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pubmed_590_18066
Patient safety and risk/complication management rank among the current megatrends in modern medicine, which has undoubtedly become more complex. In time-critical, error-prone and difficult situations, which often occur repeatedly in everyday clinical practice, guidelines are inappropriate for acting rapidly and intelligently. With the establishment and consistent use of standard operating procedures like in commercial aviation, a possible strategic approach is available. These medical aids to decision-making - quick reference cards - are short, optimized instructions that enable a standardized procedure in case of medical claims.
10.1007/s00120-014-3492-6
pubmed_954_15091
OBJECTIVES The learning and teaching of different singing styles, such as operatic and Chinese folk singing, was often found to be very challenging in professional music education because of the complexity of varied musical properties and vocalizations. By studying the acoustical and musical parameters of the singing voice, this study identified distinctive tuning characteristics of a particular folk music in China-Hua'er music-to inform the ineffective folk singing practices, which were hampered by the neglect of inherent tuning issues in music. METHODS Thirteen unaccompanied folk song examples from four folk singers were digitally audio recorded in a sound studio. Using an analyzing toolkit consisting of Praat, PeakFit, and MS Excel, the fundamental frequencies (F0) of these song examples were extracted into sets of "anchor pitches" mostly used, which were further divided into 253 F0 clusters. The interval structures of anchor pitches within each song were analyzed and then compared across 13 examples providing parameters that indicate the tuning preference of this particular singing style. RESULTS The data analyses demonstrated that all singers used a tuning pattern consisting of five major anchor pitches suggesting a nonequal-tempered bias in singing. This partly verified the pentatonic scale proposed in previous empirical research but also argued a potential misunderstanding of the studied folk music scale that failed to take intrinsic tuning issues into consideration. CONCLUSIONS This study suggests that, in professional music training, any tuning strategy should be considered in terms of the reference pitch and likely tuning systems. Any accompanying instruments would need to be tuned to match the underlying tuning bias.
pubmed_954_15091
pubmed_497_8746
The authors reported that a subgroup of schizophrenic patients performed well on a tone serial position task but was impaired on an auditory word serial position task (Wexler, Stevens, Bowers, Cerniak, & Goldman-Rakic, 1998). This study assessed 30 schizophrenic and 32 controls (matched for comparable tone discrimination) on 4 versions of the verbal serial position tasks and 2 tone serial position tasks. Patients performed poorly on all verbal tasks but performed comparably to controls when tones served as stimuli. Proactive interference and visual presentation further compounded the verbal deficits. Deficits persisted with pronounceable nonword stimuli. These findings provide evidence of specific deficits in language-related processing, although the authors could not rule out the possibility that the differential effects that were observed between the tone and word tasks, and particularly among the verbal tasks, may result from differing discriminating power of the different tests.
pubmed_497_8746
pubmed_306_25258
A microextraction procedure based on vortex-assisted surfactant-enhanced-emulsification liquid-liquid microextraction with solidification of floating organic droplet (VSLLME-SFO) for preconcentration of neonicotinoid pesticides, including acetamiprid, clotianidin, nitenpyram, imidacloprid, and thiamethoxam, has been developed. In VSLLME-SFO process, the addition of surfactant (as an emulsifier), could be enhance the mass-transfer from the aqueous solution into the extraction solvent. The extraction solvent could be dispersed into the aqueous by vortex process. Other experimental parameters affected the extraction efficiency, including the kind and concentration of salt, concentration and volume of HCl, kind and concentration of surfactant and its volume, kind and volume of extraction solvent, vortex time and the centrifugation extraction time, were also optimized. The optimum extraction conditions of VSLLME-SFO were 10.00 mL of sample, 0.3% (w/v) Na2SO4, 50 µL of 0.050 mol L(-1) SDS, 1.0 mol L(-1) HCl (400 µL), 150 µL of octanol, vortex time 1 min and centrifugation time 10 min. The sediment phase was analyzed by subjecting it to HPLC using a mobile phase of 25% acetonitrile in water, at a flow rate of 1.0 mL min(-1), and photodiode array detection at 254 nm. Under the optimum extraction conditions, high enrichment factors (20-100 fold) and low limit of detection (0.1-0.5 μg L(-1)) could be obtained. This method provided high sensitivity, low toxic organic solvents used, and simplicity of the extraction processes. The proposed method was successfully applied in the analysis of neonicotinoids in fruit juice and water samples.
pubmed_306_25258
pubmed_914_18525
Pulmonary artery obstruction and subsequent lung ischemia have been shown to induce systemic angiogenesis despite preservation of normoxia. The underlying mechanisms, however, remain poorly understood. In a mouse model of lung ischemia induced by left pulmonary artery ligation (LPAL), we showed previously, the formation of a new systemic vasculature to the ischemic lung. We hypothesize that LPAL in the mouse increases reactive oxygen species (ROS) production, and these molecules play an initiating role in subsequent lung neovascularization. We used oxidant-sensitive dyes (DHE and H(2)DCF-DA) to quantify ROS and measured the antioxidant-reduced glutathione (GSH) and its oxidized form (GSSG) as indicators of ROS levels after LPAL. The magnitude of systemic neovascularization was determined by measuring systemic blood flow to the left lung with radiolabeled microspheres 14 days after LPAL. An increase in ROS was observed early (30 min: 55% increase in H(2)DCF-DA) after LPAL, with a return to baseline by 24 h. GSH/GSSG was decreased (∼50%) 4 h after LPAL, suggesting earlier ROS upregulation. Mice treated with the antioxidant N-acetylcysteine showed attenuated angiogenesis (62% of wild-type LPAL), and mice lacking Nrf2, a transcription factor important for antioxidant synthesis, resulted in increased neovascularization (207% of wild-type LPAL). Overall, GSH/GSSG was inversely associated with the magnitude of neovascularization. These results demonstrate that LPAL induces an early and transient ROS upregulation, and ROS appear to play a role in promoting ischemia-induced angiogenesis.
10.1152/ajplung.00002.2010
pubmed_228_11892
PURPOSE The antioxidant enzymes pathway is considered the most important pathway involved in the repair of reactive oxygen species (ROS)-induced damage. Therefore, we investigate the possible association between polymorphisms of Cu/Zn superoxide dismutase (SOD1), catalase (CAT), and glutathione peroxidase (GPX) genes and age -related cataract development. METHODS The study included 415 cataract patients (121 patients with cortical, 109 with nuclear, 59 with posterior subcapsular, and 126 with mixed type) and 386 healthy control group of similar age. Genotyping of SOD1-251A/G, CAT-21A/T, and GPX1-198C/T was done by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. Differences in the frequencies were estimated using the χ(2) test and risk was estimated with an unconditional logistic regression after adjusting for age and gender. RESULTS SOD1 G/G genotype frequency was significantly higher in cataract patients (p=0.012, OR=1.642, 95% CI=1.129-2.389). SOD1 A/A genotypes (p=0.001, OR=0.613, 95% CI=0.461-0.817) seem to have a protective role against cataract, and the G allele (p=0.001, OR=1.479, 95% CI=1.208-1.810) plays a dangeous effect against in the development of cataract. In CAT-21A/T and GPX1-198C/T polymorphisms, there were no significant differences in the variant homozygous frequencies in patients compared to controls (p=0.226, OR=1.358, 95% CI=0.839-2.199; p=0.521, OR=1.205, 95% CI=0.726-2.001, respectively). Stratification by the subtypes revealed that association between SOD polymorphism and cataract was in cortical and mixed type cataract. The genotype frequency of the GG and AA of SOD1-251A/G was significantly different in cortical and mixed type cataract group (p=0.031; OR: 1.805, 95% CI: 1.076-3.026; p=0.002; OR: 2.229, 95% CI: 1.364-3.645; p=0.026; OR: 0.608, 95% CI: 0.396-0.933; p=0.001; OR: 0.474, 95% CI: 0.305-0.734, respectively) compared to healthy controls. CONCLUSIONS Results suggest that the G/G genotype of the SOD1-251A/G polymorphism may be associated with an increased risk of cataract. However, in CAT-21A/T and GPX1-198C/T polymorphisms, there were no significant differences in the variant homozygous frequencies in patients compared to controls.
pubmed_228_11892
pubmed_602_12331
BACKGROUND Propionibacterium acnes is the predominant organism in acne lesions, but the sensitivity of different biotypes of P. acnes to therapeutic agents has seldom been reported. METHODS To characterize biotypes of P. acnes and to measure the effects of Keigai-rengyo-to (KRT) and minocycline (MINO) on clinical P. acnes isolates. RESULTS Propionibacterium acnes biotype III (BIII) is the most common form of identified acne lesion, followed by P. acnes biotype I. BIII was isolated from mild, moderate and severe severity and the average lipase activity of BIII was higher than that of Biotypes I, II, IV and V. No significant differences in the decrease of free fatty acid production elicited by KRT or by MINO were found between BIII and the other biotypes. The degree of decreased butyric acid production was greater than that of propionic acid production in the medium supplemented with MINO. The percent decrease of butyric acid production elicited by 1 mg/mL of KRT was the same as that elicited by 0.1 microg/mL of MINO. Among biotypes of P. acnes, the minimal inhibitory concentrations of agents tested were generally higher in erythritol-positive biotypes than in erythritol-negative biotypes. CONCLUSION The high frequency of BIII might be responsible for the severity of acne in patients. It seems that if the same concentrations of MINO and KRT are used, the antilipase activity of MINO is stronger than that of KRT. Minocycline also has a direct anti-lipase activity against P. acnes. The mechanism underlying the influence of erythritol on the susceptibility of P. acnes to these agents remains unknown.
10.1111/j.1365-4632.2004.01887.x
pubmed_1080_3510
Cancer chemotherapy has been remarkably successful in the treatment of several types of malignancies, but has also been demonstrated to cause leukaemia and perhaps other cancer in long-term survivors. Radiotherapy also carries a carcinogenic risk. A large case-control study of second cancer has been carried out, with the aim of quantifying the risk due to chemotherapy and radiotherapy. One of the most important goals of this study is the estimation of the temporal pattern of risk following chemotherapy. Methods are presented for modelling risk as a function of type of treatment and the interval since treatment. The methods are applications of generally available linear regression programs for epidemiological data, and could be equally well applied to studies of occupationally induced cancer.
10.1002/sim.4780081109
pubmed_332_668
OBJECTIVES Cochlear implantees have improved speech production skills compared with those using hearing aids, as reflected in their acoustic measures. When compared to normal hearing controls, implanted children had fronted vowel space and their /s/ and /∫/ noise frequencies overlapped. Acoustic analysis of speech provides an objective index of perceived differences in speech production which can be precursory in planning therapy. The objective of this study was to compare acoustic characteristics of speech in cochlear implantees with those of normal hearing age matched peers to understand implications. METHODS Group 1 consisted of 15 children with prelingual bilateral severe-profound hearing loss (age, 5-11 years; implanted between 4-10 years). Prior to an implant behind the ear, hearing aids were used; prior & post implantation subjects received at least 1 year of aural intervention. Group 2 consisted of 15 normal hearing age matched peers. Sustained productions of vowels and words with selected consonants were recorded. Using Praat software for acoustic analysis, digitized speech tokens were measured for F1, F2, and F3 of vowels; centre frequency (Hz) and energy concentration (dB) in burst; voice onset time (VOT in ms) for stops; centre frequency (Hz) of noise in /s/; rise time (ms) for affricates. A t-test was used to find significant differences between groups. RESULTS Significant differences were found in VOT for /b/, F1 and F2 of /e/, and F3 of /u/. No significant differences were found for centre frequency of burst, energy concentration for stops, centre frequency of noise in /s/, or rise time for affricates. These findings suggest that auditory feedback provided by cochlear implants enable subjects to monitor production of speech sounds. CONCLUSION Acoustic analysis of speech is an essential method for discerning characteristics which have or have not been improved by cochlear implantation and thus for planning intervention.
10.3342/ceo.2012.5.S1.S14
pubmed_258_19259
Pathogenic variants in the β1-catenin (CTNNB1) gene have been identified in patients with various diseases, including syndromic intellectual disability, autism spectrum disorder, familial exudative vitreoretinopathy, and neurodevelopmental disorder with spastic diplegia and visual defects (NEDSDV). We report on the clinical, genetic, neuroimaging, and neurophysiological data of a 15-year-old patient with complex hereditary spastic paraplegias with exotropia, dyskinesia, and cerebellar signs and a so-far unreported demyelinating (mainly sensory) polyneuropathy in her lower limbs. She carries the novel, de novo, likely pathogenic heterozygous c.603_605delinsAATA, p.(Met202Ilefs*6) frameshift variant in the CTNNB1 gene. Although peripheral neuropathy was not previously associated with NEDSDV, in light of the role of β1-catenin as a junction protein in the peripheral as well as in the central nervous system documented in experimental studies, it might represent a causally linked and under-reported finding to be further explored.
10.1002/ajmg.a.62902
pubmed_396_13451
OBJECTIVE To study the epidemiological, clinical, and microbiological features of Plesiomonas shigelloides infection in Hong Kong. DESIGN Retrospective study. SETTING Infectious Disease Unit of a district hospital, Hong Kong. PATIENTS Patients with laboratory-confirmed cases of Plesiomonas shigelloides infection between 1 January 1995 and 31 December 1998. MAIN OUTCOME MEASURES Epidemiological and clinical data, antibiotic sensitivity, and clinical outcome. RESULTS There was an increasing trend in the number of isolates of Plesiomonas shigelloides obtained and the prevalence of the bacterium. A total of 197 isolates were obtained from 188 patients, and most isolates (172; 87.3%) were obtained during the summer. Clinical and epidemiological data were available for 167 patients (85 males, 82 females). Patient age ranged from 1 month to 95 years; the mean and median ages of the patients older than 15 years were 51.0 and 40.5 years, respectively (n=132). Only 35 (21.0%) of the 167 patients had a history of travel outside Hong Kong, whereas 21 (12.6%) had a history of consuming seafood or uncooked food; 39 (23.4%) had underlying medical conditions. Most patients (165; 98.8%) had symptoms of Plesiomonas shigelloides infection. Nine (5.4%) patients had had chronic diarrhoea for more than 2 weeks; watery and bloody diarrhoea was discharged by 122 (73.1%) and 42 (25.1%) of the patients, respectively. All 197 Plesiomonas shigelloides isolates were sensitive to ofloxacin, or levofloxacin and ceftriaxone. Resistance or partial resistance was recorded for ampicillin (72%), tetracycline (67%), co-trimoxazole (12%), and chloramphenicol (5%). The majority of patients (142/167; 85.0%) had self-limiting cases of infection, but 25 patients were given antibiotics for more severe symptoms at the time of presentation; there were two deaths. CONCLUSIONS The occurrence of Plesiomonas shigelloides infection in Hong Kong is increasing, although most cases of are self-limiting.
pubmed_396_13451
pubmed_756_11112
Focal segmental glomerulosclerosis (FSGS) is extremely rare among paraneoplastic nephrotic syndromes. We herein report a case of lung adenocarcinoma with nephrotic syndrome caused by paraneoplastic FSGS. A 68-year-old man visited our hospital for an evaluation of a right hilar mass on chest radiography and supraclavicular lymphadenopathy. Because an aspiration biopsy of the supraclavicular lymph node revealed adenocarcinoma, the patient was diagnosed with lung adenocarcinoma. He also had nephrotic syndrome, and the pathological findings of the renal biopsy demonstrated FSGS. Standard-dose carboplatin-containing chemotherapy led to a partial response for lung cancer and improved the patient's nephrotic syndrome without causing any adverse renal effects.
10.2169/internalmedicine.52.0485
pubmed_616_3214
Activity-based protein profiling has emerged as a powerful tool for visualizing glycosidases in complex biological samples. Several configurational cyclophellitol isomers have been shown to display high selectivity as probes for glycosidases processing substrates featuring the same configuration. Here, a set of deoxygenated cyclophellitols are presented which enable inter-class profiling of β-glucosidases and β-galactosidases.
10.1039/c7cc07730k
pubmed_671_10940
Rotation therapy has been accepted as a standard method of treatment for many years, but is use has been confined almost entirely to telecobalt therapy. This has been due to the difficulty in maintaining a constant output, and therefore a constant dose per degree of gantry rotation, when using a linear accelerator. This paper presents a new form of step-rotation therapy avoids this difficulty and is suitable for use with any modern linac to which remote gantry drive has been added. Apart from the advantages of smaller penumbra and shorter treating time on linear accelerator, in this technique both computation and delivery of dose is done in steps, and therefore the computed dose distribution matches the actual expected distribution. A further advantage is the ability to change the weighting at each step, which gives more control over the final distribution. Other problems which have been inherent in telecobalt rotation therapy are also avoided, such as matching treatment time and arcing time, and correcting for the discrepancies resulting from mismatch.
10.1016/s0009-9260(80)80187-5
pubmed_1132_20769
BACKGROUND The objective of this study is the comparison of a new intragastric balloon recently introduced, the Adjustable Balloon System (ABS), with the BioEnterics intragastric balloon (BIB) in terms of tolerance, safety, and weight loss parameters. METHODS A case-control study was done: 40 patients were matched with 80 controls. To achieve the same duration therapy (12 months), a single ABS positioning was compared with a BIB followed by another BIB (6 + 6 months). Length of procedure, hospital stay, complications, and weight loss parameters after 6 months (time of first BIB removal) and after 12 months from baseline (time of Spatz and second BIB removal) were considered. Statistical analysis was done by means of Student's t test, χ2 test, or Fisher's test. P < 0.05 was considered significant. RESULTS Mortality, positioning, and extraction complications were absent. Both the devices were well tolerated with slight duration of post placement symptoms. During this study, the Spatz balloon was adjusted with inflation of 200 cm(3) of saline (total, 800 cm(3)) in 9/40 (22.5 %) patients, for poor weight loss after first 6-months treatment. In the Spatz group, there occurred 7/40 complications linked to the device and in 6/7 patients the balloon was removed. At the end of the study, the weight loss parameters were similar between groups: BMI 31.0 ± 11.8 (Spatz group) vs 31.3 ± 12.3 (BIB group) (p = Ns). CONCLUSIONS The idea of dynamic balloon therapy needs to be confirmed with wider series. The rate of complication reported is very high, and several studies regarding safety and efficacy are needed.
10.1007/s11695-013-0891-5
pubmed_266_4950
Common wild rice contains valuable resources of novel alleles for rice improvement. It is well known that genetic populations provide the basis for a wide range of genetic and genomic studies. In particular, chromosome segment substitution lines (CSSLs) ais a powerful tool for fine mapping of quantitative traits, new gene discovery and marker-assisted breeding. In this study, 132 CSSLs were developed from a cultivated rice (Oryza sativa) cultivar (93-11) and common wild rice (Oryza rufipogon Griff. DP30) by selfing-crossing, backcrossing and marker-assisted selection (MAS). Based on the high-throughput sequencing of the 93-11 and DP30, 285 pairs of Insertion-deletions (InDel) markers were selected with an average distance of 1.23 Mb. The length of this DP30-CSSLs library was 536.4 cM. The coverage rate of substitution lines cumulatively overlapping the whole genome of DP30 was about 91.55%. DP30-CSSLs were used to analyze the variation for 17 traits leading to the detection of 36 quantitative trait loci (QTLs) with significant phenotypic effects. A cold-tolerant line (RZ) was selected to construct a secondary mapping F2 population, which revealed that qCT2.1 is in the 1.7 Mb region of chromosome 2. These CSSLs may, therefore, provide powerful tools for genome wide large-scale gene discovery in wild rice. This research will also facilitate fine mapping and cloning of QTLs and genome-wide study of wild rice. Moreover, these CSSLs will provide a foundation for rice variety improvement.
10.3390/genes11090980
pubmed_784_11953
We have examined the conditions for dissolution by live cells of an extracellular matrix composed of reconstituted type I collagen fibrils, using three different cell types which express varying constitutive or inducible levels of procollagenase and collagenase inhibitor. The two major conclusions from these studies were that (i) expression of collagenase is a necessary but not sufficient requirement for dissolution of the collagen fibrils and that (ii) activation of procollagenase is a rate-limiting step. Cells which secreted high levels of procollagenase dissolved collagen fibrils only to the extent that they were able to activate the enzyme. Cells which also expressed inhibitor failed to activate procollagenase in the culture medium and did not dissolve the collagen fibrils unless procollagenase-activation was assisted by exogenous proteinase activity. Cells that did not express inhibitor ultimately did activate procollagenase but the process was slow and incomplete. Introduction of exogenous proteinase activity either in the form of plasminogen, plasmin, or trypsin stimulated collagen breakdown by several fold. Analysis of the culture medium sampled from such cultures showed that the stimulating effect of exogenous proteinases could be ascribed to three separate, but synergistic events: elevated expression of procollagenase, conversion of procollagenase to active form and inactivation of collagenase inhibitor. Two lines of evidence suggested that the dissolution of collagen fibrils in these cultures was mediated by a collagenase-dependent pathway: (i) the rate of dissolution closely mirrored the level of expression of collagenase and (ii) the process was blocked by inhibitory collagenase-specific antibodies.
pubmed_784_11953
pubmed_153_1775
BACKGROUND In the histopathological diagnostics of synovitis and the synovium-like interface membrane (SLIM) the identification of crystals and crystal-like deposits and the associated inflammatory reactions play an important role. The multitude of endogenous crystals, the range of implant materials and material combinations, and the variability in the formation process of different particles explain the high morphological particle heterogeneity which complicates the diagnostic identification of diagnostic particles. STUDY DESIGN AND METHODS A simple histopathological particle algorithm has been designed which allows methodological particle identification based on (1) conventional transmitted light microscopy with a guide to particle size, shape and color, (2) optical polarization criteria and (3) enzyme histochemical properties (oil red staining and Prussian blue reaction). These methods, the importance for particle identification and the differential diagnostics from non-prosthetic materials are summarized in the so-called histopathological particle algorithm. RESULTS A total of 35 cases of synovitis and SLIM were analyzed and validated according to these criteria. Based on these criteria and a dichotomous differentiation the complete spectrum of particles in the SLIM and synovia can be defined histopathologically. CONCLUSION For histopathological diagnosis a particle score for synovitis and SLIM is recommended to evaluate (1) the predominant type of prothetic wear debris with differentiation between microparticles, and macroparticles, (2) the presence of non-prosthesis material particles and (3) the quantification of particle-association necrosis and lymphocytosis. An open, continuously updated web-based particle algorithm would be helpful to address the issue of particle heterogeneity and include all new particle materials generated in a rapidly changing field.
10.1007/s00393-013-1315-6
pubmed_93_25398
UNLABELLED Mammaglobin may be a potential serum biomarker for the differential diagnosis of breast cancer. 260 serum samples were collected from 127 untreated breast cancer patients and 133 healthy volunteers to analyze the sera expression of mammaglobin and its implications for both. The expression vector of pGEX-4T-2-Mammaglobin and pBVIL1-Mammaglobin were constructed and transformed into E.coli.HB101 for expression. The mice were immunized with the purified recombinant protein to prepare monoclonal antibody and to detect by ELISA the serum of normal people and breast cancer patients. Recombinant mammaglobin antigen was effectively expressed in E.coli. Two hybridoma cell lines were obtained after the mice were immunized by pGEX-4T-2-mammaglobin. 133 cases of normal serum and 127 cases of breast cancer serum were analyzed by ELISA. The sera expression level of mammaglobin in breast cancer group (average OD value 0.645±0.223) was significantly (p KEYWORDS mammaglobin; cloning expression; monoclonal antibody; serologic study; breast cancer.
10.4149/neo_2011_05_436
pubmed_539_4960
Prenatal alcohol exposure can cause a whole spectrum of central nervous system (CNS) sequelae that persist throughout the life span and manifest in a spectrum of effects from clinically indistinguishable to severely impairing. The greatest impact of alcohol as a teratogen is to the brain-the greatest need is for holistic treatment and management of the associated mental disorders. The interaction of this subtle brain damage with the complex psychosocial circumstances surrounding the birth of a child to a mother with alcohol problems can further compound development and result in costly and devastating social consequences. Research is urgently needed on the chronic neuropsychiatric sequelae of these subtle birth defects of the brain. Identification of these fetal alcohol spectrum disorders (FASD) in the psychiatric nomenclature is a necessary step to focus the attention and resources of the mental health field on this personally and socially significant problem.
10.1053/scnp.2000.6729
pubmed_785_2085
A system which allows magnetic resonance (MR) and ultrasound (US) image data to be acquired simultaneously has been developed. B-mode and Doppler US were performed inside the bore of a clinical 1.5 T MRI scanner using a clinical 1-4 MHz US transducer with an 8-metre cable. Susceptibility artefacts and RF noise were introduced into MR images by the US imaging system. RF noise was minimised by using aluminium foil to shield the transducer. A study of MR and B-mode US image signal-to-noise ratio (SNR) as a function of transducer-phantom separation was performed using a gel phantom. This revealed that a 4 cm separation between the phantom surface and the transducer was sufficient to minimise the effect of the susceptibility artefact in MR images. MR-US imaging was demonstrated in vivo with the aid of a 2 mm VeroWhite 3D-printed spherical target placed over the thigh muscle of a rat. The target allowed single-point registration of MR and US images in the axial plane to be performed. The system was subsequently demonstrated as a tool for the targeting and visualisation of high intensity focused ultrasound exposure in the rat thigh muscle.
10.1155/2014/914347
pubmed_2_8422
In order to report specifically on the use of adjuvant endocrine therapy (ET) in the oldest old breast cancer (BC) patients, we compared treatment patterns including drug compliance and persistence in a cohort of patients who were ≥ 80 years at diagnosis (n = 79) with those of "younger elderly" patients who were 60-79 years old (n = 358). The geriatric cohort more commonly declined the recommended ET (non-compliance: 13.0% vs. 4.5%, p = 0.011). Of the patients who initiated ET, only a minority of the older patients completed the planned therapy duration of five years (39.6% vs. 71.3%, p < 0.001). However, when applying strict criteria for non-persistence, this was found in comparable frequency (17.0% vs. 12.0%, p = 0.370). In older patients, medication was more often discontinued by the physician due to serious medical reasons independent of BC (17.0% vs. 4.7%, p = 0.003). Older women were treated by a general practitioner more often and not by an oncologist (54.4% vs. 23.9%, p < 0.001). Studies on compliance/persistence on cancer therapy in the oldest old demand a detailed follow-up of the patients and the consideration of principles of geriatric medicine. Efforts should be made to make sure that all physicians, but above all general practitioners, who are predominantly involved in the treatment of elderly BC patients, are provided with current knowledge and skills, as to ensure optimal patient management.
pubmed_2_8422
pubmed_721_6102
We report our findings of Bence Jones proteins (monoclonal free light chains of immunoglobulins) in concentrated urines of patients with multiple sclerosis, by using agarose electrophoresis and immunofixation. The lack of such findings in urines from healthy subjects and patients with other neurological disorders should stimulate further investigation.
pubmed_721_6102
pubmed_132_17635
We present magnetic characterization of a binary rare-earth intermetallic compound Er(5)Si(3), crystallizing in Mn(5)Si(3)-type hexagonal structure, through magnetization, heat capacity, electrical resistivity and magnetoresistance measurements. Our investigations confirm that the compound exhibits two magnetic transitions with decreasing temperature, the first one at 35 K and the second one at 15 K. The present results reveal that the second magnetic transition is a disorder-broadened first-order transition, as shown by thermal hysteresis in the measured data. Another important finding is that, below 15 K, there is a magnetic-field-induced transition with a hysteretic effect with the electrical resistance getting unusually enhanced at this transition and the magnetoresistance is found to exhibit intriguing magnetic-field dependence, indicating novel magnetic phase coexistence phenomenon. It thus appears that this compound is characterized by interesting magnetic anomalies in the temperature-magnetic-field phase diagram.
10.1088/0953-8984/23/49/496001
pubmed_272_7298
Conscious behavioral intentions can frequently fail under conditions of attentional depletion. In attempting to trace the cognitive origin of this effect, we hypothesized that failures of action control--specifically, oculomotor movement--can result from the imposition of fronto-executive load. To evaluate this prediction, participants performed an antisaccade task while simultaneously completing a working-memory task that is known to make variable demands on prefrontal processes (n-back task, see Jonides et al., 1997). The results of two experiments are reported. As expected, antisaccade error rates were increased in accordance with the fronto-executive demands of the n-back task (Experiment 1). In addition, the debilitating effects of working-memory load were restricted to the inhibitory component of the antisaccade task (Experiment 2). These findings corroborate the view that working memory operations play a critical role in the suppression of prepotent behavioral responses.
10.1162/089892902317205357
pubmed_912_25027
BACKGROUND The goal of this study was to identify a simple and effective way of calculating levothyroxine doses for postsurgical hypothyroidism. METHODS Levothyroxine dosage was calculated using a weight (μg/kg)-based formula for patients who underwent thyroidectomy for benign disease from 2001 to 2011. Other formulas using age, sex, ideal body weight, body mass index, and body surface area were also evaluated. RESULTS Four hundred four patients were included; 85% were women. The mean initial levothyroxine dosage was 1.4 μg/kg, which resulted in thyroid-stimulating hormone normalization in 59%, suppression in 23%, and elevation in 18% of patients. After dose adjustments, the mean therapeutic levothyroxine doses after total thyroidectomy and lobectomy were 1.5 and 1.3 μg/kg, respectively. A regression model incorporating other patient factors did not produce a more reliable dosing regimen. CONCLUSION A 1.5- and 1.3-μg/kg dosage calculation based on actual weight is currently the best estimation for levothyroxine replacement therapy after thyroidectomy.
pubmed_912_25027
pubmed_814_16962
Mammalian orthoreovirus (MRV) is a safe and effective cancer killing virus that has completed Phase I-III clinical trials against numerous cancer types. While many patients experience benefit from MRV therapy, pre-defined set points necessary for FDA approval have not been reached. Therefore, additional research into MRV biology and the effect of viral therapy on different tumor genetic subtypes and microenvironments is necessary to identify tumors most amenable to MRV virotherapy. In this work we analyzed the stage of viral infection necessary to inhibit HIF-1α, an aggressive cancer activator induced by hypoxia. We demonstrated that two viral capsid proteins were not necessary and that a step parallel with virus core movement across the endosomal membrane was required for this inhibition. Altogether, this work clarifies the mechanisms of MRV-induced HIF-1α inhibition and provides biological relevance for using MRV to inhibit the devastating effects of tumor hypoxia.
10.1016/j.virol.2021.02.014
pubmed_146_9911
A non-radioactive digoxigenin cDNA probe for detection of avian encephalomyelitis virus (AEV) was developed. The cDNA probe hybridized specifically with a fragment of VP1 gene of AEV genome was found to be sensitive with as little as 10 pg target DNA fragment in a sensitivity test. Infected chicken embryos were strongly labelled by testing the probe against a range of AEV strains, and no non-specific reaction was observed in non-infected chicken embryos as well as five other avian pathogenic virus-infected samples used as negative controls. Furthermore, the cDNA probe was capable of detecting AEV from chicken embryo brain at 3 days post-inoculation as compared with an immunofluorescence assay, which required up to 5 days of incubation in the embryos. In clinical application, five out of 16 clinical brain samples that were negative by the immunofluorescence assay were positive for AEV by the cDNA probe. Both the sensitivity and specificity of the developed cDNA probe indicated that it is a highly promising and reliable diagnostic tool for the detection of AEV infections.
10.1080/03079450801929933
pubmed_617_9231
Pharmacogenetics and pharmacogenomics are two major emerging trends in medical sciences, which influence the success of drug development and therapeutics. In current times, though pharmacogenetic studies are being done extensively for research, its application for drug development needs to get started on a large scale. The major determinants of success of a new drug compound, viz safety and efficacy, have become more predictable, with the advent of pharmacogenetic studies. There is a need felt for pharmacogenomic studies, where the effects of multiple genes are assessed with the study of entire genome.Pharmacogenetic studies can be used at various stages of drug development. The effect of drug target polymorphisms on drug response can be assessed and identified. In clinical studies, pharmacogenetic tests can be used for stratification of patients based on their genotype, which corresponds to their metabolizing capacity. This prevents the occurrence of severe adverse drug reactions and helps in better outcome of clinical trials. This can also reduce attrition of drug compounds. Further, the variations in drug response can be better studied with the wider application of pharmacogenomic methods like genome wide scans, haplotype analysis and candidate gene approaches. The cost of pharmacogenetic testing has become very low, with the advent of newer high throughput genotyping systems. However, the cost of pharmacogenomic methods continues to be very high. As the treatment with several drugs is being more and more pharmacogeneticaly guided (e.g. warfarin and irinotecan), the FDA has laid down guidelines for pharmaceutical firms regarding submission of pharmacogenetic data for their drug products in labelling.
10.4103/0253-7613.43158
pubmed_549_10022
AIM The increasing prevalence of fatty liver disease requires routine assessment methods. Proton magnetic resonance spectroscopy ((1)H MRS) is increasingly used for steatosis measurement, but due to cost, is unlikely to become a widely-used screening tool. Ultrasound is cheaper and more widely available, although subject to observer variability. Our aim was to determine the sensitivity and specificity of ultrasound against (1)H MRS, using MRS as a gold standard, for the detection and quantification of hepatic fat content. METHODS Fifty adults participated (43 men, seven women) in this study. Hepatic steatosis was assessed by ultrasound and (1)H MRS. Images were graded by two independent radiologists to classify severity and distribution of liver fat. RESULTS Ultrasound detected liver fat infiltration in 82% of cases measurable by (1)H MRS, while liver fat was detectable in 44% of cases graded absent by ultrasound. Ultrasound grading was subjective, with the radiologists in agreement in 53% of cases (kappa = 0.39, P = 0.002). Considerable overlap in intrahepatocellular lipid content was observed between different grades: absent (0.0-1.58%), mild (2.2-16.2%), moderate (4.9-26.7%) and severe (8.1-76.8%) steatosis. Ultrasound could not detect liver fat levels below 2% as measured by (1)H MRS Conclusion: Ultrasound is less sensitive than (1)H MRS in detecting very low levels of liver fat content, but is sensitive to fatty infiltration greater than 2%. There is a tendency of higher ultrasound grades to correlate with higher degrees of fatty infiltration, although some overlap exists. Our findings are still consistent with ultrasound being useful as a low cost screening tool.
10.1111/j.1872-034X.2009.00620.x
pubmed_776_2739
We have studied the effect of acute and chronic lithium treatment on the activity of striatal neurons recorded from corticostriatal slices. Under control conditions, tetanic stimulation of glutamatergic corticostriatal terminals caused long-term depression (LTD) of excitatory synaptic potentials. Acute lithium treatment did not affect the peak of the induction phase, but it reduced the following phases of LTD. LTD was completely blocked in slices obtained from rats chronically injected with LiCl. Lithium treatment failed to affect the intrinsic membrane properties of striatal neurons and the presynaptic inhibitory effects of carbachol and t-ACPD. We suggest that the lithium-induced blockade of LTD may contribute to the therapeutic action of lithium salts in mania and depression.
10.1016/0896-6273(93)90210-i
pubmed_378_16108
Hematopoietic progenitor cells (HPCs) represent an ideal target for gene therapy treatment of human immunodeficiency virus (HIV) infection. However, gene delivery into quiescent HPCs by retroviral or lentiviral vectors remains relatively poor. We evaluated a selection scheme based on the expression of a variant of inosine monophosphate dehydrogenase 2 (IMPDH2), the rate-limiting enzyme in the de novo purine biosynthesis pathway. As lymphocytes depend more than other cell types on de novo synthesis of purines, IMPDH inhibitors such as mycophenolic acid (MPA) can selectively expand lymphocytes overexpressing the enzymes. We used HIV vectors to deliver an IMPDH variant into T cells and HPCs. We showed that the transduced T cells became resistant to MPA selection. By expressing a short hairpin RNA gene targeted to the HIV gag transcript, the MPA-selected T cells became resistant to HIV-1 infection. Monocyte/macrophages derived from the transduced HPCs differentiated normally and exhibited normal function as measured by B7 up-regulation and phagocytosis when stimulated. Our results suggest that this system may be applicable as a selection strategy to enrich transduced T lymphocytes and mononuclear cells in vivo for HIV gene therapy.
10.1016/j.ymthe.2006.02.017
pubmed_286_237
The present study explores the notion of an out-group fear learning bias that is characterized by facilitated fear acquisition toward harm-doing out-group members. Participants were conditioned with two in-group and two out-group faces as conditioned stimuli. During acquisition, one in-group and one out-group face was paired with an aversive shock whereas the other in-group and out-group face was presented without shock. Psychophysiological measures of fear conditioning (skin conductance and pupil size) and explicit and implicit liking exhibited increased differential responding to out-group faces compared to in-group faces. However, the results did not clearly indicate that harm-doing out-group members were more readily associated with fear than harm-doing in-group members. In contrast, the out-group face not paired with shock decreased conditioned fear and disliking at least to the same extent that the shock-associated out-group face increased these measures. Based on these results, we suggest an account of the out-group fear learning bias that relates to an attentional bias to process in-group information.
10.1016/j.biopsycho.2017.08.060
pubmed_807_2152
The foxa regulatory gene is of central importance for endoderm specification across Bilateria, and this gene lies at an essential node of the well-characterized sea urchin endomesoderm gene regulatory network (GRN). Here we experimentally dissect the cis-regulatory system that controls the complex pattern of foxa expression in these embryos. Four separate cis-regulatory modules (CRMs) cooperate to control foxa expression in different spatial domains of the endomesoderm, and at different times. A detailed mutational analysis revealed the inputs to each of these cis-regulatory modules. The complex and dynamic expression of foxa is regulated by a combination of repressors, a permissive switch, and multiple activators. A mathematical kinetic model was applied to study the dynamic response of foxa cis-regulatory modules to transient inputs. This study shed light on the mesoderm-endoderm fate decision and provides a functional explanation, in terms of the genomic regulatory code, for the spatial and temporal expression of a key developmental control gene.
10.1073/pnas.1004824107
pubmed_1099_979
In pines, self-pollination rates can be as high as 34% yet only 5% of viable seed is a product of self-fertilization. This decline in selfed seed viability is the consequence of post-fertilization exclusion mechanisms operating via the embryo lethal system. Recent molecular marker dissection studies suggest that the embryo lethal system is composed of semilethal factors dispersed across the genome, but it is not clear whether overdominant lethal factors are rare or representative. The study objective was to determine if overdominance was rare for the embryo lethal system in conifers. Three cohorts of selfed offspring from a single Pinus taeda parent were genotyped for nuclear microsatellites. Maximum likelihood tests based on distorted segregation ratios for single markers and for interval mapping were used to infer the degree of dominance. Four hypotheses about overdominance lethal factors were tested: (1) overdominant lethal factors rarely occur within the embryo lethal system, (2) overdominant lethal factors are rarely detected because they are transient and display stage-specific expression, (3) overdominant lethal factors are rarely detected due to tight linkage with rare marker alleles and (4) dominance estimation is unbiased by gametic selection. Four out of the seven chromosomal segments were linked to an overdominant lethal factor. One of these four segments had symmetric overdominance, an effect which persisted from embryo maturity through germination. Four overdominant lethal factors were linked to common and rare marker alleles. Gametic selection was not a source of bias in dominance estimation. Overdominant or pseudo-overdominant lethal factors are a common component of the conifer embryo lethal system.
10.1038/sj.hdy.6800354
pubmed_715_8520
We report a 58-year-old Afro-Caribbean woman who presented with more than 20 dermatofibromas on the body particularly on the back, arms and legs. These developed spontaneously over the course of 5 years. She also had a long-standing 5 x 2-cm area of lipoatrophy on the right upper arm and a 2-year history of several inflammatory subcutaneous nodules developing on the upper chest and left breast. These were confirmed histologically as lupus profundus. Apart from a mild arthritis, she had no other markers for systemic lupus erythematosus and was systemically well. Multiple dermatofibromas are rare. There are around 30 reports of multiple dermatofibromas associated with systemic diseases. More than half of these cases were associated with systemic lupus erythematosus, with or without systemic steroid therapy and about one-third were associated with HIV infection. Although the mechanism is unknown, it appears that multiple dermatofibromas are associated with autoimmune diseases or altered immune states. This is the first case of multiple dermatofibromas associated with lupus profundus. The knowledge of such associations may contribute to the understanding of the pathogenesis of dermatofibromas, which is as yet unknown.
10.1111/j.1365-2230.2004.01663.x
pubmed_191_12661
This study describes the validation of short tandem repeat (STR) systems for the resolution of cases of disputed parentage where only a single parent is available for testing or where the claimed relationship of both parents is in doubt and also cases where sibship must be tested. Three separate multiplex systems the Second Generation Multiplex, Powerplex 1.2 and FFFL have been employed, giving a total of 16 STR loci. Both empirical and theoretical approaches to the validation have been adopted. Appropriate equations have been derived to calculate likelihood ratios for different relationships, incorporating a correction for subpopulation effects. An F(ST) point estimate of 1% has been applied throughout. Empirically, 101 cases of alleged father, alleged mother and child where analysed using six SLP systems and also using the three multiplex STR systems. Of the 202 relationships tested, 197 were independently resolved by both systems, providing either clear evidence of non-parentage or strong support for the relationship.
10.1007/s004140100212
pubmed_921_82
The authors assessed temporal trends in acquired immunodeficiency syndrome (AIDS) survival for 15,271 persons in San Francisco, California, diagnosed between 1987 and 1996 with an opportunistic illness included in the 1987 AIDS case definition. Predictors of survival were evaluated for 5,686 persons who were diagnosed between 1993 and 1996 and met the 1993 AIDS case definition. Median survival was 19 months for persons diagnosed between 1987 and 1989, 17 months for persons diagnosed between 1990 and 1992, 15 months for persons diagnosed between 1993 and 1994, and 31 months for persons diagnosed between 1995 and 1996. Decreased mortality was associated with use of antiretroviral therapy without protease inhibitors before AIDS (relative hazard (RH) = 0.88, 95% confidence interval (CI): 0.8, 1.0) and after AIDS (RH = 0.83, 95% CI: 0.7, 0.9) and use of antiretroviral agents with protease inhibitors before AIDS (RH = 0.25, 95% CI: 0.2, 0.3) and after AIDS (RH = 0.36, 95% CI: 0.3, 0.4). Increased mortality was found for persons aged > or = 40 years (RH = 1.43, 95% CI: 1.3, 1.6), persons initially diagnosed with an opportunistic illness (RH = 1.97, 95% CI: 1.8, 2.2), and homosexual injection drug users (RH = 1.33, 95% CI: 1.2, 1.5). Survival after AIDS has increased. Treatment with antiretroviral agents, particularly protease inhibitors, strongly predicts improved survival.
10.1093/aje/152.2.178
pubmed_617_11493
OBJECT Juxtafacet cysts (JFCs) in usual locations have recently been shown to have joint connections. The pathogenesis of JFCs in unusual locations has remained obscure. The authors hypothesize that all JFCs, including atypical ones, are joint derived. METHODS In this study the authors sought to explain the occurrence and formation of clinical outliers of spinal JFCs. In Part I, they performed an extensive literature search to identify case reports of spinal intraneural cysts that have been unappreciated despite the fact that they should occur. In Part II, they studied far-lateral (extraforaminal) cysts treated at their institution and reported in the literature. The presence of a joint connection was specifically looked for since this finding has not been widely appreciated. RESULTS In Part I, 3 isolated case reports of spinal intraneural JFCs without reported joint connections were identified: 2 involving L-5 and 1, C-8. In Part II, 6 cases involving patients with far-lateral JFCs treated at the authors' institution were reviewed and all 6 had joint connections. Two of these cases had been previously published, although their joint connections were not appreciated. In 2 of the newly reported cases, arthrography confirmed a communication between the facet and the cyst. Only 1 of 5 cases in the literature had a recognized joint connection. CONCLUSIONS The authors believe that all JFCs are joint derived. This explanation for intraneural and extraneural JFCs in typical locations would be consistent with the unified articular (synovial) theory and the pathogenesis for intraneural and extraneural ganglion cyst formation in the limbs. Facet joints appear no different from other synovial joints occurring elsewhere. Understanding the pathogenesis of these cysts will help target treatment to the joint, improve surgical outcomes, and decrease recurrences.
10.3171/2009.7.SPINE09257
pubmed_911_16929
BACKGROUND Asthma is a complex-trait disease caused by complicated interactions among multiple genetic and environmental risk factors. The clinical symptoms of asthma, such as periodic airway obstruction, hyperresponsiveness and mucus hypersecretion, are mediated by acute and chronic bronchial inflammation. METHODS To better understand the mechanisms by which allergen-induced acute inflammation leads to chronic asthma accompanied by irreversible airway remodeling, we analyzed time course transcriptional responses in the lungs of model mice that were exposed to aerosolized ovalbumin for up to 9 weeks after an initial sensitization. RESULTS We observed increased levels of total plasma IgE and histological changes in lung tissues from the ovalbumin-treated mice, which is consistent with the typical inflammatory phenotypes of asthma pathogenesis. Our oligonucleotide microarray analyses revealed a total of 776 differentially expressed genes induced by antigenic challenge (> or =1.5-fold change, p < 0.05). Of these genes, most of the immune-responsive genes were transiently up-regulated in the early phase of the allergen treatment (within a week) with a concomitant up-regulation of genes involved in mucus production. These genes were not differentially regulated in the mice challenged for a longer period of time (up to 6 weeks). We also identified some of the genes implicated in extracellular matrix remodeling, for which the time course expression did not necessarily coincide with the expression patterns of immune-responsive genes. CONCLUSION Our data suggest that there is a complex interregulatory genetic network associated with the structural changes that accompany the progression of the allergic inflammatory reaction in chronic asthma.
10.1159/000112502
pubmed_768_9714
OBJECTIVE Penoscrotal webbing (PSW) is a common reason for deferral of neonatal circumcision. Reports of successful procedures and outcomes in the literature are sparse. We have performed double-V scrotoplasty (DVS), a modification of a V-Y technique, in 138 patients with excellent results. PATIENTS AND METHODS We retrospectively reviewed the charts of boys who had undergone DVS for PSW since January 2009 by a single surgeon (S.A.A.). The indications, intraoperative findings, concomitant procedures, outcomes, and complications were recorded. RESULTS A total of 138 DVSs were performed. Concomitant genital surgeries included 81 hidden penis repairs and 10 other (hernia, hypospadias, chordee, orchidopexy). The median age at the time of surgery was 9.6 months (6.1 months-9.8 years). Patients were evaluated about 1 month postoperatively. In seven cases (5%), minor skin separation occurred at the penoscrotal junction but all healed completely. Superficial skin infection occurred in one patient. None required reoperation and cosmetic results were subjectively excellent. CONCLUSIONS PSW has been corrected in 138 patients without significant complications and with excellent results. This is the largest known peer-reviewed series evaluating a surgical technique for congenital PSW repair. We believe our technique is simple, reproducible, and, with no diverging suture lines lateral to the median raphe, improves cosmesis.
pubmed_768_9714
pubmed_409_17307
Authors present specially adapted visual acuity charts for "low vision" patients. For them refraction must be surveyed as often as possible.
pubmed_409_17307
pubmed_1036_994
In the processing and analysis of diffusion tensor imaging (DTI) data, certain predefined morphological features of diffusion tensors are often represented as simplified scalar indices, termed diffusion anisotropy indices (DAIs). When comparing tensor morphologies across differing voxels of an image, or across corresponding voxels in different images, DAIs are mathematically and statistically more tractable than are the full tensors, which are probabilistic ellipsoids consisting of three orthogonal vectors that each has a direction and an associated scalar magnitude. We have developed a new DAI, the "ellipsoidal area ratio" (EAR), to represent the degree of anisotropy in the morphological features of a diffusion tensor. The EAR is a normalized geometrical measure of surface curvature in the 3D diffusion ellipsoid. Monte Carlo simulations and applications to the study of in vivo human data demonstrate that, at low noise levels, EAR provides a similar contrast-to-noise ratio (CNR) but a higher signal-to-noise ratio (SNR) than does fractional anisotropy (FA), which is currently the most popular anisotropy index in active use. Moreover, at the high noise levels encountered most commonly in real-world DTI datasets, EAR compared with FA is consistently much more robust to perturbations from noise and it provides a higher CNR, features useful for the analysis of DTI data that are inherently noise sensitive.
10.1016/j.mri.2008.07.018
pubmed_57_20328
The non-structural protein 1 (NS1) of avian influenza virus was defined as one of the virulent factors. To understand the effect of NS1 protein of influenza virus H5N1 isolated in Thailand on type I (α/β) interferon (IFN) synthesis, five reverse genetic viruses were constructed and used as models. The viruses were generated using NS genomic segment from A/Peurto Rico/8/1934 (H1N1) and four avian influenza viruses isolated from the first outbreak in Thailand. All the viruses have the rest of the genome from A/Peurto Rico/8/1934 (H1N1). The constructed viruses were named (1) NS1 PR8/34, (2) NS1 wild type, (3) NS1 L15FD53G, (4) NS1 N171I and (5) NS1 E71K, respectively. The type I (α/β) IFN gene expression in control and infected primary chicken embryonic fibroblast cells were analyzed by quantitative polymerase chain reaction. The results show that the inhibition of IFN-β gene expression by NS1 wild type infected cells is stronger than NS1 N171I, NS1 E71K, NS1 PR8/34 and NS1 L15FD53G, respectively. The data suggest that the difference of amino acid sequence of NS1 protein contributes to the IFN-β antagonist. In contrast, the difference of the NS1 protein does not influence in the IFN-α antagonistic activity.
10.1007/s13337-013-0158-8
pubmed_294_19037
To elucidate the role of endogeneous cyclic AMP in the protection against airway mucosal dysfunction induced by air pollutants, we studied the effect of sulfur dioxide (SO2) on ciliary motility in rabbit cultured tracheal epithelium in vitro. Exposure of cells to perfusate bubbled with SO2 rapidly decreased ciliary beat frequency (CBF), as assessed by a photoelectric method, from 971 +/- 12 to 718 +/- 28 beats/min by 3 ppm SO2 and from 963 +/- 22 to 635 +/- 34 beats/min by 10 ppm SO2 (p < 0.001, in each case). This effect was reversed by washing out the SO2-containing medium and was accompanied by a corresponding decrease in intracellular levels of cyclic AMP. Preincubation of the epithelial cells with salbutamol, vasoactive intestinal peptide, prostaglandin E2 or 3-isobutyl-1-methylxanthine increased cyclic AMP levels and inhibited the decreases in both CBF and cyclic AMP in response to the subsequent application of SO2 at 3 ppm, whereas dexamethasone had no effect. These results suggest that SO2 decreases airway ciliary motility through the reduction of intracellular cyclic AMP concentration, and that drugs that increase endogeneous cyclic AMP may prevent the SO2-induced impairment of mucociliary transport in the respiratory tract.
pubmed_294_19037
pubmed_135_23735
Epilepsy is one of the most common and disabling chronic neurological diseases affecting people of all ages. Major challenges of epilepsy management include the persistently high percentage of drug-refractoriness among patients, the absence of disease-modifying treatments, and its diagnosis and prognosis. To date, long-term video-electroencephalogram (EEG) recordings remain the gold standard for an epilepsy diagnosis. However, this is very costly, has low throughput, and in some instances has very limited availability. Therefore, much effort is put into the search for non-invasive diagnostic tests. Purinergic signalling, via extracellularly released adenosine triphosphate (ATP), is gaining increasing traction as a therapeutic strategy for epilepsy treatment which is supported by evidence from both experimental models and patients. This includes in particular the ionotropic P2X7 receptor. Besides that, other components from the ATPergic signalling cascade such as the metabotropic P2Y receptors (e.g., P2Y1 receptor) and ATP-release channels (e.g., pannexin-1), have also been shown to contribute to seizures and epilepsy. In addition to the therapeutic potential of purinergic signalling, emerging evidence has also shown its potential as a diagnostic tool. Following seizures and epilepsy, the concentration of purines in the blood and the expression of different compounds of the purinergic signalling cascade are significantly altered. Herein, this review will provide a detailed discussion of recent findings on the diagnostic potential of purinergic signalling for epilepsy management and the prospect of translating it for clinical application. This article is part of the Special Issue on 'Purinergic Signaling: 50 years'.
10.1016/j.neuropharm.2022.109303
pubmed_339_7008
Low molecular weight heparins (LMWHs) have been demonstrated to be at least as safe and effective as unfractionated heparin (UFH) in the initial management of deep vein thrombosis (DVT). However, the effectiveness of using LMWH in the ambulatory management of DVT in a 'real-life' setting has yet to be evaluated. This multicentre retrospective study involving 697 patients considers the outcome data of patients under- going ambulatory DVT treatment with tinzaparin (Innohep(R), Leo Pharmaceuticals, Risborough, Buckinghamshire, UK). During the 6 months following presentation, 17 (2.5%) patients had confirmed thromboembolic complications, of which 14 occurred subsequent to the initial LMWH treatment phase ('late'). There were no deaths in this group. Bleeding complications were reported in 23 (3.4%) patients, with 13 of these being classified as 'late'. Of these, two events were considered major resulting in hospitalization and death. Hospitalization for all causes was 6.8% (45 patients) with 32 patients being admitted for thromboembolic or bleeding complications. Overall mortality was 6.7%. These results compare favourably with published clinical trial data. This study demonstrates that ambulatory treatment of proven DVT with LMWH is both safe and effective.
10.1046/j.1365-2257.2001.00403.x
pubmed_584_3378
We report here the synthesis and characterization of two new classes of chelating fibers, namely, (1) polymercaptopropylsilsesquioxane (PMPS) and (2) copper(II) ferrocyanide complexed with poly[1-(2-aminoethyl)-3-aminopropyl]silsesquioxane (Cu-FC-PAEAPS) fibers. These fibers were evaluated for selective removal of trace amount of mercury and cesium ions respectively in the presence of competing metal ions from water. The PMPS and Cu-FC-PAEAPS fibers were prepared by coating their corresponding soluble prepolymers, which are derived from mercaptopropyltrimethoxysilane and [1-(2-aminoethyl)-3-aminopropyl]trimethoxysilane monomers, respectively, on a glass fiber substrate, followed by a cross-linking step at 120 degrees C. The fibers were characterized through infrared spectroscopy, scanning electron microscopy (SEM), and thermogravimetric analysis (TGA). These novel materials are extremely efficient in removing low concentrations of mercury and cesium ions from water in the presence of high concentrations of sodium or potassium ions. They were shown to remove trace mercury and cesium contaminants effectively to well below parts per billion concentrations under a variety of conditions.
10.1021/es0343104
pubmed_730_4296
Photosynthetic prokaryotes that assimilate CO2 under anoxic conditions may also grow chemolithoautotrophically with O2 as the electron acceptor. Among the nonsulfur purple bacteria, two species (Rhodobacter capsulatus and Rhodopseudomonas acidophilus), exhibit aerobic chemolithoautotrophic growth with hydrogen as the electron donor. Although wild-type strains of Rhodobacter sphaeroides grow poorly, if at all, with hydrogen plus oxygen in the dark, we report here the isolation of a spontaneous mutant (strain HR-CAC) of Rba. sphaeroides strain HR that is fully capable of this mode of growth. Rba. sphaeroides and Rba. capsulatus fix CO2 via the reductive pentose phosphate pathway and synthesize two forms of ribulose 1, 5-bisphosphate carboxylase/oxygenase (RubisCO). RubisCO levels in the aerobic-chemolithoautotrophic-positive strain of Rba. sphaeroides were similar to those in wild-type strains of Rba. sphaeroides and Rba. capsulatus during photoheterotrophic and photolithoautotrophic growth. Moreover, RubisCO levels of Rba. sphaeroides strain HR-CAC approximated levels obtained in Rba. capsulatus when the organisms were grown as aerobic chemolithoautotrophs. Either form I or form II RubisCO was able to support aerobic chemolithoautotrophic growth of Rba. capsulatus strain SB 1003 and Rba. sphaeroides strain HR-CAC at a variety of CO2 concentrations, although form II RubisCO began to lose the capacity to support aerobic CO2 fixation at high O2 to CO2 ratios. The latter property and other facets of the physiology of this system suggest that Rba. sphaeroides and Rba. capsulatus strains may be effectively employed for the biological selection of RubisCO molecules of altered substrate specificity.
10.1007/s002030050609
pubmed_211_8299
The aim of this study was to make a comparative analysis between the bone response to machined and sandblasted implants. The sandblasting was done with 150-microns aluminum oxide particles. Under scanning electron microscopic examination, the machined implants presented typical machining grooves, while a very rough, highly irregular surface with depressions and indentations was present on the sandblasted implants. Light microscopy showed a different bone growth pattern on machined (implantopetal growth) and sandblasted (implantofugal growth) implants. No negative effects on the rate of bone growth were observed in spite of the presence of aluminum ions. The histomorphometric analysis showed that sandblasted implants presented, from the third week onwards, a significantly higher contact percentage (P < .0001). These values could point to higher osteoconductivity as a result of the higher surface roughness of sandblasted surfaces.
pubmed_211_8299
pubmed_5_14021
Hematopoietic lineage cell-specific protein 1 (HS1), a tyrosine multiphosphorylated protein implicated in receptor-mediated apoptosis and proliferative responses, is shown here to become Ser/Thr phosphorylated upon incubation of platelets with radiolabeled inorganic phosphate. The in vivo Ser/Thr phosphorylation of HS1 is enhanced by okadaic acid and reduced by specific inhibitors of casein kinase (CK)2. In vitro, HS1 is an excellent substrate for either CK2 alpha subunit alone (Km = 47 nM) or CK2 holoenzyme, tested in the presence of polylysine (Km = 400 nM). Phosphorylation reaches a stoichiometry of about 2 mol phosphate per mol HS1 and occurs mainly at threonyl residue(s), mostly located in the N-terminal region, but also at seryl residue(s) residing in the central core of the molecule (208-402), as judged from experiments with deleted forms of HS1. Ser/Thr phosphorylation of HS1, either induced in vivo by okadaic acid or catalysed in vitro by CK2, potentiates subsequent phosphorylation at tyrosyl residues. These data indicate the possibility that regulation of HS1 may also be under the control of Ser/Thr phosphorylation, and suggest that in quiescent cells CK2 could play a role in inducing constitutive Tyr phosphorylation of HS1 in the absence of stimuli that activate the protein tyrosine kinase pathway.
10.1046/j.1432-1033.2000.01333.x
pubmed_701_16259
Mycotoxin contamination of crops may cause economic losses at all levels of food and feed production including crop and animal production, and crop distribution and processing. The national economy would be affected adversely by losses incurred by crop and livestock producers and the multiplier effect this has on other industries as a result of the reduced spending power of producers. Costs of chemical analyses, quality control and regulatory programs, research and development, extension services, law suits, and the cost of human illnesses must all be borne by the national economy. The value of the losses encountered depends on grain, animal, and animal product prices, interest rates, degree of contamination, and other economic variables. Even during favourable seasons it is likely that millions of dollars are lost as a result of the contamination of crops with mycotoxins. Many compounds and treatments have been tested in order to reduce mycotoxin concentrations in food and feed or to alleviate their adverse effects on animals. Some of these treatments show promising prospects for commercial application, while others have had commercial applications already. However, until reliable, cost-effective, commercially applicable methods are more widely available, problems associated with mycotoxin contamination and the economic losses resulting, will continue to be seen in food and agriculture industries.
10.1002/nt.2620030406
pubmed_661_6902
Morphologic observation of the peripheral blood smear from a patient with chronic granulocytic leukemia suggested the presence of eosinophilic and basophilic granules in the same individual granulocyte. To unambiguously identify eosinophilic and basophilic granules simultaneously in the same preparation, the authors developed a cytochemical staining procedure using basophil-specific toluidine blue and eosinophil-specific cyanide-resistant peroxidase. Using this new dual stain, they demonstrated that ten out of ten chronic granulocytic leukemia patients they examined had cells that contained both eosinophilic and basophilic granules. The identity of the granules was corroborated by electron microscopic studies. These observations suggest that lineage confusion is common in chronic granulocytic leukemia.
10.1093/ajcp/87.1.66
pubmed_929_18044
OBJECTIVE To explore sexual sensation seeking (SSS) among an ethnically-diverse sample of first-year college students and their hookup behaviors. PARTICIPANTS 1,480 first-year college students who hooked up in the last 30 days were recruited from four universities in 2016. METHODS Students completed an online survey before completing an online STI and alcohol prevention intervention. RESULTS Male and sexual minority students had significantly higher SSS scores compared to female and heterosexual students respectively. Students with higher SSS scores were less likely to report condom use at last vaginal and anal hookup, more likely to hookup under the influence of alcohol and participate in a wide range of sexual behaviors. There were no significant mean differences in SSS scores by level of intoxication during their last hookup. CONCLUSION These findings highlight the role of SSS in predicting sexual risk behaviors of first-year college students and the overall low SSS scores among this sample.
10.1080/07448481.2020.1713136
pubmed_582_17007
An instrument used to measure the content of soil organic matter was developed based on spectroscopy. The instrument consists of an optical unit and an electronic unit. The optical unit is used to collect the reflecting light from soil surface and change the filtered light into the electrical signal. The electronic unit includes an amplifying circuit, an A/D circuit, and a display and storage circuit. Three wavebands of filters, 530, 765, and 850 nm, were selected in the performance test in order to determine the optimal one. The soil samples tested include two types, dried soil and air-dry soil. The result shows that there is highest correlation between the reflectance and the content of soil organic matter at the wavelength of 850 nm (r2 = 0.930) for dried soil. While the coefficient of determination r2 is abouu 0.711 for air-dry soil at the same wavelength. Although the actual precision is lower because of the soil moisture, it is practical in real-time measurement in the field.
pubmed_582_17007
pubmed_1124_1399
BACKGROUND The aim of this study was to demonstrate that 3-days of induction immunosuppression with thymoglobulin was as effective and safe as a 7-day course and reduced initial hospitalization after transplantation. METHODS This was a prospective, nonrandomized trial of 40 consecutive patients receiving thymoglobulin induction for 3 days and followed for 1 year. An historical group of 48 patients that received 7 days of thymoglobulin served as controls. RESULTS At 1 year, acute rejection (5 vs. 4%), graft survival (95 vs. 98%) and patient survival were similar; a composite end point of freedom from death, rejection, or graft loss, the event-free graft survival, was similar as was the safety profile. In the 3-day group, lymphocyte depletion was more sustained and initial hospitalization was significantly shorter (6 vs. 8 days). CONCLUSION Three-day induction with thymoglobulin is as effective and safe as seven days, decreases initial hospitalization and causes more sustained lymphocyte depletion.
10.1097/00007890-200202150-00025
pubmed_897_8535
BACKGROUND & AIMS Altered intestinal barrier function has been implicated in the pathophysiology of ulcerative colitis (UC) in genetic, functional, and epidemiological studies. Mast cells and corticotropin-releasing factor (CRF) regulate the mucosal barrier in human colon. Because eosinophils are often increased in colon tissues of patients with UC, we assessed interactions among mast cells, CRF, and eosinophils in the mucosal barrier of these patients. METHODS Transmucosal fluxes of protein antigens (horseradish peroxidase) and paracellular markers ((51)Cr-EDTA, fluorescein isothiocyanate-dextran 4000) were studied in noninflamed, colonic mucosal biopsy samples collected from 26 patients with UC and 53 healthy volunteers (controls); samples were mounted in Ussing chambers. We also performed fluorescence and electron microscopy of human tissue samples, assessed isolated eosinophils, and performed mechanistic studies using in vitro cocultured eosinophils (15HL-60), mast cells (HMC-1), and a colonic epithelial cell line (T84). RESULTS Colon tissues from patients with UC had significant increases in permeability to protein antigens compared with controls. Permeability was blocked by atropine (a muscarinic receptor antagonist), α-helical CRF(9-41) (a CRF receptor antagonist), and lodoxamide (a mast-cell stabilizer). Eosinophils were increased in number in UC tissues (compared with controls), expressed the most M2 and M3 muscarinic receptors of any mucosal cell type, and had immunoreactivity to CRF. In coculture studies, carbachol activation of eosinophils caused production of CRF and activation of mast cells, which increased permeability of T84 epithelial cells to macromolecules. CONCLUSIONS We identified a neuroimmune intercellular circuit (from cholinergic nerves, via eosinophils to mast cells) that mediates colonic mucosal barrier dysfunction in patients with UC. This circuit might exacerbate mucosal inflammation.
10.1053/j.gastro.2011.01.042
pubmed_616_1528
Mass blooms of purple sulfur bacteria growing seasonally on green stranded macroalgae have a major impact on the microbial composition and functionality of intertidal mats. To explore the active anoxygenic phototrophic community in purple bacterial mats from the Roscoff Aber Bay (Brittany, France), we conducted a combined approach including molecular and high-resolution secondary ion mass spectrometry (NanoSIMS) analyses. To investigate the dynamics of carbon and nitrogen assimilation activities, NanoSIMS was coupled with a stable isotope probing (SIP) experiment and a compound specific isotope analysis (CSIA) of fatty acid methyl ester (FAME). Sediment samples were incubated with 13C- and/or 15N-labeled acetate, pyruvate, bicarbonate and ammonium. NanoSIMS analysis of 13C - and 15N -incubated samples showed elevated incorporations of 13C - and 15N in the light and of 13C -acetate in the dark into dense populations of spherical cells that unambiguously dominated the mats. These results confirmed CSIA data that ranked vaccenic acid, an unambiguous marker of purple sulfur bacteria, as the most strongly enriched in the light after 13C -acetate amendment and indicated that acetate uptake, the most active in the mat, was not light-dependent. Analysis of DNA- and cDNA-derived pufM gene sequences revealed that Thiohalocapsa-related clones dominated both libraries and were the most photosynthetically active members of the mat samples. This study provides novel insights into the contribution of purple sulfur bacteria to the carbon cycle during their seasonal developments at the sediment surface in the intertidal zone.
10.3389/fmicb.2017.01995
pubmed_720_10046
8-oxodeoxyguanosine (8-oxodG), a major oxidised base modification, has been investigated to study its impact on DNA replication in hyperthermophilic Archaea. Here we show that 8-oxodG is formed in the genome of growing cells, with elevated levels following exposure to oxidative stress. Functional characterisation of cell-free extracts and the DNA polymerisation enzymes, PolB, PolD, and the p41/p46 complex, alone or in the presence of accessory factors (PCNA and RPA) indicates that translesion synthesis occurs under replicative conditions. One of the major polymerisation effects was stalling, but each of the individual proteins could insert and extend past 8-oxodG with differing efficiencies. The introduction of RPA and PCNA influenced PolB and PolD in similar ways, yet provided a cumulative enhancement to the polymerisation performance of p41/p46. Overall, 8-oxodG translesion synthesis was seen to be potentially mutagenic leading to errors that are reminiscent of dA:8-oxodG base pairing.
pubmed_720_10046
pubmed_512_19994
Introduction. Goitre with euthyroid function or with subclinical or mild hyperthyroidism due to thyroid autonomy is common. In anthroposophic medicine various thyroid disorders are treated with Colchicum autumnale (CAU). We examined the effects of CAU in patients with goitre of both functional states. Patients and methods. In an observational study, 24 patients with goitre having suppressed thyroid stimulating hormone (TSH) levels with normal or slightly elevated free thyroxine (fT4) and free triiodothyronine (fT3) (group 1, n = 12) or normal TSH, fT3, and fT4 (group 2, n = 12) were included. After 3 months and after 6 to 12 months of CAU treatment, we investigated clinical pathology using the Hyperthyroid Symptom Scale (HSS), hormone status (TSH, fT4, and fT3), and thyroidal volume (tV). Results. After treatment with CAU, in group 1 the median HSS decreased from 4.5 (2.3-11.8) to 2 (1.3-3) (p < 0.01) and fT3 decreased from 3.85 (3.5-4.78) to 3.45 (3.3-3.78) pg/mL (p < 0.05). In group 2 tV (13.9% (18.5%-6.1%)) and TSH (p < 0.01) were reduced. Linear regression for TSH and fT3 in both groups indicated a regulative therapeutic effect of CAU. Conclusions. CAU positively changed the clinical pathology of subclinical hyperthyroidism and thyroidal volume in patients with euthyroid goitre by normalization of the regulation of thyroidal hormones.
10.1155/2016/2541912
pubmed_291_5952
Recognition of NKG2D ligands by natural killer (NK) cells plays an important role during antitumoral responses. To address how NKG2D engagement affects intratumoral NK cell dynamics, we performed intravital microscopy in a Rae-1β-expressing solid tumor. This NKG2D ligand drove NK cell accumulation, activation, and motility within the tumor. NK cells established mainly dynamic contacts with their targets during tumor regression. In sharp contrast, cytotoxic T lymphocytes (CTLs) formed stable contacts in tumors expressing their cognate antigen. Similar behaviors were observed during effector functions in lymph nodes. In vitro, contacts between NK cells and their targets were cytotoxic but did not elicit sustained calcium influx nor adhesion, whereas CTL contact stability was critically dependent on extracellular calcium entry. Altogether, our results offer mechanistic insight into how NK cells and CTLs can exert cytotoxic activity with remarkably different contact dynamics.
10.1016/j.immuni.2010.09.016
pubmed_215_12611
The study of isolated segments of aorta has shown that prolongated exposure of rats to gamma-radiation with 50 cGy dose (with a dose rate of 2.8 x 10(7) Gy/s) causes the decrease in endothelium-dependent dilatation responses to M-cholinoreceptors stimulation. During oxygenation the post-radiation changes are displayed within one month, and under functional loads, specifically, during perfusion by hypoxic and anoxic solutions--in more remote terms of the post-radiation period.
pubmed_215_12611
pubmed_973_21515
Although conceptualizations of perfectionism have emphasized adaptive as well as maladaptive expressions of the construct, how these different dimensions or types of perfectionists might be reflected in comprehensive personality assessment instruments is unknown. An initial sample of 267 university students completed the Minnesota Multiphasic Personality Inventory-2 (MMPI-2; Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer, 2001), Millon Index of Personality Styles Revised (MIPS-R; Millon, 2004), and Almost Perfect Scale-Revised (Slaney, Mobley, Trippi, Ashby, & Johnson, 1996). Analyses indicated that dimensions and types of perfectionism were associated, in expected directions, with select scores on the MMPI-2 and MIPS-R.
10.1080/00223890903510407
pubmed_960_3543
Microbial cells operate under governing constraints that limit their range of possible functions. With the availability of annotated genome sequences, it has become possible to reconstruct genome-scale biochemical reaction networks for microorganisms. The imposition of governing constraints on a reconstructed biochemical network leads to the definition of achievable cellular functions. In recent years, a substantial and growing toolbox of computational analysis methods has been developed to study the characteristics and capabilities of microorganisms using a constraint-based reconstruction and analysis (COBRA) approach. This approach provides a biochemically and genetically consistent framework for the generation of hypotheses and the testing of functions of microbial cells.
10.1038/nrmicro1023
pubmed_737_13826
A structural polymorphism of nucleic acids, which depends on the concentration of cations and the conditions of hydration, are strongly involved with interactions between DNA and proteins. In this paper, we report that different DNA sequences bound to hyperthermostable TATA-box-binding protein (PhoTBP) at different combinations of temperature and salt concentration in in vitro selection experiments. As a result of the interaction of-these selected DNAs with PhoTBP, characteristic changes in the numbers of water molecules and ions occurred under each condition of the selection experiment. This finding could help us to understand the solvent environment-dependent preference for base sequences in protein–DNA interactions.
10.1039/b914828k
pubmed_967_1980
The excretion of sulfated steroids was investigated in the urine and feces of six boys aged 9 months to 7 years and 10 months who had recessive X-linked ichthyosis. Profiles of urinary total steroids as well as sulfated steroids were normal. Cholesterol sulfate excretion in the urine was not elevated. In the feces 2-20% of total cholesterol was cholesterol sulfate, whereas in the feces of 28 healthy children no cholesterol sulfate was demonstrable. In the 6 patients total cholesterol excretion (500-2,500 mumol/kg feces) was also elevated in comparison with the 28 healthy controls (150-700 mumol/kg feces, mean 365 mumol/kg feces).
10.1007/BF00413356
pubmed_1123_24024
Majority of municipal (urban) solid waste (MSW) is disposed of in landfills (anaerobic composting). However, this disposal system is reported to produce hazardous environmental impacts and new policies are initiated to protect the environment from such impacts by discouraging the practice of disposal of solid waste in landfills. Eco-friendly disposal alternatives to landfills need to be explored. One of the technological options for treatment and disposal of organic solid wastes is vermicomposting. Commercial vermicomposting is reported to be practicable for treatment and disposal of many organic solids and byproducts in agricultural production and processing industries. However, this alternative has not been tried for MSW on large scale. This paper highlights the application of vermicomposting for treatment of organic solid waste, generated at urban residential area at Pune [organic component of this urban solid waste (MSW)]. Vermicomposting was tried on this segregated solid waste using exotic species of earthworm--Eudrilus eugeniae--commonly called 'African Night Crawler'. Bench scale reactor studies were carried out on organic solid waste under controlled optimum environmental conditions (moisture content: 48-52 percent, pH: 7.0-7.2, temperature: ambient), with variable vermi-loading [40-80 g of worms/kg of urban solid waste (MSW)]. Characteristics of solid waste were monitored through conventional parameters and additional environmental parameters like BOD5 and COD. The results of investigative studies are encouraging and indicate that organic solid waste can be treated in a reasonable period of 32-34 days through vermicomposting with around 60 percent reduction in the volume.
pubmed_1123_24024
pubmed_841_20532
A full-length cDNA encoding a novel protein named PARF-1 was isolated from Arabidopsis thaliana. PARF-1 is the first eukaryotic protein to be identified that displays a domain structure which includes a FYVE-finger domain, a Pleckstrin Homology (PH) domain, as well as multiple Regulator of Chromosome Condensation-1 (RCC1) repeats. Northern blot analysis revealed that PARF-1 mRNA is present at high levels in flowers, but only at very low levels in other tissues. Recombinant PARF-1 fusion proteins expressed in E. coli were found to display unique binding specificities for monophosphorylated phosphoinositide lipids. The unusual domain structure of PARF-1 combined with its phosphoinositide specificity suggests that it may fulfil unexpected functions in higher plants.
10.1093/jexbot/53.368.565
pubmed_586_13026
By means of the system of ion-selective electrodes the coupling transport of K+, H+ and Cl- ions in liposome suspension was studied. Nigericin and tributyl tin (TBT) were used as inductors of cation and anion exchange. Effect of pH gradient created on the membrane on ionic transport was studied. The latter was shown to control the antiport exchange of both, cations and anions. At the joint effect of nigericin and TBT the yield of K+ and Cl- ions from liposomes independent of the pH gradient was observed.
pubmed_586_13026
pubmed_289_762
This study explored subjectively perceived and objectively rated family dysfunction using the self-report Family Assessment Device (FAD) and observer-rated McMaster Clinical Rating Scale (MCRS), respectively. Perceived differences in family functioning ratings between 86 depressed patients and their partners and the degree of agreement between the subjective and objective rating scales were analyzed. There were significant correlations for perceived family functioning between the patients and their partners. There were moderate to significant correlations between patients' perceptions on five of the seven dimensions of the FAD (excluding problem solving and roles) and those dimensions of the MCRS. Findings showed moderate to significant correlations between six dimensions of the FAD and MCRS, excluding problem solving. Results on the FAD and MCRS were significantly correlated and considered equivalent. This suggests that these two instruments can be used individually or in combination to provide a comprehensive understanding of family functioning of couples with a depressed partner.
10.1097/NMD.0b013e31828e115a
pubmed_994_7662
UNLABELLED The rapid development of CRISPR-Cas9 mediated genome editing techniques has given rise to a number of online and stand-alone tools to find and score CRISPR sites for whole genomes. Here we describe the Wellcome Trust Sanger Institute Genome Editing database (WGE), which uses novel methods to compute, visualize and select optimal CRISPR sites in a genome browser environment. The WGE database currently stores single and paired CRISPR sites and pre-calculated off-target information for CRISPRs located in the mouse and human exomes. Scoring and display of off-target sites is simple, and intuitive, and filters can be applied to identify high-quality CRISPR sites rapidly. WGE also provides a tool for the design and display of gene targeting vectors in the same genome browser, along with gene models, protein translation and variation tracks. WGE is open, extensible and can be set up to compute and present CRISPR sites for any genome. AVAILABILITY AND IMPLEMENTATION The WGE database is freely available at www.sanger.ac.uk/htgt/wge CONTACT : [email protected] or [email protected] SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
10.1093/bioinformatics/btv308
pubmed_728_10455
In spite of an important metabolic role of the liver in the synthesis and degradation of hormonal peptides and seco-steroïds, the clinical occurrence of disturbed regulation of calcium and phosphorus metabolism is rare in hepatic disorders. 23 patients suffering from alcoholic cirrhosis were studied. All had normal plasma calcium and phosphorus concentration as well as immunoreactive parathyroid hormone levels. 25 hydroxyvitamin D3 levels were decreased. Immunoreactive calcitonin were increased in relation to the increase in plasma alkaline phosphatase activity. The causes and consequences of these endocrine disturbances are discussed.
pubmed_728_10455
pubmed_481_20355
"Whiplash injuries" are frequent sequelae of motor vehicle accidents. While conventional imaging methods such as X-ray, including special and functional lateral projections, continue to be the first-choice evaluation methods, they frequently do not reveal injuries to the soft tissues. Cross-sectional methods such as CT and MRT may therefore be indicated for further workup in given clinical situations. In this paper the role of the entire spectrum of imaging methods is reviewed. Emphasis is placed on so-called functional CT, which allows detection of rotational instabilities of the upper cervical spine. These are difficult to evaluate clinically or by standard imaging studies, yet they may be a frequent cause of chronic whiplash syndrome. Furthermore, some results of morphologic studies of the alar ligaments by MRT are presented. Although experience to date is limited, it is likely that MRT of the occipitocervical junction region due to its potential to reveal exquisite anatomical detail, will gain in importance in the future.
pubmed_481_20355
pubmed_378_12715
A 76-year-old man suddenly experienced floating sensation, transient vertigo, and nausea. Neurological examination was unremarkable except for hypotonia and mild ataxia in the limbs, but orthostatic nausea and vomiting forced him to take a quiet, recumbent position. Magnetic resonance imaging of the brain showed cerebellar infarction restricted to the bilateral inferior vermis. During a course of recovery, he fell down in any directions while standing unattended. He was unable to keep the center of gravity on the feet base in an upright posture. The inferior vermis may participate in maintaining the center of gravity while standing.
pubmed_378_12715
pubmed_1015_5453
The in vitro release profiles of the F-series of prostaglandins were determined from a silicone rubber matrix of constant surface area. Silicone rubber was selective toward prostaglandin transport and offers potential as a controlled-release delivery system. Drug release patterns were dependent on the lipophilicity of the prostaglandin molecule. For dinoprost (prostaglandin F2 alpha), the following sequences was observed: methyl ester greater than free acid greater than tromethamine salt. The biologically potent carboprost methyl [(15S)-15-methylprostaglandin F2 alpha methyl ester] was release considerably faster than the methyl ester of the parent dinoprost molecule, while release of the tromethamine salt of the two prostaglandins was similar. Permeability rates of the salts were depressed substantially when compared to their respective C-1 methyl esters. Results from independent membrane transport studies supported the observed dependence of steady-state flux on the chemical structure of the prostaglandin molecule. Plots of the amount released per unit area versus the square root of time were linear except for the initial drug release phase, and the total amount of prostaglandin released increased as the initial loading dose was raised. The data were analyzed according to a physical model describing drug release from inert matrix systems. The observed concentration dependence was consistent with the predictions of the model.
10.1002/jps.2600700525
pubmed_315_4924
Structures of the cytochrome b(6)f complex obtained from the thermophilic cyanobacterium Mastigocladus laminosus and the green alga Chlamydomonas reinhardtii, whose appearance in evolution is separated by 10(9) years, are almost identical. Two monomers with a molecular weight of 110,000, containing eight subunits and seven natural prosthetic groups, are separated by a large lipid-containing "quinone exchange cavity". A unique heme, heme x, that is five-coordinated and high-spin, with no strong field ligand, occupies a position close to intramembrane heme b(n). This position is filled by the n-side bound quinone, Q(n), in the cytochrome bc(1) complex of the mitochondrial respiratory chain. The structure and position of heme x suggest that it could function in ferredoxin-dependent cyclic electron transport as well as being an intermediate in a quinone cycle mechanism for electron and proton transfer. The significant differences between the cyanobacterial and algal structures are as follows. (i) On the n-side, a plastoquinone molecule is present in the quinone exchange cavity in the cyanobacterial complex, and a sulfolipid is bound in the algal complex at a position corresponding to a synthetic DOPC lipid molecule in the cyanobacterial complex. (ii) On the p-side, in both complexes a quinone analogue inhibitor, TDS, passes through a portal that separates the large cavity from a niche containing the Fe(2)S(2) cluster. However, in the cyanobacterial complex, TDS is in an orientation that is the opposite of its position in the algal structure and bc(1) complexes, so its headgroup in the M. laminosus structure is 20 A from the Fe(2)S(2) cluster.
10.1021/bi049444o
pubmed_106_11733
The solvation parameter model is used to create systems maps for the separation of neutral organic compounds on a Chromolith Performance RP-18e octadecylsiloxane-bonded silica-based monolithic column for water-acetonitrile and water-methanol mobile phase compositions from 10 to 70% (v/v) organic solvent. These results demonstrate that the retention properties of the monolithic column are similar to those of conventional octadecylsiloxane-bonded silica particle-packed columns. It is further shown that the selectivity for the monolithic column falls within the selectivity range for typical particle-packed columns at two mobile phase compositions for which a direct comparison is possible.
10.1016/s0021-9673(03)00845-8
pubmed_254_20387
Carcinoma of the accessory axillary breast is uncommon, with an incidence of 0.2 to 0.6%. We report a patient whose biopsy of a suspicious lesion in the axilla present for one year revealed invasive ductal carcinoma (IDC). There was presence of breast tissue and absence of lymphoid tissue in the biopsy, suggesting a breast malignancy. Magnetic resonance mammography was suggestive of the lesion well away from the normal breast, confirming an accessory axillary breast. She was offered wide local excision of the lesion with axillary lymph node dissection and modified radical mastectomy (MRM), and she chose the latter. Her post-operative biopsy showed the involvement of all the 25 lymph nodes harvested. Any suspicious lesion in the axilla should be promptly worked up for malignancy. Accessory axillary breast carcinoma, if confirmed, can be addressed with wide local excision along with axillary lymph node dissection. However, further studies should clarify this and the outcomes.
10.7759/cureus.11844
pubmed_551_19899
In their paper "Copy number variations in 6q14.1 and 5q13.2 are associated with alcohol dependence" Lin and colleagues report on the association between alcohol dependence and 2 duplication CNVs in the genome sequence, one containing 8 genes within its boundaries and another that contains no genes. In this commentary, I point out some of the opportunities and challenges that arise from such a finding.
10.1111/j.1530-0277.2012.01915.x
pubmed_713_13693
OBJECTIVES We examined whether adult stress reactivity accounts for the relationship between early life adversity (ELA) and psychological, physical, and cognitive outcomes. METHODS We examined the relationship between ELA, stress reactivity, psychological well-being, physical health, and cognitive function in two separate datasets - a cross-sectional community sample of older adults (N = 510) aged 60 and older, and waves I-III of the Midlife in the United States (MIDUS) dataset. Age, sex, and income served as covariates in all analyses. Bootstrapped mediation models were used to assess recent stress as a mediator between ELA and mid- to late-life outcomes. RESULTS ELA was significantly associated with adult stress, anxiety, depression, health conditions, and object cognitive assessments. Adult stress partially accounted for the relationships between ELA and depression, anxiety, health conditions, and memory problems. CONCLUSION Our findings demonstrate that ELA may influence increased stress in older age, which confers additional risks for developing depression, anxiety, health problems, and cognitive decline. It is possible that intervening on adult stress may reduce risk for both psychological and physical pathology across the lifespan. Further research is needed to develop targeted interventions for mid and late-life stress to improve overall health as individuals age.
10.1080/13607863.2021.1910787
pubmed_456_24769
A genetic influence on spontaneous pneumothoraces-those occurring without a traumatic or iatrogenic cause-is supported by several lines of evidence: 1) pneumothorax can cluster in families (i.e., familial spontaneous pneumothorax), 2) mutations in the FLCN gene have been found in both familial and sporadic cases, and 3) pneumothorax is a known complication of several genetic syndromes. Herein, we review known genetic contributions to both sporadic and familial pneumothorax. We summarize the pneumothorax-associated genetic syndromes, including Birt-Hogg-Dubé syndrome, Marfan syndrome, vascular (type IV) Ehlers-Danlos syndrome, alpha-1 antitrypsin deficiency, tuberous sclerosis complex/lymphangioleiomyomatosis, Loeys-Dietz syndrome, cystic fibrosis, homocystinuria, and cutis laxa, among others. At times, pneumothorax is their herald manifestation. These syndromes have serious potential extrapulmonary complications (e.g., malignant renal tumors in Birt-Hogg-Dubé syndrome), and surveillance and/or treatment is available for most disorders; thus, establishing a diagnosis is critical. To facilitate this, we provide an algorithm to guide the clinician in discerning which cases of spontaneous pneumothorax may have a genetic or familial contribution, which cases warrant genetic testing, and which cases should prompt an evaluation by a geneticist.
10.1164/rccm.201807-1212CI
pubmed_870_8766
In two years of a routine screening programme for the detection of neural-tube defects over 6000 women had serum-alpha-fetoprotein (A.F.P.) measured. As a result, 80 women carrying live singleton fetuses were offered amniocentesis under ultrasound control. All neural-tube defects detected at birth were recorded and necropsies were done routinely on abortuses, thus permitting evaluation of the screening programme in terms of false negatives and false positives. 16 amniotic-fluid A.F.P.s were abnormal, 1 for an unaffected fetus; and 2 others were normal for fetuses which had closed lesions. At the serum-A.F.P. stage, 3 lesions were missed. The detection-rate compares favourably with those of other series. However, in a pilot study, routine ultrasonic assessment of gestation yielded a substantial proportion of cases where a serum-A.F.P. deemed normal or abnormal when gestation was assessed clinically would have been misleading. Loss of normal fetuses subsequent to amniocentesis (5 in this series) also has to be taken into account.
10.1016/s0140-6736(78)92054-8
pubmed_1107_20606
New technologies, such as magnetic resonance imaging, are frequently cited as major contributors to the growth of national health care expenditure. The cost-effectiveness of this modality is commonly challenged, and the lack of health economic documentation increases the level of criticism. Some common methods for evaluating imaging methods with regard to efficacy, cost, and benefits are, therefore, reviewed. Limitations in the assessment of diagnostic imaging are discussed, together with some suggestions as to which methodological approaches may be useful in this field of research.
10.1002/jmri.1880060106
pubmed_578_3132
BACKGROUND The National Asthma Education and Prevention Program (NAEPP) Expert Panel Report 3 guidelines advise the addition of ipratropium bromide to short-acting β-agonist therapy for the treatment of patients with severe acute asthma exacerbation. METHODS This was a prospective, double-blind, randomized, controlled study involving 141 adults, presenting to two EDs with acute severe asthma exacerbation. Patients were treated using a standardized pathway with levalbuterol plus ipratropium or levalbuterol alone. Primary outcomes were changes from baseline in the percentage of predicted forced expiratory volume in 1 second (FEV₁) at 30 minutes and 60 minutes after completion of treatment. Secondary outcomes included hospitalization and relapse rates. Occurrence of adverse events was recorded. RESULTS Sixty-seven patients in the levalbuterol plus ipratropium group and 74 patients in the levalbuterol group completed the study. Overall, there was no significant difference in the improvement in percent predicted FEV₁ between the two groups at 30 minutes [difference in change between study groups at 30 minutes: 1% (95% CI: ?3 to 2%) or at 60 minutes: 3% (95% CI: 1-6%)] No difference was noted in hospitalization rates between the treatment groups [combination therapy group, 33%; single therapy group, 47%, difference: -14% (95% CI: -30 to 20%)]. Post-hoc analysis revealed that patients receiving ipratropium in addition to levalbuterol were 1.5 times more likely to experience side effects (palpitations) than patients treated with levalbuterol alone (RR 1.5; 95% CI: 1.2-1.9) No differences in relapse rates were noted between the groups. Post-hoc analysis revealed more side effects in patients receiving levalbuterol plus ipratropium. CONCLUSION We were unable to demonstrate superiority of adding ipratropium to levalbuterol in alleviating obstruction as measured by FEV₁ or in decreasing the need for hospitalization among adult patients presenting to the ED with acute severe asthma exacerbation.
10.3109/02770903.2010.517337
pubmed_74_15872
Drug repositioning, the approach to explore existing drugs for use in new therapeutic indications, has emerged as an alternative drug development strategy. In this study, we found that a mucolytic drug, N-acetylcysteine (NAC) showed antibacterial activity against Vibrio cholerae. NAC can provide acid stress that selectively inhibited the growth of V. cholerae among other bacterial pathogens. To address the antibacterial mechanism of NAC against V. cholerae, six acr (acetylcys-teine-resistant) mutants were isolated from 3,118 random transposon insertion clones. The transposon insertion sites of the six mutants were mapped at the five genes. All these mutants did not display NAC resistance under acidic conditions, despite their resistance to NAC under alkaline conditions, indicating that the NAC resistance directed by the acr mutations was independent of the unusual pH-sensitivity of V. cholerae. Furthermore, all these mutants displayed attenuated virulence and reduced biofilm formation, suggesting that the acr genes are required for pathogenesis of V. cholerae. This study validates the relevance of drug repositioning for antibacterials with new modes of action and will provide an insight into a novel antibacterial therapy for V. cholerae infections to minimize side effects and resistance emergence.
10.1007/s12275-020-9590-9
pubmed_236_8656
PURPOSE To evaluate the effect of the combination of vincristine, dactinomycin, and doxorubicin with (regimen J) or without (regimen DD-RT) cyclophosphamide on the relapse-free survival of children with stages II to IV Wilms' tumor and focal or diffuse anaplasia. PATIENTS AND METHODS We reviewed the clinical courses of all randomized patients from National Wilms' Tumor Study (NWTS)-3 and NWTS-4 with stages II to IV anaplastic Wilms' tumor, and determined the 4-year relapse-free survival rate separately for those with focal or diffuse anaplasia. Anaplasia was evaluated using newly developed topographic definitions for focal and diffuse anaplasia. RESULTS The 4-year relapse-free survival rate for five children with focal anaplasia who received regimen DD-RT was 80.0%, compared with 100.0% for eight children who received regimen J (P = .68). The 4-year relapse-free survival rate for 29 children with diffuse anaplasia treated with regimen DD-RT was 27.2%, compared with 54.8% for 30 children treated with regimen J (P = .02). CONCLUSION We conclude that children with focal anaplasia have an excellent prognosis when treated with vincristine, doxorubicin, and dactinomycin. The addition of cyclophosphamide to the three-drug treatment regimen improved the 4-year relapse-free survival rate of children with stage II to IV diffuse anaplasia. This result suggests that further intensification of the treatment regimen for children with diffuse anaplasia may result in an additional improvement in prognosis.
10.1200/JCO.1994.12.10.2126
pubmed_72_20333
The cytochrome P450 monooxygenases play a major role in insecticide detoxification and become a target for development of insecticide synergists. In this study, a collection of rhinacanthins (rhinacanthin-D, -E, -G, -N, -Q, and -H/I) purified from Rhinacanthus nasutus, in addition to previously purified rhinacanthin-B and -C, were isolated. These compounds displayed various degrees of inhibition against benzyloxyresorufin-O-debenzylation mediated by CYP6AA3 and CYP6P7 which were implicated in pyrethroid resistance in Anopheles minimus malaria vector. Inhibition modes and kinetics were determined for each of rhinacanthins. Cell-based inhibition assays by rhinacanthins employing 3-(4, 5-dimethylthiazol-2-y-l)-2, 5-diphenyltetrazolium bromide (MTT) cytotoxicity test were explored their synergistic effects with cypermethrin toxicity on CYP6AA3- and CYP6P7-expressing Spodoptera frugiperda (Sf9) cells. Rhinacanthin-B, -D, -E, -G, and -N exhibited mechanism-based inhibition against CYP6AA3, an indication of irreversible inhibition, while rhinacanthin-B, -D, -G, and -N were mechanism-based inhibitors of CYP6P7. There was structure-function relationship of these rhinacanthins in inhibition effects against both enzymes. In vitro enzymatic inhibition assays revealed that there were synergistic interactions among rhinacanthins, except rhinacanthin-B and -Q, in inhibition against both enzymes. These rhinacanthins exerted synergism with cypermethrin toxicity on Sf9 cells expressing each of the two P450 enzymes via P450 inhibition and in addition could interact in synergy to further increase cypermethrin toxicity. The inhibition potentials, synergy among rhinacanthins in inhibition against the P450 detoxification enzymes, and synergism with cypermethrin toxicity of the R. nasutus constituents of reported herein could be beneficial to implement effective resistance management of mosquito vector control.
10.1007/s00436-015-4461-8
pubmed_1004_15796
Experimental hyperthyreosis was stimulated by intraventricular injections of sodium solithyroxin (T4) suspension on 1% starch gel during 10 days at a dose of 10 microg/100 g of body mass (n = 15) or 20 microg/100 g of body mass (n = 15). Renal function was tested by 5 % water loading after 24 hrs. since the last T4 injection. Urine and blood plasma samples were analyzed for creatinine; in addition, urine was analyzed for sodium and potassium ions of titrated acids, ammonium cations, and pH. Thyroxin was found to decrease creatinine clearance and expedite renal excretion of sodium and potassium ions irrespective of the amount of exogenous T4; at the same time, exaggerated excretion of titrated acids and ammonium cations correlated with T4 dose.
pubmed_1004_15796
pubmed_195_894
To determine if primary selective laser trabeculoplasty (SLT) can be repeated with clinical benefit in patients with primary open-angle glaucoma (POAG). Forty-two eyes of 42 patients with POAG were studied. All patients underwent primary SLT treatment of 40-50 shots to the trabecular meshwork over 360°. The treatment response at the initial post-SLT visit (4 weeks), and second post-SLT visit (mean 4 months), clinical success and duration of clinical success were measured. SLT was repeated in all patients after failure to maintain target intraocular pressure (IOP). The same parameters were measured after repeat SLT. The main outcome measures were success of treatment (as defined by reduction of IOP by at least 20 % and below an individually determined target pressure), duration of treatment success and reduction in IOP. No significant difference between initial and repeat treatments was found for mean reduction in IOP or success rate, or duration of success. Survival analysis found significantly longer benefit for repeat treatment compared to initial treatment (P < 0.01). Repeat SLT treatment in eyes with POAG has similar efficacy to primary SLT treatment with respect to reduction in IOP and success rates, produces a longer duration of treatment success.
10.1007/s10792-013-9729-3
pubmed_300_3524
INTRODUCTION Pancreatic cancer recurrence is often difficult to detect by conventional imaging. Our aim was to evaluate the impact of fluorodeoxyglucose-positron emission tomography (FDG-PET) in the diagnosis of recurrent pancreatic cancer. METHODS One-hundred thirty-eight patients were followed after resection for pancreatic cancer. Sixty-six underwent only CT and were excluded. Seventy-two patients also had FDG-PET. Recurrent patients were divided in two groups: group-1, CT positive and group 2, CT non diagnostic, FDG-PET positive. Characteristics and survival curves of the two groups were compared. Significance was set at p < 0.05. RESULTS Overall, tumors recurred in 63 of 72 (87.5%) patients; two patients had a second cancer resected, thanks to FDG-PET. Tumor relapse was detected by CT in 35 patients and by FDG-PET in 61. Prognostic factors were similar in groups 1 and 2. Five out of 35 group 1 patients underwent surgery (two R0, two bypass, and one exploratory). Ten out of 28 group 2 patients underwent surgery (four R0, two R2, two bypass, and two exploratory). FDG-PET influenced treatment strategies in 32 of 72 patients (44.4%). Group 2 patients survived longer (P = 0.09), but the difference was not significant. Disease-free survival was similar in groups 1 and 2. CONCLUSION Tumor relapse is detected earlier by FDG-PET than by CT. FDG-PET can help select the best candidates for surgical exploration, although the real benefit is still to be defined. It influences treatment strategies in a significant percentage of patients. An earlier diagnosis did not influence survival due to the lack of effective therapies.
10.1007/s11605-009-1010-8
pubmed_86_4465
OBJECTIVE To describe current immunization requirements and policies in North American medical schools both at matriculation and before students begin clinical clerkships. DESIGN Survey of all allopathic medical schools in the United States and Canada. PARTICIPANTS One hundred and fifteen medical schools. MEASUREMENTS AND MAIN RESULTS Twenty-eight percent of medical schools had no immunization requirements for matriculating medical students. Thirty-one percent of the schools had no rubella immunity requirement, 40% had no measles immunity requirement, and 44% had no polio immunity requirement for matriculating students. For students beginning clinical clerkships, 18%, 35%, and 40% of schools did not require rubella, measles, and polio immunity, respectively. Only 19% and 4% of schools required hepatitis B and influenza immunizations, respectively, at any time during training. Between 20% and 30% of schools accepted student self-report as evidence of rubella and measles immunity. CONCLUSIONS Despite expert guidelines, current medical school immunization policies for matriculating medical students are inadequate. Methods to assess, monitor compliance with, and facilitate student immunization are needed. Medical schools should review their immunization policies to comply with published guidelines.
10.7326/0003-4819-113-8-628
pubmed_551_56
BACKGROUND This study compared the difference between patellofemoral kinematics derived simultaneously from patellar bone pin and skin sensors during full range of tibiofemoral joint movement. METHODS Movements at the tibiofemoral and patellofemoral joints during passive full extension-flexion of the knees in three un-embalmed human cadavers were studied with four electromagnetic tracking sensors at a sampling rate of 30 Hz. A total of four sensors were attached on distal femur, proximal tibia, the surface of a tailor-made patella mold and at the tip of a plastic bone pin planted in the patellar body through a window on the mold. Paired-sample Wilcoxon signed rank test was used to compare peak motions computed from different sensors. The correlation of the movement-time curves derived from different sensors was tested by coefficient of multiple correlations (CMC) in different sections of tibiofemoral joint range. RESULTS Peak motions detected by skin sensor for patellar lateral tilt (p=0.045), distal translation (p=0.021), lateral shift (p=0.032), and anterior-posterior shift of patella (p=0.03 and 0.01 respectively) were higher than that by the bone pin sensor. The overall CMC values for anterior-posterior translation and medial-lateral shift were lower than movements in other planes of movement. The CMC values in initial range were higher than that in the middle and end range in all planes of movement. CONCLUSIONS Patellofemoral kinematics derived from skin sensors may not be representative of the underlying patellar motion. Kinematics reported from the skin sensors should be carefully interpreted.
pubmed_551_56
pubmed_687_5366
BACKGROUND Ischemic stroke can induce changes in mitochondrial morphology and function. As a regulatory gene in mitochondria, optic atrophy 1 (OPA1) plays a pivotal role in the regulation of mitochondrial dynamics and other related functions. However, its roles in cerebral ischemia-related conditions are barely understood. METHODS Cultured rat primary cortical neurons were respectively transfected with OPA1-v1ΔS1-encoding and OPA1-v1-encoding lentivirus before exposure to 2-h oxygen-glucose deprivation (OGD) and subsequent reoxygenation (OGD/R). Adult male SD rats received an intracranial injection of AAV-OPA1-v1ΔS1 and were subjected to 90 min of transient middle cerebral artery occlusion (tMCAO) followed by reperfusion. OPA1 expression and function were detected by in vitro and in vivo assays. RESULTS OPA1 was excessively cleaved after cerebral ischemia/reperfusion injury, both in vitro and in vivo. Under OGD/R condition, compared with that of the LV-OPA1-v1-treated group, the expression of OPA1-v1ΔS1 efficiently restored L-OPA1 level and alleviated neuronal death and mitochondrial morphological damage. Meanwhile, the expression of OPA1-v1ΔS1 markedly improved cerebral ischemia/reperfusion-induced motor function damage, attenuated brain infarct volume, neuronal apoptosis, mitochondrial bioenergetics deficits, oxidative stress, and restored the morphology of mitochondrial cristae and mitochondrial length. It also preserved the mitochondrial integrity and reinforced the mtDNA content and expression of mitochondrial biogenesis factors in ischemic rats. INTERPRETATION Our results demonstrate that the stabilization of L-OPA1 protects ischemic brains by reducing neuronal apoptosis and preserving mitochondrial function, suggesting its significance as a promising therapeutic target for stroke prevention and treatment.
10.1016/j.redox.2020.101503
pubmed_1078_1349
Little is known about the prevalence and outcome of paediatric limb fractures in rural African children. The objective of our study was to assess the prevalence and outcome of paediatric and adolescent limb fractures in this population. We performed a retrospective population survey of 355 secondary school students with a mean age of 16.9 years in Katete, Zambia. Fracture type and cause were assessed using anamnestic data and physical examination. In the surveyed group 52 students (29 male, 23 female) sustained 56 fractures. We found a fracture prevalence rate of 15-19% in male and 11% in female students. The most common fracture was that of the wrist (39%). Forty-eight fractures (86%) were treated in a general hospital, and 4 (7%) in rural health centres. Only 4 students with a fracture (7%) did not receive medical treatment at all. Sport was the most common cause of fractures in the surveyed group (41%). Of all fractures, 25% led to significant impairment.
pubmed_1078_1349
pubmed_496_23587
[reaction: see text] Schmidt glycosylation of the appropriately protected 3,4-dihydroxycinnamate methyl ester with 2,3,4-triacetoxyfucopyranosyltrichloroacetimidate gives aryl glycoside in high yield and diastereoselectivity. 2-Sulfation of fucose, installation of taurine, and global deprotection of the remaining protecting groups affords the fucose-aglycon conjugate of saccharomicin. This synthesis which arises from L-fucose also establishes the absolute configuration of the reducing terminus of the saccharomicin oligosaccharide.
10.1021/ol051971s
pubmed_484_22039
1-3% persons infected with H. pylori develop atrophic gastritis annually. Probability of stomach mucous membrane atrophy in such patients is 50%. H. pylori increases risk of carcinoma development 4-6 times. Experimental infection of mice and mongol gebrils results in neoplasia. CagA- and VacA-positive H. pylori strains have the most pronounced effect in relation to enhancement of inflammation and mucous membrane atrophy. The association was noticed between certain human gene alleles IL-1, IL-10, TNF-alpha on the one hand, incidence of stomach carcinoma and atrophic gastritis with hypochlorohydria, on the other. Results of efficiency of H. pylori treatment in inverse development of gastritis are contradictory. Nevertheless, such therapy is studied as a possible method of carcinoma prophylaxis.
pubmed_484_22039
pubmed_827_22524
The derangement of glucose metabolism is found frequently in all forms of hyperparathyroidism. Both in primary (PHPT) and secondary hyperparathyroidism (SHPT) PTH excess is thought to be involved in deteriorating insulin sensitivity and secretion though their different clinical and pathophysiological conditions. In PHPT these abnormalities are related to a high frequency of Type 2 diabetes mellitus and also impaired glucose tolerance according to recent clinical studies, without differences between symptomatic and asymptomatic clinical presentation. In chronic renal failure (CRF), the disorders of glucose metabolism due to SHPT do not bear an increased risk for diabetes whereas they seem to be involved in the progression of atherosclerotic vascular damage which connotes CRF. Moreover, clinical and experimental studies have shown that vitamin D deficiency associated with glucose metabolism abnormalities favors the development of the metabolic syndrome. The potential for metabolic and cardiovascular harm related to hyperparathyroidism, especially PHPT, is the most interesting issue for clinical endocrinologists. This short review of the clinical and pathophysiological data of literature on glucose homeostasis disorders in hyperparathyroidism focuses on its potential clinical and therapeutic impact, particularly in the management of PHPT.
10.1007/BF03345264
pubmed_160_9247
Immunoglobulin (Ig) therapy is an important method of treatment for a number of immunological, hematological, neurological and dermatological disorders. Over the years, the range of indications in which Ig therapy, either replacement or immunomodulatory, is effective has substantially increased. Although Ig therapy was originally limited to intramuscular injection, intravenous infusion has became the most frequent route of administration, followed by subcutaneous injection. This article presents current information on indications, mechanisms of action, efficacy and practical aspects of intravenous and subcutaneous Ig replacement/immunomodulatory therapy as well as associated adverse reactions.
10.1586/eci.10.104
pubmed_857_11780
BACKGROUND AND PURPOSE We examined responses of rabbit pial arterioles to three different stimuli before and after induction of cortical spreading depression. METHODS In urethane-anesthetized rabbits equipped with a closed cranial window, we measured pial arteriolar diameter during baseline conditions, topical application of calcitonin gene-related peptide (CGRP), topical application of acetylcholine, and inhalation of 10% CO2 in air (arterial hypercapnia) before cortical spreading depression and 30, 60, and 120 minutes after cortical spreading depression. Cortical spreading depression was induced by localized application of a 5% KCl solution anterior to the arteriole being measured. RESULTS Average baseline diameter was approximately 90 microns. During cortical spreading depression, arteriolar diameter increased to a peak value that was 50 +/- 4% above baseline (n = 32). Before cortical spreading depression, arteriolar diameter changed 47 +/- 7% (n = 9) during hypercapnia, 17 +/- 3% (n = 4) during 10(-9) mol/L CGRP, 42 +/- 10% (n = 7) during 10(-7) mol/L CGRP, 29 +/- 6% (n = 4) during 10(-6) mol/L acetylcholine, and 61 +/- 13% (n = 6) during 10(-4) mol/L acetylcholine. Arteriolar responsiveness to any of these stimuli was not changed significantly by prior cortical spreading depression. CONCLUSIONS Dilator capacity of pial arterioles is still intact in urethane-anesthetized rabbits after cortical spreading depression.
10.1161/01.str.24.11.1740
pubmed_441_5396
The authors report on four unusual cases of chronic adult hydrocephalus extracted from a large personal series of patients with hydrocephalic dementia. A syndrome resembling that of normal pressure hydrocephalus was due to the following aetiologies in these patients: Paget's disease of the skull, unruptured cerebral arteriovenous malformation, colloid cyst of the third ventricle, and cerebromeningeal cysticercosis. All these patients exhibited disturbances in cerebrospinal fluid dynamics at the time of study, and were considerably improved by CSF shunting. The value of the continuous CSF pressure monitoring and the constant infusion test in selecting patients with chronic hydrocephalus for shunt therapy is emphasized.
10.1007/BF01808923