and equimolar amounts of TMC and epsilon-caprolactone (CL). The degradation process was followed by investigating the changes in the mechanical properties, mass loss, water uptake, sol content, differential scanning calorimetry, and surface chemistry through attenuated total reflectance infrared (ATR-FTIR) spectroscopy. During in vivo degradation, TMC and TMCCL elastomers exhibited surface erosion. The tissue response was of greater intensity in the case of the TMC elastomer. Both elastomers exhibited degradation in cholesterol esterase containing solutions in vitro, but no parallels were found between the rate of in vivo degradation and the rate of in vitro degradation. Only the TMCCL elastomer degraded in lipase. Degradation in a stable superoxide anion in vitro medium was consistent with the observed in vivo degradation results, indicating a dominant role of oxidation through the secretion of this reactive oxygen species by adherent phagocytic cells in the degradation of these elastomers. | 18,947,866 |
John Auer and Auer rods; controversies revisited. | John Auer first described needle or rod-shaped intracytoplasmic inclusion bodies in leukemia cells in 1906. Auer rods can be seen in myeloid neoplasms ranging from acute myeloid leukemias (AML) to myelodysplasia, but not in normal or non-neoplastic reactive states. This article briefly describes John Auer's experience and discusses debates on Auer rods, and criticizes their place in the definition of refractory anemia with excess of blasts-2 (RAEB-2) in the WHO classification of the myelodysplastic syndromes (MDS). | 18,947,869 |
Pesticide exposure resulting from treatment of lice infestation in school-aged children in Georgia. | The objective of this study was to assess pesticide exposures in children being treated for head lice with either lindane or permethrin (exposed group) and children who did not have a lice infestation and thus were not being treated with chemicals for head lice or scabies (unexposed group). In 2001, we enrolled 78 children aged 6-10 years old and collected baseline urine samples and demographic information from all the children. We subsequently collected post-exposure urine samples and questionnaire information about lice treatment from the 29 (37%) children (exposed children) who had been diagnosed and were being treated for head lice. Metabolites of the pesticides lindane and permethrin were measured in the samples. The mean age of exposed and unexposed children in the study population was 9.3 years and 8.5 years, respectively. Fourteen of the 29 exposed children used prescription lice treatments (i.e., lindane or malathion); 25 of the 29 exposed children used at least one over-the-counter permethrin treatment, either alone or in addition to prescription treatments. Exposed children in both counties had higher urinary pyrethroid metabolite levels in their post-exposure samples compared with their baseline samples. However this difference was only significant in Forsyth County children. The significantly increased post-exposure pyrethroid metabolite levels in the urine of Forsyth County children suggest that the children are exposed to pyrethroid insecticides through the use of lice shampoos. | 18,947,873 |
The factor structure of lifetime depressive spectrum in patients with unipolar depression. | While previous attempts to elucidate the factor structure of depression tended to agree on a central focus on depressed mood, other factors were not replicated across studies. By examining data from a large number of items covering the range of depressive symptoms, the aim of the present study is to contribute to the identification of the structure of depression on a lifetime perspective. The study sample consisted of 598 patients with unipolar depression who were administered the Mood Spectrum Self-Report (lifetime version) in Italian (N=415) or English (N=183). In addition to classical exploratory factor analysis using tetrachoric correlation coefficients, an IRT-based factor analysis approach was adopted to analyze the data on 74 items of the instrument that explore cognitive, mood and energy/activity features associated with depression. Six factors were identified, including 'Depressive Mood', 'Psychomotor Retardation', 'Suicidality', 'Drug/Illness related depression', 'Psychotic Features' and 'Neurovegetative Symptoms', accounting overall for 48.3% of the variance of items. Clinical information on onset of depression and duration of illness is available only for 350 subjects. Therefore, differences between sites can only be partially accounted using available data. Our study confirms the central role of depressed mood, psychomotor retardation and suicidality and identifies the factors 'Drug/Illness related depression', 'Psychotic features' and the neurovegetative dysregulation not captured by the instruments most frequently used in previous studies. The identification of patients with specific profiles on multiple factors may be useful in achieving greater precision in neuroimaging studies and in informing treatment selection. | 18,947,882 |
Myxoid calcified hamartoma and natal teeth: a case report. | We report the case of a 4-month-old Caucasian male baby who presented an uncommon mass in the anterior mandibular ridge. The patient was born with two natal mandibular incisors, which exfoliated some weeks after birth, followed by a growth of nodular lesion in the same region. Based on the clinical and histopathological features, the diagnosis was of myxoid calcified hamartoma. Immunohistochemical and scanning electron microscopic analysis of the lesion were performed. Hamartomas in the mandibular ridges associated with natal teeth are rare, but they must be considered in the differential diagnosis of common lesions, such as congenital granular cell epulis. | 18,947,888 |
Life history determines genetic structure and evolutionary potential of host-parasite interactions. | Measures of population genetic structure and diversity of disease-causing organisms are commonly used to draw inferences regarding their evolutionary history and potential to generate new variation in traits that determine interactions with their hosts. Parasite species exhibit a range of population structures and life-history strategies, including different transmission modes, life-cycle complexity, off-host survival mechanisms and dispersal ability. These are important determinants of the frequency and predictability of interactions with host species. Yet the complex causal relationships between spatial structure, life history and the evolutionary dynamics of parasite populations are not well understood. We demonstrate that a clear picture of the evolutionary potential of parasitic organisms and their demographic and evolutionary histories can only come from understanding the role of life history and spatial structure in influencing population dynamics and epidemiological patterns. | 18,947,899 |
Patterns of burn injury in the preambulatory infant. | This study was undertaken after an increasing trend in young babies presenting with severe burns was observed in Princess Margaret Hospital (PMH) in Perth, Western Australia. The aim was to explore the patterns of these injuries with a view to identifying whether they could be prevented with better parent education. Inclusion criteria was infants under 6 months of age who sustained a burns injury requiring admission or out-patient treatment in the Burns Unit of PMH between July 2005 and September 2007. Immobile infants are at significant risk of burns. In infants who are not yet mobile, environmental factors are commonly implicated, with the vast majority of burns sustained in the home. The mechanisms of injuries were scalds (43%), contact burns (39%), sunburn (11%) and TPN burns in premature infants in NICU (7%). TBSA ranged from <0.5% to 30%. Infants less than 6-month-old are at significant risk of burn; at this age the injury is usually caused by hazards in the home environment. These infants are vulnerable to inadequate first aid and require a large amount of follow-up care. Better parental education may help reduce the number of injuries we see in this age group. | 18,947,932 |
[Effects of omega 3 supplementation in pregnant women]. | Maternal nutrition is a major environmental factor, which can be modified and can affect fetal growth and development with potential long-term consequences. There is currently a strong mediatic pressure for supplementing diets with omega 3 fatty acids. Nevertheless, if beneficial effects seem to be confirmed in adults and in animal models, the evidence for favourable effects of omega 3 supplementation in pregnant women are less obvious. Indeed, there is a trend showing a positive effect on cerebral development, but long term effects have not been demonstrated and both the quantity of omega 3 and the omega 3:omega 6 ratios are not precisely determined. Numerous studies are needed, both in pregnant animal models and in patients, to unravel these effects. | 18,947,942 |
LC-MS/MS method for determination of hederacolchiside E, a neuroactive saponin from Pulsatilla koreana extract in rat plasma for pharmacokinetic study. | A simple, rapid, and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was applied to pharmacokinetic study of a neuroactive oleanolic-glycoside saponin, hederacolchiside E from SK-PC-B70M, a standardized extract of Pulsatilla koreana in rat. Rat plasma samples were pretreated by protein precipitation with acetonitrile, eluted from C(18) column, and analyzed using electrospray ionization (ESI)-MS/MS in negative ion mode. Digoxin was used as an internal standard. The standard curves were linear (r>0.997) over the concentration ranges of 2-500 ng/mL. The intra- and inter-day precisions were measured to be below 9% and accuracy between 90 and 111% for all quality control samples at 2, 20, 100, and 500 ng/mL (n=5). The lower limits of quantification (LLOQ) for hederacolchiside E was 2 ng/mL and the limit of detection (LOD) 0.5 ng/mL using 20 microL of plasma sample. Subsequently, hederacolchiside E was determined in rat plasma samples after oral administration of SK-PC-B70M. The mean maximum plasma concentrations of hederacolchiside E were 0.07, 0.13, and 0.36 microg/mL and the mean areas under the plasma concentration versus time curve 0.56, 1.27, and 6.46 microg h/mL at doses of 100, 200, and 400 mg/kg, respectively, which indicated non-linear pharmacokinetic pattern. In conclusion, this method was successfully applied to the pharmacokinetic study of hederacolchiside E after an oral administration of SK-PC-B70M to rats. | 18,947,958 |
Acute myocardial infarction caused by coronary embolism from infective endocarditis. | Identifying an acute myocardial infarction caused by a non-atherosclerotic process can have consequences on the short- and long-term management of the disease. In the first case reported, a 39-year-old woman with a history of hypertension, diabetes, end-stage renal disease, deep vein thrombosis, and a recent hospitalization for staphylococcal bacteremia presented to the Emergency Department (ED) with acute onset of chest pain and shortness of breath. Her electrocardiogram (ECG) showed findings of an ST-segement elevation lateral wall acute myocardial infarction (AMI). The patient's condition worsened in the ED, and thrombolytic therapy was initiated. The patient subsequently had a coronary catheterization that illustrated an irregular mitral valve and abrupt occlusions in the left anterior descending artery, suggestive of coronary embolism from a mitral valve source. This patient was later treated with intravenous antibiotics and mitral valve replacement. In the second case reported, a 56-year-old man with a history of hypertension, diabetes, and end-stage renal disease presented to the ED with shortness of breath, fever, and chest pain. His ECG was significant for ST-segment elevation in the lateral leads, suggestive of an AMI. This patient had a history of positive blood cultures in a previous admission as well as an echocardiogram revealing an aortic valve vegetation. Given the high suspicion for an infective endocarditis causing an embolic event that in turn led to the myocardial infarction, thrombolytics were withheld in the ED and the patient was transported for coronary catheterization. The coronary angiogram demonstrated abrupt cutoffs at the distal left anterior descending artery and distal left posterior descending artery suggestive of an embolic occlusion of these vessels. He was subsequently treated with intravenous antibiotics and aortic valve replacement. These two cases illustrate the importance of broadening our differential in the causes of AMI. In these cases, the recognition of an embolic event from infective endocarditis as the cause of the acute coronary syndrome allowed physicians to direct their interventions to optimize the appropriate care for each patient. | 18,947,962 |
Hepatic artery aneurysm erosion into the stomach: an unusual cause of gastrointestinal bleeding. | Hepatic artery aneurysms are the second most common visceral aneurysms. The natural history of hepatic artery aneurysms typically results in enlargement, rupture, and life-threatening hemorrhage. Atherosclerosis, traditionally, has been the most common cause of hepatic artery aneurysm. A case of a hepatic artery aneurysm invading the stomach is presented to draw attention to the clinical presentation of this potentially catastrophic entity. A 74-year-old man presented to the Emergency Department (ED) with hematemesis. He was hemodynamically stable with a hemoglobin of 10.5. Abdominal CT imaging revealed a hepatic artery aneurysm that eroded into the stomach. The erosion was successfully repaired operatively and the aneurysm was embolized. The most common symptom is epigastric pain. The clinical and radiological findings of a hepatic artery aneurysm eroding into the stomach with subsequent upper and lower gastrointestinal hemorrhage, as highlighted in the case reported, have received little prior attention in the medical literature. | 18,947,965 |
In support of Bleuler: objective evidence for increased affective ambivalence in schizophrenia based upon evocative testing. | Ambivalence and anhedonia have long been identified as schizophrenic symptoms. However, ambivalence has rarely been studied, and in most evocative studies, schizophrenia participants are not anhedonic. Affective neurosciences posit two evaluative systems (one for Positivity and one for Negativity), the coactivation of which produces ambivalence, and point to two asymmetries in affective processing: Positivity Offset (which measures our capacity to explore the environment) and Negativity Bias (a measure of reactivity to intense threat). These characteristics have not received much attention in schizophrenia research. Sixty-four individuals with schizophrenia and 32 non-patient control participants completed an evocative emotional task with pictures, sounds and words of various valences and intensities. Following each presentation, participants rated the level of pleasantness, unpleasantness, and arousal elicited by the stimulus. Finally, participants completed questionnaires on anhedonia, and practical life skills were assessed. Schizophrenia participants showed higher levels of ambivalence, greater arousal, greater Positivity Offset, and non-significantly different hedonic capacities and Negativity Bias. Ambivalence to positive stimuli significantly correlated with duration of illness, current level of psychopathology, anhedonia questionnaires and practical life skills. Schizophrenia patients with negative symptoms did not differ from patients without negative symptoms on computer tasks. Ambivalence is greater in schizophrenia, and can be understood as a de-differentiation of the activation of the two evaluative systems. Ambivalence to positive stimuli, which may reflect early-stage affective processing is associated with impairments in higher-level emotional processes and in everyday functioning. Future studies should clarify the status of anhedonia in schizophrenia. | 18,947,981 |
fMRI adaptation reveals mirror neurons in human inferior parietal cortex. | Mirror neurons, as originally described in the macaque, have two defining properties [1, 2]: They respond specifically to a particular action (e.g., bringing an object to the mouth), and they produce their action-specific responses independent of whether the monkey executes the action or passively observes a conspecific performing the same action. In humans, action observation and action execution engage a network of frontal, parietal, and temporal areas. However, it is unclear whether these responses reflect the activity of a single population that represents both observed and executed actions in a common neural code or the activity of distinct but overlapping populations of exclusively perceptual and motor neurons [3]. Here, we used fMRI adaptation to show that the right inferior parietal lobe (IPL) responds independently to specific actions regardless of whether they are observed or executed. Specifically, responses in the right IPL were attenuated when participants observed a recently executed action relative to one that had not previously been performed. This adaptation across action and perception demonstrates that the right IPL responds selectively to the motoric and perceptual representations of actions and is the first evidence for a neural response in humans that shows both defining properties of mirror neurons. | 18,948,009 |
Preliminary experience with electromagnetic navigation system in TKA. | Accuracy of implant positioning and precise reconstruction of leg alignment offers the best way to achieve good long-term results in total knee arthroplasty. Computer instrumentation was developed to improve the final position of the component and restore the mechanical axis. Current navigation systems use either optical or electromagnetic tracking. The advantage of the Electromagnetic (EM) navigation system is that no line-of-sight issues are present. However, special iron-free instruments are required. This report analyzes the postoperative radiological results of 32 knees treated using an EM system. All the measurements were recorded using software able to subtend angles automatically by five physicians, three radiologist and two orthopedic residents not involved with the surgery. Each radiograph was measured three times, in random order, and at delayed intervals. We found an ideal alignment for the mechanical axis (180+/-3 degrees ) in 30 out of 32 cases, whereas all the patients achieved a value of 90 degrees +/-3 degrees for both femoral and tibial frontal component angles. An apparently over-corrected implant position for the sagittal femoral component was reported, with a mean value of 11.2 degrees +/-3.6. The mean position of the tibial component was 90.6 degrees +/-2.8; just four measurements were outside of the +/-3 degrees of the desired value. EM is safe and there were no complications related to this system. An almost perfect correlation was found between the mechanical axis value of the EM navigation system (179.8 degrees +/-1.8) and the median value of the all reviewers (180.3 degrees +/-1.9) with a difference of 0.5 degrees . | 18,948,010 |
NK cell receptors and their MHC class I ligands in host response to cytomegalovirus: insights from the mouse genome. | The complex interaction between natural killer (NK) cells and cytomegalovirus is a paradigm of the co-evolution between genomes of large DNA viruses and their host immune systems. Both human and mouse cytomegalovirus posses numerous mechanisms to avoid NK cell detection. Linkage studies, positional cloning and functional studies in mice and cells, have led to the identification of key genes governing resistance to cytomegalovirus, including various NK cell activating receptors of major histocompatibility complex (MHC) class I. These receptors, however, seem to require either viral or host MHC class I molecules to operate recognition and elimination of the cytomegalovirus-infected cell leading to host resistance. Here we will review the genes and molecules involved in these mechanisms while contrasting their function with that of other NK cell receptors. Activating receptors of MHC class I may represent a window of therapeutic intervention during human infection with viruses, of which cytomegalovirus remains an important health threat. | 18,948,016 |
Beyond foodscapes: considering geographies of Indigenous well-being. | Direct associations between food and health have been pursued traditionally through nutrition and health policy studies; however, geography has much to offer in providing a disciplinary context that can support a critique of this literature and the recognition of the critical significance of broader associations between culture, environment and well-being. This paper explores the potential of these opportunities by reviewing existing interests in food geographies and the wider attention being given to geographies of health and well-being. We then turn to consider dimensions of Indigenous life, health and well-being and we highlight the complex intersection of people, place and 'nature-culture' relations. In particular, we propose the need to move beyond a foodscape approach and suggest how a more culturally complex reading of food and food practices may be made to enhance research and policy concerning Indigenous health and well-being. | 18,948,052 |
Distal revascularisation/replantation using the reversed radial artery. | We describe a technique using the reversed radial artery for distal revascularisation or replantation in the hand. This technique has been used for revascularisation following crush avulsion injuries associated with a large zone of trauma and polydigit replantation. The technique involves dividing the radial artery and venae comitantes proximally and mobilising it distally into the hand for anastomosis. Temporary 'syndactylisation' of adjacent digits is also described. This can be used to convert multiple digits into a single vascular unit and to provide a bed for the transposed radial vessels. These techniques are an option when there is extensive injury to distal vessels such that end-to-end anastomosis is not possible and interposition venous micrografting may be difficult or prone to failure due to poor quality recipient vessels and the need to place grafts in a traumatised bed. | 18,948,071 |
Quantification of PCR products by phosphate measurement. | Various techniques for quantification of PCR are available. Most frequently, the densitometric intensities of ethidium bromide-stained PCR products separated in gels are compared after normalizing to the levels of housekeeping gene products such as beta-actin. More precise, but extremely time consuming, is the technique of competitive PCR. Newer methods, such as tracking amplification in real-time, have high start-up and maintenance costs (e.g., TaqMan, Applied Biosystems; LightCycler, Roche; I-Cycler, Bio-Rad). Here, I describe an alternative, simple technique to quantify PCR products by determining the entire phosphate released during PCR. The method can be performed using common laboratory equipment, and the reagents needed are extremely cheap. The method is validated by measuring the induction of inducible nitric oxide synthase gene expression in cell culture and comparing the results with data obtained by LightCycler experiments and RNase protection assays. | 18,948,073 |
Multiple kinases regulate mafA expression in the pancreatic beta cell line MIN6. | MafA is a basic leucine zipper transcription factor expressed within the beta cells of the pancreas and is required to maintain normal glucose homeostasis as it is involved in various aspects of beta cell biology. MafA protein levels are known to increase in response to high glucose through mechanisms that have yet to be fully characterized. We investigated whether discrete intracellular signaling events control mafA expression. We found that the general kinase inhibitor staurosporine induces mafA expression without altering the stability of the protein. Inhibition of the MAP-kinase JNK mimics the effects of staurosporine on the expression of mafA. Calmodulin kinase and calcium signaling are also important in stimulating mafA expression by high glucose. However, staurosporine, JNK, and calmodulin kinase have different effects on the induction of insulin expression. These data reveal that MafA levels are tightly controlled by the coordinated action of multiple kinase pathways. | 18,948,074 |
Ethambutol induces PKC-dependent cytotoxic and antiproliferative effects on human retinal pigment cells. | Ethambutol (EMB)-induced ocular side effects may involve the influence on functions of retinal pigment epithelium (RPE), in addition to EMB-induced optic neuropathy. To address this issue, the molecular and cellular effects of EMB on RPE including growth regulation, morphological responses, phagocytic activity, and the relevant signaling pathways were investigated. EMB (at optimal concentration 8.0mM) can trigger cell cycle arrest in both RPE50 and ARPE19 cells, accompanied by reduced DNA synthesis. EMB also induced cytoplasmic vacuole formation in both RPE cell lines. Under transmission electric microscope, the phagosomes were replaced by vacuoles and the number of microvilli was reduced in EMB-treated cells. Animal experiments also demonstrated the vacuole formation within RPE of the EMB-treated rats. On the other hand, by in vitro phagocytosis assay using rod outer segment (ROS) as the target, we found EMB suppressed phagocytosis in the cultured RPE, which is consistent with the decreased rhodopsin uptake in the RPE of the EMB-treated rats. Furthermore, inhibitor of protein kinase C but not MAPK, prevented the EMB-induced phenotypical changes. Using a non-radioactive PKC assay, we also demonstrated the PKC activity in both RPE cell lines can be induced by EMB. In conclusion, EMB may exert toxic effects in RPE including suppression of cell growth, formation of cytoplasmic vacuoles and reduction of phagocytic functions via PKC signal pathway. | 18,948,097 |
Energetics of kinesin-1 stepping mechanism. | Kinesin-1 is a dimeric motor protein that transports cellular cargo along microtubules by using the energy released from ATP hydrolysis and moving processively in 8-nm steps. Recent novel studies at the single molecular level have provided extensive knowledge on how kinesin-1 converts the free energy of ATP hydrolysis and uses it for "walking" along microtubules. In this review, I have discussed the important topics pertaining to the energetics of kinesin-1 stepping mechanism and the consensus walking model. | 18,948,105 |
Methods of collection for salivary cortisol measurement in dogs. | Salivary cortisol has been increasingly used as a measure of stress response in studies of welfare, reaction to stress and human-animal interactions in dogs and other species. While it can be a very useful measure, there are a number of saliva collection issues made evident through studies in the human and animal fields which have not been investigated in the canine species. Collection materials and the volume of saliva that is collected; the use of salivary stimulants; and the effect of food contamination can all dramatically impact cortisol measurement, leading to spurious results. In order to further examine the limitations of the collection method and the effects of collection material and salivary stimulant on salivary cortisol levels, a series of clinical, in vitro and in vivo studies were performed. It was found that there is a large amount of inter- and intra-individual variation in salivary cortisol measurement. Beef flavoring of collection materials leads to unpredictable variability in salivary cortisol concentration. Using salivary stimulants such as citric acid also has the potential to affect cortisol concentration measurement in saliva. Hydrocellulose appears to be a useful collection material for salivary cortisol determination. Recommendations for collection materials and use of salivary stimulants are presented. | 18,948,108 |
The interaction of HMGB1 and linker histones occurs through their acidic and basic tails. | H1 and HMGB1 bind to linker DNA in chromatin, in the vicinity of the nucleosome dyad. They appear to have opposing effects on the nucleosome, H1 stabilising it by "sealing" two turns of DNA around the octamer, and HMGB1 destabilising it, probably by bending the adjacent DNA. Their presence in chromatin might be mutually exclusive. Displacement/replacement of one by the other as a result of their highly dynamic binding in vivo might, in principle, involve interactions between them. Chemical cross-linking and gel-filtration show that a 1:1 linker histone/HMGB1 complex is formed, which persists at physiological ionic strength, and that complex formation requires the acidic tail of HMGB1. NMR spectroscopy shows that the linker histone binds, predominantly through its basic C-terminal domain, to the acidic tail of HMGB1, thereby disrupting the interaction of the tail with the DNA-binding faces of the HMG boxes. A potential consequence of this interaction is enhanced DNA binding by HMGB1, and concomitantly lowered affinity of H1 for DNA. In a chromatin context, this might facilitate displacement of H1 by HMGB1. | 18,948,112 |
Bradykinin stimulates glutamate uptake via both B1R and B2R activation in a human retinal pigment epithelial cells. | We were to examine the effect of bradykinin (BK) in the regulation of glutamate transporter and its related signaling molecules in a human retinal pigment epithelial (ARPE) cells, which are important cells to support retina. d-[2,3-(3)H]-aspartate uptake, western immunoblotting, reverse transcription polymerase chain reaction, [(3)H]-arachidonic acid release, and siRNA transfection techniques were used. BK stimulated glutamate uptake as well as the mRNA expression of excitatory amino acid transporter 4 (EAAT4) and excitatory amino acid carrier 1 (EAAC1), which was blocked by treatment with bradykinin 1 receptor (B1R) and bradykinin 2 receptor (B2R) siRNA, suggesting the role of B1R and B2R in this process. The BK-induced stimulation of glutamate uptake was also blocked by [des-Arg(10)]-HOE 140, a B1R antagonist, and HOE 140, a B2R antagonist, as well as by the tyrosine kinase inhibitors genistein and herbimycin A. In addition, the BK-induced stimulation of glutamate uptake was blocked by treatment with the phospholipase A(2) inhibitors mepacrine and AACOCF(3), the cyclooxygenase (COX) inhibitor indomethacin, and the COX-2 inhibitor Dup 697. Furthermore, the BK-induced increase in COX-2 expression was blocked by the PI-3 kinase inhibitors wortmannin and LY294002, Akt inhibitor, and the protein kinase C (PKC) inhibitors staurosporine and bisindolylmaleimide I, suggesting the role of PI-3 kinase and PKC in this process. BK stimulated Akt activation and the translocation of PKC activation via the activation of B1R and B2R. BK stimulates glutamate uptake through a PKC-Akt-COX-2 signaling cascade in ARPE cells. | 18,948,121 |
VEGF regulates FGF-2 and TGF-beta1 expression in injury endothelial cells and mediates smooth muscle cells proliferation and migration. | Vascular endothelial growth factor (VEGF) is implicated in the development of restenosis after percutaneous transluminal coronary angioplasty (PTCA) as well as atherosclerosis. The purpose of our study was: 1) to evaluate the expression of endothelial cell (EC) fibroblast growth factor 2 (FGF-2) and transforming growth factor beta1 (TGF-beta1) mRNA expression following vascular injury and VEGF modulation and 2) to assess whether VEGF indirectly stimulates smooth muscle cell (SMC) migration and proliferation via growth factors released by injured EC. Bovine aortic endothelial cells (BAEC) were cultured to near confluency and were serum starved. Linear wounds were made in medium with and without VEGF. FGF-2 and TGF-beta1 mRNA expression were evaluated. Bovine aortic organ culture experiments were also carried out and growth factor expression was assessed. SMC proliferation and migration was assessed in response to EC injury medium with/without VEGF. EC injury in the presence of VEGF increased FGF-2 mRNA. EC injury also induced TGF-beta1 mRNA expression; however VEGF inhibited TGF-beta1 mRNA expression in both injured and noninjured ECs. VEGF increased FGF-2 mRNA stability and did not alter TGF-beta1 mRNA stability. SMC proliferation and migration was found to be induced by injured EC media and injury EC medium with VEGF, respectively The results demonstrate that 1) VEGF indirectly stimulates SMC proliferation and migration through stimulation of the expression of FGF-2 and 2) VEGF inhibits the expression of TGF-beta1 released by EC. Theses data further suggest an integral role for FGF-2 and TGF-beta1 in wound repair. | 18,948,122 |
The influence of whey protein and glycomacropeptide on satiety in adult humans. | Protein is often considered the most satiating macronutrient. The objective was to determine the short-term effect of mixtures of whey protein and glycomacropeptide (GMP) versus a carbohydrate control on satiety in healthy adult humans. The study was a randomised crossover Latin Square design. On 4 separate days, fifty healthy subjects (19 males and 31 females) received a subject-specific breakfast (08:00 h), a preload drink (12:00 h) and lunch (12:30 h). The preload drink was presented as a milkshake with either maltodextrin carbohydrate (control), whey protein isolate (WPI) with no GMP, WPI with naturally present 21% GMP or WPI with naturally present 21% GMP plus added GMP. Satiety was assessed using visual analogue scales (VAS) and by determining ad libitum food intake during a cafeteria style meal offered 30 min after the preload. The VAS indicated that the lower GMP treatment induced a greater feeling of fullness immediately after consumption of the preload compared with the other treatments. Energy and macronutrient intake at lunch did not differ significantly (p>0.05) between treatments although subjects chose to eat foods higher in carbohydrate and lower in protein after the protein preloads. Women consumed the least amount of protein after the protein preloads whereas no difference was found in men. There was some evidence that whey proteins and their components enhance satiety over a short-term period compared to carbohydrate but there was no consistent effect of either whey protein alone or glycomacropeptide. | 18,948,128 |
Dioxin activation of CYP1A5 promoter/enhancer regions from two avian species, common cormorant (Phalacrocorax carbo) and chicken (Gallus gallus): association with aryl hydrocarbon receptor 1 and 2 isoforms. | The present study focuses on the molecular mechanism and interspecies differences in susceptibility of avian aryl hydrocarbon receptor (AHR)-cytochrome P4501A (CYP1A) signaling pathway. By the cloning of 5'-flanking regions of CYP1A5 gene from common cormorant (Phalacrocorax carbo) and chicken (Gallus gallus), seven putative xenobiotic response elements (XREs) were identified within 2.7 kb upstream region of common cormorant CYP1A5 (ccCYP1A5), and six XREs were found within 0.9 kb of chicken CYP1A5 (ckCYP1A5). Analysis of sequential deletion and mutagenesis of the binding sites in avian CYP1A5 genes by in vitro reporter gene assays revealed that two XREs at -613 bp and -1585 bp in ccCYP1A5, and one XRE at -262 bp in ckCYP1A5 conferred TCDD-responsiveness. The binding of AHR1 with AHR nuclear translocator 1 (ARNT1) to the functional XRE in a TCDD-dependent manner was verified with gel shift assays, suggesting that avian CYP1A5 is induced by TCDD through AHR1/ARNT1 signaling pathway as well as mammalian CYP1A1 but through a distinct pathway from mammalian CYP1A2, an ortholog of the CYP1A5. TCDD-EC(50) for the transcriptional activity in both cormorant AHR1- and AHR2-ccCYP1A5 reporter construct was 10-fold higher than that in chicken AHR1-ckCYP1A5 reporter construct. In contrast, chicken AHR2 showed no TCDD-dependent response. The TCDD-EC(50) for CYP1A5 transactivation was altered by switching AHR1 between the two avian species, irrespective of the species from which the regulatory region of CYP1A5 gene originates. Therefore, the structural difference in AHR, not the CYP1A5 regulatory region may be a major factor to account for the dioxin susceptibility in avian species. | 18,948,129 |
Cane toad toxicity: an assessment of extracts from early developmental stages and adult tissues using MDCK cell culture. | Extracts of the cane toad (Bufo [Chaunus] marinus) adversely affected the growth of Mardin-Darby canine kidney (MDCK) cells during culture. In a similar manner to ouabain treatment, application of toad extracts over a 24 h period resulted in high levels of cytotoxicity, as indicated by cell detachment, increased membrane permeability and loss of mitochondrial function. Cell viability and growth were unchanged for controls (PBS) and increased with the application of Limnodynastes peronii tadpole and adult frog extracts. We investigated the general cytotoxicity of cane toad developmental stages (e.g., eggs, embryonic hatchlings, tadpoles and post-metamorphic toadlets) as well as selected adult tissues (e.g. skin, gut, liver). Our results showed that pre-metamorphic cane toad aqueous extracts used at 1 mg/ml on MDCK cells generated cytotoxicity levels comparable to ouabain treatment (3 microM). After normalisation, extracts from 2-3-month-old toadlets appeared less toxic than pre- and early metamorphic stages. Adult tissues revealed a gradient of cytotoxicity levels ranging from non-toxic brain to highly toxic dorsal skin extracts. | 18,948,131 |
From retinal circuitry to eye diseases--in memory of Henk Spekreijse. | This article summarizes our recent works on stratum-by-stratum structure-function rules for synaptic contacts between retinal bipolar cells and third-order retinal neurons in the inner plexiform layer. These rules were derived from large-scale voltage clamp recordings of various types of bipolar cells in the tiger salamander retina, and they appear applicable to bipolar cells in the mouse and other mammalian species. This review also gives a brief account of how we used pathway-specific knockout mouse models to dissect rod and cone signaling channels in the mammalian retina. Furthermore, studies on cellular and genetic mechanisms underlying several neurodegenerative retinal disorders are described. | 18,948,133 |
Characterization and application of monoclonal antibodies specific to West Nile virus envelope protein. | Recent epidemics of West Nile virus (WNV) around the world have been associated with significant rates of mortality and morbidity in humans. To develop standard WNV diagnostic tools that can differentiate WNV from Japanese encephalitis virus (JEV), four monoclonal antibodies (MAbs) specific to WNV envelope (E) protein were produced and characterized by isotyping, reactivity with denatured and native antigens, affinity assay, immunofluorescence assay (IFA), and epitope competition, as well as cross-reactivity with JEV. Two of the MAbs (6A11 and 4B3) showed stronger reactivity with E protein than the others (2F5 and 6H7) in Western blot analysis. 4B3 could bind with denatured antigen, as well as native antigens in indirect ELISA, flow cytometry analysis, and IFA; whereas 2F5 showed highest affinity with native antigen. 4B3 and 2F5 were therefore used to establish an antigen capture-ELISA (AC-ELISA) detection system. The sensitivity of this AC-ELISA was 3.95 TCID(50)/0.1 ml for WNV-infected cell culture supernatant. Notably, these MAbs showed no cross-reactivity with JEV, which suggests that they are useful for further development of highly sensitive, easy handling, and less time-consuming detection kits/tools in WNV surveillance in areas where JEV is epidemic. | 18,948,139 |
The astrocyte odyssey. | Neurons have long held the spotlight as the central players of the nervous system, but we must remember that we have equal numbers of astrocytes and neurons in the brain. Are these cells only filling up the space and passively nurturing the neurons, or do they also contribute to information transfer and processing? After several years of intense research since the pioneer discovery of astrocytic calcium waves and glutamate release onto neurons in vitro, the neuronal-glial studies have answered many questions thanks to technological advances. However, the definitive in vivo role of astrocytes remains to be addressed. In addition, it is becoming clear that diverse populations of astrocytes coexist with different molecular identities and specialized functions adjusted to their microenvironment, but do they all belong to the umbrella family of astrocytes? One population of astrocytes takes on a new function by displaying both support cell and stem cell characteristics in the neurogenic niches. Here, we define characteristics that classify a cell as an astrocyte under physiological conditions. We will also discuss the well-established and emerging functions of astrocytes with an emphasis on their roles on neuronal activity and as neural stem cells in adult neurogenic zones. | 18,948,166 |
Role of Ca2+, membrane excitability, and Ca2+ stores in failing muscle contraction with aging. | Excitation-contraction (EC) coupling in a population of skeletal muscle fibers of aged mice becomes dependent on the presence of external Ca(2+) ions (Payne, A.M., Zheng, Z., Gonzalez, E., Wang, Z.M., Messi, M.L., Delbono, O., 2004b. External Ca(2+)-dependent excitation - contraction coupling in a population of aging mouse skeletal muscle fibers. J. Physiol. 560, 137-155.). However, the mechanism(s) underlying this process remain unknown. In this work, we examined the role of (1) extracellular Ca(2+); (2) voltage-induced influx of external Ca(2+) ions; (3) sarcoplasmic reticulum (SR) Ca(2+) depletion during repeated contractions; (4) store-operated Ca(2+) entry (SOCE); (5) SR ultrastructure; (6) SR subdomain localization of the ryanodine receptor; and (7) sarcolemmal excitability in muscle force decline with aging. These experiments show that external Ca(2+), but not Ca(2+) influx, is needed to maintain force upon repetitive fiber electrical stimulation. Decline in fiber force is associated with depressed SR Ca(2+) release. SR Ca(2+) depletion, SOCE, and the putative segregated Ca(2+) release store do not play a significant role in external Ca(2+)-dependent contraction. More importantly, a significant number of action potentials fail in senescent mouse muscle fibers subjected to a stimulation frequency. These results indicate that failure to generate action potentials accounts for decreased intracellular Ca(2+) mobilization and tetanic force in aging muscle exposed to a Ca(2+)-free medium. | 18,948,183 |
Quercetin prevents necrotic cell death induced by co-exposure to benzo(a)pyrene and UVA radiation. | The phototoxicity of low-energy ultraviolet radiation, such as UVA, can be enhanced by the presence of photosensitizing agents. Hence, co-exposure of cells to benzo[a]pyrene (BaP), a widespread environmental carcinogen and photosensitizing agent, and UVA may synergistically induce DNA damage. In this study, exposure of cells to various concentrations of BaP for 1h followed by UVA irradiation (2J/cm(2)) increased DNA damage and decreased cell viability. Expression of apoptosis-related proteins (caspase-9, caspase-3, PARP, and Bax) and hypodiploid DNA content (sub-G(1)) were not changed. LDH release into the culture medium increased in a dose-dependent manner with BaP under UVA irradiation, suggesting that cell death due to BaP/UVA co-treatment occurred via necrosis. Intracellular reactive oxygen species (ROS) levels were increased significantly in the co-exposed cells, and treatment with the polyphenol quercetin, but not with sodium azide or N-acetylcysteine, decreased ROS levels and increased cell viability in BaP/UVA-treated cells. In conclusion, UVA irradiation combined with BaP synergistically promoted necrosis of A549 cells by increasing intracellular ROS levels, and quercetin prevented BaP-enhanced phototoxicity due to UVA irradiation. | 18,948,185 |
Spinal cord injury induces upregulation of Beclin 1 and promotes autophagic cell death. | Autophagy is a degradation of the cytoplasm and it induces autophagic cell death in several neurodegenerative conditions. Beclin 1, a Bcl-2-interacting protein, is known to be a promoter of autophagy. We investigated the alterations in the Beclin 1 protein expression and the involvement of autophagy and autophagic cell death after spinal cord injury using a spinal cord hemisection model in mice. In the present study, the Beclin 1 expression dramatically increased at the lesion site after hemisection. The increased expression of Beclin 1 started from 4 h, peaked at 3 d, and lasted for at least 21 d after hemisection. The Beclin 1 expression was observed in neurons, astrocytes, and oligodendrocytes. The nuclei in the Beclin 1 expressing cells were round, which should normally be observed in autophagic cell death, and they were not either shrunken or fragmented as is observed in apoptotic nuclei. The results of the present study suggested that autophagy is activated in the injured spinal cord. Furthermore, autophagic cell death is considered to clearly contribute to neural tissue damage after spinal cord injury. | 18,948,195 |
Immune response of white shrimp, Litopenaeus vannamei, after a concurrent infection with white spot syndrome virus and infectious hypodermal and hematopoietic necrosis virus. | In the present study, we investigated immunological changes in viral-infected white shrimp, Litopenaeus vannamei. White shrimp were infected with white spot syndrome virus (WSSV) or co-infected with WSSV and infectious hypodermal and hematopoietic necrosis virus (IHHNV) as detected by polymerase chain reaction (PCR). The complete (100%) mortality rate of shrimp was caused by viral infection due to immune parameters being suppressed including decreases in phenoloxidase activity, total hemocyte counts, differential hemocyte counts, and the gene expressions of prophenoloxidase and peroxinectin. In addition, increases in lipopolysaccharide and beta-1,3-glucan-binding protein of hemocytes and the hepatopancreas, and respiratory bursts per cell, and a decrease in superoxide dismutase were found in viral-infected shrimp, which may have been related to the defense against viral infection. | 18,948,207 |
Secretion from acinar cells of the exocrine pancreas: role of enteropancreatic reflexes and cholecystokinin. | Although the molecular machinery and mechanism of cell secretion in acinar cells of the exocrine pancreas is well documented and clear, only recently has the pharmacophysiology of pancreatic exocrine secretion come to light. Therefore, we focus in this article on the current understanding of the pharmacophysiology of pancreatic exocrine secretion. The pancreatic secretory response to ingestion of a meal is mediated via a complex interplay of neural, humoral and paracrine mediators. A major role in the control of the intestinal phase of pancreatic secretion is attributed to vago-vagal enteropancreatic reflexes. In the scheme of this control mechanism, afferents originating in the duodenal mucosa, and efferents mediating central input on the pancreatic ganglia, activate intrapancreatic postganglionic neurons. Experiments utilizing specific receptor antagonists demonstrate the involvement of both muscarinic M1 and M3 receptors expressed in pancreatic acinar cells. Cholecystokinin (CCK), originally implicated in the humoral secretion of pancreatic enzymes, through a direct action on acinar CCK receptors, is also essential to the enteropancreatic reflex mechanism. CCK stimulation of the exocrine pancreatic secretion through excitation of sensory afferents of the enteropancreatic reflexes, is a paracrine mode of CCK action, and is probably the only one in humans and the predominant one in rats. In dogs, however, CCK acts on the pancreas via both the humoral and a paracrine route. More recent experiments suggest further possible sites of CCK action. Additionally, at the brain stem, vago-vagal enteropancreatic reflexes may be modulated by input from higher brain centres, particularly the hypothalamic-cholinergic system in the tonic stimulation of preganglionic neurons of the dorsal motor nucleus of the vagus projecting into the pancreas. | 18,948,215 |
Effect of amino acids on cell proliferation and protein p53 expression in organotypic culture of lymphoid tissue from neonatal rats. | The effect of the larger molecular weight l-amino acids on the development of spleen explants from 1- and 21-day rats in organotypic tissue culture was studied. The amino acids asparagine, lysine, arginine, and glutamic acid inhibited the growth zone of explants of immature tissue from 1-day animals but had an opposite, stimulating, effect on mature spleen tissue of 21-day rats. Immunohistochemical analysis revealed a reciprocal correlation between the expression of the proapoptotic protein, p53, and T-cell proliferation in response to lysine, asparagine, and glutamic acid. Interestingly only arginine reduced the area of p53 expression both in explants of mature and immature spleen tissue. The ability of arginine to reduce p53 expression can be suggested as one of the mechanisms of the tumor growth stimulation. | 18,948,218 |
ATF-1 transcription factor regulates the expression of ccg-1 and cat-1 genes in response to fludioxonil under OS-2 MAP kinase in Neurospora crassa. | The ATF/CREB family transcriptional factors are regulated by stress-activated MAP kinase in yeast. The disruptants of the atf-1 gene, which encodes an ATF/CREB family transcriptional factor, were isolated and characterized in Neurospora crassa. The characteristic phenotypes in the os-2 MAP kinase strain, such as osmotic sensitivity and fludioxonil resistance, were not observed in the Deltaatf-1 strain; however, like the os-2 strain, up-regulation of the catalase gene cat-1 and the clock-controlled gene ccg-1 by treatment with fludioxonil (1 microg/mL) or 4% NaCl was almost completely abolished in the Deltaatf-1 strain. A gel shift assay indicated that ATF-1 bound to the cat-1 and ccg-1 promoters probably through the CRE motifs. The enzyme activity of large-subunit catalase CAT-1, the major conidial catalase, was not detected in the Deltaatf-1 strain, suggesting that the production of CAT-1 during formation of conidia is largely dependent on ATF-1. Among 11 clock-controlled genes, the expression of ccg-1, ccg-9, ccg-13, and ccg-14 was induced by fludioxonil in an OS-2-dependent manner; however, induction of ccg-13 and ccg-14 was observed in the Deltaatf-1 strain, suggesting the existence of another transcription factor regulated by OS-2. The homozygous cross between the Deltaatf-1 strains produced perithecia and ascospores; however, their ascospores never germinated. These findings suggest that ATF-1 acts as one of the transcriptional factors downstream of the OS-2 MAP kinase and probably regulates some genes involved in conidiation, circadian rhythm, and ascospore maturation in N. crassa. | 18,948,219 |
Accumulation of oxidatively induced clustered DNA lesions in human tumor tissues. | Increased levels of oxidatively induced DNA damage have been reported in various cases of human pathogenesis like age-related and chronic diseases. Advances in experimental carcinogenesis associate high oxidative stress with genome instability and oncogenic transformation. Cancer biomarkers are helpful for early tumor diagnostics, prediction of tumor development, and analysis of individual tumors' response to therapy as well as recurrence. The repair resistant oxidatively induced clustered DNA lesions (OCDLs) could serve as a common indicator of oxidative stress in human malignant cells or tissues. To test this hypothesis, we assessed the levels of endogenous OCDLs in several human tumor and adjacent normal tissues from patients with liver, ovary, kidney, breast and colon cancer. These tumor tissues have already been shown to accumulate higher endogenous levels of gamma-H2AX foci. For the detection of clustered DNA lesions we used the human repair enzymes APE1, OGG1 and NTH1 as well as the Escherichia coli homologue Endonuclease III. In the majority of cases we detected higher levels of OCDLs in tumor vs. normal tissues but not always with a statistically significant difference and not with uniform tissue dependence. These data suggest for the first time the importance of endogenous non-DSB clusters in human cancer and their potential use as cancer biomarkers. | 18,948,225 |
Diagnostic and treatment options for skin and soft tissue abscesses in injecting drug users with consideration of the natural history and concomitant risk factors. | Skin and soft tissue abscesses are common findings in injecting drug users (IDUs) who present to the surgical emergency department for evaluation and treatment. Although most cases can be managed by incision and drainage, they do require special considerations as compared to abscesses which are not caused by intravenous drug abuse. Skin and soft tissue abscesses treated in the emergency department between 2005 and 2007 were reviewed and a systematic literature search of skin and soft tissue abscesses in IDUs was conducted, including the etiology, occurrence, risk factors, and treatment options, thus providing the rationale for the treatment algorithm presented herein. The drugs injected, the technique by which they were injected, the attendant circumstances, as well as the immunological status of the IDUs were major factors for the development of abscesses. Skin and soft tissue abscesses in IDUs should be incised and drained under local or general anesthesia depending on the size, location, and association with neurovascular structures. Different factors have been taken into account when treating soft tissue abscesses in this population which predict their specific risks and therefore further therapy needs. The incidence of tetanus is high among IDUs compared to the general population, giving rise to the recommendation for a strict booster policy if the vaccination status is unclear when the patient presents to the emergency department. The presence of fever requires hospitalisation and evaluation for the presence of endocarditis. Foreign bodies, such as broken needles, should be ruled out by radiography, and duplex sonography should be performed to identify the presence of vascular complications. Prior to incision and drainage, prophylactic antimicrobial agents should be administered to every patient and as therapy for high-risk patients, such as immunocompromised patients and patients with fevers and chills. IDUs presenting with skin and soft tissue abscesses can be managed safely if some special issues are taken in account. The presented algorithm may help facilitate the decision-making in this context. | 18,948,233 |
Consequences of one-lung flooding: a histological and immunological investigation. | Videothoracoscopic lung sonography after partial fluid instillation could be a new method for endoscopic detection of lung lesions. Histopathological consequences of unilateral diagnostic or therapeutic lung flooding under bronchoalveolar lavage has yet to be defined. The aim of the study was to investigate histological and immunohistological alterations induced by one-lung flooding (OLF). 13 female pigs were subjected to OLF (15 ml isotonic electrolyte solution per kg for 60 minutes), and lung tissue was collected 30 minutes, 2 hours, 24 hours, 48 hours, 6 days, 8 days, and 10 weeks after flooding. Histological examinations and immunohistochemical labeling for surfactant protein A (SP-A) were performed. Cellular proliferation was measured by Ki67 immunohistochemical labeling. Apoptosis was detected through enzymatic in-situ labeling of apoptosis-induced DNA strand breaks by means of the TUNEL (TdT-mediated dUTP nick end labeling) method. Histological analyses revealed the presence of inflammatory cell infiltrates in the interstitium at 24 hours after OLF. However, no destruction of the alveolar wall and no pulmonary oedema were observed. In addition, OLF was not associated with any decrease in surfactant protein A immunoreactivity. Two hours after OLF, the number of apoptotic cells was increased (OLF: 7% vs. 0.6%, p < 0.05), but cellular proliferation was unchanged. Conversely, at 48 h after OLF, the number of apoptotic cells had returned to control levels, but cellular proliferation had increased (OLF: 5% vs. 1.1%, p < 0.05). Cellular proliferation returned to baseline levels eight days after OLF. These data demonstrate that OLF is not associated with destruction of the alveolar texture, atelectasis-provoking surfactant loss, or any irreversible damage to the pulmonary parenchyma. Lung flooding for the purpose of videothoracoscopic lung sonography is safe and justifiable. But repeated lung flooding under bronchoalveolar lavage involving the same lung area within 1 week is not to be recommended. | 18,948,235 |
Murine protein serine/threonine kinase 38 activates apoptosis signal-regulating kinase 1 via Thr 838 phosphorylation. | Murine protein serine/threonine kinase 38 (MPK38) is a member of the AMP-activated protein kinase-related serine/threonine kinase family that plays an important role in various cellular processes, including cell cycle, signaling pathways, and self-renewal of stem cells. Here we demonstrate a functional association between MPK38 and apoptosis signal-regulating kinase 1 (ASK1). The physical association between MPK38 and ASK1 was mediated through their carboxyl-terminal regulatory domains and was increased by H(2)O(2) or tumor necrosis factor alpha treatment. The use of kinase-dead MPK38 and ASK1 mutants revealed that MPK38-ASK1 complex formation was dependent on the activities of both kinases. Ectopic expression of wild-type MPK38, but not kinase-dead MPK38, stimulated ASK1 activity by Thr(838) phosphorylation and enhanced ASK1-mediated signaling to both JNK and p38 kinases. However, the phosphorylation of MKK6 and p38 by MPK38 was not detectable. In addition, MPK38-mediated ASK1 activation was induced through the increased interaction between ASK1 and its substrate MKK3. MPK38 also stimulated H(2)O(2)-mediated apoptosis by enhancing the ASK1 activity through Thr(838) phosphorylation. These results suggest that MPK38 physically interacts with ASK1 in vivo and acts as a positive upstream regulator of ASK1. | 18,948,261 |
DNA sequence context as a determinant of the quantity and chemistry of guanine oxidation produced by hydroxyl radicals and one-electron oxidants. | DNA sequence context has emerged as a critical determinant of the location and quantity of nucleobase damage caused by many oxidizing agents. However, the complexity of nucleobase and 2-deoxyribose damage caused by strong oxidants such as ionizing radiation and the Fenton chemistry of Fe2+-EDTA/H2O2 poses a challenge to defining the location of nucleobase damage and the effects of sequence context on damage chemistry in DNA. To address this problem, we developed a gel-based method that allows quantification of nucleobase damage in oxidized DNA by exploiting Escherichia coli exonuclease III to remove fragments containing direct strand breaks and abasic sites. The rigor of the method was verified in studies of guanine oxidation by photooxidized riboflavin and nitrosoperoxycarbonate, for which different effects of sequence context have been demonstrated by other approaches (Margolin, Y., Cloutier, J. F., Shafirovich, V., Geacintov, N. E., and Dedon, P. C. (2006) Nat. Chem. Biol. 2, 365-366). Using duplex oligodeoxynucleotides containing all possible three-nucleotide sequence contexts for guanine, the method was used to assess the role of DNA sequence context in hydroxyl radical-induced guanine oxidation associated with gamma-radiation and Fe2+-EDTA/H2O2. The results revealed both differences and similarities for G oxidation by hydroxyl radicals and by one-electron oxidation by riboflavin-mediated photooxidation, which is consistent with the predominance of oxidation pathways for hydroxyl radicals other than one-electron oxidation to form guanine radical cations. Although the relative quantities of G oxidation produced by hydroxyl radicals were more weakly correlated with sequence-specific ionization potential than G oxidation produced by riboflavin, damage produced by both hydroxyl radical generators and riboflavin within two- and three-base runs of G showed biases in location that are consistent with a role for electron transfer in defining the location of the damage products. Furthermore, both gamma-radiation and Fe2+-EDTA/H2O2 showed relatively modest effects of sequence context on the proportions of different damage products sensitive to E. coli formamidopyrimidine DNA glycosylase and hot piperidine, although GT-containing sequence contexts displayed subtle biases in damage chemistry (formamidopyrimidine DNA glycosylase/piperidine ratio). Overall, the results are consistent with the known chemistry of guanine oxidation by hydroxyl radical and demonstrate that charge migration plays a relatively minor role in determining the location and chemistry of hydroxyl radical-mediated oxidative damage to guanine in DNA. | 18,948,263 |
Glycolytic oscillations in isolated rabbit ventricular myocytes. | Previous studies have shown that glycolysis can oscillate periodically, driven by feedback loops in regulation of key glycolytic enzymes by free ADP and other metabolites. Here we show both theoretically and experimentally in cardiac myocytes that when the capacity of oxidative phosphorylation and the creatine kinase system to buffer the cellular ATP/ADP ratio is suppressed, glycolysis can cause large scale periodic oscillations in cellular ATP levels (0.02-0.067 Hz), monitored from glibenclamide-sensitive changes in action potential duration or intracellular free Mg2+. Action potential duration oscillations originate primarily from glycolysis, since they 1) occur in the presence of cyanide or rotenone, 2) are suppressed by iodoacetate, 3) are accompanied by at most very small mitochondrial membrane potential oscillations, and 4) exhibit an anti-phase relationship to NADH fluorescence. By uncoupling energy supply-demand balance, glycolytic oscillations may promote injury and electrophysiological heterogeneity during acute metabolic stresses, such as acute myocardial ischemia in which both oxidative phosphorylation and creatine kinase activity are inhibited. | 18,948,270 |
Chk2 oligomerization studied by phosphopeptide ligation: implications for regulation and phosphodependent interactions. | Chk2/CHEK2/hCds1 is a modular serine-threonine kinase involved in transducing DNA damage signals. Phosphorylation by ataxia telangiectasia-mutated kinase (ATM) promotes Chk2 self-association, autophosphorylation, and activation. Here we use expressed protein ligation to generate a Chk2 N-terminal regulatory region encompassing a fork-head-associated (FHA) domain, a stoichiometrically phosphorylated Thr-68 motif and intervening linker. Hydrodynamic analysis reveals that Thr-68 phosphorylation stabilizes weak FHA-FHA interactions that occur in the unphosphorylated species to form a high affinity dimer. Although clearly a prerequisite for Chk2 activation in vivo, we show that dimerization modulates potential phosphodependent interactions with effector proteins and substrates through either the pThr-68 site, or the canonical FHA phosphobinding surface with which it is tightly associated. We further show that the dimer-occluded pThr-68 motif is released by intra-dimer autophosphorylation of the FHA domain at the highly conserved Ser-140 position, a major pThr contact in all FHA-phosphopeptide complex structures, revealing a mechanism of Chk2 dimer dissociation following kinase domain activation. | 18,948,271 |
MAPU 2.0: high-accuracy proteomes mapped to genomes. | The MAPU 2.0 database contains proteomes of organelles, tissues and cell types measured by mass spectrometry (MS)-based proteomics. In contrast to other databases it is meant to contain a limited number of experiments and only those with very high-resolution and -accuracy data. MAPU 2.0 displays the proteomes of organelles, tissues and body fluids or conversely displays the occurrence of proteins of interest in all these proteomes. The new release addresses MS-specific problems including ambiguous peptide-to-protein assignments and it provides insight into general functional features on the protein level ranging from gene ontology classification to comprehensive SwissProt annotation. Moreover, the derived proteomic data are used to annotate the genomes using Distributed Annotation Service (DAS) via EnsEMBL services. MAPU 2.0 is a model for a database specifically designed for high-accuracy proteomics and a member of the ProteomExchange Consortium. It is available on line at http://www.mapuproteome.com. | 18,948,283 |
What next for preimplantation genetic screening? More randomized controlled trials needed? | The recent debate on preimplantation genetic screening (PGS) has raised questions about its routine use in clinical practice. It has been suggested that the most effective way to resolve the debate about the usefulness of PGS is to perform more well-designed and well-executed randomized controlled trials (RCTs). However, in view of the lack of evidence for the effectiveness of PGS and the accumulating evidence for its harmfulness, it is our opinion that it is unethical to perform additional RCTs for the indication advanced maternal age using cleavage stage biopsy. | 18,948,310 |
The role of the bronchial provocation challenge tests in the diagnosis of exercise-induced bronchoconstriction in elite swimmers. | The International Olympic Committee-Medical Commission (IOC-MC) accepts a number of bronchial provocation tests for the diagnosis of exercise-induced bronchoconstriction (EIB) in elite athletes, none of which have been studied in elite swimmers. With the suggestion of a different pathogenesis involved in the development of EIB in swimmers, there is a possibility that the recommended test for EIB in elite athletes, the eucapnic voluntary hyperpnoea (EVH) challenge, may be missing the diagnosis in elite swimmers. The aim of this study was to assess the effectiveness of the EVH challenge, the field swim challenge and the laboratory cycle challenge in the diagnosis of EIB in elite swimmers. 33 elite swimmers were evaluated on separate days for the presence of EIB using 3 different bronchial provocation challenge tests: an 8 minute field swim challenge, a 6 minute laboratory EVH challenge, and an 8 minute laboratory cycle challenge. Change in forced expiratory volume in 1 second (FEV(1)) pre and post test protocol. A fall in FEV(1) from baseline of > or =10% post challenge was diagnostic of EIB. Only 1 of the 33 subjects (3%) had a positive field swim challenge with a fall in FEV(1) of 16% from baseline. 18 of the 33 subjects (55%) had a positive EVH challenge, with a mean fall in FEV(1) of 20.4 (SD 11.7)% from baseline. 4 of the subjects (12%) had a positive laboratory cycle challenge, with a mean fall in FEV(1) of 14.8 (4.7)% from baseline. Only 1 of the 33 subjects was positive to all 3 challenges. These results suggest that the EVH challenge is a highly sensitive challenge for identifying EIB in elite swimmers, in contrast to the laboratory and field-based exercise challenge tests, which significantly underdiagnose the condition. The EVH challenge, a well-established and standardised test for EIB in elite winter and summer land-based athletes, should thus be used for the diagnosis of EIB in elite swimmers, as recommended by the IOC-MC. | 18,948,353 |
Relationships between motor impairments and activity limitations in patients with neuromuscular disorders. | The strength and nature of the relationships between motor impairments and activity limitations assessed by the ACTIVLIM questionnaire were investigated in 245 patients with neuromuscular disorders. Measures of motor impairments consisted of: (1) a grip strength test using a Jamar dynamometer, (2) a Manual Muscle Testing bilaterally performed in 18 muscle groups and (3) a gait speed spontaneously adopted by the patients using the 10 m timed walking test. Activity limitations were poorly correlated with grip strength in both hands (r = 0.3 and 0.36) and moderately correlated with gait speed (r = 0.53). Spearman's coefficients of correlation between the manual muscle testing and activity limitations were moderate to very poor (rho = 0.5 to 0.17). The relationships between motor impairments and activity limitations are not straightforward in patients with neuromuscular disorders, indicating that the activity limitations should be separately assessed and cannot be simply inferred from motor impairment measures. | 18,948,363 |
Prediction of recurrent venous thromboembolism by endogenous thrombin potential and D-dimer. | Increased thrombin generation is associated with an increased risk of recurrent venous thromboembolism. We investigated the relation between endogenous thrombin potential (ETP) and risk of recurrent venous thromboembolism and evaluated whether prediction of recurrence can be improved by a combined analysis of ETP and D-dimer. We followed 861 patients with first spontaneous venous thromboembolism and determined ETP and D-dimer after discontinuation of anticoagulation. Patients with natural inhibitor deficiency, lupus anticoagulant, or cancer were excluded. The study endpoint was symptomatic recurrent venous thromboembolism. One hundred thirty patients (15.1%) had recurrence. High ETP (> or = 100%) conferred a 1.6-fold increased risk of recurrence (95% CI 1.1-2.3) after adjustment for age, sex, factor V Leiden, factor II G20210A, and duration of anticoagulation. After adjustment for D-dimer, risk of recurrence remained significantly higher among patients with high ETP [hazard ratio 1.6 (95% CI 1.01-2.4)]. After adjustment for ETP, high D-dimer (> or = 0.5 mg/L) conferred a 1.8-fold (95% CI 1.1-2.8) increased risk of recurrence. Compared with patients with low ETP and low D-dimer, risk of recurrence was 2.8-fold (95% CI 1.5-5.3) higher among patients with both high ETP and high D-dimer after adjustment for potential confounders. ETP and D-dimer are independent predictors of recurrent venous thromboembolism. Assessing risk of recurrence can be optimized by combining these indicators of thrombin generation. | 18,948,369 |
Use of joint mobilization in a patient with severely restricted hip motion following bilateral hip resurfacing arthroplasty. | Hip resurfacing arthroplasty (HRA) is an alternative for management of end-stage osteoarthritis (OA) in young patients with high activity demands and offers several advantages over total hip arthroplasty. Severely restricted hip motion is a rare complication of the surgery. The purpose of this case report is to describe the treatment for a patient who developed severely restricted hip motion following bilateral HRA. A 43-year-old, athletic man underwent bilateral HRA and developed severely restricted hip motion. At 3 months postoperatively, the patient had approximately 90 degrees of hip flexion and 10 degrees of lateral rotation bilaterally. A multimodal treatment approach with an emphasis on joint mobilization was incorporated to improve hip joint mobility by restoring accessory motion. The patient's passive range of motion (PROM) and Harris Hip Score (HHS) at the time of discharge showed clinically significant improvements. Total disability, as measured by the HHS, improved by 13 points, and total PROM increased 82 degrees in the right hip and 101 degrees in the left hip. The patient became independent and had full return to all activities and sports. The patient showed clinically meaningful improvements in PROM measurements and functional activities during a course of care using a multimodal treatment approach with an emphasis on joint mobilization. This is the first case report to describe the treatment for a patient who developed severely restricted hip motion following bilateral HRA. | 18,948,372 |
Human flavin-containing monooxygenase 2.1 catalyzes oxygenation of the antitubercular drugs thiacetazone and ethionamide. | The second-line antitubercular drugs thiacetazone (TAZ) and ethionamide (ETA) are bioactivated by the mycobacterial enzyme EtaA. We report here that human flavin-containing monooxygenase 2.1 (FMO2.1), which is expressed predominantly in the lung, catalyzes oxygenation of TAZ. The metabolites generated, the sulfenic acid, sulfinic acid, and carbodiimide derivatives, are the same as those produced by EtaA and human FMO1 and FMO3. Two of the metabolites, the sulfenic acid and carbodiimide, are known to be harmful to mammalian cells. FMO2.1 also catalyzes oxygenation of ETA, producing the S-oxide. We have developed a novel spectrophotometric assay for TAZ oxygenation. The assay was used to determine kinetic parameters for TAZ oxygenation catalyzed by human FMO1, FMO2.1, and FMO3 and by EtaA. Although the K(M) values for the four enzyme-catalyzed reactions are similar, k(cat) and, consequently, k(cat)/K(M) (the specificity constant) for FMO2.1-catalyzed TAZ oxygenation are much higher than those of FMO1, FMO3, or EtaA. This indicates that FMO2.1 is more effective in catalyzing TAZ oxygenation than are the other three enzymes and thus is likely to contribute substantially to the metabolism of TAZ, decreasing the availability of the prodrug to mycobacteria and producing toxic metabolites. Because of a genetic polymorphism, Europeans and Asians lack FMO2.1. However, in sub-Saharan Africa, a region in which tuberculosis is a major health problem, a substantial proportion of individuals express FMO2.1. Thus, our results may explain some of the observed interindividual differences in response to TAZ and ETA and have implications for the treatment of tuberculosis in sub-Saharan Africa. | 18,948,378 |
Real-time visualization of ultrasound-guided retrobulbar blockade: an imaging study. | Retrobulbar anaesthesia allows eye surgery in awake patients. Severe complications of the blind techniques are reported. Ultrasound-guided needle introduction and direct visualization of the spread of local anaesthetic may improve quality and safety of retrobulbar anaesthesia. Therefore, we developed a new ultrasound-guided technique using human cadavers. In total, 20 blocks on both sides in 10 embalmed human cadavers were performed. Using a small curved array transducer and a long-axis approach, a 22 G short bevel needle was introduced under ultrasound guidance lateral and caudal of the eyeball until the needle tip was seen 2 mm away from the optic nerve. At this point, 2 ml of contrast dye as a substitute for local anaesthetic was injected. Immediately after the injection, the spread of the contrast dye was documented by means of CT scans performed in each cadaver. The CT scans showed the distribution of the contrast dye in the muscle cone and behind the posterior sclera in all but one case. No contrast dye was found inside the optic nerve or inside the eyeball. In one case, there could be an additional trace of contrast dye behind the orbita. Our new ultrasound-guided technique has the potential to improve safety and efficacy of the procedure by direct visualization of the needle placement and the distribution of the injected fluid. Furthermore, the precise injection near the optic nerve could lead to a reduction of the amount of the local anaesthetic needed with fewer related complications. | 18,948,389 |
Spread of invasive Spanish Staphylococcus aureus spa-type t067 associated with a high prevalence of the aminoglycoside-modifying enzyme gene ant(4')-Ia and the efflux pump genes msrA/msrB. | We carried out a nationwide study aimed at the determination of the molecular epidemiology and antibiotic resistance mechanisms of invasive Staphylococcus aureus in 21 Spanish hospitals. The distributions of molecular markers, including antibiotic resistance genes, were investigated in 203 S. aureus, comprising 90 methicillin-resistant S. aureus (MRSA) and 113 methicillin-susceptible S. aureus (MSSA). Antimicrobial susceptibility was determined by standard methods. Panton-Valentine leucocidin (PVL) detection, staphylococcal cassette chromosome mec (SCCmec) types and agr types were performed/determined by PCR. All isolates were genotyped by PFGE after digestion of chromosomal DNA with SmaI. Multilocus sequence typing and spa-typing were also performed. In MRSA isolates, 74.4% were agr allotype II and were positive for SCCmec IV. Sixty-nine spa-types were identified, 18 in MRSA and 57 in MSSA. Both MRSA and MSSA variants were detected in six spa-types (8.7%). The majority of S. aureus (51.2%) were grouped into four spa-types (t067, t002, t012 and t008). The spa-type t067 was detected in 18 of the 21 (85.7%) participating hospitals, including both MRSA and MSSA in six of them; in total, 25.9% of our isolates were spa-type t067 (49% in MRSA) in comparison with 0.6% in a central spa-typing database. The prevalence of the ant(4')-Ia and msrA/msrB genes was significantly higher in the MRSA spa-type t067 than in the other MRSA spa-types. Association between spa-type t067 and ST125 is described here for the first time. A high prevalence (36.4%) of PVL-positive MSSA was detected. A higher than expected prevalence of spa-type t067 isolates was found among invasive MRSA in Spain. The oxacillin, tobramycin, erythromycin and ciprofloxacin resistance profile of spa-type t067 isolates was linked to the presence of ant(4')-Ia and msrA or msrB genes. | 18,948,410 |
A once-weekly R207910-containing regimen exceeds activity of the standard daily regimen in murine tuberculosis. | R207910 (TMC207 or J) is a member of the diarylquinolines, a new family of antituberculous drugs with high bactericidal activity when given daily in the murine model of tuberculosis. R207910 exhibits a long half-life and thus is a good candidate for once-weekly therapy of tuberculosis. To study the activity of once-weekly R207910 monotherapy and combinations of R207910 with other antituberculous agents (isoniazid, rifapentine, moxifloxacin, and pyrazinamide). The established infection model of murine tuberculosis was used. Colony counts were determined in the lungs. Eight weeks of monotherapy reduced the bacillary load by 3 to 4 log(10) for rifapentine and by 5 to 6 log(10) for R207910 (P < 0.05). The addition of rifapentine and isoniazid or moxifloxacin did not improve the bactericidal activity of R207910 monotherapy. In contrast, the triple combination of R207910 plus rifapentine plus pyrazinamide given once weekly for 2 months (i.e., a total of only eight administrations), was significantly (P < 0.05) more active than R207910 monotherapy or other R207910 combinations, and led to lung culture negativity in 9 of 10 mice, whereas all lungs were culture positive in the groups treated with other drug combinations. Moreover, R207910 plus rifapentine plus pyrazinamide given once weekly was more active than the current standard regimen of rifampin plus isoniazid plus pyrazinamide given five times per week. The unprecedented activity of the triple combination of R207910 plus rifapentine plus pyrazinamide suggests that it may be feasible to develop a fully intermittent once-weekly regimen. | 18,948,422 |
Distribution and function of monoacylglycerol lipase in the gastrointestinal tract. | The endogenous cannabinoid system plays an important role in the regulation of gastrointestinal function in health and disease. Endocannabinoid levels are regulated by catabolic enzymes. Here, we describe the presence and localization of monoacylglycerol lipase (MGL), the major enzyme responsible for the degradation of 2-arachidonoylglycerol. We used molecular, biochemical, immunohistochemical, and functional assays to characterize the distribution and activity of MGL. MGL mRNA was present in rat ileum throughout the wall of the gut. MGL protein was distributed in the muscle and mucosal layers of the ileum and in the duodenum, proximal colon, and distal colon. We observed MGL expression in nerve cell bodies and nerve fibers of the enteric nervous system. There was extensive colocalization of MGL with PGP 9.5 and calretinin-immunoreactive neurons, but not with nitric oxide synthase. MGL was also present in the epithelium and was highly expressed in the small intestine. Enzyme activity levels were highest in the duodenum and decreased along the gut with lowest levels in the distal colon. We observed both soluble and membrane-associated enzyme activities. The MGL inhibitor URB602 significantly inhibited whole gut transit in mice, an action that was abolished in cannabinoid 1 receptor-deficient mice. In conclusion, MGL is localized in the enteric nervous system where endocannabinoids regulate intestinal motility. MGL is highly expressed in the epithelium, where this enzyme may have digestive or other functions yet to be determined. | 18,948,437 |
Evaluation of two methods for continuous cardiac output assessment during exercise in chronic heart failure patients. | The purpose of this study was to evaluate the accuracy of two techniques for the continuous assessment of cardiac output in patients with chronic heart failure (CHF): a radial artery pulse contour analysis method that uses an indicator dilution method for calibration (LiDCO) and an impedance cardiography technique (Physioflow), using the Fick method as a reference. Ten male CHF patients (New York Heart Association class II-III) were included. At rest, cardiac output values obtained by LiDCO and Physioflow were compared with those of the direct Fick method. During exercise, the continuous Fick method was used as a reference. Exercise, performed on a cycle ergometer in upright position, consisted of two constant-load tests at 30% and 80% of the ventilatory threshold and a symptom-limited maximal test. Both at rest and during exercise LiDCO showed good agreement with reference values [bias +/- limits of agreement (LOA), -1% +/- 28% and 2% +/- 28%, respectively]. In contrast, Physioflow overestimated reference values both at rest and during exercise (bias +/- LOA, 48% +/- 60% and 48% +/- 52%, respectively). Exercise-related within-patient changes of cardiac output, expressed as a percent change, showed for both techniques clinically acceptable agreement with reference values (bias +/- LOA: 2% +/- 26% for LiDCO, and -2% +/- 36% for Physioflow, respectively). In conclusion, although the limits of agreement with the Fick method are pretty broad, LiDCO provides accurate measurements of cardiac output during rest and exercise in CHF patients. Although Physioflow overestimates cardiac output, this method may still be useful to estimate relative changes during exercise. | 18,948,448 |
Quantifying carbon dioxide and methane emissions and carbon dynamics from flooded boreal forest soil. | The boreal forest is subject to natural and anthropogenic disturbances, but the production of greenhouse gases as a result of flooding for hydroelectric power generation has received little attention. It was hypothesized that flooded soil would result in greater CO(2) and CH(4) emissions and carbon (C) fractionation compared with non-flooded soil. To evaluate this hypothesis, soil C and nitrogen (N) dynamics, CO(2) and CH(4) mean production rates, and (13)C fractionation in laboratory incubations at 14 and 21 degrees C under non-flooded and flooded conditions and its effect on labile and recalcitrant C sources were determined. A ferro-humic Podzol was collected at three different sites at the Experimental Lakes Area, Canada, with a high (19,834 g C m(-2)), medium (18,066 g C m(-2)), and low (11,060 g C m(-2)) soil organic C (SOC) stock. Soil organic C and total N stocks (g m(-2)) and concentrations (g kg(-1)) were significantly different (p < 0.05) among soil horizons within each of the three sites. Stable isotope analysis showed a significant enrichment in delta(13)C and delta(15)N with depth and an enrichment in delta(13)C and delta(15)N with decreasing SOC and N concentration. The mean CO(2) and CH(4) production rates were greatest in soil horizons with the highest SOC stock and were significantly higher at 21 degrees C and in flooded treatments. The delta(13)C of the evolved CO(2) (delta(13)C-CO(2)) became significantly enriched with time during decomposition, and the greatest degree of fractionation occurred in the organic Litter, Fungal, and Humic forest soil horizons and in soil with a high SOC stock compared with the mineral horizon and soil with a lower SOC stock. The delta(13)C-CO(2) was significantly depleted in flooded treatments compared with non-flooded treatments. | 18,948,456 |
Is colloid-facilitated phosphorus leaching triggered by phosphorus accumulation in sandy soils? | The leaching of colloidal phosphorus (P(coll)) contributes to P losses from agricultural soils. In an irrigation experiment with undisturbed soil columns, we investigated whether the accumulation of P in soils due to excess P additions enhances the leaching of colloids and P(coll) from sandy soils. Furthermore, we hypothesized that large concentrations of P(coll) occur at the onset of leaching events and that P(coll) mobilized from topsoils is retained in subsoils. Soil columns of different P saturation and depth (0-25 and 0-40 cm) were collected at a former disposal site for liquid manure and at the Thyrow fertilization experiment in northeastern Germany. Concentrations of total dissolved P, P(coll), Fe(coll), Al(coll), optical density, zeta potential, pH, and electrical conductivity of the leachates were determined. Colloidal P concentrations ranged from 0.46 to 10 micromol L(-1) and contributed between 1 and 37% to total P leaching. Large P(coll) concentrations leached from the P-rich soil of the manure disposal site were rather related to a large P-content of colloids than to the mobilization of additional colloids. Concentrations of colloids and P(coll) in leachates from P-poor and P-rich columns from Thyrow did not differ significantly. In contrast, accumulation of P in the Werbellin and the Thyrow soil consistently increased dissolved P concentrations to maximum values as high as 300 micromol L(-1). We observed no first-flush of colloids and P(coll) at the beginning of the leaching event. Concentrations of P(coll) leached from 40-cm soil columns were not smaller than those leached from 25-cm columns. Our results illustrate that an accumulation of P in sandy soils does not necessarily lead to an enhanced leaching of colloids and P(coll), because a multitude of factors independent from the P status of soils control the mobility of colloids. In contrast, P accumulation generally increases dissolved P concentrations in noncalcareous soils due to the saturation of the P sorption capacity. This indicates that leaching of dissolved P might be a more widespread environmental problem in areas with P-saturated sandy soils than leaching of P(coll). | 18,948,463 |
Persistence of culturable Escherichia coli fecal contaminants in dairy alpine grassland soils. | Our knowledge of Escherichia coli (E. coli) ecology in the field is very limited in the case of dairy alpine grassland soils. Here, our objective was to monitor field survival of E. coli in cow pats and underlying soils in four different alpine pasture units, and to determine whether the soil could constitute an environmental reservoir. E. coli was enumerated by MPN using a selective medium. E. coli survived well in cow pats (10(7) to 10(8) cells g(-1) dry pat), but cow pats disappeared within about 2 mo. In each pasture unit, constant levels of E. coli (10(3) to 10(4) cells g(-1) dry soil) were recovered from all topsoil (0-5 cm) samples regardless of the sampling date, that is, under the snow cover, immediately after snow melting, or during the pasture season (during and after the decomposition of pats). In deeper soil layers below the root zone (5-25 cm), E. coli persistence varied according to soil type, with higher numbers recovered in poorly-drained soils (10(3) to 10(4) cells g(-1) dry soil) than in well-drained soils (< 10(2) cells g(-1) dry soil). A preliminary analysis of 38 partial uidA sequences of E. coli from pat and soils highlighted a cluster containing sequences only found in this work. Overall, this study raises the possibility that fecal E. coli could have formed a naturalized (sub)population, which is now part of the indigenous soil community of alpine pasture grasslands, the soil thus representing an environmental reservoir of E. coli. | 18,948,484 |
Evaluating slurry broadcasting and injection to ley for phosphorus losses and fecal microorganisms in surface runoff. | The recent growth in the size of dairy cattle farms and the concentration of farms into smaller areas in Finland may increase local water pollution due to increased manure production and slurry application to grass. Therefore, a field study was conducted to monitor losses of total phosphorus (TP), dissolved reactive phosphorus (DRP), and fecal microorganisms in surface runoff from a perennial ley. Cattle slurry was added once a year in June 1996-1997 (Study I) and biannually in June and October 1998-2000 (Study II). The slurry was surface broadcast or injected into the clay soil. The field had a slope of 0.9 to 1.7%. Mineral fertilizer was applied on control plots. Biannual slurry broadcasting increased DRP (p < 0.001) and TP losses (p < 0.001) and numbers of fecal microorganisms in surface runoff waters. The highest losses of TP (2.7 kg ha(-1) yr(-1)) and DRP (2.2 kg ha(-1) yr(-1)) and the highest numbers of fecal coliforms (880 colony-forming units [CFU] per 100 mL) and somatic coliphages (2700 plaque-forming units [PFU] per 100 mL) were measured after broadcasting slurry to wet soil followed by rainfall in fall 1998. Injection reduced the TP and DRP losses in surface runoff by 79 and 86%, respectively, compared with broadcasting (17 Oct. 1998-27 Oct. 1999). Corresponding numbers for fecal coliforms were 350 CFU (100 mL)(-1) and for somatic coliphages were 110 PFU (100 mL)(-1) in surface runoff after injection in October 1998. Slurry injection should be favored when spreading slurry amendments to grassland to avoid losses of P and fecal microorganisms in runoff to surface waters. | 18,948,488 |
Regulation of microtubule dynamics by reaction cascades around chromosomes. | During spindle assembly, chromosomes generate gradients of microtubule stabilization through a reaction-diffusion process, but how this is achieved is not well understood. We measured the spatial distribution of microtubule aster asymmetry around chromosomes by incubating centrosomes and micropatterned chromatin patches in frog egg extracts. We then screened for microtubule stabilization gradient shapes that would generate such spatial distributions with the use of computer simulations. Only a long-range, sharply decaying microtubule stabilization gradient could generate aster asymmetries fitting the experimental data. We propose a reaction-diffusion model that combines the chromosome generated Ran-guanosine triphosphate-Importin reaction network to a secondary phosphorylation network as a potential mechanism for the generation of such gradients. | 18,948,504 |
The Gonzo Scientist. Flunking Spore. | The blockbuster video game Spore is being marketed as a science-based adventure that brings evolution, cell biology, and even astrophysics to the masses. But after grading the game's science with a team of researchers, the Gonzo Scientist has some bad news. | 18,948,523 |
Functional traits and niche-based tree community assembly in an Amazonian forest. | It is debated whether species-level differences in ecological strategy, which play a key role in much of coexistence theory, are important in structuring highly diverse communities. We examined the co-occurrence patterns of over 1100 tree species in a 25-hectare Amazonian forest plot in relation to field-measured functional traits. Using a null model approach, we show that co-occurring trees are often less ecologically similar than a niche-free (neutral) model predicts. Furthermore, we find evidence for processes that simultaneously drive convergence and divergence in key aspects of plant strategy, suggesting that at least two distinct niche-based processes are occurring. Our results show that strategy differentiation among species contributes to the maintenance of diversity in one of the most diverse tropical forests in the world. | 18,948,539 |
H2S as a physiologic vasorelaxant: hypertension in mice with deletion of cystathionine gamma-lyase. | Studies of nitric oxide over the past two decades have highlighted the fundamental importance of gaseous signaling molecules in biology and medicine. The physiological role of other gases such as carbon monoxide and hydrogen sulfide (H2S) is now receiving increasing attention. Here we show that H2S is physiologically generated by cystathionine gamma-lyase (CSE) and that genetic deletion of this enzyme in mice markedly reduces H2S levels in the serum, heart, aorta, and other tissues. Mutant mice lacking CSE display pronounced hypertension and diminished endothelium-dependent vasorelaxation. CSE is physiologically activated by calcium-calmodulin, which is a mechanism for H2S formation in response to vascular activation. These findings provide direct evidence that H2S is a physiologic vasodilator and regulator of blood pressure. | 18,948,540 |
Age-dependent, polyclonal hyperactivation of T cells is reduced in TNF-negative gld/gld mice. | The generalized lymphoproliferative disorder (gld) mouse strain is characterized by severe splenomegaly/lymphadenopathy, the production of autoimmune antibodies, and the appearance of CD4/CD8-negative T cells. An additional TNF deficiency of gld/gld mice attenuates the course of the disorder through a yet-unknown mechanism. In this study, we could demonstrate that the reduced splenomegaly and lymphadenopathy in B6.gld/gld.TNF-/- mice were correlated with a decreased peripheral T cell proliferation rate and a delayed polyclonal activation. A comparative analysis of naïve T cells and memory/effector T cells showed an age-dependent difference in the T cell activation pattern in the spleen of B6.gld/gld and B6.gld/gld.TNF-/- mice. T cells from B6.gld/gld.TNF-/- spleens and lymph nodes showed significantly higher levels of CCR7 and CD62 ligand on their surface compared with B6.gld/gld mice when mice of the same age were compared. Additionally, we found an increased titer of the Th1 cytokine IFN-gamma in the serum of B6.gld/gld mice, whereas the concentration of IFN-gamma was markedly reduced in the serum of B6.gld/gld.TNF-/- mice. These findings support the hypothesis that increased T cell activation and proliferation in the presence of TNF contribute to the exacerbation of the gld syndrome. | 18,948,547 |
Molecular and functional interactions among monocytes, platelets, and endothelial cells and their relevance for cardiovascular diseases. | Platelets, monocytes, and endothelial cells are instrumental in the development and progression of cardiovascular diseases. Inflammation, a key process underlying cardiovascular disorders, is accompanied and amplified by activation of platelets and consequent binding of such platelets to the endothelium. There, platelet-derived chemokines, in conjunction with increased expression of adhesion molecules, promote the recruitment of circulating monocytes that will eventually migrate across the endothelial lining of the vessel into the tissues. Additionally, platelets may already become activated in the circulation and may form platelet-monocyte complexes, which show increased adhesive and migratory capacities themselves but also facilitate recruitment of noncomplexed leukocytes. They should therefore be considered as important mediators of inflammation. In molecular terms, these events are additionally governed by chemokines released and presented by the endothelium as well as the different classes of endothelial adhesion molecules that regulate the interactions among the various cell types. Most important in this respect are the selectins and their ligands, such as P-selectin glycoprotein (GP) ligand 1, and the integrins binding to Ig-like cell adhesion molecules as well as to GP, such as von Willebrand factor, present in the extracellular matrix or on activated endothelium. This review aims to provide an overview of these complex interactions and of their functional implications for inflammation and development of cardiovascular disease. | 18,948,548 |
L-carnitine supplementation and physical exercise restore age-associated decline in some mitochondrial functions in the rat. | In mammals, during the aging process, an atrophy of the muscle fibers, an increase in body fat mass, and a decrease in skeletal muscle oxidative capacities occur. Compounds and activities that interact with lipid oxidative metabolism may be useful in limiting damages that occur in aging muscle. In this study, we evaluated the effect of L-carnitine and physical exercise on several parameters related to muscle physiology. We described that supplementing old rats with L-carnitine at 30 mg/kg body weight for 12 weeks (a) allowed the restoration of L-carnitine level in muscle cells, (b) restored muscle oxidative activity in the soleus, and (c) induced positive changes in body composition: a decrease in abdominal fat mass and an increase in muscle capabilities without any change in food intake. Moderate physical exercise was also effective in (a) limiting fat mass gain and (b) inducing an increase in the capacities of the soleus to oxidize fatty acids. | 18,948,552 |
Cumulative deficits and physiological indices as predictors of mortality and long life. | We evaluated the predictive potential for long-term (24-year) survival and longevity (85+ years) of an index of cumulative deficits (DI) and six physiological indices (pulse pressure, diastolic blood pressure, pulse rate, serum cholesterol, blood glucose, and hematocrit) measured in mid- to late life (44-88 years) for participants of the 9th and 14th Framingham Heart Study examinations. For all ages combined, the DI, pulse pressure, and blood glucose are the strongest determinants of both long-term survival and longevity, contributing cumulatively to their explanation. Diastolic blood pressure and hematocrit are less significant determinants of both of these outcomes. The pulse rate is more relevant to survival, whereas serum cholesterol is more relevant to longevity. Only the DI is a significant predictor of longevity and mortality for each 5-year age group ranging from 45 to 85 years. The DI appears to be a more important determinant of long-term risks of death and longevity than are the physiological indices. | 18,948,555 |
Loss of ephrin-A5 function disrupts lens fiber cell packing and leads to cataract. | Cell-cell interactions organize lens fiber cells into highly ordered structures to maintain transparency. However, signals regulating such interactions have not been well characterized. We report here that ephrin-A5, a ligand of the Eph receptor tyrosine kinases, plays a key role in lens fiber cell shape and cell-cell interactions. Lens fiber cells in mice lacking ephrin-A5 function appear rounded and irregular in cross-section, in contrast to their normal hexagonal appearance in WT lenses. Cataracts eventually develop in 87% of ephrin-A5 KO mice. We further demonstrate that ephrin-A5 interacts with the EphA2 receptor to regulate the adherens junction complex by enhancing recruitment of beta-catenin to N-cadherin. These results indicate that the Eph receptors and their ligands are critical regulators of lens development and maintenance. | 18,948,590 |
Roles of RIG-I N-terminal tandem CARD and splice variant in TRIM25-mediated antiviral signal transduction. | The caspase recruitment domain (CARD) of intracellular adaptors and sensors plays a critical role in the assembly of signaling complexes involved in innate host defense against pathogens and in the regulation of inflammatory responses. The cytosolic receptor retinoic acid-inducible gene-I (RIG-I) recognizes viral RNA in a 5'-triphosphate-dependent manner and initiates an antiviral signaling cascade. Upon viral infection, the N-terminal CARDs of RIG-I undergo the K(63)-linked ubiquitination induced by tripartite motif protein 25 (TRIM25), critical for the interaction of RIG-I with its downstream signaling partner MAVS/VISA/IPS-1/Cardif. Here, we demonstrate the distinct roles of RIG-I first and second CARD in TRIM25-mediated RIG-I ubiquitination: TRIM25 binds the RIG-I first CARD and subsequently ubiquitinates its second CARD. The T(55)I mutation in RIG-I first CARD abolishes TRIM25 interaction, whereas the K(172)R mutation in the second CARD eliminates polyubiquitin attachment. The necessity of the intact tandem CARD for RIG-I function is further evidenced by a RIG-I splice variant (SV) whose expression is robustly up-regulated upon viral infection. The RIG-I SV carries a short deletion (amino acids 36-80) within the first CARD and thereby loses TRIM25 binding, CARD ubiquitination, and downstream signaling ability. Furthermore, because of its robust inhibition of virus-induced RIG-I multimerization and RIG-I-MAVS signaling complex formation, this SV effectively suppresses the RIG-I-mediated IFN-beta production. This study not only elucidates the vital role of the intact tandem CARD for TRIM25-mediated RIG-I activation but also identifies the RIG-I SV as an off-switch regulator of its own signaling pathway. | 18,948,594 |
Cause and effect in childhood obesity: solutions for a national epidemic. | Childhood obesity has reached epidemic proportions in the United States. As a result, children are at increased risk for myriad preventable acute and chronic medical problems--many of which are associated with increased morbidity and mortality. In addition, childhood obesity has serious psychosocial consequences, such as low self-esteem, lower quality of life, and depression. The multifaceted causes and solutions to this pervasive health issue are discussed in the present review, as are pertinent health policy issues. Osteopathic physicians and other healthcare providers can play an important role in patient and family education, direct care, and advocacy. | 18,948,638 |
Mutation analysis of RAP1 gene in papillary thyroid carcinomas. | In human papillary thyroid carcinomas (PTCs), the genetic alterations of RET/PTC, RAS or BRAF account for about 60-70% of cases with practically no overlap, providing strong genetic evidence that constitutive active signaling along MAPK pathway is critical for PTC development. In the remaining 30-40% of the cases, the oncogenes are still unknown. RAP1 is a member of the RAS family of small G proteins transmitting signals from the TSH-R to MAPK pathway using cAMP-dependent mechanism in thyroid cells. RAP1 was shown to have both mitogenic and tumorigenic properties in certain systems; however, the potential role of RAP1 mutation in thyroid carcinogenesis has yet to be elucidated. In this study, we analyzed the mutational status of RAP1 gene in 36 Russian patients with PTCs without RET/PTC rearrangement, BRAF mutation or RAS mutation. No mutations in either RAP1A or RAP1B genes were found. These results suggest that RAP1 mutation does not play an important role in PTC pathogenesis. | 18,948,674 |
Chiasmal and/or optic nerve apoplexy due to rupture of vascular malformation--case report--. | An 8-year-old boy presented with a rare case of optic nerve apoplexy caused by an arteriovenous malformation (AVM) manifesting as severe headache and blurred vision. Computed tomography (CT) showed a hyperdense suprasellar mass. Magnetic resonance (MR) imaging indicated a hematoma in the right optic nerve. MR angiography showed normal vessels. Right fronto-temporal craniotomy identified an aggregate of abnormal, nidus-like vessels adhering to the medial surface of the swollen right optic nerve and a drainer-like ectatic red vein. The diagnosis was probable AVM. To avoid optic nerve damage, the malformation was left intact. Two years later, the boy was readmitted with headache. CT showed bleeding, and angiography revealed feeder arteries and nidus in the suprasellar lesion. The diagnosis was optic nerve apoplexy due to AVM. His symptoms improved without intervention within days. He has not experienced any recurrence of the bleeding for 2 years. | 18,948,681 |
Lipomatous meningioma with concomitant acute subdural hematoma--case report--. | A 55-year-old man presented with a rare lipomatous meningioma associated with acute subdural hematoma manifesting as sudden onset of severe headache, but no neurological deficit. No evidence of trauma or underlying predisposition to hemorrhage was seen. Fluid-attenuated inversion-recovery magnetic resonance imaging showed a thin hyperintense area in the right temporal convexity, and an extra-axial mass appearing as mixed hypointensity and hyperintensity. Two weeks later, right temporal craniotomy was performed and the tumor was totally resected with the attached dura. The hematoma was localized at the inferior margin of the mass and connected directly with the tumor. Histological examination of the resected specimen revealed typical meningothelial meningioma admixed with mature adipose tissue. Longstanding intratumoral congestion probably caused hyaline deposition in the tissue, leading to vessel rupture. | 18,948,682 |
Spontaneous epidural pneumocephalus. | A 20-year-old male presented with an extremely rare spontaneous epidural pneumocephalus which was successfully treated by a single neurosurgical intervention. The patient had a habit of nose blowing and a 1-year history of progressive headache and nausea. Cranial computed tomography (CT) revealed a 2 x 7 cm right temporo-occipital epidural pneumocephalus with extensive hyperpneumatization of the mastoid cells. Right temporo-occipital craniotomy with a right superficial temporal artery and vein flap repair resulted in radiographic resolution of the pneumocephalus, and he remained neurologically free of symptoms at 1-year follow-up examination. Early identification and monitoring of symptomatic pneumocephalus followed by decompression and prevention of infection via closure of the bone defect can avoid possible serious consequences. The underlying mechanisms may involve a congenital petrous bone defect and a ball-valve effect due to excessive nose blowing in our case. | 18,948,684 |
Correlation of gut hormones with irritable bowel syndrome. | Irritable bowel syndrome (IBS) is a functional bowel disorder which is characterized by abdominal pain and disturbed bowel habits. The pathophysiological mechanism is complex and still remains incompletely clear. Alterations at both the central and the peripheral level are thought to contribute to the symptoms of IBS, including psychosocial factors, visceral hypersensitivity and abnormal gastrointestinal motility and secretion. Several gut peptides contribute to the regulation of gastrointestinal function, but little is known about gut hormone secretion in IBS. We evaluated the concentrations of cholecystokinin (CCK), vasoactive intestinal peptide (VIP), somatostatin, substance P, neuropeptide Y (NPY) in plasma and in sigmoid tissue in 40 patients with IBS and 15 age- and gender-matched controls by using radioimmunoassay. IBS patients had higher plasma level of CCK (p < 0.01), and the level of CCK in the sigmoid was also increased compared with controls (p < 0.05). The levels of somatostatin and substance P in fasting plasma and in the sigmoid were not different between IBS patients and control subjects (p > 0.05), but the levels of VIP in sigmoid tissue or in plasma were higher in IBS patients than in control group (p < 0.01). The NPY levels in both plasma and the sigmoid were significantly lower in IBS patients than in controls (p < 0.05). Plasma NPY level in patients with IBS with diarrhea as a predominant bowel pattern was lower than in patients with IBS with constipation as a predominant bowel pattern. IBS patients have increased levels of CCK and VIP and decreased NPY levels in fasting plasma and sigmoid tissue. These alterations of VIP, CCK and NPY may play a role in the pathogenesis of IBS. | 18,948,690 |
Physiological roles for G protein-regulated adenylyl cyclase isoforms: insights from knockout and overexpression studies. | Cyclic AMP is a universal second messenger, produced by a family of adenylyl cyclase (AC) enzymes. The last three decades have brought a wealth of new information about the regulation of cyclic AMP production by ACs. Nine hormone-sensitive, membrane-bound AC isoforms have been identified in addition to a tenth isoform that lacks membrane spans and more closely resembles the cyanobacterial AC enzymes. New model systems for purifying and characterizing the catalytic domains of AC have led to the crystal structure of these domains and the mapping of numerous interaction sites. However, big hurdles remain in unraveling the roles of individual AC isoforms and their regulation in physiological systems. In this review we explore the latest on AC knockout and overexpression studies to better understand the roles of G protein regulation of ACs in the brain, olfactory bulb, and heart. | 18,948,702 |
Maternal origin of the human aneuploidies. Are homolog synapsis and recombination to blame? Notes (learned) from the underbelly. | Aneuploidy is the leading cause of mental deficiency in human newborns. Indirect studies suggest that, in most of the cases, the extra chromosome comes from an inaccurate meiotic division. But, particularly, all results seem to indicate that oogenesis is more prone to err than is spermatogenesis. Unfortunately, due to the time-frame in which meiosis takes place in the mammalian males and females, most of the studies performed so far have focused on analyzing male meiosis. Recently, some studies focusing on human meiosis have been published. Some of them revealed important sex-specific differences that may be involved in the predominant involvement of the human female in the genesis of aneuploidy. In this article, the current knowledge we have about human female meiotic synapsis and recombination is summarized and we try to relate it to the human aneuploidy origin. | 18,948,712 |
Radiosurgery for cavernous malformations in basal ganglia, thalamus and brainstem. | Long-term results of radiosurgery for cavernous malformations in basal ganglia and the brainstem are presented. Eighty-four cases, 50 males and 34 females, ranging in age from 10 to 68 years (mean: 38.2 years) are described. The lesions were located in the brainstem (63), thalamus (14) or basal ganglia (7). The mean lesion size was 14.3mm. Mean maximum and marginal treatment doses were 23.3 and 13.4 Gy, respectively. Brainstem lesions were significantly smaller than the lesions in basal ganglia and the thalamus. During a mean follow-up of 55 months, nearly half of the lesions showed some shrinkage, while in the other half there were no obvious changes. Only 4 of the 84 (4.8%) showed progression. Rebleeding occurred in 14 cases (16.7%),16 times in total. Among these, 12 hemorrhages occurred during the first 24 months after radiosurgery, and the incidence decreased markedly thereafter. Bleeding rates during the first and second years were 9.5 and 4.7%/year/case, respectively. However, the rate significantly decreased thereafter. As for complications, perifocal edema was seen in 18% of basal ganglia-thalamus and in 3.2% of brainstem lesion cases. In conclusion, radiosurgery for cavernous malformations of the basal ganglia-thalamus and brainstem is warranted because a decreased bleeding rate and lower morbidity can be expected. | 18,948,717 |
Treatment of functional disorders with gamma knife thalamotomy. | Gamma knife (GK) thalamotomy for functional disorders, primarily Parkinson disease and central pain, are described herein. The goal was to extend our present indications for selective thalamotomy. Our target for tremor surgery is about 45% of the thalamic length. Thus, this principle was applied to deciding the GK thalamotomy target. In most of our cases, the protocol was 130 Gy, delivered in one shot with a 4-mm collimator. The time courses of thalamic lesion changes and clinical improvement after irradiation were assessed. Thus, despite thalamic reaction changes being variable, we achieved a clinical success rate of approximately 80% with negligible complications. | 18,948,728 |
Insulin and aging. | In invertebrates, signaling pathways homologous to mammalian insulin and insulin-like growth factor (IGF-1) signal transduction have a major role in the control of longevity. There are numerous indications that these pathways also influence aging in mammals, but separating the role of insulin from the effects of IGF-1 and growth hormone (GH) is difficult. In mice, selective disruption of the insulin receptor in the adipose tissue extends longevity. Increases in lifespan were also reported in mice with deletion of insulin receptor substrate 1 (IRS1) in whole body or IRS2 only in the brain. GH deficiency or resistance in mutant mice leads to hypoinsulinemia and enhanced insulin sensitivity along with remarkably extended longevity. These characteristics resemble animals subjected to calorie restriction. Studies of physiological characteristics and polymorphisms of insulin-related genes in exceptionally long-lived people suggest a role of insulin signaling in the control of human aging. | 18,948,730 |
Gene regulation by SINES and inosines: biological consequences of A-to-I editing of Alu element inverted repeats. | The Alu elements are conserved approximately 300 nucleotide long repeat sequences that belong to the SINE family of retrotransposons found abundantly in primate genomes. Although the vast majority of Alu elements appear to be genetically inert, it has been tempting to consider the great majority of them as "junk DNA." However, a growing line of evidence suggests that transcribed Alu RNAs are in fact functionally involved in a number of diverse biological processes. Pairs of inverted Alu repeats in RNA can form duplex structures that lead to A-to-I editing by the ADAR enzymes. In this review we discuss the possible biological effects of Alu editing, with particular focus on the regulation of gene expression by inverted Alu repeats in the 3'-UTR regions of mRNAs. | 18,948,735 |
In vitro adipose tissue engineering using an electrospun nanofibrous scaffold. | Electrospun 3-dimensional nanofibrous scaffolds share morphologic similarities to collagen fibrils, and promote favorable biologic responses of seeded cells. In this study, we have fabricated a 3-dimensional nanofibrous scaffold made of poly L-lactic acid, and examined its ability to support and maintain the adipogenic differentiation of human bone marrow-derived mesenchymal stem cells in vitro. After a 21-day incubation, oil red O staining of constructs treated with adipogenic supplements revealed positive adipose-like staining, compared with lack of staining in untreated cultures. Semi-quantitative RT-PCR analysis of human bone marrow-derived mesenchymal stem cells cultured in adipogenic medium revealed highly elevated levels of adipogenesis-associated genes (1797-fold for lipoprotein lipase, and 5.6-fold for peroxisome proliferator-activated receptor gamma). Immunofluorescence staining of cellular constructs in adipogenic culture media showed the presence of lipoprotein lipase vesicles, a characteristic feature of adipose tissue. These results suggest that the poly L-lactic acid-based nanofibrous scaffold is a promising candidate for adult stem cell-based engineering of adipose tissue. | 18,948,788 |
An introduction to the chimeric deep inferior epigastric artery perforator (DIEAP)-rectus abdominis muscle flap. | A muscle perforator flap is a unique form of fasciocutaneous flap whose circulation is derived from musculocutaneous perforators, but without including any muscle. This anatomic relationship intuitively should readily allow the formation of branch-based chimeric or polyflaps consisting of a cutaneous perforator flap and its corresponding muscle as a combined flap, both ultimately supplied by a common source vessel. Many versions of the rectus abdominis musculocutaneous flap based on the deep inferior epigastric vessels are well known, but formation of a chimeric flap consisting of its component parts has heretofore not been reported. This treatise is intended primarily to provide an anatomic description that introduces the deep inferior epigastric artery perforator (DIEAP)-rectus abdominis muscle chimeric flap, with a clinical example that mainly demonstrated its usefulness to be the aesthetic advantage of a concomitant abdominoplasty. | 18,948,790 |
Wernicke encephalopathy after bariatric surgery: a systematic review. | To review the clinical essentials of Wernicke encephalopathy (WE) after bariatric surgery. An estimated 205,000 bariatric surgical procedures were performed in the United States in 2007. Such procedures may potentially lead to severe nutritional complications. Literature searches were performed in Medline, Embase, and abstract collections. Inclusion criteria were WE after bariatric surgery, diagnosed by the presence of two or more of the following signs: mental status changes, eye movement abnormalities, cerebellar dysfunction, and dietary deficiency. Of 104 reported cases of WE after bariatric surgery, 84 cases were included. Gastric bypass or a restrictive procedure had been performed in 80 cases (95%). Admission to hospital for WE occurred within 6 months of surgery in 79 cases (94%). Frequent vomiting was a risk factor in 76 cases (90%) and had lasted for a median of 21 days at admission. Intravenous glucose administration without thiamine was a risk factor in 15 cases (18%). Brain magnetic resonance imaging identified lesions characteristic of WE in 14 of 30 cases (47%). Incomplete recovery was observed in 41 cases (49%); memory deficits and gait difficulties were frequent sequela. The recent increase in the use of bariatric surgery in the United States was associated with an increase in reported WE cases. The number of WE cases after bariatric surgery is substantially higher than previously reported. Surgeons, allied health providers, and patients need to be aware of the predisposing factors and symptoms to prevent and optimize the management of this condition. | 18,948,797 |
Eosinophilia associated with chronic pancreatitis. | Eosinophilia (>0.5 x 10/L eosinophils [EOSs] in the peripheral blood) has been overlooked in the study of chronic pancreatitis (CP). The purpose of this study was to investigate the clinical significance and causes of eosinophilia by analyzing the features of CP cases with eosinophilia. We retrospectively analyzed the clinical features of CP patients with eosinophilia and compared them with CP patients without eosinophilia. There were 28 cases (15.6%) of CP with eosinophilia among 180 CP patients. The ratio of male to female patients was 8.3:1. The mean patient age at the time of diagnosis was 49.0 (+/- 16.2) years. The peak value of EOSs in the patients' peripheral blood was 0.935 (+/- 0.600) x 10/L. The incidence of eosinophilia in autoimmune pancreatitis was significantly higher than in non-autoimmune pancreatitis CP cases. The incidence of pancreatic ascites, pancreatic enlargement, or jaundice in CP cases with eosinophilia was significantly higher than in those without eosinophilia. There was no obvious infiltration of EOSs in the pancreatic tissues of 16 pathology or cytology specimens. The occurrence of eosinophilia during the course of CP is not unusual. This may be related to autoimmune mechanisms, serous membrane response, or the progression of pancreatic inflammation and fibrosis. | 18,948,836 |
The protective effect of sesamol against mitochondrial oxidative stress and hepatic injury in acetaminophen-overdosed rats. | An acetaminophen (APAP) overdose induces oxidative stress and acute hepatic injury or even death. We investigated the prophylactic effect of sesamol (SM) on mitochondrial oxidative stress, hydroxyl-radical-generated lipid peroxidation, and hepatic injury in APAP-overdosed rats. Six male Wistar rats (APAP group) were given only oral APAP (1,000 mg/kg) to induce mitochondrial oxidative-stress-associated hepatic injury, and another six (ASM group) were given the same dose of oral APAP, and then, immediately afterward, were injected with SM (10 mg/kg, i.p.), to assess its prophylactic effects. In the APAP group, APAP had significantly increased the levels of 1) serum aspartate transaminase and alanine transaminase, 2) centrilobular necrosis, 3) ferrous ions, 4) hydrogen peroxide, 5) hydroxyl radicals, and 6) lipid peroxidation, and decreased 7) mitochondrial aconitase activity in the rats' liver tissue 24 h later. In the ASM group, SM had prevented significant rises in the levels of 1) to 6) and a significant decrease (7). Therefore, we hypothesize that the protective effect of SM in APAP-overdosed rats is associated with maintaining the mitochondrial aconitase activity, ferrous ions (Fe2+), and hydrogen peroxide levels and inhibiting hydroxyl-radical-associated lipid peroxidation and hepatic injury. | 18,948,843 |
Paediatric stoma care nursing in the UK and Ireland. | Improving quality of care and developing and maintaining high standards of care are issues that are high on the NHS, nursing, and paediatric care agendas. Stoma formation will have an impact on the wellbeing and lifestyle of the person and their family, whatever the person's age. The specialty of stoma care nursing in the UK and Ireland is well established. However, the sub-specialty of paediatric stoma care nursing is much smaller in its 'membership' and its client group. There are differences in the needs of, and the associated care of, paediatric stoma patients even within this overall patient group. Paediatric stoma care nurses are in an ideal position to increase awareness about the specialty and improve standards of nursing care for neonates, children, adolescents and their families. However, until the establishment of the Paediatric Stoma Nurse Group (PSNG) in 2005, this 'position' had not being utilized. This article discusses the ongoing work of the PSNG to devise standards of paediatric stoma care nursing, best practice guidelines, relevant patient/parental information and establish itself as a valuable, proactive and independent forum for all healthcare professionals involved in the care of children with stomas. | 18,948,856 |
Effective surgical treatment of the carotid sinus sindrome. | Elderly patients frequently suffer from dizziness and syncope; however, an underlying disease may not always be identified. Three patients aged 69, 71 and 56, respectively, experienced spells of dizziness and syncope. Massage of the carotid sinus demonstrated the presence of a carotid sinus syndrome (CSS), an abnormal baroreflex response of the carotid sinus that leads to asystole and extreme hypotension. Conventional treatment is generally by insertion of a pacemaker. These patients, however, were referred to the vascular surgery department of our hospital for removal of adventitial layers of proximal portions of the internal carotid artery. Recovery was uneventful; all three are now free of symptoms. CSS should be considered in the differential diagnosis of dizziness and syncope. Surgical denervation of the carotid artery is a valid treatment option, especially in the vasodepressive or mixed type of CSS. | 18,948,872 |
Recombinant activated factor VII for treatment of refractory hemorrhage after surgery for acute aortic dissection. | Despite appropriate treatment, surgery for aortic dissection is frequently associated with bleeding problems. In these series we report on the employment of recombinant activated factor VII (rFVIIa) for refractory hemorrhage after emergency surgery for acute type A aortic dissection, used to face the problems of postoperative blood loss and transfusion requirements. Despite the good results of the therapy, a patient presented with thrombosis of the left cavernous sinus. Although a risk of thromboembolic complications has to be considered, rFVIIa is a reasonable rescue option in life-threatening hemorrhage and enlarges our hemostatic armamentarium in surgery for acute aortic dissection. | 18,948,874 |
Detection of protozoan and bacterial pathogens of public health importance in faeces of Corvus spp. (large-billed crow). | Parasites and bacteria are reported in the faeces of birds in the current study. Fresh faecal samples of the large-billed crow (Corvus spp.) were collected from the study site at Bangsar, an urban setting in Kuala Lumpur, Malaysia. These samples were transported to laboratory and analysed for parasites and bacteria. Pre-prepared XLD agar plates were used for culturing the bacteria in the laboratory. Using the API 20ETM Test Strips, 9 different species of bacteria were identified belonging to the family Enterobacteriacea. They were Citrobacter freundii, Enterobacter cloacae, Proteus mirabilis, Klebsiella pneumoniae, Kluyvera ascorbata, Salmonella arizonae, Salmonella typhi, Shigella flexneri and Shigella sonnei. The protozoan parasites detected include Cryptosporidium spp., Cyclospora spp., Blastocystis spp., and Capillaria hepatica and Ascaris lumbricoidus ova. Environmental air samples collected on agar plates using an air sampler in the area only produced fungal colonies. Some of these pathogens found in the crows are of zoonotic importance, especially Cryptosporidium, Blastocystis, Cyclopsora, Salmonella, Shigella and Kluyvera. The finding of Kluyvera spp. in crows in our current study highlights its zoonotic potential in an urban setting. | 18,948,884 |
A study of parasitic infections in the luminal contents and tissue sections of appendix specimens. | Appendicitis has a worldwide prevalence and affects all age groups. The aetiology of acute appendicitis is still much debated, many factors have been implicated. The pathology is likely to be due to obstruction of the lumen of the appendix. Parasites, both helminths and protozoa have been suggested to be the cause of acute appendicitis. Studies have demonstrated that parasites are present in the appendix specimens removed from surgery methods. | 18,948,889 |
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